Biology Newsfeed

Act for science

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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From a tweet, a March for Science is born

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Grad students, postdocs with U.S. visas face uncertainty

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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World's most endangered marine mammal down to 30

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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New Zealand's endemic dolphins are hanging by a thread

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Why are grizzlies dying on Canada's railway tracks?

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Rules of evidence

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Politics vs. data on needle swaps

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Clear findings, smoggy debate

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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No easy answers

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Putting the brakes on highway deaths

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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A simple recipe for saving lives

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Genetic divide

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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How to be heard

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Data for all?

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Science advice in the Trump White House

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Finding enzymes in the gut metagenome

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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TZAP or not to zap telomeres

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Mobile elements control stem cell potency

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Flipping nanoscopy on its head

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Measurement error and the replication crisis

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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M. G. K. Menon (1928-2016)

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Convergence: The future of health

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Precaution: Open gene drive research

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Precaution: Risks of public participation

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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What drives divergence?

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Double trouble for the Deccan Traps

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Robustness of protein networks

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Intraneuronal control of protein expression

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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A target for intracranial aneurysms

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Starving the pathogen

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Transitional approach to entanglement

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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A protein to trim too-long telomeres

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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A radical idea for blood pressure control

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Change for good

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Superresolution imaging in sharper focus

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Chemically guided functional profiling

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Targeting proteins at the other sulfur

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Multifunctional displays

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Regrow like an axolotl

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Interfering with bad cholesterol

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Gluing up hemagglutinin

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Child growth sensitivity to rainfall variability

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Fluorine frolicking with eight friends

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Skills to pay the bills?

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Redox-based reagents for chemoselective methionine bioconjugation

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

Cysteine can be specifically functionalized by a myriad of acid-base conjugation strategies for applications ranging from probing protein function to antibody-drug conjugates and proteomics. In contrast, selective ligation to the other sulfur-containing amino acid, methionine, has been precluded by its intrinsically weaker nucleophilicity. Here, we report a strategy for chemoselective methionine bioconjugation through redox reactivity, using oxaziridine-based reagents to achieve highly selective, rapid, and robust methionine labeling under a range of biocompatible reaction conditions. We highlight the broad utility of this conjugation method to enable precise addition of payloads to proteins, synthesis of antibody-drug conjugates, and identification of hyperreactive methionine residues in whole proteomes.

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Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

We introduce MINFLUX, a concept for localizing photon emitters in space. By probing the emitter with a local intensity minimum of excitation light, MINFLUX minimizes the fluorescence photons needed for high localization precision. In our experiments, 22 times fewer fluorescence photons are required as compared to popular centroid localization. In superresolution microscopy, MINFLUX attained ~1-nm precision, resolving molecules only 6 nanometers apart. MINFLUX tracking of single fluorescent proteins increased the temporal resolution and the number of localizations per trace by a factor of 100, as demonstrated with diffusing 30S ribosomal subunits in living Escherichia coli. As conceptual limits have not been reached, we expect this localization modality to break new ground for observing the dynamics, distribution, and structure of macromolecules in living cells and beyond.

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Decoupled ecomorphological evolution and diversification in Neogene-Quaternary horses

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

Evolutionary theory has long proposed a connection between trait evolution and diversification rates. In this work, we used phylogenetic methods to evaluate the relationship of lineage-specific speciation rates and the mode of evolution of body size and tooth morphology in the Neogene and Quaternary radiation of horses (7 living and 131 extinct species). We show that diversification pulses are a recurrent feature of equid evolution but that these pulses are not correlated with rapid bursts in phenotypic evolution. Instead, rapid cladogenesis seems repeatedly associated with extrinsic factors that relaxed diversity bounds, such as increasing productivity and geographic dispersals into the Old World. This evidence suggests that diversity dynamics in Equinae were controlled mainly by ecological limits under diversity dependence rather than rapid ecomorphological differentiation.

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Gene duplication can impart fragility, not robustness, in the yeast protein interaction network

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

The maintenance of duplicated genes is thought to protect cells from genetic perturbations, but the molecular basis of this robustness is largely unknown. By measuring the interaction of yeast proteins with their partners in wild-type cells and in cells lacking a paralog, we found that 22 out of 56 paralog pairs compensate for the lost interactions. An equivalent number of pairs exhibit the opposite behavior and require each other’s presence for maintaining their interactions. These dependent paralogs generally interact physically, regulate each other’s abundance, and derive from ancestral self-interacting proteins. This reveals that gene duplication may actually increase mutational fragility instead of robustness in a large number of cases.

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Activity-dependent spatially localized miRNA maturation in neuronal dendrites

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

MicroRNAs (miRNAs) regulate gene expression by binding to target messenger RNAs (mRNAs) and preventing their translation. In general, the number of potential mRNA targets in a cell is much greater than the miRNA copy number, complicating high-fidelity miRNA-target interactions. We developed an inducible fluorescent probe to explore whether the maturation of a miRNA could be regulated in space and time in neurons. A precursor miRNA (pre-miRNA) probe exhibited an activity-dependent increase in fluorescence, suggesting the stimulation of miRNA maturation. Single-synapse stimulation resulted in a local maturation of miRNA that was associated with a spatially restricted reduction in the protein synthesis of a target mRNA. Thus, the spatially and temporally regulated maturation of pre-miRNAs can be used to increase the precision and robustness of miRNA-mediated translational repression.

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TZAP: A telomere-associated protein involved in telomere length control

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

Telomeres are found at the end of chromosomes and are important for chromosome stability. Here we describe a specific telomere-associated protein: TZAP (telomeric zinc finger–associated protein). TZAP binds preferentially to long telomeres that have a low concentration of shelterin complex, competing with the telomeric-repeat binding factors TRF1 and TRF2. When localized at telomeres, TZAP triggers a process known as telomere trimming, which results in the rapid deletion of telomeric repeats. On the basis of these results, we propose a model for telomere length regulation in mammalian cells: The reduced concentration of the shelterin complex at long telomeres results in TZAP binding and initiation of telomere trimming. Binding of TZAP to long telomeres represents the switch that triggers telomere trimming, setting the upper limit of telomere length.

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A switch from canonical to noncanonical autophagy shapes B cell responses

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

Autophagy is important in a variety of cellular and pathophysiological situations; however, its role in immune responses remains elusive. Here, we show that among B cells, germinal center (GC) cells exhibited the highest rate of autophagy during viral infection. In contrast to mechanistic target of rapamycin complex 1–dependent canonical autophagy, GC B cell autophagy occurred predominantly through a noncanonical pathway. B cell stimulation was sufficient to down-regulate canonical autophagy transiently while triggering noncanonical autophagy. Genetic ablation of WD repeat domain, phosphoinositide–interacting protein 2 in B cells alone enhanced this noncanonical autophagy, resulting in changes of mitochondrial homeostasis and alterations in GC and antibody-secreting cells. Thus, B cell activation prompts a temporal switch from canonical to noncanonical autophagy that is important in controlling B cell differentiation and fate.

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New Products

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

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Deficiency of microRNA miR-34a expands cell fate potential in pluripotent stem cells

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) efficiently generate all embryonic cell lineages but rarely generate extraembryonic cell types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse pluripotent stem cells, yielding both embryonic and extraembryonic lineages and strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features of totipotent two-cell blastomeres. miR-34a restricts the acquisition of expanded cell fate potential in pluripotent stem cells, and it represses MERVL expression through transcriptional regulation, at least in part by targeting the transcription factor Gata2. Our studies reveal a complex molecular network that defines and restricts pluripotent developmental potential in cultured ESCs and iPSCs.

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Merging paleobiology with conservation biology to guide the future of terrestrial ecosystems

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

Conservation of species and ecosystems is increasingly difficult because anthropogenic impacts are pervasive and accelerating. Under this rapid global change, maximizing conservation success requires a paradigm shift from maintaining ecosystems in idealized past states toward facilitating their adaptive and functional capacities, even as species ebb and flow individually. Developing effective strategies under this new paradigm will require deeper understanding of the long-term dynamics that govern ecosystem persistence and reconciliation of conflicts among approaches to conserving historical versus novel ecosystems. Integrating emerging information from conservation biology, paleobiology, and the Earth sciences is an important step forward on the path to success. Maintaining nature in all its aspects will also entail immediately addressing the overarching threats of growing human population, overconsumption, pollution, and climate change.

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A prominent glycyl radical enzyme in human gut microbiomes metabolizes trans-4-hydroxy-L-proline

ScienceNOW - Posted: January 1st, 1970, 3:00am UTC

The human microbiome encodes vast numbers of uncharacterized enzymes, limiting our functional understanding of this community and its effects on host health and disease. By incorporating information about enzymatic chemistry into quantitative metagenomics, we determined the abundance and distribution of individual members of the glycyl radical enzyme superfamily among the microbiomes of healthy humans. We identified many uncharacterized family members, including a universally distributed enzyme that enables commensal gut microbes and human pathogens to dehydrate trans-4-hydroxy-l-proline, the product of the most abundant human posttranslational modification. This "chemically guided functional profiling" workflow can therefore use ecological context to facilitate the discovery of enzymes in microbial communities.

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The science-policy interface

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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London's biomedical behemoth opens its doors

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A painstaking overhaul for cardiac safety testing

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Duke fraud case highlights financial risks for universities

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mentoring's moment

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Tumors set time

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Effects of a warming Arctic

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Induced pluripotent stem cells, past and future

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The great debate

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Coordinate efforts on EU invasive species

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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USGS scientists open to change

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Rescued wildlife in China remains at risk

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Language representation in the dog brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Discerning dengue vaccine protection

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Signposts for synapses

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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How antibodies protect against HIV-1

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Divergent responses, same receptor

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Copper-catalyzed radical relay

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Warm Arctic--cold continents?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Strontium's loss is iridium's gain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Hormone clearance and morphogenesis in plants

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Genetic underpinnings of atrial fibrillation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Targeting just one of two C-H bonds

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Just passing through

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Drinking water--and what else?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mechanical coupling of heart cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Pacemaker cells for insulin release

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Measuring impacts of technology on growth

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Brain mapping by barcode

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Radiative human body cooling by nanoporous polyethylene textile

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Thermal management through personal heating and cooling is a strategy by which to expand indoor temperature setpoint range for large energy saving. We show that nanoporous polyethylene (nanoPE) is transparent to mid-infrared human body radiation but opaque to visible light because of the pore size distribution (50 to 1000 nanometers). We processed the material to develop a textile that promotes effective radiative cooling while still having sufficient air permeability, water-wicking rate, and mechanical strength for wearability. We developed a device to simulate skin temperature that shows temperatures 2.7° and 2.0°C lower when covered with nanoPE cloth and with processed nanoPE cloth, respectively, than when covered with cotton. Our processed nanoPE is an effective and scalable textile for personal thermal management.

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Ligand-accelerated enantioselective methylene C(sp3)-H bond activation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Effective differentiation of prochiral carbon–hydrogen (C–H) bonds on a single methylene carbon via asymmetric metal insertion remains a challenge. Here, we report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that enable asymmetric palladium insertion into prochiral C–H bonds on a single methylene carbon center. We apply these palladium complexes to catalytic enantioselective functionalization of β-methylene C–H bonds in aliphatic amides. Using bidentate ligands to accelerate C–H activation of otherwise unreactive monodentate substrates is crucial for outcompeting the background reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion of enantioselectivity. The potential of ligand acceleration in C–H activation is also demonstrated by enantioselective β-C–H arylation of simple carboxylic acids without installing directing groups.

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Plant development regulated by cytokinin sinks

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Morphogenetic signals control the patterning of multicellular organisms. Cytokinins are mobile signals that are perceived by subsets of plant cells. We found that the responses to cytokinin signaling during Arabidopsis development are constrained by the transporter PURINE PERMEASE 14 (PUP14). In our experiments, the expression of PUP14 was inversely correlated to the cytokinin signaling readout. Loss of PUP14 function allowed ectopic cytokinin signaling accompanied by aberrant morphogenesis in embryos, roots, and the shoot apical meristem. PUP14 protein localized to the plasma membrane and imported bioactive cytokinins, thus depleting apoplastic cytokinin pools and inhibiting perception by plasma membrane–localized cytokinin sensors to create a sink for active ligands. We propose that the spatiotemporal cytokinin sink patterns established by PUP14 determine the cytokinin signaling landscape that shapes the morphogenesis of land plants.

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Neural mechanisms for lexical processing in dogs

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

During speech processing, human listeners can separately analyze lexical and intonational cues to arrive at a unified representation of communicative content. The evolution of this capacity can be best investigated by comparative studies. Using functional magnetic resonance imaging, we explored whether and how dog brains segregate and integrate lexical and intonational information. We found a left-hemisphere bias for processing meaningful words, independently of intonation; a right auditory brain region for distinguishing intonationally marked and unmarked words; and increased activity in primary reward regions only when both lexical and intonational information were consistent with praise. Neural mechanisms to separately analyze and integrate word meaning and intonation in dogs suggest that this capacity can evolve in the absence of language.

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Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe "secondary-like" infection and, thus, the numbers hospitalized for dengue. In moderate transmission settings, we predict positive impacts overall but increased risks of hospitalization with dengue disease for individuals who are vaccinated when seronegative. However, in high-transmission settings, vaccination benefits both the whole population and seronegative recipients. Our analysis can help inform policy-makers evaluating this and other candidate dengue vaccines.

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De novo synaptogenesis induced by GABA in the developing mouse cortex

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Dendrites of cortical pyramidal neurons contain intermingled excitatory and inhibitory synapses. We studied the local mechanisms that regulate the formation and distribution of synapses. We found that local -aminobutyric acid (GABA) release on dendrites of mouse cortical layer 2/3 pyramidal neurons could induce gephyrin puncta and dendritic spine formation via GABA type A receptor activation and voltage-gated calcium channels during early postnatal development. Furthermore, the newly formed inhibitory and excitatory synaptic structures rapidly gained functions. Bidirectional manipulation of GABA release from somatostatin-positive interneurons increased and decreased the number of gephyrin puncta and dendritic spines, respectively. These results highlight a noncanonical function of GABA as a local synaptogenic element shaping the early establishment of neuronal circuitry in mouse cortex.

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Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

HIV-1–specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception of virus and the mechanism of antibody-mediated protection remain unclear. We administered a fully protective dose of the bNAb PGT121 to rhesus monkeys and challenged them intravaginally with SHIV-SF162P3. In PGT121-treated animals, we detected low levels of viral RNA and viral DNA in distal tissues for seven days following challenge. Viral RNA–positive tissues showed transcriptomic changes indicative of innate immune activation, and cells from these tissues initiated infection after adoptive transfer into naïve hosts. These data demonstrate that bNAb-mediated protection against a mucosal virus challenge can involve clearance of infectious virus in distal tissues.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Research integrity revisited

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Why the rest of the world is marching

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Personalized tumor vaccines keep cancer in check

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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U.S. report calls for research integrity board

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Epidemic Insurance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Detecting molecular hydrogen on Enceladus

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Allotropy by design--Carbon nanohoops

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Eating ecosystems

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Embryogenesis in a dish

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Managing cell and human identity

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Embracing the unqualified opinion

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A river runs through it

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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After Chile's fires, reforest private land

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Targeting nonviral antigens in viral-driven cancer

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Transporter layers for greater stability

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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One antibody for all and all antibodies for one

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Quantifying hunting-induced defaunation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A target for preventing kidney damage

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The negative impact of EU enlargement

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Stitching one alkyl group to another

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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In vitro embryogenesis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Machines learn what people know implicitly

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Making an unbiased library

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Coupling transcription and translation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The evolving Ebola virus host response

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Regulatory T cells sans FoxP3

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Near and far effects on gene expression

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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TB exploits zombie cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Protectin and resolvin gut inflammation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Smashing ions to test a theory

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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YAP is crucial for lung branching morphogenesis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Synthesis of a carbon nanobelt

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The synthesis of a carbon nanobelt, comprising a closed loop of fully fused edge-sharing benzene rings, has been an elusive goal in organic chemistry for more than 60 years. Here we report the synthesis of one such compound through iterative Wittig reactions followed by a nickel-mediated aryl-aryl coupling reaction. The cylindrical shape of its belt structure was confirmed by x-ray crystallography, and its fundamental optoelectronic properties were elucidated by ultraviolet-visible absorption, fluorescence, and Raman spectroscopic studies, as well as theoretical calculations. This molecule could potentially serve as a seed for the preparation of structurally well-defined carbon nanotubes.

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Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fc receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity—including fever, viremia, and viral loads in spinal cord and testes—and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.

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The impact of hunting on tropical mammal and bird populations

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Hunting is a major driver of biodiversity loss, but a systematic large-scale estimate of hunting-induced defaunation is lacking. We synthesized 176 studies to quantify hunting-induced declines of mammal and bird populations across the tropics. Bird and mammal abundances declined by 58% (25 to 76%) and by 83% (72 to 90%) in hunted compared with unhunted areas. Bird and mammal populations were depleted within 7 and 40 kilometers from hunters’ access points (roads and settlements). Additionally, hunting pressure was higher in areas with better accessibility to major towns where wild meat could be traded. Mammal population densities were lower outside protected areas, particularly because of commercial hunting. Strategies to sustainably manage wild meat hunting in both protected and unprotected tropical ecosystems are urgently needed to avoid further defaunation.

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Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI)

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Single-cell genomics is important for biology and medicine. However, current whole-genome amplification (WGA) methods are limited by low accuracy of copy-number variation (CNV) detection and low amplification fidelity. Here we report an improved single-cell WGA method, Linear Amplification via Transposon Insertion (LIANTI), which outperforms existing methods, enabling micro-CNV detection with kilobase resolution. This allowed direct observation of stochastic firing of DNA replication origins, which differs from cell to cell. We also show that the predominant cytosine-to-thymine mutations observed in single-cell genomics often arise from the artifact of cytosine deamination upon cell lysis. However, identifying single-nucleotide variations (SNVs) can be accomplished by sequencing kindred cells. We determined the spectrum of SNVs in a single human cell after ultraviolet radiation, revealing their nonrandom genome-wide distribution.

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Architecture of a transcribing-translating expressome

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

DNA transcription is functionally coupled to messenger RNA (mRNA) translation in bacteria, but how this is achieved remains unclear. Here we show that RNA polymerase (RNAP) and the ribosome of Escherichia coli can form a defined transcribing and translating "expressome" complex. The cryo–electron microscopic structure of the expressome reveals continuous protection of ~30 nucleotides of mRNA extending from the RNAP active center to the ribosome decoding center. The RNAP-ribosome interface includes the RNAP subunit α carboxyl-terminal domain, which is required for RNAP-ribosome interaction in vitro and for pronounced cell growth defects upon translation inhibition in vivo, consistent with its function in transcription-translation coupling. The expressome structure can only form during transcription elongation and explains how translation can prevent transcriptional pausing, backtracking, and termination.

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Nanoscale-length control of the flagellar driveshaft requires hitting the tethered outer membrane

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The bacterial flagellum exemplifies a system where even small deviations from the highly regulated flagellar assembly process can abolish motility and cause negative physiological outcomes. Consequently, bacteria have evolved elegant and robust regulatory mechanisms to ensure that flagellar morphogenesis follows a defined path, with each component self-assembling to predetermined dimensions. The flagellar rod acts as a driveshaft to transmit torque from the cytoplasmic rotor to the external filament. The rod self-assembles to a defined length of ~25 nanometers. Here, we provide evidence that rod length is limited by the width of the periplasmic space between the inner and outer membranes. The length of Braun's lipoprotein determines periplasmic width by tethering the outer membrane to the peptidoglycan layer.

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Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus–associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens. T cells targeting viral tumor antigens did not display preferential in vivo expansion. Both viral and nonviral tumor antigen–specific T cells resided predominantly in the programmed cell death 1 (PD-1)–expressing T cell compartment, which suggests that PD-1 blockade may unleash diverse antitumor T cell reactivities. These findings suggest a new paradigm of targeting nonviral antigens in immunotherapy of virally associated cancers.

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Crystal structure of the overlapping dinucleosome composed of hexasome and octasome

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Nucleosomes are dynamic entities that are repositioned along DNA by chromatin remodeling processes. A nucleosome repositioned by the switch-sucrose nonfermentable (SWI/SNF) remodeler collides with a neighbor and forms the intermediate "overlapping dinucleosome." Here, we report the crystal structure of the overlapping dinucleosome, in which two nucleosomes are associated, at 3.14-angstrom resolution. In the overlapping dinucleosome structure, the unusual "hexasome" nucleosome, composed of the histone hexamer lacking one H2A-H2B dimer from the conventional histone octamer, contacts the canonical "octasome" nucleosome, and they intimately associate. Consequently, about 250 base pairs of DNA are left-handedly wrapped in three turns, without a linker DNA segment between the hexasome and octasome moieties. The overlapping dinucleosome structure may provide important information to understand how nucleosome repositioning occurs during the chromatin remodeling process.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Webinar | Translational applications in exosome research: From biomarker discovery to drug delivery

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Skiing for science

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Mammalian embryogenesis requires intricate interactions between embryonic and extraembryonic tissues to orchestrate and coordinate morphogenesis with changes in developmental potential. Here, we combined mouse embryonic stem cells (ESCs) and extraembryonic trophoblast stem cells (TSCs) in a three-dimensional scaffold to generate structures whose morphogenesis is markedly similar to that of natural embryos. By using genetically modified stem cells and specific inhibitors, we show that embryogenesis of ESC- and TSC-derived embryos—ETS-embryos—depends on cross-talk involving Nodal signaling. When ETS-embryos develop, they spontaneously initiate expression of mesoderm and primordial germ cell markers asymmetrically on the embryonic and extraembryonic border, in response to Wnt and BMP signaling. Our study demonstrates the ability of distinct stem cell types to self-assemble in vitro to generate embryos whose morphogenesis, architecture, and constituent cell types resemble those of natural embryos.

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Early animal fossils at risk

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A new neglected crop: cannabis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Society labels harassment as research misconduct

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Sam Ting's last tease

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Facilitating conservation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Biased inheritance protects older bacteria from harm

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Decoding hormones for a stem cell niche

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Culture clash

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Dramatizing Deepwater Horizon

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The interaction of human population, food production, and biodiversity protection

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Research suggests that the scale of human population and the current pace of its growth contribute substantially to the loss of biological diversity. Although technological change and unequal consumption inextricably mingle with demographic impacts on the environment, the needs of all human beings—especially for food—imply that projected population growth will undermine protection of the natural world. Numerous solutions have been proposed to boost food production while protecting biodiversity, but alone these proposals are unlikely to staunch biodiversity loss. An important approach to sustaining biodiversity and human well-being is through actions that can slow and eventually reverse population growth: investing in universal access to reproductive health services and contraceptive technologies, advancing women’s education, and achieving gender equality.

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Ecosystem management as a wicked problem

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Ecosystems are self-regulating systems that provide societies with food, water, timber, and other resources. As demands for resources increase, management decisions are replacing self-regulating properties. Counter to previous technical approaches that applied simple formulas to estimate sustainable yields of single species, current research recognizes the inherent complexity of ecosystems and the inability to foresee all consequences of interventions across different spatial, temporal, and administrative scales. Ecosystem management is thus more realistically seen as a "wicked problem" that has no clear-cut solution. Approaches for addressing such problems include multisector decision-making, institutions that enable management to span across administrative boundaries, adaptive management, markets that incorporate natural capital, and collaborative processes to engage diverse stakeholders and address inequalities. Ecosystem management must avoid two traps: falsely assuming a tame solution and inaction from overwhelming complexity. An incremental approach can help to avoid these traps.

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Biodiversity losses and conservation responses in the Anthropocene

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Biodiversity is essential to human well-being, but people have been reducing biodiversity throughout human history. Loss of species and degradation of ecosystems are likely to further accelerate in the coming years. Our understanding of this crisis is now clear, and world leaders have pledged to avert it. Nonetheless, global goals to reduce the rate of biodiversity loss have mostly not been achieved. However, many examples of conservation success show that losses can be halted and even reversed. Building on these lessons to turn the tide of biodiversity loss will require bold and innovative action to transform historical relationships between human populations and nature.

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Beyond the roots of human inaction: Fostering collective effort toward ecosystem conservation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The term "environmental problem" exposes a fundamental misconception: Disruptions of Earth’s ecosystems are at their root a human behavior problem. Psychology is a potent tool for understanding the external and internal drivers of human behavior that lead to unsustainable living. Psychologists already contribute to individual-level behavior-change campaigns in the service of sustainability, but attention is turning toward understanding and facilitating the role of individuals in collective and collaborative actions that will modify the environmentally damaging systems in which humans are embedded. Especially crucial in moving toward long-term human and environmental well-being are transformational individuals who step outside of the norm, embrace ecological principles, and inspire collective action. Particularly in developed countries, fostering legions of sustainability leaders rests upon a fundamental renewal of humans’ connection to the natural world.

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Losing its character

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Capturing chemokines in chronic wounds

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Multiple images of a type Ia supernova

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Gut anaerobes protect against pathogen invasion

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Safe anaerobic metabolism

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Ancestral legacy effects

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Micromanaging muscle cell fusion

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Resident memory responses to cancer

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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What's in a drop of blood?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Double duty for mammary stem cell niche

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Watching nanomaterials transform in time

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Drug efflux machinery inherited asymmetrically

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A transcription factor drug for asthma

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Facilitating refuges

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Countering chemo's effects on fertility

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The physics of social butterflies

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The eyes have it

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Disordered proteins make a dynamic switch

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Nanostructured high-strength alloys

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The African naked mole-rat’s (Heterocephalus glaber) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease.

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Biased partitioning of the multidrug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood. We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria.

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Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The high susceptibility of neonates to infections has been assumed to be due to immaturity of the immune system, but the mechanism remains unclear. By colonizing adult germ-free mice with the cecal contents of neonatal and adult mice, we show that the neonatal microbiota is unable to prevent colonization by two bacterial pathogens that cause mortality in neonates. The lack of colonization resistance occurred when Clostridiales were absent in the neonatal microbiota. Administration of Clostridiales, but not Bacteroidales, protected neonatal mice from pathogen infection and abrogated intestinal pathology upon pathogen challenge. Depletion of Clostridiales also abolished colonization resistance in adult mice. The neonatal bacteria enhanced the ability of protective Clostridiales to colonize the gut.

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Transgenerational transmission of environmental information in C. elegans

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The environment experienced by an animal can sometimes influence gene expression for one or a few subsequent generations. Here, we report the observation that a temperature-induced change in expression from a Caenorhabditis elegans heterochromatic gene array can endure for at least 14 generations. Inheritance is primarily in cis with the locus, occurs through both oocytes and sperm, and is associated with altered trimethylation of histone H3 lysine 9 (H3K9me3) before the onset of zygotic transcription. Expression profiling reveals that temperature-induced expression from endogenous repressed repeats can also be inherited for multiple generations. Long-lasting epigenetic memory of environmental change is therefore possible in this animal.

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Microtubules acquire resistance from mechanical breakage through intralumenal acetylation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Eukaryotic cells rely on long-lived microtubules for intracellular transport and as compression-bearing elements. We considered that long-lived microtubules are acetylated inside their lumen and that microtubule acetylation may modify microtubule mechanics. Here, we found that tubulin acetylation is required for the mechanical stabilization of long-lived microtubules in cells. Depletion of the tubulin acetyltransferase TAT1 led to a significant increase in the frequency of microtubule breakage. Nocodazole-resistant microtubules lost upon removal of acetylation were largely restored by either pharmacological or physical removal of compressive forces. In in vitro reconstitution experiments, acetylation was sufficient to protect microtubules from mechanical breakage. Thus, acetylation increases mechanical resilience to ensure the persistence of long-lived microtubules.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The new tissue culture

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Stromal Gli2 activity coordinates a niche signaling program for mammary epithelial stem cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The stem cell niche is a complex local signaling microenvironment that sustains stem cell activity during organ maintenance and regeneration. The mammary gland niche must support its associated stem cells while also responding to systemic hormonal regulation that triggers pubertal changes. We find that Gli2, the major Hedgehog pathway transcriptional effector, acts within mouse mammary stromal cells to direct a hormone-responsive niche signaling program by activating expression of factors that regulate epithelial stem cells as well as receptors for the mammatrophic hormones estrogen and growth hormone. Whereas prior studies implicate stem cell defects in human disease, this work shows that niche dysfunction may also cause disease, with possible relevance for human disorders and in particular the breast growth pathogenesis associated with combined pituitary hormone deficiency.

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Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C⁺ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease.

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Syria, slums, and health security

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Meet the science marchers

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Claim of very early humans in Americas shocks researchers

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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In surprise, tooth decay afflicts hunter-gatherers

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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DNA from cave soil reveals ancient human occupants

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The vaccine wars

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The science of persuasion

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Vaccine myths

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Vaccines on trial

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The natural capital of city trees

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Linking stem cells to germ cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Extracting the contents of living cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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H. Boyd Woodruff (1917-2017)

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Documenting decline in U.S. economic mobility

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A state of denial

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Scienceblind: Why Our Intuitive Theories About the World Are So Often Wrong

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mexico's invasive species plan in context

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Community network for deaf scientists

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Nature's treasure hunt

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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S&T Policy Forum examines evolving opioid epidemic

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Forum's fight for science

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Aspiring to do better than one's parents

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Pattern formation in the brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Getting phosphorus into healthy shape

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Taking a look at fungal bioluminescence

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Imaging an atomic soliton train

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Zinc can compete with lithium

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Sensitive and specific CRISPR diagnostics

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Thinking local about building

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Single-cell diversity in the brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Germ cells on demand

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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An old cancer drug's degrading new look

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Using quasar pairs to measure smoothness

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Plant the right tree

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Interferon-independent antiviral defense

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Liver T cells in obesity-associated diabetes

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The making of the human brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Planning for a rise

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Delaying demise

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Virtues of splitting up water-splitting

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The fading American dream: Trends in absolute income mobility since 1940

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

We estimated rates of "absolute income mobility"—the fraction of children who earn more than their parents—by combining data from U.S. Census and Current Population Survey cross sections with panel data from de-identified tax records. We found that rates of absolute mobility have fallen from approximately 90% for children born in 1940 to 50% for children born in the 1980s. Increasing Gross Domestic Product (GDP) growth rates alone cannot restore absolute mobility to the rates experienced by children born in the 1940s. However, distributing current GDP growth more equally across income groups as in the 1940 birth cohort would reverse more than 70% of the decline in mobility. These results imply that reviving the "American dream" of high rates of absolute mobility would require economic growth that is shared more broadly across the income distribution.

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Pcdh{alpha}c2 is required for axonal tiling and assembly of serotonergic circuitries in mice

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Serotonergic neurons project their axons pervasively throughout the brain and innervate various target fields in a space-filling manner, leading to tiled arrangements of their axon terminals to allow optimal allocation of serotonin among target neurons. Here we show that conditional deletion of the mouse protocadherin α (Pcdhα) gene cluster in serotonergic neurons disrupts local axonal tiling and global assembly of serotonergic circuitries and results in depression-like behaviors. Genetic dissection and expression profiling revealed that this role is specifically mediated by Pcdhαc2, which is the only Pcdhα isoform expressed in serotonergic neurons. We conclude that, in contrast to neurite self-avoidance, which requires single-cell identity mediated by Pcdh diversity, a single cell-type identity mediated by the common C-type Pcdh isoform is required for axonal tiling and assembly of serotonergic circuitries.

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Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdhα, Pcdhβ, and Pcdh). Here, we show that all three gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons (OSNs) with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb. Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters (tricluster deletion) led to a severe axonal arborization defect and loss of self-avoidance. By contrast, when endogenous Pcdh diversity is overridden by the expression of a single–tricluster gene repertoire (α and β and ), OSN axons fail to converge to form glomeruli, likely owing to contact-mediated repulsion between axons expressing identical combinations of Pcdh isoforms.

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Rechargeable nickel-3D zinc batteries: An energy-dense, safer alternative to lithium-ion

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The next generation of high-performance batteries should include alternative chemistries that are inherently safer to operate than nonaqueous lithium-based batteries. Aqueous zinc-based batteries can answer that challenge because monolithic zinc sponge anodes can be cycled in nickel–zinc alkaline cells hundreds to thousands of times without undergoing passivation or macroscale dendrite formation. We demonstrate that the three-dimensional (3D) zinc form-factor elevates the performance of nickel–zinc alkaline cells in three fields of use: (i) >90% theoretical depth of discharge (DODZn) in primary (single-use) cells, (ii) >100 high-rate cycles at 40% DODZn at lithium-ion–commensurate specific energy, and (iii) the tens of thousands of power-demanding duty cycles required for start-stop microhybrid vehicles.

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Formation of matter-wave soliton trains by modulational instability

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Nonlinear systems can exhibit a rich set of dynamics that are inherently sensitive to their initial conditions. One such example is modulational instability, which is believed to be one of the most prevalent instabilities in nature. By exploiting a shallow zero-crossing of a Feshbach resonance, we characterize modulational instability and its role in the formation of matter-wave soliton trains from a Bose-Einstein condensate. We examine the universal scaling laws exhibited by the system and, through real-time imaging, address a long-standing question of whether the solitons in trains are created with effectively repulsive nearest-neighbor interactions or rather evolve into such a structure.

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A multifunctional catalyst that stereoselectively assembles prodrugs

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The catalytic stereoselective synthesis of compounds with chiral phosphorus centers remains an unsolved problem. State-of-the-art methods rely on resolution or stoichiometric chiral auxiliaries. Phosphoramidate prodrugs are a critical component of pronucleotide (ProTide) therapies used in the treatment of viral disease and cancer. Here we describe the development of a catalytic stereoselective method for the installation of phosphorus-stereogenic phosphoramidates to nucleosides through a dynamic stereoselective process. Detailed mechanistic studies and computational modeling led to the rational design of a multifunctional catalyst that enables stereoselectivity as high as 99:1.

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Nucleic acid detection with CRISPR-Cas13a/C2c2

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting clustered regularly interspaced short palindromic repeats (CRISPR) effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous ribonuclease activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity. We use this Cas13a-based molecular detection platform, termed Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK), to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify mutations in cell-free tumor DNA. Furthermore, SHERLOCK reaction reagents can be lyophilized for cold-chain independence and long-term storage and be readily reconstituted on paper for field applications.

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Ancient genomic changes associated with domestication of the horse

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The genomic changes underlying both early and late stages of horse domestication remain largely unknown. We examined the genomes of 14 early domestic horses from the Bronze and Iron Ages, dating to between ~4.1 and 2.3 thousand years before present. We find early domestication selection patterns supporting the neural crest hypothesis, which provides a unified developmental origin for common domestic traits. Within the past 2.3 thousand years, horses lost genetic diversity and archaic DNA tracts introgressed from a now-extinct lineage. They accumulated deleterious mutations later than expected under the cost-of-domestication hypothesis, probably because of breeding from limited numbers of stallions. We also reveal that Iron Age Scythian steppe nomads implemented breeding strategies involving no detectable inbreeding and selection for coat-color variation and robust forelimbs.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Webinar | Getting the best data from your cells: From tissue culture to final analysis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Standing up to fear

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders.

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Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Indisulam is an aryl sulfonamide drug with selective anticancer activity. Its mechanism of action and the basis for its selectivity have so far been unknown. Here we show that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. Mutations in RBM39 that prevent its recruitment to CUL4-DCAF15 increase RBM39 stability and confer resistance to indisulam’s cytotoxicity. RBM39 associates with precursor messenger RNA (pre-mRNA) splicing factors, and inactivation of RBM39 by indisulam causes aberrant pre-mRNA splicing. Many cancer cell lines derived from hematopoietic and lymphoid lineages are sensitive to indisulam, and their sensitivity correlates with DCAF15 expression levels. Two other clinically tested sulfonamides, tasisulam and chloroquinoxaline sulfonamide, share the same mechanism of action as indisulam. We propose that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides).

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RETINOBLASTOMA RELATED1 mediates germline entry in Arabidopsis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

To produce seeds, flowering plants need to specify somatic cells to undergo meiosis. Here, we reveal a regulatory cascade that controls the entry into meiosis starting with a group of redundantly acting cyclin-dependent kinase (CDK) inhibitors of the KIP-RELATED PROTEIN (KRP) class. KRPs function by restricting CDKA;1–dependent inactivation of the Arabidopsis Retinoblastoma homolog RBR1. In rbr1 and krp triple mutants, designated meiocytes undergo several mitotic divisions, resulting in the formation of supernumerary meiocytes that give rise to multiple reproductive units per future seed. One function of RBR1 is the direct repression of the stem cell factor WUSCHEL (WUS), which ectopically accumulates in meiocytes of triple krp and rbr1 mutants. Depleting WUS in rbr1 mutants restored the formation of only a single meiocyte.

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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New crop pest takes Africa at lightning speed

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Going green on the silver screen

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Beyond Hamilton's rule

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Surprising states of order for linear diblock copolymers

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Inflammation by way of macrophage metabolism

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Transcription factors read epigenetics

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Thomas Earl Starzl (1926-2017)

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Unmask temporal trade-offs in climate policy debates

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A climate policy pathway for near- and long-term benefits

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Resetting the bar for graduate admissions

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The roadless dunes less traveled

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Response to Comment on "Density functional theory is straying from the path toward the exact functional"

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Kepp argues in his Comment, among other concerns, that the atomic densities we have considered are not relevant to molecular bonding. However, this does not change the main conclusion of our study, that unconstrained fitting of flexible functional forms can make a density functional more interpolative but less widely predictive.

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Artificial intelligence masters poker

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Shhh, you're disturbing the ecosystem

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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On the history of Bantu speakers

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A way to switch off IBD

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Give us our daily protein

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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LAMP shines a light on Zika virus

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Finding drugs for fragile X syndrome

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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When polymers behave like metals

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Wet, soft, squishy, and tunable

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Self-organization for sensory brushes

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Positives and negatives of methylated CpG

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Inducing DNA methylation where it wasn't

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Genetic interactions drive selection

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Inter-innate cooperation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Climate extremes stress ecosystems

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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RPE cranks it up a Notch

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The three-dimensional world in the brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Committees, candidates, and gender

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

CpG islands (CGIs) are primarily promoter-associated genomic regions and are mostly unmethylated within highly methylated mammalian genomes. The mechanisms by which CGIs are protected from de novo methylation remain elusive. Here we show that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation. By targeting the DNA mismatch repair gene MLH1 CGI, we could generate a PSC model of a cancer-related epimutation. Furthermore, we successfully corrected aberrant imprinting in induced PSCs derived from an Angelman syndrome patient. Our results provide insights into how CpG-free DNA induces de novo CGI methylation and broaden the application of targeted epigenome editing for a better understanding of human development and disease.

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Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. Consequently, IL-10 promotes mitophagy that eliminates dysfunctional mitochondria characterized by low membrane potential and a high level of reactive oxygen species. In the absence of IL-10 signaling, macrophages accumulate damaged mitochondria in a mouse model of colitis and inflammatory bowel disease patients, and this results in dysregulated activation of the NLRP3 inflammasome and production of IL-1β.

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The complex effects of ocean acidification on the prominent N2-fixing cyanobacterium Trichodesmium

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Acidification of seawater caused by anthropogenic carbon dioxide (CO2) is anticipated to influence the growth of dinitrogen (N2)–fixing phytoplankton, which contribute a large fraction of primary production in the tropical and subtropical ocean. We found that growth and N2-fixation of the ubiquitous cyanobacterium Trichodesmium decreased under acidified conditions, notwithstanding a beneficial effect of high CO2. Acidification resulted in low cytosolic pH and reduced N2-fixation rates despite elevated nitrogenase concentrations. Low cytosolic pH required increased proton pumping across the thylakoid membrane and elevated adenosine triphosphate production. These requirements were not satisfied under field or experimental iron-limiting conditions, which greatly amplified the negative effect of acidification.

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Noise pollution is pervasive in U.S. protected areas

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Anthropogenic noise threatens ecological systems, including the cultural and biodiversity resources in protected areas. Using continental-scale sound models, we found that anthropogenic noise doubled background sound levels in 63% of U.S. protected area units and caused a 10-fold or greater increase in 21%, surpassing levels known to interfere with human visitor experience and disrupt wildlife behavior, fitness, and community composition. Elevated noise was also found in critical habitats of endangered species, with 14% experiencing a 10-fold increase in sound levels. However, protected areas with more stringent regulations had less anthropogenic noise. Our analysis indicates that noise pollution in protected areas is closely linked with transportation, development, and extractive land use, providing insight into where mitigation efforts can be most effective.

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Branch-specific plasticity of a bifunctional dopamine circuit encodes protein hunger

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Free-living animals must not only regulate the amount of food they consume but also choose which types of food to ingest. The shifting of food preference driven by nutrient-specific hunger can be essential for survival, yet little is known about the underlying mechanisms. We identified a dopamine circuit that encodes protein-specific hunger in Drosophila. The activity of these neurons increased after substantial protein deprivation. Activation of this circuit simultaneously promoted protein intake and restricted sugar consumption, via signaling to distinct downstream neurons. Protein starvation triggered branch-specific plastic changes in these dopaminergic neurons, thus enabling sustained protein consumption. These studies reveal a crucial circuit mechanism by which animals adjust their dietary strategy to maintain protein homeostasis.

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Negative selection in humans and fruit flies involves synergistic epistasis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Negative selection against deleterious alleles produced by mutation influences within-population variation as the most pervasive form of natural selection. However, it is not known whether deleterious alleles affect fitness independently, so that cumulative fitness loss depends exponentially on the number of deleterious alleles, or synergistically, so that each additional deleterious allele results in a larger decrease in relative fitness. Negative selection with synergistic epistasis should produce negative linkage disequilibrium between deleterious alleles and, therefore, an underdispersed distribution of the number of deleterious alleles in the genome. Indeed, we detected underdispersion of the number of rare loss-of-function alleles in eight independent data sets from human and fly populations. Thus, selection against rare protein-disrupting alleles is characterized by synergistic epistasis, which may explain how human and fly populations persist despite high genomic mutation rates.

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Dispersals and genetic adaptation of Bantu-speaking populations in Africa and North America

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Bantu languages are spoken by about 310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1318 individuals from 35 populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with local populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Impact of cytosine methylation on DNA binding specificities of human transcription factors

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.

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Self-organized Notch dynamics generate stereotyped sensory organ patterns in Drosophila

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The emergence of spatial patterns in developing multicellular organisms relies on positional cues and cell-cell communication. Drosophila sensory organs have informed a paradigm in which these operate in two distinct steps: Prepattern factors drive localized proneural activity, then Notch-mediated lateral inhibition singles out neural precursors. Here we show that self-organization through Notch signaling also establishes the proneural stripes that resolve into rows of sensory bristles on the fly thorax. Patterning, initiated by a gradient of Delta ligand expression, progresses through inhibitory signaling between and within stripes. Thus, Notch signaling can support self-organized tissue patterning as a prepattern is transduced by cell-cell interactions into a refined arrangement of cellular fates.

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Academia under fire in Hungary

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Pinpointing HIV spread in Africa poses risks

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Who will watch the Amazon?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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In a first, natural selection defeats a biocontrol insect

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Newest member of human family is surprisingly young

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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China cracks down on coastal fisheries

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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NIH to cap grants for well-funded investigators

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Fears of Ebola resurgence quickly dispelled in Liberia

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Where have all the insects gone?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Myriad take two: Can genomic databases remain secret?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Biodefense in the 21st century

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Faulty logic

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Personalized printing for human health

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Shipping iron around in small packages

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Intricacy anchored by uranium

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mapping the world's dry forests

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Cancer immunotherapy according to GARP

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Humans have a good sense of smell

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Maximizing growth by sharing

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A more pathological amyloid-{beta} oligomer

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Tug of war with anti-PD-1

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Disrupting housefly gene reverses sex

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Macrophages feel the heart beat

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Targeting senescence to combat osteoarthritis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Crop resistance to parasites

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Selection acts on the neighbors

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Multiple human diseases ensue from a hereditary or acquired deficiency of iron-transporting protein function that diminishes transmembrane iron flux in distinct sites and directions. Because other iron-transport proteins remain active, labile iron gradients build up across the corresponding protein-deficient membranes. Here we report that a small-molecule natural product, hinokitiol, can harness such gradients to restore iron transport into, within, and/or out of cells. The same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin-deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient zebrafish. These findings illuminate a general mechanistic framework for small molecule–mediated site- and direction-selective restoration of iron transport. They also suggest that small molecules that partially mimic the function of missing protein transporters of iron, and possibly other ions, may have potential in treating human diseases.

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Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The integration of endocytic routes is critical to regulate receptor signaling. A nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor (EGFR) is activated at high ligand concentrations and targets receptors to degradation, attenuating signaling. Here we performed an unbiased molecular characterization of EGFR-NCE. We identified NCE-specific regulators, including the endoplasmic reticulum (ER)–resident protein reticulon 3 (RTN3) and a specific cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)–ER contact sites that were required for the formation and/or maturation of NCE invaginations. Ca²⁺ release at these sites, triggered by inositol 1,4,5-trisphosphate (IP3)–dependent activation of ER Ca²⁺ channels, was needed for the completion of EGFR internalization. Thus, we identified a mechanism of EGFR endocytosis that relies on ER-PM contact sites and local Ca²⁺ signaling.

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Holliday junction resolvases mediate chloroplast nucleoid segregation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Holliday junctions, four-stranded DNA structures formed during homologous recombination, are disentangled by resolvases that have been found in prokaryotes and eukaryotes but not in plant organelles. Here, we identify monokaryotic chloroplast 1 (MOC1) as a Holliday junction resolvase in chloroplasts by analyzing a green alga Chlamydomonas reinhardtii mutant defective in chloroplast nucleoid (DNA-protein complex) segregation. MOC1 is structurally similar to a bacterial Holliday junction resolvase, resistance to ultraviolet (Ruv) C, and genetically conserved among green plants. Reduced or no expression of MOC1 in Arabidopsis thaliana leads to growth defects and aberrant chloroplast nucleoid segregation. In vitro biochemical analysis and high-speed atomic force microscopic analysis revealed that A. thaliana MOC 1 (AtMOC1) binds and cleaves the core of Holliday junctions symmetrically. MOC1 may mediate chloroplast nucleoid segregation in green plants by resolving Holliday junctions.

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Coupling between distant biofilms and emergence of nutrient time-sharing

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Bacteria within communities can interact to organize their behavior. It has been unclear whether such interactions can extend beyond a single community to coordinate the behavior of distant populations. We discovered that two Bacillus subtilis biofilm communities undergoing metabolic oscillations can become coupled through electrical signaling and synchronize their growth dynamics. Coupling increases competition by also synchronizing demand for limited nutrients. As predicted by mathematical modeling, we confirm that biofilms resolve this conflict by switching from in-phase to antiphase oscillations. This results in time-sharing behavior, where each community takes turns consuming nutrients. Time-sharing enables biofilms to counterintuitively increase growth under reduced nutrient supply. Distant biofilms can thus coordinate their behavior to resolve nutrient competition through time-sharing, a strategy used in engineered systems to allocate limited resources.

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Male sex in houseflies is determined by Mdmd, a paralog of the generic splice factor gene CWC22

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Across species, animals have diverse sex determination pathways, each consisting of a hierarchical cascade of genes and its associated regulatory mechanism. Houseflies have a distinctive polymorphic sex determination system in which a dominant male determiner, the M-factor, can reside on any of the chromosomes. We identified a gene, Musca domestica male determiner (Mdmd), as the M-factor. Mdmd originated from a duplication of the spliceosomal factor gene CWC22 (nucampholin). Targeted Mdmd disruption results in complete sex reversal to fertile females because of a shift from male to female expression of the downstream genes transformer and doublesex. The presence of Mdmd on different chromosomes indicates that Mdmd translocated to different genomic sites. Thus, an instructive signal in sex determination can arise by duplication and neofunctionalization of an essential splicing regulator.

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Big data, big picture: Metabolomics meets systems biology

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Webinar | Generating CRISPR mouse models: Challenges and solutions

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Lucking into science

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Visualizing dynamic microvillar search and stabilization during ligand detection by T cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

During immune surveillance, T cells survey the surface of antigen-presenting cells. In searching for peptide-loaded major histocompatibility complexes (pMHCs), they must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on T cells act as sensory organs to enable search, but their strategy has been unknown. We used lattice light-sheet and quantum dot–enabled synaptic contact mapping microscopy to show that anomalous diffusion and fractal organization of microvilli survey the majority of opposing surfaces within 1 minute. Individual dwell times were long enough to discriminate pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized microvilli. Stabilization was independent of tyrosine kinase signaling and the actin cytoskeleton, suggesting selection for avid TCR microclusters. This work defines the efficient cellular search process against which ligand detection takes place.

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Poor human olfaction is a 19th-century myth

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

It is commonly believed that humans have a poor sense of smell compared to other mammalian species. However, this idea derives not from empirical studies of human olfaction but from a famous 19th-century anatomist’s hypothesis that the evolution of human free will required a reduction in the proportional size of the brain’s olfactory bulb. The human olfactory bulb is actually quite large in absolute terms and contains a similar number of neurons to that of other mammals. Moreover, humans have excellent olfactory abilities. We can detect and discriminate an extraordinary range of odors, we are more sensitive than rodents and dogs for some odors, we are capable of tracking odor trails, and our behavioral and affective states are influenced by our sense of smell.

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Migration--the choices we face

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Sea trash traps face doubts

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Genome writing project confronts technology hurdles

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Island extinctions weren't inevitable

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Busting myths of origin

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The pain of exile

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Battling bias

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Introducing ORCID

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A mobility boost for research

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Private strategy, public policy

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Countering European brain drain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mismatched supply and demand

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Immigrant patents boost growth

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Reservoir of foreign talent

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Migration today: Displaced scientists

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Nitrogen pollution knows no bounds

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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ATP controls the crowd

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Repulsive behavior in germinal centers

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Multiscale measurements for materials modeling

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Defining the topography of a planetary body

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Chew on this

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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ATP boosts protein solubility

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Drying natural gas efficiently

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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River systems reveal planetary tectonics

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Blocking somatic genes to make sperm

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A brain region for social cognition

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Why antioxidants do not prevent preeclampsia

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Taking HIV to the gut

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Guiding immune cells to the center

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Watching defects in heated thin films

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A brainy treatment for heart failure

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Neural crest rules the gut

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Just one drop will do it

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mom tells virus what to do

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Genes and BMI conspire to make fatty liver

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mutualists endow certain appetites

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Research experience is not just for students

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

To selectively express cell type–specific transcripts during development, it is critical to maintain genes required for other lineages in a silent state. Here, we show in the Drosophila male germline stem cell lineage that a spermatocyte-specific zinc finger protein, Kumgang (Kmg), working with the chromatin remodeler dMi-2 prevents transcription of genes normally expressed only in somatic lineages. By blocking transcription from normally cryptic promoters, Kmg restricts activation by Aly, a component of the testis-meiotic arrest complex, to transcripts for male germ cell differentiation. Our results suggest that as new regions of the genome become open for transcription during terminal differentiation, blocking the action of a promiscuous activator on cryptic promoters is a critical mechanism for specifying precise gene activation.

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Lineage-dependent spatial and functional organization of the mammalian enteric nervous system

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The enteric nervous system (ENS) is essential for digestive function and gut homeostasis. Here we show that the amorphous neuroglia networks of the mouse ENS are composed of overlapping clonal units founded by postmigratory neural crest–derived progenitors. The spatial configuration of ENS clones depends on proliferation-driven local interactions of ENS progenitors with lineally unrelated neuroectodermal cells, the ordered colonization of the serosa-mucosa axis by clonal descendants, and gut expansion. Single-cell transcriptomics and mutagenesis analysis delineated dynamic molecular states of ENS progenitors and identified RET as a regulator of neurogenic commitment. Clonally related enteric neurons exhibit synchronous activity in response to network stimulation. Thus, lineage relationships underpin the organization of the peripheral nervous system.

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Higher predation risk for insect prey at low latitudes and elevations

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Biotic interactions underlie ecosystem structure and function, but predicting interaction outcomes is difficult. We tested the hypothesis that biotic interaction strength increases toward the equator, using a global experiment with model caterpillars to measure predation risk. Across an 11,660-kilometer latitudinal gradient spanning six continents, we found increasing predation toward the equator, with a parallel pattern of increasing predation toward lower elevations. Patterns across both latitude and elevation were driven by arthropod predators, with no systematic trend in attack rates by birds or mammals. These matching gradients at global and regional scales suggest consistent drivers of biotic interaction strength, a finding that needs to be integrated into general theories of herbivory, community organization, and life-history evolution.

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A dedicated network for social interaction processing in the primate brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Primate cognition requires interaction processing. Interactions can reveal otherwise hidden properties of intentional agents, such as thoughts and feelings, and of inanimate objects, such as mass and material. Where and how interaction analyses are implemented in the brain is unknown. Using whole-brain functional magnetic resonance imaging in macaque monkeys, we discovered a network centered in the medial and ventrolateral prefrontal cortex that is exclusively engaged in social interaction analysis. Exclusivity of specialization was found for no other function anywhere in the brain. Two additional networks, a parieto-premotor and a temporal one, exhibited both social and physical interaction preference, which, in the temporal lobe, mapped onto a fine-grain pattern of object, body, and face selectivity. Extent and location of a dedicated system for social interaction analysis suggest that this function is an evolutionary forerunner of human mind-reading capabilities.

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21st-century rise in anthropogenic nitrogen deposition on a remote coral reef

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

With the rapid rise in pollution-associated nitrogen inputs to the western Pacific, it has been suggested that even the open ocean has been affected. In a coral core from Dongsha Atoll, a remote coral reef ecosystem, we observe a decline in the ¹⁵N/¹⁴N of coral skeleton–bound organic matter, which signals increased deposition of anthropogenic atmospheric N on the open ocean and its incorporation into plankton and, in turn, the atoll corals. The first clear change occurred just before 2000 CE, decades later than predicted by other work. The amplitude of change suggests that, by 2010, anthropogenic atmospheric N deposition represented 20 ± 5% of the annual N input to the surface ocean in this region, which appears to be at the lower end of other estimates.

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ATP as a biological hydrotrope

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Hydrotropes are small molecules that solubilize hydrophobic molecules in aqueous solutions. Typically, hydrotropes are amphiphilic molecules and differ from classical surfactants in that they have low cooperativity of aggregation and work at molar concentrations. Here, we show that adenosine triphosphate (ATP) has properties of a biological hydrotrope. It can both prevent the formation of and dissolve previously formed protein aggregates. This chemical property is manifested at physiological concentrations between 5 and 10 millimolar. Therefore, in addition to being an energy source for biological reactions, for which micromolar concentrations are sufficient, we propose that millimolar concentrations of ATP may act to keep proteins soluble. This may in part explain why ATP is maintained in such high concentrations in cells.

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A placental growth factor is silenced in mouse embryos by the zinc finger protein ZFP568

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Insulin-like growth factor 2 (IGF2) is the major fetal growth hormone in mammals. We identify zinc finger protein 568 (ZFP568), a member of the rapidly evolving Kruppel-associated box–zinc finger protein (KRAB-ZFP) family linked primarily to silencing of endogenous retroelements, as a direct repressor of a placental-specific Igf2 transcript (designated Igf2-P0) in mice. Loss of Zfp568, which causes gastrulation failure, or mutation of the ZFP568-binding site at the Igf2-P0 promoter causes inappropriate Igf2-P0 activation. Deletion of Igf2 can completely rescue Zfp568 gastrulation phenotypes through late gestation. Our data highlight the exquisite selectivity with which members of the KRAB-ZFP family repress their targets and identify an additional layer of transcriptional control of a key growth factor regulating fetal and placental development.

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Mining microbes: Creating genomic tools to fight disease

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Three-dimensional Ca2+ imaging advances understanding of astrocyte biology

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Astrocyte communication is typically studied by two-dimensional calcium ion (Ca²⁺) imaging, but this method has not yielded conclusive data on the role of astrocytes in synaptic and vascular function. We developed a three-dimensional two-photon imaging approach and studied Ca²⁺ dynamics in entire astrocyte volumes, including during axon-astrocyte interactions. In both awake mice and brain slices, we found that Ca²⁺ activity in an individual astrocyte is scattered throughout the cell, largely compartmented between regions, preponderantly local within regions, and heterogeneously distributed regionally and locally. Processes and endfeet displayed frequent fast activity, whereas the soma was infrequently active. In awake mice, activity was higher than in brain slices, particularly in endfeet and processes, and displayed occasional multifocal cellwide events. Astrocytes responded locally to minimal axonal firing with time-correlated Ca²⁺ spots.

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Ephrin B1-mediated repulsion and signaling control germinal center T cell territoriality and function

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Follicular T helper (TFH) cells orchestrate the germinal center (GC) reaction locally. Local mechanisms regulating their dynamics and helper functions are not well defined. Here we found that GC-expressed ephrin B1 (EFNB1) repulsively inhibited T cell to B cell adhesion and GC TFH retention by signaling through TFH-expressed EPHB6 receptor. At the same time, EFNB1 promoted interleukin-21 production from GC TFH cells by signaling predominantly through EPHB4. Consequently, EFNB1-null GCs were associated with defective production of plasma cells despite harboring excessive TFH cells. In a competitive GC reaction, EFNB1-deficient B cells more efficiently interacted with TFH cells and produced more bone-marrow plasma cells, likely as a result of gaining more contact-dependent help. Our results reveal a contact-dependent repulsive guidance system that controls GC TFH dynamics and effector functions locally.

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SESAME and beyond

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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New Ebola outbreak rings alarm bells early

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Courts ponder how public animal reports must be

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The strange case of the orange petunias

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Strike disrupts research at Puerto Rico's top university

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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How the Himalayas primed the Indonesian tsunami

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Fossil power, guilt free

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Classical-quantum sensors keep better time

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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How to fight corruption

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Whole cell maps chart a course for 21st-century cell biology

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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High fidelity

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Built on Bones: 15,000 Years of Urban Life and Death

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Editorial retraction

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Brazil's public universities in crisis

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Genomic databases: A WHO affair

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Comment on "Dissolved organic sulfur in the ocean: Biogeochemistry of a petagram inventory"

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Ksionzek et al. (Reports, 28 October 2016, p. 456) provide important data describing the distribution of dissolved organic sulfur (DOS) in the Atlantic Ocean. Here, we show that mixing between water masses is sufficient to explain the observed distribution of DOS, concluding that the turnover time of refractory DOS that Ksionzek et al. present cannot be deduced from their data.

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Response to Comment on "Dissolved organic sulfur in the ocean: Biogeochemistry of a petagram inventory"

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Dittmar et al. proposed that mixing alone can explain our observed decrease in marine dissolved organic sulfur with age. However, their simple model lacks an explanation for the origin of sulfur-depleted organic matter in the deep ocean and cannot adequately reproduce our observed stoichiometric changes. Using radiocarbon age also implicitly models the preferential cycling of sulfur that they are disputing.

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Breaking down miRNAs

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Trapping RNA polymerase in the act

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mapping the proteome

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Flicking the Berry phase switch

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Who needs to know where species live?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Unintended victims of fighting corruption

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Creating a weakness in prostate cancer

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Risks of reef erosion

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Roadmaps for building the neonatal brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The NET effect of viral-triggered asthma

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Building a better mantle with BEAMS

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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PPR a risk to Europe

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Perovskite ferroelectric bond-switching

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Ring attractor dynamics in the Drosophila central brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Ring attractors are a class of recurrent networks hypothesized to underlie the representation of heading direction. Such network structures, schematized as a ring of neurons whose connectivity depends on their heading preferences, can sustain a bump-like activity pattern whose location can be updated by continuous shifts along either turn direction. We recently reported that a population of fly neurons represents the animal’s heading via bump-like activity dynamics. We combined two-photon calcium imaging in head-fixed flying flies with optogenetics to overwrite the existing population representation with an artificial one, which was then maintained by the circuit with naturalistic dynamics. A network with local excitation and global inhibition enforces this unique and persistent heading representation. Ring attractor networks have long been invoked in theoretical work; our study provides physiological evidence of their existence and functional architecture.

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Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The neuronal substrate for binge eating, which can at times lead to obesity, is not clear. We find that optogenetic stimulation of mouse zona incerta (ZI) -aminobutyric acid (GABA) neurons or their axonal projections to paraventricular thalamus (PVT) excitatory neurons immediately (in 2 to 3 seconds) evoked binge-like eating. Minimal intermittent stimulation led to body weight gain; ZI GABA neuron ablation reduced weight. ZI stimulation generated 35% of normal 24-hour food intake in just 10 minutes. The ZI cells were excited by food deprivation and the gut hunger signal ghrelin. In contrast, stimulation of excitatory axons from the parasubthalamic nucleus to PVT or direct stimulation of PVT glutamate neurons reduced food intake. These data suggest an unexpected robust orexigenic potential for the ZI GABA neurons.

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Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. The pathways that mediate mature miRNA decay are less well understood than those that mediate miRNA biogenesis. We found that functional miRNAs are degraded in human cells by the endonuclease Tudor-SN (TSN). In vitro, recombinant TSN initiated the decay of both protein-free and Argonaute 2–loaded miRNAs via endonucleolytic cleavage at CA and UA dinucleotides, preferentially at scissile bonds located more than five nucleotides away from miRNA ends. Cellular targets of TSN-mediated decay defined using microRNA sequencing followed this rule. Inhibiting TSN-mediated miRNA decay by CRISPR-Cas9 knockout of TSN inhibited cell cycle progression by up-regulating a cohort of miRNAs that down-regulates mRNAs that encode proteins critical for the G1-to-S phase transition. Our study indicates that targeting TSN nuclease activity could inhibit pathological cell proliferation.

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RNA polymerase motions during promoter melting

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

All cellular RNA polymerases (RNAPs), from those of bacteria to those of man, possess a clamp that can open and close, and it has been assumed that the open RNAP separates promoter DNA strands and then closes to establish a tight grip on the DNA template. Here, we resolve successive motions of the initiating bacterial RNAP by studying real-time signatures of fluorescent reporters placed on RNAP and DNA in the presence of ligands locking the clamp in distinct conformations. We report evidence for an unexpected and obligatory step early in the initiation involving a transient clamp closure as a prerequisite for DNA melting. We also present a 2.6-angstrom crystal structure of a late-initiation intermediate harboring a rotationally unconstrained downstream DNA duplex within the open RNAP active site cleft. Our findings explain how RNAP thermal motions control the promoter search and drive DNA melting in the absence of external energy sources.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Stressing mental health

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A subcellular map of the human proteome

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.

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Ancestral alliances: Plant mutualistic symbioses with fungi and bacteria

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Within the plant microbiota, mutualistic fungal and bacterial symbionts are striking examples of microorganisms playing crucial roles in nutrient acquisition. They have coevolved with their hosts since initial plant adaptation to land. Despite the evolutionary distances that separate mycorrhizal and nitrogen-fixing symbioses, these associations share a number of highly conserved features, including specific plant symbiotic signaling pathways, root colonization strategies that circumvent plant immune responses, functional host-microbe interface formation, and the central role of phytohormones in symbiosis-associated root developmental pathways. We highlight recent and emerging areas of investigation relating to these evolutionarily conserved mechanisms, with an emphasis on the more ancestral mycorrhizal associations, and consider to what extent this knowledge can contribute to an understanding of plant-microbiota associations as a whole.

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Erratum for the Research Article "Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15" by T. Han, M. Goralski, N. Gaskill, E. Capota, J. Kim, T. C. Ting, Y. Xie, N. S. Williams, D. Nijhawan

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Shortsighted priorities

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mysterious unchanging DNA finds a purpose in life

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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NIH overhead plan draws fire

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Egyptian mummy DNA, at last

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Siberia yields earliest evidence for dog breeding

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The post-op brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Bat patrol

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Decoding the evolution of species

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Gearing up molecular rotary motors

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A microbiome variable in the HIV-prevention equation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Applying plasmonics to a sustainable future

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Committing to socially responsible seafood

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Making the rounds

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Idiosyncratic desires

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The pet trade's role in defaunation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Sex matters: Report experimenter gender

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Chemical safety must extend to ecosystems

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Building coral skeletons

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A step on the path to a Lassa vaccine

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Entangle, swap, purify, repeat

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Vaginal microbiome influences HIV acquisition

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Human impacts on rainfall distribution

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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No escape for KRAS mutant tumors

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Detecting unusual oscillations

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Probing the structure of the magnetopause

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A versatile synthesis of pleuromutilin

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Differentiating myeloid cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Flexible geckos

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Arabidopsis out of Africa

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Structural basis for antibody-mediated neutralization of Lassa virus

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health.

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Biological control of aragonite formation in stony corals

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Little is known about how stony corals build their calcareous skeletons. There are two prevailing hypotheses: that it is a physicochemically dominated process and that it is a biologically mediated one. Using a combination of ultrahigh-resolution three-dimensional imaging and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy, we show that mineral deposition is biologically driven. Randomly arranged, amorphous nanoparticles are initially deposited in microenvironments enriched in organic material; they then aggregate and form ordered aragonitic structures through crystal growth by particle attachment. Our NMR results are consistent with heterogeneous nucleation of the solid mineral phase driven by coral acid-rich proteins. Such a mechanism suggests that stony corals may be able to sustain calcification even under lower pH conditions that do not favor the inorganic precipitation of aragonite.

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Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women. We investigated whether vaginal microbiota modulated tenofovir gel microbicide efficacy in the CAPRISA (Centre for the AIDS Program of Research in South Africa) 004 trial. Two major vaginal bacterial community types—one dominated by Lactobacillus (59.2%) and the other where Gardnerella vaginalis predominated with other anaerobic bacteria (40.8%)—were identified in 688 women profiled. Tenofovir reduced HIV incidence by 61% (P = 0.013) in Lactobacillus-dominant women but only 18% (P = 0.644) in women with non-Lactobacillus bacteria, a threefold difference in efficacy. Detectible mucosal tenofovir was lower in non-Lactobacillus women, negatively correlating with G. vaginalis and other anaerobic bacteria, which depleted tenofovir by metabolism more rapidly than target cells convert to pharmacologically active drug. This study provides evidence linking vaginal bacteria to microbicide efficacy through tenofovir depletion via bacterial metabolism.

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A modular and enantioselective synthesis of the pleuromutilin antibiotics

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The tricyclic diterpene fungal metabolite (+)-pleuromutilin has served as a starting point for antibiotic development. Semisynthetic modification of its glycolic acid subunit at C14 provided the first analogs fit for human use, and derivatization at C12 led to 12-epi-pleuromutilins with extended-spectrum antibacterial activity, including activity against Gram-negative pathogens. Given the inherent limitations of semisynthesis, however, accessing derivatives of (+)-pleuromutilin with full control over their structure presents an opportunity to develop derivatives with improved antibacterial activities. Here we disclose a modular synthesis of pleuromutilins by the convergent union of an enimide with a bifunctional iodoether. We illustrate our approach through synthesis of (+)-12-epi-mutilin, (+)-11,12-di-epi-mutilin, (+)-12-epi-pleuromutilin, (+)-11,12-di-epi-pleuromutilin, and (+)-pleuromutilin itself in 17 to 20 steps.

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mTORC1 activity repression by late endosomal phosphatidylinositol 3,4-bisphosphate

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Nutrient sensing by mechanistic target of rapamycin complex 1 (mTORC1) on lysosomes and late endosomes (LyLEs) regulates cell growth. Many factors stimulate mTORC1 activity, including the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] by class I phosphatidylinositol 3-kinases (PI3Ks) at the plasma membrane. We investigated mechanisms that repress mTORC1 under conditions of growth factor deprivation. We identified phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], synthesized by class II PI3K β (PI3KC2β) at LyLEs, as a negative regulator of mTORC1, whereas loss of PI3KC2β hyperactivated mTORC1. Growth factor deprivation induced the association of PI3KC2β with the Raptor subunit of mTORC1. Local PI(3,4)P2 synthesis triggered repression of mTORC1 activity through association of Raptor with inhibitory 14-3-3 proteins. These results unravel an unexpected function for local PI(3,4)P2 production in shutting off mTORC1.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Webinar | Monitoring immune function by imaging flow cytometry

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A genetic signature of the evolution of loss of flight in the Galapagos cormorant

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

We have a limited understanding of the genetic and molecular basis of evolutionary changes in the size and proportion of limbs. We studied wing and pectoral skeleton reduction leading to flightlessness in the Galapagos cormorant (Phalacrocorax harrisi). We sequenced and de novo assembled the genomes of four cormorant species and applied a predictive and comparative genomics approach to find candidate variants that may have contributed to the evolution of flightlessness. These analyses and cross-species experiments in Caenorhabditis elegans and in chondrogenic cell lines implicated variants in genes necessary for transcriptional regulation and function of the primary cilium. Cilia are essential for Hedgehog signaling, and humans affected by skeletal ciliopathies suffer from premature bone growth arrest, mirroring skeletal features associated with loss of flight.

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Erratum for the Letter "Brazil's public universities in crisis" by C. C. Siqueira and C. F. D. Rocha

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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The dishonest HONEST Act

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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News at a glance

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Oldest members of our species discovered in Morocco

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Romanian researchers decry sudden power grab

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Circular DNA throws biologists for a loop

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Data Check: Critics challenge NIH finding that bigger labs aren't necessarily better

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Rethinking the dreaded r-word

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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India resurrects forgotten leprosy vaccine

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Can U.S. states and cities overcome Paris exit?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Saving the 'God of ugly things

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Science reads for the summer of '17

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Nanomaterials for stimulating nerve growth

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Poisons, antidotes, and selfish genes

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Specific repair by discerning macrophages

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Fund global health: Save lives and money

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Minority investigators lack NIH funding

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Repair and Regeneration

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Self-repairing cells: How single cells heal membrane ruptures and restore lost structures

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Many organisms and tissues display the ability to heal and regenerate as needed for normal physiology and as a result of pathogenesis. However, these repair activities can also be observed at the single-cell level. The physical and molecular mechanisms by which a cell can heal membrane ruptures and rebuild damaged or missing cellular structures remain poorly understood. This Review presents current understanding in wound healing and regeneration as two distinct aspects of cellular self-repair by examining a few model organisms that have displayed robust repair capacity, including Xenopus oocytes, Chlamydomonas, and Stentor coeruleus. Although many open questions remain, elucidating how cells repair themselves is important for our mechanistic understanding of cell biology. It also holds the potential for new applications and therapeutic approaches for treating human disease.

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Inflammation and metabolism in tissue repair and regeneration

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Tissue repair after injury is a complex, metabolically demanding process. Depending on the tissue’s regenerative capacity and the quality of the inflammatory response, the outcome is generally imperfect, with some degree of fibrosis, which is defined by aberrant accumulation of collagenous connective tissue. Inflammatory cells multitask at the wound site by facilitating wound debridement and producing chemokines, metabolites, and growth factors. If this well-orchestrated response becomes dysregulated, the wound can become chronic or progressively fibrotic, with both outcomes impairing tissue function, which can ultimately lead to organ failure and death. Here we review the current understanding of the role of inflammation and cell metabolism in tissue-regenerative responses, highlight emerging concepts that may expand therapeutic perspectives, and briefly discuss where important knowledge gaps remain.

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Regenerating optic pathways from the eye to the brain

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Humans are highly visual. Retinal ganglion cells (RGCs), the neurons that connect the eyes to the brain, fail to regenerate after damage, eventually leading to blindness. Here, we review research on regeneration and repair of the optic system. Intrinsic developmental growth programs can be reactivated in RGCs, neural activity can enhance RGC regeneration, and functional reformation of eye-to-brain connections is possible, even in the adult brain. Transplantation and gene therapy may serve to replace or resurrect dead or injured retinal neurons. Retinal prosthetics that can restore vision in animal models may too have practical power in the clinical setting. Functional restoration of sight in certain forms of blindness is likely to occur in human patients in the near future.

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Cardiac regeneration strategies: Staying young at heart

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The human heart is continually operating as a muscular pump, contracting, on average, 80 times per minute to propel 8000 liters of blood through body tissues each day. Whereas damaged skeletal muscle has a profound capacity to regenerate, heart muscle, at least in mammals, has poor regenerative potential. This deficiency is attributable to the lack of resident cardiac stem cells, combined with roadblocks that limit adult cardiomyocytes from entering the cell cycle and completing division. Insights for regeneration have recently emerged from studies of animals with an elevated innate capacity for regeneration, the innovation of stem cell and reprogramming technologies, and a clearer understanding of the cardiomyocyte genetic program and key extrinsic signals. Methods to augment heart regeneration now have potential to counteract the high morbidity and mortality of cardiovascular disease.

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Why radiation causes dry mouth

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Designing molecular disorder

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Local macrophage clean-up

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A clue to a drug's neurotoxicity?

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Plasmodium leftovers cause bone loss

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Bacterial sensing mechanism revealed

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Tracing development of the dendritic cell lineage

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Swapping boron acids for carbon acids

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Selfish genetic interactions in nematodes

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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General relativity weighs a white dwarf

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Moving beyond mice for vaccine studies

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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From glassy carbon to mixed carbon

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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DNA damage linked to fitness loss in aging

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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HIV reprograms progenitor cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Down to the guts of climate change

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A learning environment designed for experts

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Old cancer drugs with a modern mechanism

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A checkup on density functional theory

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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A maternal-effect selfish genetic element in Caenorhabditis elegans

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Selfish genetic elements spread in natural populations and have an important role in genome evolution. We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode Caenorhabditis elegans. The element is made up of sup-35, a maternal-effect toxin that kills developing embryos, and pha-1, its zygotically expressed antidote. pha-1 has long been considered essential for pharynx development on the basis of its mutant phenotype, but this phenotype arises from a loss of suppression of sup-35 toxicity. Inactive copies of the sup-35/pha-1 element show high sequence divergence from active copies, and phylogenetic reconstruction suggests that they represent ancestral stages in the evolution of the element. Our results suggest that other essential genes identified by genetic screens may turn out to be components of selfish elements.

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Palladium-catalyzed carbon-sulfur or carbon-phosphorus bond metathesis by reversible arylation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Compounds bearing aryl-sulfur and aryl-phosphorus bonds have found numerous applications in drug development, organic materials, polymer science, and homogeneous catalysis. We describe palladium-catalyzed metathesis reactions of both compound classes, each of which proceeds through a reversible arylation manifold. The synthetic power and immediate utility of this approach are demonstrated in several applications that would be challenging to achieve by means of traditional cross-coupling methods. The C(sp²)–S bond metathesis protocol was used in the depolymerization of a commercial thermoplastic polymer and in the late-stage derivatization of a drug. The C(sp²)–P variant led to the convenient preparation of a variety of phosphorus heterocycles, including a potential chiral ligand and fluorescent organic materials, via a ring-closing transformation.

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Polymeric peptide pigments with sequence-encoded properties

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization of catecholic small molecules, the physical properties of melanins are influenced by covalent and noncovalent disorder. We report the use of tyrosine-containing tripeptides as tunable precursors for polymeric pigments. In these structures, phenols are presented in a (supra-)molecular context dictated by the positions of the amino acids in the peptide sequence. Oxidative polymerization can be tuned in a sequence-dependent manner, resulting in peptide sequence–encoded properties such as UV absorbance, morphology, coloration, and electrochemical properties over a considerable range. Short peptides have low barriers to application and can be easily scaled, suggesting near-term applications in cosmetics and biomedicine.

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Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)– and IL-13–dependent host responses during helminth infection. Here we show that IL-4 or IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory and tissue repair genes in the lungs after helminth infection or in the gut after induction of colitis. By contrast, the recognition of apoptotic cells was dispensable for cytokine-dependent induction of pattern recognition receptor, cell adhesion, or chemotaxis genes in macrophages. Detection of apoptotic cells can therefore spatially compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble cytokines such as IL-4 or IL-13.

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Local amplifiers of IL-4R{alpha}-mediated macrophage activation promote repair in lung and liver

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of type 2–mediated macrophage activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL-4)–dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth. In the peritoneal cavity and liver, C1q enhancement of type 2 macrophage activation was required for liver repair after bacterial infection, but resulted in fibrosis after peritoneal dialysis. IL-4 drives production of these structurally related defense collagens, SP-A and C1q, and the expression of their receptor, myosin 18A. These findings reveal the existence within different tissues of an amplification system needed for local type 2 responses.

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PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Recruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long noncoding RNAs. Here, we show that the noncanonical Polycomb group RING finger 3/5 (PCGF3/5)–PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA expression. PCGF3/5–PRC1–mediated ubiquitylation of histone H2A signals recruitment of other noncanonical PRC1 complexes and of PRC2, the latter leading to deposition of histone H3 lysine 27 methylation chromosome-wide. Pcgf3/5 gene knockout results in female-specific embryo lethality and abrogates Xist-mediated gene repression, highlighting a key role for Polycomb in Xist-dependent chromosome silencing. Our findings overturn existing models for Polycomb recruitment by Xist RNA and establish precedence for H2AK119u1 in initiating Polycomb domain formation in a physiological context.

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Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

A recent phase 1 trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474 led to the death of one volunteer and produced mild-to-severe neurological symptoms in four others. Although the cause of the clinical neurotoxicity is unknown, it has been postulated, given the clinical safety profile of other tested FAAH inhibitors, that off-target activities of BIA 10-2474 may have played a role. Here we use activity-based proteomic methods to determine the protein interaction landscape of BIA 10-2474 in human cells and tissues. This analysis revealed that the drug inhibits several lipases that are not targeted by PF04457845, a highly selective and clinically tested FAAH inhibitor. BIA 10-2474, but not PF04457845, produced substantial alterations in lipid networks in human cortical neurons, suggesting that promiscuous lipase inhibitors have the potential to cause metabolic dysregulation in the nervous system.

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New Products

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Research on a razor's edge

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Mapping the human DC lineage through the integration of high-dimensional techniques

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here, we combine two high-dimensional technologies—single-cell messenger RNA sequencing (scmRNAseq) and cytometry by time-of-flight (CyTOF)—to identify human blood CD123⁺CD33⁺CD45RA⁺ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed subpopulations, including one early uncommitted CD123^high pre-DC subset and two CD45RA⁺CD123^low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.

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Mechanism of transmembrane signaling by sensor histidine kinases

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

One of the major and essential classes of transmembrane (TM) receptors, present in all domains of life, is sensor histidine kinases, parts of two-component signaling systems (TCSs). The structural mechanisms of TM signaling by these sensors are poorly understood. We present crystal structures of the periplasmic sensor domain, the TM domain, and the cytoplasmic HAMP domain of the Escherichia coli nitrate/nitrite sensor histidine kinase NarQ in the ligand-bound and mutated ligand-free states. The structures reveal that the ligand binding induces rearrangements and pistonlike shifts of TM helices. The HAMP domain protomers undergo leverlike motions and convert these pistonlike motions into helical rotations. Our findings provide the structural framework for complete understanding of TM TCS signaling and for development of antimicrobial treatments targeting TCSs.

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Decarboxylative borylation

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

The widespread use of alkyl boronic acids and esters is frequently hampered by the challenges associated with their preparation. We describe a simple and practical method to rapidly access densely functionalized alkyl boronate esters from abundant carboxylic substituents. This broad-scope nickel-catalyzed reaction uses the same activating principle as amide bond formation to replace a carboxylic acid moiety with a boronate ester. Application to peptides allowed expedient preparations of α-amino boronic acids, often with high stereoselectivity, thereby facilitating synthesis of the alkyl boronic acid drugs Velcade and Ninlaro as well as a boronic acid version of the iconic antibiotic vancomycin. The reaction also enabled the discovery and extensive biological characterization of potent human neutrophil elastase inhibitors, which offer reversible covalent binding properties.

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

ScienceNOW - Posted: January 1st, 1970, 2:00am UTC

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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Erratum for the Report "A nontoxic pain killer designed by modeling of pathological receptor conformations" by V. Spahn, G. Del Vecchio, D. Labuz, A. Rodriguez-Gaztelumendi, N. Massaly, J. Temp, V. Durmaz, P. Sabri, M. Reidelbach, H. Machelska, M. Weber,

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