Act for science
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Act for scienceRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
News at a glanceRead more
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From a tweet, a March for Science is born
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
From a tweet, a March for Science is bornRead more
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Grad students, postdocs with U.S. visas face uncertainty
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Grad students, postdocs with U.S. visas face uncertaintyRead more
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World's most endangered marine mammal down to 30
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
World's most endangered marine mammal down to 30Read more
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New Zealand's endemic dolphins are hanging by a thread
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
New Zealand's endemic dolphins are hanging by a threadRead more
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Why are grizzlies dying on Canada's railway tracks?
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Why are grizzlies dying on Canada's railway tracks?Read more
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Rules of evidence
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Rules of evidenceRead more
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Politics vs. data on needle swaps
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Politics vs. data on needle swapsRead more
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Clear findings, smoggy debate
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Clear findings, smoggy debateRead more
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No easy answers
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
No easy answersRead more
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Putting the brakes on highway deaths
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Putting the brakes on highway deathsRead more
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A simple recipe for saving lives
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
A simple recipe for saving livesRead more
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Genetic divide
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Genetic divideRead more
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How to be heard
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
How to be heardRead more
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Data for all?
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Data for all?Read more
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Science advice in the Trump White House
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Science advice in the Trump White HouseRead more
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Finding enzymes in the gut metagenome
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Finding enzymes in the gut metagenomeRead more
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TZAP or not to zap telomeres
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
TZAP or not to zap telomeresRead more
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Mobile elements control stem cell potency
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Mobile elements control stem cell potencyRead more
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Flipping nanoscopy on its head
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Flipping nanoscopy on its headRead more
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Measurement error and the replication crisis
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Measurement error and the replication crisisRead more
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M. G. K. Menon (1928-2016)
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
M. G. K. Menon (1928-2016)Read more
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Convergence: The future of health
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Convergence: The future of healthRead more
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Precaution: Open gene drive research
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Precaution: Open gene drive researchRead more
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Precaution: Risks of public participation
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Precaution: Risks of public participationRead more
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What drives divergence?
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
What drives divergence?Read more
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Double trouble for the Deccan Traps
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Double trouble for the Deccan TrapsRead more
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Robustness of protein networks
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Robustness of protein networksRead more
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Intraneuronal control of protein expression
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Intraneuronal control of protein expressionRead more
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A target for intracranial aneurysms
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
A target for intracranial aneurysmsRead more
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Starving the pathogen
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Starving the pathogenRead more
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Transitional approach to entanglement
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Transitional approach to entanglementRead more
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A protein to trim too-long telomeres
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
A protein to trim too-long telomeresRead more
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A radical idea for blood pressure control
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
A radical idea for blood pressure controlRead more
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Change for good
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Change for goodRead more
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Superresolution imaging in sharper focus
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Superresolution imaging in sharper focusRead more
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Chemically guided functional profiling
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Chemically guided functional profilingRead more
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Targeting proteins at the other sulfur
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Targeting proteins at the other sulfurRead more
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Multifunctional displays
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Multifunctional displaysRead more
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Regrow like an axolotl
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Regrow like an axolotlRead more
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Interfering with bad cholesterol
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Interfering with bad cholesterolRead more
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Gluing up hemagglutinin
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Gluing up hemagglutininRead more
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Child growth sensitivity to rainfall variability
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Child growth sensitivity to rainfall variabilityRead more
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Fluorine frolicking with eight friends
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Fluorine frolicking with eight friendsRead more
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Skills to pay the bills?
ScienceNOW - Posted: January 1st, 1970, 3:00am UTC
Skills to pay the bills?Read more
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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
New ProductsRead more
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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
The science-policy interfaceRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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London's biomedical behemoth opens its doors
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
London's biomedical behemoth opens its doorsRead more
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A painstaking overhaul for cardiac safety testing
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A painstaking overhaul for cardiac safety testingRead more
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Duke fraud case highlights financial risks for universities
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Duke fraud case highlights financial risks for universitiesRead more
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Mentoring's moment
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mentoring's momentRead more
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Tumors set time
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Tumors set timeRead more
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Effects of a warming Arctic
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Effects of a warming ArcticRead more
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Induced pluripotent stem cells, past and future
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Induced pluripotent stem cells, past and futureRead more
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The great debate
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The great debateRead more
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Coordinate efforts on EU invasive species
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Coordinate efforts on EU invasive speciesRead more
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USGS scientists open to change
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
USGS scientists open to changeRead more
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Rescued wildlife in China remains at risk
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Rescued wildlife in China remains at riskRead more
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Language representation in the dog brain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Language representation in the dog brainRead more
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Discerning dengue vaccine protection
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Discerning dengue vaccine protectionRead more
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Signposts for synapses
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Signposts for synapsesRead more
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How antibodies protect against HIV-1
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
How antibodies protect against HIV-1Read more
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Divergent responses, same receptor
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Divergent responses, same receptorRead more
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Copper-catalyzed radical relay
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Copper-catalyzed radical relayRead more
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Warm Arctic--cold continents?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Warm Arctic--cold continents?Read more
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Strontium's loss is iridium's gain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Strontium's loss is iridium's gainRead more
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Hormone clearance and morphogenesis in plants
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Hormone clearance and morphogenesis in plantsRead more
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Genetic underpinnings of atrial fibrillation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Genetic underpinnings of atrial fibrillationRead more
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Targeting just one of two C-H bonds
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Targeting just one of two C-H bondsRead more
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Just passing through
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Just passing throughRead more
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Drinking water--and what else?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Drinking water--and what else?Read more
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Mechanical coupling of heart cells
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mechanical coupling of heart cellsRead more
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Pacemaker cells for insulin release
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Pacemaker cells for insulin releaseRead more
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Measuring impacts of technology on growth
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Measuring impacts of technology on growthRead more
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Brain mapping by barcode
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Brain mapping by barcodeRead more
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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
New ProductsRead more
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Research integrity revisited
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Research integrity revisitedRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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Why the rest of the world is marching
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Why the rest of the world is marchingRead more
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Personalized tumor vaccines keep cancer in check
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Personalized tumor vaccines keep cancer in checkRead more
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U.S. report calls for research integrity board
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
U.S. report calls for research integrity boardRead more
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Epidemic Insurance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Epidemic InsuranceRead more
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Detecting molecular hydrogen on Enceladus
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Detecting molecular hydrogen on EnceladusRead more
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Allotropy by design--Carbon nanohoops
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Allotropy by design--Carbon nanohoopsRead more
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Eating ecosystems
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Eating ecosystemsRead more
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Embryogenesis in a dish
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Embryogenesis in a dishRead more
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Managing cell and human identity
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Managing cell and human identityRead more
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Embracing the unqualified opinion
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Embracing the unqualified opinionRead more
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A river runs through it
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A river runs through itRead more
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After Chile's fires, reforest private land
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
After Chile's fires, reforest private landRead more
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Targeting nonviral antigens in viral-driven cancer
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Targeting nonviral antigens in viral-driven cancerRead more
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Transporter layers for greater stability
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Transporter layers for greater stabilityRead more
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One antibody for all and all antibodies for one
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
One antibody for all and all antibodies for oneRead more
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Quantifying hunting-induced defaunation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Quantifying hunting-induced defaunationRead more
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A target for preventing kidney damage
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A target for preventing kidney damageRead more
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The negative impact of EU enlargement
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The negative impact of EU enlargementRead more
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Stitching one alkyl group to another
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Stitching one alkyl group to anotherRead more
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In vitro embryogenesis
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
In vitro embryogenesisRead more
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Machines learn what people know implicitly
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Machines learn what people know implicitlyRead more
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Making an unbiased library
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Making an unbiased libraryRead more
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Coupling transcription and translation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Coupling transcription and translationRead more
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The evolving Ebola virus host response
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The evolving Ebola virus host responseRead more
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Regulatory T cells sans FoxP3
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Regulatory T cells sans FoxP3Read more
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Near and far effects on gene expression
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Near and far effects on gene expressionRead more
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TB exploits zombie cells
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
TB exploits zombie cellsRead more
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Protectin and resolvin gut inflammation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Protectin and resolvin gut inflammationRead more
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Smashing ions to test a theory
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Smashing ions to test a theoryRead more
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YAP is crucial for lung branching morphogenesis
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
YAP is crucial for lung branching morphogenesisRead more
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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
New ProductsRead more
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Webinar | Translational applications in exosome research: From biomarker discovery to drug delivery
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Webinar | Translational applications in exosome research: From biomarker discovery to drug deliveryRead more
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Skiing for science
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Skiing for scienceRead more
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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
News at a glanceRead more
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Early animal fossils at risk
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Early animal fossils at riskRead more
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A new neglected crop: cannabis
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A new neglected crop: cannabisRead more
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Society labels harassment as research misconduct
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Society labels harassment as research misconductRead more
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Sam Ting's last tease
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Sam Ting's last teaseRead more
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Facilitating conservation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Facilitating conservationRead more
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Biased inheritance protects older bacteria from harm
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Biased inheritance protects older bacteria from harmRead more
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Decoding hormones for a stem cell niche
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Decoding hormones for a stem cell nicheRead more
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Culture clash
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Culture clashRead more
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Dramatizing Deepwater Horizon
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Dramatizing Deepwater HorizonRead more
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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
Losing its characterRead more
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Capturing chemokines in chronic wounds
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Capturing chemokines in chronic woundsRead more
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Multiple images of a type Ia supernova
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Multiple images of a type Ia supernovaRead more
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Gut anaerobes protect against pathogen invasion
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Gut anaerobes protect against pathogen invasionRead more
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Safe anaerobic metabolism
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Safe anaerobic metabolismRead more
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Ancestral legacy effects
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Ancestral legacy effectsRead more
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Micromanaging muscle cell fusion
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Micromanaging muscle cell fusionRead more
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Resident memory responses to cancer
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Resident memory responses to cancerRead more
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What's in a drop of blood?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
What's in a drop of blood?Read more
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Double duty for mammary stem cell niche
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Double duty for mammary stem cell nicheRead more
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Watching nanomaterials transform in time
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Watching nanomaterials transform in timeRead more
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Drug efflux machinery inherited asymmetrically
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Drug efflux machinery inherited asymmetricallyRead more
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A transcription factor drug for asthma
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A transcription factor drug for asthmaRead more
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Facilitating refuges
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Facilitating refugesRead more
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Countering chemo's effects on fertility
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Countering chemo's effects on fertilityRead more
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The physics of social butterflies
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The physics of social butterfliesRead more
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The eyes have it
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The eyes have itRead more
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Disordered proteins make a dynamic switch
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Disordered proteins make a dynamic switchRead more
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Nanostructured high-strength alloys
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Nanostructured high-strength alloysRead more
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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
New ProductsRead more
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The new tissue culture
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The new tissue cultureRead more
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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
Syria, slums, and health securityRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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Meet the science marchers
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Meet the science marchersRead more
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Claim of very early humans in Americas shocks researchers
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Claim of very early humans in Americas shocks researchersRead more
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In surprise, tooth decay afflicts hunter-gatherers
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
In surprise, tooth decay afflicts hunter-gatherersRead more
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DNA from cave soil reveals ancient human occupants
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
DNA from cave soil reveals ancient human occupantsRead more
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The vaccine wars
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The vaccine warsRead more
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The science of persuasion
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The science of persuasionRead more
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Vaccine myths
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Vaccine mythsRead more
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Vaccines on trial
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Vaccines on trialRead more
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The natural capital of city trees
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The natural capital of city treesRead more
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Linking stem cells to germ cells
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Linking stem cells to germ cellsRead more
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Extracting the contents of living cells
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Extracting the contents of living cellsRead more
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H. Boyd Woodruff (1917-2017)
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
H. Boyd Woodruff (1917-2017)Read more
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Documenting decline in U.S. economic mobility
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Documenting decline in U.S. economic mobilityRead more
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A state of denial
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A state of denialRead more
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Scienceblind: Why Our Intuitive Theories About the World Are So Often Wrong
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Scienceblind: Why Our Intuitive Theories About the World Are So Often WrongRead more
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Mexico's invasive species plan in context
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mexico's invasive species plan in contextRead more
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Community network for deaf scientists
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Community network for deaf scientistsRead more
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Nature's treasure hunt
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Nature's treasure huntRead more
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S&T Policy Forum examines evolving opioid epidemic
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
S&T Policy Forum examines evolving opioid epidemicRead more
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Forum's fight for science
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Forum's fight for scienceRead more
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Aspiring to do better than one's parents
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Aspiring to do better than one's parentsRead more
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Pattern formation in the brain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Pattern formation in the brainRead more
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Getting phosphorus into healthy shape
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Getting phosphorus into healthy shapeRead more
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Taking a look at fungal bioluminescence
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Taking a look at fungal bioluminescenceRead more
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Imaging an atomic soliton train
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Imaging an atomic soliton trainRead more
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Zinc can compete with lithium
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Zinc can compete with lithiumRead more
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Sensitive and specific CRISPR diagnostics
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Sensitive and specific CRISPR diagnosticsRead more
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Thinking local about building
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Thinking local about buildingRead more
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Single-cell diversity in the brain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Single-cell diversity in the brainRead more
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Germ cells on demand
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Germ cells on demandRead more
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An old cancer drug's degrading new look
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
An old cancer drug's degrading new lookRead more
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Using quasar pairs to measure smoothness
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Using quasar pairs to measure smoothnessRead more
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Plant the right tree
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Plant the right treeRead more
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Interferon-independent antiviral defense
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Interferon-independent antiviral defenseRead more
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Liver T cells in obesity-associated diabetes
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Liver T cells in obesity-associated diabetesRead more
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The making of the human brain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The making of the human brainRead more
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Planning for a rise
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Planning for a riseRead more
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Delaying demise
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Delaying demiseRead more
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Virtues of splitting up water-splitting
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Virtues of splitting up water-splittingRead more
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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
New ProductsRead more
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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
Webinar | Getting the best data from your cells: From tissue culture to final analysisRead more
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Standing up to fear
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Standing up to fearRead more
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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
News at a glanceRead more
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New crop pest takes Africa at lightning speed
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
New crop pest takes Africa at lightning speedRead more
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Going green on the silver screen
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Going green on the silver screenRead more
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Beyond Hamilton's rule
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Beyond Hamilton's ruleRead more
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Surprising states of order for linear diblock copolymers
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Surprising states of order for linear diblock copolymersRead more
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Inflammation by way of macrophage metabolism
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Inflammation by way of macrophage metabolismRead more
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Transcription factors read epigenetics
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Transcription factors read epigeneticsRead more
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Thomas Earl Starzl (1926-2017)
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Thomas Earl Starzl (1926-2017)Read more
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Unmask temporal trade-offs in climate policy debates
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Unmask temporal trade-offs in climate policy debatesRead more
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A climate policy pathway for near- and long-term benefits
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A climate policy pathway for near- and long-term benefitsRead more
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Resetting the bar for graduate admissions
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Resetting the bar for graduate admissionsRead more
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The roadless dunes less traveled
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The roadless dunes less traveledRead more
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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
Artificial intelligence masters pokerRead more
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Shhh, you're disturbing the ecosystem
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Shhh, you're disturbing the ecosystemRead more
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On the history of Bantu speakers
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
On the history of Bantu speakersRead more
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A way to switch off IBD
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A way to switch off IBDRead more
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Give us our daily protein
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Give us our daily proteinRead more
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LAMP shines a light on Zika virus
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
LAMP shines a light on Zika virusRead more
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Finding drugs for fragile X syndrome
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Finding drugs for fragile X syndromeRead more
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When polymers behave like metals
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
When polymers behave like metalsRead more
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Wet, soft, squishy, and tunable
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Wet, soft, squishy, and tunableRead more
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Self-organization for sensory brushes
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Self-organization for sensory brushesRead more
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Positives and negatives of methylated CpG
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Positives and negatives of methylated CpGRead more
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Inducing DNA methylation where it wasn't
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Inducing DNA methylation where it wasn'tRead more
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Genetic interactions drive selection
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Genetic interactions drive selectionRead more
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Inter-innate cooperation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Inter-innate cooperationRead more
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Climate extremes stress ecosystems
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Climate extremes stress ecosystemsRead more
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RPE cranks it up a Notch
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
RPE cranks it up a NotchRead more
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The three-dimensional world in the brain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The three-dimensional world in the brainRead more
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Committees, candidates, and gender
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Committees, candidates, and genderRead more
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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
New ProductsRead more
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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
Academia under fire in HungaryRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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Pinpointing HIV spread in Africa poses risks
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Pinpointing HIV spread in Africa poses risksRead more
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Who will watch the Amazon?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Who will watch the Amazon?Read more
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In a first, natural selection defeats a biocontrol insect
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
In a first, natural selection defeats a biocontrol insectRead more
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Newest member of human family is surprisingly young
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Newest member of human family is surprisingly youngRead more
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China cracks down on coastal fisheries
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
China cracks down on coastal fisheriesRead more
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NIH to cap grants for well-funded investigators
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
NIH to cap grants for well-funded investigatorsRead more
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Fears of Ebola resurgence quickly dispelled in Liberia
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Fears of Ebola resurgence quickly dispelled in LiberiaRead more
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Where have all the insects gone?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Where have all the insects gone?Read more
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Myriad take two: Can genomic databases remain secret?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Myriad take two: Can genomic databases remain secret?Read more
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Biodefense in the 21st century
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Biodefense in the 21st centuryRead more
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Faulty logic
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Faulty logicRead more
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Personalized printing for human health
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Personalized printing for human healthRead more
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Shipping iron around in small packages
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Shipping iron around in small packagesRead more
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Intricacy anchored by uranium
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Intricacy anchored by uraniumRead more
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Mapping the world's dry forests
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mapping the world's dry forestsRead more
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Cancer immunotherapy according to GARP
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Cancer immunotherapy according to GARPRead more
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Humans have a good sense of smell
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Humans have a good sense of smellRead more
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Maximizing growth by sharing
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Maximizing growth by sharingRead more
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A more pathological amyloid-{beta} oligomer
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A more pathological amyloid-{beta} oligomerRead more
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Tug of war with anti-PD-1
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Tug of war with anti-PD-1Read more
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Disrupting housefly gene reverses sex
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Disrupting housefly gene reverses sexRead more
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Macrophages feel the heart beat
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Macrophages feel the heart beatRead more
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Targeting senescence to combat osteoarthritis
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Targeting senescence to combat osteoarthritisRead more
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Crop resistance to parasites
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Crop resistance to parasitesRead more
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Selection acts on the neighbors
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Selection acts on the neighborsRead more
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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
Big data, big picture: Metabolomics meets systems biologyRead more
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New Products
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
New ProductsRead more
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Webinar | Generating CRISPR mouse models: Challenges and solutions
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Webinar | Generating CRISPR mouse models: Challenges and solutionsRead more
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Lucking into science
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Lucking into scienceRead more
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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
Migration--the choices we faceRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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Sea trash traps face doubts
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Sea trash traps face doubtsRead more
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Genome writing project confronts technology hurdles
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Genome writing project confronts technology hurdlesRead more
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Island extinctions weren't inevitable
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Island extinctions weren't inevitableRead more
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Busting myths of origin
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Busting myths of originRead more
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The pain of exile
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The pain of exileRead more
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Battling bias
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Battling biasRead more
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Introducing ORCID
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Introducing ORCIDRead more
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A mobility boost for research
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A mobility boost for researchRead more
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Private strategy, public policy
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Private strategy, public policyRead more
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Countering European brain drain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Countering European brain drainRead more
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Mismatched supply and demand
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mismatched supply and demandRead more
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Immigrant patents boost growth
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Immigrant patents boost growthRead more
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Reservoir of foreign talent
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Reservoir of foreign talentRead more
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Migration today: Displaced scientists
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Migration today: Displaced scientistsRead more
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Nitrogen pollution knows no bounds
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Nitrogen pollution knows no boundsRead more
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ATP controls the crowd
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
ATP controls the crowdRead more
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Repulsive behavior in germinal centers
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Repulsive behavior in germinal centersRead more
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Multiscale measurements for materials modeling
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Multiscale measurements for materials modelingRead more
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Defining the topography of a planetary body
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Defining the topography of a planetary bodyRead more
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Chew on this
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Chew on thisRead more
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ATP boosts protein solubility
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
ATP boosts protein solubilityRead more
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Drying natural gas efficiently
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Drying natural gas efficientlyRead more
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River systems reveal planetary tectonics
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
River systems reveal planetary tectonicsRead more
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Blocking somatic genes to make sperm
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Blocking somatic genes to make spermRead more
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A brain region for social cognition
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A brain region for social cognitionRead more
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Why antioxidants do not prevent preeclampsia
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Why antioxidants do not prevent preeclampsiaRead more
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Taking HIV to the gut
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Taking HIV to the gutRead more
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Guiding immune cells to the center
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Guiding immune cells to the centerRead more
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Watching defects in heated thin films
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Watching defects in heated thin filmsRead more
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A brainy treatment for heart failure
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A brainy treatment for heart failureRead more
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Neural crest rules the gut
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Neural crest rules the gutRead more
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Just one drop will do it
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Just one drop will do itRead more
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Mom tells virus what to do
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mom tells virus what to doRead more
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Genes and BMI conspire to make fatty liver
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Genes and BMI conspire to make fatty liverRead more
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Mutualists endow certain appetites
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mutualists endow certain appetitesRead more
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Research experience is not just for students
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Research experience is not just for studentsRead more
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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
Mining microbes: Creating genomic tools to fight diseaseRead more
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New Products
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
New ProductsRead more
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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
SESAME and beyondRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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New Ebola outbreak rings alarm bells early
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
New Ebola outbreak rings alarm bells earlyRead more
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Courts ponder how public animal reports must be
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Courts ponder how public animal reports must beRead more
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The strange case of the orange petunias
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The strange case of the orange petuniasRead more
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Strike disrupts research at Puerto Rico's top university
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Strike disrupts research at Puerto Rico's top universityRead more
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How the Himalayas primed the Indonesian tsunami
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
How the Himalayas primed the Indonesian tsunamiRead more
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Fossil power, guilt free
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Fossil power, guilt freeRead more
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Classical-quantum sensors keep better time
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Classical-quantum sensors keep better timeRead more
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How to fight corruption
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
How to fight corruptionRead more
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Whole cell maps chart a course for 21st-century cell biology
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Whole cell maps chart a course for 21st-century cell biologyRead more
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High fidelity
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
High fidelityRead more
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Built on Bones: 15,000 Years of Urban Life and Death
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Built on Bones: 15,000 Years of Urban Life and DeathRead more
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Editorial retraction
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Editorial retractionRead more
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Brazil's public universities in crisis
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Brazil's public universities in crisisRead more
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Genomic databases: A WHO affair
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Genomic databases: A WHO affairRead more
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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
Breaking down miRNAsRead more
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Trapping RNA polymerase in the act
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Trapping RNA polymerase in the actRead more
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Mapping the proteome
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mapping the proteomeRead more
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Flicking the Berry phase switch
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Flicking the Berry phase switchRead more
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Who needs to know where species live?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Who needs to know where species live?Read more
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Unintended victims of fighting corruption
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Unintended victims of fighting corruptionRead more
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Creating a weakness in prostate cancer
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Creating a weakness in prostate cancerRead more
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Risks of reef erosion
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Risks of reef erosionRead more
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Roadmaps for building the neonatal brain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Roadmaps for building the neonatal brainRead more
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The NET effect of viral-triggered asthma
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The NET effect of viral-triggered asthmaRead more
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Building a better mantle with BEAMS
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Building a better mantle with BEAMSRead more
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PPR a risk to Europe
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
PPR a risk to EuropeRead more
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Perovskite ferroelectric bond-switching
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Perovskite ferroelectric bond-switchingRead more
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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
New ProductsRead more
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Stressing mental health
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Stressing mental healthRead more
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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
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. NijhawanRead more
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Shortsighted priorities
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Shortsighted prioritiesRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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Mysterious unchanging DNA finds a purpose in life
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Mysterious unchanging DNA finds a purpose in lifeRead more
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NIH overhead plan draws fire
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
NIH overhead plan draws fireRead more
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Egyptian mummy DNA, at last
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Egyptian mummy DNA, at lastRead more
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Siberia yields earliest evidence for dog breeding
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Siberia yields earliest evidence for dog breedingRead more
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The post-op brain
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The post-op brainRead more
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Bat patrol
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Bat patrolRead more
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Decoding the evolution of species
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Decoding the evolution of speciesRead more
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Gearing up molecular rotary motors
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Gearing up molecular rotary motorsRead more
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A microbiome variable in the HIV-prevention equation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A microbiome variable in the HIV-prevention equationRead more
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Applying plasmonics to a sustainable future
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Applying plasmonics to a sustainable futureRead more
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Committing to socially responsible seafood
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Committing to socially responsible seafoodRead more
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Making the rounds
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Making the roundsRead more
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Idiosyncratic desires
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Idiosyncratic desiresRead more
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The pet trade's role in defaunation
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The pet trade's role in defaunationRead more
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Sex matters: Report experimenter gender
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Sex matters: Report experimenter genderRead more
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Chemical safety must extend to ecosystems
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Chemical safety must extend to ecosystemsRead more
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Building coral skeletons
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Building coral skeletonsRead more
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A step on the path to a Lassa vaccine
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A step on the path to a Lassa vaccineRead more
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Entangle, swap, purify, repeat
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Entangle, swap, purify, repeatRead more
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Vaginal microbiome influences HIV acquisition
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Vaginal microbiome influences HIV acquisitionRead more
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Human impacts on rainfall distribution
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Human impacts on rainfall distributionRead more
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No escape for KRAS mutant tumors
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
No escape for KRAS mutant tumorsRead more
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Detecting unusual oscillations
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Detecting unusual oscillationsRead more
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Probing the structure of the magnetopause
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Probing the structure of the magnetopauseRead more
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A versatile synthesis of pleuromutilin
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A versatile synthesis of pleuromutilinRead more
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Differentiating myeloid cells
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Differentiating myeloid cellsRead more
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Flexible geckos
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Flexible geckosRead more
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Arabidopsis out of Africa
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Arabidopsis out of AfricaRead more
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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
New ProductsRead more
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Webinar | Monitoring immune function by imaging flow cytometry
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Webinar | Monitoring immune function by imaging flow cytometryRead more
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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
Erratum for the Letter "Brazil's public universities in crisis" by C. C. Siqueira and C. F. D. RochaRead more
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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
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,Read more
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The dishonest HONEST Act
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
The dishonest HONEST ActRead more
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News at a glance
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
News at a glanceRead more
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Oldest members of our species discovered in Morocco
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Oldest members of our species discovered in MoroccoRead more
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Romanian researchers decry sudden power grab
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Romanian researchers decry sudden power grabRead more
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Circular DNA throws biologists for a loop
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Circular DNA throws biologists for a loopRead more
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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
Data Check: Critics challenge NIH finding that bigger labs aren't necessarily betterRead more
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Rethinking the dreaded r-word
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Rethinking the dreaded r-wordRead more
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India resurrects forgotten leprosy vaccine
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
India resurrects forgotten leprosy vaccineRead more
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Can U.S. states and cities overcome Paris exit?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Can U.S. states and cities overcome Paris exit?Read more
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Saving the 'God of ugly things
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Saving the 'God of ugly thingsRead more
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Science reads for the summer of '17
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Science reads for the summer of '17Read more
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Nanomaterials for stimulating nerve growth
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Nanomaterials for stimulating nerve growthRead more
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Poisons, antidotes, and selfish genes
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Poisons, antidotes, and selfish genesRead more
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Specific repair by discerning macrophages
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Specific repair by discerning macrophagesRead more
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Fund global health: Save lives and money
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Fund global health: Save lives and moneyRead more
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Minority investigators lack NIH funding
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Minority investigators lack NIH fundingRead more
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Repair and Regeneration
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Repair and RegenerationRead more
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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
Why radiation causes dry mouthRead more
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Designing molecular disorder
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Designing molecular disorderRead more
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Local macrophage clean-up
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Local macrophage clean-upRead more
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A clue to a drug's neurotoxicity?
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A clue to a drug's neurotoxicity?Read more
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Plasmodium leftovers cause bone loss
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Plasmodium leftovers cause bone lossRead more
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Bacterial sensing mechanism revealed
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Bacterial sensing mechanism revealedRead more
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Tracing development of the dendritic cell lineage
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Tracing development of the dendritic cell lineageRead more
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Swapping boron acids for carbon acids
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Swapping boron acids for carbon acidsRead more
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Selfish genetic interactions in nematodes
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Selfish genetic interactions in nematodesRead more
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General relativity weighs a white dwarf
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
General relativity weighs a white dwarfRead more
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Moving beyond mice for vaccine studies
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Moving beyond mice for vaccine studiesRead more
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From glassy carbon to mixed carbon
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
From glassy carbon to mixed carbonRead more
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DNA damage linked to fitness loss in aging
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
DNA damage linked to fitness loss in agingRead more
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HIV reprograms progenitor cells
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
HIV reprograms progenitor cellsRead more
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Down to the guts of climate change
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Down to the guts of climate changeRead more
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A learning environment designed for experts
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A learning environment designed for expertsRead more
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Old cancer drugs with a modern mechanism
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Old cancer drugs with a modern mechanismRead more
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A checkup on density functional theory
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
A checkup on density functional theoryRead more
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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
New ProductsRead more
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Research on a razor's edge
ScienceNOW - Posted: January 1st, 1970, 2:00am UTC
Research on a razor's edgeRead more
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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 CD123high pre-DC subset and two CD45RA+CD123low 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.