Although sulfur is an essential element for marine primary production and critical for climate processes, little is known about the oceanic pool of nonvolatile dissolved organic sulfur (DOS). We present a basin-scale distribution of solid-phase extractable DOS in the East Atlantic Ocean and the Atlantic sector of the Southern Ocean. Although molar DOS versus dissolved organic nitrogen (DON) ratios of 0.11 ± 0.024 in Atlantic surface water resembled phytoplankton stoichiometry (sulfur/nitrogen ~ 0.08), increasing dissolved organic carbon (DOC) versus DOS ratios and decreasing methionine-S yield demonstrated selective DOS removal and active involvement in marine biogeochemical cycles. Based on stoichiometric estimates, the minimum global inventory of marine DOS is 6.7 petagrams of sulfur, exceeding all other marine organic sulfur reservoirs by an order of magnitude.
Authors: Kerstin B. Ksionzek, Oliver J. Lechtenfeld, S. Leigh McCallister, Philippe Schmitt-Kopplin, Jana K. Geuer, Walter Geibert, Boris P. Koch
Experience shapes the development and connectivity of adult-born granule cells (GCs) through mechanisms that are poorly understood. We examined the remodeling of dentate gyrus microcircuits in mice in an enriched environment (EE). Short exposure to EE during early development of new GCs accelerated their functional integration. This effect was mimicked by in vivo chemogenetic activation of a limited population of mature GCs. Slice recordings showed that mature GCs recruit parvalbumin γ-aminobutyric acid–releasing interneurons (PV-INs) that feed back onto developing GCs. Accordingly, chemogenetic stimulation of PV-INs or direct depolarization of developing GCs accelerated GC integration, whereas inactivation of PV-INs prevented the effects of EE. Our results reveal a mechanism for dynamic remodeling in which experience activates dentate networks that “prime” young GCs through a disynaptic feedback loop mediated by PV-INs.
Authors: Diego D. Alvarez, Damiana Giacomini, Sung Min Yang, Mariela F. Trinchero, Silvio G. Temprana, Karina A. Büttner, Natalia Beltramone, Alejandro F. Schinder
The United Nations Framework Convention on Climate Change Paris Agreement of December 2015 aims to maintain the global average warming well below 2°C above the preindustrial level. In the Mediterranean basin, recent pollen-based reconstructions of climate and ecosystem variability over the past 10,000 years provide insights regarding the implications of warming thresholds for biodiversity and land-use potential. We compare scenarios of climate-driven future change in land ecosystems with reconstructed ecosystem dynamics during the past 10,000 years. Only a 1.5°C warming scenario permits ecosystems to remain within the Holocene variability. At or above 2°C of warming, climatic change will generate Mediterranean land ecosystem changes that are unmatched in the Holocene, a period characterized by recurring precipitation deficits rather than temperature anomalies.
Authors: Joel Guiot, Wolfgang Cramer
The Xist long noncoding RNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing by recruiting the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the 3D structure of DNA, enabling Xist and its silencing proteins to spread across the X to silence transcription.
Authors: Chun-Kan Chen, Mario Blanco, Constanza Jackson, Erik Aznauryan, Noah Ollikainen, Christine Surka, Amy Chow, Andrea Cerase, Patrick McDonel, Mitchell Guttman
Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches to eliminate senescent cells in atherosclerosis-prone low-density lipoprotein receptor–deficient (Ldlr–/–) mice, we show that these cells are detrimental throughout disease pathogenesis. We find that foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis, where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. Together, these results demonstrate that senescent cells are key drivers of atheroma formation and maturation and suggest that selective clearance of these cells by senolytic agents holds promise for the treatment of atherosclerosis.
Authors: Bennett G. Childs, Darren J. Baker, Tobias Wijshake, Cheryl A. Conover, Judith Campisi, Jan M. van Deursen
Aerobic glycolysis (the Warburg effect) is a metabolic hallmark of activated T cells and has been implicated in augmenting effector T cell responses, including expression of the proinflammatory cytokine interferon-γ (IFN-γ), via 3′ untranslated region (3′UTR)–mediated mechanisms. Here, we show that lactate dehydrogenase A (LDHA) is induced in activated T cells to support aerobic glycolysis but promotes IFN-γ expression independently of its 3′UTR. Instead, LDHA maintains high concentrations of acetyl–coenzyme A to enhance histone acetylation and transcription of Ifng. Ablation of LDHA in T cells protects mice from immunopathology triggered by excessive IFN-γ expression or deficiency of regulatory T cells. These findings reveal an epigenetic mechanism by which aerobic glycolysis promotes effector T cell differentiation and suggest that LDHA may be targeted therapeutically in autoinflammatory diseases.
Authors: Min Peng, Na Yin, Sagar Chhangawala, Ke Xu, Christina S. Leslie, Ming O. Li
A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
As immuno-oncology takes center stage in the battle against cancer, the need for biomarkers has become even more acute, with response rates continuing in the 20%–30% range and the menu of options, including combination therapies, growing at an accelerating pace. The specific immunoarchitecture characteristics of the microenvironment in which a particular tumor grows may be both prognostic and predictive of response to these new immunotherapies. Multiplex immunofluorescence is the most effective, efficient way to identify specific immune cell types, their location, and their state of activation, as well as the presence of immunoactive molecular expression, all at the same time. This method is highly beneficial for exploring immune evasion mechanisms and finding potential biomarkers that allow researchers to assess the mechanism of action and predict and track response. This live, online seminar will take the viewer through validation of this multiplexing technique, including a comparison with singleplex immunofluorescence and standard (chromogenic) immunohistochemistry, as well as an assessment of intersite reproducibility and the influence of staining order on quantitation.View the Webinar
Authors: Janis Taube, Clifford Hoyt
Some species, such as the giraffe or bottlenose dolphin, are immediately recognizable and might seem immutable. In fact, their evolutionary stories are often more complicated. Regional populations of giraffe with distinct pelage patterns have only recently been recognized as four different species (1), and the number of species represented by what we recognize as the bottlenose dolphin was historically as many as 20, refined down to one, then two, and the question is still being resolved (2). On page 477 of this issue, de Manuel et al. (3) describe the relationship between two other iconic species in unprecedented detail, comparing whole genomes from populations of bonobo (Pan paniscus) and chimpanzee (Pan troglodytes). They report evidence for gene flow between these species, contributing to our increasing appreciation for the complexities of the process of speciation.
Author: A. Rus Hoelzel
Students learning about the eukaryotic cell are taught that mitochondria are the powerhouse of the cell, the nucleus is the information storehouse, and lysosomes are the garbage disposal. Summing up the role of the endoplasmic reticulum (ER) is more problematic, even for professional cell biologists. Classically, the ER is where membrane proteins, secreted proteins, and most lipids are synthesized. It is also the site of calcium regulation. More recent work shows that it is the site of antigen presentation by major histocompatibility complex class I molecules, and the location of the unfolded protein response, now thought to be central to several major diseases. A new frontier is its relationships with other organelles (1). On page 433 of this issue, Nixon-Abell et al. (2) describe how an armamentarium of superresolution imaging techniques reveals new aspects of the ER's very heterogeneous morphology. Indeed, the “form follows function” adage may help to make sense of this organelle's functional issues.
Author: Mark Terasaki
Marine microbes are the engines that drive global biogeochemical cycling in the oceans. They produce and cycle a dissolved organic matter (DOM) reservoir that is roughly as big as the atmospheric carbon dioxide pool (1). Interactions between DOM and marine microbes may also play a key role in the evolving climate through changes in remineralization rates (2). Historically, DOM has been thought of mainly in terms of its carbon, nitrogen, and phosphorus content. On page 456 of this issue, Ksionzek et al. (3) investigate the large pool of dissolved organic sulfur (DOS) compounds in the ocean and show that these compounds also play a key role in ocean biogeochemistry.
Author: Naomi M. Levine
We are all taught in biochemistry class that in the presence of oxygen, cells will use the tricarboxylic acid (TCA) cycle to efficiently generate adenosine 5′-triphosphate (ATP) via oxidative phosphorylation (OXPHOS). However, in 1924, the biochemist Otto Warburg observed that cancer cells do not follow this rule (1, 2). In fact, even in the presence of oxygen, cancer cells will depend on glycolysis (so-called aerobic glycolysis) to inefficiently generate ATP from glucose. More recently, there has been great interest in the observation that effector T cells will also use glycolysis to generate ATP in the presence of oxygen (3, 4). On page 481 of this issue, Peng et al. (5) make an important link between aerobic glycolysis and epigenetic regulation in T helper 1 (TH1) cell differentiation.
Authors: Chirag H. Patel, Jonathan D. Powell
For nearly three decades, the central goal in international climate policy had been to set the political agenda—to engage all countries on the need for action. So long as that was the goal, it was sufficient for policy-makers to focus on simple indicators of climate change, such as global average surface temperature With the 2015 Paris Agreement, governments launched a process that can move beyond setting agendas to coordinating national policies to manage the climate. Next month in Marrakesh, diplomats will convene to flesh out the Agreement. They need to focus on the infrastructure of data and analysis that will be needed as the Agreement becomes operational. The scientific community can help by identifying better lagging indicators to describe what has changed as policy efforts progress, and leading indicators to focus policy on the right risks as the planet warms.
Authors: Charles F. Kennel, Stephen Briggs, David G. Victor
Authors: Bin Yang, James R. Anderson, Peng Zhang, Baoguo Li
International experts on both sides share best methods for achieving evidence-informed policy
Author: Michaela Jarvis
[Association Affairs] AAAS Council reminder
Authors: Stella M. Hurtley, Valda Vinson
Author: Kristen L. Mueller
Author: Julia Fahrenkamp-Uppenbrink
Author: Beverly A. Purnell
In science news around the world, Kuwaiti leaders chose to revise a controversial law mandating DNA collection from all citizens and visitors, researchers at the National Cancer Institute in Bethesda, Maryland, admit they waited to report deaths in a cancer study, two major research institutes in California were set to merge, a researcher from the Pasteur Institute Korea breached French biosafety protocol by bringing samples of the Middle East respiratory virus on an airplane, and more. Also, researchers locate the faulty genetic switch that suppresses limb development in snakes. And Science chats with computational geneticist Yaniv Erlich of the New York Genome Center and Columbia University about his latest project, DNA.land, which aims to tap into the genetic data of up to 3 million people already tested by consumer genetic companies to make the information available to researchers.
Two research projects exploring the risks and benefits of sequencing every newborn baby's genome are now delivering early results, and both are giving pause to newborn-sequencing advocates. One suggests that exome sequencing, which reads the protein-coding regions of a genome, is not comprehensive enough to replace standard newborn blood screening for rare diseases. And the other finds that parents are surprisingly uninterested in having their newborns sequenced. A variety of reasons appear to account for the tepid response, including concerns about privacy and insurance discrimination. Together, the findings suggest newborn sequencing it not yet ready to replace existing screening programs, which rely on biochemical analysis of newborn blood spots to test for dozens of disorders.
Author: Jocelyn Kaiser
When world leaders reached a deal last month in Kigali to curb the use of hydrofluorocarbons (HFCs)—planet-warming chemicals widely used in air conditioners and refrigerators—many boasted the move would prevent nearly 0.5°C in warming by 2100. That is a big number, given that the Paris climate agreement commits nations to keeping the total global temperature increase to less than 2°C. If the HFC number is correct, it will make the Paris goal easier to achieve. But there's a bit more scientific uncertainty surrounding that half-degree claim than the politicians let on. And although scientists routinely acknowledge such uncertainty, "that's not what politicians do," says Durwood Zaelke, president of the Institute for Governance and Sustainable Development in Washington, D.C. Here's a look at how the half-degree figure was born, and what it might mean for the planet.
Author: Warren Cornwall
Last month, neuroscientist and psychiatrist Joshua Gordon, 49, took the helm of the National Institute of Mental Health (NIMH). Part of the U.S. National Institutes of Health, the $1.55 billion NIMH is the world's largest funder of mental health research. Its new director spent the last 19 years at Columbia University completing a psychiatry residency, studying mouse models of psychiatric disease, and, once a week, seeing anxious and depressed patients in his private practice. Now, Gordon faces challenges that include the complaints of clinical psychiatrists that NIMH is funding too much basic science research, shortchanging studies on existing treatments and services. Science sat down with Gordon last week.
Author: Meredith Wadman
In 2006, Magdalena Zernicka-Goetz was pregnant, unexpectedly, at age 42. A genetic test of the fetal portion of the placenta showed that roughly a third of the cells carried a serious abnormality: an extra copy of chromosome 2. The University of Cambridge in the United Kingdom professor's specialty, developmental biology, was suddenly personal. Nature could hardly have come up with a more vivid irony. Zernicka-Goetz is not only a developmental biologist; she has spent more than a decade working in mice to pinpoint when and how cells in an early embryo start to differentiate. Her child's health depended in part on a question that had already captivated her as a scientist, she recalls: How much flexibility does the developing embryo retain? While still pregnant and uncertain about her baby's fate, Zernicka-Goetz started mouse work that led to a paper this March revealing new details about embryos' remarkable ability to cope with faulty cells. In May, she caught the attention of other embryologists and the wider world with another demonstration of embryos' resilience. This time her lab showed—in concert with researchers in New York City—that human embryos created by in vitro fertilization could be kept developing in the lab for nearly 2 weeks, well past the point at which they would normally implant in the wall of the uterus. That's almost twice as long as previously achieved, and it opens the way to studying a key phase of human development that had been inaccessible. The feat has already sparked new ethical debates about limits to embryo research. Widely accepted international guidelines dictate that human embryos should not be allowed to develop longer than 14 days in culture, but some researchers are now pushing for that limit to be reconsidered.
Author: Gretchen Vogel
For a scientist found guilty of committing research misconduct, the most serious sanction the U.S. government can levy is a temporary ban on receiving a federal grant. Conventional wisdom holds that such a penalty, called debarment, is a death sentence for an academic researcher. Unable to receive federal funding and stigmatized by their unacceptable behavior, many debarred scientists quietly leave their university, much to their employers' relief. But that's not true for everyone. An investigation by Science has identified at least two dozen such researchers who have managed to resume productive academic research careers after being debarred. Their institutions have decided that rehabilitation is possible—and preferable to banishment. But little is known about the process, which takes place under a cone of silence meant to protect both the individual's privacy and the university's reputation.
Author: Jeffrey Mervis
Science faced a major obstacle when it set out to identify researchers barred from receiving government grants because of research misconduct. The problem: There is no government-wide registry of cases, and no common approach by the two agencies that police scientific misconduct. The Office of Research Integrity within the Department of Health and Human Services describes the cases of sanctioned researchers and the outcome on its website in the Federal Register, whereas the National Science Foundation redacts the name and all identifying features from its published summary of completed cases. At the same time, an obscure government website intended to prevent federal officials from inadvertently giving a grant or contract to someone who is ineligible provides a limited amount of information on those cases.
Author: Jeffrey Mervis
In July 1916, Swedish geologist Lennart von Post showed that by identifying and counting pollen preserved at different depths in Swedish peat bogs he could infer changes in forest composition through time (1–3). Following his pioneering work, pollen analysis quickly became established as a key tool for understanding past vegetation, climate, and ecosystems. Today, it is used widely to reconstruct past ecosystems and test hypotheses about drivers of ecosystem change.
Authors: H. John B. Birks, Hilary H. Birks, Brigitta Ammann
The endoplasmic reticulum (ER) is an expansive, membrane-enclosed organelle that plays crucial roles in numerous cellular functions. We used emerging superresolution imaging technologies to clarify the morphology and dynamics of the peripheral ER, which contacts and modulates most other intracellular organelles. Peripheral components of the ER have classically been described as comprising both tubules and flat sheets. We show that this system consists almost exclusively of tubules at varying densities, including structures that we term ER matrices. Conventional optical imaging technologies had led to misidentification of these structures as sheets because of the dense clustering of tubular junctions and a previously uncharacterized rapid form of ER motion. The existence of ER matrices explains previous confounding evidence that had indicated the occurrence of ER “sheet” proliferation after overexpression of tubular junction–forming proteins.
Authors: Jonathon Nixon-Abell, Christopher J. Obara, Aubrey V. Weigel, Dong Li, Wesley R. Legant, C. Shan Xu, H. Amalia Pasolli, Kirsten Harvey, Harald F. Hess, Eric Betzig, Craig Blackstone, Jennifer Lippincott-Schwartz
Cellular metabolic fluxes are determined by enzyme activities and metabolite abundances. Biochemical approaches reveal the impact of specific substrates or regulators on enzyme kinetics but do not capture the extent to which metabolite and enzyme concentrations vary across physiological states and, therefore, how cellular reactions are regulated. We measured enzyme and metabolite concentrations and metabolic fluxes across 25 steady-state yeast cultures. We then assessed the extent to which flux can be explained by a Michaelis-Menten relationship between enzyme, substrate, product, and potential regulator concentrations. This revealed three previously unrecognized instances of cross-pathway regulation, which we biochemically verified. One of these involved inhibition of pyruvate kinase by citrate, which accumulated and thereby curtailed glycolytic outflow in nitrogen-limited yeast. Overall, substrate concentrations were the strongest driver of the net rates of cellular metabolic reactions, with metabolite concentrations collectively having more than double the physiological impact of enzymes.
Authors: Sean R. Hackett, Vito R. T. Zanotelli, Wenxin Xu, Jonathan Goya, Junyoung O. Park, David H. Perlman, Patrick A. Gibney, David Botstein, John D. Storey, Joshua D. Rabinowitz
