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Preview: PNAS - RSS feed of Early Edition articles

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Proceedings of the National Academy of Sciences RSS feed -- Early Edition



 



Future urban land expansion and implications for global croplands [Sustainability Science]

2016-12-27T09:51:19-08:00

Urban expansion often occurs on croplands. However, there is little scientific understanding of how global patterns of future urban expansion will affect the world’s cultivated areas. Here, we combine spatially explicit projections of urban expansion with datasets on global croplands and crop yields. Our results show that urban expansion will...



Global urban signatures of phenotypic change in animal and plant populations [Sustainability Science]

2017-01-03T08:47:11-08:00

Humans challenge the phenotypic, genetic, and cultural makeup of species by affecting the fitness landscapes on which they evolve. Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change...



Urban sustainability in an age of enduring inequalities: Advancing theory and ecometrics for the 21st-century city [Perspectives]

2017-01-06T12:50:12-08:00

The environmental fragility of cities under advanced urbanization has motivated extensive efforts to promote the sustainability of urban ecosystems and physical infrastructures. Less attention has been devoted to neighborhood inequalities and fissures in the civic infrastructure that potentially challenge social sustainability and the capacity of cities to collectively address environmental...



Global scenarios of urban density and its impacts on building energy use through 2050 [Sustainability Science]

2017-01-09T12:10:28-08:00

Although the scale of impending urbanization is well-acknowledged, we have a limited understanding of how urban forms will change and what their impact will be on building energy use. Using both top-down and bottom-up approaches and scenarios, we examine building energy use for heating and cooling. Globally, the energy use...



Heterogeneity and scale of sustainable development in cities [Sustainability Science]

2017-05-01T12:09:28-07:00

Rapid worldwide urbanization is at once the main cause and, potentially, the main solution to global sustainable development challenges. The growth of cities is typically associated with increases in socioeconomic productivity, but it also creates strong inequalities. Despite a growing body of evidence characterizing these heterogeneities in developed urban areas,...



Solar thermochemical splitting of water to generate hydrogen [Perspectives]

2017-05-18T11:58:25-07:00

Solar photochemical means of splitting water (artificial photosynthesis) to generate hydrogen is emerging as a viable process. The solar thermochemical route also promises to be an attractive means of achieving this objective. In this paper we present different types of thermochemical cycles that one can use for the purpose. These...



Water is an active matrix of life for cell and molecular biology [Perspectives]

2017-06-07T12:43:37-07:00

Szent-Győrgi called water the “matrix of life” and claimed that there was no life without it. This statement is true, as far as we know, on our planet, but it is not clear whether it must hold throughout the cosmos. To evaluate that question requires a close consideration of the...



Dissecting and modeling zeaxanthin- and lutein-dependent nonphotochemical quenching in Arabidopsis thaliana [Plant Biology]

2017-06-26T11:48:21-07:00

Photosynthetic organisms use various photoprotective mechanisms to dissipate excess photoexcitation as heat in a process called nonphotochemical quenching (NPQ). Regulation of NPQ allows for a rapid response to changes in light intensity and in vascular plants, is primarily triggered by a pH gradient across the thylakoid membrane (∆pH). The response...



X-ray crystal structure of a reiterative transcription complex reveals an atypical RNA extension pathway [Biochemistry]

2017-06-26T11:48:24-07:00

Reiterative transcription is a noncanonical form of RNA synthesis in which a nucleotide specified by a single base in the DNA template is repetitively added to the nascent transcript. Here we determined the crystal structure of an RNA polymerase, the bacterial enzyme from Thermus thermophilus, engaged in reiterative transcription during...



Polymorphism at a mimicry supergene maintained by opposing frequency-dependent selection pressures [Evolution]

2017-07-03T11:45:37-07:00

Explaining the maintenance of adaptive diversity within populations is a long-standing goal in evolutionary biology, with important implications for conservation, medicine, and agriculture. Adaptation often leads to the fixation of beneficial alleles, and therefore it erodes local diversity so that understanding the coexistence of multiple adaptive phenotypes requires deciphering the...



Accurate age estimation in small-scale societies [Anthropology]

2017-07-10T11:44:27-07:00

Precise estimation of age is essential in evolutionary anthropology, especially to infer population age structures and understand the evolution of human life history diversity. However, in small-scale societies, such as hunter-gatherer populations, time is often not referred to in calendar years, and accurate age estimation remains a challenge. We address...



Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury [Neuroscience]

2017-07-10T11:44:29-07:00

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability, yet the mechanisms underlying the chronic cognitive deficits associated with TBI remain unknown. Consequently, there are no effective treatments for patients suffering from the long-lasting symptoms of TBI. Here, we show that TBI persistently activates the integrated stress...



Functional characterization of odorant receptors in the ponerine ant, Harpegnathos saltator [Evolution]

2017-07-10T11:44:31-07:00

Animals use a variety of sensory modalities—including visual, acoustic, and chemical—to sense their environment and interact with both conspecifics and other species. Such communication is especially critical in eusocial insects such as honey bees and ants, where cooperation is critical for survival and reproductive success. Various classes of chemoreceptors have...



Escherichia coli cytochrome c peroxidase is a respiratory oxidase that enables the use of hydrogen peroxide as a terminal electron acceptor [Microbiology]

2017-07-10T11:44:35-07:00

Microbial cytochrome c peroxidases (Ccp) have been studied for 75 years, but their physiological roles are unclear. Ccps are located in the periplasms of bacteria and the mitochondrial intermembrane spaces of fungi. In this study, Ccp is demonstrated to be a significant degrader of hydrogen peroxide in anoxic Escherichia coli....



Microscopic dynamics of charge separation at the aqueous electrochemical interface [Chemistry]

2017-07-11T09:36:45-07:00

We have used molecular simulation and methods of importance sampling to study the thermodynamics and kinetics of ionic charge separation at a liquid water–metal interface. We have considered this process using canonical examples of two different classes of ions: a simple alkali–halide pair, Na+I−, or classical ions, and the products...



A distinct subpopulation of CD25- T-follicular regulatory cells localizes in the germinal centers [Immunology and Inflammation]

2017-07-11T09:36:46-07:00

T-follicular helper (Tfh) cells differentiate through a multistep process, culminating in germinal center (GC) localized GC-Tfh cells that provide support to GC-B cells. T-follicular regulatory (Tfr) cells have critical roles in the control of Tfh cells and GC formation. Although Tfh-cell differentiation is inhibited by IL-2, regulatory T (Treg) cell...



Loss of clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways [Neuroscience]

2017-07-12T12:20:43-07:00

Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) peptide deposition in brain parenchyma as plaques and in cerebral blood vessels as cerebral amyloid angiopathy (CAA). CAA deposition leads to several clinical complications, including intracerebral hemorrhage. The underlying molecular mechanisms that regulate plaque and CAA deposition in the vast majority of...



On the promotion of human flourishing [Perspectives]

2017-07-13T11:22:58-07:00

Many empirical studies throughout the social and biomedical sciences focus only on very narrow outcomes such as income, or a single specific disease state, or a measure of positive affect. Human well-being or flourishing, however, consists in a much broader range of states and outcomes, certainly including mental and physical...



Reply to Skinnider and Magarvey: Rates of novel natural product discovery remain high [Letters (Online Only)]

2017-07-14T13:07:55-07:00

It is encouraging that our recent article examining trends in discovery rates and structural diversity for natural products (NP) (1) is generating discussion in this fascinating area (2). However, we wish to correct several misconceptions presented in the comments from Skinnider and Magarvey (3). Skinnider and Magarvey’s (3) letter incorrectly...



Statistical reanalysis of natural products reveals increasing chemical diversity [Letters (Online Only)]

2017-07-14T13:59:16-07:00

In their retrospective analysis of natural product (NP) discovery since the 1940s, Pye et al. (1) observe a gradual decline in the proportion of NPs discovered each year with low similarity to previously known compounds [defined by maximum Tanimoto coefficient (Tc) < 0.4]. Additionally, the authors report that the median...



Subunit conformational variation within individual GroEL oligomers resolved by Cryo-EM [Biophysics and Computational Biology]

2017-07-14T11:59:23-07:00

Single-particle electron cryo-microscopy (cryo-EM) is an emerging tool for resolving structures of conformationally heterogeneous particles; however, each structure is derived from an average of many particles with presumed identical conformations. We used a 3.5-Å cryo-EM reconstruction with imposed D7 symmetry to further analyze structural heterogeneity among chemically identical subunits in...



Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody [Biochemistry]

2017-07-17T12:04:00-07:00

Monoclonal antibodies provide an attractive alternative to small-molecule therapies for a wide range of diseases. Given the importance of G protein-coupled receptors (GPCRs) as pharmaceutical targets, there has been an immense interest in developing therapeutic monoclonal antibodies that act on GPCRs. Here we present the 3.0-Å resolution structure of a...



Structural determination of lipid antigens captured at the CD1d-T-cell receptor interface [Immunology and Inflammation]

2017-07-17T12:04:00-07:00

Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to...



Infants possess an abstract expectation of ingroup support [Psychological and Cognitive Sciences]

2017-07-17T12:04:00-07:00

One pervasive facet of human interactions is the tendency to favor ingroups over outgroups. Remarkably, this tendency has been observed even when individuals are assigned to minimal groups based on arbitrary markers. Why is mere categorization into a minimal group sufficient to elicit some degree of ingroup favoritism? We consider...



Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8{alpha}+ dendritic cells [Immunology and Inflammation]

2017-07-17T12:04:00-07:00

The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found...



Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate [Neuroscience]

2017-07-17T12:04:01-07:00

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders...



MitoNEET-dependent formation of intermitochondrial junctions [Cell Biology]

2017-07-17T12:04:01-07:00

MitoNEET (mNEET) is a dimeric mitochondrial outer membrane protein implicated in many facets of human pathophysiology, notably diabetes and cancer, but its molecular function remains poorly characterized. In this study, we generated and analyzed mNEET KO cells and found that in these cells the mitochondrial network was disturbed. Analysis of...



Virus found in a boreal lake links ssDNA and dsDNA viruses [Microbiology]

2017-07-17T12:04:01-07:00

Viruses have impacted the biosphere in numerous ways since the dawn of life. However, the evolution, genetic, structural, and taxonomic diversity of viruses remain poorly understood, in part because sparse sampling of the virosphere has concentrated mostly on exploring the abundance and diversity of dsDNA viruses. Furthermore, viral genomes are...



Sequential eviction of crowded nucleoprotein complexes by the exonuclease RecBCD molecular motor [Biophysics and Computational Biology]

2017-07-17T12:03:55-07:00

In physiological settings, all nucleic acids motor proteins must travel along substrates that are crowded with other proteins. However, the physical basis for how motor proteins behave in these highly crowded environments remains unknown. Here, we use real-time single-molecule imaging to determine how the ATP-dependent translocase RecBCD travels along DNA...



Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A [Medical Sciences]

2017-07-17T12:03:55-07:00

CD44 has been postulated as a cell surface coreceptor for augmenting receptor tyrosine kinase (RTK) signaling. However, how exactly CD44 triggers RTK-dependent signaling remained largely unclear. Here we report an unexpected mechanism by which the CD44s splice isoform is internalized into endosomes to attenuate EGFR degradation. We identify a CD44s-interacting...



Methylcytosine dioxygenase TET3 interacts with thyroid hormone nuclear receptors and stabilizes their association to chromatin [Biochemistry]

2017-07-17T12:03:55-07:00

Thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily that act as ligand-dependent transcription factors. Here we identified the ten-eleven translocation protein 3 (TET3) as a TR interacting protein increasing cell sensitivity to T3. The interaction between TET3 and TRs is independent of TET3 catalytic activity and...



Activation and synchronization of the oscillatory morphodynamics in multicellular monolayer [Biophysics and Computational Biology]

2017-07-17T12:03:56-07:00

Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant...



Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells [Medical Sciences]

2017-07-17T12:04:02-07:00

Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1−/−). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from...



Antibody-based assay discriminates Zika virus infection from other flaviviruses [Microbiology]

2017-07-17T12:04:02-07:00

Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation...



Metabolic profiles of exercise in patients with McArdle disease or mitochondrial myopathy [Physiology]

2017-07-17T12:04:02-07:00

McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically minimal,...



Prostaglandin dehydrogenase is a target for successful induction of cervical ripening [Physiology]

2017-07-17T12:04:03-07:00

The cervix represents a formidable structural barrier for successful induction of labor. Approximately 10% of pregnancies undergo induction of cervical ripening and labor with prostaglandin (PG) E2 or PGE analogs, often requiring many hours of hospitalization and monitoring. On the other hand, preterm cervical ripening in the second trimester predicts...



Genomic landscape of human diversity across Madagascar [Anthropology]

2017-07-17T12:04:03-07:00

Although situated ∼400 km from the east coast of Africa, Madagascar exhibits cultural, linguistic, and genetic traits from both Southeast Asia and Eastern Africa. The settlement history remains contentious; we therefore used a grid-based approach to sample at high resolution the genomic diversity (including maternal lineages, paternal lineages, and genome-wide...



Diverse continuum of CD4+ T-cell states is determined by hierarchical additive integration of cytokine signals [Systems Biology]

2017-07-17T12:04:03-07:00

During cell differentiation, progenitor cells integrate signals from their environment that guide their development into specialized phenotypes. The ways by which cells respond to complex signal combinations remain difficult to analyze and model. To gain additional insight into signal integration, we systematically mapped the response of CD4+ T cells to...



An invasive foundation species enhances multifunctionality in a coastal ecosystem [Sustainability Science]

2017-07-17T12:04:04-07:00

While invasive species often threaten biodiversity and human well-being, their potential to enhance functioning by offsetting the loss of native habitat has rarely been considered. We manipulated the abundance of the nonnative, habitat-forming seaweed Gracilaria vermiculophylla in large plots (25 m2) on southeastern US intertidal landscapes to assess impacts on...



Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS vs. FRET measurements [Biophysics and Computational Biology]

2017-07-17T12:04:04-07:00

Unfolded states of proteins and native states of intrinsically disordered proteins (IDPs) populate heterogeneous conformational ensembles in solution. The average sizes of these heterogeneous systems, quantified by the radius of gyration (RG), can be measured by small-angle X-ray scattering (SAXS). Another parameter, the mean dye-to-dye distance (RE) for proteins with...



VAMP3 and SNAP23 mediate the disturbed flow-induced endothelial microRNA secretion and smooth muscle hyperplasia [Cell Biology]

2017-07-17T12:04:04-07:00

Vascular endothelial cells (ECs) at arterial branches and curvatures experience disturbed blood flow and induce a quiescent-to-activated phenotypic transition of the adjacent smooth muscle cells (SMCs) and a subsequent smooth muscle hyperplasia. However, the mechanism underlying the flow pattern-specific initiation of EC-to-SMC signaling remains elusive. Our previous study demonstrated that...



Toll ligand Spatzle3 controls melanization in the stripe pattern formation in caterpillars [Genetics]

2017-07-17T12:04:04-07:00

A stripe pattern is an aposematic or camouflage coloration often observed among various caterpillars. However, how this ecologically important pattern is formed is largely unknown. The silkworm dominant mutant Zebra (Ze) has a black stripe in the anterior margin of each dorsal segment. Here, fine linkage mapping of 3,135 larvae...



Local destabilization, rigid body, and fuzzy docking facilitate the phosphorylation of the transcription factor Ets-1 by the mitogen-activated protein kinase ERK2 [Biochemistry]

2017-07-17T12:04:05-07:00

Mitogen-activated protein (MAP) kinase substrates are believed to require consensus docking motifs (D-site, F-site) to engage and facilitate efficient site-specific phosphorylation at specific serine/threonine-proline sequences by their cognate kinases. In contrast to other MAP kinase substrates, the transcription factor Ets-1 has no canonical docking motifs, yet it is efficiently phosphorylated...



Molecular mechanism of environmental d-xylose perception by a XylFII-LytS complex in bacteria [Biochemistry]

2017-07-17T12:04:05-07:00

d-xylose, the main building block of plant biomass, is a pentose sugar that can be used by bacteria as a carbon source for bio-based fuel and chemical production through fermentation. In bacteria, the first step for d-xylose metabolism is signal perception at the membrane. We previously identified a three-component system...



Insights into the red algae and eukaryotic evolution from the genome of Porphyra umbilicalis (Bangiophyceae, Rhodophyta) [Evolution]

2017-07-17T12:04:05-07:00

Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our...



Symmetry-related proton transfer pathways in respiratory complex I [Biophysics and Computational Biology]

2017-07-17T12:03:56-07:00

Complex I functions as the initial electron acceptor in aerobic respiratory chains of most organisms. This gigantic redox-driven enzyme employs the energy from quinone reduction to pump protons across its complete approximately 200-Å membrane domain, thermodynamically driving synthesis of ATP. Despite recently resolved structures from several species, the molecular mechanism...



Global analysis of depletion and recovery of seabed biota after bottom trawling disturbance [Sustainability Science]

2017-07-17T12:03:56-07:00

Bottom trawling is the most widespread human activity affecting seabed habitats. Here, we collate all available data for experimental and comparative studies of trawling impacts on whole communities of seabed macroinvertebrates on sedimentary habitats and develop widely applicable methods to estimate depletion and recovery rates of biota after trawling. Depletion...



Nuclear genomes distinguish cryptic species suggested by their DNA barcodes and ecology [Ecology]

2017-07-17T12:03:56-07:00

DNA sequencing brings another dimension to exploration of biodiversity, and large-scale mitochondrial DNA cytochrome oxidase I barcoding has exposed many potential new cryptic species. Here, we add complete nuclear genome sequencing to DNA barcoding, ecological distribution, natural history, and subtleties of adult color pattern and size to show that a...



Support for redistribution is shaped by compassion, envy, and self-interest, but not a taste for fairness [Psychological and Cognitive Sciences]

2017-07-17T12:03:57-07:00

Why do people support economic redistribution? Hypotheses include inequity aversion, a moral sense that inequality is intrinsically unfair, and cultural explanations such as exposure to and assimilation of culturally transmitted ideologies. However, humans have been interacting with worse-off and better-off individuals over evolutionary time, and our motivational systems may have...



Nitric oxide is an obligate bacterial nitrification intermediate produced by hydroxylamine oxidoreductase [Biochemistry]

2017-07-17T12:03:57-07:00

Ammonia (NH3)-oxidizing bacteria (AOB) emit substantial amounts of nitric oxide (NO) and nitrous oxide (N2O), both of which contribute to the harmful environmental side effects of large-scale agriculture. The currently accepted model for AOB metabolism involves NH3 oxidation to nitrite (NO2–) via a single obligate intermediate, hydroxylamine (NH2OH). Within this...



Conserved gene regulatory module specifies lateral neural borders across bilaterians [Developmental Biology]

2017-07-17T12:03:57-07:00

The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate...



Combining experimental and simulation data of molecular processes via augmented Markov models [Biophysics and Computational Biology]

2017-07-17T12:03:57-07:00

Accurate mechanistic description of structural changes in biomolecules is an increasingly important topic in structural and chemical biology. Markov models have emerged as a powerful way to approximate the molecular kinetics of large biomolecules while keeping full structural resolution in a divide-and-conquer fashion. However, the accuracy of these models is...



Body ownership determines the attenuation of self-generated tactile sensations [Psychological and Cognitive Sciences]

2017-07-17T12:03:58-07:00

Self-perception depends on the brain’s abilities to differentiate our body from the environment and to distinguish between the sensations generated as a consequence of voluntary movement and those arising from events in the external world. The first process refers to the sense of ownership of our body and relies on...



Cortical actin recovery at the immunological synapse leads to termination of lytic granule secretion in cytotoxic T lymphocytes [Immunology and Inflammation]

2017-07-17T12:03:58-07:00

CD8+ cytotoxic T lymphocytes (CTLs) eliminate virally infected cells through directed secretion of specialized lytic granules. Because a single CTL can kill multiple targets, degranulation must be tightly regulated. However, how CTLs regulate the termination of granule secretion remains unclear. Previous work demonstrated that centralized actin reduction at the immune...



Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice [Pharmacology]

2017-07-17T12:03:58-07:00

Sigma-1 antagonism potentiates the antinociceptive effects of opioid drugs, so sigma-1 receptors constitute a biological brake to opioid drug-induced analgesia. The pathophysiological role of this process is unknown. We aimed to investigate whether sigma-1 antagonism reduces inflammatory pain through the disinhibition of the endogenous opioidergic system in mice. The selective...



Severe viral respiratory infections in children with IFIH1 loss-of-function mutations [Genetics]

2017-07-17T12:03:58-07:00

Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome...



Bacterial infection imaging with [18F]fluoropropyl-trimethoprim [Medical Sciences]

2017-07-17T12:03:59-07:00

There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [18F]fluoropropyl-trimethoprim, or...



Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence [Neuroscience]

2017-07-17T12:03:59-07:00

Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD....



Dynamic responses of the adrenal steroidogenic regulatory network [Systems Biology]

2017-07-17T12:03:59-07:00

The hypothalamic–pituitary–adrenal axis is a dynamic system regulating glucocorticoid hormone synthesis in the adrenal glands. Many key factors within the adrenal steroidogenic pathway have been identified and studied, but little is known about how these factors function collectively as a dynamic network of interacting components. To investigate this, we developed...



Distinct requirements for energy metabolism in mouse primordial germ cells and their reprogramming to embryonic germ cells [Developmental Biology]

2017-07-17T12:04:06-07:00

Primordial germ cells (PGCs), undifferentiated embryonic germ cells, are the only cells that have the ability to become gametes and to reacquire totipotency upon fertilization. It is generally understood that the development of PGCs proceeds through the expression of germ cell-specific transcription factors and characteristic epigenomic changes. However, little is...



Reassessing the atmospheric oxidation mechanism of toluene [Earth, Atmospheric, and Planetary Sciences]

2017-07-17T12:04:06-07:00

Photochemical oxidation of aromatic hydrocarbons leads to tropospheric ozone and secondary organic aerosol (SOA) formation, with profound implications for air quality, human health, and climate. Toluene is the most abundant aromatic compound under urban environments, but its detailed chemical oxidation mechanism remains uncertain. From combined laboratory experiments and quantum chemical...



Cryptic oxygen cycling in anoxic marine zones [Environmental Sciences]

2017-07-17T12:04:06-07:00

Oxygen availability drives changes in microbial diversity and biogeochemical cycling between the aerobic surface layer and the anaerobic core in nitrite-rich anoxic marine zones (AMZs), which constitute huge oxygen-depleted regions in the tropical oceans. The current paradigm is that primary production and nitrification within the oxic surface layer fuel anaerobic...



Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland [Physiology]

2017-07-17T12:04:06-07:00

In wild mammals, offspring development must anticipate forthcoming metabolic demands and opportunities. Within species, different developmental strategies may be used, dependent on when in the year conception takes place. This phenotypic flexibility is initiated before birth and is linked to the pattern of day length (photoperiod) exposure experienced by the...



Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy [Immunology and Inflammation]

2017-07-17T12:04:07-07:00

In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with...



Potent competitive inhibition of human ribonucleotide reductase by a nonnucleoside small molecule [Biochemistry]

2017-07-17T12:04:07-07:00

Human ribonucleotide reductase (hRR) is crucial for DNA replication and maintenance of a balanced dNTP pool, and is an established cancer target. Nucleoside analogs such as gemcitabine diphosphate and clofarabine nucleotides target the large subunit (hRRM1) of hRR. These drugs have a poor therapeutic index due to toxicity caused by...



Evaluating optimal therapy robustness by virtual expansion of a sample population, with a case study in cancer immunotherapy [Applied Mathematics]

2017-07-17T12:04:07-07:00

Cancer is a highly heterogeneous disease, exhibiting spatial and temporal variations that pose challenges for designing robust therapies. Here, we propose the VEPART (Virtual Expansion of Populations for Analyzing Robustness of Therapies) technique as a platform that integrates experimental data, mathematical modeling, and statistical analyses for identifying robust optimal treatment...



Dynamic fluid connectivity during steady-state multiphase flow in a sandstone [Earth, Atmospheric, and Planetary Sciences]

2017-07-17T12:04:08-07:00

The current conceptual picture of steady-state multiphase Darcy flow in porous media is that the fluid phases organize into separate flow pathways with stable interfaces. Here we demonstrate a previously unobserved type of steady-state flow behavior, which we term “dynamic connectivity,” using fast pore-scale X-ray imaging. We image the flow...



Thermodynamic constraint on the depth of the global tropospheric circulation [Earth, Atmospheric, and Planetary Sciences]

2017-07-17T12:04:08-07:00

The troposphere is the region of the atmosphere characterized by low static stability, vigorous diabatic mixing, and widespread condensational heating in clouds. Previous research has argued that in the tropics, the upper bound on tropospheric mixing and clouds is constrained by the rapid decrease with height of the saturation water...



Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis [Immunology and Inflammation]

2017-07-18T08:23:53-07:00

Bacterial sepsis triggers robust activation of the complement system with subsequent generation of anaphylatoxins (C3a, C5a) and the terminal complement complex (TCC) that together contribute to organ failure and death. Here we tested the effect of RA101295, a 2-kDa macrocyclic peptide inhibitor of C5 cleavage, using in vitro whole-blood assays...



Catalysis and chemical mechanisms of calcite dissolution in seawater [Earth, Atmospheric, and Planetary Sciences]

2017-07-18T08:23:53-07:00

Near-equilibrium calcite dissolution in seawater contributes significantly to the regulation of atmospheric CO2 on 1,000-y timescales. Despite many studies on far-from-equilibrium dissolution, little is known about the detailed mechanisms responsible for calcite dissolution in seawater. In this paper, we dissolve 13C-labeled calcites in natural seawater. We show that the time-evolving...



Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth [Systems Biology]

2017-07-18T08:23:53-07:00

Cyanobacteria are an integral part of Earth’s biogeochemical cycles and a promising resource for the synthesis of renewable bioproducts from atmospheric CO2. Growth and metabolism of cyanobacteria are inherently tied to the diurnal rhythm of light availability. As yet, however, insight into the stoichiometric and energetic constraints of cyanobacterial diurnal...



Hitchhiking and epistasis give rise to cohort dynamics in adapting populations [Evolution]

2017-07-18T08:23:53-07:00

Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size...



De novo peptide sequencing by deep learning [Computer Sciences]

2017-07-18T08:23:54-07:00

De novo peptide sequencing from tandem MS data is the key technology in proteomics for the characterization of proteins, especially for new sequences, such as mAbs. In this study, we propose a deep neural network model, DeepNovo, for de novo peptide sequencing. DeepNovo architecture combines recent advances in convolutional neural...



Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain [Biochemistry]

2017-07-18T08:23:54-07:00

Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment...



Canopy structure drives orangutan habitat selection in disturbed Bornean forests [Ecology]

2017-07-18T08:23:54-07:00

The conservation of charismatic and functionally important large species is becoming increasingly difficult. Anthropogenic pressures continue to squeeze available habitat and force animals into degraded and disturbed areas. Ensuring the long-term survival of these species requires a well-developed understanding of how animals use these new landscapes to inform conservation and...



Cytosolic interaction of type III human CD38 with CIB1 modulates cellular cyclic ADP-ribose levels [Cell Biology]

2017-07-18T08:23:54-07:00

CD38 catalyzes the synthesis of the Ca2+ messenger, cyclic ADP-ribose (cADPR). It is generally considered to be a type II protein with the catalytic domain facing outside. How it can catalyze the synthesis of intracellular cADPR that targets the endoplasmic Ca2+ stores has not been resolved. We have proposed that...



Conceptual framework of the eco-physiological phases of insect diapause development justified by transcriptomic profiling [Applied Biological Sciences]

2017-07-18T08:23:54-07:00

Insects often overcome unfavorable seasons in a hormonally regulated state of diapause during which their activity ceases, development is arrested, metabolic rate is suppressed, and tolerance of environmental stress is bolstered. Diapausing insects pass through a stereotypic succession of eco-physiological phases termed “diapause development.” The phasing is varied in the...



Broadly expressed repressors integrate patterning across orthogonal axes in embryos [Developmental Biology]

2017-07-18T08:23:55-07:00

The role of spatially localized repressors in supporting embryonic patterning is well appreciated, but, alternatively, the role ubiquitously expressed repressors play in this process is not well understood. We investigated the function of two broadly expressed repressors, Runt (Run) and Suppressor of Hairless [Su(H)], in patterning the Drosophila embryo. Previous...



Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B [Biophysics and Computational Biology]

2017-07-18T08:23:55-07:00

Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they are often associated with diseases in humans. The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and in the development and progression of pancreatic cancer; however, the details of such functions are unknown. Polycomb proteins are involved in...



Reply to Le Pape et al.: Management is key to preventing marine extinctions [Letters (Online Only)]

2017-07-18T08:38:36-07:00

Our report (1) examines factors that maintain the profitability of harvesting a population as it declines. Without management, this can incentivize harvesting to extinction (2). Le Pape et al. (3) note that humans have not yet caused many marine extinctions, and argue that harvesting fish populations to complete extinction should...



Overfishing causes frequent fish population collapses but rare extinctions [Letters (Online Only)]

2017-07-18T08:47:44-07:00

Burgess et al.’s report in PNAS, “Range contraction enables harvesting to extinction” (1), provides a highly valuable perspective on the consequences of species range contractions that maintain local densities of declining populations. The authors suggest that this density-dependent contraction maintains local harvesting yields and economic incentives that enable depleted natural...



Effect of directional pulling on mechanical protein degradation by ATP-dependent proteolytic machines [Biochemistry]

2017-07-19T11:56:18-07:00

AAA+ proteases and remodeling machines couple hydrolysis of ATP to mechanical unfolding and translocation of proteins following recognition of sequence tags called degrons. Here, we use single-molecule optical trapping to determine the mechanochemistry of two AAA+ proteases, Escherichia coli ClpXP and ClpAP, as they unfold and translocate substrates containing multiple...



Nucleoredoxin guards against oxidative stress by protecting antioxidant enzymes [Plant Biology]

2017-07-19T11:56:18-07:00

Cellular accumulation of reactive oxygen species (ROS) is associated with a wide range of developmental and stress responses. Although cells have evolved to use ROS as signaling molecules, their chemically reactive nature also poses a threat. Antioxidant systems are required to detoxify ROS and prevent cellular damage, but little is...



BRCT-domain protein BRIT1 influences class switch recombination [Immunology and Inflammation]

2017-07-19T11:56:19-07:00

DNA double-strand breaks (DSBs) serve as obligatory intermediates for Ig heavy chain (Igh) class switch recombination (CSR). The mechanisms by which DSBs are resolved to promote long-range DNA end-joining while suppressing genomic instability inherently associated with DSBs are yet to be fully elucidated. Here, we use a targeted short-hairpin RNA...



Protein diversity in discrete structures at the distal tip of the trypanosome flagellum [Cell Biology]

2017-07-19T11:56:19-07:00

The distal end of the eukaryotic flagellum/cilium is important for axonemal growth and signaling and has distinct biomechanical properties. Specific flagellum tip structures exist, yet their composition, dynamics, and functions are largely unknown. We used biochemical approaches to identify seven constituents of the flagella connector at the tip of an...



Rainforest-initiated wet season onset over the southern Amazon [Environmental Sciences]

2017-07-20T11:25:41-07:00

Although it is well established that transpiration contributes much of the water for rainfall over Amazonia, it remains unclear whether transpiration helps to drive or merely responds to the seasonal cycle of rainfall. Here, we use multiple independent satellite datasets to show that rainforest transpiration enables an increase of shallow...



Functional selectivity for face processing in the temporal voice area of early deaf individuals [Psychological and Cognitive Sciences]

2017-06-26T11:48:21-07:00

Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here, we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in...



Diffusive dynamics during the high-to-low density transition in amorphous ice [Physics]

2017-06-26T11:48:34-07:00

Water exists in high- and low-density amorphous ice forms (HDA and LDA), which could correspond to the glassy states of high- (HDL) and low-density liquid (LDL) in the metastable part of the phase diagram. However, the nature of both the glass transition and the high-to-low-density transition are debated and new...



Bioinspired supramolecular fibers drawn from a multiphase self-assembled hydrogel [Chemistry]

2017-07-10T11:44:33-07:00

Inspired by biological systems, we report a supramolecular polymer–colloidal hydrogel (SPCH) composed of 98 wt % water that can be readily drawn into uniform (∼6-μm thick) “supramolecular fibers” at room temperature. Functionalized polymer-grafted silica nanoparticles, a semicrystalline hydroxyethyl cellulose derivative, and cucurbit[8]uril undergo aqueous self-assembly at multiple length scales to...



Designing toughness and strength for soft materials [Commentaries]

2017-07-21T12:50:23-07:00

Soft materials, such as hydrogels, elastomers, and plastics, are pervasive in nature and society. For example, except for teeth, nails, and bones, all other components of the human body are hydrogels, and we eat, wear, and use soft materials as foods, clothes, shoes, and car tires, just to name a...



Which way to low-density liquid water? [Commentaries]

2017-07-21T12:50:23-07:00

When rapidly cooled, a liquid undergoes dynamic arrest, forming an amorphous solid commonly called glass. Amorphous solids can also be created by different routes, for example by destabilizing the crystal structure at low temperature by applying pressure or intense radiation, or by depositing gas molecules on very cold substrates. Even...



Whether the hearing brain hears it or the deaf brain sees it, it’s ȷust the same [Commentaries]

2017-07-21T12:50:23-07:00

“Now that he’d remembered what he meant to tell her, he seemed to lose interest. She didn’t have to see his face to know this. It was in the air. It was in the pause that trailed from his remark of eight, ten, twelve seconds ago” (1). Lauren Hartke, Don...



Correction for Wu et al., Multiensemble Markov models of molecular thermodynamics and kinetics [Corrections]

2017-07-24T11:55:04-07:00

BIOPHYSICS AND COMPUTATIONAL BIOLOGY, CHEMISTRY Correction for “Multiensemble Markov models of molecular thermodynamics and kinetics,” by Hao Wu, Fabian Paul, Christoph Wehmeyer, and Frank Noé, which was first published May 25, 2016; 10.1073/pnas.1525092113 (Proc Natl Acad Sci USA 113:E3221–E3230). The authors note that the following statement should be added to...



Neural basis for hand muscle synergies in the primate spinal cord [Neuroscience]

2017-07-24T11:54:53-07:00

Grasping is a highly complex movement that requires the coordination of multiple hand joints and muscles. Muscle synergies have been proposed to be the functional building blocks that coordinate such complex motor behaviors, but little is known about how they are implemented in the central nervous system. Here we demonstrate...



PIF3 is a negative regulator of the CBF pathway and freezing tolerance in Arabidopsis [Plant Biology]

2017-07-24T11:54:54-07:00

Light and temperature are major environmental factors that coordinately control plant growth and survival. However, how plants integrate light and temperature signals to better adapt to environmental stresses is poorly understood. PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), a key transcription factor repressing photomorphogenesis, has been shown to play a pivotal role in...



Buying time promotes happiness [Social Sciences]

2017-07-24T11:54:54-07:00

Around the world, increases in wealth have produced an unintended consequence: a rising sense of time scarcity. We provide evidence that using money to buy time can provide a buffer against this time famine, thereby promoting happiness. Using large, diverse samples from the United States, Canada, Denmark, and The Netherlands...



Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development [Genetics]

2017-07-24T11:54:54-07:00

Ubiquitination, the crucial posttranslational modification that regulates the eukaryotic proteome, is carried out by a trio of enzymes, known as E1 [ubiquitin (Ub)-activating enzyme], E2 (Ub-conjugating enzyme), and E3 (Ub ligase). Although most E2s can work with any of the three mechanistically distinct classes of E3s, the E2 UBCH7 is...



BACE inhibition-dependent repair of Alzheimer’s pathophysiology [Neuroscience]

2017-07-24T11:54:55-07:00

Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral...



Effective intermediate-spin iron in O2-transporting heme proteins [Biophysics and Computational Biology]

2017-07-24T11:54:55-07:00

Proteins carrying an iron-porphyrin (heme) cofactor are essential for biological O2 management. The nature of Fe-O2 bonding in hemoproteins is debated for decades. We used energy-sampling and rapid-scan X-ray Kβ emission and K-edge absorption spectroscopy as well as quantum chemistry to determine molecular and electronic structures of unligated (deoxy), CO-inhibited...



Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance [Biochemistry]

2017-07-24T11:54:55-07:00

Relaxases are metal-dependent nucleases that break and join DNA for the initiation and completion of conjugative bacterial gene transfer. Conjugation is the main process through which antibiotic resistance spreads among bacteria, with multidrug-resistant staphylococci and streptococci infections posing major threats to human health. The MOBV family of relaxases accounts for...