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Preview: Proceedings of the National Academy of Sciences current issue

Proceedings of the National Academy of Sciences current issue



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In This Issue [This Week in PNAS]

2017-03-21T09:13:07-07:00

Enhanced vision may have enabled evolutionary shift from water to land Enlarged eyes may have aided vertebrates’ shift from water to land. The origin of limbs in the evolutionary foray of vertebrates from water to land has long claimed researchers’ interest, but the role of vision in this momentous transition,...



On the role of Mitofusin 2 in endoplasmic reticulum-mitochondria tethering [Biological Sciences]

2017-03-21T09:13:08-07:00

The recent paper by Naon et al. (1) claims that their new data “definitively” prove the role of Mitofusin 2 (Mfn2) as an endoplasmic reticulum (ER)–mitochondria tether, supporting their original proposal (2) and arguing against evidence presented by ourselves and others (3–6) suggesting that Mfn2 is a negative regulator of...



Reply to Filadi et al.: Does Mitofusin 2 tether or separate endoplasmic reticulum and mitochondria? [Biological Sciences]

2017-03-21T09:13:08-07:00

We thank Filadi et al. for their comments (1) on our paper (2), where we address whether the discrepancies between their paper (3) and our original discovery of Mitofusin (Mfn) 2 as an endoplasmic reticulum (ER)–mitochondria tether (4) resulted from: (i) clonal effects of chronic Mfn2 ablation, (ii) proximity measurement...



Does influenza drive absolute humidity? [Biological Sciences]

2017-03-21T09:13:08-07:00

Multiple lines of evidence suggest that absolute humidity and school terms affect the timing of influenza epidemics, although the contributions of these and other factors are still unresolved (1–5). In PNAS, Deyle et al. (6) applied convergent cross-mapping (CCM) to measure the impact of environmental variables on influenza activity. The...



Reply to Baskerville and Cobey: Misconceptions about causation with synchrony and seasonal drivers [Biological Sciences]

2017-03-21T09:13:08-07:00

Baskerville and Cobey (1) caution against convergent cross-mapping (CCM) as a test for causation. However, their argument is based on an incorrect application of CCM arising from misconceptions about causation with synchrony. As stated in Deyle et al. (2), it is widely believed that there is synchrony between flu incidence...



Stephen Fienberg: Superman of statistics [Retrospectives]

2017-03-21T09:13:07-07:00

Stephen E. Fienberg died on December 14, 2016 after a 4-year battle with cancer. He was husband to Joyce, father to Anthony and Howard, grandfather to six, brother to Lorne, mentor, teacher, and a prolific researcher. Most of all, he was a tireless promoter of the idea that the field...



The depressed brain in Parkinson's disease: Implications for an inflammatory biomarker [Neuroscience]

2017-03-21T09:13:07-07:00

The Need for a Biomarker in Parkinson's Disease Parkinson’s disease (PD) is an increasingly prevalent neurodegenerative disorder currently diagnosed solely on the presence of motor symptoms (i.e., tremor, rigidity, bradykinesia, and postural instability) and their response to dopamine replacement therapy. A major unmet need is the limited number and failure...



Glucagon antagonism in islet cell proliferation [Physiology]

2017-03-21T09:13:07-07:00

The peptide hormones insulin and glucagon (gcg) are inextricably linked in the normal control of glucose homeostasis and in the dysregulated glucose homeostasis that defines diabetes mellitus. Pancreatic islets secrete both insulin and gcg in a manner that is tightly juxtaposed. β Cells secrete insulin, a peptide hormone that promotes...



Keeping the nitrogen-fixation dream alive [Microbiology]

2017-03-21T09:13:07-07:00

The conversion of inert N2 gas to a metabolically tractable form, such as ammonia, is called nitrogen fixation. In biology, nitrogen fixation is a highly oxygen-sensitive process restricted to a select group of diverse microorganisms, often collectively referred to as diazotrophs, or “nitrogen eaters.” The sparse availability of fixed nitrogen,...



Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers [Chemistry]

2017-03-21T09:13:08-07:00

2,2-Bis(azidomethyl)propionic acid was prepared in four steps and 85% yield from the commercially available 2,2-bis(hydroxymethyl)propionic acid and used as the starting building block for the divergent, convergent, and double-stage convergent–divergent iterative methods for the synthesis of dendrimers and dendrons containing ethylenediamine (EDA), piperazine (PPZ), and methyl 2,2-bis(aminomethyl)propionate (COOMe) cores. These...



Determining climate effects on US total agricultural productivity [Earth, Atmospheric, and Planetary Sciences]

2017-03-21T09:13:08-07:00

The sensitivity of agricultural productivity to climate has not been sufficiently quantified. The total factor productivity (TFP) of the US agricultural economy has grown continuously for over half a century, with most of the growth typically attributed to technical change. Many studies have examined the effects of local climate on...



Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors [Engineering]

2017-03-21T09:13:08-07:00

Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are...



Entanglement of quantum clocks through gravity [Physics]

2017-03-21T09:13:08-07:00

In general relativity, the picture of space–time assigns an ideal clock to each world line. Being ideal, gravitational effects due to these clocks are ignored and the flow of time according to one clock is not affected by the presence of clocks along nearby world lines. However, if time is...



Deep-sea vent phage DNA polymerase specifically initiates DNA synthesis in the absence of primers [Biochemistry]

2017-03-21T09:13:08-07:00

A DNA polymerase is encoded by the deep-sea vent phage NrS-1. NrS-1 has a unique genome organization containing genes that are predicted to encode a helicase and a single-stranded DNA (ssDNA)-binding protein. The gene for an unknown protein shares weak homology with the bifunctional primase–polymerases (prim–pols) from archaeal plasmids but...



Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear de novo thymidylate biosynthesis [Biochemistry]

2017-03-21T09:13:08-07:00

Arsenic exposure increases risk for cancers and is teratogenic in animal models. Here we demonstrate that small ubiquitin-like modifier (SUMO)- and folate-dependent nuclear de novo thymidylate (dTMP) biosynthesis is a sensitive target of arsenic trioxide (As2O3), leading to uracil misincorporation into DNA and genome instability. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and...



Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells [Cell Biology]

2017-03-21T09:13:08-07:00

Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have...



Integrin-{beta}4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells [Cell Biology]

2017-03-21T09:13:08-07:00

Neoplastic cells within individual carcinomas often exhibit considerable phenotypic heterogeneity in their epithelial versus mesenchymal-like cell states. Because carcinoma cells with mesenchymal features are often more resistant to therapy and may serve as a source of relapse, we sought to determine whether such cells could be further stratified into functionally...



SMN deficiency in severe models of spinal muscular atrophy causes widespread intron retention and DNA damage [Cell Biology]

2017-03-21T09:13:08-07:00

Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor...



Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids [Cell Biology]

2017-03-21T09:13:08-07:00

In the adenoma-carcinoma sequence, it is proposed that intestinal polyps evolve through a set of defined mutations toward metastatic colorectal cancer (CRC). Here, we dissect this adenoma-carcinoma sequence in vivo by using an orthotopic organoid transplantation model of human colon organoids engineered to harbor different CRC mutation combinations. We demonstrate...



miR-285-Yki/Mask double-negative feedback loop mediates blood-brain barrier integrity in Drosophila [Developmental Biology]

2017-03-21T09:13:08-07:00

The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood–brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until...



Massive increase in visual range preceded the origin of terrestrial vertebrates [Evolution]

2017-03-21T09:13:08-07:00

The evolution of terrestrial vertebrates, starting around 385 million years ago, is an iconic moment in evolution that brings to mind images of fish transforming into four-legged animals. Here, we show that this radical change in body shape was preceded by an equally dramatic change in sensory abilities akin to...



The presumed ginkgophyte Umaltolepis has seed-bearing structures resembling those of Peltaspermales and Umkomasiales [Evolution]

2017-03-21T09:13:08-07:00

The origins of the five groups of living seed plants, including the single relictual species Ginkgo biloba, are poorly understood, in large part because of very imperfect knowledge of extinct seed plant diversity. Here we describe well-preserved material from the Early Cretaceous of Mongolia of the previously enigmatic Mesozoic seed...



Unified reduction principle for the evolution of mutation, migration, and recombination [Evolution]

2017-03-21T09:13:08-07:00

Modifier-gene models for the evolution of genetic information transmission between generations of organisms exhibit the reduction principle: Selection favors reduction in the rate of variation production in populations near equilibrium under a balance of constant viability selection and variation production. Whereas this outcome has been proven for a variety of...



Multiple origins of viral capsid proteins from cellular ancestors [Evolution]

2017-03-21T09:13:08-07:00

Viruses are the most abundant biological entities on earth and show remarkable diversity of genome sequences, replication and expression strategies, and virion structures. Evolutionary genomics of viruses revealed many unexpected connections but the general scenario(s) for the evolution of the virosphere remains a matter of intense debate among proponents of...



Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae [Genetics]

2017-03-21T09:13:08-07:00

Forkhead Box (Fox) proteins share the Forkhead domain, a winged-helix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to...



Myocardial aging as a T-cell-mediated phenomenon [Immunology and Inflammation]

2017-03-21T09:13:08-07:00

In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether...



Immune protection against reinfection with nonprimate hepacivirus [Medical Sciences]

2017-03-21T09:13:08-07:00

Hepatitis C virus (HCV) displays a restricted host species tropism and only humans and chimpanzees are susceptible to infection. A robust immunocompetent animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control, and prophylactic vaccine development. The closest homolog of HCV is the equine nonprimate hepacivirus (NPHV),...



Polyphosphate granule biogenesis is temporally and functionally tied to cell cycle exit during starvation in Pseudomonas aeruginosa [Microbiology]

2017-03-21T09:13:08-07:00

Polyphosphate (polyP) granule biogenesis is an ancient and ubiquitous starvation response in bacteria. Although the ability to make polyP is important for survival during quiescence and resistance to diverse environmental stresses, granule genesis is poorly understood. Using quantitative microscopy at high spatial and temporal resolution, we show that granule genesis...



Simplified and representative bacterial community of maize roots [Microbiology]

2017-03-21T09:13:08-07:00

Plant-associated microbes are important for the growth and health of their hosts. As a result of numerous prior studies, we know that host genotypes and abiotic factors influence the composition of plant microbiomes. However, the high complexity of these communities challenges detailed studies to define experimentally the mechanisms underlying the...



Modular electron-transport chains from eukaryotic organelles function to support nitrogenase activity [Microbiology]

2017-03-21T09:13:08-07:00

A large number of genes are necessary for the biosynthesis and activity of the enzyme nitrogenase to carry out the process of biological nitrogen fixation (BNF), which requires large amounts of ATP and reducing power. The multiplicity of the genes involved, the oxygen sensitivity of nitrogenase, plus the demand for...



Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons [Neuroscience]

2017-03-21T09:13:08-07:00

Ribonucleoprotein (RNP) granules are enriched in specific RNAs and RNA-binding proteins (RBPs) and mediate critical cellular processes. Purified RBPs form liquid droplets in vitro through liquid–liquid phase separation and liquid-like non–membrane-bound structures in cells. Mutations in the human RBPs TAR-DNA binding protein 43 (TDP-43) and RNA-binding protein FUS cause amyotrophic...



Synchronous circadian voltage rhythms with asynchronous calcium rhythms in the suprachiasmatic nucleus [Neuroscience]

2017-03-21T09:13:08-07:00

The suprachiasmatic nucleus (SCN), the master circadian clock, contains a network composed of multiple types of neurons which are thought to form a hierarchical and multioscillator system. The molecular clock machinery in SCN neurons drives membrane excitability and sends time cue signals to various brain regions and peripheral organs. However,...



Novel combinatorial screening identifies neurotrophic factors for selective classes of motor neurons [Neuroscience]

2017-03-21T09:13:08-07:00

Numerous neurotrophic factors promote the survival of developing motor neurons but their combinatorial actions remain poorly understood; to address this, we here screened 66 combinations of 12 neurotrophic factors on pure, highly viable, and standardized embryonic mouse motor neurons isolated by a unique FACS technique. We demonstrate potent, strictly additive,...



Correlated variability modifies working memory fidelity in primate prefrontal neuronal ensembles [Neuroscience]

2017-03-21T09:13:08-07:00

Neurons in the primate lateral prefrontal cortex (LPFC) encode working memory (WM) representations via sustained firing, a phenomenon hypothesized to arise from recurrent dynamics within ensembles of interconnected neurons. Here, we tested this hypothesis by using microelectrode arrays to examine spike count correlations (rsc) in LPFC neuronal ensembles during a...



Deactivation kinetics of acid-sensing ion channel 1a are strongly pH-sensitive [Pharmacology]

2017-03-21T09:13:08-07:00

Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that accompanies neurotransmission. In response to such brief acidic transients,...



Mechanisms regulating angiogenesis underlie seasonal control of pituitary function [Physiology]

2017-03-21T09:13:08-07:00

Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation, and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue driving seasonal reproductive cycles is the change in day length (i.e., photoperiod), encoded by the pattern of melatonin...



Lys49 myotoxin from the Brazilian lancehead pit viper elicits pain through regulated ATP release [Physiology]

2017-03-21T09:13:08-07:00

Pain-producing animal venoms contain evolutionarily honed toxins that can be exploited to study and manipulate somatosensory and nociceptive signaling pathways. From a functional screen, we have identified a secreted phospholipase A2 (sPLA2)-like protein, BomoTx, from the Brazilian lancehead pit viper (Bothrops moojeni). BomoTx is closely related to a group of...



Auxin response cell-autonomously controls ground tissue initiation in the early Arabidopsis embryo [Plant Biology]

2017-03-21T09:13:08-07:00

Plant organs are typically organized into three main tissue layers. The middle ground tissue layer comprises the majority of the plant body and serves a wide range of functions, including photosynthesis, selective nutrient uptake and storage, and gravity sensing. Ground tissue patterning and maintenance in Arabidopsis are controlled by a...



LIGO and the opening of a unique observational window on the universe [Perspectives]

2017-03-21T09:13:07-07:00

A unique window on the universe opened on September 14, 2015, with direct detection of gravitational waves by the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) detectors. This event culminated a half-century effort around the globe to develop terrestrial detectors of adequate sensitivity to achieve this goal. It also happened appropriately...



Hunter-gatherer residential mobility and the marginal value of rainforest patches [Anthropology]

2017-03-21T09:13:07-07:00

The residential mobility patterns of modern hunter-gatherers broadly reflect local resource availability, but the proximate ecological and social forces that determine the timing of camp movements are poorly known. We tested the hypothesis that the timing of such moves maximizes foraging efficiency as hunter-gatherers move across the landscape. The marginal...



Solar fuels photoanode materials discovery by integrating high-throughput theory and experiment [Applied Physical Sciences]

2017-03-21T09:13:07-07:00

The limited number of known low-band-gap photoelectrocatalytic materials poses a significant challenge for the generation of chemical fuels from sunlight. Using high-throughput ab initio theory with experiments in an integrated workflow, we find eight ternary vanadate oxide photoanodes in the target band-gap range (1.2–2.8 eV). Detailed analysis of these vanadate...



Accurate model annotation of a near-atomic resolution cryo-EM map [Biophysics and Computational Biology]

2017-03-21T09:13:07-07:00

Electron cryomicroscopy (cryo-EM) has been used to determine the atomic coordinates (models) from density maps of biological assemblies. These models can be assessed by their overall fit to the experimental data and stereochemical information. However, these models do not annotate the actual density values of the atoms nor their positional...



Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties [Biophysics and Computational Biology]

2017-03-21T09:13:07-07:00

General anesthetics have revolutionized medicine by facilitating invasive procedures, and have thus become essential drugs. However, detailed understanding of their molecular mechanisms remains elusive. A mechanism proposed over a century ago involving unspecified interactions with the lipid bilayer known as the unitary lipid-based hypothesis of anesthetic action, has been challenged...



Sensory domain contraction in histidine kinase CitA triggers transmembrane signaling in the membrane-bound sensor [Biophysics and Computational Biology]

2017-03-21T09:13:07-07:00

Bacteria use membrane-integral sensor histidine kinases (HK) to perceive stimuli and transduce signals from the environment to the cytosol. Information on how the signal is transmitted across the membrane by HKs is still scarce. Combining both liquid- and solid-state NMR, we demonstrate that structural rearrangements in the extracytoplasmic, citrate-sensing Per-Arnt-Sim...



Diverse regulation of mammary epithelial growth and branching morphogenesis through noncanonical Wnt signaling [Cell Biology]

2017-03-21T09:13:07-07:00

The mammary gland consists of an adipose tissue that, in a process called branching morphogenesis, is invaded by a ductal epithelial network comprising basal and luminal epithelial cells. Stem and progenitor cells drive mammary growth, and their proliferation is regulated by multiple extracellular cues. One of the key regulatory pathways...



Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer [Cell Biology]

2017-03-21T09:13:07-07:00

Loss of cell-cycle control is a hallmark of human cancer. Cell-cycle checkpoints are essential for maintaining genome integrity and balanced growth and division. They are specifically deregulated in cancer cells and contain regulators that represent potential therapeutic targets. Monopolar spindle 1 (Mps1; also known as TTK protein kinase) is a...



Stepwise unfolding supports a subunit model for vertebrate kinetochores [Cell Biology]

2017-03-21T09:13:07-07:00

During cell division, interactions between microtubules and chromosomes are mediated by the kinetochore, a proteinaceous structure located at the primary constriction of chromosomes. In addition to the centromere histone centromere protein A (CENP-A), 15 other members of the constitutive centromere associated network (CCAN) participate in the formation of a chromatin-associated...



Opinion: Why we need a centralized repository for isotopic data [Chemistry]

2017-03-21T09:13:07-07:00

Stable isotopes encode and integrate the origin of matter; thus, their analysis offers tremendous potential to address questions across diverse scientific disciplines (1, 2). Indeed, the broad applicability of stable isotopes, coupled with advancements in high-throughput analysis, have created a scientific field that is growing exponentially, and generating data at...



Atoms and molecules in cavities, from weak to strong coupling in quantum-electrodynamics (QED) chemistry [Chemistry]

2017-03-21T09:13:07-07:00

In this work, we provide an overview of how well-established concepts in the fields of quantum chemistry and material sciences have to be adapted when the quantum nature of light becomes important in correlated matter–photon problems. We analyze model systems in optical cavities, where the matter–photon interaction is considered from...



Metallacycle-cored supramolecular assemblies with tunable fluorescence including white-light emission [Chemistry]

2017-03-21T09:13:07-07:00

Control over the fluorescence of supramolecular assemblies is crucial for the development of chemosensors and light-emitting materials. Consequently, the postsynthetic modification of supramolecular structures via host–guest interactions has emerged as an efficient strategy in recent years that allows the facile tuning of the photophysical properties without requiring a tedious chemical...



Characterization of NiFe oxyhydroxide electrocatalysts by integrated electronic structure calculations and spectroelectrochemistry [Chemistry]

2017-03-21T09:13:07-07:00

NiFe oxyhydroxide materials are highly active electrocatalysts for the oxygen evolution reaction (OER), an important process for carbon-neutral energy storage. Recent spectroscopic and computational studies increasingly support iron as the site of catalytic activity but differ with respect to the relevant iron redox state. A combination of hybrid periodic density...



Tailoring porosity and rotational dynamics in a series of octacarboxylate metal-organic frameworks [Chemistry]

2017-03-21T09:13:07-07:00

Modulation and precise control of porosity of metal-organic frameworks (MOFs) is of critical importance to their materials function. Here we report modulation of porosity for a series of isoreticular octacarboxylate MOFs, denoted MFM-180 to MFM-185, via a strategy of selective elongation of metal-organic cages. Owing to the high ligand connectivity,...



Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells [Developmental Biology]

2017-03-21T09:13:07-07:00

During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. In the early limb bud, for instance, Sonic hedgehog (Shh) is expressed in the distal posterior mesenchyme, where...



Recombination reactions as a possible mechanism of mass-independent fractionation of sulfur isotopes in the Archean atmosphere of Earth [Earth, Atmospheric, and Planetary Sciences]

2017-03-21T09:13:07-07:00

A hierarchy of isotopically substituted recombination reactions is formulated for production of sulfur allotropes in the anoxic atmosphere of Archean Earth. The corresponding system of kinetics equations is solved analytically to obtain concise expressions for isotopic enrichments, with focus on mass-independent isotope effects due to symmetry, ignoring smaller mass-dependent effects....



Yellow taxis have fewer accidents than blue taxis because yellow is more visible than blue [Economic Sciences]

2017-03-21T09:13:07-07:00

Is there a link between the color of a taxi and how many accidents it has? An analysis of 36 mo of detailed taxi, driver, and accident data (comprising millions of data points) from the largest taxi company in Singapore suggests that there is an explicit link. Yellow taxis had...



Impact of savings groups on the lives of the poor [Economic Sciences]

2017-03-21T09:13:07-07:00

Savings-led microfinance programs operate in poor rural communities in developing countries to establish groups that save and then lend out the accumulated savings to each other. Nonprofit organizations train villagers to create and lead these groups. In a clustered randomized evaluation spanning three African countries (Ghana, Malawi, and Uganda), we...



Discovery of an endogenous Deltaretrovirus in the genome of long-fingered bats (Chiroptera: Miniopteridae) [Evolution]

2017-03-21T09:13:08-07:00

Retroviruses can create endogenous forms on infiltration into the germline cells of their hosts. These forms are then vertically transmitted and can be considered as genetic fossils of ancient viruses. All retrovirus genera, with the exception of deltaretroviruses, have had their representation identified in the host genome as a virus...



Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf-/- mouse model [Genetics]

2017-03-21T09:13:08-07:00

Inhibitors of double minute 2 protein (MDM2)–tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the TP53 gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent CDKN2A deletion in human cancer that, through inactivation of p14ARF, activates...



Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease [Immunology and Inflammation]

2017-03-21T09:13:08-07:00

Current therapies for autoimmune diseases rely on traditional immunosuppressive medications that expose patients to an increased risk of opportunistic infections and other complications. Immunoregulatory interventions that act prophylactically or therapeutically to induce antigen-specific tolerance might overcome these obstacles. Here we use the transpeptidase sortase to covalently attach disease-associated autoantigens to...



Sensing of cell stress by human {gamma}{delta} TCR-dependent recognition of annexin A2 [Immunology and Inflammation]

2017-03-21T09:13:08-07:00

Human γδ T cells comprise a first line of defense through T-cell receptor (TCR) recognition of stressed cells. However, the molecular determinants and stress pathways involved in this recognition are largely unknown. Here we show that exposure of tumor cells to various stress situations led to tumor cell recognition by...



ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression [Medical Sciences]

2017-03-21T09:13:08-07:00

The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional...



Phosphoproteins in extracellular vesicles as candidate markers for breast cancer [Medical Sciences]

2017-03-21T09:13:08-07:00

The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to...



Ablation of cytochrome P450 omega-hydroxylase 4A14 gene attenuates hepatic steatosis and fibrosis [Medical Sciences]

2017-03-21T09:13:08-07:00

Nonalcoholic fatty liver disease (NAFLD) is characterized by simple hepatic steatosis (SS), nonalcoholic steatohepatitis (NASH), hepatic fibrosis, and cirrhosis. Dysregulated fatty acid metabolism in the liver plays a critical role in the pathogenesis of NAFLD. Cytochrome P450 omega-hydroxylase 4A14 (CYP4A14) is a homolog of human CYP4A hydroxylase that catalyzes omega-hydroxylation...



mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy [Medical Sciences]

2017-03-21T09:13:08-07:00

The ovary contains oocytes within immature (primordial) follicles that are fixed in number at birth. Activation of follicles within this fixed pool causes an irreversible decline in reproductive capacity, known as the ovarian reserve, until menopause. Premenopausal women undergoing commonly used genotoxic (DNA-damaging) chemotherapy experience an accelerated loss of the...



BAP1 inhibits the ER stress gene regulatory network and modulates metabolic stress response [Medical Sciences]

2017-03-21T09:13:08-07:00

The endoplasmic reticulum (ER) is classically linked to metabolic homeostasis via the activation of unfolded protein response (UPR), which is instructed by multiple transcriptional regulatory cascades. BRCA1 associated protein 1 (BAP1) is a tumor suppressor with de-ubiquitinating enzyme activity and has been implicated in chromatin regulation of gene expression. Here...



Comparative genomics uncovers the prolific and distinctive metabolic potential of the cyanobacterial genus Moorea [Microbiology]

2017-03-21T09:13:08-07:00

Cyanobacteria are major sources of oxygen, nitrogen, and carbon in nature. In addition to the importance of their primary metabolism, some cyanobacteria are prolific producers of unique and bioactive secondary metabolites. Chemical investigations of the cyanobacterial genus Moorea have resulted in the isolation of over 190 compounds in the last...



Resuscitation of Pseudomonas aeruginosa from dormancy requires hibernation promoting factor (PA4463) for ribosome preservation [Microbiology]

2017-03-21T09:13:08-07:00

Pseudomonas aeruginosa biofilm infections are difficult to treat with antibiotic therapy in part because the biofilms contain subpopulations of dormant antibiotic-tolerant cells. The dormant cells can repopulate the biofilms following alleviation of antibiotic treatments. While dormant, the bacteria must maintain cellular integrity, including ribosome abundance, to reinitiate the de novo...



Structure of deformed wing virus, a major honey bee pathogen [Microbiology]

2017-03-21T09:13:08-07:00

The worldwide population of western honey bees (Apis mellifera) is under pressure from habitat loss, environmental stress, and pathogens, particularly viruses that cause lethal epidemics. Deformed wing virus (DWV) from the family Iflaviridae, together with its vector, the mite Varroa destructor, is likely the major threat to the world’s honey...



Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety [Neuroscience]

2017-03-21T09:13:08-07:00

Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical...



Higher-than-ballistic conduction of viscous electron flows [Physics]

2017-03-21T09:13:07-07:00

Strongly interacting electrons can move in a neatly coordinated way, reminiscent of the movement of viscous fluids. Here, we show that in viscous flows, interactions facilitate transport, allowing conductance to exceed the fundamental Landauer’s ballistic limit Gball. The effect is particularly striking for the flow through a viscous point contact,...



Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel’s selectivity filter [Physiology]

2017-03-21T09:13:08-07:00

Mode-shift or hysteresis has been reported in ion channels. Voltage-shift for gating currents is well documented for voltage-gated cation channels (VGCC), and it is considered a voltage-sensing domain's (VSD) intrinsic property. However, uncoupling the Shaker K+ channel’s pore domain (PD) from the VSD prevented the mode-shift of the gating currents....



Myosin filament activation in the heart is tuned to the mechanical task [Physiology]

2017-03-21T09:13:08-07:00

The mammalian heart pumps blood through the vessels, maintaining the dynamic equilibrium in a circulatory system driven by two pumps in series. This vital function is based on the fine-tuning of cardiac performance by the Frank–Starling mechanism that relates the pressure exerted by the contracting ventricle (end systolic pressure) to...



Coordination of auxin-triggered leaf initiation by tomato LEAFLESS [Plant Biology]

2017-03-21T09:13:08-07:00

Lateral plant organs, particularly leaves, initiate at the flanks of the shoot apical meristem (SAM) following auxin maxima signals; however, little is known about the underlying mechanisms. Here, we show that tomato leafless (lfs) mutants fail to produce cotyledons and leaves and grow a naked pin while maintaining an active...



Black-swan events in animal populations [Population Biology]

2017-03-21T09:13:08-07:00

Black swans are improbable events that nonetheless occur—often with profound consequences. Such events drive important transitions in social systems (e.g., banking collapses) and physical systems (e.g., earthquakes), and yet it remains unclear the extent to which ecological population numbers buffer or suffer from such extremes. Here, we estimate the prevalence...



Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images [Psychological and Cognitive Sciences]

2017-03-21T09:13:08-07:00

Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the...



Anatomy of news consumption on Facebook [Psychological and Cognitive Sciences]

2017-03-21T09:13:07-07:00

The advent of social media and microblogging platforms has radically changed the way we consume information and form opinions. In this paper, we explore the anatomy of the information space on Facebook by characterizing on a global scale the news consumption patterns of 376 million users over a time span...



Classroom sound can be used to classify teaching practices in college science courses [Psychological and Cognitive Sciences]

2017-03-21T09:13:07-07:00

Active-learning pedagogies have been repeatedly demonstrated to produce superior learning gains with large effect sizes compared with lecture-based pedagogies. Shifting large numbers of college science, technology, engineering, and mathematics (STEM) faculty to include any active learning in their teaching may retain and more effectively educate far more students than having...



Neural basis of impaired safety signaling in Obsessive Compulsive Disorder [Psychological and Cognitive Sciences]

2017-03-21T09:13:08-07:00

The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when...



Predicting the knowledge-recklessness distinction in the human brain [Psychological and Cognitive Sciences]

2017-03-21T09:13:08-07:00

Criminal convictions require proof that a prohibited act was performed in a statutorily specified mental state. Different legal consequences, including greater punishments, are mandated for those who act in a state of knowledge, compared with a state of recklessness. Existing research, however, suggests people have trouble classifying defendants as knowing,...



Consequences of a price incentive on free riding and electric energy consumption [Sustainability Science]

2017-03-21T09:13:07-07:00

This article shows that a simple monetary incentive can dramatically reduce electric energy consumption (EEC) in the residential sector and simultaneously achieve a more desirable allocation of EEC costs. The analyses are based on data from a policy experiment conducted in 2011 and 2012 by a private housing company in...



Correction for Koizumi et al., Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection [Corrections]

2017-03-21T09:13:09-07:00

BIOPHYSICS AND COMPUTATIONAL BIOLOGY Correction for “Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection,” by Yoshiki Koizumi, Hirofumi Ohashi, Syo Nakajima, Yasuhito Tanaka, Takaji Wakita, Alan S. Perelson, Shingo Iwami, and Koichi Watashi, which appeared in issue 8, February 21, 2017, of Proc Natl Acad Sci USA...



Correction for Jeon et al., A set of NF-{kappa}B-regulated microRNAs induces acquired TRAIL resistance in Lung cancer [Corrections]

2017-03-21T09:13:09-07:00

CELL BIOLOGY Correction for “A set of NF-κB–regulated microRNAs induces acquired TRAIL resistance in Lung cancer,” by Young-Jun Jeon, Justin Middleton, Taewan Kim, Alessandro Laganà, Claudia Piovan, Paola Secchiero, Gerard J. Nuovo, Ri Cui, Pooja Joshi, Giulia Romano, Gianpiero Di Leva, Bum-Kyu Lee, Hui-Lung Sun, Yonghwan Kim, Paolo Fadda, Hansjuerg...



Correction for Perni et al., A natural product inhibits the initiation of {alpha}-synuclein aggregation and suppresses its toxicity [Corrections]

2017-03-21T09:13:09-07:00

NEUROSCIENCE Correction for “A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity,” by Michele Perni, Céline Galvagnion, Alexander Maltsev, Georg Meisl, Martin B. D. Müller, Pavan K. Challa, Julius B. Kirkegaard, Patrick Flagmeier, Samuel I. A. Cohen, Roberta Cascella, Serene W. Chen, Ryan Limboker, Pietro Sormanni,...



Correction to Supporting Information for Kirby et al., Cumulative cultural evolution in the laboratory: An experimental approach to the origins of structure in human language [SI Correction]

2017-03-21T09:13:09-07:00

PSYCHOLOGY, EVOLUTION Correction to Supporting Information for “Cumulative cultural evolution in the laboratory: An experimental approach to the origins of structure in human language,” by Simon Kirby, Hannah Cornish, and Kenny Smith, which appeared in issue 31, August 5, 2008, of Proc Natl Acad Sci USA (105:10681–10686; first published July...