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Proceedings of the National Academy of Sciences recent issues



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In This Issue [This Week in PNAS]

2016-09-20T08:46:00-07:00

Tuberculosis and HIV coinfection SIV-infected cells in lung granuloma from macaque with extensive TB. One in three people harbor latent Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), but latent Mtb can trigger active TB. Coinfection with HIV can speed the progression of latent TB to active TB, a...



Biophotons and intelligence are not related [Biological Sciences]

2016-09-20T08:46:01-07:00

Despite enormous efforts, any correlation between “intelligence” and cognitive or physiological/anatomical properties of animal brains is still poorly understood because intelligence depends on multiple factors in parallel and not a single determinant (1). The study by Wang et al. (2) is both novel and intriguing, but we believe that the...



Biophotons related to human intelligence [Biological Sciences]

2016-09-20T08:46:01-07:00

We would like to thank Salari et al. for their interest in our paper (1) and to give a response to their concerns on the causation of spectral redshift of biophotons related to human intelligence (2). First, it is inappropriate to consider a brain slice (or whole brain) as a...



How monocytes guard the glomerulus [Immunology and Inflammation]

2016-09-20T08:46:00-07:00

In most tissues the leukocyte response to inflammatory stimuli takes place in postcapillary venules (1). Leukocytes and endothelial cells undergo a coordinated and stereotyped series of increasingly tight adhesive interactions designed to capture leukocytes from the bloodstream (2–5). This process generally culminates in migration of leukocytes across the endothelial cells...



Biomolecular archaeology of prehistoric hearths [Anthropology]

2016-09-20T08:46:00-07:00

In the last decades, organic residue analysis of ceramic artifacts has advanced our understanding of culinary practices and economies in the past. Current approaches, deploying lipid residue analysis, have allowed a wide range of prehistoric commodities processed in pottery to be identified (1, 2). Recently, organic residues analysis has allowed...



Angiogenic neovessels promote tissue hypoxia [Physiology]

2016-09-20T08:46:00-07:00

The generation of blood vessels is a key early event during embryonic development that ensures the proper formation of the vasculature to supply oxygen and nutrients to the tissue. This occurs via two processes: vasculogenesis, whereby vessels are formed de novo, and angiogenesis, whereby new vessels sprout from preexisting ones...



TDRD3 promotes Top3{beta}{#x2019}s topoisomerase activities [Biochemistry]

2016-09-20T08:46:01-07:00

Topoisomerase 3β (Top3β) can associate with the mediator protein Tudor domain-containing protein 3 (TDRD3) to participate in two gene expression processes of transcription and translation. Despite the apparent importance of TDRD3 in binding with Top3β and directing it to cellular compartments critical for gene expression, the biochemical mechanism of how...



Autoregulation of the F-BAR protein Nwk [Cell Biology]

2016-09-20T08:46:01-07:00

Membrane remodeling by Fes/Cip4 homology-Bin/Amphiphysin/Rvs167 (F-BAR) proteins is regulated by autoinhibitory interactions between their SRC homology 3 (SH3) and F-BAR domains. The structural basis of autoregulation, and whether it affects interactions of SH3 domains with other cellular ligands, remain unclear. Here we used single-particle electron microscopy to determine the structure...



Selenoprotein H, redox, and tumor formation [Developmental Biology]

2016-09-20T08:46:01-07:00

Selenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling...



Spiny plants and mammal browsers [Ecology]

2016-09-20T08:46:01-07:00

Savannas first began to spread across Africa during the Miocene. A major hypothesis for explaining this vegetation change is the increase in C4 grasses, promoting fire. We investigated whether mammals could also have contributed to savanna expansion by using spinescence as a marker of mammal herbivory. Looking at the present...



Explosive ice age diversification of kiwi [Evolution]

2016-09-20T08:46:01-07:00

Molecular dating largely overturned the paradigm that global cooling during recent Pleistocene glacial cycles resulted in a burst of species diversification although some evidence exists that speciation was commonly promoted in habitats near the expanding and retracting ice sheets. Here, we used a genome-wide dataset of more than half a...



Editing Arg codons shows rules for codon choice [Genetics]

2016-09-20T08:46:01-07:00

The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from...



Mitochondrial enzyme GPT2 in neurological disease [Genetics]

2016-09-20T08:46:01-07:00

Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)]...



Class II MHC mutants alter CD4 T-cell V region use [Immunology and Inflammation]

2016-09-20T08:46:01-07:00

The interaction of αβ T-cell antigen receptors (TCRs) with peptides bound to MHC molecules lies at the center of adaptive immunity. Whether TCRs have evolved to react with MHC or, instead, processes in the thymus involving coreceptors and other molecules select MHC-specific TCRs de novo from a random repertoire is...



PDGF-BB-induced PFT promotes cancer metastasis [Medical Sciences]

2016-09-20T08:46:01-07:00

Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte–fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that...



Cardiac endothelial Brg1 control heart hypertrophy [Medical Sciences]

2016-09-20T08:46:01-07:00

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown....



Immune control of reactivation of latent TB [Microbiology]

2016-09-20T08:46:01-07:00

The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4+ T cells believed to be the major causality. In...



GluA1 signal peptide determines AMPAR assembly [Neuroscience]

2016-09-20T08:46:01-07:00

AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and predominantly assemble as heterotetramers in the brain. Recently, the crystal structures of homotetrameric GluA2 demonstrated that AMPARs are assembled with two pairs of conformationally distinct subunits, in a dimer of dimers formation. However, the structure of heteromeric AMPARs remains unclear. Guided...



TRiC rescues BDNF and striatal atrophy in HD [Neuroscience]

2016-09-20T08:46:01-07:00

Corticostriatal atrophy is a cardinal manifestation of Huntington’s disease (HD). However, the mechanism(s) by which mutant huntingtin (mHTT) protein contributes to the degeneration of the corticostriatal circuit is not well understood. We recreated the corticostriatal circuit in microfluidic chambers, pairing cortical and striatal neurons from the BACHD model of HD...



CCR2 monocytes infiltrate after status epilepticus [Neuroscience]

2016-09-20T08:46:01-07:00

The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood–brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not...



Design of GPCR allosteric modulators [Pharmacology]

2016-09-20T08:46:01-07:00

Design of ligands that provide receptor selectivity has emerged as a new paradigm for drug discovery of G protein-coupled receptors, and may, for certain families of receptors, only be achieved via identification of chemically diverse allosteric modulators. Here, the extracellular vestibule of the M2 muscarinic acetylcholine receptor (mAChR) is targeted...



Cyclic AMP regulation of SCAP/SREBP [Pharmacology]

2016-09-20T08:46:01-07:00

Luteinizing hormone (LH) stimulates steroidogenesis largely through a surge in cyclic AMP (cAMP). Steroidogenic rates are also critically dependent on the availability of cholesterol at mitochondrial sites of synthesis. This cholesterol is provided by cellular uptake of lipoproteins, mobilization of intracellular lipid, and de novo synthesis. Whether and how these...



High-efficiency metasurfaces for visible spectrum [Applied Physical Sciences]

2016-09-20T08:46:00-07:00

Metasurfaces are planar optical elements that hold promise for overcoming the limitations of refractive and conventional diffractive optics. Original dielectric metasurfaces are limited to transparency windows at infrared wavelengths because of significant optical absorption and loss at visible wavelengths. Thus, it is critical that new materials and nanofabrication techniques be...



Biaxial ferromagnetic liquid crystal colloids [Applied Physical Sciences]

2016-09-20T08:46:00-07:00

The design and practical realization of composite materials that combine fluidity and different forms of ordering at the mesoscopic scale are among the grand fundamental science challenges. These composites also hold a great potential for technological applications, ranging from information displays to metamaterials. Here we introduce a fluid with coexisting...



Crystal structure of the Bor1 SLC4 transporter [Biochemistry]

2016-09-20T08:46:00-07:00

Boron is essential for plant growth because of its incorporation into plant cell walls; however, in excess it is toxic to plants. Boron transport and homeostasis in plants is regulated in part by the borate efflux transporter Bor1, a member of the solute carrier (SLC) 4 transporter family with homology...



Active conformation of the APC/C requires Apc1WD40 [Biochemistry]

2016-09-20T08:46:00-07:00

The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin–RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and...



Nucleosome ubiquitination by Rad6-Bre1 [Biochemistry]

2016-09-20T08:46:01-07:00

Cotranscriptional ubiquitination of histone H2B is key to gene regulation. The yeast E3 ubiquitin ligase Bre1 (human RNF20/40) pairs with the E2 ubiquitin conjugating enzyme Rad6 to monoubiquitinate H2B at Lys123. How this single lysine residue on the nucleosome core particle (NCP) is targeted by the Rad6–Bre1 machinery is unknown....



Side-chain snorkeling in transmembrane helices [Biochemistry]

2016-09-20T08:46:01-07:00

Cotranslational translocon-mediated insertion of membrane proteins into the endoplasmic reticulum is a key process in membrane protein biogenesis. Although the mechanism is understood in outline, quantitative data on the energetics of the process is scarce. Here, we have measured the effect on membrane integration efficiency of nonproteinogenic analogs of the...



Protein quake after CO dissociation in myoglobin [Biophysics and Computational Biology]

2016-09-20T08:46:01-07:00

“Protein quake” denotes the dissipation of excess energy across a protein, in response to a local perturbation such as the breaking of a chemical bond or the absorption of a photon. Femtosecond time-resolved small- and wide-angle X-ray scattering (TR-SWAXS) is capable of tracking such ultrafast protein dynamics. However, because the...



PI5P4K{alpha} generates a PIP2 pool that regulates Akt [Cell Biology]

2016-09-20T08:46:01-07:00

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably...



P31comet in rice meiosis [Cell Biology]

2016-09-20T08:46:01-07:00

The human mitotic arrest-deficient 2 (Mad2) binding protein p31comet participates in the spindle checkpoint and coordinates cell cycle events in mitosis although its function in meiosis remains unknown in all organisms. Here, we reveal P31comet as a synaptonemal complex (SC) protein in rice (Oryza sativa L.). In p31comet, homologous pairing...



Zone of anisotropy in colloidal crystallization [Chemistry]

2016-09-20T08:46:00-07:00

In this work, we present a joint experimental and molecular dynamics simulations effort to understand and map the crystallization behavior of polyhedral nanoparticles assembled via the interaction of DNA surface ligands. In these systems, we systematically investigated the interplay between the effects of particle core (via the particle symmetry and...



Covalent bonds against magnetism [Chemistry]

2016-09-20T08:46:00-07:00

Magnetism in transition metal compounds is usually considered starting from a description of isolated ions, as exact as possible, and treating their (exchange) interaction at a later stage. We show that this standard approach may break down in many cases, especially in 4d and 5d compounds. We argue that there...



Kinetic barriers to SNAREpin assembly [Chemistry]

2016-09-20T08:46:00-07:00

Neurotransmission is achieved by soluble NSF attachment protein receptor (SNARE)-driven fusion of readily releasable vesicles that are docked and primed at the presynaptic plasma membrane. After neurotransmission, the readily releasable pool of vesicles must be refilled in less than 100 ms for subsequent release. Here we show that the initial...



Minibrain and Wings apart inhibit Capicua [Developmental Biology]

2016-09-20T08:46:01-07:00

The transcriptional repressor Capicua (Cic) controls tissue patterning and restricts organ growth, and has been recently implicated in several cancers. Cic has emerged as a primary sensor of signaling downstream of the receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase (ERK) pathway, but how Cic activity is regulated in different cellular contexts...



Nutrients drive DOC accumulation at surface [Earth, Atmospheric, and Planetary Sciences]

2016-09-20T08:46:00-07:00

The inventories of carbon residing in organic matter dissolved in the ocean [dissolved organic carbon (DOC)] and in the atmosphere as CO2 are of the same order of magnitude, such that small changes in the DOC pool could have important consequences in atmospheric carbon and thus climate. DOC in the...



Olivine anisotropy and the base of the lithosphere [Earth, Atmospheric, and Planetary Sciences]

2016-09-20T08:46:00-07:00

Tectonic plates are a key feature of Earth’s structure, and their behavior and dynamics are fundamental drivers in a wide range of large-scale processes. The operation of plate tectonics, in general, depends intimately on the manner in which lithospheric plates couple to the convecting interior. Current debate centers on whether...



Thermal landscape determines thermoregulation [Ecology]

2016-09-20T08:46:01-07:00

Although most organisms thermoregulate behaviorally, biologists still cannot easily predict whether mobile animals will thermoregulate in natural environments. Current models fail because they ignore how the spatial distribution of thermal resources constrains thermoregulatory performance over space and time. To overcome this limitation, we modeled the spatially explicit movements of animals...



Can single molecules bind entire ecosystems? [Environmental Sciences]

2016-09-20T08:46:00-07:00

Off the coast of California, puffy slug-like creatures—named sea hares (Aplysia californica) for their bunny ear-like tentacles—chomp their way across underwater fields of red-brown algae. The algae produce mycosporine-like amino acids (MAAs), chemicals that give the sea hares their murky maroon hues. The animals deploy these same molecules for defense....



Oxygen kinetics of ammonium and nitrite oxidation [Environmental Sciences]

2016-09-20T08:46:01-07:00

A major percentage of fixed nitrogen (N) loss in the oceans occurs within nitrite-rich oxygen minimum zones (OMZs) via denitrification and anammox. It remains unclear to what extent ammonium and nitrite oxidation co-occur, either supplying or competing for substrates involved in nitrogen loss in the OMZ core. Assessment of the...



Responses of grassland production to global change [Environmental Sciences]

2016-09-20T08:46:01-07:00

Global changes in climate, atmospheric composition, and pollutants are altering ecosystems and the goods and services they provide. Among approaches for predicting ecosystem responses, long-term observations and manipulative experiments can be powerful approaches for resolving single-factor and interactive effects of global changes on key metrics such as net primary production...



Variation in the molecular clock of primates [Evolution]

2016-09-20T08:46:01-07:00

Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life...



Convergence of caffeine biosynthesis in plants [Evolution]

2016-09-20T08:46:01-07:00

Convergent evolution is a process that has occurred throughout the tree of life, but the historical genetic and biochemical context promoting the repeated independent origins of a trait is rarely understood. The well-known stimulant caffeine, and its xanthine alkaloid precursors, has evolved multiple times in flowering plant history for various...



Cooperation of eIF4B with eIF4A and Ded1 in vivo [Genetics]

2016-09-20T08:46:00-07:00

DEAD-box RNA helicases eukaryotic translation initiation factor 4A (eIF4A) and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. Eukaryotic translation initiation factor 4B (eIF4B) is a cofactor for eIF4A but also might function independently of eIF4A. Ribosome profiling of mutants...



PAXX C-NHEJ functions masked by XLF [Genetics]

2016-09-20T08:46:01-07:00

Classical nonhomologous end joining (C-NHEJ) is a major mammalian DNA double-strand break (DSB) repair pathway. Core C-NHEJ factors, such as XRCC4, are required for joining DSB intermediates of the G1 phase-specific V(D)J recombination reaction in progenitor lymphocytes. Core factors also contribute to joining DSBs in cycling mature B-lineage cells, including...



Identification of a lenalidomide target molecule [Immunology and Inflammation]

2016-09-20T08:46:01-07:00

Immunomodulatory drugs (IMiDs) are a family of compounds derived from thalidomide. Binding of the IMiD molecule to the Lon protease Cereblon initiates the degradation of substrates via the ubiquitin proteasome pathway. Here, we show that Cereblon forms a complex with Rabex-5, a regulator of immune homeostasis. Treatment with lenalidomide prevented...



Effector CD8+ T-cell regulation by DNMT3a [Immunology and Inflammation]

2016-09-20T08:46:01-07:00

DNMT3a is a de novo DNA methyltransferase expressed robustly after T-cell activation that regulates plasticity of CD4+ T-cell cytokine expression. Here we show that DNMT3a is critical for directing early CD8+ T-cell effector and memory fate decisions. Whereas effector function of DNMT3a knockout T cells is normal, they develop more...



Leptin promotes SLE [Immunology and Inflammation]

2016-09-20T08:46:01-07:00

Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on...



Molecular profiles of lymphatics [Immunology and Inflammation]

2016-09-20T08:46:01-07:00

Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, whereas efferent lymphatics allow only lymphocytes and antigens to leave the nodes. Despite the fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, the molecular characteristics of these different arms of the...



Mannose receptor-induced T-cell tolerance [Immunology and Inflammation]

2016-09-20T08:46:01-07:00

The mannose receptor (MR) is an endocytic receptor involved in serum homeostasis and antigen presentation. Here, we identify the MR as a direct regulator of CD8+ T-cell activity. We demonstrate that MR expression on dendritic cells (DCs) impaired T-cell cytotoxicity in vitro and in vivo. This regulatory effect of the...



Sufficient trial size to inform clinical practice [Medical Sciences]

2016-09-20T08:46:00-07:00

Medical research has evolved conventions for choosing sample size in randomized clinical trials that rest on the theory of hypothesis testing. Bayesian statisticians have argued that trials should be designed to maximize subjective expected utility in settings of clinical interest. This perspective is compelling given a credible prior distribution on...



MicroRNA panel for diagnosis of prostate cancer [Medical Sciences]

2016-09-20T08:46:01-07:00

We report the identification of a molecular signature using the Scano-miR profiling platform based on the differential expression of circulating microRNAs (miRNA, miR) in serum samples specific to patients with very high-risk (VHR) prostate cancer (PCa). Five miRNA PCa biomarkers (miR-200c, miR-605, miR-135a*, miR-433, and miR-106a) were identified as useful...



CRISPR-Cas9 creates HPFH in HSPCs [Medical Sciences]

2016-09-20T08:46:01-07:00

Hereditary persistence of fetal hemoglobin (HPFH) is a condition in some individuals who have a high level of fetal hemoglobin throughout life. Individuals with compound heterozygous β-thalassemia or sickle cell disease (SCD) and HPFH have milder clinical manifestations. Using RNA-guided clustered regularly interspaced short palindromic repeats-associated Cas9 (CRISPR-Cas9) genome-editing technology,...



Act D and RG7787 synergize to kill cancer cells [Medical Sciences]

2016-09-20T08:46:01-07:00

RG7787 is a mesothelin-targeted immunotoxin designed to have low-immunogenicity, high-cytotoxic activity and fewer side effects. RG7787 kills many types of mesothelin-expressing cancer cells lines and causes tumor regressions in mice. Safety and immunogenicity of RG7787 is now being assessed in a phase I trial. To enhance the antitumor activity of...



Mutations in pulmonary sclerosing hemangioma [Medical Sciences]

2016-09-20T08:46:01-07:00

Pulmonary sclerosing hemangioma (PSH) is a benign tumor with two cell populations (epithelial and stromal cells), for which genomic profiles remain unknown. We conducted exome sequencing of 44 PSHs and identified recurrent somatic mutations of AKT1 (43.2%) and β-catenin (4.5%). We used a second subset of 24 PSHs to confirm...



Innate antiviral gene signature after childbirth [Microbiology]

2016-09-20T08:46:01-07:00

Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the...



Genetic determinants of postpartum HCV control [Microbiology]

2016-09-20T08:46:01-07:00

Chronic hepatitis C virus (HCV) infection is characterized by exhaustion of virus-specific T-cells and stable viremia. Pregnancy is an exception. Viremia gradually climbs during gestation but sometimes declines sharply in the months following delivery. Here, we demonstrated that postpartum HCV control was associated with enhanced virus-specific T-cell immunity. Women with...



Genetic basis for hypervirulence of Campylobacter [Microbiology]

2016-09-20T08:46:01-07:00

Infections due to clonal expansion of highly virulent bacterial strains are clear and present threats to human and animal health. Association of genetic changes with disease is now a routine, but identification of causative mutations that enable disease remains difficult. Campylobacter jejuni is an important zoonotic pathogen transmitted to humans...



Unique pH dynamics in GABAergic synaptic vesicles [Neuroscience]

2016-09-20T08:46:01-07:00

GABA acts as the major inhibitory neurotransmitter in the mammalian brain, shaping neuronal and circuit activity. For sustained synaptic transmission, synaptic vesicles (SVs) are required to be recycled and refilled with neurotransmitters using an H+ electrochemical gradient. However, neither the mechanism underlying vesicular GABA uptake nor the kinetics of GABA...



Atom interactions in a photonic crystal waveguide [Physics]

2016-09-20T08:46:00-07:00

Tailoring the interactions between quantum emitters and single photons constitutes one of the cornerstones of quantum optics. Coupling a quantum emitter to the band edge of a photonic crystal waveguide (PCW) provides a unique platform for tuning these interactions. In particular, the cross-over from propagating fields E(x)∝e±ikxx outside the bandgap...



Ultrathin 2D superconductivity with strong SOC [Physics]

2016-09-20T08:46:00-07:00

We report on a study of epitaxially grown ultrathin Pb films that are only a few atoms thick and have parallel critical magnetic fields much higher than the expected limit set by the interaction of electron spins with a magnetic field, that is, the Clogston–Chandrasekhar limit. The epitaxial thin films...



Flowering regulation by chloroplasts [Plant Biology]

2016-09-20T08:46:01-07:00

Light is a major environmental factor regulating flowering time, thus ensuring reproductive success of higher plants. In contrast to our detailed understanding of light quality and photoperiod mechanisms involved, the molecular basis underlying high light-promoted flowering remains elusive. Here we show that, in Arabidopsis, a chloroplast-derived signal is critical for...



Galactolipid transfer in chloroplast envelopes [Plant Biology]

2016-09-20T08:46:01-07:00

Galactolipids [monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG)] are the hallmark lipids of photosynthetic membranes. The galactolipid synthases MGD1 and DGD1 catalyze consecutive galactosyltransfer reactions but localize to the inner and outer chloroplast envelopes, respectively, necessitating intermembrane lipid transfer. Here we show that the N-terminal sequence of DGD1 (NDGD1) is required for...



DUS16 plays essential role in pri-miRNA processing [Plant Biology]

2016-09-20T08:46:01-07:00

Canonical microRNAs (miRNAs) are embedded in duplexed stem–loops in long precursor transcripts and are excised by sequential cleavage by DICER nuclease(s). In this miRNA biogenesis pathway, dsRNA-binding proteins play important roles in animals and plants by assisting DICER. However, these RNA-binding proteins are poorly characterized in unicellular organisms. Here we...



Coordination failures in intergroup conflict [Psychological and Cognitive Sciences]

2016-09-20T08:46:00-07:00

Intergroup conflict persists when and because individuals make costly contributions to their group’s fighting capacity, but how groups organize contributions into effective collective action remains poorly understood. Here we distinguish between contributions aimed at subordinating out-groups (out-group aggression) from those aimed at defending the in-group against possible out-group aggression (in-group...



Neural signature of a specificity induction [Psychological and Cognitive Sciences]

2016-09-20T08:46:01-07:00

Recent behavioral work suggests that an episodic specificity induction—brief training in recollecting the details of a past experience—enhances performance on subsequent tasks that rely on episodic retrieval, including imagining future experiences, solving open-ended problems, and thinking creatively. Despite these far-reaching behavioral effects, nothing is known about the neural processes impacted...



Extracting screening rules from online dating data [Social Sciences]

2016-09-20T08:46:00-07:00

This paper presents a statistical framework for harnessing online activity data to better understand how people make decisions. Building on insights from cognitive science and decision theory, we develop a discrete choice model that allows for exploratory behavior and multiple stages of decision making, with different rules enacted at each...



Correction for Kopp et al., Temperature-driven global sea-level variability in the Common Era [Correction]

2016-09-20T08:46:01-07:00

SUSTAINABILITY SCIENCE Correction for “Temperature-driven global sea-level variability in the Common Era,” by Robert E. Kopp, Andrew C. Kemp, Klaus Bittermann, Benjamin P. Horton, Jeffrey P. Donnelly, W. Roland Gehrels, Carling C. Hay, Jerry X. Mitrovica, Eric D. Morrow, and Stefan Rahmstorf, which appeared in issue 11, March 15, 2016,...



Correction for Miyoshi et al., Erasure of DNA methylation, genomic imprints, and epimutations in a primordial germ-cell model derived from mouse pluripotent stem cells [Correction]

2016-09-20T08:46:01-07:00

DEVELOPMENTAL BIOLOGY Correction for “Erasure of DNA methylation, genomic imprints, and epimutations in a primordial germ-cell model derived from mouse pluripotent stem cells,” by Norikatsu Miyoshi, Jente M. Stel, Keiko Shioda, Na Qu, Junko Odahima, Shino Mitsunaga, Xiangfan Zhang, Makoto Nagano, Konrad Hochedlinger, Kurt J. Isselbacher, and Toshi Shioda, which...



In This Issue [This Week in PNAS]

2016-09-13T09:35:47-07:00

Modern diets and gut microbiome composition Red-shanked doucs (Pygathrix nemaeus) on Son Tra Peninsula, Vietnam. Rich in fat, sugar, and animal protein, the quintessential modern Western diet is often deficient in plant-derived fibers and thought to disrupt the delicate balance of human gut microbes. To explore the effects of diet...



Fairy circles or termitaria ghosts in Australia? [Biological Sciences]

2016-09-13T09:35:48-07:00

For southern African grasslands, many hypotheses have been posed and contested to explain bare circular areas (“fairy circles”) (1). Getzin et al. (2) “discovered” similar bare areas in arid grasslands of Australia and investigated their causes. Their data and modeling supported the hypothesis that soil crusting, water flow, and plant...



Fairy circles develop without termitaria [Biological Sciences]

2016-09-13T09:35:48-07:00

Bare-soil gaps in arid grasslands often appear in conjunction with termites or ants (1, 2), but should this common correlation (3) automatically infer a causal relationship? To the unfamiliar, it may be difficult to realize that plant populations can organize themselves into geometric order so as to optimize their access...



BU08028 as a safe and nonaddictive analgesic [Pharmacology]

2016-09-13T09:35:47-07:00

Pain is a major clinical, social, and economic problem, affecting more people than diabetes, heart disease, and cancer combined (1). Pain medicine represents a large family of compounds that are commonly prescribed or sold over-the-counter for treating various painful conditions. Among these medications, opioids stand out as the most efficacious...



Cutting back on the carbs [Biochemistry]

2016-09-13T09:35:47-07:00

Glycans are essential components in maintaining many important biological processes within the body, and can be found in forms ranging from simple monomers to complex polymeric assemblies. On the cell surface, oligosaccharides are presented and recognized by an array of carbohydrate-binding proteins (lectins), such as sialic acid-binding Ig-like lectins (Siglecs),...



Battling combinatorics in multidrug therapies [Systems Biology]

2016-09-13T09:35:47-07:00

Drugs are often used in combination to treat bacterial infections, viruses, and cancer. Drug combinations may exhibit increased potency, decreased dosage-related side effects, and even the capacity to slow the emergence of resistance. The increased efficacy imparted by combining drugs—so-called drug “synergy”—has been a topic of fervent interest for decades...



The TimeGeo modeling framework for urban motility [Applied Physical Sciences]

2016-09-13T09:35:48-07:00

Well-established fine-scale urban mobility models today depend on detailed but cumbersome and expensive travel surveys for their calibration. Not much is known, however, about the set of mechanisms needed to generate complete mobility profiles if only using passive datasets with mostly sparse traces of individuals. In this study, we present...



Na2 coordination by NIS [Biochemistry]

2016-09-13T09:35:48-07:00

The sodium/iodide symporter (NIS) mediates active I− transport in the thyroid—the first step in thyroid hormone biosynthesis—with a 2 Na+: 1 I− stoichiometry. The two Na+ binding sites (Na1 and Na2) and the I− binding site interact allosterically: when Na+ binds to a Na+ site, the affinity of NIS for...



Comprehensive view of an unfolded protein [Biophysics and Computational Biology]

2016-09-13T09:35:48-07:00

The properties of unfolded proteins are essential both for the mechanisms of protein folding and for the function of the large group of intrinsically disordered proteins. However, the detailed structural and dynamical characterization of these highly dynamic and conformationally heterogeneous ensembles has remained challenging. Here we combine and compare three...



A function of DCS cells as stem cell niche [Cell Biology]

2016-09-13T09:35:48-07:00

Leucine-rich repeat-containing G-protein coupled receptor 5-positive (Lgr5+) stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF, and Notch signals to neighboring Lgr5+ stem cells. Whereas the colon lacks Paneth cells, deep crypt secretory (DCS) cells are intermingled with Lgr5+ stem...



MRG15 is required for splicing and spermatogenesis [Developmental Biology]

2016-09-13T09:35:48-07:00

Splicing can be epigenetically regulated and involved in cellular differentiation in somatic cells, but the interplay of epigenetic factors and the splicing machinery during spermatogenesis remains unclear. To study these interactions in vivo, we generated a germline deletion of MORF-related gene on chromosome 15 (MRG15), a multifunctional chromatin organizer that...



Repeated replacement of an intrabacterial symbiont [Evolution]

2016-09-13T09:35:48-07:00

Stable endosymbiosis of a bacterium into a host cell promotes cellular and genomic complexity. The mealybug Planococcus citri has two bacterial endosymbionts with an unusual nested arrangement: the γ-proteobacterium Moranella endobia lives in the cytoplasm of the β-proteobacterium Tremblaya princeps. These two bacteria, along with genes horizontally transferred from other...



A1CF and AGO2, parent-of-origin effects on TGCTs [Genetics]

2016-09-13T09:35:48-07:00

Testicular tumors, the most common cancer in young men, arise from abnormalities in germ cells during fetal development. Unconventional inheritance for testicular germ cell tumor (TGCT) risk both in humans and mice implicates epigenetic mechanisms. Apolipoprotein B mRNA-editing enzyme complex 1 (APOBEC1) cytidine deaminase and Deadend-1, which are involved in...



Regulations of macrophage phagocytosis of self [Immunology and Inflammation]

2016-09-13T09:35:48-07:00

Rapid clearance of adoptively transferred Cd47-null (Cd47−/−) cells in congeneic WT mice suggests a critical self-recognition mechanism, in which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein α (SIRPα) triggers inhibitory signaling through SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and tyrosine phosphatase SHP-1/2....



IL2R{beta}-dependent signals direct T-cell exhaustion [Immunology and Inflammation]

2016-09-13T09:35:48-07:00

Exhaustion of CD8+ T cells severely impedes the adaptive immune response to chronic viral infections. Despite major advances in our understanding of the molecular regulation of exhaustion, the cytokines that directly control this process during chronicity remain unknown. We demonstrate a direct impact of IL-2 and IL-15, two common gamma-chain–dependent...



Role of TCR nanoclusters in T-cell signaling [Immunology and Inflammation]

2016-09-13T09:35:48-07:00

Antigen recognition by the T-cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains...



MRI agent detects zinc release from prostate cells [Medical Sciences]

2016-09-13T09:35:48-07:00

Many secretory tissues release Zn(II) ions along with other molecules in response to external stimuli. Here we demonstrate that secretion of Zn(II) ions from normal, healthy prostate tissue is stimulated by glucose in fasted mice and that release of Zn(II) can be monitored by MRI. An ∼50% increase in water...



Metabolic features of chronic fatigue syndrome [Medical Sciences]

2016-09-13T09:35:48-07:00

More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria...



Cell migration mediated by MYC-nick [Medical Sciences]

2016-09-13T09:35:48-07:00

MYC-nick is a cytoplasmic, transcriptionally inactive member of the MYC oncoprotein family, generated by a proteolytic cleavage of full-length MYC. MYC-nick promotes migration and survival of cells in response to chemotherapeutic agents or withdrawal of glucose. Here we report that MYC-nick is abundant in colonic and intestinal tumors derived from...



Merkel disc is an epidermal serotonergic synapse [Neuroscience]

2016-09-13T09:35:48-07:00

The evolution of sensory systems has let mammals develop complicated tactile end organs to enable sophisticated sensory tasks, including social interaction, environmental exploration, and tactile discrimination. The Merkel disc, a main type of tactile end organ consisting of Merkel cells (MCs) and Aβ-afferent endings, are highly abundant in fingertips, touch...



Dopamine, dentate gyrus, and memory encoding [Neuroscience]

2016-09-13T09:35:48-07:00

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we...



Improved safe analgesic without abuse liability [Pharmacology]

2016-09-13T09:35:48-07:00

Despite the critical need, no previous research has substantiated safe opioid analgesics without abuse liability in primates. Recent advances in medicinal chemistry have led to the development of ligands with mixed mu opioid peptide (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor agonist activity to achieve this objective. BU08028 is a novel orvinol...



Mechanism for cross-talk between RALF and ABA [Plant Biology]

2016-09-13T09:35:48-07:00

Receptor-like kinase FERONIA (FER) plays a crucial role in plant response to small molecule hormones [e.g., auxin and abscisic acid (ABA)] and peptide signals [e.g., rapid alkalinization factor (RALF)]. It remains unknown how FER integrates these different signaling events in the control of cell growth and stress responses. Under stress...



Intratumor heterogeneity and phylogeny inference [Systems Biology]

2016-09-13T09:35:48-07:00

Cancer is a disease driven by evolutionary selection on somatic genetic and epigenetic alterations. Here, we propose Canopy, a method for inferring the evolutionary phylogeny of a tumor using both somatic copy number alterations and single-nucleotide alterations from one or more samples derived from a single patient. Canopy is applied...



Mesolithic foragers consumed domesticated cereals [Anthropology]

2016-09-13T09:35:48-07:00

Researchers agree that domesticated plants were introduced into southeast Europe from southwest Asia as a part of a Neolithic “package,” which included domesticated animals and artifacts typical of farming communities. It is commonly believed that this package reached inland areas of the Balkans by ∼6200 calibrated (cal.) BC or later....



Simple stochastic model for El Nino with WWB [Applied Mathematics]

2016-09-13T09:35:47-07:00

Atmospheric wind bursts in the tropics play a key role in the dynamics of the El Niño Southern Oscillation (ENSO). A simple modeling framework is proposed that summarizes this relationship and captures major features of the observational record while remaining physically consistent and amenable to detailed analysis. Within this simple...



Topological insulators promise computing advances [Applied Physical Sciences]

2016-09-13T09:35:47-07:00

For more than 200 years, physicists have wanted to understand why electricity flows through some materials and not others. In some of the first experiments aimed at understanding conductivity, at the start of the 18th century, British autodidact Stephen Gray observed that materials like metals (and some vegetables) conduct electricity,...



Wettability control on multiphase flow [Applied Physical Sciences]

2016-09-13T09:35:47-07:00

Multiphase flow in porous media is important in many natural and industrial processes, including geologic CO2 sequestration, enhanced oil recovery, and water infiltration into soil. Although it is well known that the wetting properties of porous media can vary drastically depending on the type of media and pore fluids, the...



Origin of embrittlement in metallic glasses [Applied Physical Sciences]

2016-09-13T09:35:47-07:00

Owing to their glassy nature, metallic glasses demonstrate a toughness that is extremely sensitive to the frozen-in configurational state. This sensitivity gives rise to “annealing embrittlement,” which is often severe and in many respects limits the technological advancement of these materials. Here, equilibrium configurations (i.e., “inherent states”) of a metallic...



Near-optimal nonequilibrium protocols [Applied Physical Sciences]

2016-09-13T09:35:47-07:00

The development of sophisticated experimental means to control nanoscale systems has motivated efforts to design driving protocols that minimize the energy dissipated to the environment. Computational models are a crucial tool in this practical challenge. We describe a general method for sampling an ensemble of finite-time, nonequilibrium protocols biased toward...



Generic phase diagram of binary superlattices [Applied Physical Sciences]

2016-09-13T09:35:47-07:00

Emergence of a large variety of self-assembled superlattices is a dramatic recent trend in the fields of nanoparticle and colloidal sciences. Motivated by this development, we propose a model that combines simplicity with a remarkably rich phase behavior applicable to a wide range of such self-assembled systems. Those systems include...