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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]

2017-11-21T10:01:35-08:00

Neanderthal and modern human noses 3D reconstruction of Neanderthal skulls based on CT scans. Image courtesy of A. Balzeau (Musée de l’Homme, Paris, France). Both Neanderthals and modern humans settled in cold, dry Eurasian environments. This development may have required adaptations in internal nasal anatomy that facilitated warming and humidification...



Redox potentials in the decaheme cytochrome MtrF: Poisson-Boltzmann vs. molecular dynamics simulations [Biological Sciences]

2017-11-21T10:01:35-08:00

We previously computed the redox potentials for the 10 hemes in the decaheme cytochrome MtrF using thermodynamic integration (TI) in combination with all-atom, explicit solvent molecular dynamics (MD) simulation (1). In a recent study, Watanabe et al. (2) recomputed these potentials using a Poisson–Boltzmann (PB) continuum approach. The potentials obtained...



Reply to Breuer et al.: Molecular dynamics simulations do not provide functionally relevant values of redox potential in MtrF [Biological Sciences]

2017-11-21T10:01:35-08:00

We previously reported that Asp631 decreased the redox potential (Em) for heme 9 by 136 mV [1,362 mV according to Breuer et al. (1)] in native MtrF, whereas Asp631 protonation (corresponding to Asn631 mutation) did not significantly affect Em for heme 9, because deprotonation of other residues compensated for the...



Crossbills were unlikely resident in the Bahamas; thus, there was no population to be extirpated [Biological Sciences]

2017-11-21T10:01:35-08:00

In PNAS, Steadman and Franklin (1) make the argument that the large reduction in land area and shift in vegetation in the Bahamian Archipelago from ∼15–9 ka caused declines and extirpation of two bird species, the Eastern bluebird (Sialia sialis) and Hispaniolan crossbill (Loxia megaplaga). Their evidence for L. megaplaga...



Reply to Benkman: Hispaniolan crossbills formerly resided in the Bahamas [Biological Sciences]

2017-11-21T10:01:35-08:00

We appreciate the issues raised in Benkman’s letter (1), which is critical of our paper (2). Here, we will address these issues. Benkman (1) believes that the late Pleistocene Bahamian (Abaco island) fossils we identified as Hispaniolan crossbill (Loxia megaplaga), in fact, represent nonresident individuals of red crossbill (Loxia curvirostra)....



IL-33/ST2 signaling boosts inflammation and pain [Biological Sciences]

2017-11-21T10:01:35-08:00

We read with interest the work of Taracanova et al. (1) on the synergic effect of substance P (SP) and IL-33 over TNF-α production. Notably, IL-33 potentiates SP-induced TNF-α production by more than 100-fold in mast cells. Both IL-33 and SP increase the expression of each other receptor, and more...



Reply to Fattori et al.: Action of SP and IL-33 on mast cells [Biological Sciences]

2017-11-21T10:01:35-08:00

We thank Fattori et al. (1) for their positive comments on our report (2). Their letter (1) contains much useful information on possible additional biological effects of IL-33. However, the publications discussed in the text and figure 1 in the Fattori et al. (1) letter do not directly address our...



Prebiotic phosphorylation enabled by microdroplets [Chemistry]

2017-11-21T10:01:35-08:00

The significant acceleration of reactions in confined environments has recently been reported in the literature (1–7). The reaction environments investigated span a diverse range, including charged microdroplets (1–3), microdiameter emulsions (5), inverted micelles (8), and the surfaces of aerosol particles (9). These experimental results have made the case that the...



Haplotype resolution at the single-cell level [Genetics]

2017-11-21T10:01:35-08:00

One of the most rapidly advancing areas in genomics in recent years has been the explosion of platforms to assess properties at the single-cell level. The driving force behind these advancements has been a renaissance of sorts in how we think about the architecture and heterogeneity present in a population...



Epigenetic switch turns on genetic behavioral variations [Genetics]

2017-11-21T10:01:35-08:00

What roles do environmental factors, genes, and heredity play in shaping the behaviors of individuals? In his 1963 article entitled “Behavior genetics and individuality understood,” the pioneering behavioral geneticist Jerry Hirsch (1) eloquently articulated that “Individual differences are no accident. They are generated by properties of organisms as fundamental to...



Filament rigidity and connectivity tune the deformation modes of active biopolymer networks [Applied Physical Sciences]

2017-11-21T10:01:35-08:00

Molecular motors embedded within collections of actin and microtubule filaments underlie the dynamics of cytoskeletal assemblies. Understanding the physics of such motor-filament materials is critical to developing a physical model of the cytoskeleton and designing biomimetic active materials. Here, we demonstrate through experiments and simulations that the rigidity and connectivity...



Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology [Applied Physical Sciences]

2017-11-21T10:01:35-08:00

Implantable electrical probes have led to advances in neuroscience, brain−machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution...



Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane [Chemistry]

2017-11-21T10:01:35-08:00

The packaging and budding of Gag polyprotein and viral RNA is a critical step in the HIV-1 life cycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization...



Aggregation control in natural brush-printed conjugated polymer films and implications for enhancing charge transport [Chemistry]

2017-11-21T10:01:35-08:00

Shear-printing is a promising processing technique in organic electronics for microstructure/charge transport modification and large-area film fabrication. Nevertheless, the mechanism by which shear-printing can enhance charge transport is not well-understood. In this study, a printing method using natural brushes is adopted as an informative tool to realize direct aggregation control...



Cell-to-cell variation sets a tissue-rheology-dependent bound on collective gradient sensing [Physics]

2017-11-21T10:01:35-08:00

When a single cell senses a chemical gradient and chemotaxes, stochastic receptor–ligand binding can be a fundamental limit to the cell’s accuracy. For clusters of cells responding to gradients, however, there is a critical difference: Even genetically identical cells have differing responses to chemical signals. With theory and simulation, we...



New free-exchange model of EmrE transport [Biophysics and Computational Biology]

2017-11-21T10:01:35-08:00

EmrE is a small multidrug resistance transporter found in Escherichia coli that confers resistance to toxic polyaromatic cations due to its proton-coupled antiport of these substrates. Here we show that EmrE breaks the rules generally deemed essential for coupled antiport. NMR spectra reveal that EmrE can simultaneously bind and cotransport...



GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis [Cell Biology]

2017-11-21T10:01:35-08:00

Eukaryotic cells chemotax in a wide range of chemoattractant concentration gradients, and thus need inhibitory processes that terminate cell responses to reach adaptation while maintaining sensitivity to higher-concentration stimuli. However, the molecular mechanisms underlying inhibitory processes are still poorly understood. Here, we reveal a locally controlled inhibitory process in a...



Proof of region-specific multipotent progenitors in human breast epithelia [Cell Biology]

2017-11-21T10:01:35-08:00

The human breast parenchyma consists of collecting ducts and terminal duct lobular units (TDLUs). The TDLU is the site of origin of most breast cancers. The reason for such focal susceptibility to cancer remains poorly understood. Here, we take advantage of a region-specific heterogeneity in luminal progenitors to interrogate the...



Structure and function of yeast Atg20, a sorting nexin that facilitates autophagy induction [Cell Biology]

2017-11-21T10:01:35-08:00

The Atg20 and Snx4/Atg24 proteins have been identified in a screen for mutants defective in a type of selective macroautophagy/autophagy. Both proteins are connected to the Atg1 kinase complex, which is involved in autophagy initiation, and bind phosphatidylinositol-3-phosphate. Atg20 and Snx4 contain putative BAR domains, suggesting a possible role in...



Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-{kappa}B signal transduction, and development [Cell Biology]

2017-11-21T10:01:35-08:00

In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins...



Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis [Developmental Biology]

2017-11-21T10:01:35-08:00

Mammalian spermatogenesis is an elaborately organized differentiation process, starting with diploid spermatogonia, which include germ-line stem cells, and ending with haploid spermatozoa. The process involves four pivotal transitions occurring in physical proximity: spermatogonial differentiation, meiotic initiation, initiation of spermatid elongation, and release of spermatozoa. We report how the four transitions...



Climate extremes and predicted warming threaten Mediterranean Holocene firs forests refugia [Ecology]

2017-11-21T10:01:35-08:00

Warmer and drier climatic conditions are projected for the 21st century; however, the role played by extreme climatic events on forest vulnerability is still little understood. For example, more severe droughts and heat waves could threaten quaternary relict tree refugia such as Circum-Mediterranean fir forests (CMFF). Using tree-ring data and...



SIRP{alpha}+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen [Immunology and Inflammation]

2017-11-21T10:01:35-08:00

In secondary lymphoid organs, development and homeostasis of stromal cells such as podoplanin (Pdpn)–positive fibroblastic reticular cells (FRCs) are regulated by hematopoietic cells, but the cellular and molecular mechanisms of such regulation have remained unclear. Here we show that ablation of either signal regulatory protein α (SIRPα), an Ig superfamily...



Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin {alpha}V{beta}8 [Immunology and Inflammation]

2017-11-21T10:01:35-08:00

Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-β1 into active TGF-β1. In Tregs, TGF-β1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-β1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not...



Peptidyl arginine deiminase immunization induces anticitrullinated protein antibodies in mice with particular MHC types [Medical Sciences]

2017-11-21T10:01:35-08:00

Autoantibodies to citrullinated proteins (ACPAs) are present in two-thirds of patients with rheumatoid arthritis (RA). ACPAs are produced in the absence of identified T cell responses for each citrullinated protein. Peptidyl arginine deiminase 4 (PAD4), which binds proteins and citrullinates them, is the target of autoantibodies in early RA. This...



HIF and HOIL-1L-mediated PKC{zeta} degradation stabilizes plasma membrane Na,K-ATPase to protect against hypoxia-induced lung inȷury [Medical Sciences]

2017-11-21T10:01:35-08:00

Organisms have evolved adaptive mechanisms in response to stress for cellular survival. During acute hypoxic stress, cells down-regulate energy-consuming enzymes such as Na,K-ATPase. Within minutes of alveolar epithelial cell (AEC) exposure to hypoxia, protein kinase C zeta (PKCζ) phosphorylates the α1-Na,K-ATPase subunit and triggers it for endocytosis, independently of the...



DGR mutagenic transposition occurs via hypermutagenic reverse transcription primed by nicked template RNA [Microbiology]

2017-11-21T10:01:35-08:00

Diversity-generating retroelements (DGRs) are molecular evolution machines that facilitate microbial adaptation to environmental changes. Hypervariation occurs via a mutagenic retrotransposition process from a template repeat (TR) to a variable repeat (VR) that results in adenine-to-random nucleotide conversions. Here we show that reverse transcription of the Bordetella phage DGR is primed...



Phosphatidylserine save-me signals drive functional recovery of severed axons in Caenorhabditis elegans [Neuroscience]

2017-11-21T10:01:36-08:00

Functional regeneration after axonal injury requires transected axons to regrow and reestablish connection with their original target tissue. The spontaneous regenerative mechanism known as axonal fusion provides a highly efficient means of achieving targeted reconnection, as a regrowing axon is able to recognize and fuse with its own detached axon...



let-7 miRNA controls CED-7 homotypic adhesion and EFF-1-mediated axonal self-fusion to restore touch sensation following inȷury [Neuroscience]

2017-11-21T10:01:36-08:00

Neuronal injury often leads to devastating consequences such as loss of senses or locomotion. Restoration of function after injury relies on whether the injured axons can find their target cells. Although fusion between injured proximal axon and distal fragment has been observed in many organisms, its functional significance is not...



Definition of the hypothalamic GnRH pulse generator in mice [Neuroscience]

2017-11-21T10:01:36-08:00

The pulsatile release of luteinizing hormone (LH) is critical for mammalian fertility. However, despite several decades of investigation, the identity of the neuronal network generating pulsatile reproductive hormone secretion remains unproven. We use here a variety of optogenetic approaches in freely behaving mice to evaluate the role of the arcuate...



DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity [Neuroscience]

2017-11-21T10:01:36-08:00

Mature mammalian neurons have a limited ability to extend neurites and make new synaptic connections, but the mechanisms that inhibit such plasticity remain poorly understood. Here, we report that OFF-type retinal bipolar cells in mice are an exception to this rule, as they form new anatomical connections within their tiled...



M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment [Neuroscience]

2017-11-21T10:01:36-08:00

Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes in the axon initial segment (AIS), which is pivotal for spike generation. Here, in hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form of AIS plasticity by selectively targeting M-type K+ channels,...



An RNA structure-mediated, posttranscriptional model of human {alpha}-1-antitrypsin expression [Systems Biology]

2017-11-21T10:01:36-08:00

Chronic obstructive pulmonary disease (COPD) affects over 65 million individuals worldwide, where α-1-antitrypsin deficiency is a major genetic cause of the disease. The α-1-antitrypsin gene, SERPINA1, expresses an exceptional number of mRNA isoforms generated entirely by alternative splicing in the 5′-untranslated region (5′-UTR). Although all SERPINA1 mRNAs encode exactly the...



Radiocarbon test for demographic events in written and oral history [Anthropology]

2017-11-21T10:01:35-08:00

We extend an established simulation-based method to test for significant short-duration (1–2 centuries) demographic events known from one documented historical and one oral historical context. Case study 1 extrapolates population data from the Western historical tradition using historically derived demographic data from the catastrophic European Black Death/bubonic plague (Yersinia pestis)....



Nasal airflow simulations suggest convergent adaptation in Neanderthals and modern humans [Anthropology]

2017-11-21T10:01:35-08:00

Both modern humans (MHs) and Neanderthals successfully settled across western Eurasian cold-climate landscapes. Among the many adaptations considered as essential to survival in such landscapes, changes in the nasal morphology and/or function aimed to humidify and warm the air before it reaches the lungs are of key importance. Unfortunately, the...



Inner Workings: Medical microrobots have potential in surgery, therapy, imaging, and diagnostics [Applied Biological Sciences]

2017-11-21T10:01:35-08:00

Trypanosoma brucei, the pathogen that causes sleeping sickness, has a clever and insidious trick to help it navigate its hosts’ innards: It changes shape depending on its surroundings. In bodily fluids, the bacterium assumes a long and narrow shape to propel itself forward, whipping its tail-like flagellum and spinning like...



Oxalate-curcumin-based probe for micro- and macroimaging of reactive oxygen species in Alzheimer’s disease [Applied Biological Sciences]

2017-11-21T10:01:35-08:00

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that has a progression that is closely associated with oxidative stress. It has long been speculated that the reactive oxygen species (ROS) level in AD brains is much higher than that in healthy brains. However, evidence from living beings is scarce. Inspired...



Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy [Applied Biological Sciences]

2017-11-21T10:01:35-08:00

The TGF-β family ligands myostatin, GDF11, and activins are negative regulators of skeletal muscle mass, which have been reported to primarily signal via the ActRIIB receptor on skeletal muscle and thereby induce muscle wasting described as cachexia. Use of a soluble ActRIIB-Fc “trap,” to block myostatin pathway signaling in normal...



How social information can improve estimation accuracy in human groups [Applied Physical Sciences]

2017-11-21T10:01:35-08:00

In our digital and connected societies, the development of social networks, online shopping, and reputation systems raises the questions of how individuals use social information and how it affects their decisions. We report experiments performed in France and Japan, in which subjects could update their estimates after having received information...



Engineering of a membrane-triggered activity switch in coagulation factor VIIa [Biochemistry]

2017-11-21T10:01:35-08:00

Recombinant factor VIIa (FVIIa) variants with increased activity offer the promise to improve the treatment of bleeding episodes in patients with inhibitor-complicated hemophilia. Here, an approach was adopted to enhance the activity of FVIIa by selectively optimizing substrate turnover at the membrane surface. Under physiological conditions, endogenous FVIIa engages its...



Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model [Biochemistry]

2017-11-21T10:01:35-08:00

Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, γδ T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its...



Ribonucleotides incorporated by the yeast mitochondrial DNA polymerase are not repaired [Biochemistry]

2017-11-21T10:01:35-08:00

Incorporation of ribonucleotides into DNA during genome replication is a significant source of genomic instability. The frequency of ribonucleotides in DNA is determined by deoxyribonucleoside triphosphate/ribonucleoside triphosphate (dNTP/rNTP) ratios, by the ability of DNA polymerases to discriminate against ribonucleotides, and by the capacity of repair mechanisms to remove incorporated ribonucleotides....



Quantifying the limits of transition state theory in enzymatic catalysis [Biophysics and Computational Biology]

2017-11-21T10:01:35-08:00

While being one of the most popular reaction rate theories, the applicability of transition state theory to the study of enzymatic reactions has been often challenged. The complex dynamic nature of the protein environment raised the question about the validity of the nonrecrossing hypothesis, a cornerstone in this theory. We...



Limiting (zero-load) speed of the rotary motor of Escherichia coli is independent of the number of torque-generating units [Biophysics and Computational Biology]

2017-11-21T10:01:35-08:00

Rotation of the bacterial flagellar motor is driven by multiple torque-generating units (stator elements). The torque-generating dynamics can be understood in terms of the “duty ratio” of the stator elements, that is, the fraction of time a stator element engages with the rotor during its mechanochemical cycle. The dependence of...



Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2 [Biophysics and Computational Biology]

2017-11-21T10:01:35-08:00

The P-element–induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway plays a central role in transposon silencing and genome protection in the animal germline. A family of Tudor domain proteins regulates the piRNA pathway through direct Tudor domain–PIWI interactions. Tudor domains are known to fulfill this function by binding to methylated PIWI...



Ultraaccurate genome sequencing and haplotyping of single human cells [Biophysics and Computational Biology]

2017-11-21T10:01:35-08:00

Accurate detection of variants and long-range haplotypes in genomes of single human cells remains very challenging. Common approaches require extensive in vitro amplification of genomes of individual cells using DNA polymerases and high-throughput short-read DNA sequencing. These approaches have two notable drawbacks. First, polymerase replication errors could generate tens of...



Charged residues in the H-NS linker drive DNA binding and gene silencing in single cells [Biophysics and Computational Biology]

2017-11-21T10:01:35-08:00

Nucleoid-associated proteins (NAPs) facilitate chromosome organization in bacteria, but the precise mechanism remains elusive. H-NS is a NAP that also plays a major role in silencing pathogen genes. We used genetics, single-particle tracking in live cells, superresolution microscopy, atomic force microscopy, and molecular dynamics simulations to examine H-NS/DNA interactions in...



Diminished Ost3-dependent N-glycosylation of the BiP nucleotide exchange factor Sil1 is an adaptive response to reductive ER stress [Cell Biology]

2017-11-21T10:01:35-08:00

BiP (Kar2 in yeast) is an essential Hsp70 chaperone and master regulator of endoplasmic reticulum (ER) function. BiP’s activity is regulated by its intrinsic ATPase activity that can be stimulated by two different nucleotide exchange factors, Sil1 and Lhs1. Both Sil1 and Lhs1 are glycoproteins, but how N-glycosylation regulates their...



Syntenin mediates SRC function in exosomal cell-to-cell communication [Cell Biology]

2017-11-21T10:01:35-08:00

The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and the activity of exosomes. Exosomes are viral-like...



Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products [Chemistry]

2017-11-21T10:01:35-08:00

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH3CHOO. IR excitation of selectively deuterated...



Enzyme stabilization via computationally guided protein stapling [Chemistry]

2017-11-21T10:01:35-08:00

Thermostabilization represents a critical and often obligatory step toward enhancing the robustness of enzymes for organic synthesis and other applications. While directed evolution methods have provided valuable tools for this purpose, these protocols are laborious and time-consuming and typically require the accumulation of several mutations, potentially at the expense of...



Efficient gene knockin in axolotl and its use to test the role of satellite cells in limb regeneration [Developmental Biology]

2017-11-21T10:01:35-08:00

Salamanders exhibit extensive regenerative capacities and serve as a unique model in regeneration research. However, due to the lack of targeted gene knockin approaches, it has been difficult to label and manipulate some of the cell populations that are crucial for understanding the mechanisms underlying regeneration. Here we have established...



Ion pair particles at the air-water interface [Earth, Atmospheric, and Planetary Sciences]

2017-11-21T10:01:35-08:00

Although the role of methanesulfonic acid (HMSA) in particle formation in the gas phase has been extensively studied, the details of the HMSA-induced ion pair particle formation at the air–water interface are yet to be examined. In this work, we have performed Born–Oppenheimer molecular dynamics simulations and density functional theory...



Incremental heating of Bishop Tuff sanidine reveals preeruptive radiogenic Ar and rapid remobilization from cold storage [Earth, Atmospheric, and Planetary Sciences]

2017-11-21T10:01:35-08:00

Accurate and precise ages of large silicic eruptions are critical to calibrating the geologic timescale and gauging the tempo of changes in climate, biologic evolution, and magmatic processes throughout Earth history. The conventional approach to dating these eruptive products using the 40Ar/39Ar method is to fuse dozens of individual feldspar...



Effect of paleoseawater composition on hydrothermal exchange in midocean ridges [Earth, Atmospheric, and Planetary Sciences]

2017-11-21T10:01:35-08:00

Variations in the Mg, Ca, Sr, and SO4 concentrations of paleoseawater can affect the chemical exchange between seawater and oceanic basalt in hydrothermal systems at midocean ridges (MOR). We present a model for evaluating the nature and magnitude of these previously unappreciated effects, using available estimates of paleoseawater composition over...



Scale-dependent portfolio effects explain growth inflation and volatility reduction in landscape demography [Ecology]

2017-11-21T10:01:35-08:00

Population demography is central to fundamental ecology and for predicting range shifts, decline of threatened species, and spread of invasive organisms. There is a mismatch between most demographic work, carried out on few populations and at local scales, and the need to predict dynamics at landscape and regional scales. Inspired...



Near-infrared remotely triggered drug-release strategies for cancer treatment [Engineering]

2017-11-21T10:01:35-08:00

Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here,...



Myoanatomy of the velvet worm leg revealed by laboratory-based nanofocus X-ray source tomography [Evolution]

2017-11-21T10:01:35-08:00

X-ray computed tomography (CT) is a powerful noninvasive technique for investigating the inner structure of objects and organisms. However, the resolution of laboratory CT systems is typically limited to the micrometer range. In this paper, we present a table-top nanoCT system in conjunction with standard processing tools that is able...



Abiotic production of sugar phosphates and uridine ribonucleoside in aqueous microdroplets [Evolution]

2017-11-21T10:01:35-08:00

Phosphorylation is an essential chemical reaction for life. This reaction generates fundamental cell components, including building blocks for RNA and DNA, phospholipids for cell walls, and adenosine triphosphate (ATP) for energy storage. However, phosphorylation reactions are thermodynamically unfavorable in solution. Consequently, a long-standing question in prebiotic chemistry is how abiotic...



Epigenetic mechanisms modulate differences in Drosophila foraging behavior [Genetics]

2017-11-21T10:01:35-08:00

Little is known about how genetic variation and epigenetic marks interact to shape differences in behavior. The foraging (for) gene regulates behavioral differences between the rover and sitter Drosophila melanogaster strains, but the molecular mechanisms through which it does so have remained elusive. We show that the epigenetic regulator G9a...



Coordinated regulation of heterochromatin inheritance by Dpb3-Dpb4 complex [Genetics]

2017-11-21T10:01:35-08:00

During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the...



Key amino acid residues conferring enhanced enzyme activity at cold temperatures in an Antarctic polyextremophilic {beta}-galactosidase [Genetics]

2017-11-21T10:01:35-08:00

The Antarctic microorganism Halorubrum lacusprofundi harbors a model polyextremophilic β-galactosidase that functions in cold, hypersaline conditions. Six amino acid residues potentially important for cold activity were identified by comparative genomics and substituted with evolutionarily conserved residues (N251D, A263S, I299L, F387L, I476V, and V482L) in closely related homologs from mesophilic haloarchaea....



DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line [Genetics]

2017-11-21T10:01:35-08:00

Meiotic synapsis and recombination between homologs permits the formation of cross-overs that are essential for generating chromosomally balanced sperm and eggs. In mammals, surveillance mechanisms eliminate meiotic cells with defective synapsis, thereby minimizing transmission of aneuploidy. One such surveillance mechanism is meiotic silencing, the inactivation of genes located on asynapsed...



Metabolic control of regulatory T cell (Treg) survival and function by Lkb1 [Immunology and Inflammation]

2017-11-21T10:01:35-08:00

The metabolic programs of functionally distinct T cell subsets are tailored to their immunologic activities. While quiescent T cells use oxidative phosphorylation (OXPHOS) for energy production, and effector T cells (Teffs) rely on glycolysis for proliferation, the distinct metabolic features of regulatory T cells (Tregs) are less well established. Here...



Circadian clock cryptochrome proteins regulate autoimmunity [Immunology and Inflammation]

2017-11-21T10:01:35-08:00

The circadian system regulates numerous physiological processes including immune responses. Here, we show that mice deficient of the circadian clock genes Cry1 and Cry2 [Cry double knockout (DKO)] develop an autoimmune phenotype including high serum IgG concentrations, serum antinuclear antibodies, and precipitation of IgG, IgM, and complement 3 in glomeruli...



Science and Culture: Researchers find history in the diagrams of Euclid’s Elements [Mathematics]

2017-11-21T10:01:35-08:00

The fourth book of Euclid’s Elements, a 2,300-year-old geometry text, includes directions for constructing a 15-sided polygon inside a circle. The first step is familiar to geometry students: Draw an equilateral triangle and a regular pentagon so their vertices touch the circle and the two shapes share one vertex. In...



Natural language indicators of differential gene regulation in the human immune system [Medical Sciences]

2017-11-21T10:01:35-08:00

Adverse social conditions have been linked to a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that may contribute to social gradients in disease. However, the CNS mechanisms involved remain obscure, in part because CTRA gene-expression profiles often track external social–environmental variables more closely than they do self-reported internal...



Effect of naturally occurring Wolbachia in Anopheles gambiae s.l. mosquitoes from Mali on Plasmodium falciparum malaria transmission [Microbiology]

2017-11-21T10:01:35-08:00

A naturally occurring Wolbachia strain (wAnga-Mali) was identified in mosquitoes of the Anopheles gambiae complex collected in the Malian villages of Dangassa and Kenieroba. Phylogenetic analysis of the nucleotide sequence of two 16S rRNA regions showed that wAnga-Mali clusters with Wolbachia strains from supergroup A and has the highest homology...



Structure and mechanotransmission mechanism of the MacB ABC transporter superfamily [Microbiology]

2017-11-21T10:01:35-08:00

MacB is an ABC transporter that collaborates with the MacA adaptor protein and TolC exit duct to drive efflux of antibiotics and enterotoxin STII out of the bacterial cell. Here we present the structure of ATP-bound MacB and reveal precise molecular details of its mechanism. The MacB transmembrane domain lacks...



Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains [Microbiology]

2017-11-21T10:01:35-08:00

H3N2 viruses continuously acquire mutations in the hemagglutinin (HA) glycoprotein that abrogate binding of human antibodies. During the 2014–2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today. The 2016–2017 seasonal influenza vaccine was...



Directed evolution of SecB chaperones toward toxin-antitoxin systems [Microbiology]

2017-11-21T10:01:35-08:00

SecB chaperones assist protein export in bacteria. However, certain SecB family members have diverged to become specialized toward the control of toxin-antitoxin (TA) systems known to promote bacterial adaptation to stress and persistence. In such tripartite TA-chaperone (TAC) systems, the chaperone was shown to assist folding and to prevent degradation...



Three-dimensional visualization and a deep-learning model reveal complex fungal parasite networks in behaviorally manipulated ants [Microbiology]

2017-11-21T10:01:35-08:00

Some microbes possess the ability to adaptively manipulate host behavior. To better understand how such microbial parasites control animal behavior, we examine the cell-level interactions between the species-specific fungal parasite Ophiocordyceps unilateralis sensu lato and its carpenter ant host (Camponotus castaneus) at a crucial moment in the parasite’s lifecycle: when...



Host-based lipid inflammation drives pathogenesis in Francisella infection [Microbiology]

2017-11-21T10:01:35-08:00

Mass spectrometry imaging (MSI) was used to elucidate host lipids involved in the inflammatory signaling pathway generated at the host–pathogen interface during a septic bacterial infection. Using Francisella novicida as a model organism, a bacterial lipid virulence factor (endotoxin) was imaged and identified along with host phospholipids involved in the...



Subplate neurons are the first cortical neurons to respond to sensory stimuli [Neuroscience]

2017-11-21T10:01:35-08:00

In utero experience, such as maternal speech in humans, can shape later perception, although the underlying cortical substrate is unknown. In adult mammals, ascending thalamocortical projections target layer 4, and the onset of sensory responses in the cortex is thought to be dependent on the onset of thalamocortical transmission to...



Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney inȷury involved in GSK3{beta} signaling [Pharmacology]

2017-11-21T10:01:35-08:00

Acute kidney injury (AKI) causes severe morbidity and mortality for which new therapeutic strategies are needed. Docosahexaenoic acid (DHA), arachidonic acid (ARA), and their metabolites have various effects in kidney injury, but their molecular mechanisms are largely unknown. Here, we report that 14 (15)-epoxyeicosatrienoic acid [14 (15)-EET] and 19 (20)-epoxydocosapentaenoic...



Observation of a remarkable reduction of correlation effects in BaCr2As2 by ARPES [Physics]

2017-11-21T10:01:35-08:00

The superconducting phase in iron-based high-Tc superconductors (FeSC), as in other unconventional superconductors such as the cuprates, neighbors a magnetically ordered one in the phase diagram. This proximity hints at the importance of electron correlation effects in these materials, and Hund’s exchange interaction has been suggested to be the dominant...



High-temperature charge density wave correlations in La1.875Ba0.125CuO4 without spin-charge locking [Physics]

2017-11-21T10:01:35-08:00

Although all superconducting cuprates display charge-ordering tendencies, their low-temperature properties are distinct, impeding efforts to understand the phenomena within a single conceptual framework. While some systems exhibit stripes of charge and spin, with a locked periodicity, others host charge density waves (CDWs) without any obviously related spin order. Here we...



Poaceae-specific MS1 encodes a phospholipid-binding protein for male fertility in bread wheat [Plant Biology]

2017-11-21T10:01:35-08:00

Male sterility is an essential trait in hybrid seed production for monoclinous crops, including rice and wheat. However, compared with the high percentage of hybrid rice planted in the world, little commercial hybrid wheat is planted globally as a result of the lack of a suitable system for male sterility....



Correction for Danhart et al., Conformational and chemical selection by a trans-acting editing domain [Correction]

2017-11-21T10:01:36-08:00

BIOCHEMISTRY Correction for “Conformational and chemical selection by a trans-acting editing domain,” by Eric M. Danhart, Marina Bakhtina, William A. Cantara, Alexandra B. Kuzmishin, Xiao Ma, Brianne L. Sanford, Marija Košutić, Yuki Goto, Hiroaki Suga, Kotaro Nakanishi, Ronald Micura, Mark P. Foster, and Karin Musier-Forsyth, which was first published August...



Correction for Sansone et al., Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer [Correction]

2017-11-21T10:01:36-08:00

MEDICAL SCIENCES Correction for “Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer,” by Pasquale Sansone, Claudia Savini, Ivana Kurelac, Qing Chang, Laura Benedetta Amato, Antonio Strillacci, Anna Stepanova, Luisa Iommarini, Chiara Mastroleo, Laura Daly, Alexander Galkin, Basant Kumar Thakur, Nadine Soplop,...