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Preview: Proceedings of the National Academy of Sciences recent issues

Proceedings of the National Academy of Sciences recent issues



Proceedings of the National Academy of Sciences RSS feed -- recent issues



 



In This Issue [This Week in PNAS]

2017-12-05T12:21:07-08:00

Cas9-expressing mosquito strains pave the way toward gene drives SEM image of genome-edited adult female mosquito. Left compound eye is split up, and there are three maxillary palps instead of the normal two. Image courtesy of Michelle Bui and Alexander Knyshov (University of California, Riverside, CA). Previous efforts to use...



Still Bay and Howiesons Poort sites (South Africa) are consistent with the risk hypothesis [Social Sciences]

2017-12-05T12:21:07-08:00

d’Errico et al.’s (1) conclusion that cultural differences between the Still Bay (SB) and the Howiesons Poort (HP) sites in South Africa (SA) are not accounted for by the risk hypothesis (2) is premature. The risk hypothesis is well-modeled by interaction between risk and mobility as a driver for artifact...



Reply to Read: Middle Stone Age cultural variability and the risk hypothesis [Social Sciences]

2017-12-05T12:21:07-08:00

Read’s letter (1) on our article (2) unfortunately misinterprets the conclusions we reached and hypotheses we proposed. We struggle to find a passage in which we state that the risk hypothesis does not account for the material culture differences that we observe between the Still Bay and Howiesons Poort cultural...



Transcription start site-associated small RNAs in the PTEN gene [Biological Sciences]

2017-12-05T12:21:07-08:00

The PTEN gene is inactivated in various cancers. PTEN has a pseudogene in the human genome, PTENpg1, which up-regulates PTEN expression by acting as a miRNA sponge. Interestingly, one of the antisense RNAs from the PTENpg1 locus, PTENpg1 asRNA α, is found to epigenetically down-regulate PTEN transcription by recruitment of...



Reply to Liu et al.: Yin and yang of PTEN regulation [Biological Sciences]

2017-12-05T12:21:07-08:00

In a letter to the editor, Liu et al. (1) find that PTEN contains some transcript variants that are polyadenylated and prematurely terminated in the first intron of PTEN. These transcripts are suggested to be 5′-UTR–containing promoter-spanning and to encode for three small RNAs (sRNAs), with one of these (sRNA3)...



Differential effects of global and local climate data in assessing environmental drivers of epidemic outbreaks [Ecology]

2017-12-05T12:21:07-08:00

This Commentary is the response of a China historian to the paper by the team of biologists headed by Huidong Tian (1) on the differential effects of using long-term or short-term data to reconstruct climatic drivers of human epidemics. The Tian et al. paper is a response to an anomaly...



Shifts in time and space interact as climate warms [Ecology]

2017-12-05T12:21:07-08:00

Beetles found on Mediterranean shores in cold periods turned up in Finland in mild interglacials (1). Paleontologists see such range shifts as systematic responses to changing climate. No surprise, then, that recent global trends for poleward and upward range shifts are attributed to current warming (2, 3). However, range shifts...



The power of negative [theoretical] results [Evolution]

2017-12-05T12:21:07-08:00

In PNAS, Paul Nelson and Joanna Masel present a theoretical result showing that aging in multicellular organisms is inevitable (1). The argument is as simple as it is powerful. Cellular senescence is a well-known consequence of the second law of thermodynamics, due to mutations, epigenetic misregulation, and protein misfolding. Molecular...



Dabbling with Piezo2 for mechanosensation [Physiology]

2017-12-05T12:21:07-08:00

Nature has devised various strategies for sensing food so species can coexist and exploit different types of prey. Sharks can detect amino acids in blood as low as 1 ppb, while hawks and buzzards scan the Earth from a height of ∼10,000 feet looking for rodents. However, not all birds...



Equilibration of energy in slow-fast systems [Applied Mathematics]

2017-12-05T12:21:07-08:00

Ergodicity is a fundamental requirement for a dynamical system to reach a state of statistical equilibrium. However, in systems with several characteristic timescales, the ergodicity of the fast subsystem impedes the equilibration of the whole system because of the presence of an adiabatic invariant. In this paper, we show that...



Holocene fluctuations in human population demonstrate repeated links to food production and climate [Sustainability Science]

2017-12-05T12:21:07-08:00

We consider the long-term relationship between human demography, food production, and Holocene climate via an archaeological radiocarbon date series of unprecedented sampling density and detail. There is striking consistency in the inferred human population dynamics across different regions of Britain and Ireland during the middle and later Holocene. Major cross-regional...



EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling [Cell Biology]

2017-12-05T12:21:07-08:00

Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called “tumor-initiating cells” (TICs), with SC-like properties. Mammary SCs (MaSCs) reside in the basal compartment...



Germline Cas9 expression yields highly efficient genome engineering in a major worldwide disease vector, Aedes aegypti [Genetics]

2017-12-05T12:21:07-08:00

The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito disease vector Aedes...



Tracking the genome-wide outcomes of a transposable element burst over decades of amplification [Genetics]

2017-12-05T12:21:07-08:00

To understand the success strategies of transposable elements (TEs) that attain high copy numbers, we analyzed two pairs of rice (Oryza sativa) strains, EG4/HEG4 and A119/A123, undergoing decades of rapid amplification (bursts) of the class 2 autonomous Ping element and the nonautonomous miniature inverted repeat transposable element (MITE) mPing. Comparative...



Histone methyltransferase MMSET promotes AID-mediated DNA breaks at the donor switch region during class switch recombination [Immunology and Inflammation]

2017-12-05T12:21:07-08:00

In B cells, Ig class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID), the activity of which leads to DNA double-strand breaks (DSBs) within IgH switch (S) regions. Preferential targeting of AID-mediated DSBs to S sequences is critical for allowing diversification of antibody functions, while minimizing potential off-target...



Atypical activation of dendritic cells by Plasmodium falciparum [Immunology and Inflammation]

2017-12-05T12:21:07-08:00

Dendritic cells (DCs) are activated by pathogens to initiate and shape immune responses. We found that the activation of DCs by Plasmodium falciparum, the main causative agent of human malaria, induces a highly unusual phenotype by which DCs up-regulate costimulatory molecules and secretion of chemokines, but not of cytokines typical...



Anti-SIRP{alpha} antibody immunotherapy enhances neutrophil and macrophage antitumor activity [Immunology and Inflammation]

2017-12-05T12:21:07-08:00

Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulatory protein-α (SIRPα)...



Transcriptome-wide characterization of human cytomegalovirus in natural infection and experimental latency [Microbiology]

2017-12-05T12:21:07-08:00

The transcriptional program associated with herpesvirus latency and the viral genes regulating entry into and exit from latency are poorly understood and controversial. Here, we developed and validated a targeted enrichment platform and conducted large-scale transcriptome analyses of human cytomegalovirus (HCMV) infection. We used both an experimental hematopoietic cell model...



Origin, evolution, and global transmission of community-acquired Staphylococcus aureus ST8 [Microbiology]

2017-12-05T12:21:07-08:00

USA300 is a pandemic clonal lineage of hypervirulent, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) with specific molecular characteristics. Despite its high clinical relevance, the evolutionary origin of USA300 remained unclear. We used comparative genomics of 224 temporal and spatial diverse S. aureus isolates of multilocus sequence type (ST) 8 to reconstruct...



Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate [Agricultural Sciences]

2017-12-05T12:21:07-08:00

Insecticides are widely used to control pests in agriculture and insect vectors that transmit human diseases. However, these chemicals can have a negative effect on nontarget, beneficial organisms including bees. Discovery and deployment of selective insecticides is a major mission of modern toxicology and pest management. Pyrethroids exert their toxic...



Kinship structures create persistent channels for language transmission [Anthropology]

2017-12-05T12:21:07-08:00

Languages are transmitted through channels created by kinship systems. Given sufficient time, these kinship channels can change the genetic and linguistic structure of populations. In traditional societies of eastern Indonesia, finely resolved cophylogenies of languages and genes reveal persistent movements between stable speech communities facilitated by kinship rules. When multiple...



Opinion: Building a better past with the help of agent-based modeling [Anthropology]

2017-12-05T12:21:07-08:00

With a few exceptions, the distant past is an anonymous land occupied by people who made things and left behind a cryptic record of broken pieces. Even when the written word comes into play in human history and we can read the hieroglyphs naming an Egyptian pharaoh and describing royal...



Dynamics of a rolling robot [Applied Mathematics]

2017-12-05T12:21:07-08:00

Equations describing the rolling of a spherical ball on a horizontal surface are obtained, the motion being activated by an internal rotor driven by a battery mechanism. The rotor is modeled as a point mass mounted inside a spherical shell and caused to move in a prescribed circular orbit relative...



Beating the curse of dimension with accurate statistics for the Fokker-Planck equation in complex turbulent systems [Applied Mathematics]

2017-12-05T12:21:07-08:00

Solving the Fokker–Planck equation for high-dimensional complex dynamical systems is an important issue. Recently, the authors developed efficient statistically accurate algorithms for solving the Fokker–Planck equations associated with high-dimensional nonlinear turbulent dynamical systems with conditional Gaussian structures, which contain many strong non-Gaussian features such as intermittency and fat-tailed probability density...



Active turbulence in a gas of self-assembled spinners [Applied Physical Sciences]

2017-12-05T12:21:07-08:00

Colloidal particles subject to an external periodic forcing exhibit complex collective behavior and self-assembled patterns. A dispersion of magnetic microparticles confined at the air–liquid interface and energized by a uniform uniaxial alternating magnetic field exhibits dynamic arrays of self-assembled spinners rotating in either direction. Here, we report on experimental and...



Dynamics and control of gold-encapped gallium arsenide nanowires imaged by 4D electron microscopy [Applied Physical Sciences]

2017-12-05T12:21:07-08:00

Eutectic-related reaction is a special chemical/physical reaction involving multiple phases, solid and liquid. Visualization of a phase reaction of composite nanomaterials with high spatial and temporal resolution provides a key understanding of alloy growth with important industrial applications. However, it has been a rather challenging task. Here, we report the...



Structural insights into enzymatic [4+2] aza-cycloaddition in thiopeptide antibiotic biosynthesis [Biochemistry]

2017-12-05T12:21:07-08:00

The [4+2] cycloaddition reaction is an enabling transformation in modern synthetic organic chemistry, but there are only limited examples of dedicated natural enzymes that can catalyze this transformation. Thiopeptides (or more formally thiazolyl peptides) are a class of thiazole-containing, highly modified, macrocyclic secondary metabolites made from ribosomally synthesized precursor peptides....



Evidence for rRNA 2'-O-methylation plasticity: Control of intrinsic translational capabilities of human ribosomes [Biochemistry]

2017-12-05T12:21:07-08:00

Ribosomal RNAs (rRNAs) are main effectors of messenger RNA (mRNA) decoding, peptide-bond formation, and ribosome dynamics during translation. Ribose 2′-O-methylation (2′-O-Me) is the most abundant rRNA chemical modification, and displays a complex pattern in rRNA. 2′-O-Me was shown to be essential for accurate and efficient protein synthesis in eukaryotic cells....



Metal transporter Slc39a10 regulates susceptibility to inflammatory stimuli by controlling macrophage survival [Biochemistry]

2017-12-05T12:21:07-08:00

Zn plays a key role in controlling macrophage function during an inflammatory event. Cellular Zn homeostasis is regulated by two families of metal transporters, the SLC39A family of importers and the SLC30A family of exporters; however, the precise role of these transporters in maintaining macrophage function is poorly understood. Using...



Cholesterol-binding site of the influenza M2 protein in lipid bilayers from solid-state NMR [Biophysics and Computational Biology]

2017-12-05T12:21:07-08:00

The influenza M2 protein not only forms a proton channel but also mediates membrane scission in a cholesterol-dependent manner to cause virus budding and release. The atomic interaction of cholesterol with M2, as with most eukaryotic membrane proteins, has long been elusive. We have now determined the cholesterol-binding site of...



Catch bond drives stator mechanosensitivity in the bacterial flagellar motor [Biophysics and Computational Biology]

2017-12-05T12:21:07-08:00

The bacterial flagellar motor (BFM) is the rotary motor that rotates each bacterial flagellum, powering the swimming and swarming of many motile bacteria. The torque is provided by stator units, ion motive force-powered ion channels known to assemble and disassemble dynamically in the BFM. This turnover is mechanosensitive, with the...



Kinesin-dependent mechanism for controlling triglyceride secretion from the liver [Cell Biology]

2017-12-05T12:21:07-08:00

Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and...



Model-driven engineering of supramolecular buffering by multivalency [Chemistry]

2017-12-05T12:21:07-08:00

A supramolecular system in which the concentration of a molecule is buffered over several orders of magnitude is presented. Molecular buffering is achieved as a result of competition in a ring–chain equilibrium of multivalent ureidopyrimidinone monomers and a monovalent naphthyridine molecule which acts as an end-capper. While we previously only...



Wetter subtropics in a warmer world: Contrasting past and future hydrological cycles [Earth, Atmospheric, and Planetary Sciences]

2017-12-05T12:21:07-08:00

During the warm Miocene and Pliocene Epochs, vast subtropical regions had enough precipitation to support rich vegetation and fauna. Only with global cooling and the onset of glacial cycles some 3 Mya, toward the end of the Pliocene, did the broad patterns of arid and semiarid subtropical regions become fully...



Multiple pathways in pressure-induced phase transition of coesite [Earth, Atmospheric, and Planetary Sciences]

2017-12-05T12:21:07-08:00

High-pressure single-crystal X-ray diffraction method with precise control of hydrostatic conditions, typically with helium or neon as the pressure-transmitting medium, has significantly changed our view on what happens with low-density silica phases under pressure. Coesite is a prototype material for pressure-induced amorphization. However, it was found to transform into a...



Scale-dependent climatic drivers of human epidemics in ancient China [Ecology]

2017-12-05T12:21:07-08:00

A wide range of climate change-induced effects have been implicated in the prevalence of infectious diseases. Disentangling causes and consequences, however, remains particularly challenging at historical time scales, for which the quality and quantity of most of the available natural proxy archives and written documentary sources often decline. Here, we...



Phenological shifts conserve thermal niches in North American birds and reshape expectations for climate-driven range shifts [Ecology]

2017-12-05T12:21:07-08:00

Species respond to climate change in two dominant ways: range shifts in latitude or elevation and phenological shifts of life-history events. Range shifts are widely viewed as the principal mechanism for thermal niche tracking, and phenological shifts in birds and other consumers are widely understood as the principal mechanism for...



Fishnet model for failure probability tail of nacre-like imbricated lamellar materials [Engineering]

2017-12-05T12:21:07-08:00

Nacre, the iridescent material of the shells of pearl oysters and abalone, consists mostly of aragonite (a form of CaCO3), a brittle constituent of relatively low strength (≈10 MPa). Yet it has astonishing mean tensile strength (≈150 MPa) and fracture energy (≈350 to 1,240 J/m2). The reasons have recently become...



Intercellular competition and the inevitability of multicellular aging [Evolution]

2017-12-05T12:21:07-08:00

Current theories attribute aging to a failure of selection, due to either pleiotropic constraints or declining strength of selection after the onset of reproduction. These theories implicitly leave open the possibility that if senescence-causing alleles could be identified, or if antagonistic pleiotropy could be broken, the effects of aging might...



Drosophila protein phosphatases 2A B' Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin [Genetics]

2017-12-05T12:21:07-08:00

Proper segregation of chromosomes in meiosis is essential to prevent miscarriages and birth defects. This requires that sister chromatids maintain cohesion at the centromere as cohesion is released on the chromatid arms when the homologs segregate at anaphase I. The Shugoshin proteins preserve centromere cohesion by protecting the cohesin complex...



Cancer cells induce interleukin-22 production from memory CD4+ T cells via interleukin-1 to promote tumor growth [Immunology and Inflammation]

2017-12-05T12:21:07-08:00

IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory...



SNX8 mediates IFN{gamma}-triggered noncanonical signaling pathway and host defense against Listeria monocytogenes [Immunology and Inflammation]

2017-12-05T12:21:07-08:00

IFNγ is a cytokine that plays a key role in host defense against intracellular pathogens. In addition to the canonical JAK-STAT1 pathway, IFNγ also activates an IKKβ-mediated noncanonical signaling pathway that is essential for induction of a subset of downstream effector genes. The molecular mechanisms and functional significance of this...



Burkholderia cenocepacia integrates cis-2-dodecenoic acid and cyclic dimeric guanosine monophosphate signals to control virulence [Microbiology]

2017-12-05T12:21:07-08:00

Quorum sensing (QS) signals are used by bacteria to regulate biological functions in response to cell population densities. Cyclic diguanosine monophosphate (c-di-GMP) regulates cell functions in response to diverse environmental chemical and physical signals that bacteria perceive. In Burkholderia cenocepacia, the QS signal receptor RpfR degrades intracellular c-di-GMP when it...



Retrograde inhibition by a specific subset of interpeduncular {alpha}5 nicotinic neurons regulates nicotine preference [Neuroscience]

2017-12-05T12:21:07-08:00

Repeated exposure to drugs of abuse can produce adaptive changes that lead to the establishment of dependence. It has been shown that allelic variation in the α5 nicotinic acetylcholine receptor (nAChR) gene CHRNA5 is associated with higher risk of tobacco dependence. In the brain, α5-containing nAChRs are expressed at very...



Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimer’s disease [Neuroscience]

2017-12-05T12:21:07-08:00

The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-β peptide (Aβ) has been shown to...



Solving visual correspondence between the two eyes via domain-based population encoding in nonhuman primates [Neuroscience]

2017-12-05T12:21:07-08:00

Stereoscopic vision depends on correct matching of corresponding features between the two eyes. It is unclear where the brain solves this binocular correspondence problem. Although our visual system is able to make correct global matches, there are many possible false matches between any two images. Here, we use optical imaging...



Coexpression of NOS2 and COX2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer [Pharmacology]

2017-12-05T12:21:07-08:00

Proinflammatory signaling pathways are commonly up-regulated in breast cancer. In estrogen receptor-negative (ER−) and triple-negative breast cancer (TNBC), nitric oxide synthase-2 (NOS2) and cyclooxygenase-2 (COX2) have been described as independent predictors of disease outcome. We further explore these findings by investigating the impact of their coexpression on breast cancer survival....



Mixed-order phase transition in a colloidal crystal [Physics]

2017-12-05T12:21:07-08:00

Mixed-order phase transitions display a discontinuity in the order parameter like first-order transitions yet feature critical behavior like second-order transitions. Such transitions have been predicted for a broad range of equilibrium and nonequilibrium systems, but their experimental observation has remained elusive. Here, we analytically predict and experimentally realize a mixed-order...



Molecular basis of tactile specialization in the duck bill [Physiology]

2017-12-05T12:21:07-08:00

Tactile-foraging ducks are specialist birds known for their touch-dependent feeding behavior. They use dabbling, straining, and filtering to find edible matter in murky water, relying on the sense of touch in their bill. Here, we present the molecular characterization of embryonic duck bill, which we show contains a high density...



Maternal prolactin during late pregnancy is important in generating nurturing behavior in the offspring [Physiology]

2017-12-05T12:21:07-08:00

Although maternal nurturing behavior is extremely important for the preservation of a species, our knowledge of the biological underpinnings of these behaviors is insufficient. Here we show that the degree of a mother’s nurturing behavior is regulated by factors present during her own fetal development. We found that Cin85-deficient (Cin85−/−)...



High postural costs and anaerobic metabolism during swimming support the hypothesis of a U-shaped metabolism-speed curve in fishes [Physiology]

2017-12-05T12:21:07-08:00

Swimming performance is considered a key trait determining the ability of fish to survive. Hydrodynamic theory predicts that the energetic costs required for fishes to swim should vary with speed according to a U-shaped curve, with an expected energetic minimum at intermediate cruising speeds and increasing expenditure at low and...



Nature and origins of the lexicon in 6-mo-olds [Psychological and Cognitive Sciences]

2017-12-05T12:21:07-08:00

Recent research reported the surprising finding that even 6-mo-olds understand common nouns [Bergelson E, Swingley D (2012) Proc Natl Acad Sci USA 109:3253–3258]. However, is their early lexicon structured and acquired like older learners? We test 6-mo-olds for a hallmark of the mature lexicon: cross-word relations. We also examine whether...



Parallel epigenetic modifications induced by hatchery rearing in a Pacific salmon [Sustainability Science]

2017-12-05T12:21:07-08:00

Wild stocks of Pacific salmonids have experienced sharp declines in abundance over the past century. Consequently, billions of fish are released each year for enhancing abundance and sustaining fisheries. However, the beneficial role of this widely used management practice is highly debated since fitness decrease of hatchery-origin fish in the...



Correction to Supporting Information for Sculley et al., Eighty years of food-web response to interannual variation in discharge recorded in river diatom frustules from an ocean sediment core [SI Correction]

2017-12-05T12:21:07-08:00

ECOLOGY Correction to Supporting Information for “Eighty years of food-web response to interannual variation in discharge recorded in river diatom frustules from an ocean sediment core,” by John B. Sculley, Rex L. Lowe, Charles A. Nittrouer, Tina M. Drexler, and Mary E. Power, which was first published September 5, 2017;...



In This Issue [This Week in PNAS]

2017-11-28T10:26:29-08:00

Early evidence of Near Eastern viniculture Neolithic jar from Khramis Didi-Gora, Georgia. Image courtesy of the Georgian National Museum. As the climate in the mountainous Near East improved following the last Ice Age, Neolithic hunter-gatherers innovated viniculture of the Eurasian grapevine (Vitis vinifera). The earliest known chemical evidence for grape...



Preprint servers facilitate scientific discourse [Editorials]

2017-11-28T10:26:29-08:00

Preprints are scientific manuscripts posted online before formal peer-review and publication in journals. Preprints have become prominent in scientific publishing, which is increasingly shaped by an emphasis on speed, transparency, and accessibility. Important as they are, those factors are entwined with the journal’s primary role as an arbiter of the...



Better support for a small effective population size of Neandertals and a long shared history of Neandertals and Denisovans [Biological Sciences]

2017-11-28T10:26:30-08:00

Rogers et al. (1) compare the sharing of derived alleles among the genomes of Africans, non-Africans, a Neandertal, and a Denisovan to infer the demographic history of archaic humans. They estimate that the effective population size (Ne) of Neandertals was ∼15,000 individuals and that Neandertals and Denisovans separated from each...



Reply to Mafessoni and Prufer: Inferences with and without singleton site patterns [Biological Sciences]

2017-11-28T10:26:30-08:00

Mafessoni and Prüfer (1) (MP) make three points: (i) Low variation among Neanderthal genomes implies a small population, (ii) Neanderthal–Denisovan divergence is small relative to archaic-modern, and (iii) an analysis including singleton site patterns (in which the derived allele appears only once) supports a small Neanderthal population and a more...



Structures of the type I DNA restriction enzymes [Biological Sciences]

2017-11-28T10:26:30-08:00

The article by Liu et al. (1) on the structure of type I DNA restriction and modification enzymes purports to significantly advance our understanding of these enzymes and proposes a model for their operation. While the partial structure of one of these enzymes is interesting and defines the interface between...



Exceptional body size-extinction risk relations shed new light on the freshwater biodiversity crisis [Biological Sciences]

2017-11-28T10:26:30-08:00

In PNAS, Ripple et al. (1) show that the smallest species of reptiles, amphibians, and bony fishes suffer unusually high extinction risks given what we know about general body size–extinction risk relationships (2). The results of this study have important implications, considering that most studies exploring the community- or ecosystem-level...



Reply to Kalinkat et al.: Smallest terrestrial vertebrates are highly imperiled [Biological Sciences]

2017-11-28T10:26:30-08:00

Kalinkat et al. (1) discuss the biodiversity crisis in their reply to our article “Extinction risk is most acute for the world’s largest and smallest vertebrates” (2). We agree with Kalinkat et al. (1) that small freshwater species tend to have elevated extinction risk, an issue that we highlight in...



Dominant negative mechanism of Presenilin-1 mutations in FAD [Biochemistry]

2017-11-28T10:26:29-08:00

Alzheimer’s disease (AD) is the most common form of dementia, afflicting more than 5 million people in the United States alone. Mutations in the Presenilin genes (PSEN1 and PSEN2) are highly penetrant and account for ∼90% of all mutations identified in familial AD (FAD), highlighting their importance in the pathogenesis...



Quest for adequate biodiversity surrogates in a time of urgency [Sustainability Science]

2017-11-28T10:26:29-08:00

Earth’s biodiversity is declining at an alarming rate, in what some have dubbed the “sixth mass extinction” that life has faced in the history of our planet (1). This rapid decline of biodiversity, the realization that some of its components, such as fungi, remain relatively poorly known, and limited resources...



Converging evidence for the role of transmodal cortex in cognition [Neuroscience]

2017-11-28T10:26:29-08:00

The studies by Vidaurre et al. (1) and Vatansever et al. (2) in PNAS provide contrasting, yet complementary insights into the role that regions of transmodal cortex, including those in the default mode network (DMN) (3) and the fronto-parietal network (FPN) (4), play in cognition. Vatansever et al. (2) used...



Intrusion and extrusion of water in hydrophobic nanopores [Applied Physical Sciences]

2017-11-28T10:26:30-08:00

Heterogeneous systems composed of hydrophobic nanoporous materials and water are capable, depending on their characteristics, of efficiently dissipating (dampers) or storing (“molecular springs”) energy. However, it is difficult to predict their properties based on macroscopic theories—classical capillarity for intrusion and classical nucleation theory (CNT) for extrusion—because of the peculiar behavior...



Parallel magnetic field suppresses dissipation in superconducting nanostrips [Applied Physical Sciences]

2017-11-28T10:26:30-08:00

The motion of Abrikosov vortices in type-II superconductors results in a finite resistance in the presence of an applied electric current. Elimination or reduction of the resistance via immobilization of vortices is the “holy grail” of superconductivity research. Common wisdom dictates that an increase in the magnetic field escalates the...



Closed-loop control of targeted ultrasound drug delivery across the blood-brain/tumor barriers in a rat glioma model [Engineering]

2017-11-28T10:26:30-08:00

Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood–brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains...



Social preferences of future physicians [Economic Sciences]

2017-11-28T10:26:30-08:00

We measure the social preferences of a sample of US medical students and compare their preferences with those of the general population sampled in the American Life Panel (ALP). We also compare the medical students with a subsample of highly educated, wealthy ALP subjects as well as elite law school...



Nutritional and greenhouse gas impacts of removing animals from US agriculture [Sustainability Science]

2017-11-28T10:26:30-08:00

As a major contributor to agricultural greenhouse gas (GHG) emissions, it has been suggested that reducing animal agriculture or consumption of animal-derived foods may reduce GHGs and enhance food security. Because the total removal of animals provides the extreme boundary to potential mitigation options and requires the fewest assumptions to...



Early Neolithic wine of Georgia in the South Caucasus [Anthropology]

2017-11-28T10:26:30-08:00

Chemical analyses of ancient organic compounds absorbed into the pottery fabrics from sites in Georgia in the South Caucasus region, dating to the early Neolithic period (ca. 6,000–5,000 BC), provide the earliest biomolecular archaeological evidence for grape wine and viniculture from the Near East, at ca. 6,000–5,800 BC. The chemical...



Specific inhibition of GPCR-independent G protein signaling by a rationally engineered protein [Biochemistry]

2017-11-28T10:26:30-08:00

Activation of heterotrimeric G proteins by cytoplasmic nonreceptor proteins is an alternative to the classical mechanism via G protein-coupled receptors (GPCRs). A subset of nonreceptor G protein activators is characterized by a conserved sequence named the Gα-binding and activating (GBA) motif, which confers guanine nucleotide exchange factor (GEF) activity in...



Proteome-wide modulation of degradation dynamics in response to growth arrest [Biochemistry]

2017-11-28T10:26:30-08:00

In dividing cells, cytoplasmic dilution is the dominant route of clearance for long-lived proteins whose inherent degradation is slower than the cellular growth rate. Thus, as cells transition from a dividing to a nondividing state, there is a propensity for long-lived proteins to become stabilized relative to short-lived proteins, leading...



Insights into functions of the H channel of cytochrome c oxidase from atomistic molecular dynamics simulations [Biophysics and Computational Biology]

2017-11-28T10:26:30-08:00

Proton pumping A-type cytochrome c oxidase (CcO) terminates the respiratory chains of mitochondria and many bacteria. Three possible proton transfer pathways (D, K, and H channels) have been identified based on structural, functional, and mutational data. Whereas the D channel provides the route for all pumped protons in bacterial A-type...



RNA stem structure governs coupling of dicing and gene silencing in RNA interference [Biophysics and Computational Biology]

2017-11-28T10:26:30-08:00

PremicroRNAs (premiRNAs) possess secondary structures consisting of a loop and a stem with multiple mismatches. Despite the well-characterized RNAi pathway, how the structural features of premiRNA contribute to dicing and subsequent gene-silencing efficiency remains unclear. Using single-molecule FISH, we demonstrate that cytoplasmic mRNA, but not nuclear mRNA, is reduced during...



Analysis of high-resolution 3D intrachromosomal interactions aided by Bayesian network modeling [Biophysics and Computational Biology]

2017-11-28T10:26:30-08:00

Long-range intrachromosomal interactions play an important role in 3D chromosome structure and function, but our understanding of how various factors contribute to the strength of these interactions remains poor. In this study we used a recently developed analysis framework for Bayesian network (BN) modeling to analyze publicly available datasets for...



Recovery of taste organs and sensory function after severe loss from Hedgehog/Smoothened inhibition with cancer drug sonidegib [Cell Biology]

2017-11-28T10:26:30-08:00

Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO...



In vivo measurements of interindividual differences in DNA glycosylases and APE1 activities [Cell Biology]

2017-11-28T10:26:30-08:00

The integrity of our DNA is challenged with at least 100,000 lesions per cell on a daily basis. Failure to repair DNA damage efficiently can lead to cancer, immunodeficiency, and neurodegenerative disease. Base excision repair (BER) recognizes and repairs minimally helix-distorting DNA base lesions induced by both endogenous and exogenous...



Dual function for Tango1 in secretion of bulky cargo and in ER-Golgi morphology [Cell Biology]

2017-11-28T10:26:30-08:00

Tango1 enables ER-to-Golgi trafficking of large proteins. We show here that loss of Tango1, in addition to disrupting protein secretion and ER/Golgi morphology, causes ER stress and defects in cell shape. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect. If large cargos...



Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction [Immunology and Inflammation]

2017-11-28T10:26:30-08:00

Helminths trigger multiple immunomodulatory pathways that can protect from sepsis. Human resistin (hRetn) is an immune cell-derived protein that is highly elevated in helminth infection and sepsis. However, the function of hRetn in sepsis, or whether hRetn influences helminth protection against sepsis, is unknown. Employing hRetn-expressing transgenic mice (hRETNTg+) and...



T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire [Immunology and Inflammation]

2017-11-28T10:26:30-08:00

Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune...



Resident macrophages of pancreatic islets have a seminal role in the initiation of autoimmune diabetes of NOD mice [Immunology and Inflammation]

2017-11-28T10:26:30-08:00

Treatment of C57BL/6 or NOD mice with a monoclonal antibody to the CSF-1 receptor resulted in depletion of the resident macrophages of pancreatic islets of Langerhans that lasted for several weeks. Depletion of macrophages in C57BL/6 mice did not affect multiple parameters of islet function, including glucose response, insulin content,...



Role of estrogen receptor beta in neural differentiation of mouse embryonic stem cells [Medical Sciences]

2017-11-28T10:26:30-08:00

The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to...



Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein [Microbiology]

2017-11-28T10:26:30-08:00

Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has...



Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries [Microbiology]

2017-11-28T10:26:30-08:00

Legionella pneumophila is the causative agent of a severe pneumonia called Legionnaires’ disease. A single strain of L. pneumophila encodes a repertoire of over 300 different effector proteins that are delivered into host cells by the Dot/Icm type IV secretion system during infection. The large number of L. pneumophila effectors...



Microbial pathway for anaerobic 5'-methylthioadenosine metabolism coupled to ethylene formation [Microbiology]

2017-11-28T10:26:30-08:00

Numerous cellular processes involving S-adenosyl-l-methionine result in the formation of the toxic by-product, 5′-methylthioadenosine (MTA). To prevent inhibitory MTA accumulation and retain biologically available sulfur, most organisms possess the “universal” methionine salvage pathway (MSP). However, the universal MSP is inherently aerobic due to a requirement of molecular oxygen for one...



Sparsity enables estimation of both subcortical and cortical activity from MEG and EEG [Neuroscience]

2017-11-28T10:26:30-08:00

Subcortical structures play a critical role in brain function. However, options for assessing electrophysiological activity in these structures are limited. Electromagnetic fields generated by neuronal activity in subcortical structures can be recorded noninvasively, using magnetoencephalography (MEG) and electroencephalography (EEG). However, these subcortical signals are much weaker than those generated by...



Intact hemisphere and corpus callosum compensate for visuomotor functions after early visual cortex damage [Neuroscience]

2017-11-28T10:26:30-08:00

Unilateral damage to the primary visual cortex (V1) leads to clinical blindness in the opposite visual hemifield, yet nonconscious ability to transform unseen visual input into motor output can be retained, a condition known as “blindsight.” Here we combined psychophysics, functional magnetic resonance imaging, and tractography to investigate the functional...



Gap junctional coupling between retinal amacrine and ganglion cells underlies coherent activity integral to global object perception [Neuroscience]

2017-11-28T10:26:30-08:00

Coherent spike activity occurs between widely separated retinal ganglion cells (RGCs) in response to a large, contiguous object, but not to disjointed objects. Since the large spatial separation between the RGCs precludes common excitatory inputs from bipolar cells, the mechanism underlying this long-range coherence remains unclear. Here, we show that...



Dopamine reward prediction error signal codes the temporal evaluation of a perceptual decision report [Neuroscience]

2017-11-28T10:26:30-08:00

Learning to associate unambiguous sensory cues with rewarded choices is known to be mediated by dopamine (DA) neurons. However, little is known about how these neurons behave when choices rely on uncertain reward-predicting stimuli. To study this issue we reanalyzed DA recordings from monkeys engaged in the detection of weak...



Toroidal plasmoid generation via extreme hydrodynamic shear [Applied Physical Sciences]

2017-11-28T10:26:29-08:00

Saint Elmo’s fire and lightning are two known forms of naturally occurring atmospheric pressure plasmas. As a technology, nonthermal plasmas are induced from artificially created electromagnetic or electrostatic fields. Here we report the observation of arguably a unique case of a naturally formed such plasma, created in air at room...



In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection [Biochemistry]

2017-11-28T10:26:29-08:00

Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron...



Unprecedented pathway of reducing equivalents in a diflavin-linked disulfide oxidoreductase [Biochemistry]

2017-11-28T10:26:30-08:00

Flavoproteins participate in a wide variety of physiologically relevant processes that typically involve redox reactions. Within this protein superfamily, there exists a group that is able to transfer reducing equivalents from FAD to a redox-active disulfide bridge, which further reduces disulfide bridges in target proteins to regulate their structure and...



Dominant negative effect of the loss-of-function {gamma}-secretase mutants on the wild-type enzyme through heterooligomerization [Biochemistry]

2017-11-28T10:26:30-08:00

γ-secretase is an intramembrane protease complex consisting of nicastrin, presenilin-1/2, APH-1a/b, and Pen-2. Hydrolysis of the 99-residue transmembrane fragment of amyloid precursor protein (APP-C99) by γ-secretase produces β-amyloid (Aβ) peptides. Pathogenic mutations in PSEN1 and PSEN2, which encode the catalytic subunit presenilin-1/2 of γ-secretase, lead to familial Alzheimer’s disease in...



Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I [Biochemistry]

2017-11-28T10:26:30-08:00

Respiratory complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in mammalian cells, powers ATP synthesis by using the energy from electron transfer from NADH to ubiquinone-10 to drive protons across the energy-transducing mitochondrial inner membrane. Ubiquinone-10 is extremely hydrophobic, but in complex I the binding site for its...



Correlating cell shape and cellular stress in motile confluent tissues [Biophysics and Computational Biology]

2017-11-28T10:26:29-08:00

Collective cell migration is a highly regulated process involved in wound healing, cancer metastasis, and morphogenesis. Mechanical interactions among cells provide an important regulatory mechanism to coordinate such collective motion. Using a self-propelled Voronoi (SPV) model that links cell mechanics to cell shape and cell motility, we formulate a generalized...



Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency [Cell Biology]

2017-11-28T10:26:30-08:00

Obesity typically is linked to caloric imbalance as a result of overnutrition. Here we propose a cell-autonomous mechanism for adiposity as a result of persistent cell surface glucose transporter type 4 (GLUT4) in adipocytes resulting from impaired function of ankyrin-B (AnkB) in coupling GLUT4 to clathrin-mediated endocytosis. Adipose tissue-specific AnkB-KO...



SNARE priming is essential for maturation of autophagosomes but not for their formation [Cell Biology]

2017-11-28T10:26:30-08:00

Autophagy, a unique intracellular membrane-trafficking pathway, is initiated by the formation of an isolation membrane (phagophore) that engulfs cytoplasmic constituents, leading to generation of the autophagosome, a double-membrane vesicle, which is targeted to the lysosome. The outer autophagosomal membrane consequently fuses with the lysosomal membrane. Multiple membrane-fusion events mediated by...



Energy decomposition analysis of single bonds within Kohn-Sham density functional theory [Chemistry]

2017-11-28T10:26:29-08:00

An energy decomposition analysis (EDA) for single chemical bonds is presented within the framework of Kohn–Sham density functional theory based on spin projection equations that are exact within wave function theory. Chemical bond energies can then be understood in terms of stabilization caused by spin-coupling augmented by dispersion, polarization, and...



Selective killing of Helicobacter pylori with pH-responsive helix-coil conformation transitionable antimicrobial polypeptides [Chemistry]

2017-11-28T10:26:29-08:00

Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and...



Reviewer bias in single- versus double-blind peer review [Computer Sciences]

2017-11-28T10:26:29-08:00

Peer review may be “single-blind,” in which reviewers are aware of the names and affiliations of paper authors, or “double-blind,” in which this information is hidden. Noting that computer science research often appears first or exclusively in peer-reviewed conferences rather than journals, we study these two reviewing models in the...