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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]

2017-01-17T12:48:22-08:00

Cytopathic effects of Zika virus proteins ZIKV genome, which encodes 14 proteins and peptides (Zika ORFeome), with predicted intracellular associations. Zika virus (ZIKV) can cause microcephaly in newborn children and Guillain-Barré syndrome in adults, but the precise viral proteins that trigger the cellular changes underlying these conditions remain unknown. Using...



Relevance of Kondo physics for the temperature dependence of the bulk modulus in plutonium [Physical Sciences]

2017-01-17T12:48:23-08:00

The recent PNAS paper by Migliori et al. (1) attempts to explain the unusually strong temperature dependence of the bulk modulus of fcc plutonium (δ-Pu) by use of the disordered local moment (DLM) model. It is our opinion that this approach does not correctly incorporate the dynamic magnetism of δ-Pu....



Reply to Janoschek et al.: The excited {delta}-phase of plutonium [Physical Sciences]

2017-01-17T12:48:23-08:00

In a recent PNAS paper (1) we explain the anomalous temperature dependence of the elasticity in δ-plutonium (δ-Pu) in terms of a first-principles model that includes multiple energy configurations attributed to spin fluctuations. Our model (1) captures the highly unusual behavior of decreasing elastic moduli with increasing temperature at constant...



Astrocytes fuel the fire of lymphocyte toxicity after stroke [Neuroscience]

2017-01-17T12:48:22-08:00

Astrocytes weave their processes throughout the central nervous system (CNS), supporting and protecting delicate neurons via the regulation of cerebral blood flow, cerebral metabolism, and neurotransmission (1, 2). Astrocytes also form the backbone of the glial limitans, the unique blood–brain barrier (BBB) that sequesters the CNS away from the rest...



When bottom-up meets top-down [Applied Physical Sciences]

2017-01-17T12:48:22-08:00

Top-Down Man-Made Vs. Bottom-Up Nature In nature, materials are built in a “bottom-up” manner, relying on the self-assembly of fundamental building blocks, and have evolved over thousands of years of natural selection to achieve impressive performance. Materials in nature are sustainably designed in a hierarchical and multifunctional way to be...



When protected areas prove insufficient: Cheetah and “protection-reliant” species [Ecology]

2017-01-17T12:48:22-08:00

An understanding of the factors that affect the distribution of species is a cornerstone of ecology; yet, two-thirds of the world’s species remain undescribed (1) and estimated rates of extinction are high, but certainty around those rates is limited (2). The International Union for Conservation of Nature (IUCN) Red List...



Stochastic initiation and termination of calcium-mediated triggered activity in cardiac myocytes [Applied Physical Sciences]

2017-01-17T12:48:23-08:00

Cardiac myocytes normally initiate action potentials in response to a current stimulus that depolarizes the membrane above an excitation threshold. Aberrant excitation can also occur due to spontaneous calcium (Ca2+) release (SCR) from intracellular stores after the end of a preceding action potential. SCR drives the Na+/Ca2+ exchange current inducing...



Cell morphology drives spatial patterning in microbial communities [Biophysics and Computational Biology]

2017-01-17T12:48:23-08:00

The clearest phenotypic characteristic of microbial cells is their shape, but we do not understand how cell shape affects the dense communities, known as biofilms, where many microbes live. Here, we use individual-based modeling to systematically vary cell shape and study its impact in simulated communities. We compete cells with...



Statistical mechanical model of gas adsorption in porous crystals with dynamic moieties [Chemistry]

2017-01-17T12:48:23-08:00

Some nanoporous, crystalline materials possess dynamic constituents, for example, rotatable moieties. These moieties can undergo a conformation change in response to the adsorption of guest molecules, which qualitatively impacts adsorption behavior. We pose and solve a statistical mechanical model of gas adsorption in a porous crystal whose cages share a...



Structural characterization of nonactive site, TrkA-selective kinase inhibitors [Biochemistry]

2017-01-17T12:48:23-08:00

Current therapies for chronic pain can have insufficient efficacy and lead to side effects, necessitating research of novel targets against pain. Although originally identified as an oncogene, Tropomyosin-related kinase A (TrkA) is linked to pain and elevated levels of NGF (the ligand for TrkA) are associated with chronic pain. Antibodies...



SNX-1 and RME-8 oppose the assembly of HGRS-1/ESCRT-0 degradative microdomains on endosomes [Cell Biology]

2017-01-17T12:48:23-08:00

After endocytosis, transmembrane cargo reaches endosomes, where it encounters complexes dedicated to opposing functions: recycling and degradation. Microdomains containing endosomal sorting complexes required for transport (ESCRT)-0 component Hrs [hepatocyte growth factor-regulated tyrosine kinase substrate (HGRS-1) in Caenorhabditis elegans] mediate cargo degradation, concentrating ubiquitinated cargo and organizing the activities of ESCRT....



Dual-specificity phosphatase 5 controls the localized inhibition, propagation, and transforming potential of ERK signaling [Cell Biology]

2017-01-17T12:48:23-08:00

Deregulated extracellular signal-regulated kinase (ERK) signaling drives cancer growth. Normally, ERK activity is self-limiting by the rapid inactivation of upstream kinases and delayed induction of dual-specificity MAP kinase phosphatases (MKPs/DUSPs). However, interactions between these feedback mechanisms are unclear. Here we show that, although the MKP DUSP5 both inactivates and anchors...



Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms [Genetics]

2017-01-17T12:48:23-08:00

Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134...



GAS6 is a key homeostatic immunological regulator of host-commensal interactions in the oral mucosa [Immunology and Inflammation]

2017-01-17T12:48:23-08:00

The oral epithelium contributes to innate immunity and oral mucosal homeostasis, which is critical for preventing local inflammation and the associated adverse systemic conditions. Nevertheless, the mechanisms by which the oral epithelium maintains homeostasis are poorly understood. Here, we studied the role of growth arrest specific 6 (GAS6), a ligand...



Insights into the lifestyle of uncultured bacterial natural product factories associated with marine sponges [Microbiology]

2017-01-17T12:48:23-08:00

The as-yet uncultured filamentous bacteria “Candidatus Entotheonella factor” and “Candidatus Entotheonella gemina” live associated with the marine sponge Theonella swinhoei Y, the source of numerous unusual bioactive natural products. Belonging to the proposed candidate phylum “Tectomicrobia,” Candidatus Entotheonella members are only distantly related to any cultivated organism. The Ca. E....



Diverse evolutionary patterns of pneumococcal antigens identified by pangenome-wide immunological screening [Microbiology]

2017-01-17T12:48:23-08:00

Characterizing the immune response to pneumococcal proteins is critical in understanding this bacterium’s epidemiology and vaccinology. Probing a custom-designed proteome microarray with sera from 35 healthy US adults revealed a continuous distribution of IgG affinities for 2,190 potential antigens from the species-wide pangenome. Reproducibly elevated IgG binding was elicited by...



Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals [Microbiology]

2017-01-17T12:48:23-08:00

Directed modulation of the colonic bacteria to metabolize lactose effectively is a potentially useful approach to improve lactose digestion and tolerance. A randomized, double-blind, multisite placebo-controlled trial conducted in human subjects demonstrated that administration of a highly purified (>95%) short-chain galactooligosaccharide (GOS), designated “RP-G28,” significantly improved clinical outcomes for lactose...



Characterization of cytopathic factors through genome-wide analysis of the Zika viral proteins in fission yeast [Microbiology]

2017-01-17T12:48:23-08:00

The Zika virus (ZIKV) causes microcephaly and the Guillain-Barré syndrome. Little is known about how ZIKV causes these conditions or which ZIKV viral protein(s) is responsible for the associated ZIKV-induced cytopathic effects, including cell hypertrophy, growth restriction, cell-cycle dysregulation, and cell death. We used fission yeast for the rapid, global...



Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure [Microbiology]

2017-01-17T12:48:23-08:00

Recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. These vaccine candidates should have a low risk of deattenuation because of the many changes involved. However, their genetic stability under selective pressure is largely unknown. We evaluated phenotypic reversion of deoptimized human respiratory syncytial virus...



Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity [Neuroscience]

2017-01-17T12:48:23-08:00

Astrocytes are believed to bridge interactions between infiltrating lymphocytes and neurons during brain ischemia, but the mechanisms for this action are poorly understood. Here we found that interleukin-15 (IL-15) is dramatically up-regulated in astrocytes of postmortem brain tissues from patients with ischemic stroke and in a mouse model of transient...



REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation-differentiation balance in the developing brain [Neuroscience]

2017-01-17T12:48:23-08:00

The transcriptional events that lead to the cessation of neural proliferation, and therefore enable the production of proper numbers of differentiated neurons and glia, are still largely uncharacterized. Here, we report that the transcription factor Insulinoma-associated 1 (INSM1) forms complexes with RE1 Silencing Transcription factor (REST) corepressors RCOR1 and RCOR2...



Tbx20 controls the expression of the KCNH2 gene and of hERG channels [Physiology]

2017-01-17T12:48:23-08:00

Long QT syndrome (LQTS) exhibits great phenotype variability among family members carrying the same mutation, which can be partially attributed to genetic factors. We functionally analyzed the KCNH2 (encoding for Kv11.1 or hERG channels) and TBX20 (encoding for the transcription factor Tbx20) variants found by next-generation sequencing in two siblings...



ATG9 regulates autophagosome progression from the endoplasmic reticulum in Arabidopsis [Plant Biology]

2017-01-17T12:48:23-08:00

Autophagy is a conserved pathway for bulk degradation of cytoplasmic material by a double-membrane structure named the autophagosome. The initiation of autophagosome formation requires the recruitment of autophagy-related protein 9 (ATG9) vesicles to the preautophagosomal structure. However, the functional relationship between ATG9 vesicles and the phagophore is controversial in different...



Opportunity for marine fisheries reform in China [Sustainability Science]

2017-01-17T12:48:22-08:00

China’s 13th Five-Year Plan, launched in March 2016, provides a sound policy platform for the protection of marine ecosystems and the restoration of capture fisheries within China’s exclusive economic zone. What distinguishes China among many other countries striving for marine fisheries reform is its size—accounting for almost one-fifth of global...



Brain enlargement and dental reduction were not linked in hominin evolution [Anthropology]

2017-01-17T12:48:22-08:00

The large brain and small postcanine teeth of modern humans are among our most distinctive features, and trends in their evolution are well studied within the hominin clade. Classic accounts hypothesize that larger brains and smaller teeth coevolved because behavioral changes associated with increased brain size allowed a subsequent dental...



Programming function into mechanical forms by directed assembly of silk bulk materials [Applied Physical Sciences]

2017-01-17T12:48:22-08:00

We report simple, water-based fabrication methods based on protein self-assembly to generate 3D silk fibroin bulk materials that can be easily hybridized with water-soluble molecules to obtain multiple solid formats with predesigned functions. Controlling self-assembly leads to robust, machinable formats that exhibit thermoplastic behavior consenting material reshaping at the nanoscale,...



Matrix stiffening promotes a tumor vasculature phenotype [Applied Physical Sciences]

2017-01-17T12:48:22-08:00

Tumor microvasculature tends to be malformed, more permeable, and more tortuous than vessels in healthy tissue, effects that have been largely attributed to up-regulated VEGF expression. However, tumor tissue tends to stiffen during solid tumor progression, and tissue stiffness is known to alter cell behaviors including proliferation, migration, and cell–cell...



Resolution of single and double Holliday junction recombination intermediates by GEN1 [Biochemistry]

2017-01-17T12:48:22-08:00

Genetic recombination provides an important mechanism for the repair of DNA double-strand breaks. Homologous pairing and strand exchange lead to the formation of DNA intermediates, in which sister chromatids or homologous chromosomes are covalently linked by four-way Holliday junctions (HJs). Depending on the type of recombination reaction that takes place,...



MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus [Biochemistry]

2017-01-17T12:48:22-08:00

A locus on chromosome 9q22 harbors a SNP (rs965513) firmly associated with risk of papillary thyroid carcinoma (PTC). The locus also comprises the forkhead box E1 (FOXE1) gene, which is implicated in thyroid development, and a long noncoding RNA (lncRNA) gene, papillary thyroid cancer susceptibility candidate 2 (PTCSC2). How these...



Identification of NAD+ capped mRNAs in Saccharomyces cerevisiae [Biochemistry]

2017-01-17T12:48:22-08:00

RNAs besides tRNA and rRNA contain chemical modifications, including the recently described 5′ nicotinamide-adenine dinucleotide (NAD+) RNA in bacteria. Whether 5′ NAD-RNA exists in eukaryotes remains unknown. We demonstrate that 5′ NAD-RNA is found on subsets of nuclear and mitochondrial encoded mRNAs in Saccharomyces cerevisiae. NAD-mRNA appears to be produced...



Structural basis for regiospecific midazolam oxidation by human cytochrome P450 3A4 [Biochemistry]

2017-01-17T12:48:22-08:00

Human cytochrome P450 3A4 (CYP3A4) is a major hepatic and intestinal enzyme that oxidizes more than 60% of administered therapeutics. Knowledge of how CYP3A4 adjusts and reshapes the active site to regioselectively oxidize chemically diverse compounds is critical for better understanding structure–function relations in this important enzyme, improving the outcomes...



p53 pathway is involved in cell competition during mouse embryogenesis [Cell Biology]

2017-01-17T12:48:23-08:00

The function of tumor suppressor p53 has been under intense investigation. Acute stresses such as DNA damage are able to trigger a high level of p53 activity, leading to cell cycle arrest or apoptosis. In contrast, the cellular response of mild p53 activity induced by low-level stress in vivo remains...



TRAIL-death receptor endocytosis and apoptosis are selectively regulated by dynamin-1 activation [Cell Biology]

2017-01-17T12:48:23-08:00

Clathrin-mediated endocytosis (CME) constitutes the major pathway for uptake of signaling receptors into eukaryotic cells. As such, CME regulates signaling from cell-surface receptors, but whether and how specific signaling receptors reciprocally regulate the CME machinery remains an open question. Although best studied for its role in membrane fission, the GTPase...



Directional emission from dye-functionalized plasmonic DNA superlattice microcavities [Chemistry]

2017-01-17T12:48:22-08:00

Three-dimensional plasmonic superlattice microcavities, made from programmable atom equivalents comprising gold nanoparticles functionalized with DNA, are used as a testbed to study directional light emission. DNA-guided nanoparticle colloidal crystallization allows for the formation of micrometer-scale single-crystal body-centered cubic gold nanoparticle superlattices, with dye molecules coupled to the DNA strands that...



In vivo severity ranking of Ras pathway mutations associated with developmental disorders [Developmental Biology]

2017-01-17T12:48:23-08:00

Germ-line mutations in components of the Ras/MAPK pathway result in developmental disorders called RASopathies, affecting about 1/1,000 human births. Rapid advances in genome sequencing make it possible to identify multiple disease-related mutations, but there is currently no systematic framework for translating this information into patient-specific predictions of disease progression. As...



Adenylate cyclase A acting on PKA mediates induction of stalk formation by cyclic diguanylate at the Dictyostelium organizer [Developmental Biology]

2017-01-17T12:48:23-08:00

Coordination of cell movement with cell differentiation is a major feat of embryonic development. The Dictyostelium stalk always forms at the organizing tip, by a mechanism that is not understood. We previously reported that cyclic diguanylate (c-di-GMP), synthesized by diguanylate cyclase A (DgcA), induces stalk formation. Here we used transcriptional...



The global decline of cheetah Acinonyx jubatus and what it means for conservation [Ecology]

2017-01-17T12:48:23-08:00

Establishing and maintaining protected areas (PAs) are key tools for biodiversity conservation. However, this approach is insufficient for many species, particularly those that are wide-ranging and sparse. The cheetah Acinonyx jubatus exemplifies such a species and faces extreme challenges to its survival. Here, we show that the global population is...



Imaging individual neurons in the retinal ganglion cell layer of the living eye [Engineering]

2017-01-17T12:48:23-08:00

Although imaging of the living retina with adaptive optics scanning light ophthalmoscopy (AOSLO) provides microscopic access to individual cells, such as photoreceptors, retinal pigment epithelial cells, and blood cells in the retinal vasculature, other important cell classes, such as retinal ganglion cells, have proven much more challenging to image. The...



Higher rates of sex evolve during adaptation to more complex environments [Evolution]

2017-01-17T12:48:23-08:00

A leading hypothesis for the evolutionary maintenance of sexual reproduction proposes that sex is advantageous because it facilitates adaptation. Changes in the environment stimulate adaptation but not all changes are equivalent; a change may occur along one or multiple environmental dimensions. In two evolution experiments with the facultatively sexual rotifer...



Dinosaur incubation periods directly determined from growth-line counts in embryonic teeth show reptilian-grade development [Evolution]

2017-01-17T12:48:23-08:00

Birds stand out from other egg-laying amniotes by producing relatively small numbers of large eggs with very short incubation periods (average 11–85 d). This aspect promotes high survivorship by limiting exposure to predation and environmental perturbation, allows for larger more fit young, and facilitates rapid attainment of adult size. Birds...



Antibiotic stress selects against cooperation in the pathogenic bacterium Pseudomonas aeruginosa [Evolution]

2017-01-17T12:48:23-08:00

Cheats are a pervasive threat to public goods production in natural and human communities, as they benefit from the commons without contributing to it. Although ecological antagonisms such as predation, parasitism, competition, and abiotic environmental stress play key roles in shaping population biology, it is unknown how such stresses generally...



SIR2 suppresses replication gaps and genome instability by balancing replication between repetitive and unique sequences [Genetics]

2017-01-17T12:48:23-08:00

Replication gaps that persist into mitosis likely represent important threats to genome stability, but experimental identification of these gaps has proved challenging. We have developed a technique that allows us to explore the dynamics by which genome replication is completed before mitosis. Using this approach, we demonstrate that excessive allocation...



ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations [Genetics]

2017-01-17T12:48:23-08:00

We investigated the proposal that ankylosing spondylitis (AS) is associated with unusual ERAP1 genotypes. ERAP1 haplotypes were constructed for 213 AS cases and 46 rheumatoid arthritis controls using family data. Haplotypes were generated from five common ERAP1 single nucleotide polymorphisms (SNPs)—rs2287987 (M349V), rs30187 (K528R), rs10050860 (D575N), rs17482078 (R725Q), and rs27044...



CD74 is a novel transcription regulator [Immunology and Inflammation]

2017-01-17T12:48:23-08:00

CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor. Macrophage migration inhibitory factor binding to CD74 induces its intramembrane cleavage and the release of its cytosolic intracellular domain (CD74–ICD), which regulates cell survival. In the present study, we characterized the transcriptional activity of CD74–ICD in chronic lymphocytic...



Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epithelia [Immunology and Inflammation]

2017-01-17T12:48:23-08:00

The colonic epithelium provides an essential barrier against the environment that is critical for protecting the body and controlling inflammation. In response to injury or gut microbes, colonic epithelial cells produce extracellular hydrogen peroxide (H2O2), which acts as a potent signaling molecule affecting barrier function and host defense. In humans,...



Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation [Immunology and Inflammation]

2017-01-17T12:48:23-08:00

Alzheimer’s disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself...



Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis [Immunology and Inflammation]

2017-01-17T12:48:23-08:00

Macrophages are prominent immune cells in the tumor microenvironment that exert potent effects on cancer metastasis. However, the signals and receivers for the tumor–macrophage communication remain enigmatic. Here, we show that G protein-coupled receptor 132 (Gpr132) functions as a key macrophage sensor of the rising lactate in the acidic tumor...



Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase I independent of Cdk2 activation [Medical Sciences]

2017-01-17T12:48:23-08:00

Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosome movement during meiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I...



Cryo-EM study of slow bee paralysis virus at low pH reveals iflavirus genome release mechanism [Microbiology]

2017-01-17T12:48:23-08:00

Viruses from the family Iflaviridae are insect pathogens. Many of them, including slow bee paralysis virus (SBPV), cause lethal diseases in honeybees and bumblebees, resulting in agricultural losses. Iflaviruses have nonenveloped icosahedral virions containing single-stranded RNA genomes. However, their genome release mechanism is unknown. Here, we show that low pH...



Contribution of propriospinal neurons to recovery of hand dexterity after corticospinal tract lesions in monkeys [Neuroscience]

2017-01-17T12:48:23-08:00

The direct cortico-motoneuronal connection is believed to be essential for the control of dexterous hand movements, such as precision grip in primates. It was reported, however, that even after lesion of the corticospinal tract (CST) at the C4–C5 segment, precision grip largely recovered within 1–3 mo, suggesting that the recovery...



Science and Culture: Searching for shared inspiration, artists head to the world’s largest science experiment [Physics]

2017-01-17T12:48:22-08:00

The ATLAS particle detector, one of seven at the Large Hadron Collider (LHC), records more than 40 million data points every second, answering and spawning numerous inquiries into the mysteries of the universe. Now that information has found an unconventional medium for display: in a new work of installation art....



Core Concept: How nonequilibrium thermodynamics speaks to the mystery of life [Physics]

2017-01-17T12:48:22-08:00

In his 1944 book What is Life?, Austrian physicist Erwin Schrödinger argued that organisms stay alive precisely by staving off equilibrium. “How does the living organism avoid decay?” he asks. “The obvious answer is: By eating, drinking, breathing and (in the case of plants) assimilating. The technical term is metabolism”...



On-demand high-capacity ride-sharing via dynamic trip-vehicle assignment [Social Sciences]

2017-01-17T12:48:22-08:00

Ride-sharing services are transforming urban mobility by providing timely and convenient transportation to anybody, anywhere, and anytime. These services present enormous potential for positive societal impacts with respect to pollution, energy consumption, congestion, etc. Current mathematical models, however, do not fully address the potential of ride-sharing. Recently, a large-scale study...



Ancient human disturbances may be skewing our understanding of Amazonian forests [Sustainability Science]

2017-01-17T12:48:23-08:00

Although the Amazon rainforest houses much of Earth’s biodiversity and plays a major role in the global carbon budget, estimates of tree biodiversity originate from fewer than 1,000 forest inventory plots, and estimates of carbon dynamics are derived from fewer than 200 recensus plots. It is well documented that the...



Correction for Novack-Gottshall, Love, not war, drove the Mesozoic marine revolution [Correction]

2017-01-17T12:48:23-08:00

COMMENTARY Correction for “Love, not war, drove the Mesozoic marine revolution,” by Phillip M. Novack-Gottshall, which appeared in issue 51, December 20, 2016, of Proc Natl Acad Sci USA (113:14471–14473; first published December 9, 2016; 10.1073/pnas.1617404113). The author notes that the author name Phillip M. Novack-Gottshall should instead appear as...



Correction for Lin et al., DNA polymerase {zeta} limits chromosomal damage and promotes cell survival following aflatoxin exposure [Correction]

2017-01-17T12:48:23-08:00

CELL BIOLOGY Correction for “DNA polymerase ζ limits chromosomal damage and promotes cell survival following aflatoxin exposure,” by Ying-Chih Lin, Nichole Owen, Irina G. Minko, Sabine S. Lange, Liang Li, Michael P. Stone, Richard D. Wood, Amanda K. McCullough, and R. Stephen Lloyd, which appeared in issue 48, November 29,...



In This Issue [This Week in PNAS]

2017-01-10T10:16:49-08:00

Nanoscale braids and weaves Maypole dance. Image courtesy of WIkimedia Commons/Grenville Burrows. Within all living cells, precisely arranged protein complexes use energy from ATP to perform mechanical work. Researchers have sought to emulate these biological machines by manipulating individual atoms and molecules into custom structures. Exploiting recent advances in colloidal...



Saliva protein biomarkers and oral squamous cell carcinoma [Biological Sciences]

2017-01-10T10:16:50-08:00

The article by Yu et al. (1) in a recent issue of PNAS unveils potential salivary biomarkers for the early detection of oral squamous cell carcinoma (OSCC). Despite the groundbreaking findings demonstrated, the authors assert that the ongoing strategy for detecting OSCC (oral visual inspection and biopsy) is ineffective, because...



Reply to Galvao-Moreira and da Cruz: Saliva biomarkers to complement the visualization-based oral cancer detection [Biological Sciences]

2017-01-10T10:16:50-08:00

Galvão-Moreira and da Cruz summarize the current status of screening for oral cancer and state that “it would probably make sense if biomarkers… could be utilized as complementary tests, instead of primary screening tools, to replace the clinical examination” (1). We agree, and such is the intended use of our...



QnAs with Fraser Stoddart [QnAs]

2017-01-10T10:16:49-08:00

The design of tiny machines is not a new idea. In the 1950s, physicist Richard Feynman predicted the development of nanotechnology and embodied the idea of miniaturization in his 1959 lecture “Plenty of Room at the Bottom” (1). In recent decades, nanotechnology has come into its own and propelled the...



Methylation maintains HSC division fate [Cell Biology]

2017-01-10T10:16:49-08:00

Hematopoietic stem cells (HSCs) are responsible for maintaining a sufficient pool of self-renewing cells that can continuously differentiate into lineage-specific hematopoietic cells throughout the lifetime of an individual (1). The choice to self-renew or differentiate is most likely achieved through coordination of extrinsic and intrinsic cell fate signals that drive...



Melting the ice one layer at a time [Chemistry]

2017-01-10T10:16:49-08:00

The melting of ice is one of the most common processes on earth. Interestingly, as an ice crystal is warmed from below toward its bulk melting temperature of 0 °C a thin film of water forms on it. This water film, referred to as a premelting layer or a quasi-liquid...



Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum [Chemistry]

2017-01-10T10:16:50-08:00

Solvents are commonly used in pharmaceutical and cosmetic formulations and sanitary products and cleansers. The uptake of solvent into the skin may change the molecular organization of skin lipids and proteins, which may in turn alter the protective skin barrier function. We herein examine the molecular effects of 10 different...



Climate change damages to Alaska public infrastructure and the economics of proactive adaptation [Environmental Sciences]

2017-01-10T10:16:50-08:00

Climate change in the circumpolar region is causing dramatic environmental change that is increasing the vulnerability of infrastructure. We quantified the economic impacts of climate change on Alaska public infrastructure under relatively high and low climate forcing scenarios [representative concentration pathway 8.5 (RCP8.5) and RCP4.5] using an infrastructure model modified...



Ohr plays a central role in bacterial responses against fatty acid hydroperoxides and peroxynitrite [Biochemistry]

2017-01-10T10:16:50-08:00

Organic hydroperoxide resistance (Ohr) enzymes are unique Cys-based, lipoyl-dependent peroxidases. Here, we investigated the involvement of Ohr in bacterial responses toward distinct hydroperoxides. In silico results indicated that fatty acid (but not cholesterol) hydroperoxides docked well into the active site of Ohr from Xylella fastidiosa and were efficiently reduced by...



Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes [Cell Biology]

2017-01-10T10:16:50-08:00

Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate. However, how individual HSC makes the decision between self-renewal and differentiation remains largely unknown. Here we report that ablation of the key epigenetic regulator Uhrf1 in the hematopoietic system depletes the HSC pool, leading to hematopoietic failure and lethality....



Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response [Cell Biology]

2017-01-10T10:16:50-08:00

Protein AMPylation is a conserved posttranslational modification with emerging roles in endoplasmic reticulum homeostasis. However, the range of substrates and cell biological consequences of AMPylation remain poorly defined. We expressed human and Caenorhabditis elegans AMPylation enzymes—huntingtin yeast-interacting protein E (HYPE) and filamentation-induced by cyclic AMP (FIC)-1, respectively—in Saccharomyces cerevisiae, a...



Microbial competition in porous environments can select against rapid biofilm growth [Evolution]

2017-01-10T10:16:50-08:00

Microbes often live in dense communities called biofilms, where competition between strains and species is fundamental to both evolution and community function. Although biofilms are commonly found in soil-like porous environments, the study of microbial interactions has largely focused on biofilms growing on flat, planar surfaces. Here, we use microfluidic...



Major transitions in dinoflagellate evolution unveiled by phylotranscriptomics [Evolution]

2017-01-10T10:16:50-08:00

Dinoflagellates are key species in marine environments, but they remain poorly understood in part because of their large, complex genomes, unique molecular biology, and unresolved in-group relationships. We created a taxonomically representative dataset of dinoflagellate transcriptomes and used this to infer a strongly supported phylogeny to map major morphological and...



Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy [Immunology and Inflammation]

2017-01-10T10:16:50-08:00

Pregnancy is one of the strongest inducers of immunological tolerance. Disease activity of many autoimmune diseases including multiple sclerosis (MS) is temporarily suppressed by pregnancy, but little is known about the underlying molecular mechanisms. Here, we investigated the endocrine regulation of conventional and regulatory T cells (Tregs) during reproduction. In...



Ultrastructural anatomy of nodes of Ranvier in the peripheral nervous system as revealed by STED microscopy [Neuroscience]

2017-01-10T10:16:50-08:00

We used stimulated emission depletion (STED) superresolution microscopy to analyze the nanoscale organization of 12 glial and axonal proteins at the nodes of Ranvier of teased sciatic nerve fibers. Cytoskeletal proteins of the axon (betaIV spectrin, ankyrin G) exhibit a high degree of one-dimensional longitudinal order at nodal gaps. In...



Systematic development of small molecules to inhibit specific microscopic steps of A{beta}42 aggregation in Alzheimer’s disease [Neuroscience]

2017-01-10T10:16:50-08:00

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer’s disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop...



Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration [Neuroscience]

2017-01-10T10:16:50-08:00

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the...



Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport [Physiology]

2017-01-10T10:16:50-08:00

The thick ascending limb (TAL) of Henle’s loop drives paracellular Na+, Ca2+, and Mg2+ reabsorption via the tight junction (TJ). The TJ is composed of claudins that consist of four transmembrane segments, two extracellular segments (ECS1 and -2), and one intracellular loop. Claudins interact within the same (cis) and opposing...



Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3 [Physiology]

2017-01-10T10:16:50-08:00

Skeletal muscle contractions are initiated by an increase in Ca2+ released during excitation–contraction (EC) coupling, and defects in EC coupling are associated with human myopathies. EC coupling requires communication between voltage-sensing dihydropyridine receptors (DHPRs) in transverse tubule membrane and Ca2+ release channel ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum...



Two independent S-phase checkpoints regulate appressorium-mediated plant infection by the rice blast fungus Magnaporthe oryzae [Plant Biology]

2017-01-10T10:16:50-08:00

To cause rice blast disease, the fungal pathogen Magnaporthe oryzae develops a specialized infection structure called an appressorium. This dome-shaped, melanin-pigmented cell generates enormous turgor and applies physical force to rupture the rice leaf cuticle using a rigid penetration peg. Appressorium-mediated infection requires septin-dependent reorientation of the F-actin cytoskeleton at...



Abscisic acid signaling is controlled by a BRANCHED1/HD-ZIP I cascade in Arabidopsis axillary buds [Plant Biology]

2017-01-10T10:16:50-08:00

Shoot-branching patterns determine key aspects of plant life and are important targets for crop breeding. However, we are still largely ignorant of the genetic networks controlling locally the most important decision during branch development: whether the axillary bud, or branch primordium, grows out to give a lateral shoot or remains...



Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics [Population Biology]

2017-01-10T10:16:50-08:00

The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement...



Autophagy wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in baker's yeast fuel advances in biomedical research [Cell Biology]

2017-01-10T10:16:49-08:00

Autophagy is an ancient pathway in which parts of eukaryotic cells are self-digested within the lysosome or vacuole. This process has been studied for the past seven decades; however, we are only beginning to gain a molecular understanding of the key steps required for autophagy. Originally characterized as a hormonal...



Oxytocin reactivity during intergroup conflict in wild chimpanzees [Anthropology]

2017-01-10T10:16:49-08:00

Intergroup conflict is evident throughout the history of our species, ubiquitous across human societies, and considered crucial for the evolution of humans’ large-scale cooperative nature. Like humans, chimpanzee societies exhibit intragroup coordination and coalitionary support during violent intergroup conflicts. In both species, cooperation among group members is essential for individuals...



In operando evidence of deoxygenation in ionic liquid gating of YBa2Cu3O7-X [Applied Physical Sciences]

2017-01-10T10:16:49-08:00

Field-effect experiments on cuprates using ionic liquids have enabled the exploration of their rich phase diagrams [Leng X, et al. (2011) Phys Rev Lett 107(2):027001]. Conventional understanding of the electrostatic doping is in terms of modifications of the charge density to screen the electric field generated at the double layer....



Restriction to gene flow is associated with changes in the molecular basis of pyrethroid resistance in the malaria vector Anopheles funestus [Biochemistry]

2017-01-10T10:16:49-08:00

Resistance to pyrethroids, the sole insecticide class recommended for treating bed nets, threatens the control of major malaria vectors, including Anopheles funestus. Effective management of resistance requires an understanding of the dynamics and mechanisms driving resistance. Here, using genome-wide transcription and genetic diversity analyses, we show that a shift in...



IDH1 deficiency attenuates gluconeogenesis in mouse liver by impairing amino acid utilization [Biochemistry]

2017-01-10T10:16:49-08:00

Although the enzymatic activity of isocitrate dehydrogenase 1 (IDH1) was defined decades ago, its functions in vivo are not yet fully understood. Cytosolic IDH1 converts isocitrate to α-ketoglutarate (α-KG), a key metabolite regulating nitrogen homeostasis in catabolic pathways. It was thought that IDH1 might enhance lipid biosynthesis in liver or...



Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation [Biochemistry]

2017-01-10T10:16:49-08:00

Mutations in PARK2 and PARK6 genes are responsible for the majority of hereditary Parkinson’s disease cases. These genes encode the E3 ubiquitin ligase parkin and the protein kinase PTEN-induced kinase 1 (PINK1), respectively. Together, parkin and PINK1 regulate the mitophagy pathway, which recycles damaged mitochondria following oxidative stress. Native parkin...



APE2 Zf-GRF facilitates 3'-5' resection of DNA damage following oxidative stress [Biochemistry]

2017-01-10T10:16:50-08:00

The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3′-5′ nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high...



Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes [Biochemistry]

2017-01-10T10:16:50-08:00

The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by prosurvival Bcl-2 proteins. C-terminal Bax transmembrane domain interactions were implicated recently in Bax pore formation. Here, we show that the...



Arginine substitution of a cysteine in transmembrane helix M8 converts Na+,K+-ATPase to an electroneutral pump similar to H+,K+-ATPase [Biochemistry]

2017-01-10T10:16:50-08:00

Na+,K+-ATPase and H+,K+-ATPase are electrogenic and nonelectrogenic ion pumps, respectively. The underlying structural basis for this difference has not been established, and it has not been revealed how the H+,K+-ATPase avoids binding of Na+ at the site corresponding to the Na+-specific site of the Na+,K+-ATPase (site III). In this study,...



Single-pixel interior filling function approach for detecting and correcting errors in particle tracking [Biophysics and Computational Biology]

2017-01-10T10:16:49-08:00

We present a general method for detecting and correcting biases in the outputs of particle-tracking experiments. Our approach is based on the histogram of estimated positions within pixels, which we term the single-pixel interior filling function (SPIFF). We use the deviation of the SPIFF from a uniform distribution to test...



Whole-GUV patch-clamping [Biophysics and Computational Biology]

2017-01-10T10:16:50-08:00

Studying how the membrane modulates ion channel and transporter activity is challenging because cells actively regulate membrane properties, whereas existing in vitro systems have limitations, such as residual solvent and unphysiologically high membrane tension. Cell-sized giant unilamellar vesicles (GUVs) would be ideal for in vitro electrophysiology, but efforts to measure...



Asymmetric unwrapping of nucleosomal DNA propagates asymmetric opening and dissociation of the histone core [Biophysics and Computational Biology]

2017-01-10T10:16:50-08:00

The nucleosome core particle (NCP) is the basic structural unit for genome packaging in eukaryotic cells and consists of DNA wound around a core of eight histone proteins. DNA access is modulated through dynamic processes of NCP disassembly. Partly disassembled structures, such as the hexasome (containing six histones) and the...



Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells [Cell Biology]

2017-01-10T10:16:50-08:00

Novel APOBEC1 target 1 (Nat1) (also known as “p97,” “Dap5,” and “Eif4g2”) is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the...



Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice [Cell Biology]

2017-01-10T10:16:50-08:00

The Golgi apparatus lies at the heart of the secretory pathway where it is required for secretory trafficking and cargo modification. Disruption of Golgi architecture and function has been widely observed in neurodegenerative disease, but whether Golgi dysfunction is causal with regard to the neurodegenerative process, or is simply a...



Experimental and theoretical evidence for bilayer-by-bilayer surface melting of crystalline ice [Chemistry]

2017-01-10T10:16:49-08:00

On the surface of water ice, a quasi-liquid layer (QLL) has been extensively reported at temperatures below its bulk melting point at 273 K. Approaching the bulk melting temperature from below, the thickness of the QLL is known to increase. To elucidate the precise temperature variation of the QLL, and...



Transparent amorphous oxide semiconductors for organic electronics: Application to inverted OLEDs [Chemistry]

2017-01-10T10:16:49-08:00

Efficient electron transfer between a cathode and an active organic layer is one key to realizing high-performance organic devices, which require electron injection/transport materials with very low work functions. We developed two wide-bandgap amorphous (a-) oxide semiconductors, a-calcium aluminate electride (a-C12A7:e) and a-zinc silicate (a-ZSO). A-ZSO exhibits a low work...



Influenza A surface glycosylation and vaccine design [Chemistry]

2017-01-10T10:16:49-08:00

We have shown that glycosylation of influenza A virus (IAV) hemagglutinin (HA), especially at position N-27, is crucial for HA folding and virus survival. However, it is not known whether the glycosylation of HA and the other two major IAV surface glycoproteins, neuraminidase (NA) and M2 ion channel, is essential...



Origin of hydrophobicity and enhanced water hydrogen bond strength near purely hydrophobic solutes [Chemistry]

2017-01-10T10:16:50-08:00

Hydrophobicity plays an important role in numerous physicochemical processes from the process of dissolution in water to protein folding, but its origin at the fundamental level is still unclear. The classical view of hydrophobic hydration is that, in the presence of a hydrophobic solute, water forms transient microscopic “icebergs” arising...



Holocene carbonate record of Lake Kivu reflects the history of hydrothermal activity [Earth, Atmospheric, and Planetary Sciences]

2017-01-10T10:16:49-08:00

The sediment record of Lake Kivu reveals a complex volcanogenic and climatic Holocene history. Investigation of the inorganic carbonate record dates the onset of carbonate deposition in the mid-Holocene in Kivu’s deep northern and eastern basins and identifies conditions enabling deposition. The magnitude and timing of carbonate-rich sedimentation is not...



The importance of urban gardens in supporting children's biophilia [Ecology]

2017-01-10T10:16:49-08:00

Exposure to and connection with nature is increasingly recognized as providing significant well-being benefits for adults and children. Increasing numbers of children growing up in urban areas need access to nature to experience these benefits and develop a nature connection. Under the biophilia hypothesis, children should innately affiliate to nature....



Climatic regulation of the neurotoxin domoic acid [Environmental Sciences]

2017-01-10T10:16:49-08:00

Domoic acid is a potent neurotoxin produced by certain marine microalgae that can accumulate in the foodweb, posing a health threat to human seafood consumers and wildlife in coastal regions worldwide. Evidence of climatic regulation of domoic acid in shellfish over the past 20 y in the Northern California Current...



Reversal of a cyanobacterial bloom in response to early warnings [Environmental Sciences]

2017-01-10T10:16:50-08:00

Directional change in environmental drivers sometimes triggers regime shifts in ecosystems. Theory and experiments suggest that regime shifts can be detected in advance, and perhaps averted, by monitoring resilience indicators such as variance and autocorrelation of key ecosystem variables. However, it is uncertain whether management action prompted by a change...