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Proceedings of the National Academy of Sciences RSS feed -- Early Edition



 



Solar thermochemical splitting of water to generate hydrogen [Perspectives]

2017-05-18T11:58:25-07:00

Solar photochemical means of splitting water (artificial photosynthesis) to generate hydrogen is emerging as a viable process. The solar thermochemical route also promises to be an attractive means of achieving this objective. In this paper we present different types of thermochemical cycles that one can use for the purpose. These...



Water is an active matrix of life for cell and molecular biology [Perspectives]

2017-06-07T12:43:37-07:00

Szent-Győrgi called water the “matrix of life” and claimed that there was no life without it. This statement is true, as far as we know, on our planet, but it is not clear whether it must hold throughout the cosmos. To evaluate that question requires a close consideration of the...



Microscopic dynamics of charge separation at the aqueous electrochemical interface [Chemistry]

2017-07-11T09:36:45-07:00

We have used molecular simulation and methods of importance sampling to study the thermodynamics and kinetics of ionic charge separation at a liquid water–metal interface. We have considered this process using canonical examples of two different classes of ions: a simple alkali–halide pair, Na+I−, or classical ions, and the products...



Molecular characterization of water and surfactant AOT at nanoemulsion surfaces [Chemistry]

2017-07-31T11:51:02-07:00

Nanoemulsions and microemulsions are environments where oil and water can be solubilized in one another to provide a unique platform for many different biological and industrial applications. Nanoemulsions, unlike microemulsions, have seen little work done to characterize molecular interactions at their surfaces. This study provides a detailed investigation of the...



Mechanism of ion adsorption to aqueous interfaces: Graphene/water vs. air/water [Chemistry]

2017-08-21T12:06:10-07:00

The adsorption of ions to aqueous interfaces is a phenomenon that profoundly influences vital processes in many areas of science, including biology, atmospheric chemistry, electrical energy storage, and water process engineering. Although classical electrostatics theory predicts that ions are repelled from water/hydrophobe (e.g., air/water) interfaces, both computer simulations and experiments...



XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction [Biophysics and Computational Biology]

2017-08-23T11:33:34-07:00

The M2 proton channel of influenza A is a drug target that is essential for the reproduction of the flu virus. It is also a model system for the study of selective, unidirectional proton transport across a membrane. Ordered water molecules arranged in “wires” inside the channel pore have been...



Self-healing catalysis in water [Chemistry]

2017-09-05T09:11:22-07:00

Principles for designing self-healing water-splitting catalysts are presented together with a formal kinetics model to account for the key chemical steps needed for self-healing. Self-healing may be realized if the catalysts are able to self-assemble at applied potentials less than that needed for catalyst turnover. Solution pH provides a convenient...



Specific cation effects at aqueous solution-vapor interfaces: Surfactant-like behavior of Li+ revealed by experiments and simulations [Chemistry]

2017-10-09T11:49:04-07:00

It is now well established by numerous experimental and computational studies that the adsorption propensities of inorganic anions conform to the Hofmeister series. The adsorption propensities of inorganic cations, such as the alkali metal cations, have received relatively little attention. Here we use a combination of liquid-jet X-ray photoelectron experiments...



Supercooled and glassy water: Metastable liquid(s), amorphous solid(s), and a no-man’s land [Perspectives]

2017-11-13T11:40:55-08:00

We review the recent research on supercooled and glassy water, focusing on the possible origins of its complex behavior. We stress the central role played by the strong directionality of the water–water interaction and by the competition between local energy, local entropy, and local density. In this context we discuss...



Hydrophobicity of proteins and nanostructured solutes is governed by topographical and chemical context [Chemistry]

2017-11-20T11:40:46-08:00

Hydrophobic interactions drive many important biomolecular self-assembly phenomena. However, characterizing hydrophobicity at the nanoscale has remained a challenge due to its nontrivial dependence on the chemistry and topography of biomolecular surfaces. Here we use molecular simulations coupled with enhanced sampling methods to systematically displace water molecules from the hydration shells...



Induced GnasR201H expression from the endogenous Gnas locus causes fibrous dysplasia by up-regulating Wnt/{beta}-catenin signaling [Genetics]

2017-11-20T11:40:47-08:00

Fibrous dysplasia (FD; Online Mendelian Inheritance in Man no. 174800) is a crippling skeletal disease caused by activating mutations of the GNAS gene, which encodes the stimulatory G protein Gαs. FD can lead to severe adverse conditions such as bone deformity, fracture, and severe pain, leading to functional impairment and...



Correction for Kang et al., Increased intracellular Ca2+ concentrations prevent membrane localization of PH domains through the formation of Ca2+-phosphoinositides [Corrections]

2017-11-27T11:47:21-08:00

BIOCHEMISTRY Correction for “Increased intracellular Ca2+ concentrations prevent membrane localization of PH domains through the formation of Ca2+-phosphoinositides,” by Jin Ku Kang, Ok-Hee Kim, June Hur, So Hee Yu, Santosh Lamichhane, Jin Wook Lee, Uttam Ojha, Jeong Hee Hong, Cheol Soon Lee, Ji-Young Cha, Young Jae Lee, Seung-Soon lm, Young...



Unleashing meiotic crossovers in hybrid plants [Genetics]

2017-11-28T10:25:16-08:00

Meiotic crossovers shuffle parental genetic information, providing novel combinations of alleles on which natural or artificial selection can act. However, crossover events are relatively rare, typically one to three exchange points per chromosome pair. Recent work has identified three pathways limiting meiotic crossovers in Arabidopsis thaliana that rely on the...



Rapid adaptive evolution in novel environments acts as an architect of population range expansion [Evolution]

2017-11-28T10:25:17-08:00

Colonization and expansion into novel landscapes determine the distribution and abundance of species in our rapidly changing ecosystems worldwide. Colonization events are crucibles for rapid evolution, but it is not known whether evolutionary changes arise mainly after successful colonization has occurred, or if evolution plays an immediate role, governing the...



Ultrafast 25-fs relaxation in highly excited states of methyl azide mediated by strong nonadiabatic coupling [Chemistry]

2017-11-29T12:11:47-08:00

Highly excited electronic states are challenging to explore experimentally and theoretically—due to the large density of states and the fact that small structural changes lead to large changes in electronic character with associated strong nonadiabatic dynamics. They can play a key role in astrophysical and ionospheric chemistry, as well as...



Contributions of primate prefrontal cortex and medial temporal lobe to temporal-order memory [Neuroscience]

2017-11-30T12:05:33-08:00

Neuropsychological and neurophysiological studies have emphasized the role of the prefrontal cortex (PFC) in maintaining information about the temporal order of events or items for upcoming actions. However, the medial temporal lobe (MTL) has also been considered critical to bind individual events or items to their temporal context in episodic...



Photochemistry of highly excited states [Commentaries]

2017-11-30T12:05:33-08:00

These days on earth we are photochemically reasonably well shielded. The far UV radiation is filtered by the ozone and other components of the atmosphere. In the ionosphere and beyond there is much challenging chemistry induced by such higher-energy photons. The shielding by the atmosphere also makes demands on such...



G{alpha}s protein binds ubiquitin to regulate epidermal growth factor receptor endosomal sorting [Cell Biology]

2017-11-30T12:05:33-08:00

The Gαs subunit is classically involved in the signal transduction of G protein-coupled receptors (GPCRs) at the plasma membrane. Recent evidence has revealed noncanonical roles for Gαs in endosomal sorting of receptors to lysosomes. However, the mechanism of action of Gαs in this sorting step is still poorly characterized. Here,...



MotI (DgrA) acts as a molecular clutch on the flagellar stator protein MotA in Bacillus subtilis [Microbiology]

2017-12-01T12:06:16-08:00

Stator elements consisting of MotA4MotB2 complexes are anchored to the cell wall, extend through the cell membrane, and interact with FliG in the cytoplasmic C ring rotor of the flagellum. The cytoplasmic loop of MotA undergoes proton-driven conformational changes that drive flagellar rotation. Functional regulators inhibit motility by either disengaging...



Metabolic activity induces membrane phase separation in endoplasmic reticulum [Biophysics and Computational Biology]

2017-12-01T12:06:17-08:00

Membrane phase behavior has been well characterized in model membranes in vitro under thermodynamic equilibrium state. However, the widely observed differences between biological membranes and their in vitro counterparts are placing more emphasis on nonequilibrium factors, including influx and efflux of lipid molecules. The endoplasmic reticulum (ER) is the largest...



Profile of Joachim Frank, Richard Henderson, and Jacques Dubochet, 2017 Nobel Laureates in Chemistry [Profiles]

2017-12-01T12:06:17-08:00

In 2017, the Nobel Prize in Chemistry was awarded to three key pioneers in the birth and development of cryoelectron microscopy (cryo-EM): Jacques Dubochet, Joachim Frank, and Richard Henderson. As a starting graduate student in England, moving from physics to biology and the study of macromolecular structure, I had the...



Rapid diagnostic testing platform for iron and vitamin A deficiency [Engineering]

2017-12-04T11:45:43-08:00

Micronutrient deficiencies such as those of vitamin A and iron affect a third of the world’s population with consequences such as night blindness, higher child mortality, anemia, poor pregnancy outcomes, and reduced work capacity. Many efforts to prevent or treat these deficiencies are hampered by the lack of adequate, accessible,...



Relationship between season of birth, temperature exposure, and later life wellbeing [Sustainability Science]

2017-12-04T11:45:43-08:00

We study how exposure to extreme temperatures in early periods of child development is related to adult economic outcomes measured 30 y later. Our analysis uses administrative earnings records for over 12 million individuals born in the United States between 1969 and 1977, linked to fine-scale, daily weather data and...



Percolative core formation in planetesimals enabled by hysteresis in metal connectivity [Earth, Atmospheric, and Planetary Sciences]

2017-12-04T11:45:44-08:00

The segregation of dense core-forming melts by porous flow is a natural mechanism for core formation in early planetesimals. However, experimental observations show that texturally equilibrated metallic melt does not wet the silicate grain boundaries and tends to reside in isolated pockets that prevent percolation. Here we use pore-scale simulations...



Molecular and functional resemblance of differentiated cells derived from isogenic human iPSCs and SCNT-derived ESCs [Applied Biological Sciences]

2017-12-04T11:45:44-08:00

Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear reprogramming by transcription factors (i.e., induced pluripotent stem cells, iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and preclinical application of differentiated cells generated by different reprogramming mechanisms have yet to be evaluated. Here we investigated the molecular...



TRPV1 is a physiological regulator of {mu}-opioid receptors [Pharmacology]

2017-12-04T11:45:44-08:00

Opioids are powerful analgesics, but also carry significant side effects and abuse potential. Here we describe a modulator of the μ-opioid receptor (MOR1), the transient receptor potential channel subfamily vanilloid member 1 (TRPV1). We show that TRPV1 binds MOR1 and blocks opioid-dependent phosphorylation of MOR1 while leaving G protein signaling...



Terminal attack trajectories of peregrine falcons are described by the proportional navigation guidance law of missiles [Engineering]

2017-12-04T11:45:44-08:00

The ability to intercept uncooperative targets is key to many diverse flight behaviors, from courtship to predation. Previous research has looked for simple geometric rules describing the attack trajectories of animals, but the underlying feedback laws have remained obscure. Here, we use GPS loggers and onboard video cameras to study...



Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors [Chemistry]

2017-12-04T11:45:44-08:00

Histone deacetylases (HDACs) regulate myriad cellular processes by catalyzing the hydrolysis of acetyl–l-lysine residues in histone and nonhistone proteins. The Zn2+-dependent class IIb enzyme HDAC6 regulates microtubule function by deacetylating α-tubulin, which suppresses microtubule dynamics and leads to cell cycle arrest and apoptosis. Accordingly, HDAC6 is a target for the...



Selected reaction monitoring approach for validating peptide biomarkers [Medical Sciences]

2017-12-04T11:45:45-08:00

We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate...



Structural studies of Chikungunya virus maturation [Biophysics and Computational Biology]

2017-12-04T11:45:45-08:00

Cleavage of the alphavirus precursor glycoprotein p62 into the E2 and E3 glycoproteins before assembly with the nucleocapsid is the key to producing fusion-competent mature spikes on alphaviruses. Here we present a cryo-EM, 6.8-Å resolution structure of an “immature” Chikungunya virus in which the cleavage site has been mutated to...



Electrostatic confinement and manipulation of DNA molecules for genome analysis [Chemistry]

2017-12-04T11:45:45-08:00

Very large DNA molecules enable comprehensive analysis of complex genomes, such as human, cancer, and plants because they span across sequence repeats and complex somatic events. When physically manipulated, or analyzed as single molecules, long polyelectrolytes are problematic because of mechanical considerations that include shear-mediated breakage, dealing with the massive...



Islet cells share promoter hypomethylation independently of expression, but exhibit cell-type-specific methylation in enhancers [Medical Sciences]

2017-12-04T11:45:46-08:00

DNA methylation at promoters is an important determinant of gene expression. Earlier studies suggested that the insulin gene promoter is uniquely unmethylated in insulin-expressing pancreatic β-cells, providing a classic example of this paradigm. Here we show that islet cells expressing insulin, glucagon, or somatostatin share a lack of methylation at...



Early childhood stress exposure, reward pathways, and adult decision making [Psychological and Cognitive Sciences]

2017-12-04T11:45:46-08:00

Individuals who have experienced chronic and high levels of stress during their childhoods are at increased risk for a wide range of behavioral problems, yet the neurobiological mechanisms underlying this association are poorly understood. We measured the life circumstances of a community sample of school-aged children and then followed these...



Structural insights into the roles of the IcmS-IcmW complex in the type IVb secretion system of Legionella pneumophila [Microbiology]

2017-12-04T11:45:47-08:00

The type IVb secretion system (T4BSS) of Legionella pneumophila is a multiple-component apparatus that delivers ∼300 virulent effector proteins into host cells. The injected effectors modulate host cellular processes to promote bacterial infection and proliferation. IcmS and IcmW are two conserved small, acidic adaptor proteins that form a binary complex...



Dynamics of translation can determine the spatial organization of membrane-bound proteins and their mRNA [Biophysics and Computational Biology]

2017-12-04T11:45:47-08:00

Unlike most macromolecules that are homogeneously distributed in the bacterial cell, mRNAs that encode inner-membrane proteins can be concentrated near the inner membrane. Cotranslational insertion of the nascent peptide into the membrane brings the translating ribosome and the mRNA close to the membrane. This suggests that kinetic properties of translation...



Multiple oscillatory rhythms determine the temporal organization of perception [Neuroscience]

2017-12-04T11:45:48-08:00

Incoming sensory input is condensed by our perceptual system to optimally represent and store information. In the temporal domain, this process has been described in terms of temporal windows (TWs) of integration/segregation, in which the phase of ongoing neural oscillations determines whether two stimuli are integrated into a single percept...



Naturalization of European plants on other continents: The role of donor habitats [Ecology]

2017-12-04T11:45:48-08:00

The success of European plant species as aliens worldwide is thought to reflect their association with human-disturbed environments. However, an explicit test including all human-made, seminatural and natural habitat types of Europe, and their contributions as donor habitats of naturalized species to the rest of the globe, has been missing....



Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome [Biochemistry]

2017-12-05T09:02:38-08:00

Phosphorylation is a major regulator of protein interactions; however, the mechanisms by which regulation occurs are not well understood. Here we identify a salt-bridge competition or “theft” mechanism that enables a phospho-triggered swap of protein partners by Raf Kinase Inhibitory Protein (RKIP). RKIP transitions from inhibiting Raf-1 to inhibiting G-protein–coupled...



Transverse fields to tune an Ising-nematic quantum phase transition [Physics]

2017-12-05T09:02:39-08:00

The paradigmatic example of a continuous quantum phase transition is the transverse field Ising ferromagnet. In contrast to classical critical systems, whose properties depend only on symmetry and the dimension of space, the nature of a quantum phase transition also depends on the dynamics. In the transverse field Ising model,...



Molecular basis for the recognition of the human AAUAAA polyadenylation signal [Biochemistry]

2017-12-05T09:02:39-08:00

Nearly all eukaryotic messenger RNA precursors must undergo cleavage and polyadenylation at their 3′-end for maturation. A crucial step in this process is the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular mechanism of this recognition has been a long-standing problem. Here, we report the cryo-electron microscopy structure...



Crystal structure of human IRAK1 [Biophysics and Computational Biology]

2017-12-05T09:02:39-08:00

Interleukin 1 (IL-1) receptor-associated kinases (IRAKs) are serine/threonine kinases that play critical roles in initiating innate immune responses against foreign pathogens and other types of dangers through their role in Toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) mediated signaling pathways. Upon ligand binding, TLRs and IL-1Rs recruit adaptor proteins,...



SbcC-SbcD and ExoI process convergent forks to complete chromosome replication [Cell Biology]

2017-12-05T09:02:39-08:00

SbcC-SbcD are the bacterial orthologs of Mre11-Rad50, a nuclease complex essential for genome stability, normal development, and viability in mammals. In vitro, these enzymes degrade long DNA palindromic structures. When inactivated along with ExoI in Escherichia coli, or Sae2 in eukaryotes, palindromic amplifications arise and propagate in cells. However, long...



What Chern-Simons theory assigns to a point [Mathematics]

2017-12-05T09:02:39-08:00

We answer the questions, “What does Chern–Simons theory assign to a point?” and “What kind of mathematical object does Chern–Simons theory assign to a point?” Our answer to the first question is representations of the based loop group. More precisely, we identify a certain class of projective unitary representations of...



Efficient targeted DNA editing and replacement in Chlamydomonas reinhardtii using Cpf1 ribonucleoproteins and single-stranded DNA [Plant Biology]

2017-12-05T09:02:40-08:00

The green alga Chlamydomonas reinhardtii is an invaluable reference organism to research fields including algal, plant, and ciliary biology. Accordingly, decades-long standing inefficiencies in targeted nuclear gene editing broadly hinder Chlamydomonas research. Here we report that single-step codelivery of CRISPR/Cpf1 ribonucleoproteins with single-stranded DNA repair templates results in precise and...



An inclusive Research Education Community (iREC): Impact of the SEA-PHAGES program on research outcomes and student learning [Microbiology]

2017-12-07T12:44:38-08:00

Engaging undergraduate students in scientific research promises substantial benefits, but it is not accessible to all students and is rarely implemented early in college education, when it will have the greatest impact. An inclusive Research Education Community (iREC) provides a centralized scientific and administrative infrastructure enabling engagement of large numbers...



Default neglect in attempts at social influence [Psychological and Cognitive Sciences]

2017-12-08T12:05:14-08:00

Current theories suggest that people understand how to exploit common biases to influence others. However, these predictions have received little empirical attention. We consider a widely studied bias with special policy relevance: the default effect, which is the tendency to choose whichever option is the status quo. We asked participants...



How reduced excitonic coupling enhances light harvesting in the main photosynthetic antennae of diatoms [Biophysics and Computational Biology]

2017-12-11T11:51:08-08:00

Strong excitonic interactions are a key design strategy in photosynthetic light harvesting, expanding the spectral cross-section for light absorption and creating considerably faster and more robust excitation energy transfer. These molecular excitons are a direct result of exceptionally densely packed pigments in photosynthetic proteins. The main light-harvesting complexes of diatoms,...



Sclerostin influences body composition by regulating catabolic and anabolic metabolism in adipocytes [Medical Sciences]

2017-12-11T11:51:09-08:00

Sclerostin has traditionally been thought of as a local inhibitor of bone acquisition that antagonizes the profound osteoanabolic capacity of activated Wnt/β-catenin signaling, but serum sclerostin levels in humans exhibit a correlation with impairments in several metabolic parameters. These data, together with the increased production of sclerostin in mouse models...



Impact of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the costs of mitigation [Medical Sciences]

2017-12-11T11:51:09-08:00

Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact...



Proteasomes tether to two distinct sites at the nuclear pore complex [Cell Biology]

2017-12-11T11:51:09-08:00

The partitioning of cellular components between the nucleus and cytoplasm is the defining feature of eukaryotic life. The nuclear pore complex (NPC) selectively gates the transport of macromolecules between these compartments, but it is unknown whether surveillance mechanisms exist to reinforce this function. By leveraging in situ cryo-electron tomography to...



Correction for Giang et al., Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus [Corrections]

2017-12-11T11:51:09-08:00

MEDICAL SCIENCES Correction for “Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus,” by Erick Giang, Marcus Dorner, Jannick C. Prentoe, Marlène Dreux, Matthew J. Evans, Jens Bukh, Charles M. Rice, Alexander Ploss, Dennis R. Burton, and Mansun Law, which was first published April 4, 2012;...



Perception and misperception of surface opacity [Psychological and Cognitive Sciences]

2017-12-11T11:51:10-08:00

A fundamental problem in extracting scene structure is distinguishing different physical sources of image structure. Light reflected by an opaque surface covaries with local surface orientation, whereas light transported through the body of a translucent material does not. This suggests the possibility that the visual system may use the covariation...



Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci [Medical Sciences]

2017-12-11T11:51:10-08:00

The CRISPR-Cas9 nuclease system holds enormous potential for therapeutic genome editing of a wide spectrum of diseases. Large efforts have been made to further understanding of on- and off-target activity to assist the design of CRISPR-based therapies with optimized efficacy and safety. However, current efforts have largely focused on the...



SE2 reaction in noncarbon system: Metal-halide catalysis for dehydrogenation of ammonia borane [Chemistry]

2017-12-11T11:51:10-08:00

An electrophilic substitution (SE) reaction of BN isosteres has been investigated for the dehydrogenation of ammonia borane (AB) by metal chlorides (MCl2) using various ab initio calculations. In contrast to the typical SE reaction occurring at the carbon atom, the nitrogen atom in AB serves as the reaction center for...



De novo reconstitution reveals the proteins required for skeletal muscle voltage-induced Ca2+ release [Physiology]

2017-12-11T11:51:10-08:00

Skeletal muscle contraction is triggered by Ca2+ release from the sarcoplasmic reticulum (SR) in response to plasma membrane (PM) excitation. In vertebrates, this depends on activation of the RyR1 Ca2+ pore in the SR, under control of conformational changes of CaV1.1, located ∼12 nm away in the PM. Over the...



Correction for Possner and Caldeira, Geophysical potential for wind energy over the open oceans [Corrections]

2017-12-11T11:51:10-08:00

ENVIRONMENTAL SCIENCES, SUSTAINABILITY SCIENCE Correction for “Geophysical potential for wind energy over the open oceans,” by Anna Possner and Ken Caldeira, which was first published October 9, 2017; 10.1073/pnas.1705710114 (Proc Natl Acad Sci USA 114:11338–11343). The authors note that Fig. 6 appeared incorrectly. The corrected figure and its legend appear...



Comparative transcriptomics as a guide to natural product discovery and biosynthetic gene cluster functionality [Biochemistry]

2017-12-11T11:51:11-08:00

Bacterial natural products remain an important source of new medicines. DNA sequencing has revealed that a majority of natural product biosynthetic gene clusters (BGCs) maintained in bacterial genomes have yet to be linked to the small molecules whose biosynthesis they encode. Efforts to discover the products of these orphan BGCs...



Accelerating fishes increase propulsive efficiency by modulating vortex ring geometry [Physiology]

2017-12-11T11:51:11-08:00

Swimming animals need to generate propulsive force to overcome drag, regardless of whether they swim steadily or accelerate forward. While locomotion strategies for steady swimming are well characterized, far less is known about acceleration. Animals exhibit many different ways to swim steadily, but we show here that this behavioral diversity...



Discovery of the leinamycin family of natural products by mining actinobacterial genomes [Biochemistry]

2017-12-11T11:51:11-08:00

Nature’s ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach...



Beta oscillations reflect supramodal information during perceptual judgment [Neuroscience]

2017-12-11T11:51:11-08:00

Previous work on perceptual decision making in the sensorimotor system has shown population dynamics in the beta band, corresponding to the encoding of stimulus properties and the final decision outcome. Here, we asked how oscillatory dynamics in the medial premotor cortex (MPC) contribute to supramodal perceptual decision making. We recorded...



Critical dynamics in population vaccinating behavior [Ecology]

2017-12-11T11:51:12-08:00

Vaccine refusal can lead to renewed outbreaks of previously eliminated diseases and even delay global eradication. Vaccinating decisions exemplify a complex, coupled system where vaccinating behavior and disease dynamics influence one another. Such systems often exhibit critical phenomena—special dynamics close to a tipping point leading to a new dynamical regime....



Chemical physics of water [Introductions]

2017-12-11T11:51:12-08:00

There is hardly any aspect of our lives that is not profoundly influenced by water. From climate to commerce and agriculture to health, water shapes our physical environment, regulates the major energy exchanges that determine climate on Earth, and is the matrix that supports the physical and chemical processes of...



Sex determination of human remains from peptides in tooth enamel [Anthropology]

2017-12-11T11:51:12-08:00

The assignment of biological sex to archaeological human skeletons is a fundamental requirement for the reconstruction of the human past. It is conventionally and routinely performed on adults using metric analysis and morphological traits arising from postpubertal sexual dimorphism. A maximum accuracy of ∼95% is possible if both the cranium...



Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL [Biophysics and Computational Biology]

2017-12-11T11:51:12-08:00

Microbial pathogens employ sophisticated virulence strategies to cause infections in humans. The intracellular pathogen Legionella pneumophila encodes RidL to hijack the host scaffold protein VPS29, a component of retromer and retriever complexes critical for endosomal cargo recycling. Here, we determined the crystal structure of L. pneumophila RidL in complex with...



Network analysis identifies chromosome intermingling regions as regulatory hotspots for transcription [Biophysics and Computational Biology]

2017-12-11T11:51:12-08:00

The 3D structure of the genome plays a key role in regulatory control of the cell. Experimental methods such as high-throughput chromosome conformation capture (Hi-C) have been developed to probe the 3D structure of the genome. However, it remains a challenge to deduce from these data chromosome regions that are...



Identification of cancer genes that are independent of dominant proliferation and lineage programs [Medical Sciences]

2017-12-11T11:51:12-08:00

Large, multidimensional cancer datasets provide a resource that can be mined to identify candidate therapeutic targets for specific subgroups of tumors. Here, we analyzed human breast cancer data to identify transcriptional programs associated with tumors bearing specific genetic driver alterations. Using an unbiased approach, we identified thousands of genes whose...



Correction for Matthews et al., Optimal nutrient exchange and immune responses operate in partner specificity in the cnidarian-dinoflagellate symbiosis [Corrections]

2017-12-11T11:51:13-08:00

CELL BIOLOGY Correction for “Optimal nutrient exchange and immune responses operate in partner specificity in the cnidarian-dinoflagellate symbiosis,” by Jennifer L. Matthews, Camerron M. Crowder, Clinton A. Oakley, Adrian Lutz, Ute Roessner, Eli Meyer, Arthur R. Grossman, Virginia M. Weis, and Simon K. Davy, which was first published November 20,...



Dispersal limitation promotes the diversification of the mammalian gut microbiota [Evolution]

2017-12-11T11:51:13-08:00

The gut bacterial communities of mammals have profound effects on host fitness, but the processes that generate and maintain gut bacterial diversity remain poorly understood. We mapped compositional variation (i.e., β-diversity) in the gut microbiotas of 136 pairs of wild mammalian species living throughout the Americas to assess how the...



PSMA-targeted polyinosine/polycytosine vector induces prostate tumor regression and invokes an antitumor immune response in mice [Applied Biological Sciences]

2017-12-11T11:51:13-08:00

There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine–polyethyleneglycol (PEI–PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of...



Correction for Gerth et al., Intersectin associates with synapsin and regulates its nanoscale localization and function [Corrections]

2017-12-11T11:51:13-08:00

NEUROSCIENCE Correction for “Intersectin associates with synapsin and regulates its nanoscale localization and function,” by Fabian Gerth, Maria Jäpel, Arndt Pechstein, Gaga Kochlamazashvili, Martin Lehmann, Dmytro Puchkov, Franco Onofri, Fabio Benfenati, Alexander G. Nikonenko, Tanja Maritzen, Christian Freund, and Volker Haucke, which was first published October 23, 2017; 10.1073/pnas.1715341114 (Proc...



Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11{beta}-hydroxysteroid dehydrogenase type 2 deficiency [Medical Sciences]

2017-12-11T11:51:13-08:00

Mutations in 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) cause an extraordinarily rare autosomal recessive disorder, apparent mineralocorticoid excess (AME). AME is a form of low renin hypertension that is potentially fatal if untreated. Mutations in the HSD11B2 gene result either in severe AME or a milder phenotype (type 2 AME)....



FKBP12 contributes to {alpha}-synuclein toxicity by regulating the calcineurin-dependent phosphoproteome [Neuroscience]

2017-12-11T11:51:13-08:00

Calcineurin is an essential Ca2+-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α-syn) toxicity, a protein implicated in Parkinson’s Disease (PD) and other neurodegenerative diseases. Calcineurin can be inhibited with Tacrolimus through the recruitment and inhibition of the 12-kDa cis-trans proline isomerase FK506-binding protein (FKBP12). Whether calcineurin/FKBP12 represents a...



Kinetics of drug-ribosome interactions defines the cidality of macrolide antibiotics [Biochemistry]

2017-12-11T11:51:14-08:00

Antibiotics can cause dormancy (bacteriostasis) or induce death (cidality) of the targeted bacteria. The bactericidal capacity is one of the most important properties of antibacterial agents. However, the understanding of the fundamental differences in the mode of action of bacteriostatic or bactericidal antibiotics, especially those belonging to the same chemical...



Rapid, direct activity assays for Smoothened reveal Hedgehog pathway regulation by membrane cholesterol and extracellular sodium [Biochemistry]

2017-12-11T11:51:14-08:00

Hedgehog signaling specifies tissue patterning and renewal, and pathway components are commonly mutated in certain malignancies. Although central to ensuring appropriate pathway activity in all Hedgehog-responsive cells, how the transporter-like receptor Patched1 regulates the seven-transmembrane protein Smoothened remains mysterious, partially due to limitations in existing tools and experimental systems. Here...



O-GlcNAcylation destabilizes the active tetrameric PKM2 to promote the Warburg effect [Cell Biology]

2017-12-11T11:51:14-08:00

The Warburg effect, characterized by increased glucose uptake and lactate production, is a well-known universal across cancer cells and other proliferating cells. PKM2, a splice isoform of the pyruvate kinase (PK) specifically expressed in these cells, serves as a major regulator of this metabolic reprogramming with an adjustable activity subjected...



Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance [Engineering]

2017-12-11T11:51:14-08:00

Continuous BRAF inhibition of BRAF mutant melanomas triggers a series of cell state changes that lead to therapy resistance and escape from immune control before establishing acquired resistance genetically. We used genome-wide transcriptomics and single-cell phenotyping to explore the response kinetics to BRAF inhibition for a panel of patient-derived BRAFV600-mutant...



Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies [Medical Sciences]

2017-12-11T11:51:15-08:00

Phosphatidylethanolamine (PE) is a major phospholipid species with important roles in membrane trafficking and reorganization. Accumulating clinical data indicate that the presence of circulating antibodies against PE is positively correlated with the symptoms of antiphospholipid syndromes (APS), including thrombosis and repeated pregnancy loss. However, PE is generally sequestered inside a...



Architecture of the human PI4KIII{alpha} lipid kinase complex [Cell Biology]

2017-12-11T11:51:15-08:00

Plasma membrane (PM) phosphoinositides play essential roles in cell physiology, serving as both markers of membrane identity and signaling molecules central to the cell’s interaction with its environment. The first step in PM phosphoinositide synthesis is the conversion of phosphatidylinositol (PI) to PI4P, the precursor of PI(4,5)P2 and PI(3,4,5)P3. This...



Correction for Roehr, Core Concept: Tissue resident memory cells emerging as key player in health and disease [Corrections]

2017-12-11T11:51:15-08:00

CORE CONCEPTS Correction for “Core Concept: Tissue resident memory cells emerging as key player in health and disease,” by Bob Roehr, which was first published November 14, 2017; 10.1073/pnas.1715754114 (Proc Natl Acad Sci USA 114:12092–12093). The editors note that reference 3 appeared incorrectly. The complete corrected reference appears below. The...



Structural changes of tailless bacteriophage {Phi}X174 during penetration of bacterial cell walls [Biophysics and Computational Biology]

2017-12-11T11:51:15-08:00

Unlike tailed bacteriophages, which use a preformed tail for transporting their genomes into a host bacterium, the ssDNA bacteriophage ΦX174 is tailless. Using cryo-electron microscopy and time-resolved small-angle X-ray scattering, we show that lipopolysaccharides (LPS) form bilayers that interact with ΦX174 at an icosahedral fivefold vertex and induce single-stranded (ss)...



Predicting glycosaminoglycan surface protein interactions and implications for studying axonal growth [Biophysics and Computational Biology]

2017-12-11T11:51:15-08:00

Cell-surface carbohydrates play important roles in numerous biological processes through their interactions with various protein-binding partners. These interactions are made possible by the vast structural diversity of carbohydrates and the diverse array of carbohydrate presentations on the cell surface. Among the most complex and important carbohydrates are glycosaminoglycans (GAGs), which...



Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y [Immunology and Inflammation]

2017-12-11T11:51:15-08:00

We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely...



Machine learning shows association between genetic variability in PPARG and cerebral connectivity in preterm infants [Developmental Biology]

2017-12-11T11:51:16-08:00

Preterm infants show abnormal structural and functional brain development, and have a high risk of long-term neurocognitive problems. The molecular and cellular mechanisms involved are poorly understood, but novel methods now make it possible to address them by examining the relationship between common genetic variability and brain endophenotype. We addressed...



Cytokine signaling through Drosophila Mthl10 ties lifespan to environmental stress [Immunology and Inflammation]

2017-12-11T11:51:16-08:00

A systems-level understanding of cytokine-mediated, intertissue signaling is one of the keys to developing fundamental insight into the links between aging and inflammation. Here, we employed Drosophila, a routine model for analysis of cytokine signaling pathways in higher animals, to identify a receptor for the growth-blocking peptide (GBP) cytokine. Having...



Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases [Neuroscience]

2017-12-11T11:51:16-08:00

The neurodegenerative disorder Huntington’s disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene, translating to an elongated glutamine tract in the huntingtin...



Understanding the mechanisms of amorphous creep through molecular simulation [Engineering]

2017-12-11T11:51:16-08:00

Molecular processes of creep in metallic glass thin films are simulated at experimental timescales using a metadynamics-based atomistic method. Space–time evolutions of the atomic strains and nonaffine atom displacements are analyzed to reveal details of the atomic-level deformation and flow processes of amorphous creep in response to stress and thermal...



Population is the main driver of war group size and conflict casualties [Anthropology]

2017-12-11T11:51:17-08:00

The proportions of individuals involved in intergroup coalitional conflict, measured by war group size (W), conflict casualties (C), and overall group conflict deaths (G), have declined with respect to growing populations, implying that states are less violent than small-scale societies. We argue that these trends are better explained by scaling...



Three tRNAs on the ribosome slow translation elongation [Biophysics and Computational Biology]

2017-12-11T11:51:17-08:00

During protein synthesis, the ribosome simultaneously binds up to three different transfer RNA (tRNA) molecules. Among the three tRNA binding sites, the regulatory role of the exit (E) site, where deacylated tRNA spontaneously dissociates from the translational complex, has remained elusive. Here we use two donor–quencher pairs to observe and...



Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys [Medical Sciences]

2017-12-11T11:51:17-08:00

Negative and positive feedback effects of ovarian 17β-estradiol (E2) regulating release of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) are pivotal events in female reproductive function. While ovarian feedback on hypothalamo–pituitary function is a well-established concept, the present study shows that neuroestradiol, locally synthesized in the hypothalamus, is a...



Human presence diminishes the importance of climate in driving fire activity across the United States [Sustainability Science]

2017-12-11T11:51:17-08:00

Growing human and ecological costs due to increasing wildfire are an urgent concern in policy and management, particularly given projections of worsening fire conditions under climate change. Thus, understanding the relationship between climatic variation and fire activity is a critically important scientific question. Different factors limit fire behavior in different...



Structure-based prediction of ligand-protein interactions on a genome-wide scale [Biophysics and Computational Biology]

2017-12-11T11:51:17-08:00

We report a template-based method, LT-scanner, which scans the human proteome using protein structural alignment to identify proteins that are likely to bind ligands that are present in experimentally determined complexes. A scoring function that rapidly accounts for binding site similarities between the template and the proteins being scanned is...



Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development [Developmental Biology]

2017-12-11T11:51:18-08:00

Cortical interneurons (cINs) modulate excitatory neuronal activity by providing local inhibition. During fetal development, several cIN subtypes derive from the medial ganglionic eminence (MGE), a transient ventral telencephalic structure. While altered cIN development contributes to neurodevelopmental disorders, the inaccessibility of human fetal brain tissue during development has hampered efforts to...



Designing flexible 2D transition metal carbides with strain-controllable lithium storage [Chemistry]

2017-12-11T11:51:18-08:00

Efficient flexible energy storage systems have received tremendous attention due to their enormous potential applications in self-powering portable electronic devices, including roll-up displays, electronic paper, and “smart” garments outfitted with piezoelectric patches to harvest energy from body movement. Unfortunately, the further development of these technologies faces great challenges due to...



Interferon-beta represses cancer stem cell properties in triple-negative breast cancer [Medical Sciences]

2017-12-11T11:51:18-08:00

Triple-negative breast cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed IFN/signal transducer and activator of transcription (IFN/STAT) gene signature and are often enriched for cancer stem cells (CSCs). We have found that human...



Distinct roles of N- and O-glycans in cellulase activity and stability [Biochemistry]

2017-12-11T11:51:18-08:00

In nature, many microbes secrete mixtures of glycoside hydrolases, oxidoreductases, and accessory enzymes to deconstruct polysaccharides and lignin in plants. These enzymes are often decorated with N- and O-glycosylation, the roles of which have been broadly attributed to protection from proteolysis, as the extracellular milieu is an aggressive environment. Glycosylation...



Global biogeochemical cycle of vanadium [Earth, Atmospheric, and Planetary Sciences]

2017-12-11T11:51:19-08:00

Synthesizing published data, we provide a quantitative summary of the global biogeochemical cycle of vanadium (V), including both human-derived and natural fluxes. Through mining of V ores (130 × 109 g V/y) and extraction and combustion of fossil fuels (600 × 109 g V/y), humans are the predominant force in...



Effect of oil palm sustainability certification on deforestation and fire in Indonesia [Environmental Sciences]

2017-12-11T11:51:19-08:00

Many major corporations and countries have made commitments to purchase or produce only “sustainable” palm oil, a commodity responsible for substantial tropical forest loss. Sustainability certification is the tool most used to fulfill these procurement policies, and around 20% of global palm oil production was certified by the Roundtable on...



Zooplankton can actively adjust their motility to turbulent flow [Ecology]

2017-12-11T11:51:19-08:00

Calanoid copepods are among the most abundant metazoans in the ocean and constitute a vital trophic link within marine food webs. They possess relatively narrow swimming capabilities, yet are capable of significant self-locomotion under strong hydrodynamic conditions. Here we provide evidence for an active adaptation that allows these small organisms...



Ultrafast rotation in an amphidynamic crystalline metal organic framework [Chemistry]

2017-12-11T11:51:19-08:00

Amphidynamic crystals are an emergent class of condensed phase matter designed with a combination of lattice-forming elements linked to components that display engineered dynamics in the solid state. Here, we address the design of a crystalline array of molecular rotors with inertial diffusional rotation at the nanoscale, characterized by the...



Autocatalytic surface reduction and its role in controlling seed-mediated growth of colloidal metal nanocrystals [Chemistry]

2017-12-11T11:51:19-08:00

The growth of colloidal metal nanocrystals typically involves an autocatalytic process, in which the salt precursor adsorbs onto the surface of a growing nanocrystal, followed by chemical reduction to atoms for their incorporation into the nanocrystal. Despite its universal role in the synthesis of colloidal nanocrystals, it is still poorly...