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Preview: PNAS - RSS feed of Early Edition articles

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



 



Timescales and the management of ecological systems [Sustainability Science]

2016-10-11T09:44:18-07:00

Human management of ecological systems, including issues like fisheries, invasive species, and restoration, as well as others, often must be undertaken with limited information. This means that developing general principles and heuristic approaches is important. Here, I focus on one aspect, the importance of an explicit consideration of time, which...



Impact of El Nino Southern Oscillation on infectious disease hospitalization risk in the United States [Environmental Sciences]

2016-10-24T11:56:43-07:00

Although the global climate is changing at an unprecedented rate, links between weather and infectious disease have received little attention in high income countries. The “El Niño Southern Oscillation” (ENSO) occurs irregularly and is associated with changing temperature and precipitation patterns. We studied the impact of ENSO on infectious diseases...



Quantifying and sustaining biodiversity in tropical agricultural landscapes [Sustainability Science]

2016-10-24T11:56:40-07:00

Decision-makers increasingly seek scientific guidance on investing in nature, but biodiversity remains difficult to estimate across diverse landscapes. Here, we develop empirically based models for quantifying biodiversity across space. We focus on agricultural lands in the tropical forest biome, wherein lies the greatest potential to conserve or lose biodiversity. We...



Climatic and evolutionary drivers of phase shifts in the plague epidemics of colonial India [Population Biology]

2016-10-24T11:56:35-07:00

Immune heterogeneity in wild host populations indicates that disease-mediated selection is common in nature. However, the underlying dynamic feedbacks involving the ecology of disease transmission, evolutionary processes, and their interaction with environmental drivers have proven challenging to characterize. Plague presents an optimal system for interrogating such couplings: Yersinia pestis transmission...



Interactions of social, terrestrial, and marine sub-systems in the Galapagos Islands, Ecuador [Sustainability Science]

2016-10-10T12:06:10-07:00

Galapagos is often cited as an example of the conflicts that are emerging between resource conservation and economic development in island ecosystems, as the pressures associated with tourism threaten nature, including the iconic and emblematic species, unique terrestrial landscapes, and special marine environments. In this paper, two projects are described...



Examples of coupled human and environmental systems from the extractive industry and hydropower sector interfaces [Sustainability Science]

2016-10-24T11:56:43-07:00

Large-scale corporate projects, particularly those in extractive industries or hydropower development, have a history from early in the twentieth century of creating negative environmental, social, and health impacts on communities proximal to their operations. In many instances, especially for hydropower projects, the forced resettlement of entire communities was a feature...



Whales, science, and scientific whaling in the International Court of Justice [Environmental Sciences]

2016-10-31T11:58:09-07:00

I provide a brief review of the origins of the International Convention on the Regulation of Whaling and the failure to successfully regulate whaling that led to the commercial moratorium in 1986. I then describe the Japanese Whale Research Programs Under Special Permit in the Antarctica (JARPA I, JARPA II)...



Early warning signals of regime shifts in coupled human-environment systems [Ecology]

2016-11-04T12:33:47-07:00

In complex systems, a critical transition is a shift in a system’s dynamical regime from its current state to a strongly contrasting state as external conditions move beyond a tipping point. These transitions are often preceded by characteristic early warning signals such as increased system variability. However, early warning signals...



Coordination vs. voluntarism and enforcement in sustaining international environmental cooperation [Sustainability Science]

2016-11-07T12:56:23-08:00

The fates of “transboundary” environmental systems depend on how nation states interact with one another. In the absence of a hegemon willing and able to coerce other states into avoiding a “tragedy of the commons,” shared environments will be safeguarded if international cooperation succeeds and degraded or even destroyed if...



Mg2+ regulates transcription of mgtA in Salmonella Typhimurium via translation of proline codons during synthesis of the MgtL peptide [Microbiology]

2016-11-14T12:05:49-08:00

In Salmonella enterica serovar Typhimurium, Mg2+ limitation induces transcription of the mgtA Mg2+ transport gene, but the mechanism involved is unclear. The 5′ leader of the mgtA mRNA contains a 17-codon, proline-rich ORF, mgtL, whose translation regulates the transcription of mgtA [Park S-Y et al. (2010) Cell 142:737–748]. Rapid translation...



Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system [Microbiology]

2016-11-14T12:05:51-08:00

CRISPR-Cas are prokaryotic adaptive immune systems that provide protection against bacteriophage (phage) and other parasites. Little is known about how CRISPR-Cas systems are regulated, preventing prediction of phage dynamics in nature and manipulation of phage resistance in clinical settings. Here, we show that the bacterium Pseudomonas aeruginosa PA14 uses the...



Nitrosomonas europaea cytochrome P460 is a direct link between nitrification and nitrous oxide emission [Biochemistry]

2016-11-16T13:38:09-08:00

Ammonia oxidizing bacteria (AOB) are major contributors to the emission of nitrous oxide (N2O). It has been proposed that N2O is produced by reduction of NO. Here, we report that the enzyme cytochrome (cyt) P460 from the AOB Nitrosomonas europaea converts hydroxylamine (NH2OH) quantitatively to N2O under anaerobic conditions. Previous...



Normal chromosome conformation depends on subtelomeric facultative heterochromatin in Neurospora crassa [Genetics]

2016-11-16T13:38:09-08:00

High-throughput chromosome conformation capture (Hi-C) analyses revealed that the 3D structure of the Neurospora crassa genome is dominated by intra- and interchromosomal links between regions of heterochromatin, especially constitutive heterochromatin. Elimination of trimethylation of lysine 9 on histone H3 (H3K9me3) or its binding partner Heterochromatin Protein 1 (HP1)—both prominent features...



Estimating enhanced prevaccination measles transmission hotspots in the context of cross-scale dynamics [Ecology]

2016-11-21T11:48:55-08:00

A key question in clarifying human–environment interactions is how dynamic complexity develops across integrative scales from molecular to population and global levels. Apart from its public health importance, measles is an excellent test bed for such an analysis. Simple mechanistic models have successfully illuminated measles dynamics at the city and...



A high-throughput small molecule screen identifies synergism between DNA methylation and Aurora kinase pathways for X reactivation [Genetics]

2016-11-23T13:23:57-08:00

X-chromosome inactivation is a mechanism of dosage compensation in which one of the two X chromosomes in female mammals is transcriptionally silenced. Once established, silencing of the inactive X (Xi) is robust and difficult to reverse pharmacologically. However, the Xi is a reservoir of >1,000 functional genes that could be...



Model for the architecture of caveolae based on a flexible, net-like assembly of Cavin1 and Caveolin discs [Cell Biology]

2016-11-10T14:59:28-08:00

Caveolae are invaginated plasma membrane domains involved in mechanosensing, signaling, endocytosis, and membrane homeostasis. Oligomers of membrane-embedded caveolins and peripherally attached cavins form the caveolar coat whose structure has remained elusive. Here, purified Cavin1 60S complexes were analyzed structurally in solution and after liposome reconstitution by electron cryotomography. Cavin1 adopted...



Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends [Medical Sciences]

2016-10-31T11:58:06-07:00

Plasma DNA obtained from a pregnant woman was sequenced to a depth of 270× haploid genome coverage. Comparing the maternal plasma DNA sequencing data with the parental genomic DNA data and using a series of bioinformatics filters, fetal de novo mutations were detected at a sensitivity of 85% and a...



RNA modification enzyme TruB is a tRNA chaperone [Biochemistry]

2016-11-14T12:05:55-08:00

Cellular RNAs are chemically modified by many RNA modification enzymes; however, often the functions of modifications remain unclear, such as for pseudouridine formation in the tRNA TΨC arm by the bacterial tRNA pseudouridine synthase TruB. Here we test the hypothesis that RNA modification enzymes also act as RNA chaperones. Using...



Unfolding large-scale online collaborative human dynamics [Applied Physical Sciences]

2016-12-01T12:26:55-08:00

Large-scale interacting human activities underlie all social and economic phenomena, but quantitative understanding of regular patterns and mechanism is very challenging and still rare. Self-organized online collaborative activities with a precise record of event timing provide unprecedented opportunity. Our empirical analysis of the history of millions of updates in Wikipedia...



Phosphatidylinositol 3-kinase inhibition restores Ca2+ release defects and prolongs survival in myotubularin-deficient mice [Physiology]

2016-11-28T12:01:58-08:00

Mutations in the gene encoding the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for a pediatric disease of skeletal muscle named myotubular myopathy (XLMTM). Muscle fibers from MTM1-deficient mice present defects in excitation–contraction (EC) coupling likely responsible for the disease-associated fatal muscle weakness. However, the mechanism leading to EC coupling failure...



Selective lesion of the hippocampus increases the differentiation of immature neurons in the monkey amygdala [Neuroscience]

2016-11-28T12:02:00-08:00

A large population of immature neurons is present in the ventromedial portion of the adult primate amygdala, a region that receives substantial direct projections from the hippocampal formation. Here, we show the effects of neonatal (n = 8) and adult (n = 6) hippocampal lesions on the populations of mature...



Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium [Biochemistry]

2016-12-01T12:26:55-08:00

The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using 13C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway...



The right incentives enable ocean sustainability successes and provide hope for the future [Sustainability Science]

2016-12-02T11:58:27-08:00

Healthy ocean ecosystems are needed to sustain people and livelihoods and to achieve the United Nations Sustainable Development Goals. Using the ocean sustainably requires overcoming many formidable challenges: overfishing, climate change, ocean acidification, and pollution. Despite gloomy forecasts, there is reason for hope. New tools, practices, and partnerships are beginning...



Stability, folding dynamics, and long-range conformational transition of the synaptic t-SNARE complex [Biophysics and Computational Biology]

2016-11-28T12:02:06-08:00

Synaptic soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) couple their stepwise folding to fusion of synaptic vesicles with plasma membranes. In this process, three SNAREs assemble into a stable four-helix bundle. Arguably, the first and rate-limiting step of SNARE assembly is the formation of an activated binary target (t)-SNARE complex...



C-terminal domain (CTD) phosphatase links Rho GTPase signaling to Pol II CTD phosphorylation in Arabidopsis and yeast [Plant Biology]

2016-11-28T12:02:04-08:00

Rho GTPases, including the Rho, Cdc42, Rac, and ROP subfamilies, act as pivotal signaling switches in various growth and developmental processes. Compared with the well-defined role of cytoskeletal organization in Rho signaling, much less is known regarding transcriptional regulation. In a mutant screen for phenotypic enhancers of transgenic Arabidopsis plants...



Accurate and scalable social recommendation using mixed-membership stochastic block models [Applied Physical Sciences]

2016-11-23T13:24:00-08:00

With increasing amounts of information available, modeling and predicting user preferences—for books or articles, for example—are becoming more important. We present a collaborative filtering model, with an associated scalable algorithm, that makes accurate predictions of users’ ratings. Like previous approaches, we assume that there are groups of users and of...



Optically transparent semiconducting polymer nanonetwork for flexible and transparent electronics [Engineering]

2016-11-22T08:47:30-08:00

Simultaneously achieving high optical transparency and excellent charge mobility in semiconducting polymers has presented a challenge for the application of these materials in future “flexible” and “transparent” electronics (FTEs). Here, by blending only a small amount (∼15 wt %) of a diketopyrrolopyrrole-based semiconducting polymer (DPP2T) into an inert polystyrene (PS)...



How constraints affect the hunter’s decision to shoot a deer [Sustainability Science]

2016-11-28T12:01:52-08:00

Hunting is the predominant way of controlling many wildlife populations devoid of large carnivores. It subjects animals to mortality rates that far exceed natural rates and that differ markedly in which age, sex, or size classes are removed relative to those of natural predators. To explain the emerging selection pattern...



Evaluating early-warning indicators of critical transitions in natural aquatic ecosystems [Ecology]

2016-11-22T08:47:28-08:00

Ecosystems can show sudden and persistent changes in state despite only incremental changes in drivers. Such critical transitions are difficult to predict, because the state of the system often shows little change before the transition. Early-warning indicators (EWIs) are hypothesized to signal the loss of system resilience and have been...



Siderophore-based microbial adaptations to iron scarcity across the eastern Pacific Ocean [Environmental Sciences]

2016-12-01T12:26:54-08:00

Nearly all iron dissolved in the ocean is complexed by strong organic ligands of unknown composition. The effect of ligand composition on microbial iron acquisition is poorly understood, but amendment experiments using model ligands show they can facilitate or impede iron uptake depending on their identity. Here we show that...



Enhanced stochastic fluctuations to measure steep adhesive energy landscapes [Applied Physical Sciences]

2016-11-23T13:23:59-08:00

Free-energy landscapes govern the behavior of all interactions in the presence of thermal fluctuations in the fields of physical chemistry, materials sciences, and the biological sciences. From the energy landscape, critical information about an interaction, such as the reaction kinetic rates, bond lifetimes, and the presence of intermediate states, can...



Retinoic acid signaling determines the fate of uterine stroma in the mouse Mullerian duct [Developmental Biology]

2016-11-22T08:47:31-08:00

The Müllerian duct develops into the oviduct, uterus, and vagina, all of which are quite distinct in their morphology and function. The epithelial fate of these female reproductive organs in developing mice is determined by factors secreted from the stroma; however, how stromal differentiation occurs in the female reproductive organs...



Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia [Genetics]

2016-11-28T12:02:06-08:00

Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P. vivax cases has actually increased. To understand better the factors underlying this resilience, we compared...



Structure and mechanism of NOV1, a resveratrol-cleaving dioxygenase [Biochemistry]

2016-11-30T12:32:31-08:00

Stilbenes are diphenyl ethene compounds produced naturally in a wide variety of plant species and some bacteria. Stilbenes are also derived from lignin during kraft pulping. Stilbene cleavage oxygenases (SCOs) cleave the central double bond of stilbenes, forming two phenolic aldehydes. Here, we report the structure of an SCO. The...



EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation [Developmental Biology]

2016-11-28T12:02:03-08:00

Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis....



Deglacial temperature history of West Antarctica [Earth, Atmospheric, and Planetary Sciences]

2016-11-28T12:01:52-08:00

The most recent glacial to interglacial transition constitutes a remarkable natural experiment for learning how Earth’s climate responds to various forcings, including a rise in atmospheric CO2. This transition has left a direct thermal remnant in the polar ice sheets, where the exceptional purity and continual accumulation of ice permit...



{beta}-Arrestin mediates the Frank-Starling mechanism of cardiac contractility [Physiology]

2016-11-28T12:01:57-08:00

The Frank–Starling law of the heart is a physiological phenomenon that describes an intrinsic property of heart muscle in which increased cardiac filling leads to enhanced cardiac contractility. Identified more than a century ago, the Frank–Starling relationship is currently known to involve length-dependent enhancement of cardiac myofilament Ca2+ sensitivity. However,...



Carrier dynamics and the role of surface defects: Designing a photocatalyst for gas-phase CO2 reduction [Chemistry]

2016-11-28T12:01:58-08:00

In2O3-x(OH)y nanoparticles have been shown to function as an effective gas-phase photocatalyst for the reduction of CO2 to CO via the reverse water–gas shift reaction. Their photocatalytic activity is strongly correlated to the number of oxygen vacancy and hydroxide defects present in the system. To better understand how such defects...



Geometry induced sequence of nanoscale Frank-Kasper and quasicrystal mesophases in giant surfactants [Applied Physical Sciences]

2016-11-28T12:02:01-08:00

Frank–Kasper (F-K) and quasicrystal phases were originally identified in metal alloys and only sporadically reported in soft materials. These unconventional sphere-packing schemes open up possibilities to design materials with different properties. The challenge in soft materials is how to correlate complex phases built from spheres with the tunable parameters of...



Data-driven parameterization of the generalized Langevin equation [Applied Mathematics]

2016-11-29T07:49:52-08:00

We present a data-driven approach to determine the memory kernel and random noise in generalized Langevin equations. To facilitate practical implementations, we parameterize the kernel function in the Laplace domain by a rational function, with coefficients directly linked to the equilibrium statistics of the coarse-grain variables. We show that such...



Near-atomic structural model for bacterial DNA replication initiation complex and its functional insights [Biochemistry]

2016-11-29T07:49:50-08:00

Upon DNA replication initiation in Escherichia coli, the initiator protein DnaA forms higher-order complexes with the chromosomal origin oriC and a DNA-bending protein IHF. Although tertiary structures of DnaA and IHF have previously been elucidated, dynamic structures of oriC–DnaA–IHF complexes remain unknown. Here, combining computer simulations with biochemical assays, we...



Design principles for nonequilibrium self-assembly [Chemistry]

2016-11-22T08:47:30-08:00

We consider an important class of self-assembly problems, and using the formalism of stochastic thermodynamics, we derive a set of design principles for growing controlled assemblies far from equilibrium. The design principles constrain the set of configurations that can be obtained under nonequilibrium conditions. Our central result provides intuition for...



Psychopathic individuals exhibit but do not avoid regret during counterfactual decision making [Psychological and Cognitive Sciences]

2016-11-28T12:01:50-08:00

Psychopathy is associated with persistent antisocial behavior and a striking lack of regret for the consequences of that behavior. Although explanatory models for psychopathy have largely focused on deficits in affective responsiveness, recent work indicates that aberrant value-based decision making may also play a role. On that basis, some have...



A functional role for intrinsic disorder in the tau-tubulin complex [Biophysics and Computational Biology]

2016-11-23T13:23:58-08:00

Tau is an intrinsically disordered protein with an important role in maintaining the dynamic instability of neuronal microtubules. Despite intensive study, a detailed understanding of the functional mechanism of tau is lacking. Here, we address this deficiency by using intramolecular single-molecule Förster Resonance Energy Transfer (smFRET) to characterize the conformational...



Heterogeneous yet stable V{delta}2(+) T-cell profiles define distinct cytotoxic effector potentials in healthy human individuals [Immunology and Inflammation]

2016-11-28T12:01:54-08:00

Human γδ T cells display potent responses to pathogens and malignancies. Of particular interest are those expressing a γδ T-cell receptor (TCR) incorporating TCRδ-chain variable-region-2 [Vδ2(+)], which are activated by pathogen-derived phosphoantigens (pAgs), or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Once activated, Vδ2(+)...



Activation of mutant TERT promoter by RAS-ERK signaling is a key step in malignant progression of BRAF-mutant human melanomas [Medical Sciences]

2016-11-23T13:23:57-08:00

Although activating BRAF/NRAS mutations are frequently seen in melanomas, they are not sufficient to drive malignant transformation and require additional events. Frequent co-occurrence of mutations in the promoter for telomerase reverse transcriptase (TERT), along with BRAF alterations, has recently been noted and correlated with poorer prognosis, implicating a functional link...



KLB is associated with alcohol drinking, and its gene product {beta}-Klotho is necessary for FGF21 regulation of alcohol preference [Genetics]

2016-11-28T12:01:53-08:00

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as...



Egr2 and Egr3 in regulatory T cells cooperatively control systemic autoimmunity through Ltbp3-mediated TGF-{beta}3 production [Immunology and Inflammation]

2016-11-30T12:32:30-08:00

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4+ regulatory T cells, CD4+CD25−LAG3+ cells,...



Meeting the Sustainable Development Goals leads to lower world population growth [Sustainability Science]

2016-11-29T07:49:51-08:00

Here we show the extent to which the expected world population growth could be lowered by successfully implementing the recently agreed-upon Sustainable Development Goals (SDGs). The SDGs include specific quantitative targets on mortality, reproductive health, and education for all girls by 2030, measures that will directly and indirectly affect future...



Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics [Neuroscience]

2016-11-28T12:01:57-08:00

Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (μ-ILEDs) with wireless control and...



Mechanism of the intrinsic arginine finger in heterotrimeric G proteins [Biophysics and Computational Biology]

2016-11-28T12:02:03-08:00

Heterotrimeric G proteins are crucial molecular switches that maintain a large number of physiological processes in cells. The signal is encoded into surface alterations of the Gα subunit that carries GTP in its active state and GDP in its inactive state. The ability of the Gα subunit to hydrolyze GTP...



An {alpha}/{beta}-hydrolase fold protein in the biosynthesis of thiostrepton exhibits a dual activity for endopeptidyl hydrolysis and epoxide ring opening/macrocyclization [Biochemistry]

2016-11-23T13:23:56-08:00

Thiostrepton (TSR), an archetypal bimacrocyclic thiopeptide antibiotic that arises from complex posttranslational modifications of a genetically encoded precursor peptide, possesses a quinaldic acid (QA) moiety within the side-ring system of a thiopeptide-characteristic framework. Focusing on selective engineering of the QA moiety, i.e., by fluorination or methylation, we have recently designed...



Aerosol indirect effect from turbulence-induced broadening of cloud-droplet size distributions [Earth, Atmospheric, and Planetary Sciences]

2016-11-28T12:01:50-08:00

The influence of aerosol concentration on the cloud-droplet size distribution is investigated in a laboratory chamber that enables turbulent cloud formation through moist convection. The experiments allow steady-state microphysics to be achieved, with aerosol input balanced by cloud-droplet growth and fallout. As aerosol concentration is increased, the cloud-droplet mean diameter...



Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation [Immunology and Inflammation]

2016-11-22T08:47:29-08:00

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type...



Functional split brain in a driving/listening paradigm [Psychological and Cognitive Sciences]

2016-11-28T12:01:51-08:00

We often engage in two concurrent but unrelated activities, such as driving on a quiet road while listening to the radio. When we do so, does our brain split into functionally distinct entities? To address this question, we imaged brain activity with fMRI in experienced drivers engaged in a driving...



Permissive roles of cytokines interleukin-7 and Flt3 ligand in mouse B-cell lineage commitment [Immunology and Inflammation]

2016-11-29T07:49:50-08:00

Hematopoietic cells are continuously generated throughout life from hematopoietic stem cells, thus making hematopoiesis a favorable system to study developmental cell lineage commitment. The main factors incorporating environmental signals to developing hematopoietic cells are cytokines, which regulate commitment of hematopoietic progenitors to the different blood lineages by acting either in...



Enhanced limonene production in cyanobacteria reveals photosynthesis limitations [Chemistry]

2016-11-23T13:23:56-08:00

Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained...



Exploration of joint redundancy but not task space variability facilitates supervised motor learning [Neuroscience]

2016-11-29T07:49:51-08:00

The number of joints and muscles in a human arm is more than what is required for reaching to a desired point in 3D space. Although previous studies have emphasized how such redundancy and the associated flexibility may play an important role in path planning, control of noise, and optimization...



Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis [Systems Biology]

2016-12-01T12:26:55-08:00

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets...



In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease [Biochemistry]

2016-11-29T07:49:50-08:00

Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex interplay...



The structure of the catechin-binding site of human sulfotransferase 1A1 [Biochemistry]

2016-11-23T13:23:57-08:00

We are just beginning to understand the allosteric regulation of the human cytosolic sulfotransferase (SULTs) family—13 disease-relevant enzymes that regulate the activities of hundreds, if not thousands, of signaling small molecules. SULT1A1, the predominant isoform in adult liver, harbors two noninteracting allosteric sites, each of which binds a different molecular...



Spatiotemporal imaging of small GTPases activity in live cells [Cell Biology]

2016-11-29T07:49:49-08:00

Ras-like small GTPases function as molecular switches and regulate diverse cellular events. To examine the dynamics of signaling requires spatiotemporal visualization of their activity in the cell. Current small GTPase sensors rely on specific effector domains that are available for only a small number of GTPases and compete for endogenous...



Distinct cortical and striatal actions of a {beta}-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties [Neuroscience]

2016-12-01T12:26:54-08:00

The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R...



Nicotinic receptors in mouse prefrontal cortex modulate ultraslow fluctuations related to conscious processing [Neuroscience]

2016-12-02T11:58:27-08:00

The prefrontal cortex (PFC) plays an important role in cognitive processes, including access to consciousness. The PFC receives significant cholinergic innervation and nicotinic acetylcholine receptors (nAChRs) contribute greatly to the effects of acetylcholine signaling. Using in vivo two-photon imaging of both awake and anesthetized mice, we recorded spontaneous, ongoing neuronal...



Rapid emergence and mechanisms of resistance by U87 glioblastoma cells to doxorubicin in an in vitro tumor microfluidic ecology [Ecology]

2016-11-22T08:47:29-08:00

In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients...



TNF{alpha}-stimulated gene-6 (TSG6) activates macrophage phenotype transition to prevent inflammatory lung inȷury [Medical Sciences]

2016-11-28T12:01:59-08:00

TNFα-stimulated gene-6 (TSG6), a 30-kDa protein generated by activated macrophages, modulates inflammation; however, its mechanism of action and role in the activation of macrophages are not fully understood. Here we observed markedly augmented LPS-induced inflammatory lung injury and mortality in TSG6−/− mice compared with WT (TSG6+/+) mice. Treatment of mice...



Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation [Developmental Biology]

2016-11-28T12:01:57-08:00

Blastocyst implantation is a complex process requiring coordination of a dynamic sequence of embryo–uterine interactions. Blood vessels enter the uterus from the mesometrium, demarcating the uterus into mesometrial (M) and antimesometrial (AM) domains. Implantation occurs along the uterine longitudinal axis within specialized implantation chambers (crypts) that originate within the evaginations...



Programmable and reversible plasmon mode engineering [Applied Physical Sciences]

2016-11-28T12:02:04-08:00

Plasmonic nanostructures with enhanced localized optical fields as well as narrow linewidths have driven advances in numerous applications. However, the active engineering of ultranarrow resonances across the visible regime—and within a single system—has not yet been demonstrated. This paper describes how aluminum nanoparticle arrays embedded in an elastomeric slab may...



MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1-IRF3 signaling axis [Immunology and Inflammation]

2016-11-22T08:47:28-08:00

The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of...



MyTH4-FERM myosins have an ancient and conserved role in filopod formation [Cell Biology]

2016-11-23T13:24:00-08:00

The formation of filopodia in Metazoa and Amoebozoa requires the activity of myosin 10 (Myo10) in mammalian cells and of Dictyostelium unconventional myosin 7 (DdMyo7) in the social amoeba Dictyostelium. However, the exact roles of these MyTH4-FERM myosins (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in the initiation...



Continuous flow synthesis of ZSM-5 zeolite on the order of seconds [Engineering]

2016-11-28T12:02:05-08:00

The hydrothermal synthesis of zeolites carried out in batch reactors takes a time so long (typically, on the order of days) that the crystallization of zeolites has long been believed to be very slow in nature. We herein present a synthetic process for ZSM-5, an industrially important zeolite, on the...



High thermoelectricpower factor in graphene/hBN devices [Physics]

2016-11-23T13:24:00-08:00

Fast and controllable cooling at nanoscales requires a combination of highly efficient passive cooling and active cooling. Although passive cooling in graphene-based devices is quite effective due to graphene’s extraordinary heat conduction, active cooling has not been considered feasible due to graphene’s low thermoelectric power factor. Here, we show that...



Elucidating the druggable interface of protein-protein interactions using fragment docking and coevolutionary analysis [Biophysics and Computational Biology]

2016-11-29T07:49:49-08:00

Protein−protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for...



Structural insights into the LCIB protein family reveals a new group of {beta}-carbonic anhydrases [Biochemistry]

2016-12-01T12:26:54-08:00

Aquatic microalgae have evolved diverse CO2-concentrating mechanisms (CCMs) to saturate the carboxylase with its substrate, to compensate for the slow kinetics and competing oxygenation reaction of the key photosynthetic CO2-fixing enzyme rubisco. The limiting CO2-inducible B protein (LCIB) is known to be essential for CCM function in Chlamydomonas reinhardtii. To...



Tau prions from Alzheimer’s disease and chronic traumatic encephalopathy patients propagate in cultured cells [Neuroscience]

2016-11-28T12:01:53-08:00

Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer’s disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick’s disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from...



Evaluating the evaluation of cancer driver genes [Statistics]

2016-11-22T12:53:50-08:00

Sequencing has identified millions of somatic mutations in human cancers, but distinguishing cancer driver genes remains a major challenge. Numerous methods have been developed to identify driver genes, but evaluation of the performance of these methods is hindered by the lack of a gold standard, that is, bona fide driver...



Supramolecular PEGylation of biopharmaceuticals [Applied Physical Sciences]

2016-11-28T12:02:02-08:00

The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body....



Framework for making better predictions by directly estimating variables’ predictivity [Biophysics and Computational Biology]

2016-11-29T07:49:51-08:00

We propose approaching prediction from a framework grounded in the theoretical correct prediction rate of a variable set as a parameter of interest. This framework allows us to define a measure of predictivity that enables assessing variable sets for, preferably high, predictivity. We first define the prediction rate for a...



Noninvasive prenatal testing to analyze the fetal genome [Commentaries]

2016-11-30T12:32:30-08:00

Prenatal genetic testing has changed markedly since the original introduction of amniocentesis as a means to evaluate the fetal karyotype. Because it has long been recognized that maternal age is highly associated with risk for Down syndrome, maternal age became the first screening test for aneuploidy. Later development of screening...



Two crystal structures reveal design for repurposing the C-Ala domain of human AlaRS [Biochemistry]

2016-11-28T12:02:04-08:00

The 20 aminoacyl tRNA synthetases (aaRSs) couple each amino acid to their cognate tRNAs. During evolution, 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms. AlaRS is the single exception, with an...



Two for the price of one: RNA modification enzymes as chaperones [Commentaries]

2016-11-30T12:32:30-08:00

Although folding of nascent proteins often requires assistance from molecular chaperones, the extent to which newly made RNAs need other macromolecules to help them reach their native states is less studied. One class of proteins and ribonucleoproteins (RNPs) that is proposed to assist RNA folding consists of the enzymes that...



Antagonists of growth hormone-releasing hormone receptor induce apoptosis specifically in retinoblastoma cells [Medical Sciences]

2016-11-23T13:23:58-08:00

Retinoblastoma (RB) is the most common intraocular cancer in children worldwide. Current treatments mainly involve combinations of chemotherapies, cryotherapies, and laser-based therapies. Severe or late-stage disease may require enucleation or lead to fatality. Recently, RB has been shown to arise from cone precursor cells, which have high MDM2 levels to...



Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice [Immunology and Inflammation]

2016-11-23T13:23:59-08:00

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine....



Multistep regulation of autophagy by WNK1 [Cell Biology]

2016-11-28T12:01:56-08:00

The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inhibits autophagy, an intracellular...



High-performance multiplexed fluorescence in situ hybridization in culture and tissue with matrix imprinting and clearing [Systems Biology]

2016-11-22T08:47:30-08:00

Highly multiplexed single-molecule FISH has emerged as a promising approach to spatially resolved single-cell transcriptomics because of its ability to directly image and profile numerous RNA species in their native cellular context. However, background—from off-target binding of FISH probes and cellular autofluorescence—can become limiting in a number of important applications,...



Map reading, navigating from maps, and the medial temporal lobe [Neuroscience]

2016-11-28T12:01:54-08:00

We administered map-reading tasks in which participants navigated an array of marks on the floor by following paths on hand-held maps that made up to nine turns. The burden on memory was minimal because the map was always available. Nevertheless, because the map was held in a fixed position in...



Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes [Microbiology]

2016-12-01T12:26:53-08:00

The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We...



Correction for Che et al., Elevated vitamin E content improves all-trans {beta}-carotene accumulation and stability in biofortified sorghum [Corrections]

2016-11-28T12:01:51-08:00

PLANT BIOLOGY Correction for “Elevated vitamin E content improves all-trans β-carotene accumulation and stability in biofortified sorghum,” by Ping Che, Zuo-Yu Zhao, Kimberly Glassman, David Dolde, Tiger X. Hu, Todd J. Jones, Silas Obukosia, Florence Wambugu, and Marc C. Albertsen, which appeared in issue 39, September 27, 2016, of Proc...



Unraveling the architecture of caveolae [Commentaries]

2016-11-28T12:02:02-08:00

The eukaryotic cell surface is composed of many distinct membrane domains that are formed by the cooperative interactions of different proteins and lipids. These domains are important for membrane trafficking and cell signaling and are modulated in turn by changes in the cell environment. Caveolae (“little caves”) are ∼60-nm membrane...



DNA methylome of the 20-gigabase Norway spruce genome [Genetics]

2016-11-28T12:02:01-08:00

DNA methylation plays important roles in many biological processes, such as silencing of transposable elements, imprinting, and regulating gene expression. Many studies of DNA methylation have shown its essential roles in angiosperms (flowering plants). However, few studies have examined the roles and patterns of DNA methylation in gymnosperms. Here, we...



Zika virus cell tropism in the developing human brain and inhibition by azithromycin [Microbiology]

2016-11-29T07:49:51-08:00

The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the...



Global analysis of genomic instability caused by DNA replication stress in Saccharomyces cerevisiae [Genetics]

2016-11-28T12:01:55-08:00

DNA replication stress (DRS)-induced genomic instability is an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability, we measured the rates of genomic alterations throughout the genome in a yeast strain with lowered expression of the replicative DNA polymerase δ. By a genetic test, we showed...



Scalable manufacturing of biomimetic moldable hydrogels for industrial applications [Engineering]

2016-11-28T12:01:56-08:00

Hydrogels are a class of soft material that is exploited in many, often completely disparate, industrial applications, on account of their unique and tunable properties. Advances in soft material design are yielding next-generation moldable hydrogels that address engineering criteria in several industrial settings such as complex viscosity modifiers, hydraulic or...



Correction for Lanotte et al., Red cells’ dynamic morphologies govern blood shear thinning under microcirculatory flow conditions [Corrections]

2016-11-28T12:01:54-08:00

APPLIED PHYSICAL SCIENCES, BIOPHYSICS AND COMPUTATIONAL BIOLOGY Correction for “Red cells’ dynamic morphologies govern blood shear thinning under microcirculatory flow conditions,” by Luca Lanotte, Johannes Mauer, Simon Mendez, Dmitry A. Fedosov, Jean-Marc Fromental, Viviana Claveria, Franck Nicoud, Gerhard Gompper, and Manouk Abkarian, which appeared in issue 47, November 22, 2016,...



Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4 [Immunology and Inflammation]

2016-12-08T12:34:17-08:00

Aquaporin-4 (AQP4)-specific T cells are expanded in neuromyelitis optica (NMO) patients and exhibit Th17 polarization. However, their pathogenic role in CNS autoimmune inflammatory disease is unclear. Although multiple AQP4 T-cell epitopes have been identified in WT C57BL/6 mice, we observed that neither immunization with those determinants nor transfer of donor...



Hierarchical CRMP2 posttranslational modifications control NaV1.7 function [Neuroscience]

2016-12-08T12:34:17-08:00

Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding...



Probing conformational dynamics of an enzymatic active site by an in situ single fluorogenic probe under piconewton force manipulation [Chemistry]

2016-12-08T12:34:18-08:00

Unraveling the conformational details of an enzyme during the essential steps of a catalytic reaction (i.e., enzyme–substrate interaction, enzyme–substrate active complex formation, nascent product formation, and product release) is challenging due to the transient nature of intermediate conformational states, conformational fluctuations, and the associated complex dynamics. Here we report our...



Computational design of a homotrimeric metalloprotein with a trisbipyridyl core [Biophysics and Computational Biology]

2016-12-08T12:34:18-08:00

Metal-chelating heteroaryl small molecules have found widespread use as building blocks for coordination-driven, self-assembling nanostructures. The metal-chelating noncanonical amino acid (2,2′-bipyridin-5yl)alanine (Bpy-ala) could, in principle, be used to nucleate specific metalloprotein assemblies if introduced into proteins such that one assembly had much lower free energy than all alternatives. Here we...



Evolution of a mass spectrometry-grade protease with PTM-directed specificity [Chemistry]

2016-12-08T12:34:19-08:00

Mapping posttranslational modifications (PTMs), which diversely modulate biological functions, represents a significant analytical challenge. The centerpiece technology for PTM site identification, mass spectrometry (MS), requires proteolytic cleavage in the vicinity of a PTM to yield peptides for sequencing. This requirement catalyzed our efforts to evolve MS-grade mutant PTM-directed proteases. Citrulline,...



Emergent structures and dynamics of cell colonies by contact inhibition of locomotion [Biophysics and Computational Biology]

2016-12-05T11:59:53-08:00

Cells in tissues can organize into a broad spectrum of structures according to their function. Drastic changes of organization, such as epithelial–mesenchymal transitions or the formation of spheroidal aggregates, are often associated either to tissue morphogenesis or to cancer progression. Here, we study the organization of cell colonies by means...