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



 



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...



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...



Remote electrochemical modulation of pKa in a rotaxane by co-conformational allostery [Chemistry]

2017-12-18T11:50:17-08:00

Allosteric control, one of Nature’s most effective ways to regulate functions in biomolecular machinery, involves the transfer of information between distant sites. The mechanistic details of such a transfer are still an object of intensive investigation and debate, and the idea that intramolecular communication could be enabled by dynamic processes...



Q&As with Marsha I. Lester [QnAs]

2017-12-26T09:29:38-08:00

Evidence of Earth’s changing environment is abundant, from diminished polar ice caps to increased frequency of catastrophic storms. However, the chemical reactions in our atmosphere that can contribute to a changing climate are less well known. A physical chemist at the University of Pennsylvania who studies the troposphere, Marsha I....



Dynamic force spectroscopy of synthetic oligorotaxane foldamers [Chemistry]

2017-12-26T09:29:39-08:00

Wholly synthetic molecules involving both mechanical bonds and a folded secondary structure are one of the most promising architectures for the design of functional molecular machines with unprecedented properties. Here, we report dynamic single-molecule force spectroscopy experiments that explore the energetic details of donor–acceptor oligorotaxane foldamers, a class of molecular...



Productivity, biodiversity, and pathogens influence the global hunter-gatherer population density [Ecology]

2017-12-27T11:27:27-08:00

The environmental drivers of species distributions and abundances are at the core of ecological research. However, the effects of these drivers on human abundance are not well-known. Here, we report how net primary productivity, biodiversity, and pathogen stress affect human population density using global ethnographic hunter-gatherer data. Our results show...



A mixed modality approach towards Xi reactivation for Rett syndrome and other X-linked disorders [Genetics]

2017-12-27T11:27:29-08:00

The X-chromosome harbors hundreds of disease genes whose associated diseases predominantly affect males. However, a subset, including neurodevelopmental disorders, Rett syndrome (RTT), fragile X syndrome, and CDKL5 syndrome, also affects females. These disorders lack disease-specific treatment. Because female cells carry two X chromosomes, an emerging treatment strategy has been to...



Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration [Neuroscience]

2018-01-02T10:10:51-08:00

Genetic studies of Wallerian degeneration have led to the identification of signaling molecules (e.g., dSarm/Sarm1, Axundead, and Highwire) that function locally in axons to drive degeneration. Here we identify a role for the Drosophila C2H2 zinc finger transcription factor Pebbled [Peb, Ras-responsive element binding protein 1 (RREB1) in mammals] in...



Hamilton's inclusive fitness maintains heritable altruism polymorphism through rb = c [Evolution]

2018-01-02T10:10:52-08:00

How can altruism evolve or be maintained in a selfish world? Hamilton’s rule shows that the former process will occur when rb > c—the benefits to the recipients of an altruistic act b, weighted by the relatedness between the social partners r, exceed the costs to the altruists c—drives altruistic...



Transient visual pathway critical for normal development of primate grasping behavior [Neuroscience]

2018-01-03T13:45:45-08:00

An evolutionary hallmark of anthropoid primates, including humans, is the use of vision to guide precise manual movements. These behaviors are reliant on a specialized visual input to the posterior parietal cortex. Here, we show that normal primate reaching-and-grasping behavior depends critically on a visual pathway through the thalamic pulvinar,...



Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis [Economic Sciences]

2018-01-04T12:34:24-08:00

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given...



Genetics of the human face: Identification of large-effect single gene variants [Genetics]

2018-01-04T12:34:24-08:00

To discover specific variants with relatively large effects on the human face, we have devised an approach to identifying facial features with high heritability. This is based on using twin data to estimate the additive genetic value of each point on a face, as provided by a 3D camera system....



Demography and mating system shape the genome-wide impact of purifying selection in Arabis alpina [Plant Biology]

2018-01-04T12:34:24-08:00

Plant mating systems have profound effects on levels and structuring of genetic variation and can affect the impact of natural selection. Although theory predicts that intermediate outcrossing rates may allow plants to prevent accumulation of deleterious alleles, few studies have empirically tested this prediction using genomic data. Here, we study...



Reply to Entcheva: The impact of T-tubules on action potential propagation in cardiac tissue [Letters (Online Only)]

2018-01-05T17:33:42-08:00

Since our observation that T-tubules can fail to propagate action potentials in diseased hearts (1), our studies have focused on understanding the consequences of these electrical defects for local Ca2+ release (2) and force production (3). More recently, we have started to explore the causes of electrical defects (4), focusing...



Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa [Medical Sciences]

2018-01-05T12:13:26-08:00

Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in...



Contrasting responses of functional diversity to major losses in taxonomic diversity [Ecology]

2018-01-05T12:13:26-08:00

Taxonomic diversity of benthic marine invertebrate shelf species declines at present by nearly an order of magnitude from the tropics to the poles in each hemisphere along the latitudinal diversity gradient (LDG), most steeply along the western Pacific where shallow-sea diversity is at its tropical maximum. In the Bivalvia, a...



Uncovering an electrically heterogeneous cardiomyocyte by FRAP-quantified diffusion in the T-tubules [Letters (Online Only)]

2018-01-05T19:44:20-08:00

A recent elegant study in PNAS by Scardigli et al. (1) provides a subcellular look at the electrical properties within the cardiomyocyte transverse T-tubular system [transverse-axial tubular system (TATS)] by extrapolation from FRAP-based diffusion measurements of fluorescent dextran and geometric considerations. It was shown that the disarray of the T-tubules...



PfCDPK1 is critical for malaria parasite gametogenesis and mosquito infection [Microbiology]

2018-01-08T11:59:20-08:00

Efforts to knock out Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) from asexual erythrocytic stage have not been successful, indicating an indispensable role of the enzyme in asexual growth. We recently reported generation of a transgenic parasite with mutant CDPK1 [Bansal A, et al. (2016) MBio 7:e02011-16]. The mutant CDPK1...



Glycoengineering of antibody (Herceptin) through yeast expression and in vitro enzymatic glycosylation [Biochemistry]

2018-01-08T11:59:20-08:00

Monoclonal antibodies (mAbs) have been developed as therapeutics, especially for the treatment of cancer, inflammation, and infectious diseases. Because the glycosylation of mAbs in the Fc region influences their interaction with effector cells that kill antibody-targeted cells, and the current method of antibody production is relatively expensive, efforts have been...



CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation [Medical Sciences]

2018-01-08T11:59:21-08:00

We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been...



Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism [Medical Sciences]

2018-01-08T11:59:21-08:00

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on...



Unified description of H-atom-induced chemicurrents and inelastic scattering [Chemistry]

2018-01-08T11:59:21-08:00

The Born–Oppenheimer approximation (BOA) provides the foundation for virtually all computational studies of chemical binding and reactivity, and it is the justification for the widely used “balls and springs” picture of molecules. The BOA assumes that nuclei effectively stand still on the timescale of electronic motion, due to their large...



Testing the impact and durability of a group malleability intervention in the context of the Israeli-Palestinian conflict [Psychological and Cognitive Sciences]

2018-01-08T11:59:22-08:00

Fostering perceptions of group malleability (teaching people that groups are capable of change and improvement) has been shown to lead to short-term improvements in intergroup attitudes and willingness to make concessions in intractable conflicts. The present study, a field intervention involving 508 Israelis from three locations in Israel, replicated and...



Correction for Liu et al., Earliest hydraulic enterprise in China, 5,100 years ago [Corrections]

2018-01-08T11:59:22-08:00

ANTHROPOLOGY, ENVIRONMENTAL SCIENCES Correction for “Earliest hydraulic enterprise in China, 5,100 years ago,” by Bin Liu, Ningyuan Wang, Minghui Chen, Xiaohong Wu, Duowen Mo, Jianguo Liu, Shijin Xu, and Yijie Zhuang, which was first published December 4, 2017; 10.1073/pnas.1710516114 (Proc Natl Acad Sci USA 114:13637–13642). The authors note that on...



TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells [Neuroscience]

2018-01-08T11:59:22-08:00

Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. Transient receptor potential melastatin 5 (TRPM5), a sodium-selective TRP channel, functions as a common downstream component in sweet, bitter, and umami signaling pathways. In the absence of TRPM5, mice...



Fenofibrate prevents skeletal muscle loss in mice with lung cancer [Medical Sciences]

2018-01-08T11:59:22-08:00

The cancer anorexia cachexia syndrome is a systemic metabolic disorder characterized by the catabolism of stored nutrients in skeletal muscle and adipose tissue that is particularly prevalent in nonsmall cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments and increased mortality. The aim of the present study...



Pyruvate induces torpor in obese mice [Physiology]

2018-01-08T11:59:23-08:00

Mice subjected to cold or caloric deprivation can reduce body temperature and metabolic rate and enter a state of torpor. Here we show that administration of pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with diet-induced or genetic obesity. This is associated with marked hypothermia, decreased activity, and...



Chronic anthropogenic noise disrupts glucocorticoid signaling and has multiple effects on fitness in an avian community [Ecology]

2018-01-08T11:59:23-08:00

Anthropogenic noise is a pervasive pollutant that decreases environmental quality by disrupting a suite of behaviors vital to perception and communication. However, even within populations of noise-sensitive species, individuals still select breeding sites located within areas exposed to high noise levels, with largely unknown physiological and fitness consequences. We use...



Chemical encoding of risk perception and predator detection among estuarine invertebrates [Systems Biology]

2018-01-08T11:59:23-08:00

An effective strategy for prey to survive in habitats rich in predators is to avoid being noticed. Thus, prey are under selection pressure to recognize predators and adjust their behavior, which can impact numerous community-wide interactions. Many animals in murky and turbulent aquatic environments rely on waterborne chemical cues. Previous...



Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors [Pharmacology]

2018-01-08T11:59:23-08:00

Many ion channels, including Nav1.7, Cav1.3, and Kv1.3, are linked to human pathologies and are important therapeutic targets. To develop efficacious and safe drugs, subtype-selective modulation is essential, but has been extremely difficult to achieve. We postulate that this challenge is caused by the poor assay design, and investigate the...



Emergence of cooperation and division of labor in the primitively eusocial wasp Ropalidia marginata [Evolution]

2018-01-08T11:59:23-08:00

In most primitively eusocial wasps new nests are initiated by a single female or by small groups of females. To study the emergence of division of labor (DOL) among the nest foundresses and to determine its possible effect on nest productivity we maintained newly eclosed females of Ropalidia marginata in...



DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions [Genetics]

2018-01-08T11:59:24-08:00

Ig heavy chain (IgH) class switch recombination (CSR) in B lymphocytes switches IgH constant regions to change antibody functions. CSR is initiated by DNA double-strand breaks (DSBs) within a donor IgH switch (S) region and a downstream acceptor S region. CSR is completed by fusing donor and acceptor S region...



Signaling by the Epstein-Barr virus LMP1 protein induces potent cytotoxic CD4+ and CD8+ T cell responses [Immunology and Inflammation]

2018-01-08T11:59:24-08:00

The B-lymphotropic Epstein–Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and...



Structural heterogeneity and intersubȷect variability of A{beta} in familial and sporadic Alzheimer’s disease [Neuroscience]

2018-01-08T11:59:24-08:00

Point mutations in the amyloid-β (Aβ) coding region produce a combination of mutant and WT Aβ isoforms that yield unique clinicopathologies in familial Alzheimer’s disease (fAD) and cerebral amyloid angiopathy (fCAA) patients. Here, we report a method to investigate the structural variability of amyloid deposits found in fAD, fCAA, and...



Detergent-extracted Volvox model exhibits an anterior-posterior gradient in flagellar Ca2+ sensitivity [Plant Biology]

2018-01-08T11:59:24-08:00

Volvox rousseletii is a multicellular spheroidal green alga containing ∼5,000 cells, each equipped with two flagella (cilia). This organism shows striking photobehavior without any known intercellular communication. To help understand how the behavior of flagella is regulated, we developed a method to extract the whole organism with detergent and reactivate...



Structure of the C1r-C1s interaction of the C1 complex of complement activation [Immunology and Inflammation]

2018-01-08T11:59:24-08:00

The multiprotein complex C1 initiates the classical pathway of complement activation on binding to antibody–antigen complexes, pathogen surfaces, apoptotic cells, and polyanionic structures. It is formed from the recognition subcomponent C1q and a tetramer of proteases C1r2C1s2 as a Ca2+-dependent complex. Here we have determined the structure of a complex...



Influence of anterior midcingulate cortex on drinking behavior during thirst and following satiation [Neuroscience]

2018-01-08T11:59:25-08:00

In humans, activity in the anterior midcingulate cortex (aMCC) is associated with both subjective thirst and swallowing. This region is therefore likely to play a prominent role in the regulation of drinking in response to dehydration. Using functional MRI, we investigated this possibility during a period of “drinking behavior” represented...



Reverse chemical ecology approach for the identification of an oviposition attractant for Culex quinquefasciatus [Applied Biological Sciences]

2018-01-08T11:59:25-08:00

Pheromones and other semiochemicals play a crucial role in today’s integrated pest and vector management strategies. These semiochemicals are typically discovered by bioassay-guided approaches. Here, we applied a reverse chemical ecology approach; that is, we used olfactory proteins to lead us to putative semiochemicals. Specifically, we used 7 of the...



Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity [Medical Sciences]

2018-01-08T11:59:25-08:00

Protein-based drugs are very active in treating cancer, but their efficacy can be limited by the formation of neutralizing antidrug antibodies (ADAs). Recombinant immunotoxins are proteins that are very effective in patients with leukemia, where immunity is suppressed, but induce ADAs, which compromise their activity, in patients with intact immunity....



Freshwater salinization syndrome on a continental scale [Earth, Atmospheric, and Planetary Sciences]

2018-01-08T11:59:25-08:00

Salt pollution and human-accelerated weathering are shifting the chemical composition of major ions in fresh water and increasing salinization and alkalinization across North America. We propose a concept, the freshwater salinization syndrome, which links salinization and alkalinization processes. This syndrome manifests as concurrent trends in specific conductance, pH, alkalinity, and...



Preferences for moral vs. immoral traits in others are conditional [Psychological and Cognitive Sciences]

2018-01-08T11:59:26-08:00

The preference for morality in others is regarded as a dominant factor in person perception. Moral traits are thought to foster liking, and immoral traits are thought to foster disliking, irrespective of the context in which they are embedded. We report the results of four studies that oppose this view....



Power law tails in phylogenetic systems [Physics]

2018-01-08T11:59:26-08:00

Covariance analysis of protein sequence alignments uses coevolving pairs of sequence positions to predict features of protein structure and function. However, current methods ignore the phylogenetic relationships between sequences, potentially corrupting the identification of covarying positions. Here, we use random matrix theory to demonstrate the existence of a power law...



Women live longer than men even during severe famines and epidemics [Population Biology]

2018-01-08T11:59:26-08:00

Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes...



In situ detection of live-to-dead bacteria ratio after inactivation by means of synchronous fluorescence and PCA [Chemistry]

2018-01-08T11:59:27-08:00

The determination of live and dead bacteria is of considerable significance for preventing health care-associated infection in hospitals, field clinics, and other areas. In this study, the viable (live) and nonviable (dead) bacteria in a sample were determined by means of their fluorescence spectra and principal component analysis (PCA). Data...



Suppression of frontal eye field neuronal responses with maintained fixation [Neuroscience]

2018-01-08T11:59:27-08:00

The decision of where to make an eye movement is thought to be driven primarily by responses to stimuli in neurons’ receptive fields (RFs) in oculomotor areas, including the frontal eye field (FEF) of prefrontal cortex. It is also thought that a saccade may be generated when the accumulation of...



Host and parasite thermal ecology jointly determine the effect of climate warming on epidemic dynamics [Ecology]

2018-01-08T11:59:27-08:00

Host–parasite systems have intricately coupled life cycles, but each interactor can respond differently to changes in environmental variables like temperature. Although vital to predicting how parasitism will respond to climate change, thermal responses of both host and parasite in key traits affecting infection dynamics have rarely been quantified. Through temperature-controlled...



Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies [Biophysics and Computational Biology]

2018-01-08T11:59:28-08:00

HIV is a highly mutable virus, and over 30 years after its discovery, a vaccine or cure is still not available. The isolation of broadly neutralizing antibodies (bnAbs) from HIV-infected patients has led to renewed hope for a prophylactic vaccine capable of combating the scourge of HIV. A major challenge...



Functional characterization of the mucus barrier on the Xenopus tropicalis skin surface [Biochemistry]

2018-01-08T11:59:28-08:00

Mucosal surfaces represent critical routes for entry and exit of pathogens. As such, animals have evolved strategies to combat infection at these sites, in particular the production of mucus to prevent attachment and to promote subsequent movement of the mucus/microbe away from the underlying epithelial surface. Using biochemical, biophysical, and...



Modeling lethal X-linked genetic disorders in pigs with ensured fertility [Applied Biological Sciences]

2018-01-08T11:59:28-08:00

Genetically engineered pigs play an indispensable role in the study of rare monogenic diseases. Pigs harboring a gene responsible for a specific disease can be efficiently generated via somatic cell cloning. The generation of somatic cell-cloned pigs from male cells with mutation(s) in an X chromosomal gene is a reliable...



Dysregulation of cotranscriptional alternative splicing underlies CHARGE syndrome [Developmental Biology]

2018-01-08T11:59:28-08:00

CHARGE syndrome—which stands for coloboma of the eye, heart defects, atresia of choanae, retardation of growth/development, genital abnormalities, and ear anomalies—is a severe developmental disorder with wide phenotypic variability, caused mainly by mutations in CHD7 (chromodomain helicase DNA-binding protein 7), known to encode a chromatin remodeler. The genetic lesions responsible...



GBA1 deficiency negatively affects physiological {alpha}-synuclein tetramers and related multimers [Neuroscience]

2018-01-08T11:59:28-08:00

Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase...



Ion dissolution mechanism and kinetics at kink sites on NaCl surfaces [Applied Physical Sciences]

2018-01-08T11:59:29-08:00

Desolvation barriers are present for solute–solvent exchange events, such as ligand binding to an enzyme active site, during protein folding, and at battery electrodes. For solution-grown crystals, desolvation at kink sites can be the rate-limiting step for growth. However, desolvation and the associated kinetic barriers are poorly understood. In this...



Single-crystal metal growth on amorphous insulating substrates [Engineering]

2018-01-08T11:59:29-08:00

Metal structures on insulators are essential components in advanced electronic and nanooptical systems. Their electronic and optical properties are closely tied to their crystal quality, due to the strong dependence of carrier transport and band structure on defects and grain boundaries. Here we report a method for creating patterned single-crystal...



Ecological and evolutionary dynamics of interconnectedness and modularity [Applied Mathematics]

2018-01-08T11:59:29-08:00

In this contribution, we develop a theoretical framework for linking microprocesses (i.e., population dynamics and evolution through natural selection) with macrophenomena (such as interconnectedness and modularity within an ecological system). This is achieved by developing a measure of interconnectedness for population distributions defined on a trait space (generalizing the notion...



Dynamics of charged excitons in electronically and morphologically homogeneous single-walled carbon nanotubes [Chemistry]

2018-01-08T11:59:29-08:00

The trion, a three-body charge-exciton bound state, offers unique opportunities to simultaneously manipulate charge, spin, and excitation in one-dimensional single-walled carbon nanotubes (SWNTs) at room temperature. Effective exploitation of trion quasi-particles requires fundamental insight into their creation and decay dynamics. Such knowledge, however, remains elusive for SWNT trion states, due...



Melanopsin- and L-cone-induced pupil constriction is inhibited by S- and M-cones in humans [Neuroscience]

2018-01-08T11:59:29-08:00

The human retina contains five photoreceptor types: rods; short (S)-, mid (M)-, and long (L)-wavelength–sensitive cones; and melanopsin-expressing ganglion cells. Recently, it has been shown that selective increments in M-cone activation are paradoxically perceived as brightness decrements, as opposed to L-cone increments. Here we show that similar effects are also...



Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy [Cell Biology]

2018-01-08T11:59:30-08:00

The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in...



Phenotypic selection as the biological mode of epigenetic conversion and reversion in cell transformation [Medical Sciences]

2018-01-08T11:59:30-08:00

Exposure of certain cell lines to methylcholanthrene, X-rays, or physiological growth constraint leads to preneoplastic transformation in all or most of the treated cells. After attaining confluence, a fraction in those cells progress to full transformation, as evidenced by their ability to form discrete foci distinguishable from the surrounding cells...



Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes [Neuroscience]

2018-01-08T11:59:30-08:00

Increasing evidence suggests that early neurodevelopmental defects in Huntington’s disease (HD) patients could contribute to the later adult neurodegenerative phenotype. Here, by using HD-derived induced pluripotent stem cell lines, we report that early telencephalic induction and late neural identity are affected in cortical and striatal populations. We show that a...



Reply to Mitteldorf and Fahy: Aging is still inevitable [Letters (Online Only)]

2018-01-08T13:00:43-08:00

We stand by our claim that aging is inevitable in multicellular organisms. However, our model of somatic evolution uses sign arguments and so does not inform the rate of aging nor the extent to which aging can be delayed. While we use the term “somatic mutation,” we explicitly define this...



Questioning the inevitability of aging [Letters (Online Only)]

2018-01-08T13:08:39-08:00

Paul Nelson and Joanna Masel (1) are the most recent theorists to bypass evolution and seek an abstract answer to the question, “What is the cause of aging?” Their mathematics is not in question, but the process of somatic evolution that they model bears no obvious relation to aging as...



ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the neural crest and derived cells [Developmental Biology]

2018-01-09T08:58:08-08:00

Mutations in anaplastic lymphoma kinase (ALK) are implicated in somatic and familial neuroblastoma, a pediatric tumor of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related leukocyte tyrosine kinase (LTK). In the zebrafish Danio rerio, DrLtk,...



The social genome of friends and schoolmates in the National Longitudinal Study of Adolescent to Adult Health [Social Sciences]

2018-01-09T08:58:09-08:00

Humans tend to form social relationships with others who resemble them. Whether this sorting of like with like arises from historical patterns of migration, meso-level social structures in modern society, or individual-level selection of similar peers remains unsettled. Recent research has evaluated the possibility that unobserved genotypes may play an...



Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species [Microbiology]

2018-01-09T08:58:09-08:00

The fungal genus of Aspergillus is highly interesting, containing everything from industrial cell factories, model organisms, and human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse Aspergillus species (A. campestris, A. novofumigatus, A. ochraceoroseus, and A. steynii) have been...



Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function [Biochemistry]

2018-01-09T08:58:09-08:00

Cytokine signaling through the JAK/STAT pathway controls multiple cellular responses including growth, survival, differentiation, and pathogen resistance. An expansion in the gene regulatory repertoire controlled by JAK/STAT signaling occurs through the interaction of STATs with IRF transcription factors to form ISGF3, a complex that contains STAT1, STAT2, and IRF9 and...



Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington’s disease [Neuroscience]

2018-01-09T08:58:09-08:00

Golgi stress response is emerging as a physiologic process of comparable importance to endoplasmic reticulum (ER) and mitochondrial stress responses. However, unlike ER stress, the identity of the signal transduction pathway involved in the Golgi stress response has been elusive. We show that the Golgi stressor monensin acts via the...



Dual evolutionary origin of insect wings supported by an investigation of the abdominal wing serial homologs in Tribolium [Evolution]

2018-01-09T08:58:10-08:00

The origin of insect wings is still a highly debated mystery in biology, despite the importance of this evolutionary innovation. There are currently two prominent, but contrasting wing origin hypotheses (the tergal origin hypothesis and the pleural origin hypothesis). Through studies in the Tribolium beetle, we have previously obtained functional...



Growth is required for perception of water availability to pattern root branches in plants [Plant Biology]

2018-01-09T08:58:10-08:00

Water availability is a potent regulator of plant development and induces root branching through a process termed hydropatterning. Hydropatterning enables roots to position lateral branches toward regions of high water availability, such as wet soil or agar media, while preventing their emergence where water is less available, such as in...



Reply to De Dreu: Shared partner nationality promotes ingroup favoritism in cooperation [Letters (Online Only)]

2018-01-09T09:16:12-08:00

In Romano et al. (1), we report an experimental study conducted across 17 societies that found that individuals gave more in the trust game to ingroup members (partner from own nationality), compared with outgroup members (partner from one of the other 16 nationalities) and strangers (partner with unknown nationality). This...



Giving decision-makers nondiagnostic person information promotes trust within and across nations [Letters (Online Only)]

2018-01-09T10:57:30-08:00

Humans trust others, enabling them to negotiate agreement and to create long-term bonds (1). However, because trusting others makes people vulnerable to exploitation, it is difficult to see how indiscriminate trust could have evolved (2–4). Romano et al. (2) suggest a solution to this conundrum. Fitting evolutionary theory (3, 4),...



IKK{alpha} inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting maȷor redox regulatory pathways [Pharmacology]

2018-01-10T12:30:23-08:00

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus,...



Predicting tipping points in mutualistic networks through dimension reduction [Ecology]

2018-01-08T11:59:27-08:00

Complex networked systems ranging from ecosystems and the climate to economic, social, and infrastructure systems can exhibit a tipping point (a “point of no return”) at which a total collapse of the system occurs. To understand the dynamical mechanism of a tipping point and to predict its occurrence as a...



From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection [Pharmacology]

2017-12-26T09:29:36-08:00

The HIV-1 pandemic affecting over 37 million people worldwide continues, with nearly one-half of the infected population on highly active antiretroviral therapy (HAART). Major therapeutic challenges remain because of the emergence of drug-resistant HIV-1 strains, limitations because of safety and toxicity with current HIV-1 drugs, and patient compliance for lifelong,...



Lumpy species coexistence arises robustly in fluctuating resource environments [Ecology]

2017-12-20T11:41:46-08:00

The effect of life-history traits on resource competition outcomes is well understood in the context of a constant resource supply. However, almost all natural systems are subject to fluctuations of resources driven by cyclical processes such as seasonality and tidal hydrology. To understand community composition, it is therefore imperative to...



Linked networks for learning and expressing location-specific threat [Neuroscience]

2018-01-11T12:08:07-08:00

Learning locations of danger within our environment is a vital adaptive ability whose neural bases are only partially understood. We examined fMRI brain activity while participants navigated a virtual environment in which flowers appeared and were “picked.” Picking flowers in the danger zone (one-half of the environment) predicted an electric...



Future of nonnucleoside reverse transcriptase inhibitors [Commentaries]

2018-01-11T12:08:07-08:00

The nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are small molecules that bind to HIV-1 RT at a site distinct from the DNA polymerase active site of the enzyme and block retroviral reverse transcription via an allosteric mechanism of action (1). Nevirapine (NVP) was the first NNRTI approved in 1996 by...



Partitioning aggression [Commentaries]

2018-01-11T12:08:07-08:00

Human Nature: Nasty or Nice? Have aggression and violence been ramped up in human evolution or dialed down? This sounds like a question that empirical research might have settled long ago, but it remains strangely contentious. In PNAS, Richard Wrangham (1) proposes that debates persist because too many evolutionary anthropologists...



Toward a unifying theory of biodiversity [Commentaries]

2018-01-11T12:08:07-08:00

Ecologists have long agreed that to coexist species must be sufficiently different (1, 2). This worldview was challenged when Stephen Hubbell published his neutral theory of biodiversity showing that species that are essentially equal should also be able to evade competitive exclusion (3). Although this neutral theory inspired a fresh...



Predicting tipping points in complex environmental systems [Commentaries]

2018-01-11T12:08:07-08:00

Ecologists have long recognized that ecosystems can exist and function in one state within predictable bounds for extended periods of time and then abruptly shift to an alternate state (1–5). Desertification of grasslands, shrub expansion in the Arctic, the eutrophication of lakes, ocean acidification, the formation of marine dead zones,...



Evolutionary transition from blood feeding to obligate nonbiting in a mosquito [Evolution]

2017-12-18T11:50:13-08:00

The spread of blood-borne pathogens by mosquitoes relies on their taking a blood meal; if there is no bite, there is no disease transmission. Although many species of mosquitoes never take a blood meal, identifying genes that distinguish blood feeding from obligate nonbiting is hampered by the fact that these...



Enhancer adoption caused by genomic insertion elicits interdigital Shh expression and syndactyly in mouse [Genetics]

2017-12-18T11:50:16-08:00

Acquisition of new cis-regulatory elements (CREs) can cause alteration of developmental gene regulation and may introduce morphological novelty in evolution. Although structural variation in the genome generated by chromosomal rearrangement is one possible source of new CREs, only a few examples are known, except for cases of retrotransposition. In this...



Global warming leads to more uniform spring phenology across elevations [Ecology]

2017-12-26T09:29:38-08:00

One hundred years ago, Andrew D. Hopkins estimated the progressive delay in tree leaf-out with increasing latitude, longitude, and elevation, referred to as “Hopkins’ bioclimatic law.” What if global warming is altering this well-known law? Here, based on ∼20,000 observations of the leaf-out date of four common temperate tree species...



Large genomic insertion at the Shh locus results in hammer toes through enhancer adoption [Commentaries]

2018-01-12T12:01:58-08:00

Enhancers are cis-regulatory elements which control the expression of genes in a defined spatiotemporal pattern, enabling the normal morphogenesis of organs and structures during embryogenesis. Enhancers control their target genes independently of their orientation or distance through chromosomal looping and are thought to evolve through various mutational mechanisms (1). A...



Greening up the mountain [Commentaries]

2018-01-12T12:01:58-08:00

The progression of key plant life-history events, such as spring leaf-out and flowering, along bioclimatic gradients in elevation and latitude is one of the more conspicuous patterns in nature, and, as such, it has served as a source of opportunity, industry, inspiration, and wonder for farmers, natural scientists, and artists...



Molecular pathways to nonbiting mosquitoes [Commentaries]

2018-01-12T12:01:58-08:00

Mosquitoes are often referred to as the deadliest animals on Earth because of the devastating pathogens they are able to transmit when females bite and then feed on blood from human hosts (male mosquitoes don’t bite). In 2015 alone there were an estimated 212 million cases of malaria, resulting in...



Profile of Scott W. Lowe [Profiles]

2018-01-16T08:22:55-08:00

As a graduate student at the Massachusetts Institute of Technology, Scott Lowe became interested in cancer genetics. The phenomenon that drew his interest was called oncogene cooperation—the idea that it takes multiple oncogenes working together to turn a normal cell into a tumor cell. “That was an exciting concept because...



Molecular epidemiology reveals the role of war in the spread of HIV in Ukraine [Medical Sciences]

2018-01-16T08:22:56-08:00

Ukraine has one of the largest HIV epidemics in Europe, historically driven by people who inject drugs (PWID). The epidemic showed signs of stabilization in 2012, but the recent war in eastern Ukraine may be reigniting virus spread. We investigated the movement of HIV-infected people within Ukraine before and during...



The Bardet-Biedl syndrome protein complex is an adapter expanding the cargo range of intraflagellar transport trains for ciliary export [Cell Biology]

2018-01-16T08:22:56-08:00

Bardet–Biedl syndrome (BBS) is a ciliopathy resulting from defects in the BBSome, a conserved protein complex. BBSome mutations affect ciliary membrane composition, impairing cilia-based signaling. The mechanism by which the BBSome regulates ciliary membrane content remains unknown. Chlamydomonas bbs mutants lack phototaxis and accumulate phospholipase D (PLD) in the ciliary...



A randomized controlled design reveals barriers to citizenship for low-income immigrants [Political Sciences]

2018-01-16T08:22:56-08:00

Citizenship endows legal protections and is associated with economic and social gains for immigrants and their communities. In the United States, however, naturalization rates are relatively low. Yet we lack reliable knowledge as to what constrains immigrants from applying. Drawing on data from a public/private naturalization program in New York,...



Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory [Neuroscience]

2018-01-16T08:22:56-08:00

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs)...



miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2 [Microbiology]

2018-01-16T08:22:57-08:00

Human cytomegalovirus (HCMV) impacts more than one-half of the human population owing to its capacity to manipulate the cell and create latent reservoirs in the host. Despite an extensive understanding of HCMV biology during acute infection in fibroblasts, the molecular basis for latency in myeloid cells remains incomplete. This knowledge...



Identification of thioredoxin-interacting protein (TXNIP) as a downstream target for IGF1 action [Medical Sciences]

2018-01-16T08:22:57-08:00

Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with...



Robust prediction of individual creative ability from brain functional connectivity [Psychological and Cognitive Sciences]

2018-01-16T08:22:57-08:00

People’s ability to think creatively is a primary means of technological and cultural progress, yet the neural architecture of the highly creative brain remains largely undefined. Here, we employed a recently developed method in functional brain imaging analysis—connectome-based predictive modeling—to identify a brain network associated with high-creative ability, using functional...



Electron mean-free-path filtering in Dirac material for improved thermoelectric performance [Applied Physical Sciences]

2018-01-16T08:22:57-08:00

Recent advancements in thermoelectric materials have largely benefited from various approaches, including band engineering and defect optimization, among which the nanostructuring technique presents a promising way to improve the thermoelectric figure of merit (zT) by means of reducing the characteristic length of the nanostructure, which relies on the belief that...



Coding of episodic memory in the human hippocampus [Neuroscience]

2018-01-16T08:22:57-08:00

Neurocomputational models have long posited that episodic memories in the human hippocampus are represented by sparse, stimulus-specific neural codes. A concomitant proposal is that when sparse-distributed neural assemblies become active, they suppress the activity of competing neurons (neural sharpening). We investigated episodic memory coding in the hippocampus and amygdala by...



Ebola virus proteins NP, VP35, and VP24 are essential and sufficient to mediate nucleocapsid transport [Microbiology]

2018-01-16T08:22:58-08:00

The intracytoplasmic movement of nucleocapsids is a crucial step in the life cycle of enveloped viruses. Determination of the viral components necessary for viral nucleocapsid transport competency is complicated by the dynamic and complex nature of nucleocapsid assembly and the lack of appropriate model systems. Here, we established a live-cell...



Cooperation, clustering, and assortative mixing in dynamic networks [Evolution]

2018-01-16T08:22:58-08:00

Humans’ propensity to cooperate is driven by our embeddedness in social networks. A key mechanism through which networks promote cooperation is clustering. Within clusters, conditional cooperators are insulated from exploitation by noncooperators, allowing them to reap the benefits of cooperation. Dynamic networks, where ties can be shed and new ties...



HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice [Medical Sciences]

2018-01-16T08:22:58-08:00

Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells...



Local policy proposals can bridge Latino and (most) white Americans’ response to immigration [Psychological and Cognitive Sciences]

2018-01-16T08:22:58-08:00

In the past 15 years, the adoption of subnational immigration policies in the United States, such as those established by individual states, has gone from nearly zero to over 300 per year. These include welcoming policies aimed at attracting and incorporating immigrants, as well as unwelcoming policies directed at denying...



Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster males [Neuroscience]

2018-01-16T08:22:58-08:00

Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or...