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Preview: Proceedings of the National Academy of Sciences recent issues

Proceedings of the National Academy of Sciences recent issues



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



 



In This Issue [This Week in PNAS]

2018-01-16T09:36:18-08:00

Perineuronal nets and recall of distant fear memories PNN (green) around a parvalbumin-expressing inhibitory neuron (red) in rat V2L. Perineuronal nets (PNN) are gauzy, carbohydrate-rich structures that envelop subsets of neurons in the central nervous system, forming a long-lived extracellular matrix that stabilizes synaptic connections between neurons. PNNs are thought...



Action of steroids and plant triterpenoids on CatSper Ca2+ channels in human sperm [Biological Sciences]

2018-01-16T09:36:18-08:00

The sperm-specific Ca2+ channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration and, thereby, the swimming behavior of sperm. Human CatSper is activated by progesterone (1, 2), an oviductal hormone, which stimulates Ca2+ influx and motility responses. By patch-clamp recording from human sperm, Mannowetz et al. (3) studied...



Reply to Brenker et al.: The plant triterpenoid pristimerin inhibits calcium influx into human spermatozoa via CatSper [Biological Sciences]

2018-01-16T09:36:18-08:00

In the letter by Brenker et al. (1), the authors assessed actions of various steroids toward the human calcium channel of sperm (CatSper). The experiments, carried out with calcium imaging, are minimally supplemented by electrophysiology. The authors show that all tested steroids activate CatSper with different efficiencies. However, the plant...



Considering hypertonicity in the interpretation and analysis of cell type-specific gene expression pattern in the collecting duct [Biological Sciences]

2018-01-16T09:36:18-08:00

The different parts of the renal nephron have different functions that are related to reabsorption or secretion processes. This is mediated by genes that show a distinct expression pattern along the renal nephron segments (1). The majority of the segments contain only one epithelial cell type. However, the collecting duct...



Reply to Edemir: Physiological regulation and single-cell RNA sequencing [Biological Sciences]

2018-01-16T09:36:18-08:00

Tacitly, Edemir (1) points to an important issue in the interpretation of data from single-cell RNA-sequencing experiments. Any given cell can exist in a variety of regulatory states that are affected both by extracellular signals and the prior history of the cell. Consequently, data from single-cell RNA sequencing, such as...



Profile of David M. Sabatini [Profile]

2018-01-16T09:36:18-08:00

As a young doctoral candidate at the Johns Hopkins University School of Medicine, David M. Sabatini was allowed to choose his own research project for his thesis. He chose to investigate the molecular mechanism of rapamycin, a compound with antifungal, antitumor, and immunosuppressant properties. The decision was pivotal, because Sabatini...



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

2018-01-16T09:36:18-08:00

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



Microbial proteins for organic material degradation in the deep ocean [Ecology]

2018-01-16T09:36:18-08:00

Organic material is synthesized in the sunlit surface layer of the oceans and that is where most of it is decomposed back to carbon dioxide and other inorganic constituents. However, a small fraction escapes immediate degradation and makes its way into deeper waters, some as far as the bottom thousands...



Endless skulls most beautiful [Evolution]

2018-01-16T09:36:18-08:00

The amazing disparity of living birds is self-apparent, yet immensely challenging to fully quantify. After all, birds are represented by nearly 11,000 living species, comprising a mind-boggling spectrum of shapes, sizes, and colors (1). This incredible variability manifests in an incalculable number of ways (from habitat type to diet to...



Searching for the neural causes of criminal behavior [Neuroscience]

2018-01-16T09:36:18-08:00

All behavior is proximally caused by the brain, but the neural causes of most complex behaviors are still not understood. Much of our ignorance stems from the fact that complex behavior depends on distributed neural control. Unlike a reflex, where the arc from sensation to action can be traced through...



Dynamics and mechanisms of intracellular calcium waves elicited by tandem bubble-induced jetting flow [Engineering]

2018-01-16T09:36:18-08:00

One of the earliest events in cellular mechanotransduction is often an increase in intracellular calcium concentration associated with intracellular calcium waves (ICWs) in various physiologic or pathophysiologic processes. Although cavitation-induced calcium responses are believed to be important for modulating downstream bioeffects such as cell injury and mechanotransduction in ultrasound therapy,...



Creation of disease-inspired biomaterial environments to mimic pathological events in early calcific aortic valve disease [Engineering]

2018-01-16T09:36:18-08:00

An insufficient understanding of calcific aortic valve disease (CAVD) pathogenesis remains a major obstacle in developing treatment strategies for this disease. The aim of the present study was to create engineered environments that mimic the earliest known features of CAVD and apply this in vitro platform to decipher relationships relevant...



Migration-based selections of antibodies that convert bone marrow into trafficking microglia-like cells that reduce brain amyloid {beta} [Applied Biological Sciences]

2018-01-16T09:36:18-08:00

One goal of regenerative medicine is to repair damaged tissue. This requires not only generating new cells of the proper phenotype, but also selecting for those that properly integrate into sites of injury. In our laboratory we are using a cell-migration–based in vivo selection system to generate antibodies that induce...



Atomic mutagenesis of stop codon nucleotides reveals the chemical prerequisites for release factor-mediated peptide release [Biochemistry]

2018-01-16T09:36:18-08:00

Termination of protein synthesis is triggered by the recognition of a stop codon at the ribosomal A site and is mediated by class I release factors (RFs). Whereas in bacteria, RF1 and RF2 promote termination at UAA/UAG and UAA/UGA stop codons, respectively, eukaryotes only depend on one RF (eRF1) to...



Computational modeling of three-dimensional ECM-rigidity sensing to guide directed cell migration [Biophysics and Computational Biology]

2018-01-16T09:36:18-08:00

Filopodia have a key role in sensing both chemical and mechanical cues in surrounding extracellular matrix (ECM). However, quantitative understanding is still missing in the filopodial mechanosensing of local ECM stiffness, resulting from dynamic interactions between filopodia and the surrounding 3D ECM fibers. Here we present a method for characterizing...



Organic matter processing by microbial communities throughout the Atlantic water column as revealed by metaproteomics [Ecology]

2018-01-16T09:36:18-08:00

The phylogenetic composition of the heterotrophic microbial community is depth stratified in the oceanic water column down to abyssopelagic layers. In the layers below the euphotic zone, it has been suggested that heterotrophic microbes rely largely on solubilized particulate organic matter as a carbon and energy source rather than on...



Pairwise comparisons across species are problematic when analyzing functional genomic data [Evolution]

2018-01-16T09:36:18-08:00

There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary...



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

2018-01-16T09:36:18-08:00

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



Expression of an active G{alpha}s mutant in skeletal stem cells is sufficient and necessary for fibrous dysplasia initiation and maintenance [Genetics]

2018-01-16T09:36:18-08:00

Fibrous dysplasia (FD) is a disease caused by postzygotic activating mutations of GNAS (R201C and R201H) that encode the α-subunit of the Gs stimulatory protein. FD is characterized by the development of areas of abnormal fibroosseous tissue in the bones, resulting in skeletal deformities, fractures, and pain. Despite the well-defined...



Antagonistic regulation of trafficking to Caenorhabditis elegans sensory cilia by a Retinal Degeneration 3 homolog and retromer [Genetics]

2018-01-16T09:36:18-08:00

Sensory neurons often possess cilia with elaborate membrane structures that are adapted to the sensory modality of the host cell. Mechanisms that target sensory transduction proteins to these specialized membrane domains remain poorly understood. Here, we show that a homolog of the human retinal dystrophy gene Retinal Degeneration 3 (RD3)...



Cyclic AMP-dependent plasticity underlies rapid changes in odor coding associated with reward learning [Genetics]

2018-01-16T09:36:18-08:00

Learning and memory rely on dopamine and downstream cAMP-dependent plasticity across diverse organisms. Despite the central role of cAMP signaling, it is not known how cAMP-dependent plasticity drives coherent changes in neuronal physiology that encode the memory trace, or engram. In Drosophila, the mushroom body (MB) is critically involved in...



SRC1 promotes Th17 differentiation by overriding Foxp3 suppression to stimulate ROR{gamma}t activity in a PKC-{theta}-dependent manner [Immunology and Inflammation]

2018-01-16T09:36:18-08:00

Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the...



Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor [Immunology and Inflammation]

2018-01-16T09:36:18-08:00

Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti–PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide...



Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C [Immunology and Inflammation]

2018-01-16T09:36:18-08:00

Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic...



Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges [Immunology and Inflammation]

2018-01-16T09:36:18-08:00

The contribution of host genetic and nongenetic factors to immunological differences in humans remains largely undefined. Here, we generated bacterial-, fungal-, and viral-induced immune transcriptional profiles in an age- and sex-balanced cohort of 1,000 healthy individuals and searched for the determinants of immune response variation. We found that age and...



Gene regulation and suppression of type I interferon signaling by STAT3 in diffuse large B cell lymphoma [Medical Sciences]

2018-01-16T09:36:18-08:00

STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell–like subtype (ABC)....



Viral discovery and diversity in trypanosomatid protozoa with a focus on relatives of the human parasite Leishmania [Microbiology]

2018-01-16T09:36:18-08:00

Knowledge of viral diversity is expanding greatly, but many lineages remain underexplored. We surveyed RNA viruses in 52 cultured monoxenous relatives of the human parasite Leishmania (Crithidia and Leptomonas), as well as plant-infecting Phytomonas. Leptomonas pyrrhocoris was a hotbed for viral discovery, carrying a virus (Leptomonas pyrrhocoris ostravirus 1) with...



Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification [Neuroscience]

2018-01-16T09:36:18-08:00

The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study, we describe a novel, biphasic function for glial cell line-derived neurotrophic factor (GDNF)...



KLU suppresses megasporocyte cell fate through SWR1-mediated activation of WRKY28 expression in Arabidopsis [Plant Biology]

2018-01-16T09:36:18-08:00

Germ-line specification is essential for sexual reproduction. In the ovules of most flowering plants, only a single hypodermal cell enlarges and differentiates into a megaspore mother cell (MMC), the founder cell of the female germ-line lineage. The molecular mechanisms restricting MMC specification to a single cell remain elusive. We show...



Motor dexterity and strength depend upon integrity of the attention-control system [Psychological and Cognitive Sciences]

2018-01-16T09:36:18-08:00

Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength—by examining relationships between attention control and motor...



Preservation of the genetic diversity of a local common carp in the agricultural heritage rice-fish system [Sustainability Science]

2018-01-16T09:36:18-08:00

We examined how traditional farmers preserve the genetic diversity of a local common carp (Cyprinus carpio), which is locally referred to as “paddy field carp” (PF-carp), in a “globally important agricultural heritage system” (GIAHS), i.e., the 1,200-y-old rice–fish coculture system in Zhejiang Province, China. Our molecular and morphological analysis showed...



Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy [Applied Biological Sciences]

2018-01-16T09:36:18-08:00

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release...



Graphene-based bimorphs for micron-sized, autonomous origami machines [Applied Physical Sciences]

2018-01-16T09:36:18-08:00

Origami-inspired fabrication presents an attractive platform for miniaturizing machines: thinner layers of folding material lead to smaller devices, provided that key functional aspects, such as conductivity, stiffness, and flexibility, are persevered. Here, we show origami fabrication at its ultimate limit by using 2D atomic membranes as a folding material. As...



Evolution of real contact area under shear and the value of static friction of soft materials [Applied Physical Sciences]

2018-01-16T09:36:18-08:00

The frictional properties of a rough contact interface are controlled by its area of real contact, the dynamical variations of which underlie our modern understanding of the ubiquitous rate-and-state friction law. In particular, the real contact area is proportional to the normal load, slowly increases at rest through aging, and...



Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid [Biochemistry]

2018-01-16T09:36:18-08:00

HIV-1 reverse transcriptase (RT) contains both DNA polymerase and RNase H activities to convert the viral genomic RNA to dsDNA in infected host cells. Here we report the 2.65-Å resolution structure of HIV-1 RT engaging in cleaving RNA in an RNA/DNA hybrid. A preferred substrate sequence is absolutely required to...



Slow domain reconfiguration causes power-law kinetics in a two-state enzyme [Biophysics and Computational Biology]

2018-01-16T09:36:18-08:00

Protein dynamics are typically captured well by rate equations that predict exponential decays for two-state reactions. Here, we describe a remarkable exception. The electron-transfer enzyme quiescin sulfhydryl oxidase (QSOX), a natural fusion of two functionally distinct domains, switches between open- and closed-domain arrangements with apparent power-law kinetics. Using single-molecule FRET...



Folding of maltose binding protein outside of and in GroEL [Biophysics and Computational Biology]

2018-01-16T09:36:18-08:00

We used hydrogen exchange–mass spectrometry (HX MS) and fluorescence to compare the folding of maltose binding protein (MBP) in free solution and in the GroEL/ES cavity. Upon refolding, MBP initially collapses into a dynamic molten globule-like ensemble, then forms an obligatory on-pathway native-like folding intermediate (1.2 seconds) that brings together...



Identification of a ubiquitin-binding interface using Rosetta and DEER [Biophysics and Computational Biology]

2018-01-16T09:36:18-08:00

ExoU is a type III-secreted cytotoxin expressing A2 phospholipase activity when injected into eukaryotic target cells by the bacterium Pseudomonas aeruginosa. The enzymatic activity of ExoU is undetectable in vitro unless ubiquitin, a required cofactor, is added to the reaction. The role of ubiquitin in facilitating ExoU enzymatic activity is...



CDC42 binds PAK4 via an extended GTPase-effector interface [Biophysics and Computational Biology]

2018-01-16T09:36:18-08:00

The p21-activated kinase (PAK) group of serine/threonine kinases are downstream effectors of RHO GTPases and play important roles in regulation of the actin cytoskeleton, cell growth, survival, polarity, and development. Here we probe the interaction of the type II PAK, PAK4, with RHO GTPases. Using solution scattering we find that...



Cargo navigation across 3D microtubule intersections [Biophysics and Computational Biology]

2018-01-16T09:36:18-08:00

The eukaryotic cell’s microtubule cytoskeleton is a complex 3D filament network. Microtubules cross at a wide variety of separation distances and angles. Prior studies in vivo and in vitro suggest that cargo transport is affected by intersection geometry. However, geometric complexity is not yet widely appreciated as a regulatory factor...



Motion parallax in electric sensing [Biophysics and Computational Biology]

2018-01-16T09:36:18-08:00

A crucial step in forming spatial representations of the environment involves the estimation of relative distance. Active sampling through specific movements is considered essential for optimizing the sensory flow that enables the extraction of distance cues. However, in electric sensing, direct evidence for the generation and exploitation of sensory flow...



The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer’s disease [Chemistry]

2018-01-16T09:36:18-08:00

The BDNF mimetic compound 7,8-dihydroxyflavone (7,8-DHF), a potent small molecular TrkB agonist, displays prominent therapeutic efficacy against Alzheimer’s disease (AD). However, 7,8-DHF has only modest oral bioavailability and a moderate pharmacokinetic (PK) profile. To alleviate these preclinical obstacles, we used a prodrug strategy for elevating 7,8-DHF oral bioavailability and brain...



Hypoxia-induced transcription factor signaling is essential for larval growth of the mosquito Aedes aegypti [Developmental Biology]

2018-01-16T09:36:18-08:00

Gut microbes positively affect the physiology of many animals, but the molecular mechanisms underlying these benefits remain poorly understood. We recently reported that bacteria-induced gut hypoxia functions as a signal for growth and molting of the mosquito Aedes aegypti. In this study, we tested the hypothesis that transduction of a...



Aridity weakens population-level effects of multiple species interactions on Hibiscus meyeri [Ecology]

2018-01-16T09:36:18-08:00

Predicting how species’ abundances and ranges will shift in response to climate change requires a mechanistic understanding of how multiple factors interact to limit population growth. Both abiotic stress and species interactions can limit populations and potentially set range boundaries, but we have a poor understanding of when and where...



Unraveling submicron-scale mechanical heterogeneity by three-dimensional X-ray microdiffraction [Engineering]

2018-01-16T09:36:18-08:00

Shear banding is a ubiquitous phenomenon of severe plastic deformation, and damage accumulation in shear bands often results in the catastrophic failure of a material. Despite extensive studies, the microscopic mechanisms of strain localization and deformation damage in shear bands remain elusive due to their spatial−temporal complexities embedded in bulk...



High fire-derived nitrogen deposition on central African forests [Environmental Sciences]

2018-01-16T09:36:18-08:00

Atmospheric nitrogen (N) deposition is an important determinant of N availability for natural ecosystems worldwide. Increased anthropogenic N deposition shifts the stoichiometric equilibrium of ecosystems, with direct and indirect impacts on ecosystem functioning and biogeochemical cycles. Current simulation data suggest that remote tropical forests still receive low atmospheric N deposition...



Developmental origins of mosaic evolution in the avian cranium [Evolution]

2018-01-16T09:36:18-08:00

Mosaic evolution, which results from multiple influences shaping morphological traits and can lead to the presence of a mixture of ancestral and derived characteristics, has been frequently invoked in describing evolutionary patterns in birds. Mosaicism implies the hierarchical organization of organismal traits into semiautonomous subsets, or modules, which reflect differential...



Silk-based multilayered angle-ply annulus fibrosus construct to recapitulate form and function of the intervertebral disc [Medical Sciences]

2018-01-16T09:36:18-08:00

Recapitulation of the form and function of complex tissue organization using appropriate biomaterials impacts success in tissue engineering endeavors. The annulus fibrosus (AF) represents a complex, multilamellar, hierarchical structure consisting of collagen, proteoglycans, and elastic fibers. To mimic the intricacy of AF anatomy, a silk protein-based multilayered, disc-like angle-ply construct...



Noncanonical agonist PPAR{gamma} ligands modulate the response to DNA damage and sensitize cancer cells to cytotoxic chemotherapy [Medical Sciences]

2018-01-16T09:36:18-08:00

The peroxisome-proliferator receptor-γ (PPARγ) is expressed in multiple cancer types. Recently, our group has shown that PPARγ is phosphorylated on serine 273 (S273), which selectively modulates the transcriptional program controlled by this protein. PPARγ ligands, including thiazolidinediones (TZDs), block S273 phosphorylation. This activity is chemically separable from the canonical activation...



Cross-genus rebooting of custom-made, synthetic bacteriophage genomes in L-form bacteria [Microbiology]

2018-01-16T09:36:18-08:00

Engineered bacteriophages provide powerful tools for biotechnology, diagnostics, pathogen control, and therapy. However, current techniques for phage editing are experimentally challenging and limited to few phages and host organisms. Viruses that target Gram-positive bacteria are particularly difficult to modify. Here, we present a platform technology that enables rapid, accurate, and...



Conserved features of the primate face code [Neuroscience]

2018-01-16T09:36:18-08:00

A recent paper demonstrated that the pattern of firing rates across ∼100 neurons in the anterior medial face patch is closely related to which human face (of 2,000) had been presented to a monkey [Chang L, Tsao DY (2017) Cell 169:1013–1028]. In addition, the firing rates for these neurons can...



Somatostatin and parvalbumin inhibitory synapses onto hippocampal pyramidal neurons are regulated by distinct mechanisms [Neuroscience]

2018-01-16T09:36:18-08:00

Excitation–inhibition balance is critical for optimal brain function, yet the mechanisms underlying the tuning of inhibition from different populations of inhibitory neurons are unclear. Here, we found evidence for two distinct pathways through which excitatory neurons cell-autonomously modulate inhibitory synapses. Synapses from parvalbumin-expressing interneurons onto hippocampal pyramidal neurons are regulated...



Detection of synchronous brain activity in white matter tracts at rest and under functional loading [Neuroscience]

2018-01-16T09:36:18-08:00

Functional MRI based on blood oxygenation level-dependent (BOLD) contrast is well established as a neuroimaging technique for detecting neural activity in the cortex of the human brain. While detection and characterization of BOLD signals, as well as their electrophysiological and hemodynamic/metabolic origins, have been extensively studied in gray matter (GM),...



Lesion network localization of criminal behavior [Neuroscience]

2018-01-16T09:36:18-08:00

Following brain lesions, previously normal patients sometimes exhibit criminal behavior. Although rare, these cases can lend unique insight into the neurobiological substrate of criminality. Here we present a systematic mapping of lesions with known temporal association to criminal behavior, identifying 17 lesion cases. The lesion sites were spatially heterogeneous, including...



Removal of perineuronal nets disrupts recall of a remote fear memory [Neuroscience]

2018-01-16T09:36:18-08:00

Throughout life animals learn to recognize cues that signal danger and instantaneously initiate an adequate threat response. Memories of such associations may last a lifetime and far outlast the intracellular molecules currently found to be important for memory processing. The memory engram may be supported by other more stable molecular...



Localizing softness and stress along loops in 3D topological metamaterials [Physics]

2018-01-16T09:36:18-08:00

Topological states can be used to control the mechanical properties of a material along an edge or around a localized defect. The rigidity of elastic networks is characterized by a topological invariant called the polarization; materials with a well-defined uniform polarization display a dramatic range of edge softness depending on...



Estrogen-dependent epigenetic regulation of soluble epoxide hydrolase via DNA methylation [Physiology]

2018-01-16T09:36:18-08:00

To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE)...



When linearity prevails over hierarchy in syntax [Psychological and Cognitive Sciences]

2018-01-16T09:36:18-08:00

Hierarchical structure has been cherished as a grammatical universal. We use experimental methods to show where linear order is also a relevant syntactic relation. An identical methodology and design were used across six research sites on South Slavic languages. Experimental results show that in certain configurations, grammatical production can in...



Opinion: Measuring how countries adapt to societal aging [Social Sciences]

2018-01-16T09:36:18-08:00

Across the developed world, large increases in life expectancy over the past century, often coupled with decreasing fertility rates, have created older, top-heavy societies. The United Nations projects that by 2050 the world population of “oldest-old” aged 80 years and above will triple to 434 million (1). In the United...



Engineering posttranslational proofreading to discriminate nonstandard amino acids [Systems Biology]

2018-01-16T09:36:18-08:00

Incorporation of nonstandard amino acids (nsAAs) leads to chemical diversification of proteins, which is an important tool for the investigation and engineering of biological processes. However, the aminoacyl-tRNA synthetases crucial for this process are polyspecific in regard to nsAAs and standard amino acids. Here, we develop a quality control system...



Correction for Alonso-Mora et al., On-demand high-capacity ride-sharing via dynamic trip-vehicle assignment [Correction]

2018-01-16T09:36:18-08:00

COMPUTER SCIENCES, SOCIAL SCIENCES Correction for “On-demand high-capacity ride-sharing via dynamic trip-vehicle assignment,” by Javier Alonso-Mora, Samitha Samaranayake, Alex Wallar, Emilio Frazzoli, and Daniela Rus, which was first published January 3, 2017; 10.1073/pnas.1611675114 (Proc Natl Acad Sci USA 114:462–467). The authors note that Fig. 5D, mean travel distance, in the...



Correction for Boxell et al., Greater Internet use is not associated with faster growth in political polarization among US demographic groups [Correction]

2018-01-16T09:36:18-08:00

ECONOMIC SCIENCES Correction for “Greater Internet use is not associated with faster growth in political polarization among US demographic groups,” by Levi Boxell, Matthew Gentzkow, and Jesse M. Shapiro, which was first published September 19, 2017; 10.1073/pnas.1706588114 (Proc Natl Acad Sci USA 114:10612–10617). The authors wish to note the following:...



Retraction for Chanmanee et al., Solar photothermochemical alkane reverse combustion [Retractions]

2018-01-16T09:36:18-08:00

CHEMISTRY Retraction for “Solar photothermochemical alkane reverse combustion,” by Wilaiwan Chanmanee, Mohammad Fakrul Islam, Brian H. Dennis, and Frederick M. MacDonnell, which was first published February 22, 2016; 10.1073/pnas.1516945113 (Proc Natl Acad Sci USA 113:2579–2584). The authors wish to note the following: “We have now demonstrated that our results in...



In This Issue [This Week in PNAS]

2018-01-09T11:21:12-08:00

Whole-brain atlas of the mouse cholinergic system Horizontal view of 50 cholinergic neurons in basal forebrain reconstructed from whole-brain database. Image courtesy of Yefei Li (artist). The cholinergic system modulates neuronal activity tied to critical functions, including memory, learning, behavior, sensory processing, and sleep–wake cycles. Researchers have begun to pinpoint...



Climate change and agricultural suicides in India [Social Sciences]

2018-01-09T11:21:12-08:00

Carleton (1) claims that “temperature during India’s main agricultural growing season has a strong positive effect on annual suicide rates.” Using state-scale panel data for 1967–2013, the author suggests that an increase in 1 °C temperature in a single day can cause 70 suicides. The evidence, she argues, is consistent...



Unfounded assumptions in linking crop-damaging temperature and suicide in India [Social Sciences]

2018-01-09T11:21:12-08:00

Carleton (1) established that high temperature has caused 59,300 suicides during 1987–2013 in India and for temperatures above 20 °C, a 1 °C increase in a single day’s temperature causes ∼70 suicides in the country. The author argues that high temperature stimulates suicides through a crop-damaging agricultural channel as the...



Analyzing Indian farmer suicide rates [Social Sciences]

2018-01-09T11:21:12-08:00

Arguments about the causes of Indian farmer suicides have been widely aired in recent years, both in the media and in academic papers. It is plausible to suppose, as Carleton (1) does, that climate change has an indirect causal effect on the farmer suicide rate via reduced crop yields and...



Reply to Plewis, Murari et al., and Das: The suicide-temperature link in India and the evidence of an agricultural channel are robust [Social Sciences]

2018-01-09T11:21:12-08:00

In Carleton (1) I demonstrate that increases in growing-season temperatures in India contribute to rising suicide rates. In secondary analysis, I show correlational evidence of an agricultural channel, in which heat damages crops and crop losses induce suicide. The concerns raised by Murari et al. (2), Das (3), and Plewis...



Note on bias from averaging repeated measurements in heritability studies [Biological Sciences]

2018-01-09T11:21:12-08:00

Ge et al. (1) consider the extension of Fisher’s classic model for heritability to the case where there are repeated measurements on subjects. One approach to analyzing repeated measurements is to average observations. The authors show empirically and via simulations that estimates of heritability derived from averaging repeated measurements lead...



Reply to Risk and Zhu: Mixed-effects modeling as a principled approach to heritability analysis with repeat measurements [Biological Sciences]

2018-01-09T11:21:12-08:00

In ref. 1 we demonstrated that lumping together stable effects (e.g., unique environment) and transient effects (e.g., measurement error) in heritability analysis can be problematic when comparing traits with different levels of heritability. In particular, the conventional approach that averages repeat measurements (denoted as havg2) underestimates the heritability of a...



Fraternal birth order effect on sexual orientation explained [Psychological and Cognitive Sciences]

2018-01-09T11:21:12-08:00

Twenty years ago, Ray Blanchard and Anthony Bogaert demonstrated that the probability of a boy growing up to be gay increases for each older brother born to the same mother, the so-called fraternal birth order (FBO) effect. Their first investigation indicated that each older brother increased the probability of being...



Replication fork convergence at termination: A multistep process [Cell Biology]

2018-01-09T11:21:12-08:00

Termination of replication occurs when two forks converge, an important but understudied process. In PNAS, a report from the Courcelle group examines replication termination using deep-sequencing genomic profiling of replicating cells to obtain copy number information about head-on collision of replication forks in different genetic backgrounds (1). Mutations in the...



Interplay of structure, elasticity, and dynamics in actin-based nematic materials [Applied Physical Sciences]

2018-01-09T11:21:12-08:00

Achieving control and tunability of lyotropic materials has been a long-standing goal of liquid crystal research. Here we show that the elasticity of a liquid crystal system consisting of a dense suspension of semiflexible biopolymers can be manipulated over a relatively wide range of elastic moduli. Specifically, thin films of...



Interfacial curvature effects on the monolayer morphology and dynamics of a clinical lung surfactant [Engineering]

2018-01-09T11:21:12-08:00

The morphology of surfactant monolayers is typically studied on the planar surface of a Langmuir trough, even though most physiological interfaces are curved at the micrometer scale. Here, we show that, as the radius of a clinical lung surfactant monolayer-covered bubble decreases to ∼100 µm, the monolayer morphology changes from...



Quantitative historical analysis uncovers a single dimension of complexity that structures global variation in human social organization [Anthropology]

2018-01-09T11:21:12-08:00

Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological...



Structural basis for the regulation of {beta}-glucuronidase expression by human gut Enterobacteriaceae [Biochemistry]

2018-01-09T11:21:12-08:00

The gut microbiota harbor diverse β-glucuronidase (GUS) enzymes that liberate glucuronic acid (GlcA) sugars from small-molecule conjugates and complex carbohydrates. However, only the Enterobacteriaceae family of human gut-associated Proteobacteria maintain a GUS operon under the transcriptional control of a glucuronide repressor, GusR. Despite its potential importance in Escherichia, Salmonella, Klebsiella,...



Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA [Biochemistry]

2018-01-09T11:21:12-08:00

Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3′-5′ exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3′-end in vitro, and its...



Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1 [Biochemistry]

2018-01-09T11:21:12-08:00

The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC’s role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has...



Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy [Cell Biology]

2018-01-09T11:21:12-08:00

PARKIN, an E3 ligase mutated in familial Parkinson’s disease, promotes mitophagy by ubiquitinating mitochondrial proteins for efficient engagement of the autophagy machinery. Specifically, PARKIN-synthesized ubiquitin chains represent targets for the PINK1 kinase generating phosphoS65-ubiquitin (pUb), which constitutes the mitophagy signal. Physiological regulation of PARKIN abundance, however, and the impact on...



RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases [Cell Biology]

2018-01-09T11:21:12-08:00

Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell...



Neuronal delivery of Hedgehog directs spatial patterning of taste organ regeneration [Cell Biology]

2018-01-09T11:21:12-08:00

How organs maintain and restore functional integrity during ordinary tissue turnover or following injury represents a central biological problem. The maintenance of taste sensory organs in the tongue was shown 140 years ago to depend on innervation from distant ganglion neurons, but the underlying mechanism has remained unknown. Here, we...



Listeria monocytogenes triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy [Cell Biology]

2018-01-09T11:21:12-08:00

Xenophagy is a selective macroautophagic process that protects the host cytosol by entrapping and delivering microbes to a degradative compartment. Both noncanonical autophagic pathways and xenophagy are activated by microbes during infection, but the relative importance and function of these distinct processes are not clear. In this study, we used...



Hybrid speciation leads to novel male secondary sexual ornamentation of an Amazonian bird [Evolution]

2018-01-09T11:21:12-08:00

Hybrid speciation is rare in vertebrates, and reproductive isolation arising from hybridization is infrequently demonstrated. Here, we present evidence supporting a hybrid-speciation event involving the genetic admixture of the snow-capped (Lepidothrix nattereri) and opal-crowned (Lepidothrix iris) manakins of the Amazon basin, leading to the formation of the hybrid species, the...



Multiple origins of interdependent endosymbiotic complexes in a genus of cicadas [Evolution]

2018-01-09T11:21:12-08:00

Bacterial endosymbionts that provide nutrients to hosts often have genomes that are extremely stable in structure and gene content. In contrast, the genome of the endosymbiont Hodgkinia cicadicola has fractured into multiple distinct lineages in some species of the cicada genus Tettigades. To better understand the frequency, timing, and outcomes...



Ancient polymorphisms and divergence hitchhiking contribute to genomic islands of divergence within a poplar species complex [Evolution]

2018-01-09T11:21:12-08:00

How genome divergence eventually leads to speciation is a topic of prime evolutionary interest. Genomic islands of elevated divergence are frequently reported between diverging lineages, and their size is expected to increase with time and gene flow under the speciation-with-gene-flow model. However, such islands can also result from divergent sorting...



Histone demethylase LSD1 regulates hematopoietic stem cells homeostasis and protects from death by endotoxic shock [Immunology and Inflammation]

2018-01-09T11:21:12-08:00

Hematopoietic stem cells (HSCs) maintain a quiescent state during homeostasis, but with acute infection, they exit the quiescent state to increase the output of immune cells, the so-called “emergency hematopoiesis.” However, HSCs’ response to severe infection during septic shock and the pathological impact remain poorly elucidated. Here, we report that...



FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes [Immunology and Inflammation]

2018-01-09T11:21:13-08:00

FoxP3+ regulatory T cells (Tregs) are a central element of immunological tolerance. FoxP3 is the key determining transcription factor of the Treg lineage, interacting with numerous cofactors and transcriptional targets to determine the many facets of Treg function. Its absence leads to devastating lymphoproliferation and autoimmunity in scurfy mutant mice...



Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes [Medical Sciences]

2018-01-09T11:21:13-08:00

Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement....



Stand-alone ClpG disaggregase confers superior heat tolerance to bacteria [Microbiology]

2018-01-09T11:21:13-08:00

AAA+ disaggregases solubilize aggregated proteins and confer heat tolerance to cells. Their disaggregation activities crucially depend on partner proteins, which target the AAA+ disaggregases to protein aggregates while concurrently stimulating their ATPase activities. Here, we report on two potent ClpG disaggregase homologs acquired through horizontal gene transfer by the species...



Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization [Microbiology]

2018-01-09T11:21:13-08:00

Colonization by Streptococcus gallolyticus subsp. gallolyticus (SGG) is strongly associated with the occurrence of colorectal cancer (CRC). However, the factors leading to its successful colonization are unknown, and whether SGG influences the oncogenic process or benefits from the tumor-prone environment to prevail remains an open question. Here, we elucidate crucial...



ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations [Neuroscience]

2018-01-09T11:21:13-08:00

ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including...



Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes [Neuroscience]

2018-01-09T11:21:13-08:00

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and...



Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context [Neuroscience]

2018-01-09T11:21:13-08:00

The memory for a new episode is formed immediately upon experience and can last up to a lifetime. It has been shown that the hippocampal network plays a fundamental role in the rapid acquisition of a memory of a one-time experience, in which the novelty component of the experience promotes...



Heat activation is intrinsic to the pore domain of TRPV1 [Physiology]

2018-01-09T11:21:13-08:00

The TRPV1 channel is a sensitive detector of pain-producing stimuli, including noxious heat, acid, inflammatory mediators, and vanilloid compounds. Although binding sites for some activators have been identified, the location of the temperature sensor remains elusive. Using available structures of TRPV1 and voltage-activated potassium channels, we engineered chimeras wherein transmembrane...



ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells [Physiology]

2018-01-09T11:21:13-08:00

N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown....



ZmCCT9 enhances maize adaptation to higher latitudes [Plant Biology]

2018-01-09T11:21:13-08:00

From its tropical origin in southwestern Mexico, maize spread over a wide latitudinal cline in the Americas. This feat defies the rule that crops are inhibited from spreading easily across latitudes. How the widespread latitudinal adaptation of maize was accomplished is largely unknown. Through positional cloning and association mapping, we...



Two types of aggression in human evolution [Anthropology]

2018-01-09T11:21:12-08:00

Two major types of aggression, proactive and reactive, are associated with contrasting expression, eliciting factors, neural pathways, development, and function. The distinction is useful for understanding the nature and evolution of human aggression. Compared with many primates, humans have a high propensity for proactive aggression, a trait shared with chimpanzees...



Inactivation of porcine interleukin-1{beta} results in failure of rapid conceptus elongation [Agricultural Sciences]

2018-01-09T11:21:12-08:00

Conceptus expansion throughout the uterus of mammalian species with a noninvasive epitheliochorial type of placentation is critical establishing an adequate uterine surface area for nutrient support during gestation. Pig conceptuses undergo a unique rapid morphological transformation to elongate into filamentous threads within 1 h, which provides the uterine surface to...



Inner Workings: Fishing for artifacts beneath the waves [Anthropology]

2018-01-09T11:21:12-08:00

Fisherman Mike Anderson has accidentally hauled up all manner of oddities in his fishing gear—bits of pottery, lumps of coal, even a silver spoon. But he’d never seen anything like the heavy, jagged block pulled up by his scallop dredge as he cruised near the New England coast in the...



A mixed-scale dense convolutional neural network for image analysis [Applied Mathematics]

2018-01-09T11:21:12-08:00

Deep convolutional neural networks have been successfully applied to many image-processing problems in recent works. Popular network architectures often add additional operations and connections to the standard architecture to enable training deeper networks. To achieve accurate results in practice, a large number of trainable parameters are often required. Here, we...