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Preview: PNAS - RSS feed of Early Edition articles

PNAS - RSS feed of Early Edition articles



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



 



Future urban land expansion and implications for global croplands [Sustainability Science]

2016-12-27T09:51:19-08:00

Urban expansion often occurs on croplands. However, there is little scientific understanding of how global patterns of future urban expansion will affect the world’s cultivated areas. Here, we combine spatially explicit projections of urban expansion with datasets on global croplands and crop yields. Our results show that urban expansion will...



Deborah S. Jin 1968-2016: Trailblazer of ultracold science [Retrospectives]

2016-12-30T11:06:58-08:00

Deborah Jin, a pioneer in modern atomic and molecular physics, passed away on September 15, 2016, at age 47, after a courageous fight with cancer. She was a world renowned scientist at JILA (formerly known as the Joint Institute for Laboratory Astrophysics) in Boulder, Colorado, a joint institute of the...



Global urban signatures of phenotypic change in animal and plant populations [Sustainability Science]

2017-01-03T08:47:11-08:00

Humans challenge the phenotypic, genetic, and cultural makeup of species by affecting the fitness landscapes on which they evolve. Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change...



Forkhead box a2 (FOXA2) is essential for uterine function and fertility [Physiology]

2017-01-03T08:47:14-08:00

Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription...



CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes [Immunology and Inflammation]

2017-01-03T08:47:18-08:00

Refractory celiac disease type II (RCDII) is a severe complication of celiac disease (CD) characterized by the presence of an enlarged clonal population of innate intraepithelial lymphocytes (IELs) lacking classical B-, T-, and natural killer (NK)-cell lineage markers (Lin−IELs) in the duodenum. In ∼50% of patients with RCDII, these Lin−IELs...



A hypothalamic circuit that controls body temperature [Neuroscience]

2017-01-04T11:00:06-08:00

The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify...



Contribution of canonical nonhomologous end joining to chromosomal rearrangements is enhanced by ATM kinase deficiency [Genetics]

2017-01-05T13:40:34-08:00

A likely mechanism of chromosomal rearrangement formation involves joining the ends from two different chromosomal double-strand breaks (DSBs). These events could potentially be mediated by either of two end-joining (EJ) repair pathways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause distinct rearrangement junction patterns. The relative...



Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior [Medical Sciences]

2017-01-05T13:40:35-08:00

The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an ApcMin/+ (adenomatous polyposis coli) mouse...



Cocapture of cognate and bystander antigens can activate autoreactive B cells [Immunology and Inflammation]

2017-01-05T13:40:36-08:00

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery....



piggyBac mediates efficient in vivo CRISPR library screening for tumorigenesis in mice [Genetics]

2017-01-06T12:50:12-08:00

CRISPR/Cas9 is becoming an increasingly important tool to functionally annotate genomes. However, because genome-wide CRISPR libraries are mostly constructed in lentiviral vectors, in vivo applications are severely limited as a result of difficulties in delivery. Here, we examined the piggyBac (PB) transposon as an alternative vehicle to deliver a guide...



CRYPTOCHROME mediates behavioral executive choice in response to UV light [Neuroscience]

2017-01-06T12:50:12-08:00

Drosophila melanogaster CRYPTOCHROME (CRY) mediates behavioral and electrophysiological responses to blue light coded by circadian and arousal neurons. However, spectroscopic and biochemical assays of heterologously expressed CRY suggest that CRY may mediate functional responses to UV-A (ultraviolet A) light as well. To determine the relative contributions of distinct phototransduction systems,...



Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas [Medical Sciences]

2017-01-06T12:50:12-08:00

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778–786) generated by a focal deletion-driven alternative splicing mechanism as...



Urban sustainability in an age of enduring inequalities: Advancing theory and ecometrics for the 21st-century city [Perspectives]

2017-01-06T12:50:12-08:00

The environmental fragility of cities under advanced urbanization has motivated extensive efforts to promote the sustainability of urban ecosystems and physical infrastructures. Less attention has been devoted to neighborhood inequalities and fissures in the civic infrastructure that potentially challenge social sustainability and the capacity of cities to collectively address environmental...



Steroid signaling in mature follicles is important for Drosophila ovulation [Developmental Biology]

2017-01-09T12:10:20-08:00

Although ecdysteroid signaling regulates multiple steps in oogenesis, it is not known whether it regulates Drosophila ovulation, a process involving a matrix metalloproteinase-dependent follicle rupture. In this study, we demonstrated that ecdysteroid signaling is operating in mature follicle cells to control ovulation. Moreover, knocking down shade (shd), encoding the monooxygenase...



Centuries of thermal sea-level rise due to anthropogenic emissions of short-lived greenhouse gases [Sustainability Science]

2017-01-09T12:10:21-08:00

Mitigation of anthropogenic greenhouse gases with short lifetimes (order of a year to decades) can contribute to limiting warming, but less attention has been paid to their impacts on longer-term sea-level rise. We show that short-lived greenhouse gases contribute to sea-level rise through thermal expansion (TSLR) over much longer time...



Real-time measurement of small molecules directly in awake, ambulatory animals [Medical Sciences]

2017-01-09T12:10:22-08:00

The development of a technology capable of tracking the levels of drugs, metabolites, and biomarkers in the body continuously and in real time would advance our understanding of health and our ability to detect and treat disease. It would, for example, enable therapies guided by high-resolution, patient-specific pharmacokinetics (including feedback-controlled...



All-carbon-based porous topological semimetal for Li-ion battery anode material [Physics]

2017-01-09T12:10:22-08:00

Topological state of matter and lithium batteries are currently two hot topics in science and technology. Here we combine these two by exploring the possibility of using all-carbon-based porous topological semimetal for lithium battery anode material. Based on density-functional theory and the cluster-expansion method, we find that the recently identified...



Uranium(IV) adsorption by natural organic matter in anoxic sediments [Environmental Sciences]

2017-01-09T12:10:22-08:00

Uranium is an important carbon-free fuel source and environmental contaminant that accumulates in the tetravalent state, U(IV), in anoxic sediments, such as ore deposits, marine basins, and contaminated aquifers. However, little is known about the speciation of U(IV) in low-temperature geochemical environments, inhibiting the development of a conceptual model of...



Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage [Biochemistry]

2017-01-09T12:10:23-08:00

Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS...



Soluble klotho binds monosialoganglioside to regulate membrane microdomains and growth factor signaling [Medical Sciences]

2017-01-09T12:10:23-08:00

Soluble klotho, the shed ectodomain of the antiaging membrane protein α-klotho, is a pleiotropic endocrine/paracrine factor with no known receptors and poorly understood mechanism of action. Soluble klotho down-regulates growth factor-driven PI3K signaling, contributing to extension of lifespan, cardioprotection, and tumor inhibition. Here we show that soluble klotho binds membrane...



First-passage time approach to controlling noise in the timing of intracellular events [Applied Mathematics]

2017-01-09T12:10:24-08:00

In the noisy cellular environment, gene products are subject to inherent random fluctuations in copy numbers over time. How cells ensure precision in the timing of key intracellular events despite such stochasticity is an intriguing fundamental problem. We formulate event timing as a first-passage time problem, where an event is...



Genomic targeting of epigenetic probes using a chemically tailored Cas9 system [Biochemistry]

2017-01-09T12:10:24-08:00

Recent advances in the field of programmable DNA-binding proteins have led to the development of facile methods for genomic localization of genetically encodable entities. Despite the extensive utility of these tools, locus-specific delivery of synthetic molecules remains limited by a lack of adequate technologies. Here we combine the flexibility of...



Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism [Immunology and Inflammation]

2017-01-09T12:10:25-08:00

Three-prime repair exonuclease 1 knockout (Trex1−/−) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase–stimulator of interferon genes–TANK-binding kinase–interferon regulatory factor 3 (cGAS–STING–TBK1–IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying...



Toxic PRn poly-dipeptides encoded by the C9orf72 repeat expansion block nuclear import and export [Biochemistry]

2017-01-09T12:10:26-08:00

The toxic proline:arginine (PRn) poly-dipeptide encoded by the (GGGGCC)n repeat expansion in the C9orf72 form of heritable amyotrophic lateral sclerosis (ALS) binds to the central channel of the nuclear pore and inhibits the movement of macromolecules into and out of the nucleus. The PRn poly-dipeptide binds to polymeric forms of...



Quality control mechanisms exclude incorrect polymerases from the eukaryotic replication fork [Biochemistry]

2017-01-09T12:10:26-08:00

The eukaryotic genome is primarily replicated by two DNA polymerases, Pol ε and Pol δ, that function on the leading and lagging strands, respectively. Previous studies have established recruitment mechanisms whereby Cdc45-Mcm2-7-GINS (CMG) helicase binds Pol ε and tethers it to the leading strand, and PCNA (proliferating cell nuclear antigen)...



Ambivalent stereotypes link to peace, conflict, and inequality across 38 nations [Psychological and Cognitive Sciences]

2017-01-09T12:10:27-08:00

A cross-national study, 49 samples in 38 nations (n = 4,344), investigates whether national peace and conflict reflect ambivalent warmth and competence stereotypes: High-conflict societies (Pakistan) may need clearcut, unambivalent group images distinguishing friends from foes. Highly peaceful countries (Denmark) also may need less ambivalence because most groups occupy the...



Global scenarios of urban density and its impacts on building energy use through 2050 [Sustainability Science]

2017-01-09T12:10:28-08:00

Although the scale of impending urbanization is well-acknowledged, we have a limited understanding of how urban forms will change and what their impact will be on building energy use. Using both top-down and bottom-up approaches and scenarios, we examine building energy use for heating and cooling. Globally, the energy use...



Exposure to inequality affects support for redistribution [Political Sciences]

2017-01-09T12:10:28-08:00

The distribution of wealth in the United States and countries around the world is highly skewed. How does visible economic inequality affect well-off individuals’ support for redistribution? Using a placebo-controlled field experiment, I randomize the presence of poverty-stricken people in public spaces frequented by the affluent. Passersby were asked to...



Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors [Immunology and Inflammation]

2017-01-09T12:10:29-08:00

Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT...



Iconic photographs and the ebb and flow of empathic response to humanitarian disasters [Psychological and Cognitive Sciences]

2017-01-10T09:23:58-08:00

The power of visual imagery is well known, enshrined in such familiar sayings as “seeing is believing” and “a picture is worth a thousand words.” Iconic photos stir our emotions and transform our perspectives about life and the world in which we live. On September 2, 2015, photographs of a...



Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site [Microbiology]

2017-01-10T09:23:59-08:00

Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10,...



Different clades and traits yield similar grassland functional responses [Ecology]

2017-01-10T09:23:59-08:00

Plant functional traits are viewed as key to predicting important ecosystem and community properties across resource gradients within and among biogeographic regions. Vegetation dynamics and ecosystem processes, such as aboveground net primary productivity (ANPP), are increasingly being modeled as a function of the quantitative traits of species, which are used...



Revealing nonclassicality beyond Gaussian states via a single marginal distribution [Physics]

2017-01-11T12:02:44-08:00

A standard method to obtain information on a quantum state is to measure marginal distributions along many different axes in phase space, which forms a basis of quantum-state tomography. We theoretically propose and experimentally demonstrate a general framework to manifest nonclassicality by observing a single marginal distribution only, which provides...



Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma [Cell Biology]

2017-01-12T12:23:28-08:00

Most clear cell renal carcinomas (ccRCCs) are initiated by somatic inactivation of the VHL tumor suppressor gene. The VHL gene product, pVHL, is the substrate recognition unit of an ubiquitin ligase that targets the HIF transcription factor for proteasomal degradation; inappropriate expression of HIF target genes drives renal carcinogenesis. Loss...



Imaging proteins at the single-molecule level [Biophysics and Computational Biology]

2017-01-13T12:12:09-08:00

Imaging single proteins has been a long-standing ambition for advancing various fields in natural science, as for instance structural biology, biophysics, and molecular nanotechnology. In particular, revealing the distinct conformations of an individual protein is of utmost importance. Here, we show the imaging of individual proteins and protein complexes by...



Nrf2 mitigates LRRK2- and {alpha}-synuclein-induced neurodegeneration by modulating proteostasis [Neuroscience]

2016-12-27T09:51:23-08:00

Mutations in leucine-rich repeat kinase 2 (LRRK2) and α-synuclein lead to Parkinson’s disease (PD). Disruption of protein homeostasis is an emerging theme in PD pathogenesis, making mechanisms to reduce the accumulation of misfolded proteins an attractive therapeutic strategy. We determined if activating nuclear factor erythroid 2-related factor (Nrf2), a potential...



Dynamic PIN-FORMED auxin efflux carrier phosphorylation at the plasma membrane controls auxin efflux-dependent growth [Plant Biology]

2017-01-17T12:06:49-08:00

The directional distribution of the phytohormone auxin is essential for plant development. Directional auxin transport is mediated by the polarly distributed PIN-FORMED (PIN) auxin efflux carriers. We have previously shown that efficient PIN1-mediated auxin efflux requires activation through phosphorylation at the four serines S1–S4 in Arabidopsis thaliana. The Brefeldin A...



Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host-pathogen transcriptomes [Microbiology]

2017-01-17T12:06:50-08:00

Pathogenic bacteria need to rapidly adjust their virulence and fitness program to prevent eradication by the host. So far, underlying adaptation processes that drive pathogenesis have mostly been studied in vitro, neglecting the true complexity of host-induced stimuli acting on the invading pathogen. In this study, we developed an unbiased...



Spectroscopic evidence for bulk-band inversion and three-dimensional massive Dirac fermions in ZrTe5 [Applied Physical Sciences]

2017-01-17T12:06:50-08:00

Three-dimensional topological insulators (3D TIs) represent states of quantum matters in which surface states are protected by time-reversal symmetry and an inversion occurs between bulk conduction and valence bands. However, the bulk-band inversion, which is intimately tied to the topologically nontrivial nature of 3D Tis, has rarely been investigated by...



One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen [Biophysics and Computational Biology]

2017-01-17T12:06:50-08:00

Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance, Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in...



Human NF-{kappa}B repressing factor acts as a stress-regulated switch for ribosomal RNA processing and nucleolar homeostasis surveillance [Cell Biology]

2017-01-17T12:06:51-08:00

The nucleolus, a dynamic nuclear compartment long regarded as the cell ribosome factory, is emerging as an important player in the regulation of cell survival and recovery from stress. In larger eukaryotes, the stress-induced transcriptional response is mediated by a family of heat-shock transcription factors. Among these, HSF1, considered the...



Biophysical properties of the clinical-stage antibody landscape [Applied Biological Sciences]

2017-01-17T12:06:51-08:00

Antibodies are a highly successful class of biological drugs, with over 50 such molecules approved for therapeutic use and hundreds more currently in clinical development. Improvements in technology for the discovery and optimization of high-potency antibodies have greatly increased the chances for finding binding molecules with desired biological properties; however,...



Role of CCT chaperonin in the disassembly of mitotic checkpoint complexes [Biochemistry]

2017-01-17T12:06:51-08:00

The mitotic checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. When this checkpoint is active, a mitotic checkpoint complex (MCC), composed of the checkpoint proteins Mad2, BubR1, Bub3, and Cdc20, is assembled. MCC inhibits the ubiquitin ligase anaphase promoting complex/cyclosome...



Myofibril breakdown during atrophy is a delayed response requiring the transcription factor PAX4 and desmin depolymerization [Cell Biology]

2017-01-17T12:06:52-08:00

A hallmark of muscle atrophy is the excessive degradation of myofibrillar proteins primarily by the ubiquitin proteasome system. In mice, during the rapid muscle atrophy induced by fasting, the desmin cytoskeleton and the attached Z-band–bound thin filaments are degraded after ubiquitination by the ubiquitin ligase tripartite motif-containing protein 32 (Trim32)....



{beta}-Catenin haploinsufficiency promotes mammary tumorigenesis in an ErbB2-positive basal breast cancer model [Cell Biology]

2017-01-17T12:06:52-08:00

Aberrant activation of β-catenin through its activity as a transcription factor has been observed in a large proportion of human malignancies. Despite the improved understanding of the β-catenin signaling pathway over the past three decades, attempts to develop therapies targeting β-catenin remain challenging, and none of these targeted therapies have...



Stress granule-associated protein G3BP2 regulates breast tumor initiation [Cell Biology]

2017-01-17T12:06:52-08:00

Breast tumors contain tumorigenic cancer cells, termed “tumor-initiating cells” (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small...



Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity [Physiology]

2017-01-17T12:06:53-08:00

Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial...



Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism [Physiology]

2017-01-17T12:06:53-08:00

Cholesterol is important for normal brain function. The brain synthesizes its own cholesterol, presumably in astrocytes. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in sterol regulatory element-binding protein 2 (SREBP2)-regulated transcription. Here we show that coculture of control astrocytes with neurons enhances...



Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage [Evolution]

2017-01-17T12:06:54-08:00

Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence...



Harmonic template neurons in primate auditory cortex underlying complex sound processing [Neuroscience]

2017-01-17T12:06:54-08:00

Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the auditory system extracts harmonic structures embedded in complex sounds and uses them to form a coherent unitary entity is not fully understood. Despite the prevalence of sounds rich in harmonic structures in our everyday hearing environment, it...



Eight-coordinate fluoride in a silicate double-four-ring [Chemistry]

2017-01-17T12:06:54-08:00

Fluoride, nature’s smallest anion, is capable of covalently coordinating to eight silicon atoms. The setting is a simple and common motif in zeolite chemistry: the box-shaped silicate double-four-ring (D4R). Fluoride seeks its center. It is the strain of box deformation that keeps fluoride in the middle of the box, and...



Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria [Medical Sciences]

2017-01-17T12:06:55-08:00

The abundance of epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), the most frequent cardiac arrhythmia. However, both the origin and the factors involved in EAT expansion are unknown. Here, we found that adult human atrial epicardial cells were highly adipogenic through an epithelial–mesenchymal transition both in vitro...



The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events [Evolution]

2017-01-17T12:06:55-08:00

There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site–leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture...



Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome [Biochemistry]

2017-01-17T12:06:56-08:00

The physiological role of LepA, a paralog of EF-G found in all bacteria, has been a mystery for decades. Here, we show that LepA functions in ribosome biogenesis. In cells lacking LepA, immature 30S particles accumulate. Four proteins are specifically underrepresented in these particles—S3, S10, S14, and S21—all of which...



Human transposon insertion profiling: Analysis, visualization and identification of somatic LINE-1 insertions in ovarian cancer [Genetics]

2017-01-17T12:06:56-08:00

Mammalian genomes are replete with interspersed repeats reflecting the activity of transposable elements. These mobile DNAs are self-propagating, and their continued transposition is a source of both heritable structural variation as well as somatic mutation in human genomes. Tailored approaches to map these sequences are useful to identify insertion alleles....



Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish [Developmental Biology]

2017-01-17T12:06:56-08:00

Regeneration requires cells to regulate proliferation and patterning according to their spatial position. Positional memory is a property that enables regenerating cells to recall spatial information from the uninjured tissue. Positional memory is hypothesized to rely on gradients of molecules, few of which have been identified. Here, we quantified the...



Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation [Biophysics and Computational Biology]

2017-01-17T12:06:57-08:00

The eukaryotic CMG (Cdc45, Mcm2–7, GINS) helicase consists of the Mcm2–7 hexameric ring along with five accessory factors. The Mcm2–7 heterohexamer, like other hexameric helicases, is shaped like a ring with two tiers, an N-tier ring composed of the N-terminal domains, and a C-tier of C-terminal domains; the C-tier contains...



Combating Parkinson’s disease-associated toxicity by modulating proteostasis [Commentaries]

2017-01-17T12:06:57-08:00

The incidence of age-associated neurodegenerative disease is growing rapidly, and it is expected to triple by 2050 (1). Currently, there are no cures or treatments that significantly modify disease progression. As researchers develop an in-depth understanding of the mechanisms of neurodegeneration, common features across different diseases are becoming apparent. Chief...



Uncovering hidden variation in polyploid wheat [Agricultural Sciences]

2017-01-17T12:06:57-08:00

Comprehensive reverse genetic resources, which have been key to understanding gene function in diploid model organisms, are missing in many polyploid crops. Young polyploid species such as wheat, which was domesticated less than 10,000 y ago, have high levels of sequence identity among subgenomes that mask the effects of recessive...



Recognition of protein-linked glycans as a determinant of peptidase activity [Biochemistry]

2017-01-17T12:06:58-08:00

The vast majority of proteins are posttranslationally altered, with the addition of covalently linked sugars (glycosylation) being one of the most abundant modifications. However, despite the hydrolysis of protein peptide bonds by peptidases being a process essential to all life on Earth, the fundamental details of how peptidases accommodate posttranslational...



High Coulombic efficiency aluminum-ion battery using an AlCl3-urea ionic liquid analog electrolyte [Chemistry]

2017-01-17T12:06:58-08:00

In recent years, impressive advances in harvesting renewable energy have led to a pressing demand for the complimentary energy storage technology. Here, a high Coulombic efficiency (∼99.7%) Al battery is developed using earth-abundant aluminum as the anode, graphite as the cathode, and a cheap ionic liquid analog electrolyte made from...



Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance [Plant Biology]

2017-01-17T12:06:58-08:00

Soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the...



A natural product inhibits the initiation of {alpha}-synuclein aggregation and suppresses its toxicity [Neuroscience]

2017-01-17T12:06:59-08:00

The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles,...



Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner [Immunology and Inflammation]

2017-01-17T12:06:59-08:00

Necroptosis is a physiological cell suicide mechanism initiated by receptor-interacting protein kinase-3 (RIPK3) phosphorylation of mixed-lineage kinase domain-like protein (MLKL), which results in disruption of the plasma membrane. Necroptotic cell lysis, and resultant release of proinflammatory mediators, is thought to cause inflammation in necroptotic disease models. However, we previously showed...



Prion replication without host adaptation during interspecies transmissions [Microbiology]

2017-01-17T12:06:59-08:00

Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrPC) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in...



Repair shielding of platinum-DNA lesions in testicular germ cell tumors by high-mobility group box protein 4 imparts cisplatin hypersensitivity [Biochemistry]

2017-01-17T12:07:00-08:00

Cisplatin is the most commonly used anticancer drug for the treatment of testicular germ cell tumors (TGCTs). The hypersensitivity of TGCTs to cisplatin is a subject of widespread interest. Here, we show that high-mobility group box protein 4 (HMGB4), a protein preferentially expressed in testes, uniquely blocks excision repair of...



{alpha}-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation [Neuroscience]

2017-01-17T12:07:00-08:00

The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson’s disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy...



Measurement of cortical elasticity in Drosophila melanogaster embryos using ferrofluids [Developmental Biology]

2017-01-17T12:07:00-08:00

Many models of morphogenesis are forced to assume specific mechanical properties of cells, because the actual mechanical properties of living tissues are largely unknown. Here, we measure the rheology of epithelial cells in the cellularizing Drosophila embryo by injecting magnetic particles and studying their response to external actuation. We establish...



Thermal-driven domain and cargo transport in lipid membranes [Chemistry]

2017-01-17T12:07:01-08:00

Domain migration is observed on the surface of ternary giant unilamellar vesicles held in a temperature gradient in conditions where they exhibit coexistence of two liquid phases. The migration localizes domains to the hot side of the vesicle, regardless of whether the domain is composed of the more ordered or...



Catalytic oxidation of Li2S on the surface of metal sulfides for Li-S batteries [Chemistry]

2017-01-17T12:07:01-08:00

Polysulfide binding and trapping to prevent dissolution into the electrolyte by a variety of materials has been well studied in Li−S batteries. Here we discover that some of those materials can play an important role as an activation catalyst to facilitate oxidation of the discharge product, Li2S, back to the...



An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma [Medical Sciences]

2017-01-17T12:07:01-08:00

Circulating tumor cells (CTCs) are shed into the bloodstream by invasive cancers, but the difficulty inherent in identifying these rare cells by microscopy has precluded their routine use in monitoring or screening for cancer. We recently described a high-throughput microfluidic CTC-iChip, which efficiently depletes hematopoietic cells from blood specimens and...



Bilateral recruitment of prefrontal cortex in working memory is associated with task demand but not with age [Neuroscience]

2017-01-17T12:07:02-08:00

Elderly adults may master challenging cognitive demands by additionally recruiting the cross-hemispheric counterparts of otherwise unilaterally engaged brain regions, a strategy that seems to be at odds with the notion of lateralized functions in cerebral cortex. We wondered whether bilateral activation might be a general coping strategy that is independent...



Unlocking Tn3-family transposase activity in vitro unveils an asymetric pathway for transposome assembly [Biochemistry]

2017-01-17T12:07:02-08:00

The Tn3 family is a widespread group of replicative transposons that are notorious for their contribution to the dissemination of antibiotic resistance and the emergence of multiresistant pathogens worldwide. The TnpA transposase of these elements catalyzes DNA breakage and rejoining reactions required for transposition. It also is responsible for target...



Iron isotopes reveal distinct dissolved iron sources and pathways in the intermediate versus deep Southern Ocean [Environmental Sciences]

2017-01-17T12:07:02-08:00

As an essential micronutrient, iron plays a key role in oceanic biogeochemistry. It is therefore linked to the global carbon cycle and climate. Here, we report a dissolved iron (DFe) isotope section in the South Atlantic and Southern Ocean. Throughout the section, a striking DFe isotope minimum (light iron) is...



Zero-index structures as an alternative platform for quantum optics [Applied Physical Sciences]

2017-01-17T12:07:03-08:00

Vacuum fluctuations are one of the most distinctive aspects of quantum optics, being the trigger of multiple nonclassical phenomena. Thus, platforms like resonant cavities and photonic crystals that enable the inhibition and manipulation of vacuum fluctuations have been key to our ability to control light–matter interactions (e.g., the decay of...



Elemental sulfur aerosol-forming mechanism [Earth, Atmospheric, and Planetary Sciences]

2017-01-17T12:07:03-08:00

Elemental sulfur aerosols are ubiquitous in the atmospheres of Venus, ancient Earth, and Mars. There is now an evolving body of evidence suggesting that these aerosols have also played a role in the evolution of early life on Earth. However, the exact details of their formation mechanism remain an open...



Reply to Datchi et al.: Recovered phase CO2-V at low temperature and a newly predicted 3D-extended CO2 phase [Letters (Online Only)]

2017-01-17T12:36:07-08:00

In their letter, Datchi et al. (1) question (i) the recoverability of CO2-V at low pressure and (ii) the identification of CO2-V as a Pna21 structure in our paper (2). We argue below that both of Datchi et al.’s (1) claims are incorrect. Regarding Datchi et al.’s (1) first claim,...



Polymeric phase V of carbon dioxide has not been recovered at ambient pressure and has a unique structure [Letters (Online Only)]

2017-01-17T12:43:13-08:00

In their high-pressure study of solid CO2, Yong et al. (1) claim: (i) that they recovered the polymeric phase V (CO2-V) at ambient pressure and 191 K, and (ii) that CO2-V may exist in different crystal structures. We demonstrate below that neither of these claims is supported by their data....



COX2/mPGES1/PGE2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells [Immunology and Inflammation]

2017-01-17T12:06:32-08:00

In recent years, it has been established that programmed cell death protein ligand 1 (PD-L1)–mediated inhibition of activated PD-1+ T lymphocytes plays a major role in tumor escape from immune system during cancer progression. Lately, the anti–PD-L1 and –PD-1 immune therapies have become an important tool for treatment of advanced...



Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry [Biochemistry]

2017-01-17T12:06:33-08:00

Apolipoprotein E (apoE) plays a critical role in cholesterol transport in both peripheral circulation and brain. Human apoE is a polymorphic 299-residue protein in which the less common E4 isoform differs from the major E3 isoform only by a C112R substitution. ApoE4 interacts with lipoprotein particles and with the amyloid-β...



Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging [Immunology and Inflammation]

2017-01-17T12:06:33-08:00

The elderly have reduced humoral immunity, as manifested by increased susceptibility to infections and impaired vaccine responses. To investigate the effects of aging on B-cell receptor (BCR) repertoire evolution during an immunological challenge, we used a phylogenetic distance metric to analyze Ig heavy-chain transcript sequences in both young and elderly...



Do guanidinium and tetrapropylammonium ions specifically interact with aromatic amino acid side chains? [Biophysics and Computational Biology]

2017-01-17T12:06:34-08:00

Many ions are known to affect the activity, stability, and structural integrity of proteins. Although this effect can be generally attributed to ion-induced changes in forces that govern protein folding, delineating the underlying mechanism of action still remains challenging because it requires assessment of all relevant interactions, such as ion–protein,...



Myosin-driven transport network in plants [Cell Biology]

2017-01-17T12:06:34-08:00

We investigate the myosin XI-driven transport network in Arabidopsis using protein–protein interaction, subcellular localization, gene knockout, and bioinformatics analyses. The two major groups of nodes in this network are myosins XI and their membrane-anchored receptors (MyoB) that, together, drive endomembrane trafficking and cytoplasmic streaming in the plant cells. The network...



Comparative genomics reveals convergent evolution between the bamboo-eating giant and red pandas [Evolution]

2017-01-17T12:06:34-08:00

Phenotypic convergence between distantly related taxa often mirrors adaptation to similar selective pressures and may be driven by genetic convergence. The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens) belong to different families in the order Carnivora, but both have evolved a specialized bamboo diet and adaptive pseudothumb, representing...



Biosynthesis of the microtubule-destabilizing diterpene pseudolaric acid B from golden larch involves an unusual diterpene synthase [Biochemistry]

2017-01-17T12:06:35-08:00

The diversity of small molecules formed via plant diterpene metabolism offers a rich source of known and potentially new biopharmaceuticals. Among these, the microtubule-destabilizing activity of pseudolaric acid B (PAB) holds promise for new anticancer agents. PAB is found, perhaps uniquely, in the coniferous tree golden larch (Pseudolarix amabilis, Pxa)....



Molecular mechanism underlying ȷuvenile hormone-mediated repression of precocious larval-adult metamorphosis [Developmental Biology]

2017-01-17T12:06:35-08:00

Juvenile hormone (JH) represses precocious metamorphosis of larval to pupal and adult transitions in holometabolous insects. The early JH-inducible gene Krüppel homolog 1 (Kr-h1) plays a key role in the repression of metamorphosis as a mediator of JH action. Previous studies demonstrated that Kr-h1 inhibits precocious larval–pupal transition in immature...



In situ structure of trypanosomal ATP synthase dimer reveals a unique arrangement of catalytic subunits [Biophysics and Computational Biology]

2017-01-17T12:06:35-08:00

We used electron cryotomography and subtomogram averaging to determine the in situ structures of mitochondrial ATP synthase dimers from two organisms belonging to the phylum euglenozoa: Trypanosoma brucei, a lethal human parasite, and Euglena gracilis, a photosynthetic protist. At a resolution of 32.5 Å and 27.5 Å, respectively, the two...



Scene-selective coding by single neurons in the human parahippocampal cortex [Psychological and Cognitive Sciences]

2017-01-17T12:06:35-08:00

Imaging, electrophysiological, and lesion studies have shown a relationship between the parahippocampal cortex (PHC) and the processing of spatial scenes. Our present knowledge of PHC, however, is restricted to the macroscopic properties and dynamics of bulk tissue; the behavior and selectivity of single parahippocampal neurons remains largely unknown. In this...



Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity [Immunology and Inflammation]

2017-01-17T12:06:36-08:00

Although immunotherapy by PD-1 blockade has dramatically improved the survival rate of cancer patients, further improvement in efficacy is required to reduce the fraction of less sensitive patients. In mouse models of PD-1 blockade therapy, we found that tumor-reactive cytotoxic T lymphocytes (CTLs) in draining lymph nodes (DLNs) carry increased...



Fragility of the provision of local public goods to private and collective risks [Sustainability Science]

2017-01-17T12:06:36-08:00

Smallholder agricultural systems, strongly dependent on water resources and investments in shared infrastructure, make a significant contribution to food security in developing countries. These communities are being increasingly integrated into the global economy and are exposed to new global climate-related risks that may affect their willingness to cooperate in community-level...



Holocene ENSO-related cyclic storms recorded by magnetic minerals in speleothems of central China [Environmental Sciences]

2017-01-17T12:06:36-08:00

Extreme hydrologic events such as storms and floods have the potential to severely impact modern human society. However, the frequency of storms and their underlying mechanisms are limited by a paucity of suitable proxies, especially in inland areas. Here we present a record of speleothem magnetic minerals to reconstruct paleoprecipitation,...



Correction for Melo et al., Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing [Corrections]

2017-01-17T12:06:37-08:00

MEDICAL SCIENCES Correction for “Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing,” by Sonia Melo, Alberto Villanueva, Catia Moutinho, Veronica Davalos, Riccardo Spizzo, Cristina Ivan, Simona Rossi, Fernando Setien, Oriol Casanovas, Laia Simo-Riudalbas, Javier Carmona, Jordi Carrere, August Vidal, Alvaro...



Molecular imaging of biological systems with a clickable dye in the broad 800- to 1,700-nm near-infrared window [Biochemistry]

2017-01-17T12:06:37-08:00

Fluorescence imaging multiplicity of biological systems is an area of intense focus, currently limited to fluorescence channels in the visible and first near-infrared (NIR-I; ∼700–900 nm) spectral regions. The development of conjugatable fluorophores with longer wavelength emission is highly desired to afford more targeting channels, reduce background autofluorescence, and achieve...



Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease [Biophysics and Computational Biology]

2017-01-17T12:06:37-08:00

Although it has been known for more than 60 years that the cause of sickle cell disease is polymerization of a hemoglobin mutant, hydroxyurea is the only drug approved for treatment by the US Food and Drug Administration. This drug, however, is only partially successful, and the discovery of additional...



Competition of calcified calmodulin N lobe and PIP2 to an LQT mutation site in Kv7.1 channel [Physiology]

2017-01-17T12:06:38-08:00

Voltage-gated potassium 7.1 (Kv7.1) channel and KCNE1 protein coassembly forms the slow potassium current IKS that repolarizes the cardiac action potential. The physiological importance of the IKS channel is underscored by the existence of mutations in human Kv7.1 and KCNE1 genes, which cause cardiac arrhythmias, such as the long-QT syndrome...



Ontogenetic and life history trait changes associated with convergent ecological specializations in extinct ungulate mammals [Evolution]

2017-01-17T12:06:38-08:00

Investigating life history traits in mammals is crucial to understand their survival in changing environments. However, these parameters are hard to estimate in a macroevolutionary context. Here we show that the use of dental ontogenetic parameters can provide clues to better understand the adaptive nature of phenotypic traits in extinct...



Modification of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance [Immunology and Inflammation]

2017-01-17T12:06:38-08:00

Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in some, MMc magnitude was enough...



Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing [Plant Biology]

2017-01-17T12:06:38-08:00

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry...



Continual renewal and replication of persistent Leishmania major parasites in concomitantly immune hosts [Microbiology]

2017-01-17T12:06:39-08:00

In most natural infections or after recovery, small numbers of Leishmania parasites remain indefinitely in the host. Persistent parasites play a vital role in protective immunity against disease pathology upon reinfection through the process of concomitant immunity, as well as in transmission and reactivation, yet are poorly understood. A key...



Utility-value intervention with parents increases students’ STEM preparation and career pursuit [Psychological and Cognitive Sciences]

2017-01-17T12:06:39-08:00

During high school, developing competence in science, technology, engineering, and mathematics (STEM) is critically important as preparation to pursue STEM careers, yet students in the United States lag behind other countries, ranking 35th in mathematics and 27th in science achievement internationally. Given the importance of STEM careers as drivers of...