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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]

2017-10-17T09:41:40-07:00

Genome editing and glaucoma Genome editing treats glaucoma in mouse model. Image courtesy of iStockphoto/Natali_Mis. Mutations in the myocilin gene (MYOC) can lead to the misfolding and toxic buildup of the encoded protein in the trabecular meshwork (TM), a tissue that regulates pressure inside the eyes, triggering the death of...



Surfing of bacterial droplets: Bacillus subtilis sliding revisited [Physical Sciences]

2017-10-17T09:41:41-07:00

Hennes et al. (1) report on the collective slipping of Bacillus subtilis colonies across the agar surface, termed “colony surfing.” We read this article with great interest. However, we understand that specific points require a more detailed discussion. We would like to highlight complementary biological observations on this area previously...



Reply to Kovacs et al.: Surfing or sliding: The act of naming and its implications [Physical Sciences]

2017-10-17T09:41:41-07:00

Kovács et al. (1) have greatly contributed to the characterization of “sliding” (2–4), a flagella-independent, “passive type of [bacterial] movement, [...] powered by the pushing force of dividing cells and additional factors facilitating the expansion over surfaces” (2). They suggest that bacterial surfing (5) should be described by the same...



Purported fragile-to-Arrhenius crossover in squalane [Physical Sciences]

2017-10-17T09:41:41-07:00

Jadhao and Robbins (1) claim to have discovered a crossover from Vogel–Fulcher–Tammann (VFT) to Arrhenius in squalane occurring at a viscosity of μ=1,000 Pa⋅s using extrapolation of the simple Eyring equation to the limiting low-shear viscosity from nonequilibrium molecular dynamic simulation at high shear rates. Stickel et al. (2) introduced...



Reply to Bair: Crossover to Arrhenius behavior at high viscosities in squalane [Physical Sciences]

2017-10-17T09:41:41-07:00

As noted in our paper (1), values of the Newtonian viscosity, ηN, of squalane from Deegan et al. (2) are well fit by the Vogel–Fulcher–Tammann (VFT) equation over the measured range of temperature, T. This is entirely consistent with the fairly straight line shown for their data in the Stickel...



No experimental Fermi surface measurements have been reported or made on low-temperature martensitic lithium [Physical Sciences]

2017-10-17T09:41:41-07:00

Elatresh et al. (1) (ECAHDB) claim that the low-temperature martensitic structure of lithium “is not the heretofore assigned 9R.” This is based on comparing results of Fermi surface calculations to de Haas–van Alphen (dHvA) data from Springford and coworkers (2, 3). We note that Springford’s group took extensive steps to...



Reply to Martinez-Canales et al.: The structure(s) of lithium at low temperatures [Physical Sciences]

2017-10-17T09:41:41-07:00

In our recent article (1), we proposed that Fermiology measurements can be used as a complementary probe for determining the low-temperature state of Li. In a letter (2) criticizing our conclusions, Martinez-Canales, Loa, and Ackland (MLA) claim (i) that “obtaining dHvA signals from martensitic microstructures is usually impossible” and (ii)...



Profile of Lora V. Hooper [Profiles]

2017-10-17T09:41:40-07:00

Lora Hooper, a professor of immunology at the University of Texas Southwestern Medical Center, describes her career as “a random walk in science.” Her pursuit of science was aided by inspirational mentors who pointed her in directions she might not otherwise have taken. These unexpected turns ultimately led her to...



Synthetic genome engineering gets infectious [Microbiology]

2017-10-17T09:41:40-07:00

Since the start of this century, a handful of research groups have pursued the synthesis and large-scale engineering of genomes. Work on synthetic genomes has seen the field scale-up from the full synthesis of the small poliovirus genome (2002) (1), to a complete working synthetic bacterial genome (2010) (2), and...



Trees harness the power of microbes to survive climate change [Ecology]

2017-10-17T09:41:40-07:00

Microorganisms are the most abundant and diverse taxa on Earth. They have the ability to tolerate extreme environments, catalyze a range of metabolic functions, and rapidly evolve in response to changing environmental conditions. Imagine if plants and animals could harness these powers. In fact, microorganisms confer numerous benefits to plants...



NS1 is the fluid for “flu-transmission” [Microbiology]

2017-10-17T09:41:40-07:00

The development of modern medicine has allowed us to conquer numerous infectious diseases; however, we human beings constantly face threats from novel infectious diseases that have been previously unrecognized. These so-called “emerging infectious diseases” are often caused by zoonotic pathogens, which mostly originate in wild animals (1, 2). Human diseases,...



Mechanistic insights into electrochemical reduction of CO2 over Ag using density functional theory and transport models [Applied Physical Sciences]

2017-10-17T09:41:41-07:00

Electrochemical reduction of CO2 using renewable sources of electrical energy holds promise for converting CO2 to fuels and chemicals. Since this process is complex and involves a large number of species and physical phenomena, a comprehensive understanding of the factors controlling product distribution is required. While the most plausible reaction...



Evolutionary dynamics of language systems [Anthropology]

2017-10-17T09:41:41-07:00

Understanding how and why language subsystems differ in their evolutionary dynamics is a fundamental question for historical and comparative linguistics. One key dynamic is the rate of language change. While it is commonly thought that the rapid rate of change hampers the reconstruction of deep language relationships beyond 6,000–10,000 y,...



Cavity hydration dynamics in cytochrome c oxidase and functional implications [Biophysics and Computational Biology]

2017-10-17T09:41:41-07:00

Cytochrome c oxidase (CcO) is a transmembrane protein that uses the free energy of O2 reduction to generate the proton concentration gradient across the membrane. The regulation of competitive proton transfer pathways has been established to be essential to the vectorial transport efficiency of CcO, yet the underlying mechanism at...



Visualizing nuclear RNAi activity in single living human cells [Cell Biology]

2017-10-17T09:41:41-07:00

Nuclear RNA interference (RNAi) is mediated by the canonical RNAi machinery and can lead to transcriptional silencing, transcriptional activation, or modulation of alternative splicing patterns. These effects transpire through changes in histone and DNA modifications via RNAi-mediated recruitment of chromatin-modifying enzymes. To prove that nuclear RNAi occurs and modulates transcription...



Cytoplasmic MTOCs control spindle orientation for asymmetric cell division in plants [Cell Biology]

2017-10-17T09:41:41-07:00

Proper orientation of the cell division axis is critical for asymmetric cell divisions that underpin cell differentiation. In animals, centrosomes are the dominant microtubule organizing centers (MTOC) and play a pivotal role in axis determination by orienting the mitotic spindle. In land plants that lack centrosomes, a critical role of...



Period2 3'-UTR and microRNA-24 regulate circadian rhythms by repressing PERIOD2 protein accumulation [Genetics]

2017-10-17T09:41:41-07:00

We previously created two PER2::LUCIFERASE (PER2::LUC) circadian reporter knockin mice that differ only in the Per2 3′-UTR region: Per2::Luc, which retains the endogenous Per2 3′-UTR and Per2::LucSV, where the endogenous Per2 3′-UTR was replaced by an SV40 late poly(A) signal. To delineate the in vivo functions of Per2 3′-UTR, we...



FOXO1 opposition of CD8+ T cell effector programming confers early memory properties and phenotypic diversity [Immunology and Inflammation]

2017-10-17T09:41:41-07:00

The factors and steps controlling postinfection CD8+ T cell terminal effector versus memory differentiation are incompletely understood. Whereas we found that naive TCF7 (alias “Tcf-1”) expression is FOXO1 independent, early postinfection we report bimodal, FOXO1-dependent expression of the memory-essential transcription factor TCF7 in pathogen-specific CD8+ T cells. We determined the...



Systems-level identification of PKA-dependent signaling in epithelial cells [Medical Sciences]

2017-10-17T09:41:41-07:00

G protein stimulatory α-subunit (Gαs)-coupled heptahelical receptors regulate cell processes largely through activation of protein kinase A (PKA). To identify signaling processes downstream of PKA, we deleted both PKA catalytic subunits using CRISPR-Cas9, followed by a “multiomic” analysis in mouse kidney epithelial cells expressing the Gαs-coupled V2 vasopressin receptor. RNA-seq...



Genome-wide engineering of an infectious clone of herpes simplex virus type 1 using synthetic genomics assembly methods [Microbiology]

2017-10-17T09:41:41-07:00

Here, we present a transformational approach to genome engineering of herpes simplex virus type 1 (HSV-1), which has a large DNA genome, using synthetic genomics tools. We believe this method will enable more rapid and complex modifications of HSV-1 and other large DNA viruses than previous technologies, facilitating many useful...



Expanded subgenomic mRNA transcriptome and coding capacity of a nidovirus [Microbiology]

2017-10-17T09:41:41-07:00

Members of the order Nidovirales express their structural protein ORFs from a nested set of 3′ subgenomic mRNAs (sg mRNAs), and for most of these ORFs, a single genomic transcription regulatory sequence (TRS) was identified. Nine TRSs were previously reported for the arterivirus Simian hemorrhagic fever virus (SHFV). In the...



Structures of human-infecting Thogotovirus fusogens support a common ancestor with insect baculovirus [Microbiology]

2017-10-17T09:41:41-07:00

Thogotoviruses are emerging tick-borne zoonotic orthomyxoviruses infecting both humans and domestic animals with severe clinical consequences. These viruses utilize a single-envelope glycoprotein (Gp) to facilitate their entry into host cells. Here, we present the Gp structures of Thogoto and Dhori viruses, both of which are members of the Thogotovirus genus...



Motor origin of temporal predictions in auditory attention [Neuroscience]

2017-10-17T09:41:41-07:00

In behavior, action and perception are inherently interdependent. However, the actual mechanistic contributions of the motor system to sensory processing are unknown. We present neurophysiological evidence that the motor system is involved in predictive timing, a brain function that aligns temporal fluctuations of attention with the timing of events in...



Framework for gradual progression of cell ontogeny in the Arabidopsis root meristem [Plant Biology]

2017-10-17T09:41:41-07:00

In plants, apical meristems allow continuous growth along the body axis. Within the root apical meristem, a group of slowly dividing quiescent center cells is thought to limit stem cell activity to directly neighboring cells, thus endowing them with unique properties, distinct from displaced daughters. This binary identity of the...



Mediator subunit MED25 links the jasmonate receptor to transcriptionally active chromatin [Plant Biology]

2017-10-17T09:41:41-07:00

Jasmonoyl-isoleucine (JA-Ile), the active form of the plant hormone jasmonate (JA), is sensed by the F-box protein CORONATINE INSENSITIVE 1 (COI1), a component of a functional Skp–Cullin–F-box E3 ubiquitin ligase complex. Sensing of JA-Ile by COI1 rapidly triggers genome-wide transcriptional changes that are largely regulated by the basic helix–loop–helix transcription...



On the origin of biological construction, with a focus on multicellularity [Evolution]

2017-10-17T09:41:40-07:00

Biology is marked by a hierarchical organization: all life consists of cells; in some cases, these cells assemble into groups, such as endosymbionts or multicellular organisms; in turn, multicellular organisms sometimes assemble into yet other groups, such as primate societies or ant colonies. The construction of new organizational layers results...



Opinion: Fostering synthesis in archaeology to advance science and benefit society [Anthropology]

2017-10-17T09:41:40-07:00

In 1966 the US Congress passed the National Historic Preservation Act. Its intent: to ensure that the values embedded in historic buildings, archaeological sites, and other important places of the past honored all Americans in ways that would inspire and motivate present and future generations. In the intervening 50 years,...



Spontaneous self-dislodging of freezing water droplets and the role of wettability [Applied Physical Sciences]

2017-10-17T09:41:40-07:00

Spontaneous removal of liquid, solidifying liquid and solid forms of matter from surfaces, is of significant importance in nature and technology, where it finds applications ranging from self-cleaning to icephobicity and to condensation systems. However, it is a great challenge to understand fundamentally the complex interaction of rapidly solidifying, typically...



Li-rich antiperovskite superionic conductors based on cluster ions [Applied Physical Sciences]

2017-10-17T09:41:40-07:00

Enjoying great safety, high power, and high energy densities, all-solid-state batteries play a key role in the next generation energy storage devices. However, their development is limited by the lack of solid electrolyte materials that can reach the practically useful conductivities of 10−2 S/cm at room temperature (RT). Here, by...



Molecular mechanisms and structural features of cardiomyopathy-causing troponin T mutants in the tropomyosin overlap region [Biochemistry]

2017-10-17T09:41:41-07:00

Point mutations in genes encoding sarcomeric proteins are the leading cause of inherited primary cardiomyopathies. Among them are mutations in the TNNT2 gene that encodes cardiac troponin T (TnT). These mutations are clustered in the tropomyosin (Tm) binding region of TnT, TNT1 (residues 80–180). To understand the mechanistic changes caused...



Minimal and RNA-free RNase P in Aquifex aeolicus [Biochemistry]

2017-10-17T09:41:41-07:00

RNase P is an essential tRNA-processing enzyme in all domains of life. We identified an unknown type of protein-only RNase P in the hyperthermophilic bacterium Aquifex aeolicus: Without an RNA subunit and the smallest of its kind, the 23-kDa polypeptide comprises a metallonuclease domain only. The protein has RNase P...



Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation [Biochemistry]

2017-10-17T09:41:41-07:00

Extracellular vesicles (EVs) are small vesicles released by cells to aid cell–cell communication and tissue homeostasis. Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits found in pancreatic islets of patients with type 2 diabetes (T2D). IAPP is secreted in conjunction with insulin from pancreatic β cells...



Structure and dynamics of the RNAPII CTDsome with Rtt103 [Biochemistry]

2017-10-17T09:41:41-07:00

RNA polymerase II contains a long C-terminal domain (CTD) that regulates interactions at the site of transcription. The CTD architecture remains poorly understood due to its low sequence complexity, dynamic phosphorylation patterns, and structural variability. We used integrative structural biology to visualize the architecture of the CTD in complex with...



Mechanically switching single-molecule fluorescence of GFP by unfolding and refolding [Biophysics and Computational Biology]

2017-10-17T09:41:41-07:00

Green fluorescent protein (GFP) variants are widely used as genetically encoded fluorescent fusion tags, and there is an increasing interest in engineering their structure to develop in vivo optical sensors, such as for optogenetics and force transduction. Ensemble experiments have shown that the fluorescence of GFP is quenched upon denaturation....



Allocating dissipation across a molecular machine cycle to maximize flux [Biophysics and Computational Biology]

2017-10-17T09:41:41-07:00

Biomolecular machines consume free energy to break symmetry and make directed progress. Nonequilibrium ATP concentrations are the typical free energy source, with one cycle of a molecular machine consuming a certain number of ATP, providing a fixed free energy budget. Since evolution is expected to favor rapid-turnover machines that operate...



Detection of isolated protein-bound metal ions by single-particle cryo-STEM [Biophysics and Computational Biology]

2017-10-17T09:41:41-07:00

Metal ions play essential roles in many aspects of biological chemistry. Detecting their presence and location in proteins and cells is important for understanding biological function. Conventional structural methods such as X-ray crystallography and cryo-transmission electron microscopy can identify metal atoms on protein only if the protein structure is solved...



Chemical substitutions in the selectivity filter of potassium channels do not rule out constricted-like conformations for C-type inactivation [Biophysics and Computational Biology]

2017-10-17T09:41:41-07:00

In many K+ channels, prolonged activating stimuli lead to a time-dependent reduction in ion conduction, a phenomenon known as C-type inactivation. X-ray structures of the KcsA channel suggest that this inactivated state corresponds to a “constricted” conformation of the selectivity filter. However, the functional significance of the constricted conformation has...



Structural basis underlying complex assembly and conformational transition of the type I R-M system [Biophysics and Computational Biology]

2017-10-17T09:41:41-07:00

Type I restriction-modification (R-M) systems are multisubunit enzymes with separate DNA-recognition (S), methylation (M), and restriction (R) subunits. Despite extensive studies spanning five decades, the detailed molecular mechanisms underlying subunit assembly and conformational transition are still unclear due to the lack of high-resolution structural information. Here, we report the atomic...



Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion [Biophysics and Computational Biology]

2017-10-17T09:41:41-07:00

The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacterized. Here we report the cryoEM structure...



Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins [Cell Biology]

2017-10-17T09:41:41-07:00

The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin...



An anion-immobilized composite electrolyte for dendrite-free lithium metal anodes [Chemistry]

2017-10-17T09:41:41-07:00

Lithium metal is strongly regarded as a promising electrode material in next-generation rechargeable batteries due to its extremely high theoretical specific capacity and lowest reduction potential. However, the safety issue and short lifespan induced by uncontrolled dendrite growth have hindered the practical applications of lithium metal anodes. Hence, we propose...



Asynchronous warming and {delta}18O evolution of deep Atlantic water masses during the last deglaciation [Earth, Atmospheric, and Planetary Sciences]

2017-10-17T09:41:41-07:00

The large-scale reorganization of deep ocean circulation in the Atlantic involving changes in North Atlantic Deep Water (NADW) and Antarctic Bottom Water (AABW) played a critical role in regulating hemispheric and global climate during the last deglaciation. However, changes in the relative contributions of NADW and AABW and their properties...



Early snowmelt significantly enhances boreal springtime carbon uptake [Earth, Atmospheric, and Planetary Sciences]

2017-10-17T09:41:41-07:00

We determine the annual timing of spring recovery from space-borne microwave radiometer observations across northern hemisphere boreal evergreen forests for 1979–2014. We find a trend of advanced spring recovery of carbon uptake for this period, with a total average shift of 8.1 d (2.3 d/decade). We use this trend to...



Tree genetics defines fungal partner communities that may confer drought tolerance [Ecology]

2017-10-17T09:41:41-07:00

Plant genetic variation and soil microorganisms are individually known to influence plant responses to climate change, but the interactive effects of these two factors are largely unknown. Using long-term observational studies in the field and common garden and greenhouse experiments of a foundation tree species (Pinus edulis) and its mutualistic...



High-intensity urban light installation dramatically alters nocturnal bird migration [Ecology]

2017-10-17T09:41:41-07:00

Billions of nocturnally migrating birds move through increasingly photopolluted skies, relying on cues for navigation and orientation that artificial light at night (ALAN) can impair. However, no studies have quantified avian responses to powerful ground-based light sources in urban areas. We studied effects of ALAN on migrating birds by monitoring...



Interhost dispersal alters microbiome assembly and can overwhelm host innate immunity in an experimental zebrafish model [Ecology]

2017-10-17T09:41:41-07:00

The diverse collections of microorganisms associated with humans and other animals, collectively referred to as their “microbiome,” are critical for host health, but the mechanisms that govern their assembly are poorly understood. This has made it difficult to identify consistent host factors that explain variation in microbiomes across hosts, despite...



Phenotypic variation explains food web structural patterns [Ecology]

2017-10-17T09:41:41-07:00

Food webs (i.e., networks of species and their feeding interactions) share multiple structural features across ecosystems. The factors explaining such similarities are still debated, and the role played by most organismal traits and their intraspecific variation is unknown. Here, we assess how variation in traits controlling predator–prey interactions (e.g., body...



Elliptical orbits of microspheres in an evanescent field [Engineering]

2017-10-17T09:41:41-07:00

We examine the motion of periodically driven and optically tweezed microspheres in fluid and find a rich variety of dynamic regimes. We demonstrate, in experiment and in theory, that mean particle motion in 2D is rarely parallel to the direction of the applied force and can even exhibit elliptical orbits...



Unexpected source of Fukushima-derived radiocesium to the coastal ocean of Japan [Environmental Sciences]

2017-10-17T09:41:41-07:00

There are 440 operational nuclear reactors in the world, with approximately one-half situated along the coastline. This includes the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), which experienced multiple reactor meltdowns in March 2011 followed by the release of radioactivity to the marine environment. While surface inputs to the ocean via...



Rapid evolution of hosts begets species diversity at the cost of intraspecific diversity [Evolution]

2017-10-17T09:41:41-07:00

Ecosystems are complex food webs in which multiple species interact and ecological and evolutionary processes continuously shape populations and communities. Previous studies on eco-evolutionary dynamics have shown that the presence of intraspecific diversity affects community structure and function, and that eco-evolutionary feedback dynamics can be an important driver for its...



CRISPR-Cas9-based treatment of myocilin-associated glaucoma [Genetics]

2017-10-17T09:41:41-07:00

Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-of-function mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular...



Resistin-like molecule {beta} is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium [Immunology and Inflammation]

2017-10-17T09:41:40-07:00

The mammalian intestine is colonized by trillions of bacteria that perform essential metabolic functions for their hosts. The mutualistic nature of this relationship depends on maintaining spatial segregation between these bacteria and the intestinal epithelial surface. This segregation is achieved in part by the presence of a dense mucus layer...



Mycobacterium tuberculosis inhibits human innate immune responses via the production of TLR2 antagonist glycolipids [Immunology and Inflammation]

2017-10-17T09:41:41-07:00

Mycobacterium tuberculosis is a major human pathogen that is able to survive inside host cells and resist immune clearance. Most particularly, it inhibits several arms of the innate immune response, including phagosome maturation or cytokine production. To better understand the molecular mechanisms by which M. tuberculosis circumvents host immune defenses,...



Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5 [Medical Sciences]

2017-10-17T09:41:41-07:00

Glycoconjugate vaccines based on isolated capsular polysaccharide (CPS) save millions of lives annually by preventing invasive pneumococcal disease caused by Streptococcus pneumoniae. Some components of the S. pneumoniae glycoconjugate vaccine Prevnar13 that contains CPS antigens from 13 serotypes undergo modifications or degradation during isolation and conjugation, resulting in production problems...



Long-term restoration of visual function in end-stage retinal degeneration using subretinal human melanopsin gene therapy [Medical Sciences]

2017-10-17T09:41:41-07:00

Optogenetic strategies to restore vision in patients who are blind from end-stage retinal degenerations aim to render remaining retinal cells light sensitive once photoreceptors are lost. Here, we assessed long-term functional outcomes following subretinal delivery of the human melanopsin gene (OPN4) in the rd1 mouse model of retinal degeneration using...



Molecular basis of mammalian transmissibility of avian H1N1 influenza viruses and their pandemic potential [Microbiology]

2017-10-17T09:41:41-07:00

North American wild birds are an important reservoir of influenza A viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood. Our surveillance of avian influenza viruses (AIVs) at Delaware Bay, USA, revealed a group of similar H1N1 AIVs isolated...



Host-derived fatty acids activate type VII secretion in Staphylococcus aureus [Microbiology]

2017-10-17T09:41:41-07:00

The type VII secretion system (T7SS) of Staphylococcus aureus is a multiprotein complex dedicated to the export of several virulence factors during host infection. This virulence pathway plays a key role in promoting bacterial survival and the long-term persistence of staphylococcal abscess communities. The expression of the T7SS is activated...



Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome [Neuroscience]

2017-10-17T09:41:41-07:00

Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function...



Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis [Neuroscience]

2017-10-17T09:41:41-07:00

Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators...



Direct measurement of weakly nonequilibrium system entropy is consistent with Gibbs-Shannon form [Physics]

2017-10-17T09:41:41-07:00

Stochastic thermodynamics extends classical thermodynamics to small systems in contact with one or more heat baths. It can account for the effects of thermal fluctuations and describe systems far from thermodynamic equilibrium. A basic assumption is that the expression for Shannon entropy is the appropriate description for the entropy of...



Universal poroelastic mechanism for hydraulic signals in biomimetic and natural branches [Plant Biology]

2017-10-17T09:41:40-07:00

Plants constantly undergo external mechanical loads such as wind or touch and respond to these stimuli by acclimating their growth processes. A fascinating feature of this mechanical-induced growth response is that it can occur rapidly and at long distance from the initial site of stimulation, suggesting the existence of a...



Stress attenuates the flexible updating of aversive value [Psychological and Cognitive Sciences]

2017-10-17T09:41:41-07:00

In a dynamic environment, sources of threat or safety can unexpectedly change, requiring the flexible updating of stimulus−outcome associations that promote adaptive behavior. However, aversive contexts in which we are required to update predictions of threat are often marked by stress. Acute stress is thought to reduce behavioral flexibility, yet...



Short- and long-term effects of imprisonment on future felony convictions and prison admissions [Social Sciences]

2017-10-17T09:41:41-07:00

A substantial contributor to prison admissions is the return of individuals recently released from prison, which has come to be known as prison’s “revolving door.” However, it is unclear whether being sentenced to prison itself has a causal effect on the probability of a subsequent return to prison or on...



Projections of white and black older adults without living kin in the United States, 2015 to 2060 [Social Sciences]

2017-10-17T09:41:41-07:00

Close kin provide many important functions as adults age, affecting health, financial well-being, and happiness. Those without kin report higher rates of loneliness and experience elevated risks of chronic illness and nursing facility placement. Historical racial differences and recent shifts in core demographic rates suggest that white and black older...



Prairie strips improve biodiversity and the delivery of multiple ecosystem services from corn-soybean croplands [Sustainability Science]

2017-10-17T09:41:41-07:00

Loss of biodiversity and degradation of ecosystem services from agricultural lands remain important challenges in the United States despite decades of spending on natural resource management. To date, conservation investment has emphasized engineering practices or vegetative strategies centered on monocultural plantings of nonnative plants, largely excluding native species from cropland....



Multigenerational silencing dynamics control cell aging [Systems Biology]

2017-10-17T09:41:41-07:00

Cellular aging plays an important role in many diseases, such as cancers, metabolic syndromes, and neurodegenerative disorders. There has been steady progress in identifying aging-related factors such as reactive oxygen species and genomic instability, yet an emerging challenge is to reconcile the contributions of these factors with the fact that...



Correction for Dixon et al., Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation [Correction]

2017-10-17T09:41:41-07:00

CELL BIOLOGY Correction for “Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation,” by James E. Dixon, Disheet A. Shah, Catherine Rogers, Stephen Hall, Nicola Weston, Christopher D. J. Parmenter, Donal McNally, Chris Denning, and Kevin M. Shakesheff, which was first published March 27, 2014; 10.1073/pnas.1319685111 (Proc...



Correction for Cekanaviciute et al., Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models [Correction]

2017-10-17T09:41:41-07:00

IMMUNOLOGY AND INFLAMMATION Correction for “Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models,” by Egle Cekanaviciute, Bryan B. Yoo, Tessel F. Runia, Justine W. Debelius, Sneha Singh, Charlotte A. Nelson, Rachel Kanner, Yadira Bencosme, Yun Kyung Lee, Stephen L. Hauser, Elizabeth Crabtree-Hartman,...



Correction to Supporting Information for Palermo et al., CRISPR-Cas9 conformational activation as elucidated from enhanced molecular simulations [SI Correction]

2017-10-17T09:41:41-07:00

BIOPHYSICS AND COMPUTATIONAL BIOLOGY, BIOCHEMISTRY Correction to Supporting Information for “CRISPR-Cas9 conformational activation as elucidated from enhanced molecular simulations,” by Giulia Palermo, Yinglong Miao, Ross C. Walker, Martin Jinek, and J. Andrew McCammon, which was first published June 26, 2017; 10.1073/pnas.1707645114 (Proc Natl Acad Sci USA 114:7260–7265). The authors note...



In This Issue [This Week in PNAS]

2017-10-10T12:26:32-07:00

Genetic variations in ion channels influence human hair color Genetic variations in TPC ion channels influence hair color. Image courtesy of iStockphoto/Sasha_Litt. Levels of the human hair color pigment eumelanin, produced by cells found in the skin’s basal epidermis and hair follicles, depend on the cells’ internal pH. Previous studies...



Vulnerability of Amazonian floodplains to wildfires differs according to their typologies impeding generalizations [Biological Sciences]

2017-10-10T12:26:32-07:00

Flores et al. (1) suggest that large Amazonian floodplains are vulnerable to fire and that a future, drier climate will trigger wide-spread conversion of floodplain forests into fire-dominated savanna. Furthermore, the authors argue that fires in fluvial networks will cascade through nonflooded communities and spearhead fire-induced change in the wider...



Reply to Schongart et al.: Forest resilience variation across Amazonian floodplains [Biological Sciences]

2017-10-10T12:26:32-07:00

Our recent findings that floodplain ecosystems harbor the most fragile forests of the Amazon (1) was seen by Schöngart et al. (2) as an oversimplification of a complex ecosystem. They argue that the majority of floodplain forests are associated with fertile soils, and should therefore be highly resilient. Indeed, the...



Studying folktale diffusion needs unbiased dataset [Biological Sciences]

2017-10-10T12:26:32-07:00

Bortolini et al. (1) claim to infer patterns of folktale diffusion using genomic data. What is not said in their paper is that such a proposal is not new. For example, Korotayev and Khaltourina (2) showed statistical correlation between spatial distributions of mythological motifs and genetic markers, considerably above the...



Reply to d’Huy et al.: Navigating biases and charting new ground in the cultural diffusion of folktales [Biological Sciences]

2017-10-10T12:26:32-07:00

In their letter, d’Huy et al. (1) challenge the novelty of our study (2), and question the reliability of some our results in the light of previous folkloric research and geographic biases in the Aarne Thompson Uther (ATU) index (3). In our reply we explain how their criticisms are already...



Thomas E. Starzl: Transplantation pioneer [Retrospectives]

2017-10-10T12:26:32-07:00

Thomas E. Starzl, MD, PhD was born on March 11, 1926 in Le Mars, Iowa, the second son of Roman Frederick Starzl and Anna Laura Starzl. His parents were first-generation Americans, the children of Czechoslovakian and Irish immigrants. Roman Starzl was an editor, publisher, and owner of a newspaper. Anna...



New roles for old actors, ROS and PRMT1 [Physiology]

2017-10-10T12:26:32-07:00

Reactive oxygen species (ROS) and enzymes (e.g., arginine methyltransferase 1, PRMT1) involved in the modification of DNA and histones have been the subject of intense research during the last decade. In PNAS, a paper entitled “Reactive oxygen species extend insect life span using components of the insulin-signaling pathway” by Zhang...



RIPK1 promotes inflammation and {beta}-amyloid accumulation in Alzheimer’s disease [Neuroscience]

2017-10-10T12:26:32-07:00

Alzheimer’s disease (AD), the leading cause of dementia, is a major cause of death and a significant economic burden. In 2016, ∼700,000 Americans aged 65 and over died of AD, and the total health and social care payments for AD in the United States alone exceeded $230 billion (1). Currently,...



Measuring trends in discrimination with field experiment data [Social Sciences]

2017-10-10T12:26:32-07:00

The passage of major civil rights legislation was accompanied by a large improvement in the economic circumstances of African-Americans (1), and the public consensus against discrimination has grown over time (2). However, the significant postwar progress of African-Americans appears to have slowed or even stagnated over the last several decades...



RPE65 takes on another role in the vertebrate retina [Biochemistry]

2017-10-10T12:26:32-07:00

The high-acuity central vision of humans, and other primates, depends on a region of the central retina called the macula lutea (Latin: yellow spot), containing not only a high concentration of both cone and rod photoreceptors but also a high concentration of xanthophyll carotenoids; hence, its name (1). At the...



Bridge between type 1 diabetes in mouse and man [Medical Sciences]

2017-10-10T12:26:32-07:00

Type 1 diabetes (T1D) manifested with hyperglycemia is an autoimmune disease resulting from destruction of insulin-producing pancreatic β cells (1, 2). The nonobese diabetic (NOD) mouse is the preclinical model closest to T1D in man and has provided an invaluable understanding of basic immune pathogenesis, genetic and environmental risk factors,...



Flow-induced gelation of microfiber suspensions [Applied Physical Sciences]

2017-10-10T12:26:32-07:00

The flow behavior of fiber suspensions has been studied extensively, especially in the limit of dilute concentrations and rigid fibers; at the other extreme, however, where the suspensions are concentrated and the fibers are highly flexible, much less is understood about the flow properties. We use a microfluidic method to...



Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro [Biochemistry]

2017-10-10T12:26:32-07:00

Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are...



A peptide extension dictates IgM assembly [Biochemistry]

2017-10-10T12:26:32-07:00

Professional secretory cells can produce large amounts of high-quality complex molecules, including IgM antibodies. Owing to their multivalency, polymeric IgM antibodies provide an efficient first-line of defense against pathogens. To decipher the mechanisms of IgM assembly, we investigated its biosynthesis in living cells and faithfully reconstituted the underlying processes in...



A protean clamp guides membrane targeting of tail-anchored proteins [Biochemistry]

2017-10-10T12:26:32-07:00

Proper localization of proteins to target membranes is a fundamental cellular process. How the nature and dynamics of the targeting complex help guide substrate proteins to the target membrane is not understood for most pathways. Here, we address this question for the conserved ATPase guided entry of tail-anchored protein 3...



TPC2 polymorphisms associated with a hair pigmentation phenotype in humans result in gain of channel function by independent mechanisms [Biophysics and Computational Biology]

2017-10-10T12:26:32-07:00

Two-pore channels (TPCs) are endolysosomal cation channels. Two members exist in humans, TPC1 and TPC2. Functional roles associated with the ubiquitously expressed TPCs include VEGF-induced neoangiogenesis, LDL-cholesterol trafficking and degradation, physical endurance under fasting conditions, autophagy regulation, the acrosome reaction in sperm, cancer cell migration, and intracellular trafficking of pathogens...



Miscoding-induced stalling of substrate translocation on the bacterial ribosome [Biophysics and Computational Biology]

2017-10-10T12:26:32-07:00

Directional transit of the ribosome along the messenger RNA (mRNA) template is a key determinant of the rate and processivity of protein synthesis. Imaging of the multistep translocation mechanism using single-molecule FRET has led to the hypothesis that substrate movements relative to the ribosome resolve through relatively long-lived late intermediates...



Molecular origin of the weak susceptibility of kinesin velocity to loads and its relation to the collective behavior of kinesins [Biophysics and Computational Biology]

2017-10-10T12:26:32-07:00

Motor proteins are active enzymatic molecules that support important cellular processes by transforming chemical energy into mechanical work. Although the structures and chemomechanical cycles of motor proteins have been extensively investigated, the sensitivity of a motor’s velocity in response to a force is not well-understood. For kinesin, velocity is weakly...



Cell volume change through water efflux impacts cell stiffness and stem cell fate [Cell Biology]

2017-10-10T12:26:32-07:00

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases,...



Critical role for PI3-kinase in regulating the use of proteins as an amino acid source [Cell Biology]

2017-10-10T12:26:32-07:00

Ras-transformed cells can grow in amino acid-poor environments by recovering amino acids through macropinocytosis and lysosomal catabolism of extracellular proteins. However, when studying nontransformed fibroblasts, we found that Ras GTPases are dispensable for growth-factor–stimulated macropinocytosis and lysosomal catabolism of extracellular proteins. Instead, we establish a critical role for phosphatidylinositol 3-kinase...



Rewiring a Rab regulatory network reveals a possible inhibitory role for the vesicle tether, Uso1 [Cell Biology]

2017-10-10T12:26:32-07:00

Ypt1 and Sec4 are essential Rab GTPases that control the early and late stages of the yeast secretory pathway, respectively. A chimera consisting of Ypt1 with the switch I domain of Sec4, Ypt1-SW1Sec4, is efficiently activated in vitro by the Sec4 exchange factor, Sec2. This should lead to its ectopic...



Speed regulation of genetic cascades allows for evolvability in the body plan specification of insects [Developmental Biology]

2017-10-10T12:26:32-07:00

During the anterior−posterior fate specification of insects, anterior fates arise in a nonelongating tissue (called the “blastoderm”), and posterior fates arise in an elongating tissue (called the “germband”). However, insects differ widely in the extent to which anterior−posterior fates are specified in the blastoderm versus the germband. Here we present...



Ideal crop plant architecture is mediated by tassels replace upper ears1, a BTB/POZ ankyrin repeat gene directly targeted by TEOSINTE BRANCHED1 [Developmental Biology]

2017-10-10T12:26:32-07:00

Axillary branch suppression is a favorable trait bred into many domesticated crop plants including maize compared with its highly branched wild ancestor teosinte. Branch suppression in maize was achieved through selection of a gain of function allele of the teosinte branched1 (tb1) transcription factor that acts as a repressor of...



Network of nutrient-sensing pathways and a conserved kinase cascade integrate osmolarity and carbon sensing in Neurospora crassa [Genetics]

2017-10-10T12:26:32-07:00

Identifying nutrients available in the environment and utilizing them in the most efficient manner is a challenge common to all organisms. The model filamentous fungus Neurospora crassa is capable of utilizing a variety of carbohydrates, from simple sugars to the complex carbohydrates found in plant cell walls. The zinc binuclear...



Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow [Medical Sciences]

2017-10-10T12:26:32-07:00

It has been known for some time that atherosclerotic lesions preferentially develop in areas exposed to low SS and are characterized by a proinflammatory, apoptotic, and senescent endothelial phenotype. Conversely, areas exposed to high SS are protected from plaque development, but the mechanisms have remained elusive. Autophagy is a protective...



Cross-activating c-Met/{beta}1 integrin complex drives metastasis and invasive resistance in cancer [Medical Sciences]

2017-10-10T12:26:32-07:00

The molecular underpinnings of invasion, a hallmark of cancer, have been defined in terms of individual mediators but crucial interactions between these mediators remain undefined. In xenograft models and patient specimens, we identified a c-Met/β1 integrin complex that formed during significant invasive oncologic processes: breast cancer metastases and glioblastoma invasive...



Mapping allele with resolved carrier status of Robertsonian and reciprocal translocation in human preimplantation embryos [Medical Sciences]

2017-10-10T12:26:32-07:00

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo...



Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies [Microbiology]

2017-10-10T12:26:32-07:00

Herpesvirus entry into cells requires the coordinated action of multiple virus envelope glycoproteins, including gH, gL, and gB. For EBV, the gp42 protein assembles into complexes with gHgL heterodimers and binds HLA class II to activate gB-mediated membrane fusion with B cells. EBV tropism is dictated by gp42 levels in...



Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA [Microbiology]

2017-10-10T12:26:32-07:00

Mycobacterium tuberculosis’ success as a pathogen comes from its ability to evade degradation by macrophages. Normally macrophages clear microorganisms that activate pathogen-recognition receptors (PRRs) through a lysosomal-trafficking pathway called “LC3-associated phagocytosis” (LAP). Although M. tuberculosis activates numerous PRRs, for reasons that are poorly understood LAP does not substantially contribute to...



Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract [Microbiology]

2017-10-10T12:26:32-07:00

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of catheter-associated urinary tract infection (CAUTI), which frequently progresses to more serious invasive infections. We adapted a mouse model of CAUTI to investigate how catheterization increases an individual’s susceptibility to MRSA UTI. This analysis revealed that catheterization was required for MRSA to...



Limits of variation, specific infectivity, and genome packaging of massively recoded poliovirus genomes [Microbiology]

2017-10-10T12:26:32-07:00

Computer design and chemical synthesis generated viable variants of poliovirus type 1 (PV1), whose ORF (6,189 nucleotides) carried up to 1,297 “Max” mutations (excess of overrepresented synonymous codon pairs) or up to 2,104 “SD” mutations (randomly scrambled synonymous codons). “Min” variants (excess of underrepresented synonymous codon pairs) are nonviable except...