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Proceedings of the National Academy of Sciences recent issues



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In This Issue [This Week in PNAS]

2018-04-17T11:36:48-07:00

Brain atlas reveals differential effects of aging and Alzheimer’s disease 3D model of average anatomy of the hippocampus. Each color represents a different subfield. Existing data on the anatomical variability and 3D organization of the human hippocampus—as well as the effects of age and disease on this brain region—are limited...



Reply to Chien: Clarification of the effect of ligand on {gamma}{delta}-TCR repertoire selection [Biological Sciences]

2018-04-17T11:36:49-07:00

In our recent publication (1), we report that the EGYEL motif, previously found to promote T22-reactivity, was depleted from the mature CD24low pool of γδ-T cells that developed in H-2T–deficient mice, indicating that ligand was influencing the γδ-T cell receptor (TCR) repertoire (1). In her letter, Chien (2) suggests that...



Genetic variation in VAC14 is associated with bacteremia secondary to diverse pathogens in African children [Biological Sciences]

2018-04-17T11:36:49-07:00

Performing a genome-wide association study of Salmonella enterica serovar Typhi (S. Typhi) invasion, Alvarez et al. (1) identify a trait-associated SNP, rs8060947, in VAC14. rs8060947 is an expression quantitative trait locus for VAC14 RNA expression, and carriage of the A allele is associated with reduced VAC14 RNA and protein expression,...



Reply to Gilchrist et al.: Possible roles for VAC14 in multiple infectious diseases [Biological Sciences]

2018-04-17T11:36:49-07:00

Our studies of the SNP rs8060947 determine that the A allele is associated with increased invasion of Salmonella enterica serovar Typhi and increased susceptibility to typhoid fever (1). Gilchrist et al. (2) now provide evidence that the A allele is also associated with increased risk for bacteremia, and the association...



Does selecting ligand shape {gamma}{delta}-TCR repertoire? [Biological Sciences]

2018-04-17T11:36:49-07:00

In a recent publication entitled “Role of a selecting ligand in shaping the murine γδ-TCR repertoire,” Fahl et al. (1) report that the expression of nonclassic MHC T10 and its related molecule T22 influences the T10/T22 specific γδ-T cell receptor (TCR) repertoire. We maintain that caveats in their experimental approaches...



The labyrinth of human variation [Anthropology]

2018-04-17T11:36:48-07:00

Morphological analyses of the human temporal labyrinth (cochlea and especially the semicircular canals) have progressed (along with advances in tomography) from using the labyrinth to orient crania (1), to document the earlier hominin ancestral pattern (2), to document an apparently derived “Neandertal” configuration (3), to establish Neandertal persistence into the...



Physiological constraints on marine mammal body size [Evolution]

2018-04-17T11:36:48-07:00

Body size has widely been recognized as one of the most important determinants of organismal form and function (1). Extremes in size can be especially illuminating of the drivers and constraints in body size evolution, and marine mammals provide a remarkable set of test cases because their independent invasions of...



Auditory motion parallax [Neuroscience]

2018-04-17T11:36:48-07:00

When an object vibrates and produces an audible sound, many animals locate the position of the sound source based on only the sound. The horizontal (azimuth), vertical (elevation), and distance (range) of sound sources can often be determined, in some cases with high acuity (1). As most auditory systems have...



Thermodynamic limits of energy harvesting from outgoing thermal radiation [Applied Physical Sciences]

2018-04-17T11:36:49-07:00

We derive the thermodynamic limits of harvesting power from the outgoing thermal radiation from the ambient to the cold outer space. The derivations are based on a duality relation between thermal engines that harvest solar radiation and those that harvest outgoing thermal radiation. In particular, we derive the ultimate limit...



Roll maneuvers are essential for active reorientation of Caenorhabditis elegans in 3D media [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

Locomotion of the nematode Caenorhabditis elegans is a key observable used in investigations ranging from behavior to neuroscience to aging. However, while the natural environment of this model organism is 3D, quantitative investigations of its locomotion have been mostly limited to 2D motion. Here, we present a quantitative analysis of...



Molecular excitonic seesaws [Chemistry]

2018-04-17T11:36:49-07:00

The breaking of molecular symmetry through photoexcitation is a ubiquitous but rather elusive process, which, for example, controls the microscopic efficiency of light harvesting in molecular aggregates. A molecular excitation within a π-conjugated segment will self-localize due to strong coupling to molecular vibrations, locally changing bond alternation in a process...



Word embeddings quantify 100 years of gender and ethnic stereotypes [Computer Sciences]

2018-04-17T11:36:49-07:00

Word embeddings are a powerful machine-learning framework that represents each English word by a vector. The geometric relationship between these vectors captures meaningful semantic relationships between the corresponding words. In this paper, we develop a framework to demonstrate how the temporal dynamics of the embedding helps to quantify changes in...



Fluctuations uncover a distinct class of traveling waves [Physics]

2018-04-17T11:36:49-07:00

Epidemics, flame propagation, and cardiac rhythms are classic examples of reaction–diffusion waves that describe a switch from one alternative state to another. Only two types of waves are known: pulled, driven by the leading edge, and pushed, driven by the bulk of the wave. Here, we report a distinct class...



Soft self-assembly of Weyl materials for light and sound [Physics]

2018-04-17T11:36:49-07:00

Soft materials can self-assemble into highly structured phases that replicate at the mesoscopic scale the symmetry of atomic crystals. As such, they offer an unparalleled platform to design mesostructured materials for light and sound. Here, we present a bottom-up approach based on self-assembly to engineer 3D photonic and phononic crystals...



Topological order in the pseudogap metal [Physics]

2018-04-17T11:36:49-07:00

We compute the electronic Green’s function of the topologically ordered Higgs phase of a SU(2) gauge theory of fluctuating antiferromagnetism on the square lattice. The results are compared with cluster extensions of dynamical mean field theory, and quantum Monte Carlo calculations, on the pseudogap phase of the strongly interacting hole-doped...



Pharmacological activation of estrogen receptor beta augments innate immunity to suppress cancer metastasis [Biochemistry]

2018-04-17T11:36:49-07:00

Metastases constitute the greatest causes of deaths from cancer. However, no effective therapeutic options currently exist for cancer patients with metastasis. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor-suppressive activities in many cancers. To investigate whether modulation of ERβ could serve as a...



Mechanosensitivity of Jagged-Notch signaling can induce a switch-type behavior in vascular homeostasis [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

Hemodynamic forces and Notch signaling are both known as key regulators of arterial remodeling and homeostasis. However, how these two factors integrate in vascular morphogenesis and homeostasis is unclear. Here, we combined experiments and modeling to evaluate the impact of the integration of mechanics and Notch signaling on vascular homeostasis....



Accurate and sensitive quantification of protein-DNA binding affinity [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read...



Comprehensive, high-resolution binding energy landscapes reveal context dependencies of transcription factor binding [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

Transcription factors (TFs) are primary regulators of gene expression in cells, where they bind specific genomic target sites to control transcription. Quantitative measurements of TF–DNA binding energies can improve the accuracy of predictions of TF occupancy and downstream gene expression in vivo and shed light on how transcriptional networks are...



Spatial organization and dynamics of RNase E and ribosomes in Caulobacter crescentus [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

We report the dynamic spatial organization of Caulobacter crescentus RNase E (RNA degradosome) and ribosomal protein L1 (ribosome) using 3D single-particle tracking and superresolution microscopy. RNase E formed clusters along the central axis of the cell, while weak clusters of ribosomal protein L1 were deployed throughout the cytoplasm. These results...



Insight from the maximal activation of the signal transduction excitable network in Dictyostelium discoideum [Cell Biology]

2018-04-17T11:36:49-07:00

Cell migration requires the coordination of an excitable signal transduction network involving Ras and PI3K pathways with cytoskeletal activity. We show that expressing activated Ras GTPase-family proteins in cells lacking PTEN or other mutations which increase cellular protrusiveness transforms cells into a persistently activated state. Leading- and trailing-edge markers were...



Evolutionary emergence of the rac3b/rfng/sgca regulatory cluster refined mechanisms for hindbrain boundaries formation [Developmental Biology]

2018-04-17T11:36:49-07:00

Developmental programs often rely on parallel morphogenetic mechanisms that guarantee precise tissue architecture. While redundancy constitutes an obvious selective advantage, little is known on how novel morphogenetic mechanisms emerge during evolution. In zebrafish, rhombomeric boundaries behave as an elastic barrier, preventing cell intermingling between adjacent compartments. Here, we identify the...



Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase [Genetics]

2018-04-17T11:36:49-07:00

Inactivation of the retinoblastoma gene (RB1) product, pRB, is common in many human cancers. Targeting downstream effectors of pRB that are central to tumorigenesis is a promising strategy to block the growth of tumors harboring loss-of-function RB1 mutations. One such effector is retinoblastoma-binding protein 2 (RBP2, also called JARID1A or...



Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia [Medical Sciences]

2018-04-17T11:36:49-07:00

The pathogenesis of parathyroid gland hyperplasia is poorly understood, and a better understanding is essential if there is to be improvement over the current strategies for prevention and treatment of secondary hyperparathyroidism. Here we investigate the specific role of Klotho expressed in the parathyroid glands (PTGs) in mediating parathyroid hormone...



FAM210A is a novel determinant of bone and muscle structure and strength [Medical Sciences]

2018-04-17T11:36:49-07:00

Osteoporosis and sarcopenia are common comorbid diseases, yet their shared mechanisms are largely unknown. We found that genetic variation near FAM210A was associated, through large genome-wide association studies, with fracture, bone mineral density (BMD), and appendicular and whole body lean mass, in humans. In mice, Fam210a was expressed in muscle...



Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk [Medical Sciences]

2018-04-17T11:36:49-07:00

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave...



The Vibrio cholerae type VI secretion system can modulate host intestinal mechanics to displace gut bacterial symbionts [Microbiology]

2018-04-17T11:36:49-07:00

Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain Aeromonas...



Plasticity in early immune evasion strategies of a bacterial pathogen [Microbiology]

2018-04-17T11:36:49-07:00

Borrelia burgdorferi is one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy of B. burgdorferi, orchestrated by a surface protein annotated as BBA57, through its...



SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-{kappa}B and interferon pathways [Microbiology]

2018-04-17T11:36:49-07:00

Sterile alpha motif and HD-domain–containing protein 1 (SAMHD1) blocks replication of retroviruses and certain DNA viruses by reducing the intracellular dNTP pool. SAMHD1 has been suggested to down-regulate IFN and inflammatory responses to viral infections, although the functions and mechanisms of SAMHD1 in modulating innate immunity remain unclear. Here, we...



Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth [Microbiology]

2018-04-17T11:36:49-07:00

The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that...



Spatial eye-hand coordination during bimanual reaching is not systematically coded in either LIP or PRR [Neuroscience]

2018-04-17T11:36:49-07:00

We often orient to where we are about to reach. Spatial and temporal correlations in eye and arm movements may depend on the posterior parietal cortex (PPC). Spatial representations of saccade and reach goals preferentially activate cells in the lateral intraparietal area (LIP) and the parietal reach region (PRR), respectively....



Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover [Neuroscience]

2018-04-17T11:36:49-07:00

Memory formation is believed to result from changes in synapse strength and structure. While memories may persist for the lifetime of an organism, the proteins and lipids that make up synapses undergo constant turnover with lifetimes from minutes to days. The molecular basis for memory maintenance may rely on a...



Negative regulator of E2F transcription factors links cell cycle checkpoint and DNA damage repair [Plant Biology]

2018-04-17T11:36:49-07:00

DNA damage poses a serious threat to genome integrity and greatly affects growth and development. To maintain genome stability, all organisms have evolved elaborate DNA damage response mechanisms including activation of cell cycle checkpoints and DNA repair. Here, we show that the DNA repair protein SNI1, a subunit of the...



Phytophthora palmivora establishes tissue-specific intracellular infection structures in the earliest divergent land plant lineage [Plant Biology]

2018-04-17T11:36:49-07:00

The expansion of plants onto land was a formative event that brought forth profound changes to the earth’s geochemistry and biota. Filamentous eukaryotic microbes developed the ability to colonize plant tissues early during the evolution of land plants, as demonstrated by intimate, symbiosis-like associations in >400 million-year-old fossils. However, the...



Climate change, human impacts, and carbon sequestration in China [Introductions]

2018-04-17T11:36:48-07:00

The scale of economic growth in China during the past three decades is unprecedented in modern human history. China is now the world’s second largest economic entity, next to the United States. However, this fast economic growth puts China’s environment under increasing stresses. China can be viewed as a massive...



Processes and patterns of interaction as units of selection: An introduction to ITSNTS thinking [Evolution]

2018-04-17T11:36:48-07:00

Many practicing biologists accept that nothing in their discipline makes sense except in the light of evolution, and that natural selection is evolution’s principal sense-maker. But what natural selection actually is (a force or a statistical outcome, for example) and the levels of the biological hierarchy (genes, organisms, species, or...



Origins and spread of fluted-point technology in the Canadian Ice-Free Corridor and eastern Beringia [Anthropology]

2018-04-17T11:36:49-07:00

Fluted projectile points have long been recognized as the archaeological signature of early humans dispersing throughout the Western Hemisphere; however, we still lack a clear understanding of their appearance in the interior “Ice-Free Corridor” of western Canada and eastern Beringia. To solve this problem, we conducted a geometric morphometric shape...



Human bony labyrinth is an indicator of population history and dispersal from Africa [Anthropology]

2018-04-17T11:36:49-07:00

The dispersal of modern humans from Africa is now well documented with genetic data that track population history, as well as gene flow between populations. Phenetic skeletal data, such as cranial and pelvic morphologies, also exhibit a dispersal-from-Africa signal, which, however, tends to be blurred by the effects of local...



Hip extensor mechanics and the evolution of walking and climbing capabilities in humans, apes, and fossil hominins [Anthropology]

2018-04-17T11:36:49-07:00

The evolutionary emergence of humans’ remarkably economical walking gait remains a focus of research and debate, but experimentally validated approaches linking locomotor capability to postcranial anatomy are limited. In this study, we integrated 3D morphometrics of hominoid pelvic shape with experimental measurements of hip kinematics and kinetics during walking and...



Multiscale mixing patterns in networks [Applied Mathematics]

2018-04-17T11:36:49-07:00

Assortative mixing in networks is the tendency for nodes with the same attributes, or metadata, to link to each other. It is a property often found in social networks, manifesting as a higher tendency of links occurring between people of the same age, race, or political belief. Quantifying the level...



Dramatic pressure-sensitive ion conduction in conical nanopores [Applied Physical Sciences]

2018-04-17T11:36:49-07:00

Ion transporters in Nature exhibit a wealth of complex transport properties such as voltage gating, activation, and mechanosensitive behavior. When combined, such processes result in advanced ionic machines achieving active ion transport, high selectivity, or signal processing. On the artificial side, there has been much recent progress in the design...



Oversized galactosides as a probe for conformational dynamics in LacY [Biochemistry]

2018-04-17T11:36:49-07:00

Binding kinetics of α-galactopyranoside homologs with fluorescent aglycones of different sizes and shapes were determined with the lactose permease (LacY) of Escherichia coli by FRET from Trp151 in the binding site of LacY to the fluorophores. Fast binding was observed with LacY stabilized in an outward-open conformation (kon = 4–20...



Observation of acetyl phosphate formation in mammalian mitochondria using real-time in-organelle NMR metabolomics [Biochemistry]

2018-04-17T11:36:49-07:00

Recent studies point out the link between altered mitochondrial metabolism and cancer, and detailed understanding of mitochondrial metabolism requires real-time detection of its metabolites. Employing heteronuclear 2D NMR spectroscopy and 13C3-pyruvate, we propose in-organelle metabolomics that allows for the monitoring of mitochondrial metabolic changes in real time. The approach identified...



Molecular structural diversity of mitochondrial cardiolipins [Biochemistry]

2018-04-17T11:36:49-07:00

Current strategies used to quantitatively describe the biological diversity of lipids by mass spectrometry are often limited in assessing the exact structural variability of individual molecular species in detail. A major challenge is represented by the extensive isobaric overlap present among lipids, hampering their accurate identification. This is especially true...



Cell contraction induces long-ranged stress stiffening in the extracellular matrix [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

Animal cells in tissues are supported by biopolymer matrices, which typically exhibit highly nonlinear mechanical properties. While the linear elasticity of the matrix can significantly impact cell mechanics and functionality, it remains largely unknown how cells, in turn, affect the nonlinear mechanics of their surrounding matrix. Here, we show that...



Label-free and charge-sensitive dynamic imaging of lipid membrane hydration on millisecond time scales [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

Biological membranes are highly dynamic and complex lipid bilayers, responsible for the fate of living cells. To achieve this function, the hydrating environment is crucial. However, membrane imaging typically neglects water, focusing on the insertion of probes, resonant responses of lipids, or the hydrophobic core. Owing to a recent improvement...



Structural dynamics is a determinant of the functional significance of missense variants [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

Accurate evaluation of the effect of point mutations on protein function is essential to assessing the genesis and prognosis of many inherited diseases and cancer types. Currently, a wealth of computational tools has been developed for pathogenicity prediction. Two major types of data are used to this aim: sequence conservation/evolution...



Microbes vs. chemistry in the origin of the anaerobic gut lumen [Biophysics and Computational Biology]

2018-04-17T11:36:49-07:00

The succession from aerobic and facultative anaerobic bacteria to obligate anaerobes in the infant gut along with the differences between the compositions of the mucosally adherent vs. luminal microbiota suggests that the gut microbes consume oxygen, which diffuses into the lumen from the intestinal tissue, maintaining the lumen in a...



Direct electrochemical observation of glucosidase activity in isolated single lysosomes from a living cell [Cell Biology]

2018-04-17T11:36:49-07:00

The protein activity in individual intracellular compartments in single living cells must be analyzed to obtain an understanding of protein function at subcellular locations. The current methodology for probing activity is often not resolved to the level of an individual compartment, and the results provide an extent of reaction that...



Increased autophagy blocks HER2-mediated breast tumorigenesis [Cell Biology]

2018-04-17T11:36:49-07:00

Allelic loss of the autophagy gene, beclin 1/BECN1, increases the risk of patients developing aggressive, including human epidermal growth factor receptor 2 (HER2)-positive, breast cancers; however, it is not known whether autophagy induction may be beneficial in preventing HER2-positive breast tumor growth. We explored the regulation of autophagy in breast...



TWEAK and RIPK1 mediate a second wave of cell death during AKI [Cell Biology]

2018-04-17T11:36:49-07:00

Acute kidney injury (AKI) is characterized by necrotic tubular cell death and inflammation. The TWEAK/Fn14 axis is a mediator of renal injury. Diverse pathways of regulated necrosis have recently been reported to contribute to AKI, but there are ongoing discussions on the timing or molecular regulators involved. We have now...



Precise characterization of KRAS4b proteoforms in human colorectal cells and tumors reveals mutation/modification cross-talk [Chemistry]

2018-04-17T11:36:49-07:00

Mutations of the KRAS gene are found in human cancers with high frequency and result in the constitutive activation of its protein products. This leads to aberrant regulation of downstream pathways, promoting cell survival, proliferation, and tumorigenesis that drive cancer progression and negatively affect treatment outcomes. Here, we describe a...



Characterizing the human hippocampus in aging and Alzheimer’s disease using a computational atlas derived from ex vivo MRI and histology [Computer Sciences]

2018-04-17T11:36:49-07:00

Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 ×...



Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart [Developmental Biology]

2018-04-17T11:36:49-07:00

In the zebrafish (Danio rerio), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with...



Critical impact of vegetation physiology on the continental hydrologic cycle in response to increasing CO2 [Earth, Atmospheric, and Planetary Sciences]

2018-04-17T11:36:49-07:00

Predicting how increasing atmospheric CO2 will affect the hydrologic cycle is of utmost importance for a range of applications ranging from ecological services to human life and activities. A typical perspective is that hydrologic change is driven by precipitation and radiation changes due to climate change, and that the land...



Effects of iron on the lattice thermal conductivity of Earth’s deep mantle and implications for mantle dynamics [Earth, Atmospheric, and Planetary Sciences]

2018-04-17T11:36:49-07:00

Iron may critically influence the physical properties and thermochemical structures of Earth’s lower mantle. Its effects on thermal conductivity, with possible consequences on heat transfer and mantle dynamics, however, remain largely unknown. We measured the lattice thermal conductivity of lower-mantle ferropericlase to 120 GPa using the ultrafast optical pump-probe technique...



Constraining the climate and ocean pH of the early Earth with a geological carbon cycle model [Earth, Atmospheric, and Planetary Sciences]

2018-04-17T11:36:49-07:00

The early Earth’s environment is controversial. Climatic estimates range from hot to glacial, and inferred marine pH spans strongly alkaline to acidic. Better understanding of early climate and ocean chemistry would improve our knowledge of the origin of life and its coevolution with the environment. Here, we use a geological...



Energetic tradeoffs control the size distribution of aquatic mammals [Earth, Atmospheric, and Planetary Sciences]

2018-04-17T11:36:49-07:00

Four extant lineages of mammals have invaded and diversified in the water: Sirenia, Cetacea, Pinnipedia, and Lutrinae. Most of these aquatic clades are larger bodied, on average, than their closest land-dwelling relatives, but the extent to which potential ecological, biomechanical, and physiological controls contributed to this pattern remains untested quantitatively....



Plant diversity enhances productivity and soil carbon storage [Biological Sciences]

2018-04-17T11:36:48-07:00

Despite evidence from experimental grasslands that plant diversity increases biomass production and soil organic carbon (SOC) storage, it remains unclear whether this is true in natural ecosystems, especially under climatic variations and human disturbances. Based on field observations from 6,098 forest, shrubland, and grassland sites across China and predictions from...



Economics- and policy-driven organic carbon input enhancement dominates soil organic carbon accumulation in Chinese croplands [Biological Sciences]

2018-04-17T11:36:49-07:00

China’s croplands have experienced drastic changes in management practices, such as fertilization, tillage, and residue treatments, since the 1980s. There is an ongoing debate about the impact of these changes on soil organic carbon (SOC) and its implications. Here we report results from an extensive study that provided direct evidence...



Impact of the tree prior on estimating clock rates during epidemic outbreaks [Evolution]

2018-04-17T11:36:49-07:00

Bayesian phylogenetics aims at estimating phylogenetic trees together with evolutionary and population dynamic parameters based on genetic sequences. It has been noted that the clock rate, one of the evolutionary parameters, decreases with an increase in the sampling period of sequences. In particular, clock rates of epidemic outbreaks are often...



Everolimus rescues multiple cellular defects in laminopathy-patient fibroblasts [Genetics]

2018-04-17T11:36:49-07:00

LMNA encodes the A-type lamins that are part of the nuclear scaffold. Mutations in LMNA can cause a variety of disorders called laminopathies, including Hutchinson-Gilford progeria syndrome (HGPS), atypical Werner syndrome, and Emery-Dreifuss muscular dystrophy. Previous work has shown that treatment of HGPS cells with the mTOR inhibitor rapamycin or...



High-accuracy lagging-strand DNA replication mediated by DNA polymerase dissociation [Genetics]

2018-04-17T11:36:49-07:00

The fidelity of DNA replication is a critical factor in the rate at which cells incur mutations. Due to the antiparallel orientation of the two chromosomal DNA strands, one strand (leading strand) is replicated in a mostly processive manner, while the other (lagging strand) is synthesized in short sections called...



Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells [Genetics]

2018-04-17T11:36:49-07:00

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is...



News Feature: The quest to solve sepsis [Medical Sciences]

2018-04-17T11:36:48-07:00

Researchers are learning more about the baffling, deadly condition. Treatments are elusive, but one thing’s for certain: timing is everything. At first, it looked like the flu. So doctors in Tolima, Colombia, advised Olga Peña’s 70-year-old father to rest and get plenty of fluids. Three days later, the elder Peña...



Learned immunosuppressive placebo responses in renal transplant patients [Medical Sciences]

2018-04-17T11:36:49-07:00

Patients after organ transplantation or with chronic, inflammatory autoimmune diseases require lifelong treatment with immunosuppressive drugs, which have toxic adverse effects. Recent insight into the neurobiology of placebo responses shows that associative conditioning procedures can be employed as placebo-induced dose reduction strategies in an immunopharmacological regimen. However, it is unclear...



Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis [Medical Sciences]

2018-04-17T11:36:49-07:00

Non–small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma (KRAS). Although KRAS direct binding to and activation of PI3K is required for KRAS-driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R)...



Intron retention induced by microsatellite expansions as a disease biomarker [Medical Sciences]

2018-04-17T11:36:49-07:00

Expansions of simple sequence repeats, or microsatellites, have been linked to ∼30 neurological–neuromuscular diseases. While these expansions occur in coding and noncoding regions, microsatellite sequence and repeat length diversity is more prominent in introns with eight different trinucleotide to hexanucleotide repeats, causing hereditary diseases such as myotonic dystrophy type 2...



A small-molecule fragment that emulates binding of receptor and broadly neutralizing antibodies to influenza A hemagglutinin [Microbiology]

2018-04-17T11:36:49-07:00

The influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a...



Flavivirus internalization is regulated by a size-dependent endocytic pathway [Microbiology]

2018-04-17T11:36:49-07:00

Flaviviruses enter host cells through the process of clathrin-mediated endocytosis, and the spectrum of host factors required for this process are incompletely understood. Here we found that lymphocyte antigen 6 locus E (LY6E) promotes the internalization of multiple flaviviruses, including West Nile virus, Zika virus, and dengue virus. Perhaps surprisingly,...



Second-order spinal cord pathway contributes to cortical responses after long recoveries from dorsal column injury in squirrel monkeys [Neuroscience]

2018-04-17T11:36:49-07:00

Months after the occurrence of spinal cord dorsal column lesions (DCLs) at the cervical level, neural responses in the hand representation of somatosensory area 3b hand cortex recover, along with hand use. To examine whether the second-order spinal cord pathway contributes to this functional recovery, we injected cholera toxin subunit...



Psychophysical evidence for auditory motion parallax [Neuroscience]

2018-04-17T11:36:49-07:00

Distance is important: From an ecological perspective, knowledge about the distance to either prey or predator is vital. However, the distance of an unknown sound source is particularly difficult to assess, especially in anechoic environments. In vision, changes in perspective resulting from observer motion produce a reliable, consistent, and unambiguous...



Ectopic neurogenesis induced by prenatal antiepileptic drug exposure augments seizure susceptibility in adult mice [Neuroscience]

2018-04-17T11:36:49-07:00

Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring...



Long-term in vivo recording of circadian rhythms in brains of freely moving mice [Neuroscience]

2018-04-17T11:36:49-07:00

Endogenous circadian clocks control 24-h physiological and behavioral rhythms in mammals. Here, we report a real-time in vivo fluorescence recording system that enables long-term monitoring of circadian rhythms in the brains of freely moving mice. With a designed reporter of circadian clock gene expression, we tracked robust Cry1 transcription reporter...



Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal [Pharmacology]

2018-04-17T11:36:49-07:00

Cigarette smoking is the leading cause of preventable disease and death in the United States, with more persons dying from nicotine addiction than any other preventable cause of death. Even though smoking cessation incurs multiple health benefits, the abstinence rate remains low with current medications. Here we show that the...



The computational form of craving is a selective multiplication of economic value [Psychological and Cognitive Sciences]

2018-04-17T11:36:49-07:00

Craving is thought to be a specific desire state that biases choice toward the desired object, be it chocolate or drugs. A vast majority of people report having experienced craving of some kind. In its pathological form craving contributes to health outcomes in addiction and obesity. Yet despite its ubiquity...



China, the United States, and competition for resources that enable emerging technologies [Sustainability Science]

2018-04-17T11:36:49-07:00

Historically, resource conflicts have often centered on fuel minerals (particularly oil). Future resource conflicts may, however, focus more on competition for nonfuel minerals that enable emerging technologies. Whether it is rhenium in jet engines, indium in flat panel displays, or gallium in smart phones, obscure elements empower smarter, smaller, and...



Carbon pools in China’s terrestrial ecosystems: New estimates based on an intensive field survey [Biological Sciences]

2018-04-17T11:36:48-07:00

China’s terrestrial ecosystems have functioned as important carbon sinks. However, previous estimates of carbon budgets have included large uncertainties owing to the limitations of sample size, multiple data sources, and inconsistent methodologies. In this study, we conducted an intensive field campaign involving 14,371 field plots to investigate all sectors of...



Patterns of plant carbon, nitrogen, and phosphorus concentration in relation to productivity in China’s terrestrial ecosystems [Biological Sciences]

2018-04-17T11:36:48-07:00

Plant nitrogen (N) and phosphorus (P) content regulate productivity and carbon (C) sequestration in terrestrial ecosystems. Estimates of the allocation of N and P content in plant tissues and the relationship between nutrient content and photosynthetic capacity are critical to predicting future ecosystem C sequestration under global change. In this...



Effects of national ecological restoration projects on carbon sequestration in China from 2001 to 2010 [Biological Sciences]

2018-04-17T11:36:49-07:00

The long-term stressful utilization of forests and grasslands has led to ecosystem degradation and C loss. Since the late 1970s China has launched six key national ecological restoration projects to protect its environment and restore degraded ecosystems. Here, we conducted a large-scale field investigation and a literature survey of biomass...



Shifting plant species composition in response to climate change stabilizes grassland primary production [Biological Sciences]

2018-04-17T11:36:49-07:00

The structure and function of alpine grassland ecosystems, including their extensive soil carbon stocks, are largely shaped by temperature. The Tibetan Plateau in particular has experienced significant warming over the past 50 y, and this warming trend is projected to intensify in the future. Such climate change will likely alter...



Robust, linear correlations between growth rates and {beta}-lactam-mediated lysis rates [Systems Biology]

2018-04-17T11:36:49-07:00

It is widely acknowledged that faster-growing bacteria are killed faster by β-lactam antibiotics. This notion serves as the foundation for the concept of bacterial persistence: dormant bacterial cells that do not grow are phenotypically tolerant against β-lactam treatment. Such correlation has often been invoked in the mathematical modeling of bacterial...



Role of metabolic spatiotemporal dynamics in regulating biofilm colony expansion [Systems Biology]

2018-04-17T11:36:49-07:00

Cell fate determination is typically regulated by biological networks, yet increasing evidences suggest that cell−cell communication and environmental stresses play crucial roles in the behavior of a cell population. A recent microfluidic experiment showed that the metabolic codependence of two cell populations generates a collective oscillatory dynamic during the expansion...



Correction for Ramus et al,. An invasive foundation species enhances multifunctionality in a coastal ecosystem [Correction]

2018-04-17T11:36:49-07:00

ECOLOGY, SUSTAINABILITY SCIENCE Correction for “An invasive foundation species enhances multifunctionality in a coastal ecosystem,” by Aaron P. Ramus, Brian R. Silliman, Mads S. Thomsen, and Zachary T. Long, which was first published July 17, 2017; 10.1073/pnas.1700353114 (Proc Natl Acad Sci USA 114:8580–8585). The editors note that a conflict of...



Correction for Chen et al., B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction [Correction]

2018-04-17T11:36:49-07:00

IMMUNOLOGY AND INFLAMMATION Correction for “B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction,” by Ling Chen, Takeshi Azuma, Weiwei Yu, Xu Zheng, Liqun Luo, and Lieping Chen, which was first published March 5, 2018; 10.1073/pnas.1722043115 (Proc Natl Acad Sci USA 115:3126–3131). The...



Correction for Li et al., Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload [Correction]

2018-04-17T11:36:49-07:00

MEDICAL SCIENCES Correction for “Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload,” by Hongliang Li, Chengwei He, Jinhua Feng, Yan Zhang, Qizhu Tang, Zhouyan Bian, Xue Bai, Heng Zhou, Hong Jiang, Scott P. Heximer, Mu Qin, He Huang, Peter. P....



Correction for Itkin et al., The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii [Correction]

2018-04-17T11:36:49-07:00

PLANT BIOLOGY Correction for “The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii,” by Maxim Itkin, Rachel Davidovich-Rikanati, Shahar Cohen, Vitaly Portnoy, Adi Doron-Faigenboim, Elad Oren, Shiri Freilich, Galil Tzuri, Nadine Baranes, Shmuel Shen, Marina Petreikov, Rotem Sertchook, Shifra Ben-Dor, Hugo Gottlieb, Alvaro Hernandez, David R....



In This Issue [This Week in PNAS]

2018-04-10T12:01:40-07:00

Pheromone distinguishes termite royalty from worker castes Primary queen of R. flavipes with attendant workers. Image courtesy of Matt Bertone (North Carolina State University, Raleigh, NC). For eusocial insects, caste systems prescribe crucial social and reproductive division of labor. Nestmates primarily recognize one another and their roles within the colony...



Our humanity contains multitudes: Dehumanization is more than overlooking mental capacities [Social Sciences]

2018-04-10T12:01:41-07:00

A longstanding conclusion of work on dehumanization is that the denial of humanity facilitates violence, in part by loosening restraints against harming others (1–3). Rai et al. (4) propose that dehumanization only begets instrumental violence. They claim that dehumanization does not facilitate moral violence because moral violence necessitates blame and...



Reply to Fincher et al.: Conceptual specificity in dehumanization research is a feature, not a bug [Social Sciences]

2018-04-10T12:01:41-07:00

Fincher et al. (1) argue that our conceptualization of dehumanization as “the failure to engage in social cognition of other human minds” (2) is too narrow. Importantly, Fincher et al. (1) do not dispute our actual findings. They agree that reduced perception of mental and emotional states in victims generates...



Profile of Dorothy L. Cheney and Robert M. Seyfarth [Profiles]

2018-04-10T12:01:40-07:00

Field studies in Africa over the past four decades by ethologists Dorothy Cheney and Robert Seyfarth have uncovered a trove of insights into the behavior, communication, and social cognition of nonhuman primates. The pair’s research further reveals evolutionary antecedents of the human mind. University of Pennsylvania professors emeriti, Cheney and...



Global amphibian declines have winners and losers [Ecology]

2018-04-10T12:01:40-07:00

Global change imperils a large swath of the planet’s biodiversity, portending a future with decreasing species richness and functioning of natural ecosystems (1). However, the effects of global change are highly variable across scales (2). For example, while the data are contentious, patterns of local stability or increases in species...



BDNF signaling: Harnessing stress to battle mood disorder [Neuroscience]

2018-04-10T12:01:40-07:00

The link between the onset of major depressive disorder (MDD) and loss of neurotrophins in the brain is of interest to clinicians and basic scientists. MDD is caused by a combination of genetic, environmental, and psychological factors. Trauma, chronic health problems, and substance abuse are risks (1), as are grief...



Good news and bad news of blue carbon [Ecology]

2018-04-10T12:01:40-07:00

Traditionally, ocean acidification researchers have focused on how secular changes in carbon dioxide (CO2) or pH will impact organisms. Global mean pH is estimated to have decreased by 0.1 pH units (representing a 28% increase in acidity) since the preindustrial age and may drop another 0.3 pH units by the...



Water-like anomalies as a function of tetrahedrality [Applied Physical Sciences]

2018-04-10T12:01:41-07:00

Tetrahedral interactions describe the behavior of the most abundant and technologically important materials on Earth, such as water, silicon, carbon, germanium, and countless others. Despite their differences, these materials share unique common physical behaviors, such as liquid anomalies, open crystalline structures, and extremely poor glass-forming ability at ambient pressure. To...



Local protein solvation drives direct down-conversion in phycobiliprotein PC645 via incoherent vibronic transport [Chemistry]

2018-04-10T12:01:41-07:00

The mechanisms controlling excitation energy transport (EET) in light-harvesting complexes remain controversial. Following the observation of long-lived beats in 2D electronic spectroscopy of PC645, vibronic coherence, the delocalization of excited states between pigments supported by a resonant vibration, has been proposed to enable direct excitation transport from the highest-energy to...



Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles [Chemistry]

2018-04-10T12:01:41-07:00

The development of safe and efficacious gene vectors has limited greatly the potential for therapeutic treatments based on messenger RNA (mRNA). Lipid nanoparticles (LNPs) formed by an ionizable cationic lipid (here DLin-MC3-DMA), helper lipids (distearoylphosphatidylcholine, DSPC, and cholesterol), and a poly(ethylene glycol) (PEG) lipid have been identified as very promising...



Escalation of competition into conflict in competitive networks of Formula One drivers [Social Sciences]

2018-04-10T12:01:41-07:00

This article investigates the factors that escalate competition into dangerous conflict. Recent sociological theorizing claims that such escalations are particularly likely in dyads of structurally equivalent people (i.e., actors who have the same relations with the same third parties). Using panel data on Formula One races from 1970 through 2014,...



MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis [Biochemistry]

2018-04-10T12:01:41-07:00

The MDM2 homolog MDMX oncoprotein is indispensable for inhibition of p53 during normal embryonic development and malignant transformation, yet how MDMX harnesses p53 functions is unclear. In addition to a canonical N-terminal p53-binding domain, recent work suggests the central acidic domain of MDMX regulates p53 interaction through intramolecular mimicry and...



IpdAB, a virulence factor in Mycobacterium tuberculosis, is a cholesterol ring-cleaving hydrolase [Biochemistry]

2018-04-10T12:01:41-07:00

Mycobacterium tuberculosis (Mtb) grows on host-derived cholesterol during infection. IpdAB, found in all steroid-degrading bacteria and a determinant of pathogenicity, has been implicated in the hydrolysis of the last steroid ring. Phylogenetic analyses revealed that IpdAB orthologs form a clade of CoA transferases (CoTs). In a coupled assay with a...