Τετάρτη 18 Μαρτίου 2020


Eye movements support behavioral pattern completion [Psychological and Cognitive Sciences]
The ability to recall a detailed event from a simple reminder is supported by pattern completion, a cognitive operation performed by the hippocampus wherein existing mnemonic representations are retrieved from incomplete input. In behavioral studies, pattern completion is often inferred through the false endorsement of lure (i.e., similar) items as...
Proceedings of the National Academy of Sciences current issue
14h
Connectivity at the origins of domain specificity in the cortical face and place networks [Psychological and Cognitive Sciences]
It is well established that the adult brain contains a mosaic of domain-specific networks. But how do these domain-specific networks develop? Here we tested the hypothesis that the brain comes prewired with connections that precede the development of domain-specific function. Using resting-state fMRI in the youngest sample of newborn humans...
Proceedings of the National Academy of Sciences current issue
14h
Metabolic and genetic basis for auxotrophies in Gram-negative species [Systems Biology]
Auxotrophies constrain the interactions of bacteria with their environment, but are often difficult to identify. Here, we develop an algorithm (AuxoFind) using genome-scale metabolic reconstruction to predict auxotrophies and apply it to a series of available genome sequences of over 1,300 Gram-negative strains. We identify 54 auxotrophs, along with the...
Proceedings of the National Academy of Sciences current issue
14h
Speakers are able to categorize vowels based on tongue somatosensation [Psychological and Cognitive Sciences]
Auditory speech perception enables listeners to access phonological categories from speech sounds. During speech production and speech motor learning, speakers’ experience matched auditory and somatosensory input. Accordingly, access to phonetic units might also be provided by somatosensory information. The present study assessed whether humans can identify vowels using somatosensory feedback,...
Proceedings of the National Academy of Sciences current issue
14h
Regulation of stomatal development by stomatal lineage miRNAs [Plant Biology]
Stomata in the plant epidermis play a critical role in growth and survival by controlling gas exchange, transpiration, and immunity to pathogens. Plants modulate stomatal cell fate and patterning through key transcriptional factors and signaling pathways. MicroRNAs (miRNAs) are known to contribute to developmental plasticity in multicellular organisms; however, no...
Proceedings of the National Academy of Sciences current issue
14h
Carbon export from leaves is controlled via ubiquitination and phosphorylation of sucrose transporter SUC2 [Plant Biology]
All multicellular organisms keep a balance between sink and source activities by controlling nutrient transport at strategic positions. In most plants, photosynthetically produced sucrose is the predominant carbon and energy source, whose transport from leaves to carbon sink organs depends on sucrose transporters. In the model plant Arabidopsis thaliana, transport...
Proceedings of the National Academy of Sciences current issue
14h
Triacylglycerol and phytyl ester synthesis in Synechocystis sp. PCC6803 [Plant Biology]
Cyanobacteria are unicellular prokaryotic algae that perform oxygenic photosynthesis, similar to plants. The cells harbor thylakoid membranes composed of lipids related to those of chloroplasts in plants to accommodate the complexes of photosynthesis. The occurrence of storage lipids, including triacylglycerol or wax esters, which are found in plants, animals, and...
Proceedings of the National Academy of Sciences current issue
14h
Transcriptional repression specifies the central cell for double fertilization [Plant Biology]
Double fertilization is a key innovation for the evolutionary success of angiosperms by which the two fertilized female gametes, the egg cell and central cell, generate the embryo and endosperm, respectively. The female gametophyte (embryo sac) enclosed in the sporophyte is derived from a one-celled haploid cell lineage. It undergoes...
Proceedings of the National Academy of Sciences current issue
14h
CUL3BPM E3 ubiquitin ligases regulate MYC2, MYC3, and MYC4 stability and JA responses [Plant Biology]
The jasmonate (JA)-pathway regulators MYC2, MYC3, and MYC4 are central nodes in plant signaling networks integrating environmental and developmental signals to fine-tune JA defenses and plant growth. Continuous activation of MYC activity is potentially lethal. Hence, MYCs need to be tightly regulated in order to optimize plant fitness. Among the...
Proceedings of the National Academy of Sciences current issue
14h
Nf1 deletion results in depletion of the Lhx6 transcription factor and a specific loss of parvalbumin+ cortical interneurons [Neuroscience]
Neurofibromatosis 1 (NF1) is caused by mutations in the NF1 gene, which encodes the protein, neurofibromin, an inhibitor of Ras activity. Cortical GABAergic interneurons (CINs) are implicated in NF1 pathology, but the cellular and molecular changes to CINs are unknown. We deleted mouse Nf1 from the medial ganglionic eminence, which...
Proceedings of the National Academy of Sciences current issue
14h
Context-dependent operation of neural circuits underlies a navigation behavior in Caenorhabditis elegans [Neuroscience]
The nervous system evaluates environmental cues and adjusts motor output to ensure navigation toward a preferred environment. The nematode Caenorhabditis elegans navigates in the thermal environment and migrates toward its cultivation temperature by moving up or down thermal gradients depending not only on absolute temperature but on relative difference between...
Proceedings of the National Academy of Sciences current issue
14h
Anterior cingulate cortex is necessary for adaptation of action plans [Neuroscience]
Previous research has focused on the anterior cingulate cortex (ACC) as a key brain region in the mitigation of the competition that arises from two simultaneously active signals. However, to date, no study has demonstrated that ACC is necessary for this form of behavioral flexibility, nor have any studies shown...
Proceedings of the National Academy of Sciences current issue
14h
Structural elucidation of the Clostridioides difficile transferase toxin reveals a single-site binding mode for the enzyme [Microbiology]
Clostridioides difficile is a Gram-positive, pathogenic bacterium and a prominent cause of hospital-acquired diarrhea in the United States. The symptoms of C. difficile infection are caused by the activity of three large toxins known as toxin A (TcdA), toxin B (TcdB), and the C. difficile transferase toxin (CDT). Reported here...
Proceedings of the National Academy of Sciences current issue
14h
Class A PBPs have a distinct and unique role in the construction of the pneumococcal cell wall [Microbiology]
In oval-shaped Streptococcus pneumoniae, septal and longitudinal peptidoglycan syntheses are performed by independent functional complexes: the divisome and the elongasome. Penicillin-binding proteins (PBPs) were long considered the key peptidoglycan-synthesizing enzymes in these complexes. Among these were the bifunctional class A PBPs, which are both glycosyltransferases and transpeptidases, and monofunctional class...
Proceedings of the National Academy of Sciences current issue
14h
Visualizing the translation and packaging of HIV-1 full-length RNA [Microbiology]
HIV-1 full-length RNA (HIV-1 RNA) plays a central role in viral replication, serving as a template for Gag/Gag-Pol translation and as a genome for the progeny virion. To gain a better understanding of the regulatory mechanisms of HIV-1 replication, we adapted a recently described system to visualize and track translation...
Proceedings of the National Academy of Sciences current issue
14h
Biphasic chemotaxis of Escherichia coli to the microbiota metabolite indole [Microbiology]
Bacterial chemotaxis to prominent microbiota metabolites such as indole is important in the formation of microbial communities in the gastrointestinal (GI) tract. However, the basis of chemotaxis to indole is poorly understood. Here, we exposed Escherichia coli to a range of indole concentrations and measured the dynamic responses of individual...
Proceedings of the National Academy of Sciences current issue
14h
A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets [Medical Sciences]
Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human...
Proceedings of the National Academy of Sciences current issue
14h
Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry [Microbiology]
Virus replication requires critical interactions between viral proteins and cellular proteins that mediate many aspects of infection, including the transport of viral genomes to the site of replication. In human papillomavirus (HPV) infection, the cellular protein complex known as retromer binds to the L2 capsid protein and sorts incoming virions...
Proceedings of the National Academy of Sciences current issue
14h
Immunotoxin SS1P is rapidly removed by proximal tubule cells of kidney, whose damage contributes to albumin loss in urine [Medical Sciences]
Recombinant immunotoxins (RITs) are chimeric proteins composed of an Fv and a protein toxin being developed for cancer treatment. The Fv brings the toxin to the cancer cell, but most of the RITs do not reach the tumor and are removed by other organs. To identify cells responsible for RIT...
Proceedings of the National Academy of Sciences current issue
14h
Abrogation of esophageal carcinoma development in miR-31 knockout rats [Medical Sciences]
MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following N-nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to...
Proceedings of the National Academy of Sciences current issue
14h
Regulation of B cell receptor-dependent NF-{kappa}B signaling by the tumor suppressor KLHL14 [Medical Sciences]
The KLHL14 gene acquires frequent inactivating mutations in mature B cell malignancies, especially in the MYD88L265P, CD79B mutant (MCD) genetic subtype of diffuse large B cell lymphoma (DLBCL), which relies on B cell receptor (BCR) signaling for survival. However, the pathogenic role of KLHL14 in DLBCL and its molecular function...
Proceedings of the National Academy of Sciences current issue
14h
Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism [Immunology and Inflammation]
T helper (Th) cells are CD4+ effector T cells that play a critical role in immunity by shaping the inflammatory cytokine environment in a variety of physiological and pathological situations. Using a combined chemico-genetic approach, we identify histone H3K27 demethylases KDM6A and KDM6B as central regulators of human Th subsets....
Proceedings of the National Academy of Sciences current issue
14h
TDP-43 {alpha}-helical structure tunes liquid-liquid phase separation and function [Biophysics and Computational Biology]
Liquid–liquid phase separation (LLPS) is involved in the formation of membraneless organelles (MLOs) associated with RNA processing. The RNA-binding protein TDP-43 is present in several MLOs, undergoes LLPS, and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). While some ALS-associated mutations in TDP-43 disrupt self-interaction and function,...
Proceedings of the National Academy of Sciences current issue
14h
Tetraspanin-6 negatively regulates exosome production [Cell Biology]
Exosomes, extracellular vesicles (EVs) of endosomal origin, emerge as master regulators of cell-to-cell signaling in physiology and disease. Exosomes are highly enriched in tetraspanins (TSPNs) and syndecans (SDCs), the latter occurring mainly in proteolytically cleaved form, as membrane-spanning C-terminal fragments of the proteins. While both protein families are membrane scaffolds...
Proceedings of the National Academy of Sciences current issue
14h
The atomistic level structure for the activated human {kappa}-opioid receptor bound to the full Gi protein and the MP1104 agonist [Biophysics and Computational Biology]
The kappa opioid receptor (κOR) is an important target for pain therapeutics to reduce depression and other harmful side effects of existing medications. The analgesic activity is mediated by κOR signaling through the adenylyl cyclase-inhibitory family of Gi protein. Here, we report the three-dimensional (3D) structure for the active state...
Proceedings of the National Academy of Sciences current issue
14h
Frameshifting preserves key physicochemical properties of proteins [Biophysics and Computational Biology]
Frameshifts in protein coding sequences are widely perceived as resulting in either nonfunctional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that, in contrast, several key physicochemical properties...
Proceedings of the National Academy of Sciences current issue
14h
Abrogation of prenucleation, transient oligomerization of the Huntingtin exon 1 protein by human profilin I [Biophysics and Computational Biology]
Human profilin I reduces aggregation and concomitant toxicity of the polyglutamine-containing N-terminal region of the huntingtin protein encoded by exon 1 (httex1) and responsible for Huntington’s disease. Here, we investigate the interaction of profilin with httex1 using NMR techniques designed to quantitatively analyze the kinetics and equilibria of chemical exchange...
Proceedings of the National Academy of Sciences current issue
14h
The functional activity of E-cadherin controls tumor cell metastasis at multiple steps [Cell Biology]
E-cadherin is a tumor suppressor protein, and the loss of its expression in association with the epithelial mesenchymal transition (EMT) occurs frequently during tumor metastasis. However, many metastases continue to express E-cadherin, and a full EMT is not always necessary for metastasis; also, positive roles for E-cadherin expression in metastasis...
Proceedings of the National Academy of Sciences current issue
14h
Cas9 interrogates DNA in discrete steps modulated by mismatches and supercoiling [Biophysics and Computational Biology]
The CRISPR-Cas9 nuclease has been widely repurposed as a molecular and cell biology tool for its ability to programmably target and cleave DNA. Cas9 recognizes its target site by unwinding the DNA double helix and hybridizing a 20-nucleotide section of its associated guide RNA to one DNA strand, forming an...
Proceedings of the National Academy of Sciences current issue
14h
An allosteric switch regulates Mycobacterium tuberculosis ClpP1P2 protease function as established by cryo-EM and methyl-TROSY NMR [Biophysics and Computational Biology]
The 300-kDa ClpP1P2 protease from Mycobacterium tuberculosis collaborates with the AAA+ (ATPases associated with a variety of cellular activities) unfoldases, ClpC1 and ClpX, to degrade substrate proteins. Unlike in other bacteria, all of the components of the Clp system are essential for growth and virulence of mycobacteria, and their inhibitors...
Proceedings of the National Academy of Sciences current issue
14h
Charge-dependent interactions of monomeric and filamentous actin with lipid bilayers [Biophysics and Computational Biology]
The cytoskeletal protein actin polymerizes into filaments that are essential for the mechanical stability of mammalian cells. In vitro experiments showed that direct interactions between actin filaments and lipid bilayers are possible and that the net charge of the bilayer as well as the presence of divalent ions in the...
Proceedings of the National Academy of Sciences current issue
14h
Active efficient coding explains the development of binocular vision and its failure in amblyopia [Biophysics and Computational Biology]
The development of vision during the first months of life is an active process that comprises the learning of appropriate neural representations and the learning of accurate eye movements. While it has long been suspected that the two learning processes are coupled, there is still no widely accepted theoretical framework...
Proceedings of the National Academy of Sciences current issue
14h
Epistatic contributions promote the unification of incompatible models of neutral molecular evolution [Biophysics and Computational Biology]
We introduce a model of amino acid sequence evolution that accounts for the statistical behavior of real sequences induced by epistatic interactions. We base the model dynamics on parameters derived from multiple sequence alignments analyzed by using direct coupling analysis methodology. Known statistical properties such as overdispersion, heterotachy, and gamma-distributed...
Proceedings of the National Academy of Sciences current issue
14h
Cyp2c44 regulates prostaglandin synthesis, lymphangiogenesis, and metastasis in a mouse model of breast cancer [Cell Biology]
Arachidonic acid epoxides generated by cytochrome P450 (CYP) enzymes have been linked to increased tumor growth and metastasis, largely on the basis of overexpression studies and the application of exogenous epoxides. Here we studied tumor growth and metastasis in Cyp2c44−/− mice crossed onto the polyoma middle T oncogene (PyMT) background....
Proceedings of the National Academy of Sciences current issue
14h
Lactate dehydrogenase inhibition synergizes with IL-21 to promote CD8+ T cell stemness and antitumor immunity [Immunology and Inflammation]
Interleukin (IL)-2 and IL-21 dichotomously shape CD8+ T cell differentiation. IL-2 drives terminal differentiation, generating cells that are poorly effective against tumors, whereas IL-21 promotes stem cell memory T cells (TSCM) and antitumor responses. Here we investigated the role of metabolic programming in the developmental differences induced by these cytokines....
Proceedings of the National Academy of Sciences current issue
14h
Assessing the role of live poultry trade in community-structured transmission of avian influenza in China [Environmental Sciences]
The live poultry trade is thought to play an important role in the spread and maintenance of highly pathogenic avian influenza A viruses (HP AIVs) in Asia. Despite an abundance of small-scale observational studies, the role of the poultry trade in disseminating AIV over large geographic areas is still unclear,...
Proceedings of the National Academy of Sciences current issue
14h
DNA polymerase {delta} proofreads errors made by DNA polymerase ϵ [Genetics]
During eukaryotic replication, DNA polymerases ε (Polε) and δ (Polδ) synthesize the leading and lagging strands, respectively. In a long-known contradiction to this model, defects in the fidelity of Polε have a much weaker impact on mutagenesis than analogous Polδ defects. It has been previously proposed that Polδ contributes more...
Proceedings of the National Academy of Sciences current issue
14h
Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia [Genetics]
Despite a growing number of ion channel genes implicated in hereditary ataxia, it remains unclear how ion channel mutations lead to loss-of-function or death of cerebellar neurons. Mutations in the gene KCNMA1, encoding the α-subunit of the BK channel have emerged as responsible for a variety of neurological phenotypes. We...
Proceedings of the National Academy of Sciences current issue
14h
Regulatory CD8 T cells that recognize Qa-1 expressed by CD4 T-helper cells inhibit rejection of heart allografts [Immunology and Inflammation]
Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg)...
Proceedings of the National Academy of Sciences current issue
14h

Unique reproductive strategy in the swamp wallaby [Developmental Biology]
Reproduction in mammals requires distinct cycles of ovulation, fertilization, pregnancy, and lactation often interspersed with periods of anoestrus when breeding does not occur. Macropodids, the largest extant species of marsupials, the kangaroos and wallabies, have a very different reproductive strategy to most eutherian mammals whereby young are born at a...
Proceedings of the National Academy of Sciences current issue
14h
The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus [Genetics]
Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and...
Proceedings of the National Academy of Sciences current issue
14h
Diet modulates brain network stability, a biomarker for brain aging, in young adults [Neuroscience]
Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between...
Proceedings of the National Academy of Sciences current issue
14h
Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation [Immunology and Inflammation]
Ocular inflammation is a major cause of visual impairment attributed to dysregulation of the immune system. Previously, we have shown that the receptor for growth-hormone–releasing hormone (GHRH-R) affects multiple inflammatory processes. To clarify the pathological roles of GHRH-R in acute ocular inflammation, we investigated the inflammatory cascades mediated by this...
Proceedings of the National Academy of Sciences current issue
14h
Sensory cilia as the Achilles heel of nematodes when attacked by carnivorous mushrooms [Genetics]
Fungal predatory behavior on nematodes has evolved independently in all major fungal lineages. The basidiomycete oyster mushroom Pleurotus ostreatus is a carnivorous fungus that preys on nematodes to supplement its nitrogen intake under nutrient-limiting conditions. Its hyphae can paralyze nematodes within a few minutes of contact, but the mechanism had...
Proceedings of the National Academy of Sciences current issue
14h
Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals [Evolution]
Understanding the molecular basis of adaptation to the environment is a central question in evolutionary biology, yet linking detected signatures of positive selection to molecular mechanisms remains challenging. Here we demonstrate that combining sequence-based phylogenetic methods with structural information assists in making such mechanistic interpretations on a genomic scale. Our...
Proceedings of the National Academy of Sciences current issue
14h
Clonemate cotransmission supports a role for kin selection in a puppeteer parasite [Evolution]
Host manipulation by parasites is a fascinating evolutionary outcome, but adaptive scenarios that often accompany even iconic examples in this popular field of study are speculative. Kin selection has been invoked as a means of explaining the evolution of an altruistic-based, host-manipulating behavior caused by larvae of the lancet fluke...
Proceedings of the National Academy of Sciences current issue
14h
Assessing thyroid cancer risk using polygenic risk scores [Genetics]
Genome-wide association studies (GWASs) have identified at least 10 single-nucleotide polymorphisms (SNPs) associated with papillary thyroid cancer (PTC) risk. Most of these SNPs are common variants with small to moderate effect sizes. Here we assessed the combined genetic effects of these variants on PTC risk by using summarized GWAS results...
Proceedings of the National Academy of Sciences current issue
14h
Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons [Genetics]
Endogenous retroviruses and long terminal repeat (LTR) retrotransposons are mobile genetic elements that are closely related to retroviruses. Desilenced endogenous retroviruses are associated with human autoimmune disorders and neurodegenerative diseases. Caenorhabditis elegans and related Caenorhabditis spp. contain LTR retrotransposons and, as described here, numerous integrated viral genes including viral envelope...
Proceedings of the National Academy of Sciences current issue
14h
Sympatric speciation of wild emmer wheat driven by ecology and chromosomal rearrangements [Evolution]
In plants, the mechanism for ecological sympatric speciation (SS) is little known. Here, after ruling out the possibility of secondary contact, we show that wild emmer wheat, at the microclimatically divergent microsite of “Evolution Canyon” (EC), Mt. Carmel, Israel, underwent triple SS. Initially, it split following a bottleneck of an...
Proceedings of the National Academy of Sciences current issue
14h
Dramatic dietary shift maintains sequestered toxins in chemically defended snakes [Evolution]
Unlike other snakes, most species of Rhabdophis possess glands in their dorsal skin, sometimes limited to the neck, known as nucho-dorsal and nuchal glands, respectively. Those glands contain powerful cardiotonic steroids known as bufadienolides, which can be deployed as a defense against predators. Bufadienolides otherwise occur only in toads (Bufonidae)...
Proceedings of the National Academy of Sciences current issue
14h
Embedded droplet printing in yield-stress fluids [Engineering]
Microfluidic tools and techniques for manipulating fluid droplets have become core to many scientific and technological fields. Despite the plethora of existing approaches to fluidic manipulation, non-Newtonian fluid phenomena are rarely taken advantage of. Here we introduce embedded droplet printing—a system and methods for the generation, trapping, and processing of...
Proceedings of the National Academy of Sciences current issue
14h
Hierarchically porous Au nanostructures with interconnected channels for efficient mass transport in electrocatalytic CO2 reduction [Engineering]
Electrocatalytic CO2 reduction is a promising way to provide renewable energy from gaseous CO2. The development of nanostructures improves energy efficiency and selectivity for value-added chemicals, but complex nanostructures limit the CO2 conversion rates due to poor mass transport during vigorous electrolysis. Herein, we propose a three-dimensional (3D) hierarchically porous...
Proceedings of the National Academy of Sciences current issue
14h
Inner Workings: Understanding the evolution of cell types to explain the roots of animal diversity [Evolution]
Sponges have the simplest of bodies, harboring a delicate system of canals through which water flows. So it was a surprise when researchers recently discovered that sponges have as many as 18 cell types, including one with hybrid immune and neuronal properties—even though sponges don’t have any brain to speak...
Proceedings of the National Academy of Sciences current issue
14h
Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions [Biophysics and Computational Biology]
Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low...
Proceedings of the National Academy of Sciences current issue
14h
Possibility for inhibited spontaneous emission in electromagnetically open parity-time-symmetric guiding structures [Applied Physical Sciences]
Remote sensing and manipulation of quantum emitters are functionalities of significant practical importance in quantum optics. Unfortunately, these abilities are considered as fundamentally challenging in systems of inhibited spontaneous emission. The reason is intimately related to the common perception that, in order to nullify the spontaneous emission decay rate, the...
Proceedings of the National Academy of Sciences current issue
14h
Coastal wetlands reduce property damage during tropical cyclones [Environmental Sciences]
Coastal wetlands dampen the impact of storm surge and strong winds. Studies on the economic valuation of this protective service provided by wetland ecosystems are, however, rare. Here, we analyze property damage caused by 88 tropical storms and hurricanes hitting the United States between 1996 and 2016 and show that...
Proceedings of the National Academy of Sciences current issue
14h
Systematic identification of engineered methionines and oxaziridines for efficient, stable, and site-specific antibody bioconjugation [Chemistry]
The field of chemical modification of proteins has been dominated by random modification of lysines or more site-specific labeling of cysteines, each with attendant challenges. Recently, we have developed oxaziridine chemistry for highly selective modification of methionine called redox-activated chemical tagging (ReACT) but have not broadly tested the molecular parameters...
Proceedings of the National Academy of Sciences current issue
14h
The impossibility of low-rank representations for triangle-rich complex networks [Computer Sciences]
The study of complex networks is a significant development in modern science, and has enriched the social sciences, biology, physics, and computer science. Models and algorithms for such networks are pervasive in our society, and impact human behavior via social networks, search engines, and recommender systems, to name a few....
Proceedings of the National Academy of Sciences current issue
14h
Communication cost of consensus for nodes with limited memory [Computer Sciences]
Motivated by applications in wireless networks and the Internet of Things, we consider a model of n nodes trying to reach consensus with high probability on their majority bit. Each node i is assigned a bit at time 0 and is a finite automaton with m bits of memory (i.e.,...
Proceedings of the National Academy of Sciences current issue
14h

Extreme mechanical resilience of self-assembled nanolabyrinthine materials [Engineering]
Low-density materials with tailorable properties have attracted attention for decades, yet stiff materials that can resiliently tolerate extreme forces and deformation while being manufactured at large scales have remained a rare find. Designs inspired by nature, such as hierarchical composites and atomic lattice-mimicking architectures, have achieved optimal combinations of mechanical...
Proceedings of the National Academy of Sciences current issue
14h
Programming colloidal bonding using DNA strand-displacement circuitry [Chemistry]
As a strategy for regulating entropy, thermal annealing is a commonly adopted approach for controlling dynamic pathways in colloid assembly. By coupling DNA strand-displacement circuits with DNA-functionalized colloid assembly, we developed an enthalpy-mediated strategy for achieving the same goal while working at a constant temperature. Using this tractable approach allows...
Proceedings of the National Academy of Sciences current issue
14h
Association of Cl with C2H2 by unified variable-reaction-coordinate and reaction-path variational transition-state theory [Chemistry]
Barrierless unimolecular association reactions are prominent in atmospheric and combustion mechanisms but are challenging for both experiment and kinetics theory. A key datum for understanding the pressure dependence of association and dissociation reactions is the high-pressure limit, but this is often available experimentally only by extrapolation. Here we calculate the...
Proceedings of the National Academy of Sciences current issue
14h
Composition-based prediction and rational manipulation of prion-like domain recruitment to stress granules [Biochemistry]
Mutations in a number of stress granule-associated proteins have been linked to various neurodegenerative diseases. Several of these mutations are found in aggregation-prone prion-like domains (PrLDs) within these proteins. In this work, we examine the sequence features governing PrLD localization to stress granules upon stress. We demonstrate that many yeast...
Proceedings of the National Academy of Sciences current issue
14h
Active volume regulation in adhered cells [Biophysics and Computational Biology]
Recent experiments reveal that the volume of adhered cells is reduced as their basal area is increased. During spreading, the cell volume decreases by several thousand cubic micrometers, corresponding to large pressure changes of the order of megapascals. We show theoretically that the volume regulation of adhered cells is determined...
Proceedings of the National Academy of Sciences current issue
14h
Investigations of the underlying mechanisms of HIF-1{alpha} and CITED2 binding to TAZ1 [Biophysics and Computational Biology]
The TAZ1 domain of CREB binding protein is crucial for transcriptional regulation and recognizes multiple targets. The interactions between TAZ1 and its specific targets are related to the cellular hypoxic negative feedback regulation. Previous experiments reported that one of the TAZ1 targets, CITED2, is an efficient competitor of another target,...
Proceedings of the National Academy of Sciences current issue
14h
RNA extension drives a stepwise displacement of an initiation-factor structural module in initial transcription [Biochemistry]
All organisms—bacteria, archaea, and eukaryotes—have a transcription initiation factor that contains a structural module that binds within the RNA polymerase (RNAP) active-center cleft and interacts with template-strand single-stranded DNA (ssDNA) in the immediate vicinity of the RNAP active center. This transcription initiation-factor structural module preorganizes template-strand ssDNA to engage the...
Proceedings of the National Academy of Sciences current issue
14h
Mechanism of proton transfer in class A {beta}-lactamase catalysis and inhibition by avibactam [Biochemistry]
Gram-negative bacteria expressing class A β-lactamases pose a serious health threat due to their ability to inactivate all β-lactam antibiotics. The acyl–enzyme intermediate is a central milestone in the hydrolysis reaction catalyzed by these enzymes. However, the protonation states of the catalytic residues in this complex have never been fully...
Proceedings of the National Academy of Sciences current issue
14h
Plasmodium chaperonin TRiC/CCT identified as a target of the antihistamine clemastine using parallel chemoproteomic strategy [Biochemistry]
The antihistamine clemastine inhibits multiple stages of the Plasmodium parasite that causes malaria, but the molecular targets responsible for its parasite inhibition were unknown. Here, we applied parallel chemoproteomic platforms to discover the mechanism of action of clemastine and identify that clemastine binds to the Plasmodium falciparum TCP-1 ring complex...
Proceedings of the National Academy of Sciences current issue
14h
Conformational control of small GTPases by AMPylation [Biochemistry]
Posttranslational modifications (PTMs) are important physiological means to regulate the activities and structures of central regulatory proteins in health and disease. Small GTPases have been recognized as important molecules that are targeted by PTMs during infections of mammalian cells by bacterial pathogens. The enzymes DrrA/SidM and AnkX from Legionella pneumophila...
Proceedings of the National Academy of Sciences current issue
14h
bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA) [Biochemistry]
Targeted degradation approaches such as proteolysis targeting chimeras (PROTACs) offer new ways to address disease through tackling challenging targets and with greater potency, efficacy, and specificity over traditional approaches. However, identification of high-affinity ligands to serve as PROTAC starting points remains challenging. As a complementary approach, we describe a class...
Proceedings of the National Academy of Sciences current issue
14h
SOX4-mediated repression of specific tRNAs inhibits proliferation of human glioblastoma cells [Biochemistry]
Transfer RNAs (tRNAs) are products of RNA polymerase III (Pol III) and essential for mRNA translation and ultimately cell growth and proliferation. Whether and how individual tRNA genes are specifically regulated is not clear. Here, we report that SOX4, a well-known Pol II-dependent transcription factor that is critical for neurogenesis...
Proceedings of the National Academy of Sciences current issue
14h
Stability of H3O at extreme conditions and implications for the magnetic fields of Uranus and Neptune [Earth, Atmospheric, and Planetary Sciences]
The anomalous nondipolar and nonaxisymmetric magnetic fields of Uranus and Neptune have long challenged conventional views of planetary dynamos. A thin-shell dynamo conjecture captures the observed phenomena but leaves unexplained the fundamental material basis and underlying mechanism. Here we report extensive quantum-mechanical calculations of polymorphism in the hydrogen–oxygen system at...
Proceedings of the National Academy of Sciences current issue
14h
In vitro selection of ribozyme ligases that use prebiotically plausible 2-aminoimidazole-activated substrates [Biochemistry]
The hypothesized central role of RNA in the origin of life suggests that RNA propagation predated the advent of complex protein enzymes. A critical step of RNA replication is the template-directed synthesis of a complementary strand. Two experimental approaches have been extensively explored in the pursuit of demonstrating protein-free RNA...
Proceedings of the National Academy of Sciences current issue
14h
Circadian control of interferon-sensitive gene expression in murine skin [Biochemistry]
The circadian clock coordinates a variety of immune responses with signals from the external environment to promote survival. We investigated the potential reciprocal relationship between the circadian clock and skin inflammation. We treated mice topically with the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) to activate IFN-sensitive gene (ISG) pathways...
Proceedings of the National Academy of Sciences current issue
14h
The neural signature of numerosity by separating numerical and continuous magnitude extraction in visual cortex with frequency-tagged EEG [Neuroscience]
The ability to handle approximate quantities, or number sense, has been recurrently linked to mathematical skills, although the nature of the mechanism allowing to extract numerical information (i.e., numerosity) from environmental stimuli is still debated. A set of objects is indeed not only characterized by its numerosity but also by...
Proceedings of the National Academy of Sciences current issue
14h
Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism [Biochemistry]
Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ...
Proceedings of the National Academy of Sciences current issue
14h
Topological transition in measurement-induced geometric phases [Physics]
The state of a quantum system, adiabatically driven in a cycle, may acquire a measurable phase depending only on the closed trajectory in parameter space. Such geometric phases are ubiquitous and also underline the physics of robust topological phenomena such as the quantum Hall effect. Equivalently, a geometric phase may...
Proceedings of the National Academy of Sciences current issue
14h
In situ healing of dendrites in a potassium metal battery [Applied Physical Sciences]
The use of potassium (K) metal anodes could result in high-performance K-ion batteries that offer a sustainable and low-cost alternative to lithium (Li)-ion technology. However, formation of dendrites on such K-metal surfaces is inevitable, which prevents their utilization. Here, we report that K dendrites can be healed in situ in...
Proceedings of the National Academy of Sciences current issue
14h
Coherent phonon dynamics in spatially separated graphene mechanical resonators [Applied Physical Sciences]
Vibrational modes in mechanical resonators provide a promising candidate to interface and manipulate classical and quantum information. The observation of coherent dynamics between distant mechanical resonators can be a key step toward scalable phonon-based applications. Here we report tunable coherent phonon dynamics with an architecture comprising three graphene mechanical resonators...
Proceedings of the National Academy of Sciences current issue
14h

Sonoselective transfection of cerebral vasculature without blood-brain barrier disruption [Applied Biological Sciences]
Treatment of many pathologies of the brain could be improved markedly by the development of noninvasive therapeutic approaches that elicit robust, endothelial cell-selective gene expression in specific brain regions that are targeted under MR image guidance. While focused ultrasound (FUS) in conjunction with gas-filled microbubbles (MBs) has emerged as a...
Proceedings of the National Academy of Sciences current issue
14h
Experimental observation of the marginal glass phase in a colloidal glass [Physics]
The replica theory of glasses predicts that in the infinite dimensional mean field limit, there exist two distinct glassy phases of matter: stable glass and marginal glass. We have developed a technique to experimentally probe these phases of matter using a colloidal glass. We avoid the difficulties inherent in measuring...
Proceedings of the National Academy of Sciences current issue
14h
Science is not a signal detection problem [Psychological and Cognitive Sciences]
The perceived replication crisis and the reforms designed to address it are grounded in the notion that science is a binary signal detection problem. However, contrary to null hypothesis significance testing (NHST) logic, the magnitude of the underlying effect size for a given experiment is best conceptualized as a random...
Proceedings of the National Academy of Sciences current issue
14h
Late-life costs of raising sons in bighorn sheep [Evolution]
Senescence, the physiological decline associated with aging, is pervasive in nature. The age at onset and rate of senescent decline vary widely among species, among populations of the same species, and even among individuals within the same population (1). Understanding the reasons for this variability is of great importance for...
Proceedings of the National Academy of Sciences current issue
14h
The effects of evolutionary adaptations on spreading processes in complex networks [Engineering]
A common theme among previously proposed models for network epidemics is the assumption that the propagating object (e.g., a pathogen [in the context of infectious disease propagation] or a piece of information [in the context of information propagation]) is transferred across network nodes without going through any modification or evolutionary...
Proceedings of the National Academy of Sciences current issue
14h
Do the social roles that women and men occupy in science allow equal access to publication? [Social Sciences]
Anyone who thinks that science is on a glide path to gender equality should read the study by Huang et al. (1) showing a publication gender gap favoring men that has increased over time as more women have entered science fields. Although the lesser publishing by women has also emerged...
Proceedings of the National Academy of Sciences current issue
14h
Histamine provides an original vista on cardiorenal syndrome [Medical Sciences]
Cardiac and renal dysfunction frequently go hand in hand in hospitalized patients, and epidemiological studies have suggested an inverse correlation between renal function and cardiovascular morbidity and mortality. This relationship exists regardless of what organ is first affected (1). It reflects upon a complex interplay between heart and kidneys, with...
Proceedings of the National Academy of Sciences current issue
14h
Reply to Jensen and Wang: Chimpanzees under pressure—Selection of a left ventricular structural and functional phenotype [Biological Sciences]
We are grateful for the interest and comments provided by Jensen and Wang (1) related to our recent paper (2). As previously noted, obtaining true resting blood pressure (BP) measurements in chimpanzees is challenging, if not impossible (1). In our study, and as described in detail in the SI Appendix...
Proceedings of the National Academy of Sciences current issue
14h
Apes, adaptations, and artifacts of anesthetics [Biological Sciences]
Shave et al. (1) provide a highly interesting comparison of cardiac form and function in humans and chimpanzees, but, while we agree that the circulation provides important constraints on exercise performance in animals, we are concerned regarding the validity of the central tenet of the high arterial blood pressure and...
Proceedings of the National Academy of Sciences current issue
14h
Reply to Li et al.: Human societies began to play a significant role in global sediment transfer 4,000 years ago [Physical Sciences]
In a recent study (1), we conducted a global synthesis of long-term records of reconstructed sediment accumulation rates (SARs) in lakes and diagnosed that a dominant anthropogenic imprint on soil erosion rates started ∼4,000 y ago. Our approach was based on the assumption that lake SARs are watershed integrators of...
Proceedings of the National Academy of Sciences current issue
14h
Complex “human-vegetation-climate” interactions in the Late Holocene and their significance for paleotemperature reconstructions [Physical Sciences]
Using 3,980 14C ages and 43,669 pollen data from 632 globally distributed lakes (∼88% of them in North America and Europe; Fig. 1A), Jenny et al. (1) demonstrate that increased soil erosion rates (Fig. 1B) and decreased tree coverage (Fig. 1C) have occurred in lake watersheds across a substantial portion...
Proceedings of the National Academy of Sciences current issue
14h
In This Issue [This Week in PNAS]
Sequestered toxins and diet shift in snakes Rhabdophis pentasupralabialis feeding on a larval firefly under captive conditions. Image courtesy of Masaya Fukuda (Kyoto University, Kyoto, Japan). The Japanese colubrid snake Rhabdophis tigrinus, which typically feeds on frogs and poisonous toads, accumulates potent toxins called bufadienolides in its neck glands. The...
Proceedings of the National Academy of Sciences current issue
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Algal photophysiology drives darkening and melt of the Greenland Ice Sheet [Ecology]
Blooms of Zygnematophycean “glacier algae” lower the bare ice albedo of the Greenland Ice Sheet (GrIS), amplifying summer energy absorption at the ice surface and enhancing meltwater runoff from the largest cryospheric contributor to contemporary sea-level rise. Here, we provide a step change in current understanding of algal-driven ice sheet...
Proceedings of the National Academy of Sciences current issue
14h

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