Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Tuesday, May 26, 2020


Dynamic morphoskeletons in development [Biophysics and Computational Biology]
Morphogenetic flows in developmental biology are characterized by the coordinated motion of thousands of cells that organize into tissues, naturally raising the question of how this collective organization arises. Using only the kinematics of tissue deformation, which naturally integrates local and global mechanisms along cell paths, we identify the dynamic...
Proceedings of the National Academy of Sciences current issue
11h
Ring currents modulate optoelectronic properties of aromatic chromophores at 25 T [Chemistry]
The properties of organic molecules can be influenced by magnetic fields, and these magnetic field effects are diverse. They range from inducing nuclear Zeeman splitting for structural determination in NMR spectroscopy to polaron Zeeman splitting organic spintronics and organic magnetoresistance. A pervasive magnetic field effect on an aromatic molecule is...
Proceedings of the National Academy of Sciences current issue
11h
Spatiotemporal regulation of PEDF signaling by type I collagen remodeling [Biophysics and Computational Biology]
Dynamic remodeling of the extracellular matrix affects many cellular processes, either directly or indirectly, through the regulation of soluble ligands; however, the mechanistic details of this process remain largely unknown. Here we propose that type I collagen remodeling regulates the receptor-binding activity of pigment epithelium-derived factor (PEDF), a widely expressed...
Proceedings of the National Academy of Sciences current issue
11h
Identifying sequence perturbations to an intrinsically disordered protein that determine its phase-separation behavior [Chemistry]
Phase separation of intrinsically disordered proteins (IDPs) commonly underlies the formation of membraneless organelles, which compartmentalize molecules intracellularly in the absence of a lipid membrane. Identifying the protein sequence features responsible for IDP phase separation is critical for understanding physiological roles and pathological consequences of biomolecular condensation, as well as...
Proceedings of the National Academy of Sciences current issue
11h
Histone H3K9 methylation promotes formation of genome compartments in Caenorhabditis elegans via chromosome compaction and perinuclear anchoring [Cell Biology]
Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization in Caenorhabditis elegans and investigate roles for compartments in regulating gene expression. Distal arms of C. elegans chromosomes, which are enriched for...
Proceedings of the National Academy of Sciences current issue
11h
Multiple epithelia are required to develop teeth deep inside the pharynx [Developmental Biology]
To explain the evolutionary origin of vertebrate teeth from odontodes, it has been proposed that competent epithelium spread into the oropharyngeal cavity via the mouth and other possible channels such as the gill slits [Huysseune et al., 2009, J. Anat. 214, 465–476]. Whether tooth formation deep inside the pharynx in...
Proceedings of the National Academy of Sciences current issue
11h
ZBED2 is an antagonist of interferon regulatory factor 1 and modifies cell identity in pancreatic cancer [Cell Biology]
Lineage plasticity is a prominent feature of pancreatic ductal adenocarcinoma (PDA) cells, which can occur via deregulation of lineage-specifying transcription factors. Here, we show that the zinc finger protein ZBED2 is aberrantly expressed in PDA and alters tumor cell identity in this disease. Unexpectedly, our epigenomic experiments reveal that ZBED2...
Proceedings of the National Academy of Sciences current issue
11h
A genetic framework for regulation and seasonal adaptation of shoot architecture in hybrid aspen [Developmental Biology]
Shoot architecture is critical for optimizing plant adaptation and productivity. In contrast with annuals, branching in perennials native to temperate and boreal regions must be coordinated with seasonal growth cycles. How branching is coordinated with seasonal growth is poorly understood. We identified key components of the genetic network that controls...
Proceedings of the National Academy of Sciences current issue
11h
Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear [Neuroscience]
Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs...
Proceedings of the National Academy of Sciences current issue
11h
Flowering plant composition shapes pathogen infection intensity and reproduction in bumble bee colonies [Ecology]
Pathogens pose significant threats to pollinator health and food security. Pollinators can transmit diseases during foraging, but the consequences of plant species composition for infection is unknown. In agroecosystems, flowering strips or hedgerows are often used to augment pollinator habitat. We used canola as a focal crop in tents and...
Proceedings of the National Academy of Sciences current issue
11h
Dynamics in a simple evolutionary-epidemiological model for the evolution of an initial asymptomatic infection stage [Ecology]
Pathogens exhibit a rich variety of life history strategies, shaped by natural selection. An important pathogen life history characteristic is the propensity to induce an asymptomatic yet productive (transmissive) stage at the beginning of an infection. This characteristic is subject to complex trade-offs, ranging from immunological considerations to population-level social...
Proceedings of the National Academy of Sciences current issue
11h
A trait-based understanding of wood decomposition by fungi [Ecology]
As the primary decomposers of organic material in terrestrial ecosystems, fungi are critical agents of the global carbon cycle. Yet our ability to link fungal community composition to ecosystem functioning is constrained by a limited understanding of the factors accounting for different wood decomposition rates among fungi. Here we examine...
Proceedings of the National Academy of Sciences current issue
11h
Temporal flexibility of gene regulatory network underlies a novel wing pattern in flies [Evolution]
Organisms have evolved endless morphological, physiological, and behavioral novel traits during the course of evolution. Novel traits were proposed to evolve mainly by orchestration of preexisting genes. Over the past two decades, biologists have shown that cooption of gene regulatory networks (GRNs) indeed underlies numerous evolutionary novelties. However, very little...
Proceedings of the National Academy of Sciences current issue
11h
Tissue-specific disruption of Kbtbd2 uncovers adipocyte-intrinsic and -extrinsic features of the teeny lipodystrophy syndrome [Physiology]
Loss of KBTBD2 in all tissues causes the teeny phenotype, characterized by insulin resistance with late failure of insulin production, severe hyperglycemia/diabetes, lipodystrophy, hepatosteatosis, and growth retardation. KBTBD2 maintains insulin sensitivity in adipocytes by restricting the abundance of p85α. However, the possible physiological contribution or contributions of KBTBD2 have not...
Proceedings of the National Academy of Sciences current issue
11h
Indirect reciprocity with simple records [Economic Sciences]
Indirect reciprocity is a foundational mechanism of human cooperation. Existing models of indirect reciprocity fail to robustly support social cooperation: Image-scoring models fail to provide robust incentives, while social-standing models are not informationally robust. Here we provide a model of indirect reciprocity based on simple, decentralized records: Each individual’s record...
Proceedings of the National Academy of Sciences current issue
11h
Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing [Genetics]
Methylation of histone H3 lysine 27 (H3K27) is widely recognized as a transcriptionally repressive chromatin modification but the mechanism of repression remains unclear. We devised and implemented a forward genetic scheme to identify factors required for H3K27 methylation-mediated silencing in the filamentous fungus Neurospora crassa and identified a bromo-adjacent homology...
Proceedings of the National Academy of Sciences current issue
11h
Increased drought severity tracks warming in the United States’ largest river basin [Environmental Sciences]
Across the Upper Missouri River Basin, the recent drought of 2000 to 2010, known as the “turn-of-the-century drought,” was likely more severe than any in the instrumental record including the Dust Bowl drought. However, until now, adequate proxy records needed to better understand this event with regard to long-term variability...
Proceedings of the National Academy of Sciences current issue
11h
Improvement in municipal wastewater treatment alters lake nitrogen to phosphorus ratios in populated regions [Environmental Sciences]
Large-scale and rapid improvement in wastewater treatment is common practice in developing countries, yet this influence on nutrient regimes in receiving waterbodies is rarely examined at broad spatial and temporal scales. Here, we present a study linking decadal nutrient monitoring data in lakes with the corresponding estimates of five major...
Proceedings of the National Academy of Sciences current issue
11h
Human decisions about when to act originate within a basal forebrain-nigral circuit [Neuroscience]
Decisions about when to act are critical for survival in humans as in animals, but how a desire is translated into the decision that an action is worth taking at any particular point in time is incompletely understood. Here we show that a simple model developed to explain when animals...
Proceedings of the National Academy of Sciences current issue
11h
Retinal capillary oximetry with visible light optical coherence tomography [Engineering]
Assessing oxygen saturation (sO2) remains challenging but is nonetheless necessary for understanding retinal metabolism. We and others previously achieved oximetry on major retinal vessels and measured the total retinal oxygen metabolic rate in rats using visible-light optical coherence tomography. Here we extend oximetry measurements to capillaries and investigate all three...
Proceedings of the National Academy of Sciences current issue
11h
A mode of cell adhesion and migration facilitated by CD44-dependent microtentacles [Engineering]
The structure and mechanics of many connective tissues are dictated by a collagen-rich extracellular matrix (ECM), where collagen fibers provide topological cues that direct cell migration. However, comparatively little is known about how cells navigate the hyaluronic acid (HA)-rich, nanoporous ECM of the brain, a problem with fundamental implications for...
Proceedings of the National Academy of Sciences current issue
11h
Unexpected formation of oxygen-free products and nitrous acid from the ozonolysis of the neonicotinoid nitenpyram [Environmental Sciences]
The neonicotinoid nitenpyram (NPM) is a multifunctional nitroenamine [(R1N)(R2N)C=CHNO2] pesticide. As a nitroalkene, it is structurally similar to other emerging contaminants such as the pharmaceuticals ranitidine and nizatidine. Because ozone is a common atmospheric oxidant, such compounds may be oxidized on contact with air to form new products that have...
Proceedings of the National Academy of Sciences current issue
11h
RNA-binding motifs of hnRNP K are critical for induction of antibody diversification by activation-induced cytidine deaminase [Immunology and Inflammation]
Activation-induced cytidine deaminase (AID) is the key enzyme for class switch recombination (CSR) and somatic hypermutation (SHM) to generate antibody memory. Previously, heterogeneous nuclear ribonucleoprotein K (hnRNP K) was shown to be required for AID-dependent DNA breaks. Here, we defined the function of major RNA-binding motifs of hnRNP K, GXXGs...
Proceedings of the National Academy of Sciences current issue
11h
A Triassic stem-salamander from Kyrgyzstan and the origin of salamanders [Evolution]
The origin of extant amphibians remains largely obscure, with only a few early Mesozoic stem taxa known, as opposed to a much better fossil record from the mid-Jurassic on. In recent time, anurans have been traced back to Early Triassic forms and caecilians have been traced back to the Late...
Proceedings of the National Academy of Sciences current issue
11h
Behavioral and environmental contributions to drosophilid social networks [Evolution]
Animals interact with each other in species-specific reproducible patterns. These patterns of organization are captured by social network analysis, and social interaction networks (SINs) have been described for a wide variety of species including fish, insects, birds, and mammals. The aim of this study is to understand the evolution of...
Proceedings of the National Academy of Sciences current issue
11h
The PDK1-FoxO1 signaling in adipocytes controls systemic insulin sensitivity through the 5-lipoxygenase-leukotriene B4 axis [Medical Sciences]
Although adipocytes are major targets of insulin, the influence of impaired insulin action in adipocytes on metabolic homeostasis remains unclear. We here show that adipocyte-specific PDK1 (3′-phosphoinositide–dependent kinase 1)-deficient (A-PDK1KO) mice manifest impaired metabolic actions of insulin in adipose tissue and reduction of adipose tissue mass. A-PDK1KO mice developed insulin...
Proceedings of the National Academy of Sciences current issue
11h
Collateral fitness effects of mutations [Evolution]
The distribution of fitness effects of mutation plays a central role in constraining protein evolution. The underlying mechanisms by which mutations lead to fitness effects are typically attributed to changes in protein specific activity or abundance. Here, we reveal the importance of a mutation’s collateral fitness effects, which we define...
Proceedings of the National Academy of Sciences current issue
11h
Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis [Microbiology]
Human T cell leukemia virus 1 (HTLV-1) causes the functionally debilitating disease HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as adult T cell leukemia lymphoma (ATLL). Although there were concerns that the mortality of HAM/TSP could be affected by the development of ATLL, prospective evidence was lacking in this area....
Proceedings of the National Academy of Sciences current issue
11h
Structural basis of peptidoglycan endopeptidase regulation [Microbiology]
Most bacteria surround themselves with a cell wall, a strong meshwork consisting primarily of the polymerized aminosugar peptidoglycan (PG). PG is essential for structural maintenance of bacterial cells, and thus for viability. PG is also constantly synthesized and turned over; the latter process is mediated by PG cleavage enzymes, for...
Proceedings of the National Academy of Sciences current issue
11h
Hepatic gap junctions amplify alcohol liver injury by propagating cGAS-mediated IRF3 activation [Medical Sciences]
Alcohol-related liver disease (ALD) accounts for the majority of cirrhosis and liver-related deaths worldwide. Activation of IFN-regulatory factor (IRF3) initiates alcohol-induced hepatocyte apoptosis, which fuels a robust secondary inflammatory response that drives ALD. The dominant molecular mechanism by which alcohol activates IRF3 and the pathways that amplify inflammatory signals in...
Proceedings of the National Academy of Sciences current issue
11h
The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function [Immunology and Inflammation]
Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with...
Proceedings of the National Academy of Sciences current issue
11h
Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin [Immunology and Inflammation]
The intestinal mucosa exists in dynamic balance with trillions of luminal microbes. Disruption of the intestinal epithelial barrier, commonly observed in mucosal inflammation and diseases such as inflammatory bowel diseases (IBDs), is often associated with dysbiosis, particularly decreases in species producing short-chain fatty acids (SCFAs), such as butyrate. It remains...
Proceedings of the National Academy of Sciences current issue
11h
Evolution of vancomycin-resistant Enterococcus faecium during colonization and infection in immunocompromised pediatric patients [Microbiology]
Patients with hematological malignancies or undergoing hematopoietic stem cell transplantation are vulnerable to colonization and infection with multidrug-resistant organisms, including vancomycin-resistant Enterococcus faecium (VREfm). Over a 10-y period, we collected and sequenced the genomes of 110 VREfm isolates from gastrointestinal and blood cultures of 24 pediatric patients undergoing chemotherapy or...
Proceedings of the National Academy of Sciences current issue
11h
Cell entry mechanisms of SARS-CoV-2 [Microbiology]
A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function,...
Proceedings of the National Academy of Sciences current issue
11h
Campylobacter jejuni BumSR directs a response to butyrate via sensor phosphatase activity to impact transcription and colonization [Microbiology]
Campylobacter jejuni monitors intestinal metabolites produced by the host and microbiota to initiate intestinal colonization of avian and animal hosts for commensalism and infection of humans for diarrheal disease. We previously discovered that C. jejuni has the capacity to spatially discern different intestinal regions by sensing lactate and the short-chain...
Proceedings of the National Academy of Sciences current issue
11h
Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex [Neuroscience]
Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field...
Proceedings of the National Academy of Sciences current issue
11h
Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase [Neuroscience]
Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play...
Proceedings of the National Academy of Sciences current issue
11h
Single-nucleus RNA sequencing of mouse auditory cortex reveals critical period triggers and brakes [Neuroscience]
Auditory experience drives neural circuit refinement during windows of heightened brain plasticity, but little is known about the genetic regulation of this developmental process. The primary auditory cortex (A1) of mice exhibits a critical period for thalamocortical connectivity between postnatal days P12 and P15, during which tone exposure alters the...
Proceedings of the National Academy of Sciences current issue
11h
TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression [Neuroscience]
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein which forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases....
Proceedings of the National Academy of Sciences current issue
11h

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