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m6A epitranscriptomic modification regulates neural progenitor-to-glial cell transition in the retina N6-methyladenosine (m6A) is the most prevalent mRNA internal modification and has been shown to regulate the development, physiology and pathology of various tissues. However, the functions of the m6A epitranscriptome ... | developmental biology |
Human variation impacting MCOLN2 restricts Salmonella Typhi replication by magnesium deprivation Human genetic diversity can reveal critical factors in host-pathogen interactions. This is especially useful for human-restricted pathogens like Salmonella enterica serovar Typhi (S. Typhi), the cause of Typhoid fever. One ... | genetics |
MuSiC2: cell type deconvolution for multi-condition bulk RNA-seq data Cell type composition of intact bulk tissues can vary across samples. Deciphering cell type composition and its changes during disease progression is an important step towards understanding disease pathogenesis. To infer cell type composition, existi... | genomics |
Specific binding of Hsp27 and phosphorylated Tau mitigates abnormal Tau aggregation-induced pathology Amyloid aggregation of phosphorylated Tau (pTau) into neurofibrillary tangles is closely associated with Alzheimers disease (AD). Several molecular chaperones have been reported to bind Tau and impede its pathological ... | biochemistry |
Characterization of a nanobody-epitope tag interaction and its application for receptor engineering Peptide epitope tags offer a valuable means for detection and manipulation of protein targets for which high quality detection reagents are not available. Most commonly used epitope tags are bound by conventional, full-s... | biochemistry |
Attention-wise masked graph contrastive learning for predicting molecular property Accurate and efficient prediction of the molecular property is one of the fundamental problems in drug research and development. Recent advancements in representation learning have been shown to greatly improve the performance of molecul... | bioinformatics |
A framework for summarizing chromatin state annotations within and identifying differential annotations across groups of samples Motivation: Genome-wide maps of epigenetic modifications are powerful resources for non-coding genome annotation. Maps of multiple epigenetics marks have been integrated into cell or tissue t... | bioinformatics |
Integrated Analysis of Tissue-specific Gene Expression in Diabetes by Tensor Decomposition-based Unsupervised Feature Extraction with Standard Deviation Optimization Can Identify Possible Associated Diseases. In the field of gene expression analysis, methods of integrating multiple gene expression profiles are still be... | bioinformatics |
Spatial cumulant models enable spatially informed treatment strategies and analysis of local interactions in cancer systems Theoretical and applied cancer studies that use individual-based models (IBMs) have been limited by the lack of a mathematical formulation that enables rigorous analysis of these models. However, ... | cancer biology |
Intracortical remodelling increases in highly-loaded bone after exercise cessation Resorption within cortices of long bones removes excess mass and damaged tissue, and increases during periods of reduced mechanical loading. Returning to high-intensity exercise may place bones at risk of failure due to increased porosit... | physiology |
Characteristics and Impact of the rNST GABA Network on Neural and Behavioral Taste Responses The rostral nucleus of the solitary tract (rNST), the initial CNS site for processing gustatory information, is comprised of two major cell types, glutamatergic excitatory and GABAergic inhibitory neurons. Many investigators ha... | neuroscience |
Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models Suppression gene drives are designed to bias their inheritance and increase in frequency in a population, disrupting an essential gene in the process. When the frequency is high enough, the population wil... | ecology |
Resting-state network hubs are causally required in memory consolidation Resting-state networks (RSNs) detected by fMRI have been associated with cognitive function, providing insights to the relationship between brain and behavior. However, whether altered RSNs are epiphenomena or essential constructs of behavior rema... | animal behavior and cognition |
Assembly-free discovery of human novel sequences using long reads DNA sequences that are absent in the human reference genome are classified as novel sequences. The discovery of these missed sequences is crucial for exploring the genomic diversity of populations and understanding the genetic basis of human diseases. Ho... | bioinformatics |
MAGNETO: an automated workflow for genome-resolved metagenomics Metagenome-Assembled Genomes (MAGs) represent individual genomes recovered from metagenomic data. MAGs are extremely useful to analyse uncultured microbial genomic diversity, as well as to characterize associated functional and metabolic potential in natur... | bioinformatics |
Cryo-EM structure of gas vesicles for buoyancy-controlled motility Gas vesicles allow a diverse group of bacteria and archaea to move in the water column by controlling their buoyancy. These gas-filled cellular nanocompartments are formed by up to micrometers long protein shells that are permeable only to gas. The mole... | biophysics |
Multi-policy models of interregional communication in the human connectome Network models of communication, e.g. shortest paths, diffusion, navigation, have become useful tools for studying structure-function relationships in the brain. These models generate estimates of communication efficiency between all pairs of br... | neuroscience |
Comparative brain structure and the neural network features of cuttlefish and squid Cuttlefishes, like their octopus cousins, are masters of camouflage by control of body pattern and skin texture to blend in with their surroundings for prey ambush and threat avoidance. Aside from significant progress on the cuttlefish ... | neuroscience |
Closed-loop and automatic tuning of pulse amplitude and width in EMG-guided controllable transcranial magnetic stimulation (cTMS) This paper proposes a tool for automatic and optimal tuning of pulse amplitude and width for sequential parameter estimation (SPE) of the membrane time constant and input-output curve in clo... | neuroscience |
Two complete genomes of male-killing Wolbachia infecting Ostrinia moth species illuminate their evolutionary dynamics and association with hosts Wolbachia is an extremely widespread endocellular symbiont which causes reproductive manipulation on various arthropod hosts. Male progenies are killed in Wolbachia-infected l... | microbiology |
Spontaneously produced lysogenic phages are an important component of the soybean Bradyrhizobium mobilome The ability to nodulate and fix atmospheric nitrogen in soybean root nodules makes soybean Bradyrhizobium spp. (SB) critical in supplying humanity's nutritional needs. The intricacies of SB-plant interactions have ... | microbiology |
Skeletal muscle cells derived from induced pluripotent stem cells: a platform for limb girdle muscular dystrophies. Limb-girdle muscular dystrophies (LGMD), caused by mutations in 29 different genes, are the fourth most prevalent group of genetic muscle diseases, leading to progressive weakness and atrophy of the skele... | cell biology |
Evolution and diversity of the TopoVI and TopoVI-like subunits with extensive divergence of the TOPOVIBL subunit Type II DNA topoisomerases regulate topology by double-stranded DNA cleavage and ligation. The TopoVI family of DNA topoisomerase, first identified and biochemically characterized in Archaea, represents, wit... | evolutionary biology |
Population genomics provide insights into the global genetic structure of Colletotrichum graminicola, the causal agent of maize anthracnose Background: Colletotrichum graminicola, the causal agent of maize anthracnose, is an important crop disease worldwide. Understanding the genetic diversity and mechanisms underlying... | genomics |
Single-molecule architecture and heterogeneity of human telomeric DNA and chromatin Telomeres are essential for linear genomes, yet their repetitive DNA content and somatic variability has hindered attempts to delineate their chromatin architectures. We performed single-molecule chromatin fiber sequencing (Fiber-seq) o... | genomics |
Single-Cell RNAseq Analysis Reveals Robust Anti-PD-1-Mediated Increase of Immune Infiltrate in Metastatic Castration-Sensitive Prostate Cancer Compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While and... | cancer biology |
Reproducibility of in-vivo electrophysiological measurements in mice Understanding whole-brain-scale electrophysiological recordings will rely on the collective work of multiple labs. Because two labs recording from the same brain area often reach different conclusions, it is critical to quantify and control for featur... | neuroscience |
Single-cell profiling coupled with lineage analysis reveals distinct sacral neural crest contributions to the developing enteric nervous During development, the enteric nervous system (ENS) arises from neural crest cells that emerge from the neural tube, migrate to and along the gut, and colonize the entire intestinal ... | developmental biology |
Scaled-expansion of the membrane associated cytoskeleton requires conserved kinesin adaptors A periodic lattice of actin rings and spectrin tetramers scaffolds the axonal membrane. How spectrin is delivered to this structure to scale its size to that of the growing axon is unknown. We found that endogenous spectrin, vi... | cell biology |
A new model of Notch signaling: Control of Notch receptor cis-inhibition via Notch ligand dimers All tissue development and replenishment relies upon the breaking of symmetries leading to the morphological and operational differentiation of progenitor cells into more specialized cells. One of the main engines driving t... | cell biology |
Multi-color live-cell STED nanoscopy of mitochondria with a gentle inner membrane stain Capturing mitochondria's intricate and dynamic structure poses a daunting challenge for optical nanoscopy. Different labeling strategies have been demonstrated for live-cell stimulated emission depletion (STED) microscopy of mitocho... | cell biology |
Visinity: Visual Spatial Neighborhood Analysis for Multiplexed Tissue Imaging Data New multiplexed tissue imaging technologies have enabled the study of normal and diseased tissues in unprecedented detail. These methods are increasingly being applied to understand how cancer cells and immune response change during tumo... | cell biology |
Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity Adult hematopoietic stem and progenitor cells (HSPCs) respond directly to inflammation and infection, resulting in both acute and persistent changes to quiescence, mobilization, and differentiation. Here w... | cell biology |
Rapid covalent labeling of a GPCR on living cells using a nanobody-epitope tag pair to interrogate receptor pharmacology Peptide epitope tags offer a valuable means for detection and manipulation of protein targets for which high quality detection reagents are not available. Most commonly used epitope tags are bound by... | biochemistry |
Sampling biases obscure the early diversification of the largest living vertebrate group Extant ray-finned fishes (Actinopterygii) dominate marine and freshwater environments, yet their spatiotemporal diversity dynamics following their origin in the Palaeozoic are poorly understood. Previous studies investigate face-va... | paleontology |
Centrosome Amplification promotes cell invasion via cell-cell contact disruption and Rap-1 activation Centrosome amplification (CA), a prominent feature of human cancers linked to genomic instability and tumourigenesis in vivo, is observed as early as pre-malignant metaplasia, increasing with progression from dysplasia... | cell biology |
A sporulation-independent way of life for Bacillus thuringiensis in the late stages of an infection The formation of endospores has been considered as the unique mode of survival and transmission of sporulating Firmicutes due to the exceptional resistance and persistence of this bacterial form. However, the persistence... | microbiology |
Thermal endurance by a hot-spring-dwelling phylogenetic relative of the mesophilic Paracoccus High temperature growth/survival was revealed in a phylogenetic relative (strain SMMA_5) of the mesophilic Paracoccus isolated from the 78-85{degrees}C water of a Trans-Himalayan sulfur-borax spring. After 12 h at 50{degrees}C... | microbiology |
Chemoenzymatic fluorescence labeling of intercellularly contacting cells using lipidated sortase A Methods to label intercellular contact attract particular attention due to their potential in cell biological and medical applications through analysis of intercellular communications. In this study, a simple and versatil... | biochemistry |
Roughening instability of growing 3D bacterial colonies How do growing bacterial colonies get their shapes? While colony morphogenesis is well-studied in 2D, many bacteria grow as large colonies in 3D environments, such as gels and tissues in the body, or soils, sediments, and subsurface porous media. Here, we describe... | biophysics |
Deformable Mirror based Optimal PSF Engineering for 3D Super-resolution Imaging Point spread function (PSF) engineering is an important technique to encode the properties (e.g., 3D positions, color, and orientation) of single molecule in the shape of the PSF, often with the help of a programmable phase modulator. Defor... | biophysics |
Computational modeling of TGF-β2:TβRI:TβRII receptor complex assembly as mediated by the TGF-β co-receptor betaglycan Transforming growth factor-{beta}1, -{beta}2, and -{beta}3 (TGF-{beta}1, -{beta}2, and -{beta}3) are secreted signaling ligands that play essential roles in tissue development, tissue maintenance, immun... | biophysics |
De novo design of peptides that form transmembrane barrel pores killing antibiotic resistant bacteria De novo design of peptides that self-assemble into transmembrane barrel pores is challenging due to the complexity of several competing interactions involving peptides, lipids, water, and ions. Here, we develop a compu... | biophysics |
Derivation of the Relationship Between the Mass and Lifespan of Living Organisms The relation p=1-a between exponents, by which the dependencies of lifespan p and growth intensity a on masses of living organisms are described, is obtained and testified. | biophysics |
Sequence-based pH-dependent prediction of protein solubility using CamSol Solubility is a property of central importance for the use of proteins in research and in applications in biotechnology and medicine. Since experimental methods for measuring protein solubility are resource-intensive and time-consuming, computati... | biophysics |
Evolution avoids a pathological stabilizing interaction in the immune protein S100A9 Protein stability constrains protein evolution. While much is known about evolutionary constraints on destabilizing mutations, much less is known about evolutionary constraints on mutations that increase protein stability. We recently ... | biophysics |
Ubiquitous bacterial polyketides induce cross-kingdom microbial interactions Although the interaction of prokaryotic and eukaryotic microorganisms is critical for the functioning of ecosystems, knowledge of the processes driving microbial interactions within communities is in its infancy. We previously reported that th... | microbiology |
Corynebacterium matruchotii fitness enhancement of adjacent streptococci by multiple mechanisms Polymicrobial biofilms are present in many environments particularly in the human oral cavity where they can prevent or facilitate the onset of disease. While recent advances have provided a clear picture of both the constit... | microbiology |
In-silico identification of Tyr232 in AMPKα2 as a dephosphorylation site for the protein tyrosine phosphatase PTP-PEST The AMP-activated protein kinase (AMPK) is known to be activated by the protein tyrosine phosphatase non-receptor type 12 (PTP-PEST) under hypoxic conditions. This activation is mediated by tyrosine de... | biochemistry |
Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack Vaccines targeting HIV-1's gp160 spike protein are stymied by high viral mutation rates and structural chicanery. gp160's membrane-proximal external region (MPER) is the target of naturally arising broadly neutralizing ant... | biophysics |
Decoding The Nuclear Genome of The Human Pathogen Babesia duncani Shed Light on its Virulence, Drug Susceptibility and Evolution among Apicomplexa Babesia species are tick-transmitted apicomplexan pathogens and the causative agents of babesiosis, a malaria-like disease of major medical and veterinary importance. Of the... | microbiology |
Identification of Banana heat responsive long non-coding RNAs and their gene expression analysis. Identification and characterization of long non-coding RNAs (lncRNAs) in the last decade has attained great attention because of their importance in gene regulatory functions in response to various plant stresses. Rising t... | molecular biology |
Chronic clinical signs of upper respiratory tract disease shape gut and respiratory microbiomes in cohabitating domestic felines. Feline upper respiratory tract disease (FURTD), often caused by infections etiologies, is a multifactorial syndrome affecting feline populations worldwide. Because of its highly transmis... | microbiology |
The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters RNA interference systems depend on the synthesis of small RNA precursors whose sequences define the target spectrum of these silencing pathways. The Drosophila Heterochromatin Protein 1 (HP1) variant Rhino permits transcription of PIWI-intera... | genetics |
Real-time single-molecule observation of chaperone-assisted protein folding The ability of Hsp70 molecular chaperones to remodel the conformation of their clients is central to their biological function; however, questions remain regarding the precise molecular mechanisms by which Hsp70 machinery interacts with the cli... | biochemistry |
Design of an ultrafast pulsed ponderomotive phase plate for cryo-electron tomography Ponderomotive phase plates have shown temporally consistent phase contrast is possible within electron microscopes via high fluence static laser modes resonating in Fabry-Perot cavities. Here, we explore using pulsed laser beams as an ... | biophysics |
Deep Reinforcement Learning for Optimal Experimental Design in Biology The field of optimal experimental design uses mathematical techniques to determine experiments that are maximally informative from a given experimental setup. Here we apply a technique from artificial intelligence---reinforcement learning---to the o... | synthetic biology |
Persistent serum protein signatures define an inflammatory subset of long COVID Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months after acute SARS-CoV-2 infection. The etiologies are unknown but may include persistent inflammation, unres... | immunology |
SARS-CoV-2 Spike N-Terminal Domain modulates TMPRSS2-dependent viral entry and fusogenicity Over 20 mutations have been identified in the N-Terminal Domain (NTD) of SARS-CoV-2 spike and yet few of them are fully characterised. Here we first examined the contribution of the NTD to infection and cell-cell fusion by const... | microbiology |
Soil nitrogen impacts the rhizosphere microbial community owing to microbial hitchhiking Microbial hitchhiking demonstrates that some nonmotile microbes utilize trans-species motility to traverse their environment; however, whether driving forces, such as plants and nitrogen, affect microbial hitchhiking is not clear. ... | microbiology |
A marine probiotic treatment against the bacterial pathogen Vibrio coralliilyticus to improve the performance of Pacific (Crassostrea gigas) and Kumamoto (C. sikamea) oyster larvae Oyster larvae reared in hatcheries on the U.S. West coast often experience severe Vibrio coralliilyticus-related mortalities early in their... | microbiology |
SIRT3 deficiency decreases oxidative-metabolism capacity but increases lifespan under caloric restriction Mitochondrial NAD+-dependent protein deacetylase Sirtuin3 (SIRT3) has been proposed to mediate calorie restriction (CR)-dependent metabolic regulation and lifespan extension. Here, we investigated the role of SIRT3... | molecular biology |
Developmentally regulated alternate 3' end cleavage of nascent transcripts controls dynamic changes in protein expression in an adult stem cell lineage Alternative polyadenylation (APA) generates transcript isoforms that differ in the position of the 3' cleavage site, resulting in the production of mRNA isoforms with d... | developmental biology |
Opportunistic binding of EcR to open chromatin drives tissue-specific developmental responses Steroid hormones perform diverse biological functions in developing and adult animals. However, the mechanistic basis for their tissue specificity remains unclear. In Drosophila, the ecdysone steroid hormone is essential for c... | developmental biology |
Inferring selection effects in SARS-CoV-2 with Bayesian Viral Allele Selection The global effort to sequence millions of SARS CoV-2 genomes has provided an unprecedented view of viral evolution. Characterizing how selection acts on SARS-CoV-2 is critical to developing effective, long-lasting vaccines and other treatmen... | genomics |
Deciphering the Impact of Genetic Variation on Human Polyadenylation Genetic variants that disrupt polyadenylation can cause or contribute to genetic disorders. Yet, due to the complex cis-regulation of polyadenylation, variant interpretation remains challenging. Here, we introduce a residual neural network model, APAR... | genomics |
Liquid-like assembly of VASP drives actin polymerization and bundling The organization of actin filaments into bundles is required for cellular processes such as motility, morphogenesis, and cell division. Filament bundling is controlled by a network of actin binding proteins. Recently, several proteins that comprise t... | biophysics |
Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during... | biophysics |
A novel ALDH1A1 inhibitor blocks platinum-induced senescence and stemness in ovarian cancer Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for emergence of chemor... | cancer biology |
Integrative multi-omics analysis reveals molecular subtypes and tumor evolution of synovial sarcoma Synovial sarcomas (SS) are malignant mesenchymal tumors characterized by the SS18-SSX fusion gene, which drives tumorigenesis by altering the composition of the BAF complex. Secondary genomic alterations that determine v... | cancer biology |
A requirement for Kruppel-Like Factor-4 in the maintenance of endothelial cell quiescence Rationale and Goal: Endothelial cells (ECs) are quiescent and critical for maintaining homeostatic functions of the mature vascular system, while disruption of quiescence is at the heart of endothelial to mesenchymal transition (E... | physiology |
The Role of Conjunctive Representations in Prioritizing and Selecting Planned Actions For flexible goal-directed behavior, prioritizing and selecting a specific action among multiple candidates is often important. Working memory has long been assumed to play a role in prioritization and planning, while bridging cross-t... | neuroscience |
Persistence of Cajal-Retzius cells in the postnatal hippocampus is required for development of dendritic spines of CA1 pyramidal cells Cajal-Retzius (CR) cells are a transient type of neuron that populate the postnatal hippocampus. The role of transient cell types and circuits have been vastly addressed in neocortical ... | neuroscience |
The evolution of information transmission in mammalian brain networks Brain communication, defined as information transmission through white-matter connections, is at the foundation of the brain's computational capacities that virtually subtend all aspects of behavior: from sensory perception shared across mammalian sp... | neuroscience |
Neuroinflammation plays a critical role in cerebral cavernous malformation disease Background: Cerebral Cavernous Malformations (CCMs) are neurovascular lesions caused by loss-of-function mutations in one of three genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3). CCMs affect ~1/200 children and adults, and no pha... | neuroscience |
Species sympatry shapes brain size evolution in Primates The main hypotheses about the evolution of animal cognition emphasise the role of conspecifics. Yet, space is often simultaneously occupied by multiple species from the same ecological guild. These sympatric species can compete for food, which may thereby stimula... | ecology |
Mutation rates and fitness consequences of mosaic chromosomal alterations in blood Mosaic chromosomal alterations (mCAs) are commonly detected in many cancers and have been found to arise decades before diagnosis. A quantitative understanding of the rate at which these events occur and their functional consequences cou... | genomics |
The effect of sociality on competitive interactions among birds Sociality can provide many benefits, including increased foraging success, reproductive opportunities, and defence against predation. How does sociality influence the dominance hierarchies of ecological competitors? Here, we address this question using a l... | animal behavior and cognition |
TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons TRPV1, a capsaicin- and heat-sensitive ion channel, is expressed by peripheral nociceptors and has been implicated in various inflammatory and neuropathic pain conditions. Although pharmacological modulation of TRPV1 has... | physiology |
Cellular And Molecular Effects Of Understudied Kinase Pregnancy Upregulated Non-Ubiquitous Calcium-Calmodulin Dependent Kinase (PNCK) In Renal Cell Carcinoma. Renal Cell Carcinoma (RCC) is a uniformly fatal disease when advanced. While immunotherapy and tyrosine kinase inhibitor-based combinations are associated with i... | molecular biology |
Molecular architecture of the C. elegans centriole Uncovering organizing principles of organelle assembly is a fundamental pursuit in the life sciences. C. elegans was key in identifying evolutionary conserved components governing assembly of the centriole organelle. However, localizing these components with high preci... | cell biology |
Structure of maize BZR1-type β-amylase BAM8 provides new insights into its noncatalytic adaptation Plant {beta}-Amylase (BAM) proteins play an essential role in growth, development, stress response, and hormone regulation. Despite their typical ({beta}/)8 barrel structure as active catalysts in starch breakdown, cataly... | biochemistry |
MPZ-T124M mouse model replicates human axonopathy and suggest alteration in axo-glia communication Myelin is essential for rapid nerve impulse propagation and axon protection. Accordingly, defects in myelination or myelin maintenance lead to secondary axonal damage and subsequent degeneration. Studies utilizing genetic... | neuroscience |
The endothelial-specific LINC00607 mediates endothelial angiogenic function Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely u... | molecular biology |
The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data Background: Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together pe... | genetics |
Chromosome-scale assembly of the lablab genome - A model for inclusive orphan crop genomics Orphan crops (also described as underutilised and neglected crops) hold the key to diversified and climate-resilient food systems. After decades of neglect, the genome sequencing of orphan crops is gathering pace, providing the ... | genomics |
spSeudoMap: Cell type mapping of spatial transcriptomics using unmatched single-cell RNA-seq data With advances in computational models, the cellular landscape can be tracked in various tissues using spatial transcriptomics. Since many single-cell RNA-seq (scRNA-seq) data have been obtained after cell sorting, such as ... | genomics |
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