Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,524 bioRxiv papers from 264,866 authors.
Most downloaded bioRxiv papers, since beginning of last month
56,139 results found. For more information, click each entry to expand.
9 downloads microbiology
Mucormycosis - an emergent, deadly fungal infection - is difficult to treat, in part because the causative species demonstrate broad clinical antifungal resistance. However, the mechanisms underlying drug resistance in these infections remain poorly understood. Our previous work demonstrated that one major agent of mucormycosis, Mucor circinelloides, can develop resistance to the antifungal agents FK506 and rapamycin through a novel, transient RNA interference-dependent mechanism known as epimutation. Epimutations silence the drug target gene and are selected by drug exposure; the target gene is re-expressed and sensitivity is restored following passage without drug. This silencing process involves generation of small RNA (sRNA) against the target gene via core RNAi pathway proteins. To further elucidate the role of epimutation in the broad antifungal resistance of Mucor, epimutants were isolated that confer resistance to another antifungal agent, 5-fluoroorotic acid (5-FOA). We identified epimutant strains that exhibit resistance to 5-FOA without mutations in PyrF or PyrG, enzymes which convert 5-FOA into the active toxic form. Using sRNA hybridization as well as sRNA library analysis, we demonstrate that these epimutants harbor sRNA against either pyrF or pyrG, and further show that this sRNA is lost after reversion to drug sensitivity. We conclude that epimutation is a mechanism capable of targeting multiple genes, enabling Mucor to develop resistance to a variety of antifungal agents. Elucidation of the role of RNAi in epimutation affords a fuller understanding of mucormycosis. Furthermore, it improves our understanding of fungal pathogenesis and adaptation to stresses, including the evolution of drug resistance.
9 downloads immunology
One paradigm of random monoallelic gene expression is that of T-cell receptor (TCR)β allelic exclusion in T lymphocytes. However, the dynamics that sustain asymmetric choice in TCRβ dual allele usage and the production of TCRβ monoallelic expressing T-cells remain poorly understood. Here, we develop a computational model to explore a scheme of TCRβ allelic exclusion based on the stochastic initiation of DNA rearrangement [V(D)J recombination] at homologous alleles in T-cell progenitors, and thus account for the genotypic profiles typically associated with allelic exclusion in differentiated T-cells. Disturbances in these dynamics at the level of an individual allele have limited consequences on these profiles, a robust feature of the system that is underscored by our simulations. Our study predicts a biological system in which locus-specific, prime epigenetic allelic activation effects set the stage to both optimize the production of TCRβ allelically excluded T-cells and curtail the emergence of their allelically included counterparts.
9 downloads ecology
Tricolored blackbird (Agelaius tricolor) is a colonial breeder, largely restricted to grasslands, wetlands, and agricultural habitats of California. Tricolored blackbird abundance declined considerably during the 20th century. Recent trends have been less clear, however, hindering efforts to evaluate the conservation needs of the species. We assessed trends in tricolored blackbird colony size using the 2008, 2011, 2014, and 2017 Triennial Tricolored Blackbird Statewide Survey, a community-science effort involving hundreds of volunteer observers. After accounting for variation in observer characteristics and survey effort, we found a clear, statistically significant decline in colony size of approximately 5% per year, which translated to a decrease in colony size of approximately 40% between 2008 and 2017. To the extent that colony size is proportional to total abundance, this decline translates to a species half-life of roughly 15 years. We conclude that tricolored blackbird is in considerable need of protection and recovery efforts.
9 downloads systems biology
Genome-scale metabolic models (GEMs) provide a functional view of the complex network of biochemical reactions in the living cell. Initially mainly applied to reconstruct the metabolism of model organisms, the availability of increasingly sophisticated reconstruction methods and more extensive biochemical databases now make it possible to reconstruct GEMs for less characterized organisms as well, and have the potential to unravel the metabolism in pathogen-host systems. Here we present a GEM for the oomycete plant pathogen Phytophthora infestans as a first step towards an integrative model with its host. We predict the biochemical reactions in different cellular compartments and investigate the gene-protein-reaction associations in this model to get an impression of the biochemical capabilities of P. infestans. Furthermore, we generate life stage-specific models to place the transcriptomic changes of genes encoding metabolic enzymes into a functional context. In sporangia and zoospores there is an overall downregulation, most strikingly reflected in the fatty acid biosynthesis pathway. To investigate the robustness of the GEM, we simulate gene deletions to predict which enzymes are essential for in vitro growth. While there is room for improvement, this first model is an essential step towards an understanding of P. infestans and its interactions with plants as a system, which will help to formulate new hypotheses on infection mechanisms and disease prevention.
9 downloads ecology
One of the most ignored aspects of bioacoustic technology employed worldwide is lack of understanding between acclimatisation and distress feeding by depredatory birds. Acclimatisation results in gradual increase in resistance to bioacoustics in comparison to distress feeding, which makes sudden surge in instances of feeding by depredatory birds. Acclimatisation and distress feeding are independent functions of feeding behaviour. Distress feeding in itself is a function of physiological conditions of bird, extent of cropped area, distance traveled to obtain food, population dynamics, other natural habitats and cropping pattern in an area and is greatly influenced by them. There are no studies conducted to understand the distress feeding of birds in agricultural landscape. Experiments proved that bioacoustics could offer protection against distress feeding by birds although at reduced efficiency.
9 downloads ecology
Many natural communities are spatially distributed, forming a network of subcommunities linked by migration. Migration patterns are often asymmetric and heterogeneous, with important consequences on the ecology and evolution of the species. Here we investigated experimentally how asymmetric migration and heterogeneous structure affect a simple metacommunity of budding yeast, formed by one strain that produces a public good and a non-producer strain that benefits from it. We find that asymmetric migration increases the fraction of producers in all subpopulations of the metacommunity. Furthermore, asymmetric migration decreases the metacommunity's tolerance to challenging environments, but increases its resilience to transient perturbations. This apparent paradox occurs because tolerance to a constant challenge depends on the weakest subpopulations of the network, while resilience to a transient perturbation depends on the strongest ones.
9 downloads evolutionary biology
Evolutionary biologists have long sought to understand the ecological processes that generate plant reproductive diversity. Recent evidence indicates that constitutive antiherbivore defenses can alter natural selection on reproductive traits, but it is unclear whether induced defenses will have the same effect and whether reduced foliar damage in defended plants is the cause of this pattern. In a factorial field experiment using common milkweed, Asclepias syriaca, we induced plant defenses using jasmonic acid (JA) and imposed foliar damage using scissors. We found that JA-induced plants experienced selection for more inflorescences that were smaller in size (fewer flowers), while control plants only experienced a trend toward selection for larger inflorescences (more flowers); all effects were independent of foliar damage. Our results demonstrate that induced defenses can alter both the strength and direction of selection on reproductive traits, and suggest that antiherbivore defenses may promote the evolution of plant reproductive diversity.
9 downloads neuroscience
In order to better understand dysfunction in dementia and psychiatric illnesses, the underlying neuronal systems that give rise to normal memory and cognitive processes need to be better understood. Based on electrophysiological recordings in animals, theta oscillations have been proposed as an intrinsic mechanism for the orchestration of memory functions, especially episodic and autobiographical. Theta oscillations are controlled by the ascending synchronising system, a set of nucleui in the pontine tegmentum and basal forebrain. At a network level, the default mode network has been shown to be responsible for episodic and autobiographical. Using resting state fMRI data, we show using an ICA approach, seed based connectivity and dynamic causal modelling that the ascending synchronising system is coupled to the medial temporal lobe nodes including the hippocampus and parahippocampal gyrus and with the default mode network. Our results provide thus support the role of theta oscillations in memory function and coordination.
9 downloads neuroscience
Recently, we presented a new approach to create high-speed amplitude modulation of femtosecond laser pulses and tag multiple excitation beams with specific modulation frequencies. In this work, we discuss the utility of this method to record calcium signals in brain tissue with two-photon frequency-division multiplexing (2P-FDM) microscopy. While frequency-multiplexed imaging appears slightly inferior in terms of image quality as compared to conventional two-photon laser scanning microscopy due to shot noise-induced cross-talk between frequency channels, applying this technique to record average signals from regions of interest (ROI) such as neuronal cell bodies was found to be promising. We use phase information associated with each pixel or waveform within a selected ROI to phase-align and recombine the signals into one extended amplitude-modulated waveform. This procedure narrows the frequency detection window, effectively decreasing noise contributions from other frequency channels. Using theoretical analysis, numerical simulations, and in vitro imaging we demonstrate a reduction of cross-talk by more than an order of magnitude and predict the usefulness of 2P-FDM for functional studies of brain activity.
9 downloads bioinformatics
Comprehensive two dimensional gas chromatography-mass spectrometry is a powerful method for analyzing complex mixtures of volatile compounds. This method produces a large amount of raw data that requires downstream processing to align signals of interest (peaks) across multiple samples and match peak characteristics to reference standard libraries prior to downstream statistical analysis. To address the paucity of applications addressing this need, we have developed an R package that implements retention time and mass spectra similarity threshold-free alignments, seamlessly integrates retention time standards for universally reproducible alignments, performs common ion filtering, and provides compatibility with multiple peak quantification methods. We demonstrate the packages utility on a controlled mix of metabolite standards separated under variable chromatography conditions and data generated from cell lines.
9 downloads biochemistry
It has been discovered that the development of schistosome is hampered in immunodeficient mice, e.g. nude mice lacking T-lymphocytes and the severe combined immune deficient (SCID) mice lacking both T- and B-lymphocytes. However, it’s still unresolved about the underlying regulatory mechanisms of the retarded growth and development of schistosomes in their immunodeficient definitive host. In this study, therefore, five replicates of male or female Schistosoma japonicum samples with twenty male or female worms in each sample, were collected from SCID mice or BALB/c mice at five weeks post infection and used to perform metabonomic analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, for elucidating the growth and development regulation of schistosome in their definitive hosts from the metabolomic aspect. Based on the identified 1015 ion features in ESI+ mode and 342 ion features in ESI- mode, multivariate modelling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) identified distinct metabolic profiles that clearly differentiated both male and female worms in SCID mice from those in BALB/c mice, respectively. Common and uniquely perturbed metabolites and their involved metabolic pathways were identified in male and female worms from SCID mice when compared with those from BALB/c mice. The results also revealed that more differential metabolites were found in female worms (one metabolite was up-regulated and forty metabolites were down-regulated) than male worms (nine metabolites were up-regulated and twenty metabolites were down-regulated) between SCID mice and BALB/c mice. The top five increased metabolites of male worms in SCID mice when compared with those in BALB/c mice were PC(22:6/20:1), L-allothreonine, L-serine, glycerophosphocholine and 5-aminoimidazole ribonucleotide. And the top five decreased metabolites of male worms in SCID mice when compared with those in BALB/c mice were PC(16:0/0:0), PAF C-16, PE(18:1/0:0), adenosine and butenoyl PAF. Most of the differential metabolites of female worms in SCID mice had lower levels when compared with the normal female worms in BALB/c mice, except for retinyl ester with a higher level. The top five decreased metabolites of female worms in SCID mice when compared with those in BALB/c mice were adrenic acid, 5-phosphoribosylamine, PC(16:0/0:0), PC(22:6/20:1) and ergothioneine. The involved metabolic pathways of the differential metabolites in male worms between SCID mice and BALB/c mice mainly included taurine and hypotaurine metabolism, glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, alpha-linolenic acid metabolism, etc. The involved metabolic pathways of differential metabolites in female worms included mainly pyrimidine metabolism, sphingolipid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, etc. These findings suggested a correlation between the retarded growth and development of schistosome in SCID mice and their perturbed metabolic profiles, which also provided a new insight into the regulation mechanisms of growth and development of S. japonicum worms from the metabolic level, and provided clues for discovery of drugs or vaccines against the parasites and parasitic disease.
9 downloads molecular biology
The cAMP dependent protein kinase (PKA) signaling is a broad specificity pathway that plays important roles in the transduction of environmental signals triggering precise physiological responses. cAMP-signal transduction specificity is achieved and controlled at several levels. The Saccharomyces cereviciae PKA holoenzyme contains two catalytic subunits encoded by TPK1, TPK2 and TPK3 genes, and two regulatory subunits encoded by BCY1 gene. In this work we studied the activity of these gene promoters using a reporter-synthetic genetic array screen, with the goal of identifying novel regulators of PKA subunits expression. Gene Ontology (GO) analysis of the identified regulators showed that they were enriched in the category of transcriptional regulators, but also in less expected categories such as lipid and phosphate metabolism. The pathways identified show simultaneous regulation of all four promoters or only specifically of some of them. Further characterization of these pathways effects on promoter activity and mRNA levels pointed to inositol, inositol polyphosphates, choline and phosphate as novel upstream signals that regulate transcription of PKA subunit genes. In addition, within each category there are genes that regulate only one of the promoters and genes that regulate more than one of them at the same time. These results support the role of transcription regulation of each PKA subunit in cAMP specificity signaling. Interestingly, known targets of PKA phosphorylation are associated with the identified pathways, opening the possibility of a reciprocal regulation, PKA would be coordinating different metabolic pathways and these processes would in turn, regulate expression of the kinase subunits
9 downloads biophysics
The membrane protein Photosystem II subunit S (PsbS) is a pH sensor that plays an essential role in signaling light stress in plants to prevent photo oxidation and generation of detrimental reactive species. PsbS detects thylakoid lumen acidification in excess light conditions via two glutamates facing the lumen, however, its molecular mechanism for activation has remained elusive. We performed an infrared and 2-dimensional infrared spectroscopic analysis of wild type Physcomitrella patens PsbS and of mutants in which the active glutamates have been replaced: E71Q, E176Q (the equivalent of E69Q and E173Q in spinach PsbS) and the double mutant E71Q/E176Q. We discovered that E71 exerts allosteric control of PsbS dimerization, while E176 is essential for the secondary structural response to low pH. Based on our results, we propose a molecular pH response mechanism that involves re-positioning of the amphipathic short helix facing the lumen, whereby it moves from the aqueous phase into the hydrophobic membrane phase upon lowering the pH. This structural mechanism may be a shared motif of protein molecular switches of the light-harvesting family and its elucidation could open new routes for crops engineering to improve photosynthetic production of biomass.
9 downloads neuroscience
microRNAs (miRNAs) have emerged as potent regulators of learning, recent memory and extinction. However, our understanding of miRNAs directly involved in regulating complex psychiatric conditions perpetuated by aberrant memory, such as in posttraumatic stress disorder (PTSD), remains limited. To begin to address the role of miRNAs in persistent memory, we performed small-RNA sequencing on basolateral amygdala (BLA) tissue to identify miRNAs altered by auditory fear conditioning (FC) one month after training. mir-598-3p, a highly conserved miRNA previously unstudied in the brain, was downregulated in the BLA. Further decreasing BLA mir-598-3p levels did not alter the expression or extinction of the remote fear memory. Given that stress is a critical component in PTSD, we next assessed the impact of stress-enhanced fear learning (SEFL) on mir-598-3p levels, finding the miRNA is elevated in the BLA of male, but not female, mice susceptible to the effects of stress in SEFL. Accordingly, intra-BLA inhibition of mir-598-3p interfered with expression and extinction of the remote fear memory in male, but not female, mice. This effect could not be attributed to an anxiolytic effect of miRNA inhibition. Finally, bioinformatic analysis following quantitative proteomics on BLA tissue collected 30 days post-SEFL training identified putative mir-598-3p targets and related pathways mediating the differential susceptibility, with evidence for regulation of the actin cytoskeleton.
9 downloads plant biology
Brassicales is a diverse angiosperm order with about 4,700 recognized species. Here, we assembled and described the complete plastid genomes from four species of Brassicales: Capparis urophylla F.Chun (Capparaceae), Carica papaya L. (Caricaceae), Cleome rutidosperma DC. (Cleomaceae), and Moringa oleifera Lam. (Moringaceae), including two plastid genomes newly assembled for two families (Capparaceae and Moringaceae). The four plastid genomes are 159,680 base pairs on average in length and encode 78 protein-coding genes. The genomes each contains a typical structure of a Large Single-Copy (LSC) region and a Small Single-Copy (SSC) region separated by two Inverted Repeat (IR) regions. We performed the maximum-likelihood (ML) phylogenetic analysis using three different data sets of 66 protein-coding genes (ntAll, ntNo3rd and AA). Our phylogenetic results from different dataset are congruent, and are consistent with previous phylogenetic studies of Brassiales.
9 downloads neuroscience
In social contexts individuals frequently act as social chameleons, synchronizing their responses with those of others. Such synchrony is believed to play an important role, promoting mutual emotional and social states. However, synchrony in facial signals, which serve as the main communicative channel between people, has not been systematically studied. To address this gap, we investigated the social spread of smiling dynamics in a naturalistic social setting and assessed its affiliative function. We also studied whether smiling synchrony between people is linked with convergence in their autonomic and emotional responses. To that aim we measured moment-by-moment changes in zygomatic electromyography and cardiovascular activity in dyads of previously unacquainted participants, who co-viewed emotional movies together. We found a robust, dyad-specific, zygomatic synchrony in co-viewing participants, after controlling for movie-driven effects. During the positive movie, zygomatic synchrony co-varied with cardiovascular synchrony and with convergence in positive feelings. No such links were found for the negative movie. Centrally, zygomatic synchrony in both emotional contexts predicted subsequently reported affiliative feelings of dyad members. These results demonstrate that a naturally unfolding smiling behavior is highly contagious. They further suggest that zygomatic synchrony functions as a social facilitator, eliciting affiliation towards previously unknown others.
9 downloads genetics
Separase is a highly conserved protease required for chromosome segregation. Although observations that separase also regulates membrane trafficking events have been made, it is still not clear how separase achieves this function. Here we present an extensive ENU mutagenesis suppressor screen aimed at identifying suppressors of sep-1(e2406), a temperature sensitive maternal effect embryonic lethal separase mutant. We screened nearly a million haploid genomes, and isolated sixty-eight suppressed lines. We identified fourteen independent intragenic sep-1(e2406) suppressed lines. These intragenic alleles map to seven SEP-1 residues within the N-terminus, compensating for the original mutation within the poorly conserved N-terminal domain. Interestingly, 47 of the suppressed lines have novel mutations throughout the entire coding region of the pph-5 phosphatase, indicating that this is an important regulator of separase. We also found that a mutation near the MEEVD motif of HSP-90, which binds and activates PPH-5, also rescues sep-1(e2406) mutants. Finally, we identified six potentially novel suppressor lines that fall into five complementation groups. These new alleles provide the opportunity to more exhaustively investigate the regulation and function of separase.
9 downloads ecology
Energy and matter fluxes essential for all life are modulated by spatial and temporal shifts in microbial community structure resulting from environmental and dispersal filtering, emphasizing the continued need to characterize microbial biogeography. Yet, application of metapopulation theory, traditionally used in general ecology for understanding shifts in biogeographical patterns among macroorganisms, has not been tested extensively for defining marine microbial populations filtered by environmental conditions and dispersal limitation at global ocean scales. Here we show, from applying metapopulation theory on two major global ocean datasets, that microbial populations exhibit core- and satellite distributions with cosmopolitan compared to geographically restricted distributions of populations. We found significant bimodal occupancy-frequency patterns (the different number of species occupying different number of patches) at varying spatial scales, where shifts from bimodal to unimodal patterns indicated environmental and dispersal filtering. Such bimodal occupancy-frequency patterns were validated in Longhurst's classical biogeographical framework and in silico where observed bimodal patterns often aligned with specific biomes and provinces described by Longhurst and where found to be non-random in randomized datasets and mock communities. Taken together, our results show that application of metapopulation theory provides a framework for determining distinct microbial biomes maintained by environmental and dispersal filtering.
9 downloads evolutionary biology
Roberto Amato, Richard D. Pearson, Jacob Almagro-Garcia, Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Eleanor Drury, Jim Stalker, Olivo Miotto, Rick M. Fairhurst, Dominic P Kwiatkowski
Background: Antimalarial failure is rapidly spreading across parts of Southeast Asia where dihydroartemisinin-piperaquine (DHA-PPQ) is used as first line treatment. The first published reports came from western Cambodia in 2013. Here we analyse genetic changes in the Plasmodium falciparum population of western Cambodia in the six years prior to that. Methods: We analysed genome sequence data on 1492 P. falciparum samples from Southeast Asia, including 464 collected in western Cambodia between 2007 and 2013. Different epidemiological origins of resistance were identified by haplotypic analysis of the kelch13 artemisinin resistance locus and the plasmepsin 2-3 piperaquine resistance locus. Findings: We identified over 30 independent origins of artemisinin resistance, of which the KEL1 lineage accounted for 91% of DHA-PPQ-resistant parasites. In 2008, KEL1 combined with PLA1, the major lineage associated with piperaquine resistance. By 2012, the KEL1/PLA1 co-lineage had reached over 60% frequency in western Cambodia and had spread to northern Cambodia. Interpretation: The KEL1/PLA1 co-lineage emerged in the same year that DHA-PPQ became the first line antimalarial drug in western Cambodia and spread aggressively thereafter, displacing other artemisinin-resistant parasite lineages. These findings have significant implications for management of the global health risk associated with the current outbreak.
9 downloads neuroscience
Sleep plays an important role in consolidation of recent memories. However, the mechanisms of consolidation remain poorly understood. In this study, using a realistic computational model of the thalamocortical network, we demonstrated that sleep spindles (the hallmark of N2 stage sleep) and slow oscillations (the hallmark of N3 stage sleep) both facilitate spike sequence replay as necessary for consolidation. When multiple memories were trained, the local nature of spike sequence replay during spindles allowed replay of the memories independently, while during slow oscillations replay of the weak memory was competing to the strong memory replay. This led to the weak memory extinction unless when sleep spindles (N2 sleep) preceded slow oscillations (N3 sleep), as observed during natural sleep. Our study presents a mechanistic explanation for the role of sleep rhythms in memory consolidation and proposes a testable hypothesis how the natural structure of sleep stages provides an optimal environment to consolidate memories.
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