bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular signatures of sexual communication in the phlebotomine sand flies
Authors: Hickner Paul V. , Timoshevskaya Nataliya , Nowling RJ , Labbé Frédéric , Nguyen Andrew D. , McDowell Mary Ann , Spiegel Carolina N. , Syed Zainulabeuddin 
Published: August 2020

AbstractPhlebotomine sand flies employ an elaborate system of pheromone communication wherein males produce pheromones that attracts other males to leks (thus acting as aggregation pheromone) and females to the lekking males (sex pheromone). In addition, the type of pheromone produced varies among populations. Despite the numerous studies on sand fly chemical communication, little is known of their chemosensory genome. Chemoreceptors interact with chemicals in an organism’s environment to elicit essential behaviors such as the identification of suitable mates and food sources, thus, they play important roles during adaptation and speciation. Major chemoreceptor gene families, odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs) together detect and discriminate the chemical landscape. Here, we annotated the chemoreceptor repertoire in the genomes ofLutzomyia longipalpisandPhlebotomus papatasi, major phlebotomine vectors in the New World and Old World, respectively. Comparison with other sequenced Diptera revealed a large and unique expansion where over 80% of the ~140 ORs belong to a single, taxonomically restricted clade. We next conducted comprehensive analysis of the chemoreceptors in 63Lu. longipalpisindividuals from four different locations in Brazil representing allopatric and sympatric populations and three aggregation-sex pheromone types (chemotypes). Population structure based on single nucleotide polymorphisms (SNPs) and gene copy number in the chemoreceptors corresponded with their putative chemotypes, and corroborate previous studies that identified multiple populations. Our work provides genomic insights into the underlying behavioral evolution of sexual communication in theL. longipalpisspecies complex in Brazil, and highlights the importance of accounting for the ongoing speciation in central and South AmericanLutzomyiathat could have important implications for vectorial capacity.
Transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis
Authors: Yarani Reza , Palasca Oana , Doncheva Nadezhda T. , Anthon Christian , Pilecki Bartosz , Svane Cecilie A. S. , Mirza Aashiq H. , Litman Thomas , Holmskov Uffe , Bang-Berthelsen Claus Heiner , Vilien Mogens , Jensen Lars J. , Gorodkin Jan , Pociot Flemming 
Published: August 2020

1.AbstractBACKGROUND & AIMSUlcerative colitis (UC) is an inflammatory bowel disorder with unknown etiology. Given its complex nature,in vivostudies to investigate its pathophysiology is vital. Animal models play an important role in molecular profiling necessary to pinpoint mechanisms that contribute to human disease. Thus, we aim to identify common conserved gene expression signatures and differentially regulated pathways between human UC and a mouse model hereof, which can be used to identify UC patients from healthy individuals and to suggest novel treatment targets and biomarker candidates.METHODSTherefore, we performed high-throughput total and small RNA sequencing to comprehensively characterize the transcriptome landscape of the most widely used UC mouse model, the dextran sodium sulfate (DSS) model. We used this data in conjunction with publicly available human UC transcriptome data to compare gene expression profiles and pathways.RESULTSWe identified differentially regulated protein-coding genes, long non-coding RNAs and microRNAs from colon and blood of UC mice and further characterized the involved pathways and biological processes through which these genes may contribute to disease development and progression. By integrating human and mouse UC datasets, we suggest a set of 51 differentially regulated genes in UC colon and blood that may improve molecular phenotyping, aid in treatment decisions, drug discovery and the design of clinical trials.CONCLUSIONGlobal transcriptome analysis of the DSS-UC mouse model supports its use as an efficient high-throughput tool to discover new targets for therapeutic and diagnostic applications in human UC through identifying relationships between gene expression and disease phenotype.
Curcumin-Sophorolipid nano-conjugate inhibitsCandida albicansfilamentation and biofilm development
Authors: Rajasekar Vidhyashree , Darne Priti , Prabhune Asmita , Kao Richard Y. T. , Solomon Adline Princy , Ramage Gordon , Samaranayake Lakshman , Neelakantan Prasanna 
Published: August 2020

AbstractCandida albicansis an opportunistic fungal pathogen that is highly resistant to contemporary antifungals, and a major reason for this appears to be their predominant, filamentation-mediated, biofilm lifestyle. Hence, agents that inhibit biofilms and filamentation of the yeast offer promise as next-generation antifungals. Curcumin is a natural polyphenol with several beneficial pharmacological attributes, yet limitations such as poor solubility, acid, and enzyme tolerance have impeded its practical utility. Sophorolipids are biologically-derived surfactants that serve as efficient carriers and delivery agents of hydrophobic molecules, such as curcumin, into biofilms. The aim of this study was to investigate the effects of a novel, curcumin-sophorolipid (CU-ASL) nano-conjugate onCandida albicansbiofilms and filamentation. The effects of CU and ASL, in combination, and alone, were investigated on planktonic cells of the yeast. The effects of sub-inhibitory concentrations of the compounds were investigated on biofilm biomass and biofilm architecture. Their effects on filamentation was compared by scanning electron microscopic imaging, and gene expression analysis by qRT-PCR. Our results demonstrated that sub-inhibitory concentration of CU-ASL (9.37 µg/mL) significantly inhibited candidal adhesion to substrates, and subsequent biofilm development, maturation, and filamentation. This effect was associated with significant downregulation of a select group of biofilm, adhesins, and hyphal regulatory genes. In conclusion, the curcumin-sophorolipid nano-conjugate is a potent inhibitor of the two major virulence attributes ofC. albicans, biofilm formation and filamentation, thus highlighting its promise as a putative anti-candidal agent with low toxicity and biofilm penetrative potential.
Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection
Authors: Wang Cheng , Wang Shaobo , Chen Yin , Zhao Jianqi , Han Songling , Zhao Gaomei , Kang Jing , Liu Yong , Wang Liting , Wang Xiaoyang , Xu Yang , Wang Song , Huang Yi , Wang Junping , Zhao Jinghong 
Published: August 2020

ABSTRACTThe ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg−1of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-acheive memrbane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19.Graphical Table of Contents
Regression dynamic causal modeling for resting-state fMRI
Authors: Frässle Stefan , Harrison Samuel J. , Heinzle Jakob , Clementz Brett A. , Tamminga Carol A. , Sweeney John A. , Gershon Elliot S. , Keshavan Matcheri S. , Pearlson Godfrey D. , Powers Albert , Stephan Klaas E. 
Published: August 2020

Abstract“Resting-state” functional magnetic resonance imaging (rs-fMRI) is widely used to study brain connectivity. So far, researchers have been restricted to measures of functional connectivity that are computationally efficient but undirected, or to effective connectivity estimates that are directed but limited to small networks.Here, we show that a method recently developed for task-fMRI – regression dynamic causal modeling (rDCM) – extends to rs-fMRI and offers both directional estimates and scalability to whole-brain networks. First, simulations demonstrate that rDCM faithfully recovers parameter values over a wide range of signal-to-noise ratios and repetition times. Second, we test construct validity of rDCM in relation to an established model of effective connectivity, spectral DCM. Using rs-fMRI data from nearly 200 healthy participants, rDCM produces biologically plausible results consistent with estimates by spectral DCM. Importantly, rDCM is computationally highly efficient, reconstructing whole-brain networks (>200 areas) within minutes on standard hardware. This opens promising new avenues for connectomics.
Wnt/PCP-primed intestinal stem cells directly differentiate into enteroendocrine or Paneth cells
Authors: Böttcher Anika , Büttner Maren , Tritschler Sophie , Sterr Michael , Aliluev Alexandra , Oppenländer Lena , Burtscher Ingo , Sass Steffen , Irmler Martin , Beckers Johannes , Ziegenhain Christoph , Enard Wolfgang , Schamberger Andrea C. , Verhamme Fien M. , Eickelberg Oliver , Theis Fabian J. , Lickert Heiko 
Published: August 2020

SUMMARYA detailed understanding of intestinal stem cell (ISC) self-renewal and differentiation is required to better treat chronic intestinal diseases. However, different models of ISC lineage hierarchy1–6and segregation7–12are debated. Here we report the identification of Lgr5+ISCs that expressFlattop(Fltp), a Wnt/planar cell polarity (PCP) reporter and effector gene. Lineage labelling revealed that Wnt/PCP-activatedFltp+ISCs are primed either towards the enteroendocrine or the Paneth cell lineagein vivo. Integration of time-resolved lineage labelling with genome-wide and targeted single-cell gene expression analysis allowed us to delineate the ISC differentiation path into enteroendocrine and Paneth cells at the molecular level. Strikingly, we found that both lineages are directly recruited from ISCs via unipotent transition states, challenging the existence of formerly predicted bi- or multipotent secretory progenitors7–12. Transitory cells that mature into Paneth cells are quiescent and express both stem cell and secretory lineage genes, indicating that these cells are the previously described Lgr5+labelretaining cells7. Wnt/PCP-activated Lgr5+ISCs are indistinguishable from Wnt/β-catenin-activated Lgr5+ISCs based on the expression of stem-cell signature or secretory lineagespecifying genes but possess less self-renewal activity. This suggests that lineage priming and cell-cycle exit is triggered at the post-transcriptional level by polarity cues and a switch from canonical to non-canonical Wnt/PCP signalling. Taken together, we identified the Wnt/PCP pathway as a new niche signal and polarity cue regulating stem cell fate. Active Wnt/PCP signalling represents one of the earliest events in ISC lineage priming towards the Paneth and enteroendocrine cell fate, preceding lateral inhibition and expression of secretory lineagespecifying genes. Thus, our findings provide a better understanding of the niche signals and redefine the mechanisms underlying ISC lineage hierarchy and segregation.
L1CAM is not Associated with Extracellular Vesicles in Human Cerebrospinal Fluid or Plasma
Authors: Norman Maia , Ter-Ovanesyan Dmitry , Trieu Wendy , Lazarovits Roey , Kowal Emma J.K. , Lee Ju Hyun , Chen-Plotkin Alice S. , Regev Aviv , Church George M. , Walt David R. 
Published: August 2020

AbstractNeuron-derived extracellular vesicles (NDEVs) present a tremendous opportunity to learn about the biochemistry of brain cells in living patients. L1CAM is a transmembrane protein expressed in neurons that is presumed to be found on NDEVs in human biofluids. Previous studies have used L1CAM immuno-isolation from human plasma to isolate NDEVs for neurodegenerative disease diagnostics. We developed a panel of ultrasensitive Single Molecule Array (Simoa) assays for known EV markers, as well as L1CAM, and applied it to study EVs in human plasma and cerebrospinal fluid (CSF). We fractionated plasma and CSF by size exclusion chromatography (SEC) and density gradient centrifugation (DGC) to separate EVs from free proteins. We observed that L1CAM did not elute in the EV fractions, but rather eluted in the free protein fractions. We found that L1CAM is present as a free protein in human plasma and CSF, possibly due to proteolytic cleavage and/or alternative splicing. We further demonstrate that the isoforms found in CSF and plasma are different. These data collectively establish that L1CAM in plasma is not EV associated and should therefore not be used for NDEV isolation. Importantly, the framework and tools described herein will allow for evaluation of other potential candidate markers for isolation of NDEVs.
Coronacept – a potent immunoadhesin against SARS-CoV-2
Authors: Cohen-Dvashi Hadas , Weinstein Jonathan , Katz Michael , Eilon Maayan , Mor Yuval , Shimon Amir , Strobelt Romano , Shemesh Maya , Fleishman Sarel J , Diskin Ron 
Published: August 2020

AbstractAngiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Computational analysis of mammalian ACE2 orthologues suggests various residues at the interface with the viral receptor binding domain that could facilitate tighter interaction compared to the human-ACE2. Introducing several mutations to the human-ACE2 resulted with significantly augmented affinity to the viral spike complex. This modified human-ACE2 fused to an Fc portion of an antibody makes a potent immunoadhesin that effectively targets SARS-CoV-2.
The SOD-2 protein is the single active SOD enzyme inC. elegans
Authors: Fernando Lourds M. , Adeel Silwat , Basar Mohammed Abul , Allen Anna K. , Duttaroy Atanu 
Published: August 2020

ABSTRACTThe nematodeC. eleganshas a contingent of fivesodgenes, one of the largest among aerobic organism. Earlier studies revealed each of the fivesodgenes is capable of making perfectly active SOD proteins in heterologous expressions systems therefore none appears to be a pseudogene. Yet deletion of the entire contingent ofsodgenes fails to impose any effect on the survival ofC. elegansexcept these animals appear more sensitive to extraneously applied oxidative stress condition. We asked how many of the fivesodgenes are actually active inC. elegansthrough an in-gel SOD activity analysis. Here we provide evidence that out of the five genes only the mitochondrial SOD gene is active inC. elegans, albeit at a much lesser amount compared toD. melanogasterandE. coli. Mutant analysis further confirmed that among the mitochondrial forms, SOD-2 is the only naturally active SOD inC. elegans.
Diverse roles ofMAX1homologues in rice
Authors: Marzec Marek , Situmorang Apriadi , Brewer Philip B. , Brąszewska-Zalewska Agnieszka 
Published: August 2020

AbstractCytochrome P450 enzymes encoded byMORE AXILLARY GROWTH1(MAX1)-like genes produce most of the structural diversity of strigolactones during the final steps of strigolactone biosynthesis. The diverse copies ofMAX1inOryza sativaprovide a resource to investigate why plants produce such a wide range of strigolactones. Here we performedin silicoanalyses of transcription factors and microRNAs that may regulate each riceMAX1, and compared the results with available data aboutMAX1expression profiles and genes co-expressed withMAX1genes. Data suggest that distinct mechanisms regulate the expression of eachMAX1. Moreover, there may be novel functions forMAX1homologues, such as the regulation of flower development or responses to heavy metals. In addition, individualMAX1scould be involved in specific functions, such as the regulation of seed development or wax synthesis in rice. Our analysis reveals potential new avenues of strigolactone research that may otherwise not be obvious.
Interhemispheric transfer of working memories
Authors: Brincat Scott L. , Donoghue Jacob A. , Mahnke Meredith K. , Kornblith Simon , Lundqvist Mikael , Miller Earl K. 
Published: August 2020

SUMMARYVisual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered location from one hemifield to the other. Before the shift, spike rates and oscillatory power showed clear signatures of memory laterality. After the shift, the lateralization inverted, consistent with transfer of the memory trace from one hemisphere to the other. Transferred traces initially used different neural ensembles from feedforward-induced ones but they converged at the end of the delay. Around the time of transfer, synchrony between the two prefrontal hemispheres peaked in theta and beta frequencies, with a directionality consistent with memory trace transfer. This illustrates how dynamics between the two cortical hemispheres can stitch together WM traces across visual hemifields.
Visualizing Population Structure with Variational Autoencoders
Authors: Battey C. J. , Coffing Gabrielle C. , Kern Andrew D. 
Published: August 2020

AbstractDimensionality reduction is a common tool for visualization and inference of population structure from genotypes, but popular methods either return too many dimensions for easy plotting (PCA) or fail to preserve global geometry (t-SNE and UMAP). Here we explore the utility of variational autoencoders (VAEs) – generative machine learning models in which a pair of neural networks seek to first compress and then recreate the input data – for visualizing population genetic variation. VAEs incorporate non-linear relationships, allow users to define the dimensionality of the latent space, and in our tests preserve global geometry better than t-SNE and UMAP. Our implementation, which we callpopvae, is available as a command-line python program atgithub.com/kr-colab/popvae. The approach yields latent embeddings that capture subtle aspects of population structure in humans andAnophelesmosquitoes, and can generate artificial genotypes characteristic of a given sample or population.
Role of microRNA-145 in DNA damage signalling and senescence in vascular smooth muscle cells of Type 2 diabetic patients
Authors: Hemmings Karen E , Riches-Suman Kirsten , Bailey Marc A , O’Regan David J , Turner Neil A , Porter Karen E 
Published: August 2020

AbstractIncreased cardiovascular morbidity and mortality in individuals with type 2 diabetes (T2DM) is a significant clinical problem. Despite advancements in achieving good glycaemic control, this patient population remains susceptible to macrovascular complications. We previously discovered that vascular smooth muscle cells (SMC) cultured from T2DM patients exhibit persistent phenotypic aberrancies distinct from those of individuals without a diagnosis of T2DM. Notably, persistently elevated expression levels of microRNA-145 co-exist with characteristics consistent with aging, DNA damage and senescence. We hypothesised that increased expression of microRNA-145 plays a functional role in DNA damage signalling and subsequent cellular senescence specifically in SMC cultured from the vasculature of T2DM patients. In this study, markers of DNA damage and senescence were unambiguously and permanently elevated in native T2DM versus non-diabetic (ND)-SMC. Exposure of ND cells to the DNA-damaging agent etoposide inflicted a senescent phenotype, increased expression of apical kinases of the DNA damage pathway and elevated expression levels of microRNA-145. Overexpression of microRNA-145 in ND-SMC revealed evidence of functional links between them; notably increased secretion of senescence-associated cytokines and chronic activation of stress-activated intracellular signalling pathways, particularly the mitogen-activated protein kinase, p38α. Exposure to conditioned media from microRNA-145 overexpressing cells resulted in chronic p38α signalling in naïve cells, evidencing a paracrine induction and reinforcement of cell senescence. We conclude that targeting of microRNA-145 may provide a route to novel interventions to eliminate DNA-damaged and senescent cells in the vasculature and to this end further detailed studies are warranted.
A combined RAD-Seq and WGS approach reveals the genomic basis of yellow color variation in bumble beeBombus terrestris
Authors: Rahman Sarthok Rasique , Cnaani Jonathan , Kinch Lisa N. , Grishin Nick V. , Hines Heather M. 
Published: August 2020

AbstractBackgroundIn the model bumble bee speciesB. terrestris, both males and females exhibit black coloration on the third thoracic and first metasomal segments. We discovered a fortuitous lab-generated mutant in which this typical black coloration is replaced by yellow. As this same color variant is found in several sister lineages toB. terrestriswithin theBombus s.s. subgenus, this could be a result of ancestral allele sorting.ResultsUtilizing a combination of RAD-Seq and whole-genome re-sequencing approaches, we localized the color-generating variant to a single SNP in the protein-coding sequence of a homeobox transcription factor,cut. Sanger sequencing confirmed fixation of this SNP between wildtype and yellow mutants. Protein domain analysis revealed this SNP to generate an amino acid change (Ala38Pro) that modifies the conformation of coiled-coil structural elements which lie outside the characteristic DNA binding domains. We found all Hymenopterans includingB. terrestrissister lineages possess the non-mutant allele, indicating different mechanism(s) are involved in the same black to yellow transition in nature.ConclusionsCutis a highly pleiotropic gene important for multiple facets of development, yet this mutation generated no noticeable external phenotypic effects outside of setal characteristics. Reproductive capacity was observed to be reduced, however, with queens being less likely to mate and produce female offspring, in a manner similar to workers. Our research implicates a novel developmental player in pigmentation, and potentially caste as well, thus contributing to a better understanding of the evolution of diversity in both of these processes.