bluuebunny/crossref_metadata_2025 huggingface dataset:
Landscapes of transposable elements inApisspecies by meta-analysis
Authors: Yokoi Kakeru , Kimura Kiyoshi , Bono Hidemasa
Published: April 2020

Transposable elements (TEs) are grouped into several classes with diverse sequences. Owing to their diversity, studies involving the detection, classification, and annotation of TEs are difficult tasks. Moreover, simple comparisons of TEs among different species with different methods can lead to misinterpretations. The genome data of several honey bee (Apis) species are available in public databases. Therefore, we conducted a meta-analysis of TEs, using 11 sets of genome data forApisspecies, in order to establish the basal TE data (termed here as the ‘landscape of TEs’). Consensus TE sequences were constructed and their distributions in theApisgenomes were determined. Our results showed that TEs from several limited families mainly consisted ofApisTEs and that more DNA/TcMar-Mariner consensus sequences and copies were present in allApisgenomes tested. In addition, more consensus sequences and copy numbers of DNA/TcMar-Mariner were detected inApis melliferathan in otherApisspecies. These results suggest that TcMar-Mariner might exertA. mellifera-specific effects on the hostA. melliferaspecies. In conclusion, our unified approach enabled comparison ofApisgenome sequences to determine the TE landscape, which provide novel evolutionary insights intoApisspecies.

Simple Summary

Studies on the detection of transposable elements and their annotations have posed several challenges. For example, simple comparisons of transposable elements in different species using different methods can lead to misinterpretations. Thus, assembling data for transposable elements analyzed by unified methods is important for comparison purposes. Therefore, we performed a meta-analysis of transposable elements identified using genome datasets from 5Apisspecies (11 sets of genome data) and specific software to detect the transposable elements, which revealed the landscapes of transposable elements. We examined the types and locations of transposable elements in theApisgenomes. The landscapes of transposable elements showed that several limited transposable element families consisted mainly ofApis-associated transposable elements. These limited families include DNA/TcMar-Mariner and DNA/CMC-EnSpm. In addition, more DNA/TcMar-Mariner consensus sequences and copies were detected inApis melliferathan in otherApisspecies. These data suggest that TcMar-Mariner might exertA. mellifera-specific effects in the hostA. melliferaspecies. Our landscape data provide new insights intoApistransposable elements; furthermore, detailed analyses of our data could pave the way for new biological insights in this field.
Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s disease
Authors: Womack Tasha R. , Vollert Craig , Nwoko Odochi , Schmitt Monika , Montazari Sagi , Beckett Tina , Mayerich David , Murphy Michael Paul , Eriksen Jason L.
Published: April 2020

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies, while epidemiological and experimental evidence suggests that the use of anti-inflammatory agents may be neuroprotective. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid disease pathologies. Mice overexpressing both amyloid and PGI2exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2control mice. PGI2overexpression accelerated the development of amyloid accumulation in the brain and selectively increased the production of soluble amyloid-β 42. PGI2damaged the microvasculature through alterations in vascular length and branching; amyloid expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.
α-Linolenic acid modulates phagocytosis of extracellular Tau and induces microglial migration
Authors: Desale Smita Eknath , Chinnathambi Subashchandrabose
Published: April 2020

The seeding effect of extracellular Tau species is an emerging aspect to study the Tauopathies in Alzheimer’s disease. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. Omega-3 fatty acids are known to exert the anti-inflammatory property to microglia by modulating cell membrane compositions that influence various receptors expression and signaling cascade. The immunomodulatory function of omega-3 fatty acids exerts anti-inflammatory properties to microglia. Owing to the imparted anti-inflammatory nature enhance phagocytosis and increased migration property has been observed in microglia. The increased phagocytosis of extracellular Tau monomer and aggregates has been observed upon ALA exposure to microglia cells. The intracellular degradation of internalized Tau species was targeted by early and late endosomal markers Rab5 and Rab7. The increased levels of LAMP-2A and colocalization with internalized Tau indicated the degradationvialysosome. These results indicate the degradation of internalized Tau species in the presence of ALA instead of getting accumulated in the cell. The enhanced migratory ability of microglia in the presence of ALA induces the MTOC repolarization. Tau seeds greatly contribute to the spread of disease, one way to reduce the spreading is to reduce the presence of extracellular Tau seed. Microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids. Our results suggest that dietary fatty acids ALA significantly enhances phagocytosis and intracellular degradation of internalized Tau. Enhanced migration supports the phagocytosis process. Our approach provides insights into the beneficial role of ALA as an anti-inflammatory dietary supplement to treat AD.
Exploring systematic biases, rooting methods and morphological evidence to unravel the evolutionary history of the genusFicus(Moraceae)
Authors: Rasplus Jean-Yves , Rodriguez Lillian Jennifer , Sauné Laure , Peng Yang-Qiong , Bain Anthony , Kjellberg Finn , Harrison Rhett D. , Pereira Rodrigo A.S. , Ubaidillah Rosichon , Tollon-Cordet Christine , Gautier Mathieu , Rossi Jean-Pierre , Cruaud Astrid
Published: April 2020

Despite their ecological and evolutionary importance as key components of tropical ecosystems, the phylogeny of fig trees is still unresolved. We use restriction-site-associated DNA (RAD) sequencing (ca420kb) and 102 morphological characters to elucidate the relationships between 70 species ofFicusrepresenting all known subgenera and sections and five outgroups. We compare morphological and molecular results to highlight discrepancies and reveal possible inference bias. We analyse marker and taxon properties that may bias molecular inferences, with existing softwares and a new approach based on iterative principal component analysis to reduce variance between clusters of samples. For the first time, with both molecular and morphological data, we recover a monophyletic subgenusUrostigmaand a clade with all gynodioecious fig trees. However, our analyses show that it is not possible to homogenize evolutionary rates and GC content for all taxa prior to phylogenetic inference and that four competing positions for the root of the molecular tree are possible. The placement of the long-branched sectionPharmacosyceaas sister to all other fig trees is not supported by morphological data and considered as a result of a long branch attraction artefact to the outgroups. Regarding morphological features and indirect evidence from the pollinator tree of life, the topology that divides the genusFicusinto monoeciousversusgynodioecious species appears most likely. Active pollination is inferred as the ancestral state for all topologies, ambiguity remains for ancestral breeding system including for the favored topology, and it appears most likely that the ancestor of fig trees was a freestanding tree. Increasing sampling may improve results and would be at least as relevant as maximizing the number of sequenced regions given the strong heterogeneity in evolutionary rates, and to a lesser extent, base composition among species. Despite morphological plasticity and frequent homoplasy of multiple characters, we advocate giving a central role to morphology in our understanding of the evolution ofFicus, especially as it can help detect insidious systematic errors that tend to become more pronounced with larger molecular data sets.
Introduction of a leaky stop codon as molecular tool inChlamydomonas reinhardtii
Authors: Caspari Oliver D
Published: April 2020

Expression of proteins in the chloroplast or mitochondria of the model green algaChlamydomonas reinhardtiican be achieved by directly inserting transgenes into organellar genomes, or through nuclear expression and post-translational import. A number of tools have been developed in the literature for achieving high expression levels from the nuclear genome despite messy genomic integration and widespread silencing of transgenes. Here, recent advances in the field are combined and two systems of bicistronic expression, based on ribosome reinitiation or ribosomal skip induced by a viral 2A sequence, are compared side-by-side. Further, the small subunit of Rubisco (RBCS) was developed as a functional nuclear reporter for successful chloroplast import and restoration of photosynthesis: To be able to combine RBCS with a Venus fluorescent reporter without compromising photosynthetic activity, a leaky stop codon is introduced as a novel molecular tool that allows the simultaneous expression of functional and fluorescently tagged versions of the protein from a single construct.
Uncovering of cytochrome P450 anatomy by SecStrAnnotator
Authors: Midlik Adam , Navrátilová Veronika , Moturu Taraka Ramji , Koča Jaroslav , Svobodová Radka , Berka Karel
Published: April 2020

Protein structural families are groups of homologous proteins defined by the organization of secondary structure elements (SSEs). Nowadays, many families contain vast numbers of structures, and the SSEs can help to orient within them. Communities around specific protein families have even developed specialized SSE annotations, always assigning the same name to the equivalent SSEs in homologous proteins. A detailed analysis of the groups of equivalent SSEs provides an overview of the studied family and enriches the analysis of any particular protein at hand.

We developed a workflow for the analysis of the secondary structure anatomy of a protein family. We applied this analysis to the model family of cytochromes P450 (CYPs) – a family of important biotransformation enzymes with a community-wide used SSE annotation. We report the occurrence, typical length and amino acid sequence for the equivalent SSE groups, the conservation/variability of these properties and relationship to the substrate recognition sites. We also suggest a generic residue numbering scheme for the CYP family. Comparing the bacterial and eukaryotic part of the family highlights the significant differences and reveals an anomalous group of bacterial CYPs with some typically eukaryotic features. Application of our workflow to other families could produce equally surprising findings.
DTA expression in mTas1r3+ cells lead to male infertility
Authors: Li Feng , Niu Bowen , Liu Lingling
Published: April 2020

TAS1R taste receptors and their associated heterotrimeric G protein gustducin are strongly expressed in testis and sperm, but their functions and distribution in these tissues were unknown. Using transgenic mouse models, we show that taste signal transduction cascades (mTas1r3-Gnat3-Trmp5) are observed in testis form GFP transgenic mice. It is mTas1rs and mTas2rs, not Gnat3, that was expressed in leydig and sertoli cells. The pattern of mTas1r3 expression was different from that of mTas2r105 expression in seminiferous epithelium. Analysis of the seminiferous epithelium cycle show that both mTas1r3 and mTas2r105 is expressed in the spermatid stage, but mTas2r5 expression is found in spermatocyte stage. Conditional deletion of mTas1r3+ cells leads to male infertility, but do not affect the expression of taste signal transduction cascade during the spermatogenesis. The current results indicate a critical role for mTas1r3+ cell in sperm development and maturation.
IGF-1 facilitates extinction of conditioned fear
Authors: Noriega-Prieto José A. , Maglio Laura E. , Maroto Irene B. , Martin-Cortecero Jesús , Muñoz-Callejas Antonio , Callejo-Móstoles Marta , de Sevilla David Fernández
Published: April 2020

Insulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, degenerative diseases, spatial learning, and anxiety-like behavioral processes. While IGF-1 regulates neuronal activity in many areas of the brain, its effect on synaptic plasticity and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the infralimbic cortex. Besides, IGF-1 mediates a long-term depression of both inhibitory and excitatory synaptic transmission that results in a longterm potentiation of the postsynaptic potentials. We demonstrate that these synaptic and intrinsic regulatory processes mediated by IGF-1 favor the fear extinction memory. These results show novel functional consequences of IGF-1 signaling on animal behavior tasks dependent on the prefrontal cortex, revealing IGF-1 as a key element in the control of the fear extinction memory.

Impact Statement

IGF-1 modulates the neuronal firing and synaptic plasticity in infralimbic cortex, favoring the extinction memory
Severe asthma is associated with a remodeling of the pulmonary arteries in horses
Authors: Ceriotti Serena , Bullone Michela , Leclere Mathilde , Ferrucci Francesco , Lavoie Jean-Pierre
Published: April 2020

Pulmonary hypertension andcor pulmonaleare complications of severe equine asthma, as a consequence of pulmonary hypoxic vasoconstriction. However, as pulmonary hypertension is only partially reversible by oxygen administration, other etiological factors are likely involved. In human chronic obstructive pulmonary disease, pulmonary artery remodeling contributes to the development of pulmonary hypertension. In rodent models, pulmonary vascular remodeling is present as a consequence of allergic airway inflammation. The present study investigated the presence of remodeling of the pulmonary arteries in severe equine asthma, its distribution throughout the lungs, and its reversibility following long-term antigen avoidance strategies and inhaled corticosteroid administration. Using histomorphometry, the total wall area of pulmonary arteries from different regions of the lung of asthmatic horses and controls was measured. The smooth muscle mass of pulmonary arteries was also estimated on lung sections stained for α-smooth muscle actin. Reversibility of vascular changes in asthmatic horses was assessed after 1 year of antigen avoidance alone or treatment with inhaled fluticasone. Pulmonary arteries showed increased wall area in apical and caudodorsal lung regions of asthmatic horses in both exacerbation and remission. The pulmonary arteries smooth muscle mass was similarly increased. Both treatments reversed the increase in wall area. However, normalization of the vascular smooth muscle mass was observed only after treatment with antigen avoidance, but not with fluticasone. In conclusion, severe equine asthma is associated with remodeling of the pulmonary arteries consisting in an increased smooth muscle mass. The resulting narrowing of the artery lumen could enhance hypoxic vasoconstriction, contributing to pulmonary hypertension. Vascular smooth muscle mass normalization is better achieved by antigen avoidance than with inhaled corticosteroids.
The application of community ecology theory to co-infections in wildlife hosts
Authors: Ramsay Chloe , Rohr Jason R.
Published: April 2020

Priority effect theory, a foundational concept from community ecology, states that the order and timing of species arrival during species assembly can affect species composition. Although this theory has been applied to co-infecting parasite species, it has almost always been with a single time lag between co-infecting parasites. Thus, how the timing of parasite species arrival affects co-infections and disease remains poorly understood. To address this gap in the literature, we exposed post-metamorphic Cuban tree frogs (Osteopilus septentrionalis) to Ranavirus, the fungusBatrachochytrium dendrobatidis(Bd), a nematodeAplectana hamatospicula, or pairs of these parasites either simultaneously or sequentially at a range of time lags and quantified load of the secondary parasite and host growth, survival and parasite tolerance. Prior exposure to Bd orA. hamatospiculasignificantly increased viral loads relative to hosts singly infected with Ranavirus, whereasA. hamatospiculaloads in hosts were higher when co-exposed to Bd than when co-exposed to Ranavirus. There was a significant positive relationship between time since Ranavirus infection and Bd load, and prior exposure toA. hamatospiculadecreased Bd loads compared to simultaneous co-infection with these parasites. Infections with Bd and Ranavirus either singly or in co-infections decreased host growth and survival. This research reveals that time lags between co-infections can affect parasite loads, in line with priority effects theory. As co-infections in the field are unlikely to be simultaneous, an understanding of when co-infections are impacted by time lags between parasite exposures may play a major role in controlling problematic co-infections.
Adaptive rescheduling of error monitoring in multitasking
Authors: Steinhauser Robert , Steinhauser Marco
Published: April 2020

The concurrent execution of temporally overlapping tasks leads to considerable interference between the subtasks. This also impairs control processes associated with the detection of performance errors. In the present study, we investigated how the human brain adapts to this interference between task representations in such multitasking scenarios. In Experiment 1, participants worked on a dual-tasking paradigm with partially overlapping execution of two tasks (T1 and T2), while we recorded error-related scalp potentials. The error positivity (Pe), a correlate of higher-level error evaluation, was reduced after T1 errors but occurred after a correct T2-response instead. MVPA-based and regression-based single-trial analysis revealed that the immediate Pe and deferred Pe are negatively correlated, suggesting a trial-wise trade-off between immediate and postponed error processing. Experiment 2 confirmed this finding and additionally showed that this result is not due to credit-assignment errors in which a T1 error is falsely attributed to T2. For the first time reporting a Pe that is temporally detached from its eliciting error event by a considerable amount of time, this study illustrates how reliable error detection in dual-tasking is maintained by a mechanism that adaptively schedules error processing, thus demonstrating a remarkable flexibility of the human brain when adapting to multitasking situations.

Significance Statement

Multitasking situations are associated with impaired performance, as the brain needs to allocate resources to more than one task at a time. This also makes it more difficult to detect one’s own performance errors in such complex scenarios. In two experiments, we recorded error-related electroencephalographic (EEG) activity and found that the commonly assumed fixed temporal succession of control processes in error monitoring can be strategically interrupted. Individual processes of error detection can be temporally rescheduled to after completion of competing tasks. This reduces interference between the neural task representations and supports a more efficient execution of concurrent tasks in multitasking.
Breakage of the Oligomeric CaMKII Hub by the Regulatory Segment of the Kinase
Authors: Karandur Deepti , Bhattacharyya Moitrayee , Xia Beryl , Lee Young Kwang , Muratcioglu Serena , McAffee Darren , McSpadden Ethan D. , Qiu Baiyu , Groves Jay , Williams Evan , Kuriyan John
Published: April 2020

Ca2+/calmodulin dependent protein kinase II (CaMKII) is a dodecameric or tetradecameric enzyme with crucial roles in neuronal signaling and cardiac function. Activation of CaMKII is reported to trigger the exchange of subunits between holoenzymes, which can increase spread of the active state. Using mass spectrometry, we now show that peptides derived from the sequence of the CaMKII-α regulatory segment can bind to the CaMKII-α hub assembly and break it into smaller oligomers. Molecular dynamics simulations show that the regulatory segments can dock spontaneously at the interface between hub subunits, trapping large fluctuations in hub structure. Single-molecule fluorescence intensity analysis of human CaMKII-α isolated from mammalian cells shows that activation of CaMKII-α results in the destabilization of the holoenzyme. Our results show how the release of the regulatory segment by activation and phosphorylation could allow it to destabilize the hub, producing smaller CaMKII assemblies that can reassemble to form new holoenzymes.
Efficient chromatin accessibility mappingin situby nucleosome-tethered tagmentation
Authors: Henikoff Steven , Henikoff Jorja G. , Kaya-Okur Hatice S. , Ahmad Kami
Published: April 2020

Chromatin accessibility mapping is a powerful approach to identify potential regulatory elements. A popular example is ATAC-seq, whereby Tn5 transposase inserts sequencing adapters into accessible DNA (‘tagmentation’). CUT&Tag is a tagmentation-based epigenomic profiling method in which antibody tethering of Tn5 to a chromatin epitope of interest profiles specific chromatin features in small samples and single cells. Here we show that by simply modifying the tagmentation conditions for histone H3K4me2 or H3K4me3 CUT&Tag, antibody-tethered tagmentation of accessible DNA sites is redirected to produce chromatin accessibility maps that are indistinguishable from the best ATAC-seq maps. Thus, chromatin accessibility maps can be produced in parallel with CUT&Tag maps of other epitopes with all steps from nuclei to amplified sequencing-ready libraries performed in single PCR tubes in the laboratory or on a home workbench. As H3K4 methylation is produced by transcription at promoters and enhancers, our method identifies transcription-coupled accessible regulatory sites.
Auditory features modelling reveals sound envelope representation in striate cortex
Authors: Martinelli Alice , Handjaras Giacomo , Betta Monica , Leo Andrea , Cecchetti Luca , Pietrini Pietro , Ricciardi Emiliano , Bottari Davide
Published: April 2020

The striate cortex is no longer considered exclusively visual in its function. Proofs that its activity is modulated by acoustic inputs have accrued. By employing category-based and feature modeling approaches, here we characterized V1 activity (in absence of retinal input) during the processing of natural and synthetically derived sounds. First, we showed that distinct sound categories could be dissociated by the analysis of V1 multivoxel response patterns. Hence, we assessed whether a hallmark of sound neural representations is mapped in V1. In each sound category, we modeled sound envelopes and assessed whether these were represented at the single-voxel level in the striate cortex and, as a control, in the temporal cortex. The hierarchical organization of sound categories allowed to exert control over dimensions that could spuriously lead to sound envelope V1 mapping. Variations of sound amplitude over time were successfully decoded in V1 regardless of the category class. Results confirm that the human striate cortex receives acoustic category-based input and demonstrate that V1 is a genuine locus of sound envelope representation.
Maintenance of variation in virulence and reproduction in populations of an agricultural plant pathogen
Authors: Dutta Anik , Croll Daniel , McDonald Bruce A. , Barrett Luke G.
Published: April 2020

Genetic diversity within pathogen populations is critically important for predicting pathogen evolution, disease outcomes and prevalence. However, we lack a good understanding of the processes maintaining genetic variation and constraints on pathogen life-history evolution. Here, we analyzed interactions between 12 wheat host genotypes and 145 strains ofZymoseptoria triticifrom five global populations to investigate the evolution and maintenance of variation in pathogen virulence and reproduction. We found a strong positive correlation between virulence and reproduction, with substantial variation in both traits maintained within each pathogen population. On average, highly virulent isolates exhibited higher fecundity, which might increase transmission potential in agricultural fields planted to homogeneous hosts at a high density. We further showed that pathogen strains with a narrow host range (i.e. specialists) for fecundity were on average less virulent, and those with a broader host range (i.e. generalists) for virulence were on average less fecund on a given specific host. These trade-offs costs associated with host specialization might constrain the directional evolution of virulence and fecundity. We conclude that selection favoring pathogen strains that are virulent across diverse hosts, coupled with selection that maximizes fecundity on specific hosts, may explain the maintenance of these pathogenicity traits within and among pathogen populations.
In situreprogramming of gut bacteria by oral delivery
Authors: Hsu Bryan B. , Plant Isaac N. , Lyon Lorena , Anastassacos Frances M. , Way Jeffrey C. , Silver Pamela A.
Published: April 2020

Abundant links between the gut microbiota and human health indicate that the modification of bacterial function could be a powerful therapeutic strategy. The inaccessibility of the gut and inter-connections between gut bacteria and the host make it difficult to precisely target bacterial functions without disrupting the microbiota and/or host physiology. Herein we describe a multidisciplinary approach to modulate the expression of a specific bacterial gene within the gut by oral administration. We first demonstrate that an engineered temperate phage λ expressing a programmable dCas9 represses a targetedE. coligene in the mammalian gut. To facilitate phage administration while minimizing disruption to host processes, we develop an aqueous-based encapsulation formulation with a microbiota-based release mechanism and show that it facilitates the oral delivery of phagein vivo. Finally we combine these technologies and show that bacterial gene expression in the mammalian gut can be precisely modifiedin situwith a single oral dose.
UNCURL-App: Interactive database-driven analysis of scRNA-Seq data
Authors: Zhang Yue , Mao Shunfu , Mukherjee Sumit , Kannan Sreeram , Seelig Georg
Published: April 2020

Motivation

Analysis of single cell RNA sequencing (scRNA-seq) datasets is a complex and time-consuming process, requiring both biological knowledge and technical skill. With the rapid growth in scRNA-seq datasets, there is a need to simplify and systematize this process.

Results

We introduce UNCURL-App, an online GUI-based interactive tool which integrates the scRNA-seq analysis pipeline with prior knowledge. UNCURL-App introduces two key innovations: First, cell type databases are integrated directly with the rest of the analysis process, allowing the user to identify potential cell types or pathways directly from the data. Second, tools for interactive re-analysis allow the user to create, merge, or delete clusters. In addition, UNCURL-App integrates multiple stages of the data analysis pipeline into a single interface, including dimensionality reduction, clustering, differential expression, and cell type identification.

Availability

The web tool is available athttps://uncurl.cs.washington.edu/. Source code is available athttps://github.com/yjzhang/uncurl_app

Contact

gseelig@uw.edu
Structure-based design of hepatitis C virus E2 glycoprotein improves serum binding and cross-neutralization
Authors: Pierce Brian G. , Keck Zhen-Yong , Wang Ruixue , Lau Patrick , Garagusi Kyle , Elkholy Khadija , Toth Eric A. , Urbanowicz Richard A. , Guest Johnathan D. , Agnihotri Pragati , Kerzic Melissa C. , Marin Alexander , Andrianov Alexander K. , Ball Jonathan K. , Mariuzza Roy A. , Fuerst Thomas R. , Foung Steven K.H.
Published: April 2020

An effective vaccine for hepatitis C virus (HCV) is a major unmet need, and it requires an antigen that elicits immune responses to key conserved epitopes. Based on structures of antibodies targeting HCV envelope glycoprotein E2, we designed immunogens to modulate the structure and dynamics of E2 and favor induction of bNAbs in the context of a vaccine. These designs include a point mutation in a key conserved antigenic site to stabilize its conformation, as well as redesigns of an immunogenic region to add a new N-glycosylation site and mask it from antibody binding. Designs were experimentally characterized for binding to a panel of human monoclonal antibodies (HMAbs) and the coreceptor CD81 to confirm preservation of epitope structure and preferred antigenicity profile. Selected E2 designs were tested for immunogenicity in mice, with and without hypervariable region 1, which is an immunogenic region associated with viral escape. One of these designs showed improvement in polyclonal immune serum binding to HCV pseudoparticles and neutralization of isolates associated with antibody resistance. These results indicate that antigen optimization through structure-based design of the envelope glycoproteins is a promising route to an effective vaccine for HCV.
Neuropsychiatric copy number variants exert shared effects on human brain structure
Authors: Modenato Claudia , Kumar Kuldeep , Moreau Clara , Martin-Brevet Sandra , Huguet Guillaume , Schramm Catherine , Martineau Jean-Louis , Martin Charles-Olivier , Younis Nadine , Tamer Petra , Douard Elise , Thébault-Dagher Fanny , Côté V. , Charlebois A.R. , Deguire F. , Maillard Anne M. , Rodriguez-Herreros Borja , Pain Aurèlie , Richetin Sonia ,   16p11.2 European Consortium,   Simons Variation in Individuals Project (VIP) Consortium, Kushan Leila , Melie-Garcia Lester , Silva Ana I. , van den Bree Marianne B.M. , Linden David E.J. , Owen Michael J. , Hall Jeremy , Lippé Sarah , Chakravarty Mallar , Bzdok Danilo , Bearden Carrie E. , Draganski Bogdan , Jacquemont Sébastien
Published: April 2020

Background

Copy Number Variants (CNVs) associated with autism and schizophrenia have large effects on brain anatomy. Yet, neuroimaging studies have been conducted one mutation at a time. We hypothesize that neuropsychiatric CNVs may exert general effects on brain morphometry because they confer risk for overlapping psychiatric conditions.

Methods

We analyzed T1-weighted MRIs and characterized shared patterns on brain anatomy across 8 neuropsychiatric CNVs. Clinically ascertained samples included 1q21.1 (n=48), 16p11.2 (n=156), or 22q11.2 (n=96) and 331 non-carriers. Non-clinically ascertained samples from the UK Biobank included 1q21.1 (n=19), 16p11.2 (n=8), 22q11.2 (n=9), 15q11.2 (n=148) and 965 non-carriers. Canonical correlation analysis (CCA) and univariate models were used to interrogate brain morphometry changes across 8 CNVs.

Results

Eight CNVs affect regional brain volumes along two main gene-morphometry dimensions identified by CCA. While fronto-temporal regions contributed to dimension 1, dimension 2 was driven by subcortical, parietal and occipital regions. Consistently, voxel-wise whole-brain analyses identified the same regions involved in patterns of alteration present across the 4 deletions and duplications. These neuroanatomical patterns are similar to those observed in cross-psychiatric disorder meta-analyses. Deletions and duplications at all 4 loci show mirror effects at either the global and/or the regional level.

Conclusion

Neuropsychiatric CNVs share neuroanatomical signatures characterized by a parsimonious set of brain dimensions. The latter may underlie the risk conferred by CNVs for a similar spectrum of neuropsychiatric conditions.
Analysis of the COVID-19 epidemic in french overseas department Mayotte based on a modified deterministic and stochastic SEIR model
Authors: Manou-Abi Solym Mawaki , Balicchi Julien
Published: April 2020

In order to anticipate a future trends in the development of the novel coronavirus COVID-19 epidemic started early at march 13, in the french overseas department Mayotte, we consider in this paper a modified deterministic and stochastic epidemic model. The model divides the total population into several possible states or compartment: susceptible (S), exposed (E) infected and being under an incubation period, infected (I) being infectious, simple or mild removed RM, severe removed (including hospitalized) RS and death cases (D). The adding of the two new compartment RM and RS are driven by data which together replace the original R compartment in the classical SEIR model.

We first fit the constant transmission rate parameter to the epidemic data in Mayotte during an early exponential growth phase using an algorithm with a package of the software R and based on a Maximum Likewood estimator. This allows us to predict the epidemic without any control in order to understand how the control measure and public policies designed are having the desired impact of controlling the epidemic. To do this, we introduce a temporally varying decreasing transmission rate parameter with a control or quarantine parameter q. Then we pointed out some values of q to maintain control which is critical in Mayotte given the fragility of its health infrastructure and the significant fraction of the population without access to water.
Areas of global importance for terrestrial biodiversity, carbon, and water
Authors: Jung Martin , Arnell Andy , de Lamo Xavier , García-Rangel Shaenandhoa , Lewis Matthew , Mark Jennifer , Merow Cory , Miles Lera , Ondo Ian , Pironon Samuel , Ravilious Corinna , Rivers Malin , Schepashenko Dmitry , Tallowin Oliver , van Soesbergen Arnout , Govaerts Rafaël , Boyle Bradley L. , Enquist Brian J. , Feng Xiao , Gallagher Rachael V. , Maitner Brian , Meiri Shai , Mulligan Mark , Ofer Gali , Hanson Jeffrey O. , Jetz Walter , Di Marco Moreno , McGowan Jennifer , Rinnan D. Scott , Sachs Jeffrey D. , Lesiv Myroslava , Adams Vanessa , Andrew Samuel C. , Burger Joseph R. , Hannah Lee , Marquet Pablo A. , McCarthy James K. , Morueta-Holme Naia , Newman Erica A. , Park Daniel S. , Roehrdanz Patrick R. , Svenning Jens-Christian , Violle Cyrille , Wieringa Jan J. , Wynne Graham , Fritz Steffen , Strassburg Bernardo B.N. , Obersteiner Michael , Kapos Valerie , Burgess Neil , Schmidt-Traub Guido , Visconti Piero
Published: April 2020

Summary paragraph

To meet the ambitious objectives of biodiversity and climate conventions, countries and the international community require clarity on how these objectives can be operationalized spatially, and multiple targets be pursued concurrently1. To support governments and political conventions, spatial guidance is needed to identify which areas should be managed for conservation to generate the greatest synergies between biodiversity and nature’s contribution to people (NCP). Here we present results from a joint optimization that maximizes improvements in species conservation status, carbon retention and water provisioning and rank terrestrial conservation priorities globally. We found that, selecting the top-ranked 30% (respectively 50%) of areas would conserve 62.4% (86.8%) of the estimated total carbon stock and 67.8% (90.7%) of all clean water provisioning, in addition to improving the conservation status for 69.7% (83.8%) of all species considered. If priority was given to biodiversity only, managing 30% of optimally located land area for conservation may be sufficient to improve the conservation status of 86.3% of plant and vertebrate species on Earth. Our results provide a global baseline on where land could be managed for conservation. We discuss how such a spatial prioritisation framework can support the implementation of the biodiversity and climate conventions.
BRD4 Interacts with GATA4 to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes
Authors: Padmanabhan Arun , Alexanian Michael , Linares-Saldana Ricardo , González-Terán Bárbara , Andreoletti Gaia , Huang Yu , Connolly Andrew J. , Kim Wonho , Hsu Austin , Duan Qiming , Winchester Sarah A. B. , Haldar Saptarsi M. , Jain Rajan , Srivastava Deepak
Published: April 2020

Gene regulatory networks control tissue plasticity during basal homeostasis and disease in a cell-type specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how tissue-specificity of their function is achieved are poorly understood. BRD4, a member of the BET (Bromo- and Extra-Terminal domain) family of ubiquitously expressed acetyl-lysine reader proteins, plays a pivotal role as a coactivator of enhancer signaling across diverse tissue types in both health and disease, and has been implicated as a pharmacologic target in heart failure. However, the cell-specific role of BRD4 in adult cardiomyocytes remains unknown. Here, we show that cardiomyocyte-specific deletion of BRD4 in adult mice leads to acute deterioration of cardiac contractile function with mutant animals demonstrating a transcriptomic signature enriched for decreased expression of genes critical for mitochondrial energy production. Genome-wide occupancy data show that BRD4 enriches at many downregulated genes and preferentially co-localizes with GATA4, a lineage determining cardiac transcription factor not previously implicated in regulation of adult cardiac metabolism. Co-immunoprecipitation assays demonstrate that BRD4 and GATA4 form a complex in a bromodomain-independent manner, revealing a new interaction partner for BRD4 that has functional consequences for target transactivation and may allow for locus and tissue specificity. These results highlight a novel role for a BRD4-GATA4 module in cooperative regulation of a cardiomyocyte specific gene program governing bioenergetic homeostasis in the adult heart.
Modelling the spatial-temporal distributions and associated determining factors of a keystone pelagic fish
Authors: Andrews Samantha , Leroux Shawn J. , Fortin Marie-Josée
Published: April 2020

Mobile pelagic species habitat is structured around dynamic oceanographic and ecological processes which operate and interact horizontally and vertically throughout the water column and change over time. However, pelagic species movements and distributions are often poorly understood. We use the Maxent species distribution model to assess how changes in the relative importance of modelled oceanographic (e.g., temperature) and climatic variables (e.g., the North Atlantic Oscillation) over 17-years affect the monthly average horizontal and vertical distribution of a keystone pelagic forage species, Atlantic Canadian capelin (Mallotus villosus). We show the range and distribution of capelin occurrence probabilities vary across horizontal and vertical axes over time, with binary presence/absence predictions indicating capelin occupy between 0.72% (April) and 3.45% (November) of the total modelled space. Furthermore, our analysis reveals that the importance of modelled oceanographic variables, such as temperature, vary between months (44% permutation importance in August to 2% in May). By capturing the spatial dynamics of capelin over horizontal, vertical, and temporal axes, our analysis builds on work that improves our understanding and predictive modelling ability of pelagic species distributions under current and future conditions for pro-active ecosystem-based management.
CRISPR/Cas9-based inactivation of human papillomavirus oncogenes E6 and E7 induces senescence in cervical cancer cells
Authors: Inturi Raviteja , Jemth Per
Published: April 2020

Human papillomaviruses (HPVs) such as HPV16 and HPV18 can cause cancers of the cervix, vagina, vulva, penis, anus and oropharynx. Continuous expression of the HPV viral oncoproteins E6 and E7 are essential for transformation and maintenance of cancer cells. Therefore, therapeutic targeting of E6 and E7 genes can potentially be used to treat HPV-related cancers. Previous CRISPR/Cas9 studies on inactivation of E6 and E7 genes confirmed cell cycle arrest and apoptosis. Here we report that CRISPR/Cas9-based knockout of E6 and E7 can also trigger cellular senescence in HPV18 immortalized HeLa cells. Specifically, HeLa cells in which E6 and E7 were inactivated exhibited characteristic senescence markers like enlarged cell and nucleus surface area, increased β-galactosidase expression, and loss of lamin B1 with detection of cytoplasmic chromatin fragments. Furthermore, the knockout of HPV18 E6 and E7 proteins resulted in upregulation of p53/p21 and pRb/p21 levels in senescent cells. These senescent cells were devoid of characteristic apoptotic markers and re-introduction of codon-modified HPV18 E6 decreased p53 levels. Taken together, our study demonstrates that cellular senescence is as an alternative outcome of HPV oncogene inactivation by the CRISPR/Cas9 methodology.
Review of histopathologic findings of endometrial biopsy done at a tertiary referral hospital in urban Ethiopia
Authors: Tolu Lemi B , Kabtamu Solomon , Abedella Mustefa , Feyissa Garumma Tolu , Senbeto Elias
Published: April 2020

Background

An endometrial sampling procedure is a gold standard for the diagnostic evaluation of women with abnormal uterine bleeding (AUB) with primary aim to identify the cause, especially to determine whether carcinoma or premalignant lesions are present. The objective of the study is therefore to review endometrial biopsy specimen histopathological findings and associated factors at a tertiary referral hospital in urban Ethiopia.

Methodology

This is a two years retrospective analysis of cases of patients for whom endometrial biopsy was taken at a territory referral hospital in urban Ethiopia. Odd’s ratios, 95% confidence interval and p-value set at 0.05 were used to determine the statistical significance of the associations.

Results

A total of 277 patient records were analyzed and mean and the median age of the study patients were 41.89 and 40.00 years respectively. The commonest histopathologic finding was endometrial polyp 66 (23.83%), followed by proliferative endometrium 47 (16.97%) and secretory endometrium 25(9.03%). Endometrial hyperplasia, endometrial malignancy, and pregnancy complications were reported in 9 (3.25%), 13 (4.69%), and 25 (9.03%) of cases respectively. Endometritis was detected in 20(7.22%), while Tuberculous (TB) endometritis was reported in 3(1.08%) of cases only. Inconclusive and inadequate sample was reported in 30 (10.83%) and 34 (12.27%) of cases respectively. Endometrial polyp was associated with 40-49 years of age (OR= 12.56, 95% CI: 2.58-61.23).

Conclusions

Endometrial polyp was the commonest histopathologic finding followed by proliferative and secretory endometrium respectively. Rate of sample inadequacy is higher than most of the study reports which mandates to improve sampling technique to increase sample adequacy and routine transvaginal ultrasound for endometrial evaluation especially for those postmenopausal women to decide the necessity of endometrial sampling.
The relict ecosystem ofGymnosporia senegalensis(Lam.) Loes. in an agricultural plastic sea: past, present and future scenarios
Authors: Mendoza-Fernández Antonio J. , Martínez-Hernández Fabián , Salmerón-Sánchez Esteban , Pérez-García Francisco J. , Teruel Blas , Merlo Encarna , Mota Juan
Published: April 2020

Gymnosporia senegalensisis a shrub belonging to theCelastraceaefamily, which is native to tropical savannahs. Its only European populations are distributed discontinuously along the south-eastern coast of the Iberian Peninsula, forming plant communities with great ecological value, unique in Europe. As it is an endangered species that makes up plant communities with great palaeoecological significance, the development of species distribution models is of major interest under different climatic scenarios, past, present and future, based on the fact that the climate could play a relevant role in the distribution of this species as well as in the conformation of the communities in which it is integrated. Palaeoecological models were generated for the Maximum Interglacial, Last Maximum Glacial and Middle Holocene periods. The results obtained showed that the widest distribution of this species, and the maximum suitability of its habitat, occurred during the Last Glacial Maximum, when the temperatures of the peninsular southeast were not as contrasting as those of the rest of the European continent and were favored by higher rainfall. Under these conditions, large territories could act as shelters during the glacial period, a hypothesis reflected in the model’s results for this period, which exhibit a further expansion ofG. senegalensis’ ecological niche. The future projection of models in around 2070, for four Representative Concentration Pathway (RCP) according to the fifth report of the Intergovernmental Panel on Climate Change IPCC, showed that the most favorable areas for this species would be Campo de Dalias (southern portion of Almeria province) as it presents the bioclimatic characteristics of greater adjustment toG. senegalensis’ ecological niche model. Currently, these areas are almost totally destroyed and heavily altered by intensive agriculture under plastic, also causing a severe fragmentation of the habitat, which implies a prospective extinction scenario in the near future.