bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opportunity or catastrophe? Effect of sea salt on host-parasite survival and reproduction
Authors: Yu Ao , Vannatta J. Trevor , Gutierrez Stephanie O. , Minchella Dennis J. 
Published: June 2021

AbstractSeawater intrusion caused by anthropogenic climate change may affect freshwater species and their parasites. While brackish water certainly impacts freshwater systems globally, its impact on disease transmission is largely unknown. This study examined the effect of artificial seawater on host-parasite interactions using a freshwater snail host, Biomphalaria alexandrina, and the human trematode parasite Schistosoma mansoni. Four components were analyzed to evaluate the impact of increasing salinity on disease transmission: snail survival, snail reproduction, infection prevalence, and the survival of the parasite infective stage (cercariae). We found a decrease in snail survival, snail egg mass production, and snail infection prevalence as salinity increases. However, cercarial survival peaked at an intermediate salinity value. Our results suggest that seawater intrusion into freshwaters has the potential to decrease schistosome transmission to humans.Author SummaryClimate change will have numerous impacts on many systems, including host-parasite systems. One mechanism by which climate change with impact host-parasite interactions is by rising sea levels flooding coastal regions, increasing salinity in many freshwaters. Host-parasite interactions are a key component of freshwater ecosystems, but the effects of sea water intrusion on host-parasite dynamics are largely unknown. In this study, we quantify the effects of sea salt concentration on the model host-parasite system, Biomphalaria alexandrina and Schistosoma mansoni. We demonstrate a significant, negative relationship between sea salt concentration and host-parasite survival and reproduction. The increase in freshwater salinity associated with sea level rise has the potential to decrease parasite transmission and disease burden in humans and wildlife.Abstract Figure
PHARP: A pig haplotype reference panel for genotype imputation
Authors: Wang Zhen , Zhang Zhenyang , Chen Zitao , Sun Jiabao , Cao Caiyun , Wu Fen , Xu Zhong , Zhao Wei , Sun Hao , Guo Longyu , Zhang Zhe , Wang Qishan , Pan Yuchun 
Published: June 2021

ABSTRACTPigs not only function as a major meat source worldwide but also are commonly used as an animal model for studying human complex traits. A large haplotype reference panel has been used to facilitate efficient phasing and imputation of relatively sparse genome-wide microarray chips and low-coverage sequencing data. Using the imputed genotypes in the downstream analysis, such as GWASs, TWASs, eQTL mapping and genomic prediction (GS), is beneficial for obtaining novel findings. However, currently, there is still a lack of publicly available and high-quality pig reference panels with large sample sizes and high diversity, which greatly limits the application of genotype imputation in pigs. In response, we built the pig Haplotype Reference Panel (PHARP) database. PHARP provides a reference panel of 2,012 pig haplotypes at 34 million SNPs constructed using whole-genome sequence data from more than 49 studies of 71 pig breeds. It also provides Web-based analytical tools that allow researchers to carry out phasing and imputation consistently and efficiently. PHARP is freely accessible at http://alphaindex.zju.edu.cn/PHARP/index.php. We demonstrate its applicability for pig commercial 50K SNP arrays, by accurately imputing 2.6 billion genotypes at a concordance rate value of 0.971 in 81 Large White pigs (~ 17× sequencing coverage). We also applied our reference panel to impute the low-density SNP chip into the high-density data for three GWASs and found novel significantly associated SNPs that might be casual variants.
Investigating the concept of accessibility for predicting novel RNA-RNA interactions
Authors: Reißer Sabine , Meyer Irmtraud M 
Published: June 2021

ABSTRACTState-of-the-art methods for predicting novel trans RNA-RNA interactions use the so-called accessibility as key concept. It estimates whether a region in a given RNA sequence is accessible for forming trans interactions, using a thermodynamic model which quantifies its secondary structure features. RNA-RNA interactions are then predicted by finding the minimum free energy base-pairing between the two transcripts, taking into account the accessibility as energy penalty.We investigated the underlying assumptions of this approach using the two methods RNAplex and IntaRNA on two datasets, containing sRNA-mRNA and snoRNA-rRNA interactions, respectively.We find that (1) known trans RNA-RNA interactions frequently overlap regions containing RNA structure features, (2) the estimated accessibility reflects sRNA structures fairly well, but often disagrees with structure annotations of longer transcripts, (3) the prediction performance of RNA-RNA interaction prediction methods is independent of the quality of the estimated accessibility profiles, and (4) one important overall effect of accessibility profiles is to prevent the thermodynamic model from predicting too long interactions.Based on our findings, we conclude that the accessibility concept to the minimum free energy approach to predicting novel RNA-RNA interactions has conceptual limitations and discuss potential ways of improving the field in the future.
A large chromosomal inversion shapes gene expression in seaweed flies (Coelopa frigida)
Authors: Berdan Emma L. , Mérot Claire , Pavia Henrik , Johannesson Kerstin , Wellenreuther Maren , Butlin Roger K. 
Published: June 2021

ABSTRACTInversions often underlie complex adaptive traits, but the genic targets inside them are largely unknown. Gene expression profiling provides a powerful way to link inversions with their phenotypic consequences. We examined the effects of the Cf-Inv(1) inversion in the seaweed fly Coelopa frigida on gene expression variation across sexes and life stages. Our analyses revealed that Cf-Inv(1) shapes global expression patterns but the extent of this effect is variable with much stronger effects in adults than larvae. Furthermore, within adults, both common as well as sex specific patterns were found. The vast majority of these differentially expressed genes mapped to Cf-Inv(1). However, genes that were differentially expressed in a single context (i.e. in males, females or larvae) were more likely to be located outside of Cf-Inv(1). By combining our findings with genomic scans for environmentally associated SNPs, we were able to pinpoint candidate variants in the inversion that may underlie mechanistic pathways that determine phenotypes. Together the results in this study, combined with previous findings, support the notion that the polymorphic Cf-Inv(1) inversion in this species is a major factor shaping both coding and regulatory variation resulting in highly complex adaptive effects.
The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner
Authors: Hamelin David J. , Fournelle Dominique , Grenier Jean-Christophe , Schockaert Jana , Kovalchik Kevin , Kubiniok Peter , Mostefai Fatima , Duquette Jérôme D. , Saab Frederic , Sirois Isabelle , Smith Martin A. , Pattijn Sofie , Soudeyns Hugo , Decaluwe Hélène , Hussin Julie , Caron Etienne 
Published: June 2021

SUMMARYThe rapid, global dispersion of SARS-CoV-2 since its initial identification in December 2019 has led to the emergence of a diverse range of variants. The initial concerns regarding the virus were quickly compounded with concerns relating to the impact of its mutated forms on viral infectivity, pathogenicity and immunogenicity. To address the latter, we seek to understand how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic, before mass vaccination. We analyzed a total of 330,246 high quality SARS-CoV-2 genome assemblies sampled across 143 countries and all major continents. Strikingly, we found that specific mutational patterns in SARS-CoV-2 diversify T cell epitopes in an HLA supertype-dependent manner. In fact, we observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family. In addition, we show that this predicted global loss of epitopes is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7 supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic. Together, our study lays the foundation to help understand how SARS-CoV-2 mutants shape the repertoire of T cell targets and T cell immunity across human populations. The proposed theoretical framework has implications in viral evolution, disease severity, vaccine resistance and herd immunity.
Lack of p62 impairs glycogen aggregation and exacerbates pathology in a mouse model of myoclonic epilepsy of Lafora
Authors: Pellegrini Pasquale , Hervera Arnau , Varea Olga , Brewer M. Kathryn , López-Soldado Iliana , Guitart Anna , Aguilera Mònica , Prat Neus , del Río José Antonio , Guinovart Joan J. , Duran Jordi 
Published: June 2021

ABSTRACTBackgroundLafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates—the so-called Lafora Bodies (LBs)—in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glycogen and various associated proteins, including p62, an autophagy adaptor that participates in the aggregation and clearance of misfolded proteins.MethodsTo study the role of p62 in the formation of LBs and its participation in the pathology of LD, we generated a mouse model of the disease (malinKO) lacking p62.ResultsDeletion of p62 prevented LB accumulation in skeletal muscle and cardiac tissue. In the brain, the absence of p62 altered LB morphology and increased susceptibility to epilepsy.ConclusionsThese results demonstrate that p62 participates in the formation of LBs and suggest that the sequestration of abnormal glycogen into LBs is a protective mechanism through which to reduce the deleterious consequences of its accumulation in the brain.
ProFuMCell and ProModb: web services for analyzing interaction-based functionally localized protein modules in a cell
Authors: Das Barnali , Mitra Pralay 
Published: June 2021

AbstractThe modular organization of a cell which can be determined by its interaction network allows us to understand a mesh of cooperation among the functional modules. Therefore, cellular level identification of functional modules aids in understanding the functional and structural characteristics of the biological network of a cell and also assists in determining or comprehending the evolutionary signal. We develop ProFuM-Cell that performs real-time web scraping for generating clusters of the cellular level functional units of an organism. ProFuMCell constructs the Protein Locality Graphs and clusters the cellular level functional units of an organism by utilizing experimentally verified data from various online sources. Also, we develop ProModb, a database service that houses precomputed whole-cell protein-protein interaction network-based functional modules of an organism using ProFuMCell. Our web service is entirely synchronized with the KEGG pathway database and allows users to generate spatially localized protein modules for any organism belonging to the KEGG genome using its real-time web scraping characteristics. Hence, the server will host as many organisms as is maintained by the KEGG database. Our web services provide the users a comprehensive and integrated tool for an efficient browsing and extraction of the spatial locality-based protein locality graph and the functional modules constructed by gathering experimental data from several interaction databases and pathway maps. We believe that our web services will be beneficial in pharmacological research, where a novel research domain called modular pharmacology has initiated the study on the diagnosis, prevention, and treatment of deadly diseases using functional modules.Graphical TOC Entry
Single-Cell Sequencing Reveals Lineage-Specific Dynamic Genetic Regulation of Gene Expression During Human Cardiomyocyte Differentiation
Authors: Elorbany Reem , Popp Joshua M , Rhodes Katherine , Strober Benjamin J , Barr Kenneth , Qi Guanghao , Gilad Yoav , Battle Alexis 
Published: June 2021

AbstractDynamic and temporally specific gene regulatory changes may underlie unexplained genetic associations with complex disease. During a dynamic process such as cellular differentiation, the overall cell type composition of a tissue (or an in vitro culture) and the gene regulatory profile of each cell can both experience significant changes over time. To identify these dynamic effects in high resolution, we collected single-cell RNA-sequencing data over a differentiation time course from induced pluripotent stem cells to cardiomyocytes, sampled at 7 unique time points in 19 human cell lines. We employed a flexible approach to map dynamic eQTLs whose effects vary significantly over the course of bifurcating differentiation trajectories, including many whose effects are specific to one of these two lineages. Our study design allowed us to distinguish true dynamic eQTLs affecting a specific cell lineage from expression changes driven by potentially non-genetic differences between cell lines such as cell composition. Additionally, we used the cell type profiles learned from single-cell data to deconvolve and re-analyze data from matched bulk RNA-seq samples. Using this approach, we were able to identify a large number of novel dynamic eQTLs in single cell data while also attributing dynamic effects in bulk to a particular lineage. Overall, we found that using single cell data to uncover dynamic eQTLs can provide new insight into the gene regulatory changes that occur among heterogeneous cell types during cardiomyocyte differentiation.
Deciphering biological evolution exploiting the topology of Protein Locality Graph
Authors: Das Barnali , Mitra Pralay 
Published: June 2021

AbstractThe conventional sequence comparison-based evolutionary studies ignore other evolutionary constraints like interaction among proteins, functions of proteins and genes etc. A lot of speculations exist in literature regarding the presence of species divergence at the level of the Protein Interaction Networks. Additionally, it has been conjectured that the intra-module connections stay conserved whereas the inter-module connections change during evolution. The most important components of the biological networks are the functional modules which are more conserved among the evolutionary closer species. Here, we demonstrate an alternative method to decipher biological evolution by exploiting the topology of a spatially localized Protein Interaction Network called Protein Locality Graph (PLG). Our lossless graph compression from PLG to a power graph called Protein Cluster Interaction Network (PCIN) results in a 90% size reduction and aids in improving computational time. Further, we exploit the topology of PCIN and demonstrate our capability of deriving the correct species tree by focusing on the cross-talk between the protein modules exclusively. Our results provide new evidence that traces of evolution are not only present at the level of the Protein-Protein Interactions, but are also very much present at the level of the inter-module interactions.
CNS antigen-specific control of early B-lineage development in the meninges
Authors: Wang Yan , Chen Dianyu , Xu Di , Huang Chao , He Danyang , Xu Heping 
Published: June 2021

AbstractThe random V(D)J recombination of immunoglobulins (Ig) loci often creates autoreactive B cell progenitors expressing self-recognized B-cell receptors (BCRs)1, which are eliminated or inactivated through an autoantigen-dependent central tolerance checkpoint to prevent autoimmune reactions2,3, a process thought to be restricted to the bone marrow (BM) in the adult mammals4. Here we report that early developing B cells are also present in the meninges of mice at all ages. Single cell RNA-sequencing (scRNA-seq) analysis revealed a consecutive trajectory of meningeal developing B cells in mice and non-human primates (NHPs). Parabiosis together with lineage tracing of hematopoietic stem cells (HSCs) showed that meningeal developing B cells are continuously replenished from the HSC-derived progenitors via a circulationindependent route. Importantly, autoreactive immature B cells which recognize myelin oligodendrocyte glycoprotein (MOG)5, a central nervous system (CNS)-specific antigen, are eliminated from the meninges but not BM. Furthermore, genetic deletion of MOG restored the self-reactive B cells in the meninges. Thus, we propose that meninges function as a unique reservoir for B cell development, allowing in situ negative selection of CNS-antigen-autoreactive B cells to ensure a local non-self-reactive immune repertoire.
The impact of mutational processes on structural genomic plasticity in cancer cells
Authors: Funnell Tyler , O’Flanagan Ciara H , Williams Marc J , McPherson Andrew , McKinney Steven , Kabeer Farhia , Lee Hakwoo , Masud Tehmina , Eirew Peter , Yap Damian , Zhang Allen W , Lim Jamie L P , Wang Beixi , Brimhall Jazmine , Biele Justina , Ting Jerome , Liu Yi Fei , Beatty Sean , Lai Daniel , Pham Jenifer , Grewal Diljot , Abrams Douglas , Havasov Eliyahu , Leung Samantha , Bojilova Viktoria , Moore Richard A , Rusk Nicole , Uhlitz Florian , Ceglia Nicholas , Weiner Adam C , Douglas J Maxwell , Zamarin Dmitriy , Weigelt Britta , Kim Sarah H , Da Cruz Paula Arnaud , Reis-Filho Jorge S. , Li Yangguang , Xu Hong , de Algara Teresa Ruiz , Lee So Ra , Llanos Viviana Cerda ,   IMAXT consortium, Shah Sohrab P. , Aparicio Samuel 
Published: June 2021

ABSTRACTStructural genome alterations are determinants of cancer ontogeny and therapeutic response. While bulk genome sequencing has enabled delineation of structural variation (SV) mutational processes which generate patterns of DNA damage, we have little understanding of how these processes lead to cell-to-cell variations which underlie selection and rates of accrual of different genomic lesions. We analysed 309 high grade serous ovarian and triple negative breast cancer genomes to determine their mutational processes, selecting 22 from which we sequenced >22,000 single cell whole genomes across a spectrum of mutational processes. We show that distinct patterns of cell-to-cell variation in aneuploidy, copy number alteration (CNA) and segment length occur in homologous recombination deficiency (HRD) and fold-back inversion (FBI) phenotypes. Widespread aneuploidy through induction of HRD throughBRCA1andBRCA2inactivation was mirrored by continuous whole genome duplication in HRD tumours, contrasted with early ploidy fixation in FBI. FBI tumours exhibited copy number distributions skewed towards gains, widespread clone-specific variation in amplitude of high-level amplifications, often impacting oncogenes, and break-point variability consistent with progressive genomic diversification, which we termed serriform structural variation (SSV). SSVs were consistent with a CNA-based molecular clock reflecting a continual and distributed process across clones within tumours. These observations reveal previously obscured genome plasticity and evolutionary properties with implications for cancer evolution, therapeutic targeting and response.
Efficacy of heat-killed and formalin-killed vaccines againstTilapia tilapinevirusin juvenile Nile tilapia (Oreochromis niloticus)
Authors: Mai Thao Thu , Kayansamruaj Pattanapon , Taengphu Suwimon , Senapin Saengchan , Costa Janina Z. , del-Pozo Jorge , Thompson Kim D. , Rodkhum Channarong , Dong Ha Thanh 
Published: June 2021

AbstractTilapia tilapinevirus(also known as tilapia lake virus, TiLV) is considered to be a new threat to the global tilapia industry. The objective of this study was to develop simple cell culture-based heat-killed (HKV) and formalin-killed (FKV) vaccines for the prevention of disease caused by TiLV. The fish were immunized with 100 µL of either HKV or FKV by intraperitoneal injection with each vaccine containing 1.8 × 106TCID50inactivated virus. A booster vaccination was carried out at 21-day post vaccination (dpv) using the same protocol. The fish were then challenged with a lethal dose of TiLV at 28 dpv. The expression of five immune genes (IgM, IgD, IgT, CD4andCD8) in the head kidney and spleen of experimental fish was assessed at 14 and 21 dpv and again after the booster vaccination at 28 dpv. TiLV-specific IgM responses were measured by ELISA at the same time points. The results showed that both vaccines conferred significant protection, with relative percentage survival (RPS) of 71.3% and 79.6% for HKV and FKV, respectively. Significant up-regulation ofIgMandIgTwas observed in the head kidney of fish vaccinated with HKV at 21 dpv, whileIgM, IgDandCD4expression increased in the head kidney of fish receiving FKV at the same time point. After booster vaccination,IgTand CD8transcripts were significantly increased in the spleen of fish vaccinated with the HKV, but not with FKV. Both vaccines induced a specific IgM response in both serum and mucus. In summary, this study showed that both HKV and FKV are promising injectable vaccines for the prevention of disease caused by TiLV in Nile tilapia.
TRPC3 and NALCN channels drive pacemaking in substantia nigra dopaminergic neurons
Authors: Um Ki Bum , Hahn Suyun , Kim So Woon , Lee Yoon Je , Birnbaumer Lutz , Kim Hyun Jin , Park Myoung Kyu 
Published: June 2021

AbstractMidbrain dopamine (DA) neurons are slow pacemakers that maintain extracellular DA levels. During the interspike intervals, subthreshold slow depolarization underlies autonomous pacemaking and determines its rate. However, the ion channels that determine slow depolarization are unknown. Here we show that TRPC3 and NALCN channels together form sustained inward currents responsible for the slow depolarization of nigral DA neurons. Specific TRPC3 channel blockade completely blocked DA neuron pacemaking, but the pacemaking activity in TRPC3 knock-out (KO) mice was perfectly normal, suggesting the presence of compensating ion channels. Blocking NALCN channels abolished pacemaking in both TRPC3 KO and wild-type mice. The NALCN current and mRNA and protein expression are increased in TRPC3 KO mice, indicating that NALCN compensates for TRPC3 currents. In normal conditions, TRPC3 and NALCN contribute equally to slow depolarization. Therefore, we conclude that TRPC3 and NALCN are two major leak channels that drive robust pacemaking in nigral DA neurons.