bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using computational simulations to quantify genetic load and predict extinction risk
Authors: Kyriazis Christopher C. , Robinson Jacqueline A. , Lohmueller Kirk E. 
Published: August 2022

AbstractSmall and isolated wildlife populations face numerous threats to extinction, among which is the deterioration of fitness due to an accumulation of deleterious genetic variation. Genomic tools are increasingly used to quantify the impacts of deleterious variation in small populations; however, these approaches remain limited by an inability to accurately predict the selective and dominance effects of individual mutations. Computational simulations of deleterious genetic variation offer an alternative and complementary tool that can help overcome these limitations, though such approaches have yet to be widely employed. In this Perspective, we aim to encourage conservation genomics researchers to adopt greater use of computational simulations to aid in quantifying and predicting the threat that deleterious genetic variation poses to extinction. We first provide an overview of the components of a simulation of deleterious genetic variation, describing the key parameters involved in such models. Next, we clarify several misconceptions about an essential simulation parameter, the distribution of fitness effects (DFE) of new mutations, and review recent debates over what the most appropriate DFE parameters are. We conclude by comparing modern simulation tools to those that have long been employed in population viability analysis, weighing the pros and cons of a ‘genomics-informed’ simulation approach, and discussing key areas for future research. Our aim is that this Perspective will facilitate broader use of computational simulations in conservation genomics, enabling a deeper understanding of the threat that deleterious genetic variation poses to biodiversity.
Identification, characterization of Apyrase (APY) gene family in rice (Oryza sativa) and analysis of the expression pattern under various stress conditions
Authors: Chowdhury Aniqua Tasnim , Hasan Md. Nazmul , Bhuiyan Fahmid H , Islam Md. Qamrul , Nayon Md. Rakib Wazed , Rahaman Md. Mashiur , Hoque Hammadul , Jewel Nurnabi Azad , Ashrafuzzaman Md , Prodhan Shamsul H. 
Published: August 2022

AbstractApyrase (APY) is a nucleoside triphosphate (NTP) diphosphohydrolase (NTPDase) which is a member of the superfamily of guanosine diphosphatase 1 (GDA1) - cluster of differentiation 39 (CD39) nucleoside phosphatase. Under various circumstances like stress, cell growth, the extracellular adenosine triphosphate (eATP) level increases, causing a detrimental influence on cells such as cell growth retardation, ROS production, NO burst, and apoptosis. Apyrase hydrolyses eATP accumulated in the extracellular membrane during stress, wounds, into adenosine diphosphate (ADP) and adenosine monophosphate (AMP) and regulates the stress- responsive pathway in plants. This study was designed for the identification, characterization, and for analysis ofAPYgene expression inOryza sativa. This investigation discovered nineAPYs in rice, including both endo- and ecto-apyrase. According to duplication event analysis, in the evolution ofOsAPYs, a significant role is performed by segmental duplication. Their role in stress control, hormonal responsiveness, and the development of cells is supported by the corresponding cis-elements present in their promoter regions. According to expression profiling by RNA-seq data, the genes were expressed in various tissues. Upon exposure to a variety of biotic as well as abiotic stimuli, including anoxia, drought, submergence, alkali, heat, dehydration, salt, and cold, they showed a differential expression pattern. The expression analysis from the RT-qPCR data also showed expression under various abiotic stress conditions, comprising cold, salinity, cadmium, drought, submergence, and especially heat stress. This finding will pave the way for futurein-vivoanalysis, unveil the molecular mechanisms ofAPYgenes in stress response, and contribute to the development of stress- tolerant rice varieties.
Genes encoding cytochrome P450 monooxygenases and glutathione S-transferases associated with herbicide resistance evolved before the origin of land plants
Authors: Casey Alexandra , Dolan Liam 
Published: August 2022

AbstractCytochrome P450 (CYP) monooxygenases and glutathione S-transferases (GST) are enzymes that catalyse chemical modifications of a range of organic compounds. Herbicide tolerance is associated with higher levels of CYP and GST gene expression in some herbicide-resistant weed populations compared to sensitive populations of the same species. By comparing the protein sequences of 9 representative species of the Archaeplastida – the lineage which includes red algae, glaucophyte algae, chlorophyte algae, and streptophytes – and generating phylogenetic trees, we identified the CYP and GST proteins that existed in the common ancestor of the Archaeplastida. All CYP clans and all but one land plant GST classes present in land plants evolved before the divergence of streptophyte algae and land plants from their last common ancestor. We also demonstrate that there are more genes encoding CYP and GST proteins in land plants than in algae. The larger numbers of genes among land plants largely results from gene duplications in CYP clans 71, 72, and 85 and in the GST Phi and Tau classes. Enzymes that either chemically alter herbicides or confer herbicide resistance belong to CYP clans 71 and 72 and the GST Phi and Tau classes. These results demonstrate that the clan and class diversity in extant plant CYP and GST proteins evolved in the Proterozoic before the divergence of land plants and streptophyte algae from a last common ancestor. Then, early in embryophyte evolution during the Palaeozoic, gene duplication in four of the twelve CYP clans, and in two of the fourteen GST classes, led to the large numbers of CYP and GST proteins found in extant land plants. It is among the genes of CYP clans 71 and 72 and GST classes Phi and Tau that alleles conferring herbicide resistance evolved in the last fifty years.
The Spike protein of SARS-coV2 19B (S) clade mirrors critical features of viral adaptation and coevolution
Authors: Hussein Bidour K. , Ibrahium Omnia M. , Alamin Marwa F. , Ahmed Lamees A.M , Abuswar Safa A.E , Abdelraheem Mohammed H. , Ibrahim Muntaser E. 
Published: August 2022

AbstractPathogens including viruses evolve in tandem with diversity in their animal and human hosts. For SARS-coV2, the focus is generally for understanding such coevolution on the virus spike protein since it demonstrates high mutation rates compared to other genome regions, particularly in the receptor-binding domain (RBD).Viral sequences of the SARS-coV2 19B (S) clade and variants of concern from different continents, were investigated, with a focus on the A.29 lineage which presented with different mutational patterns within the 19B (S) lineages in order to learn more about how SARS-coV2 may have evolved and adapted to widely diverse populations globally.Results indicated that SARS-coV2 went through evolutionary constrains and intense selective pressure, particularly in Africa. This was manifested in a departure from neutrality with excess nonsynonymous mutations and a negative Tajima D consistent with rapid expansion and directional selection as well as deletion and deletion-frameshifts in the N-terminal domain (NTD region) of the spike protein.In conclusion, viral transmission during epidemics through population of diverse genomic structure and marked complexity may be a significant factor for the virus to acquire distinct patterns of mutations within these populations in order to ensure its survival and fitness, hence in the emergence of novel variants and strains.ImportanceIn this study, we justify the fact that the virus’s evolution varies across continents, with each continent showing different amounts and patterns of mutations and deletions, which was manifested in the 19B (S) clade of SARS-coV2, particularly in areas with high population complexity, such as Africa, despite the low rate of sampling and data sharing. The findings show that SARS-coV2 was subject to evolutionary constraints and intense selective pressure. This study will contribute to the scanty amount of research on the SARS-coV2 coevolution and adaptation, in which the host variation is of great significance in understanding the intricacies of viral host coevolution.
Worldwide late-Quaternary population declines in extant megafauna are due to Homo sapiens rather than climate
Authors: Bergman Juraj , Pedersen Rasmus Ø. , Lundgren Erick J. , Lemoine Rhys T. , Monsarrat Sophie , Schierup Mikkel H. , Svenning Jens-Christian 
Published: August 2022

AbstractThe worldwide loss of large animal species over the past 100,000 years is evident from the fossil record, with climate and human impact as the most likely causes of megafauna extinctions. To help distinguish between these two scenarios, we analysed whole-genome sequence data of 142 species to infer their population size histories during the Quaternary. We modelled differences in population dynamics among species using ecological factors, paleoclimate and human presence as covariates. We report a significant population decline towards the present time in more than 90% of species, with larger megafauna experiencing the strongest decline. We find that population decline became ubiquitous approximately 100,000 years ago, with the majority of species experiencing their lowest population sizes during this period. We assessed the relative impact of climate fluctuations and human presence on megafauna dynamics and found that climate has limited explanatory power for late-Quaternary shifts in megafauna population sizes, which are largely explained by Homo sapiens arrival times. As a consequence of megafauna decline, total biomass and metabolic input provided by these species has drastically reduced to less than 25% compared to 100,000 years ago. These observations imply that the worldwide expansion of H. sapiens caused a major restructuring of ecosystems at global scale.
Spectral Representation of EEG Data using Learned Graphs with Application to Motor Imagery Decoding
Authors: Miri Maliheh , Abootalebi Vahid , Saeedi-Sourck Hamid , Van De Ville Dimitri , Behjat Hamid 
Published: August 2022

AbstractElectroencephalography (EEG) data entail a complex spatiotemporal structure that reflects ongoing organization of brain activity. Characterization of the spatial patterns is an indispensable step in numerous EEG processing pipelines within the setting of brain-computer interface systems as well as cognitive neuroscience. We present an approach for transforming EEG data into a spectral representation by using the harmonic basis of a graph structure that is learned from the data. The harmonic basis is obtained by integrating principles from graph learning and graph signal processing (GSP). First, we learn subject-specific graphs from each subject’s EEG data. Second, by eigendecomposition of the normalized Laplacian matrix of each subject’s graph, an orthonormal basis is obtained onto which each EEG map can be decomposed, providing a spectral representation of the data. We show that energy of the EEG maps is strongly associated with low frequency components of the learned basis, reflecting the smooth topography of EEG maps as expected. As a proof-of-concept for this alternative view of EEG data, we consider the task of decoding two-class motor imagery (MI) data. To this aim, the spectral representations are first mapped into a discriminative subspace for differentiating two-class data using a projection matrix obtained by the Fukunaga-Koontz transform (FKT), providing a minimal subspace from which features are extracted. An SVM classifier is then trained and tested on the resulting features to differentiate MI classes. The proposed method is evaluated on Dataset IVa of the BCI Competition III and its performance is compared to using features extracted from a subject-specific functional connectivity matrix and four state-of-the-art alternative methods. Experimental results indicate the superiority of the proposed method over alternative approaches, reflecting the added benefit of i) decomposing EEG data using data-driven, subject-specific harmonic bases, and ii) accounting for class-specific temporal variations in spectral profiles via the FKT. The proposed method and results underline the importance of integrating spatial and temporal characteristics of EEG signals in extracting features that can more powerfully differentiate MI classes.
rde-3 reduces piRNA-mediated silencing and abolishes inherited silencing in C. elegans
Authors: Priyadarshini Monika , AlHarbi Sarah , Frøkjær-Jensen Christian 
Published: August 2022

AbstractSmall RNA-mediated silencing of target genes can persist across generations and C. elegans is a well-established model for studying the molecular basis for epigenetic inheritance. We recently developed a piRNA-based inherited silencing assay that causes a high incidence of males by targeting him-5 and him-8. Acute gene silencing is determined in the presence of the piRNAi extra-chromosomal array and inherited silencing after loss of the piRNA trigger. This assay has the advantage of targeting endogenous genes that are easily scored in mutant backgrounds and obviates the need for mutant validation and genetic crosses, which can influence inherited silencing. Here we show an example of the assay by testing acute and inherited piRNA-mediated him-5 silencing in ribonucleotidyltransferase rde-3 (ne3370) mutant animals. In the absence of rde-3, acute silencing was reduced but still detectable, whereas inherited silencing was abolished.
High throughput analysis of vacuolar acidification
Authors: Zhang Chi , Balutowski Adam , Feng Yilin , Calderin Jorge D. , Fratti Rutilio A. 
Published: August 2022

AbstractEukaryotic cells are compartmentalized into membrane-bound organelles, allowing each organelle to maintain the specialized conditions needed for their specific functions. One of the features that change between organelles is luminal pH. In the endocytic and secretory pathways, luminal pH is controlled by isoforms and concentration of the vacuolar-type H+-ATPase (V-ATPase). In the endolysosomal pathway, copies of complete V-ATPase complexes accumulate as membranes mature from early endosomes to late endosomes and lysosomes. Thus, each compartment becomes more acidic as maturation proceeds. Lysosome acidification is essential for the breakdown of macromolecules delivered from endosomes as well as cargo from different autophagic pathways, and dysregulation of this process is linked to various diseases. Thus, it is important to understand the regulation of the V-ATPase. Here we describe a high-throughput method for screening inhibitors/activators of V-ATPase activity using Acridine Orange (AO) as a fluorescent reporter for acidified yeast vacuolar lysosomes. Through this method, the acidification of purified vacuoles can be measured in real-time in half-volume 96-well plates or a larger 384-well format. This not only reduces the cost of expensive low abundance reagents, but it drastically reduces the time needed to measure individual conditions in large volume cuvettes.
Quantitative reconstitution of yeast RNA processing bodies
Authors: Currie Simon L , Xing Wenmin , Muhlrad Denise , Decker Carolyn J , Parker Roy , Rosen Michael K 
Published: August 2022

AbstractMany biomolecular condensates appear to form through liquid-liquid phase separation (LLPS). Individual condensate components can often undergo LLPS in vitro, capturing some features of the native structures. However, natural condensates contain dozens of components with different concentrations, dynamics, and contributions to compartment formation. Most biochemical reconstitutions of condensates have not benefitted from quantitative knowledge of these cellular features nor attempted to capture natural complexity. Here, we build on prior quantitative cellular studies to reconstitute yeast RNA processing bodies (P bodies) from purified components. Individually, five of the seven highly-concentrated P-body proteins form homotypic condensates at cellular protein and salt concentrations, using both structured domains and intrinsically disordered regions. Combining the seven proteins together at their cellular concentrations with RNA, yields phase separated droplets with partition coefficients and dynamics of most proteins in reasonable agreement with cellular values. The dynamics of most proteins in the reconstitution are also comparable to cellular values. RNA delays the maturation of proteins within, and promotes reversibility of, P bodies. Our ability to quantitatively recapitulate the composition and dynamics of a condensate from its most concentrated components suggests that simple interactions between these components carry much of the information that defines the physical properties of the cellular structure.
Integrated single-cell functional and molecular profiling of extracellular vesicle secretion in metastatic breast cancer
Authors: Fathi Mohsen , Martinez-Paniagua Melisa , Rezvan Ali , Montalvo Melisa J. , Mohanty Vakul , Chen Ken , Mani Sendurai A , Varadarajan Navin 
Published: August 2022

AbstractExtracellular vesicles (EVs) regulate the tumor microenvironment by facilitating transport of biomolecular cargo including RNA, protein, and metabolites. The biological effects of EV-mediated transport have been studied using supra-physiological concentrations of EVs, but the cells that are responsible for EV secretion and the mechanisms that support EV secretion are not well characterized. We developed an integrated method based on arrays of nanowells to identify individual cells with differences in EV secretion and used an automated robot to perform linked single-cell RNA-sequencing on cloned single cells from the metastatic breast cancer cell line, MDAMB231. Gene expression profiles of clonal cells with differences in EV secretion were analyzed, and a four-gene signature of breast cancer EV secretion was identified: HSP90AA1, HSPH1, EIF5, and DIAPH3. We functionally validated this gene signature by testing it across different cell lines with different metastatic potential demonstrating that the signature correlated with levels of EV secretion. Analysis of the TCGA and METABRIC datasets showed that this signature is associated with poor survival, more invasive breast cancer types, and reduced CD8+ T cell infiltration in human tumors. We anticipate that our method for directly identifying the molecular determinants of EV secretion will have broad applications across cell types and diseases.
Dynamics, signals and influencing factors of CD4 T cell activation revealed by single cell RNA-seq
Authors: Liu Hongyi , Li Hui , Liu Yifei , Wang Xuefei , Yu Shiya , Shen Xiangru , Zhang Qi , Hong Ni , Jin Wenfei 
Published: August 2022

AbstractT cell activation is a key event in adaptive immunity. However, factors affecting T cell activation have not been systematically analyzed. Here, we analyzed stimulated CD4 T cells with anti-CD3/CD28 under several conditions to explore the factors affecting T cell activation. We defined stimulated T overlapped with resting T on UMAP as inert T. Inert T expressed activated T specific genes and cytokines, indicating it is a special functional state. Stimulated T derived from peripheral CD4 T has higher fraction of effector T (TEFF) while stimulated T derived from CD4 TNhas higher fraction of proliferation T and interferon highly expressed T (IFNhiT). CD4 T was more likely to differentiate into TEFFand less likely to differentiate into heat shock protein specific T (HSPhiT) and IFNhiT in the presence of CD8 T. Interestingly,CXCR4lowT responded to stimulation more efficiently thanCXCR4hiT. These information facilitates we design stimulation to obtain ideal activated T.
Pleiotropic roles for mycobacterial DinB2 in frameshift and substitution mutagenesis
Authors: Dupuy Pierre , Ghosh Shreya , Adefisayo Oyindamola , Bean James , Gupta Richa , Shuman Stewart , Glickman Michael 
Published: August 2022

ABSTRACTTranslesion synthesis mediated by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are widely distributed promutagenic translesion polymerases. The role of DinBs in mycobacterial mutagenesis was unclear until recent studies revealed a role for mycobacterial DinB1 in substitution and frameshift mutagenesis, overlapping with that of translesion polymerase DnaE2. M. smegmatis encodes two additional DinBs (DinB2 and DinB3) and M. tuberculosis encodes DinB2, but the roles of these polymerases in mycobacterial damage tolerance and mutagenesis is unknown. The biochemical properties of DinB2, including facile utilization of ribonucleotides and 8-oxo-guanine, suggest that DinB2 could be a promutagenic polymerase. Here we examine the effects of DinB2 and DinB3 overexpression in mycobacterial cells. We demonstrate that DinB2 can drive diverse substitution mutations conferring antibiotic resistance. DinB2 induces frameshift mutations in homopolymeric sequences, both in vitro and in vivo. DinB2 switches from less to more mutagenic in the presence of manganese in vitro. This study indicates that DinB2 may contribute to mycobacterial mutagenesis and antibiotic resistance acquisition in combination with DinB1 and DnaE2.
Comparative assessment of morphology, anatomy and phylogeny of two exceptionally rare narrow endemic Tephrosia spp. (Leguminosae) from the Indian subcontinent
Authors: Vanzara Akash , Bhambra Gagandeep Kaur , Nagar Padamnabhi S. 
Published: August 2022

AbstractLeguminosae is the third most abundant family of angiosperm in the world, and have a distinct difference that serves to identify and differentiate closely related species. Among 650 genera and 18,000 species of legumes in India, Tephrosia is the most emerged genus, of which two endangered and narrow endemic species Tephrosia jamnagarensis Sant and T. colina var. lanuginocarpa Sharma, possess a greater challenges for biological, ecological, and competitive improvement than other plants. Both the species are very unique and only found in a few isolated pockets of Gujarat around the globe. Therefore, in light of this, the present research aims to understand how morphological, anatomical, and genetically both species vary based on their variability nature are contextualized in an Indian context. Studies carried out on Morpho-anatomical observations and classical taxonomic approaches, such as the axillary cyme vs terminal raceme in T. jamnagarensis vs T. colina var. lanuginocarpa Sharma, the corolla being 4.5 cm long vs 1.5 cm long, the wings being 5.5 cm long vs 1.40 cm long, the keel being 3.4 cm long vs 1.5 cm long. First, ever genetic identity of the plants was assessed by using matK gene of the rbcl chloroplast region, and phylogenetic trees were constructed using sister clade separation. Sequences of both the plant species and others species that are found in India were submitted to NCBI and the embryonic stage of seeds were then used to examine seed morphology and propagation.