bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Angiotensin II on the Gut Microbiome of Mice: Findings from a Retrospective Study
Authors: Muralitharan Rikeish R. , Nakai Michael E. , Snelson Matthew , Zheng Tenghao , Dinakis Evany , Xie Liang , Jama Hamdi , Paterson Madeleine , Shihata Waled , Wassef Flavia , Vinh Antony , Drummond Grant R. , Kaye David M. , Mackay Charles R. , Marques Francine Z. 
Published: April 2023

AbstractIntroductionAnimal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external factors not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations.Methods and ResultsWe conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomised into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P=0.0137) and β-diversity (i.e., composition of the microbiome, P<0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid-producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P<0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%).ConclusionsOur large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.
Senescence triggers intracellular acidification and lysosomal alkalinization via ATP6AP2 attenuation in breast cancer cells
Authors: Li Wei , Kawaguchi Kosuke , Tanaka Sunao , He Chenfeng , Maeshima Yurina , Suzuki Eiji , Toi Masakazu 
Published: April 2023

AbstractSeveral chemotherapy drugs induce the senescence of cancer cells; however, the mechanism underlying intracellular pH dysregulation in senescent cells remains unclear. Adenosine triphosphatase H+ transporting accessory protein 2 (ATP6AP2) plays a critical role in maintaining pH homeostasis in cellular compartments. We here report a new function of ATP6AP2 in senescent breast cancer cells induced by doxorubicin and abemaciclib treatment. ATP6AP2 expression was significantly downregulated in senescent cells, leading to aberrant pH levels that impaired lysosome function and caused immune response changes. The drugs caused cell cycle arrest and proliferation suppression through the upregulation of senescence-related genes. Additionally, senescent cells showed altered inflammatory and immune transcriptional profiles by reprogramming the senescence-associated secretory phenotype. These findings suggest that ATP6AP2-mediated pH regulation during therapy-induced senescence may be linked to immune changes in senescent cancer cells. These findings provide novel insights into understanding the cellular mechanisms underlying the response to anti-cancer drugs.
Phyloecology ofnrfA-ammonifiers and their relative importance with denitrifiers in global terrestrial biomes
Authors: Saghaï Aurélien , Pold Grace , Jones Christopher M. , Hallin Sara 
Published: April 2023

AbstractNitrate ammonification is important for soil nitrogen retention. However, the ecology of nitrate ammonifiers and their prevalence compared with denitrifiers, being competitors for nitrate, are overlooked. Here, we screened more than 1 million genomes fornrfA, encoding the nitrite reductase in nitrate ammonification. Nearly 50% of the nitrate ammonifier assemblies carry at least one denitrification gene and, contrary to the current paradigm, have higher potential for nitrous oxide production than reduction. We then used a phylogeny-based approach to recruitnrfAand denitrification nitrite reductase gene fragments in 1,861 metagenomes covering the major terrestrial biomes. Denitrification genes dominated, except in tundra, and random forest modelling teased apart the influence of the soil C/N on nitrate ammonifier vs denitrifier abundances, showing an effect of nitrate rather than carbon content. This study demonstrates the multiple roles nitrate ammonifiers play in nitrogen cycling and the factors ultimately controlling the fate of nitrate in soil.
A model for co-occurrent assortative mating and vertical cultural transmission and its impact on measures of genetic associations
Authors: Herzig Anthony F. , Noûs Camille , Pierre Aude Saint , Perdry Hervé 
Published: April 2023

AbstractAssortative mating for a given phenotype is the phenomenon by which mates select each other based on their phenotypic similarity. Other phenomena can create positive correlation between the parents’ and the offspring’s environment: vertical cultural transmission, or dynastic effects. When these phenomena occur together, they induce a gene-environment correlation at the population scale. It will impact genetic measures of associations such as SNP effect size and SNP-heritability.In this paper, we provide a complete mathematical modeling of this phenomenon, in the classical framework of the polygenic additive model. We then derive its consequences on typical genetic epidemiology study designs. We validate our calculations through simple forward-time simulations.
Decoupling of evolutionary changes in mRNA and protein levels
Authors: Jiang Daohan , Cope Alexander L. , Zhang Jianzhi , Pennell Matt 
Published: April 2023

AbstractVariation in gene expression across lineages is thought to explain much of the observed phenotypic variation and adaptation. The protein is closer to the target of natural selection but gene expression is typically measured as the amount of mRNA. The broad assumption that mRNA levels are good proxies for protein levels has been undermined by a number of studies reporting moderate or weak correlations between the two measures across species. One biological explanation for this discrepancy is that there has been compensatory evolution between the mRNA level and regulation of translation. However, we do not understand the evolutionary conditions necessary for this to occur nor the expected strength of the correlation between mRNA and protein levels. Here we develop a theoretical model for the coevolution of mRNA and protein levels and investigate the dynamics of the model over time. We find that compensatory evolution is widespread when there is stabilizing selection on the protein level, which is true across a variety of regulatory pathways. When the protein level is under directional selection, the mRNA level of a gene and its translation rate of the same gene were negatively correlated across lineages but positively correlated across genes. These findings help explain results from comparative studies of gene expression and potentially enable researchers to disentangle biological and statistical hypotheses for the mismatch between transcriptomic and proteomic studies.
Bacterial mixed cultures followed mixed-order kinetics during mono-azo dye decolourization and degradation in batch studies
Authors: Jain Kunal R. , Chapla Digantkumar , Shah Amita , Madamwar Datta 
Published: April 2023

AbstractOver the years little has been focused on kinetic and thermodynamic aspect of bioremediation studies on dyes. In this study, detailed kinetic and thermodynamic analyses of results obtained during a primary study on a mono-azo dye: Reactive violet 5R (RV5), decolourization and degradation by bacterial mixed cultures SB4 were performed. Various kinetic models (zero-, first- and second-order behaviour and Monod model) were applied to understand the decolourization mechanism in batch process. Similarly, steady-state kinetics for determination of Michaelis-constant and maximal dye removal rate was derived. With increasing RV5 concentration, the specific decolourization rate had increased from 0.61mg/L/h to 1.38mg/L/h. The apparent kinetics of RV5 decolourization reaction followed mixed-order behaviour. The process was endothermic. The enthalpy and entropy values calculated to 45.6kJ/mol and 146J/mol/K, respectively, with an activation energy of 87kJ/mol. The Gibbs free energy change suggests that, decolourization reaction under experimental conditions was non-spontaneous below 20°C but was spontaneous at higher temperatures.
Comparative single cell epigenomic analysis of gene regulatory programs in the rodent and primate neocortex
Authors: Zemke Nathan R , Armand Ethan J , Wang Wenliang , Lee Seoyeon , Zhou Jingtian , Li Yang Eric , Liu Hanqing , Tian Wei , Nery Joseph R. , Castanon Rosa G , Bartlett Anna , Osteen Julia K , Li Daofeng , Zhuo Xiaoyu , Xu Vincent , Miller Michael , Krienen Fenna M. , Zhang Qiangge , Taskin Naz , Ting Jonathan , Feng Guoping , McCarroll Steven A , Callaway Edward M , Wang Ting , Behrens M Margarita , Lein Ed S , Ecker Joseph R , Ren Bing 
Published: April 2023

AbstractSequence divergence ofcis-regulatory elements drives species-specific traits, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains to be elucidated. We investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset, and mouse with single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome, and chromosomal conformation profiles from a total of over 180,000 cells. For each modality, we determined species-specific, divergent, and conserved gene expression and epigenetic features at multiple levels. We find that cell type-specific gene expression evolves more rapidly than broadly expressed genes and that epigenetic status at distal candidatecis-regulatory elements (cCREs) evolves faster than promoters. Strikingly, transposable elements (TEs) contribute to nearly 80% of the human-specific cCREs in cortical cells. Through machine learning, we develop sequence-based predictors of cCREs in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Lastly, we show that epigenetic conservation combined with sequence similarity helps uncover functionalcis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.
GATA transcription factor in common bean: a comprehensive genome-wide functional characterization, identification, and abiotic stress response evaluation
Authors: Abdulla Mohamed Farah , Mostafa Karam , Aydin Abdullah , Kavas Musa 
Published: April 2023

AbstractThe GATA transcription factor has been extensively studied for its regulatory role in various biological processes in many plant species. The functional and molecular mechanism of GATA TFs in regulating tolerance to abiotic stress has not yet been studied in the common bean, a popular and commercially important crop affected by the intensifying climate change. This study analyzed the functional identity of the GATA gene family in the P. vulgaris genome under different abiotic and phytohormonal stress. TheGATAgene family was systematically investigated in theP. vulgarisgenome, and 31PvGATATFs were identified. The collinearity between the common bean, rice, andArabidopsiswas studied, and collinearity with Arabidopsis was higher than in rice. Among the 31PvGATAs, 18 showed duplicated events, which suggests the importance of gene duplication in contribution to GATA gene expansion. Furthermore, all thePvGATAgenes were classified into four major subfamilies, with eight, three, six, and 13 members in each subfamily (subfamilies I, II, III, and IV), respectively. A single GATA domain was also present in all PvGATA protein sequences, however, members of subfamily II contained additional domains like CCT and tify domains. The study also predicted and analyzed the promoter cis-regulatory elements (CREs). A total of 799 CREs was predicted in thePvGATAs, categorized into three categories, namely growth and development regulatory elements, stress-responsive elements, and phytohormone-responsive elements. The growth and development regulatory elements had the largest share of CREs in the promoter region ofPvGATAgenes. Additionally, we used qRT-PCR to investigate the expression profiles of fivePvGATAgenes in the common bean roots under abiotic and phytohormone treatments. The results suggest thatPvGATA1/10/25/28may play crucial roles in regulating plant resistance against salt and drought stress at 24 hours and may be involved in phytohormone-mediated stress signaling pathways. This study provides a comprehensive analysis of thePvGATAgene family, which can serve as a foundation for future research on the function ofGATATfs in abiotic stress tolerance in common bean plants.
Darapladib, an inhibitor of Lp-PLA2, sensitizes cancer cells to ferroptosis by remodeling lipid metabolism
Authors: Oh Mihee , Jang Seo Young , Lee Ji-Yoon , Kim Jong Woo , Jung Youngae , Seo Jinho , Han Tae-Su , Jang Eunji , Son Hye Young , Kim Dain , Kim Min Wook , Song Kwon-Ho , Oh Kyoung-Jin , Kim Won Kon , Bae Kwang-Hee , Huh Yong-Min , Han Baek-Soo , Lee Sang Chul , Hwang Geum-Sook , Lee Eun-Woo 
Published: April 2023

AbstractArachidonic and adrenic acids in the membrane play key roles in ferroptosis, but how these fatty acids are manipulated in cells is largely unknown. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen identified that darapladib (SB-480848), an inhibitor of Lp-PLA2, synergistically induced ferroptosis with GPX4 inhibitors. Notably, darapladib was able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, Lp-PLA2 was located in the membrane and cytoplasm and suppressed ferroptosis, suggesting the critical role of intracellular Lp-PLA2. Lipidomic analysis showed that phosphatidylethanolamine (PE) species were generally enriched, while lysophosphatidylethanolamine (lysoPE) and free fatty acid levels were reduced, upon darapladib treatment. Finally, combination treatment with darapladib and PACMA31, a GPX4 inhibitor, efficiently inhibited tumor growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.
The practice of breast self-examination and associated factors among female healthcare professionals working in selected hospitals in Kigali, Rwanda: A Cross Section Study
Authors: Wolde Mulugeta Tenna , Okova Rosemary , Habtu Michael , Wondafrash Mekitie , Bekele Abebe 
Published: April 2023

AbstractBackgroundBreast self-examination is considered one of the main screening methods in detecting earlier stages of breast cancer. It is a useful technique if practiced every month by women above 20 years since globally breast cancer among women contributed to 685,000 deaths in 2020. However, the practice of breast self-examination among healthcare professionals is low in many developing countries. Therefore, this research was intended to measure the level of breast self-examination practice and determine associated factors among female healthcare professionals working in selected hospitals in Kigali, Rwanda.MethodsA cross-sectional study was conducted among 221 randomly selected female healthcare professionals in four district hospitals in Kigali, Rwanda. A self-administered structured questionnaire was used as data collection instrument. The predictor variables were socio-demographic and obstetrics variables, knowledge on breast cancer and breast self-examination, attitude towards breast cancer and breast self-examination. Sample statistics such as frequencies, proportions and mean were used to recapitulate the findings in univariate analysis. Multiple logistic regression analysis was employed to identify statistically significant variables that predict breast self-examination practice. Adjusted odds ratio and 95% confidence level were reported. P-value < 0.05 was used to declare statistical significance.ResultsBreast self-examination was practiced by 43.5% of female healthcare professionals. This prevalence is low compared to other studies. Attitude towards breast self-examination and breast cancer was the only predictor variable that was significantly associated with breast self-examination practice [AOR=1.032; 95% CI (1.001, 1.065), p-value=0.042]. However, number of pregnancy and number of children were not significantly associated with BSE practice in the multi-variate analysis. In addition, knowledge and attitude were linearly correlated with r=0.186, p=0.005.ConclusionsThe breast self-examination practice was found to be low. Attitude toward breast cancer and breast self-examination was positively associated with BSE practice. Moreover, attitude and knowledge were linearly associated. This suggests the need for continuous medical education on breast self-examination and breast cancer to increase the knowledge & BSE practice level of female healthcare professionals.
The analysis of risk factors associated with multimorbidity of anaemia, malaria, and malnutrition among children aged 6- 59 months in Nigeria
Authors: Obasohan Phillips Edomwonyi , Walters Stephen J. , Jacques Richard , Khatab Khaled 
Published: April 2023

AbstractIn the last ten years multimorbidity in children under the age of five years has becoming an emerging health issue in developing countries. The absence of a proper understanding of the causes, risk factors, and prevention of these new health disorders (multimorbidity) in children is a significant cause for concern, if the sustainable development goal 3 of ensuring healthy lives and the promotion of well-being for all especially in the associated aim of ending preventable deaths of new-borns and children must be achieved by 2030. In the past, most studies conducted in Nigeria and some other least developed nations of the world focused on these multiple diseases by employing conventional analytical techniques to examine them separately as distinct disease entities. But the study of multimorbidity of anaemia, malaria, and malnutrition has not been done, especially in children. This study aims to investigate the multiple overlaps in the impact of individual and contextual variables on the prevalence of multimorbidity among children aged 6 to 59 months in Nigeria. The study used two nationally representative cross-sectional surveys, the 2018 Nigeria Demographic and Health Survey and the 2018 National Human Development Report.A series of multilevel mixed effect ordered logistic regression models were used to investigate the associations between child/parent/household variables (at level 1), community-related variables (at level 2) and area-related variables (at level 3), and the multimorbidity outcome (no disease, one disease only, two or more diseases). The interaction effects between child’s sex, age, and household wealth quintiles and the outcome while accounting for some covariates in the model were also investigated. The result shows that 48.3% (4,917/10,184) of the sample of children aged 6-59 months cohabit with two or more of the disease outcomes. Child’s sex, age, maternal education, mother’s anaemia status. household wealth quintiles, the proportion of community wealth status, states with high human development index, region, and place of residence, were among the significant predictors of MAMM (p<0.05). There was a significant interaction effect between a child’s age and wealth status when some other covariates were accounted for. The prevalence of MAMM observed in the sample is large, with almost half of the children living with two or more of the diseases at the time of the survey and several potentially modifiable risk factors have been identified. If suitable actions are not urgently taken, Nigeria’s ability to actualise the SDG 3 will be in grave danger. Therefore, possible actions to ameliorate this problem include developing and implementing a suitable policy that will pave the way for integrated care models to be developed.
An in-depth comparison of linear and non-linear joint embedding methods for bulk and single-cell multi-omics
Authors: Makrodimitris Stavros , Pronk Bram , Abdelaal Tamim , Reinders Marcel 
Published: April 2023

AbstractMulti-omic analyses contribute to understanding complex biological processes, but also to making reliable predictions about, for example, disease outcomes. Several linear joint dimensionality reduction methods exist, but recently neural networks are more commonly used to embed different-omics into the same non-linear manifold. We compared linear to non-linear joint embedding methods using bulk and single-cell data. For modality imputation, non-linear methods had a clear advantage. Comparisons in downstream supervised tasks lead to the following insights: First, concatenating the principal components of each modality is a competitive baseline for multi-modal prediction. If only one modality was available at test time, joint embeddings yielded significant performance improvements with respect to a unimodal predictor. Second, imputed omics profiles can be fed to classifiers trained on real data with limited performance drops. Overall, the product-of-experts architecture performed well in most tasks while a common encoder of concatenated modalities performed poorly.
Cellular Senescence is a Double-Edged Sword in Regulating Aged Immune Responses to Influenza
Authors: Torrance Blake L. , Panier Hunter A. , Cadar Andreia N. , Martin Dominique E. , Lorenzo Erica C. , Jellison Evan R. , Bartley Jenna M. , Haynes Laura 
Published: April 2023

AbstractClearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective deletion of p16-expressing senescent cells upon administration of ganciclovir (GCV). While p16-expressing senescent cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although deletion of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV treated mice. GCV treated mice were unable to mount an optimal memory response and demonstrated increased viral load following a heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.