bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural variation in fruiting body morphology in the amoebaDictyostelium discoideum
Authors: Broersma Cathleen M.E. , McFadyen Sean , Ostrowski Elizabeth A. 
Published: July 2024

AbstractReproductive altruism, where some individuals reproduce and others do not, is considered one of the pinnacles of cooperative societies. However, the optimal level of reproductive altruism is likely to depend on inclusive fitness considerations, including the relatedness of reproducing to non-reproducing individuals, as well as the benefits and costs accruing to each, respectively. In the social amoebaDictyostelium discoideum, thousands of cells aggregate to form a multicellular fruiting body. During this process, some cells die, forming a rigid stalk that supports the rest of the cells, which become viable spores. The level of stalk investment by the social group can therefore be considered a metric of altruism investment. Importantly, genetically unrelated cells can co-aggregate to produce ‘chimeric’ fruiting bodies, and selection can favour genotypes that behave selfishly by preferentially forming spores and avoiding forming the stalk. Owing to the extreme differences in fitness consequences of stalk cells versus spores, the level of altruism investment is likely to be under strong selection. Here we examined clonal fruiting body morphology in four natural populations to assess the extent to which stalk investment varies within populations and is maintained to different extents among populations. We found variation in fruiting body size and stalk investment, at both a cm-scale and between geographically isolated populations. These findings indicate the divergent evolution of altruism investment with and among populations and demonstrate widespread potential for cheating.
Integrated multiomic profiling reveals SWI/SNF subunit-specific pathway alterations and targetable vulnerabilities
Authors: Santamarina Jorge Bretones , Astier Clémence , Garrido Marlène , Daage Leo Colmet , Roumeliotis Theodoros I. , Anthony Elodie , Pardo Mercedes , Chasseriaud Marianne , Gestraud Pierre , Ngo Carine , Morel Daphné , Chabanon Roman , Choudhary Jyoti , Del Nery Elaine , Postel-Vinay Sophie , Ballesta Annabelle 
Published: July 2024

SummaryMutations in subunits of the SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex occur in ≈20% of cancers and represent a highly unmet medical need. To identify novel therapeutic approaches, we systematically characterized transcriptomic and proteomic changes caused by the loss of SWI/SNF subunits or other epigenetic enzymes in isogenic cell lines, which we subsequently integrated with high-throughput drug screening and independent genetic screens of the DepMap project. Using an optimized bioinformatics pipeline for pathway enrichment, we identifiedMetabolism of proteinsas the most frequently dysregulated Reactome pathway category in SWI/SNF-defective cell lines. Drug screening and multiomic integration revealed multiple chemicals selectively cytotoxic for SWI/SNF-defective models, including CBP/EP300 or mitochondrial respiration inhibitors. A novel algorithm for the analysis of DepMap CRISPR screens independently identified synthetic lethality between SWI/SNF defects andEP300or mitochondrial respiration genes, which we further revalidated in disease-relevant models. These results unravel novel genetic dependencies for SWI/SNF-defective cancers.
Genetic variation in the speciesArabidopsis thalianareveals the existence of natural heat resilience factors for meiosis
Authors: Zhao Jiayi , Fu Huiqi , Wang Zhengze , Zhang Min , Liang Yaoqiong , Cui Xueying , Pan Wenjing , Ren Ziming , Wu Zhihua , Zhang Yujie , Gui Xin , Huo Li , Lei Xiaoning , Wang Chong , Schnittger Arp , Pawlowski Wojciech P. , Liu Bing 
Published: July 2024

AbstractHeat interferes with multiple meiotic processes leading to genome instability and sterility in flowering plants, including many crops. Despite its importance for food security, the mechanisms underlying heat tolerance of meiosis are poorly understood. In this study, we analyzed different meiotic processes in the Arabidopsis (Arabidopsis thaliana) accessions Columbia (Col) and Landsbergerecta(Ler), their F1 hybrids and F2 offspring under heat stress (37°C). At 37°C, Col exhibits significantly reduced formation of double-stand breaks (DSBs) and completely abolished homolog pairing, synapsis and crossover (CO) formation. Strikingly, Lerand Ler/Col hybrids are much less affected than Col. Interestingly, only 10% ∼ 20% of F2 offspring exhibit the same heat tolerance of meiotic recombination as parents, indicating that heat resilience in Leris controlled by the interplay of several loci. Moreover, F2 offspring show defective chromosome condensation in interkinesis, and untimely sister-chromatid segregation and/or chromosome fragmentation, the levels of which exceed those in either inbreds and/or hybrids thus implying a transgressive effect on heat tolerance of meiosis. Furthermore, correlation and cytogenetic analysis suggest that homolog pairing and/or synapsis have an impact on heat tolerance of chromosome morphology and stability during post-recombination stages under heat stress. Taken together, this study reveals the existence of natural heat resilience factors for meiosis in Arabidopsis, which have the great potential to be exploited in breeding programs.Author summaryEnvironmental temperature alterations affect meiotic recombination and/or chromosome segregation thus perturbing genetic makeup and genome stability in plants. We have previously reported that CO formation is fully abolished inArabidopsis thalianaaccession Col under heat stress (36°C-38°C) due to reduced DSB formation and impaired homolog pairing. Here, we show that inArabidopsis thalianaaccession Lerunder the same high temperature conditions, both DSB and CO formation occur normally, and homolog pairing is mildly impacted, which indicate a striking difference in heat tolerance of meiotic recombination from Col. Remarkably, Col/Lerhybrids display the same heat tolerance as Ler, however, only 10% ∼ 20% of F2 offspring behave the same as parents. Moreover, we found higher levels of defects in chromosome morphology and integrity, and sister-chromatid segregation in F2 population than those in both inbreds and hybrids, which suggest a transgressive effect influencing heat tolerance of meiosis. Our findings reveal that heat resilience in Arabidopsis is controlled by the interplay of multiple genomic loci, holding a great potential to be exploited in crop breeding.
Antibacterial activity of tamoxifen derivatives against methicillin-resistantStaphylococcus aureus
Authors: Panadero Irene Molina , Torres Javier Falcón , Hmadcha Karim , Princiotto Salvatore , Cutarella Luigi , Mori Mattia , Dallavalle Sabrina , Christodoulou Michael S. , Smani Younes 
Published: July 2024

ABSTRACTThe present work aimed to discover new tamoxifen derivatives with antimicrobial potential, particularly targeting methicillin-resistantStaphylococcus aureus(MRSA).The MIC of 22 tamoxifen derivatives was determined againstS. aureusreference and MRSA strains, using microdilution assays. The antibacterial effects of selected tamoxifen derivatives against MRSA (USA7) were assessed through bacterial growth assays. Bacterial membrane permeability and molecular docking assays were performed.The MIC of the tamoxifen derivatives against MRSA ranged from to 16 to >64 μg/mL. Bacterial growth assays demonstrated that tamoxifen derivatives2,5, and6reduced dose-dependently the growth of the USA7 strain. Moreover, treatment of MRSA with derivatives2and5resulted in increased membrane permeabilization without being the cell wall their molecular target.These data suggest that tamoxifen derivatives exhibit antibacterial activity against MRSA, potentially broadening the spectrum of available drug treatments for combating antimicrobial-resistant Gram-positive bacteria.ImportanceThe development of new antimicrobial therapeutic strategies requires immediate attention to avoid the tens of millions of deaths predicted to occur by 2050 as a result of multidrug-resistant (MDR) bacterial infections. In this study, we assessed the antibacterial activity of 22 tamoxifen derivatives against methicillin-resistant Staphylococcus aureus (MRSA). We found that three tamoxifen derivatives exhibited antibacterial activity against MRSA clinical isolats, presenting MIC50values between 16 and 64 μg/mL and reducing bacterial growth over 24 h. Additionally, this antibacterial activity for two of the derivatives was accompanied by increased membrane permeability of MRSA. Our results suggest that tamoxifen derivatives might be used as a potential therapeutic alternative for treating MRSA strains in an animal model of infection.
Ecotype-specific genomic features within theEscherichiacryptic clade IV
Authors: Saraceno Martín , Frankel Nicolás , Graziano Martín 
Published: July 2024

AbstractEscherichiacryptic clades represent a relatively unexplored taxonomic cluster believed to exhibit characteristics associated with a free-living lifestyle, which is known as the environmental hypothesis. This hypothesis suggests that certainEscherichiastrains harbour traits that favour their environmental persistence, thus expanding the ecological commensal niche of the genus. While surveyingEscherichiadiversity in an urban South American stream we isolated the first environmental cryptic clade IV strain in South America (339_SF). Here we report the genomic characterization of 339_SF strain in the context of existing genomic information for cryptic clade IV. A comparative analysis of genomes within the same clade stemming from diverse ecological sources and geographical locations reveals close phylogenetic proximity between our isolate and strains of environmental origin. In the genomes of cryptic clade IV strains that were isolated from environmental niches we observed enrichment of functional genes related to responses to adverse environmental conditions and a low number of genes with clinical relevance among. Our findings highlight substantial intra-group genomic structuring linked to ecological origin and shed light on the genomic mechanisms underlying the naturalization phenomena within theEscherichiagenus.
A Cost-effective, High-throughput, Highly Accurate Genotyping Method for Outbred Populations
Authors: Chen Denghui , Chitre Apurva S. , Nguyen Khai-Minh H. , Cohen Katarina , Peng Beverly , Ziegler Kendra S. , Okamoto Faith , Lin Bonnie , Johnson Benjamin B. , Sanches Thiago M. , Cheng Riyan , Polesskaya Oksana , Palmer Abraham A. 
Published: July 2024

AbstractAffordable sequencing and genotyping methods are essential for large scale genome-wide association studies. While genotyping microarrays and reference panels for imputation are available for human subjects, non-human model systems often lack such options. Our lab previously demonstrated an efficient and cost-effective method to genotype heterogeneous stock rats using double-digest genotyping-by-sequencing. However, low-coverage whole-genome sequencing offers an alternative method that has several advantages. Here, we describe a cost-effective, high-throughput, high-accuracy genotyping method for N/NIH heterogeneous stock rats that can use a combination of sequencing data previously generated by double-digest genotyping-by-sequencing and more recently generated by low-coverage whole-genome-sequencing data. Using double-digest genotyping-by-sequencing data from 5,745 heterogeneous stock rats (mean 0.21x coverage) and low-coverage whole-genome-sequencing data from 8,760 heterogeneous stock rats (mean 0.27x coverage), we can impute 7.32 million bi-allelic single-nucleotide polymorphisms with a concordance rate >99.76% compared to high-coverage (mean 33.26x coverage) whole-genome sequencing data for a subset of the same individuals. Our results demonstrate the feasibility of using sequencing data from double-digest genotyping-by-sequencing or low-coverage whole-genome-sequencing for accurate genotyping, and demonstrate techniques that may also be useful for other genetic studies in non-human subjects.Article SummaryHeterogeneous stock rats were derived by interbreeding eight inbred founders in 1984, and have been maintained as an outbred population for more than 100 generations. Heterogeneous stock rats offer a high degree of genetic and phenotypic diversity, and have been extensively used for genetic studies. Here, we describe a cost-effective and high-throughput genotyping method for heterogeneous stock rats. We applied the method to 15,552 heterogeneous stock rats. The resulting genotypes were highly accurate. These techniques may be useful for genetic studies in other non-human subjects.
A systematic literature review to evaluate the effect of maternal education on under-five mortalities in Nigeria, with recommendations for sustainable development
Authors: Umoru Dominic D. 
Published: July 2024

AbstractIntroductionThesecond target of the SDG3 hopes to reduce under-5 mortalities (U5M) to at least as low as 25 per 1000 live births by 2030. However, U5M remain high in Nigeria and maternal education has been recognized as a predicting factor. This systematic literature review aims to evaluate the relationship between maternal education and under-five mortalities in Nigeria and make recommendations.MethodsA systematic search of PubMed, CINAHL, EMBASE and Maternity and Infant Care databases was conducted between 1st August 2021 and 31stJuly 2022. Included articles were appraised using Critical Appraisal Tool for Analytical Cross-sectional Studies developed by the Joanna Briggs Institute (JBI), 2017. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA, 2009) guidelines was used for data extraction.ResultA total of 215 articles were retrieved out of which 33 were removed due to duplications. After screening, 27 were assessed out of which 14 were finally included. The result indicates that there was less odd of U5M among children whose mothers had at least primary education and suggests that the risk of dying further reduces with higher levels of maternal education. This result corroborates that of earlier studies.ConclusionReduction in U5M depends on understanding of the impact of maternal education. Therefore, policies should strive to bridge the gaps in female literacy by creating better access to education for Nigerian women.Key messageU5M remains high in Nigeria despite an improving global figure. Aside the direct causes, maternal education has been identified as one remote predictor of child deaths before the age of 5. Although some isolated studies have tried to prove this, there is still need for more evidence to support this thinking, given the potential of such findings to influence policies related to child health. Therefore, this SLR hopes to synthesize evidence based on what is already known with the goal to influence local policies on child survival.
Preclinical Development of a Romidepsin Nanoparticle Demonstrates Superior Tolerability and Efficacy in Models of Human T-Cell Lymphoma and Large Granular Lymphocyte Leukemia
Authors: Pal Ipsita , Illendula Anuradha , Joyner Andrea , Manavalan John Sanil , Deddens Tess M. , Sabzevari Ariana , Damera Deepthi P. , Zuberi Samir , Marchi Enrica , Fox Todd E. , Dunlap-Brown Marya E. , Jayappa Kallesh D. , Craig Jeffrey W. , Loughran Thomas P. , Feith David J. , O’Connor Owen A. 
Published: July 2024

AbstractHistone deacetylase (HDAC) inhibitors are a widely recognized and valued treatment option for patients with relapsed or refractory peripheral T cell lymphomas (PTCL). Romidepsin is a relatively selective Class I HDAC inhibitor originally approved for patients with relapsed or refractory (R/R) cutaneous T cell lymphoma (CTCL) and subsequently R/R PTCL. Unfortunately, the FDA approval of romidepsin for R/R PTCL was withdrawn due to a negative Phase 4 post-marketing requirement (PMR), diminishing further the treatment options for patients with PTCL. Herein we describe the development of a first-in-class polymer nanoparticle of romidepsin (Nanoromidepsin) using an innovative amphiphilic di-block copolymer-based nanochemistry platform. Nanoromidepsin exhibited superior pharmacologic disposition, with improved tolerability and safety in murine models of T-cell lymphoma. Nanoromidepsin also exhibited superior anti-tumor efficacy in multiple models includingin vitroT cell lymphoma (TCL) cell lines,ex vivoLGL leukemia primary patient samples, and murine TCL xenografts. Nanoromidepsin demonstrated greater accumulation in tumors and a statistically significant improvement in overall survival (OS) compared to romidepsin in murine xenograft models. These findings collectively justify the clinical development of Nanoromidepsin in patients with T-cell malignancies.
Comprehensive Analysis of Exportins Expression and its Prognostic Significance in Colon Adenocarcinoma: Insights from Public Databases
Authors: Kalia Punita , Nair Rohini Ravindran , Yadav Suresh Singh 
Published: July 2024

ABSTRACTColon cancer remains a significant health burden globally, necessitating deeper investigation. Identification and targeting of prognostic markers can significantly improve the current therapeutic approaches for colon cancer. The differential nuclear transport (import and export) of cellular proteins, plays an important role in tumor progression. Exportins, critical mediators of nuclear export, have emerged as potential players in cancer pathogenesis. However, their precise roles and prognostic significance in colon adenocarcinoma remain elusive. This study was designed to comprehensively analyse the expression and prognostic significance of all seven exportins in Colon Adenocarcinoma (COAD) using the online public database. We used public databases UALCAN, C-Bio portal, Human Protein Atlas (HPA), and DAVID, to investigate exportins in COAD patients. Kaplan-Meier plotter, Gene ontology (GO), TIMER, STRING, and KEGG were used to analyse data and draw conclusions. Our observations showed a significant correlation of exportins expression with clinical parameters, used to predict a patient’s prognosis in general, such as advancing tumor stage, overall/relapse-free survival, and immune cell infiltrations. Mutation analysis showed the presence of amplifications, missense mutations in XPO2 and XPO4, and deep deletions in XPO7 genes contributing to disease progression and patients survival. This study highlights the potential use of exportins as novel prognostic biomarkers and therapeutic targets for colon adenocarcinoma progression and management.
MALDI-TOF MS profiling and its contribution to mosquito-borne diseases: a systematic review
Authors: Costa Monique Melo , Corbel Vincent , Hamouda Refka Ben , Almeras Lionel 
Published: July 2024

AbstractMosquito-borne diseases are responsible for hundreds of thousands of deaths per year. The identification and control of the vectors that transmit pathogens to humans are crucial for disease prevention and management. Currently, morphological and molecular approaches are the standard methods used for vector identification, however, they present several limitations. In the last decade, matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) profiling emerged as an innovative technology in Biological Sciences and is now considered as a relevant tool for the identification of pathogens and arthropods. Beyond species identification, this tool can be relevant for the determination of different life traits of arthropod vectors. The purpose of the present systematic review was to highlight the contribution of MALDI-TOF MS to the surveillance and control of mosquito-borne diseases. Published articles from January 2003 to September 2023 were retrieved, considering different aspects of mosquito life traits which could be determinant in the transmission of diseases and vector management. The screening of scientific literature resulted in the selection of 54 published articles that assessed MALDI-TOF MS profiling to study various biological factors such species identification, life expectancy, gender, trophic preferences, microbiota and insecticide resistance. Although a large majority of the selected articles focused on species identification, the present review shows that MALDI-TOF MS profiling is promising for identifying various mosquito life traits with rapidity, high throughput capacity, reliability and low cost. The strength and weakness of this proteomic tool for vector control and surveillance are discussed.
UK mosquitoes are competent to transmit Usutu virus at native temperatures
Authors: Pilgrim Jack , Metelmann Soeren , Widlake Emma , Seechurn Nicola , Vaux Alexander , Mansfield Karen L , Tanianis-Hughes Jola , Sherlock Ken , Johnson Nicholas , Medlock Jolyon , Baylis Matthew , Blagrove Marcus SC 
Published: July 2024

AbstractUsutu virus (USUV) is an emerging zoonotic virus transmitted primarily byCulexmosquitoes. Since its introduction into Europe from Africa during the late 20thcentury, it has caused mortality within populations of passerine birds and captive owls, and can on occasion lead to disease in humans. USUV was first detected in the UK in 2020 and has become endemic, having been detected in either birds and/or mosquitoes every subsequent year. Importantly, the vector competence of indigenous mosquitoes for the circulating UK (London) USUV strain at representative regional temperatures is still to be elucidated. This study assessed the vector competence of five field-caught mosquito species/biotypes,Culex pipiensbiotypemolestus,Culex pipiensbiotypepipiens,Culex torrentium,Culiseta annulataandAedes detritusfor the London USUV strain, with infection rates (IR) and transmission rates (TR) evaluated between 7 to 28 days post-infection. Infection and transmission were observed in all species/biotypes aside fromAe. detritusandCx. torrentium. ForCx. pipiensbiotypemolestus, transmission potential suggests these populations should be monitored further for their role in transmission to humans. Furthermore, bothCx. pipiensbiotypepipiensandCs. annulatawere shown to be competent vectors at 19°C indicating the potential for geographical spread of the virus to other UK regions.
Quantifiable Blood TCR Repertoire Components Associated with Immune Aging
Authors: Hu Jing , Pan Mingyao , Reid Brett , Tworoger Shelley , Li Bo 
Published: July 2024

AbstractT cell senescence results in decayed adaptive immune protection in older individuals, with decreased or increased abundance of certain T cell phenotypic subpopulations. However, no study has linked aging to the dynamic changes of T cell clones. Through a newly develop computational framework, Repertoire Functional Units (RFU), we investigated over 6,500 TCR repertoire sequencing samples from multiple human cohorts. Our analysis identified age-associated RFUs repeatedly and consistently across different cohorts. Quantification of RFU decreases with aging revealed accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifested a potential link between these RFUs and improved clinical outcomes during acute viral infections, such as lower ICU admission and reduced risk of developing complications. Finally, our investigation of bone-marrow transplantation patients indicated a secondary expansion of the age-associated clones upon receiving stem cells from younger donors. Together, our results suggest the existence of certain clones or a ‘TCR clock’ that could reflect the immune functions in aging populations.