bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression in soft-shell clam (Mya arenaria) transmissible cancer reveals survival mechanisms during host infection and seawater transfer
Authors: Hart Samuel F.M. , Garrett Fiona E. S. , Kerr Jesse S. , Metzger Michael J. 
Published: September 2024

ABSTRACTTransmissible cancers are unique instances in which cancer cells escape their original host and spread through a population as a clonal lineage, documented in Tasmanian Devils, dogs, and ten bivalve species. For a cancer to repeatedly transmit to new hosts, these lineages must evade strong barriers to transmission, notably the metastasis-like physical transfer to a new host body and rejection by that host’s immune system. We quantified gene expression in a transmissible cancer lineage that has spread through the soft-shell clam (Mya arenaria) population to investigate potential drivers of its success as a transmissible cancer lineage, observing extensive differential expression of genes and gene pathways. We observed upregulation of genes involved with genotoxic stress response, ribosome biogenesis and RNA processing, and downregulation of genes involved in tumor suppression, cell adhesion, and immune response. We also observe evidence that widespread genome instability affects the cancer transcriptome via gene fusions, copy number variation, and transposable element insertions. Finally, we incubated cancer cells in seawater, the presumed host-to-host transmission vector, and observed conserved responses to halt metabolism, avoid apoptosis and survive the low-nutrient environment. Interestingly, many of these responses are also present in healthy clam cells, suggesting that bivalve hemocytes may have inherent seawater survival responses that may partially explain why transmissible cancers are so common in bivalves. Overall, this study reveals multiple mechanisms this lineage may have evolved to successfully spread through the soft-shell clam population as a contagious cancer, utilizing pathways known to be conserved in human cancers as well as pathways unique to long-lived transmissible cancers.
Fresh Human Retinal scRNA-seq Atlas Reveals a Novel Cone Subtype and Cellular Diversity
Authors: Yang Luning , Tao Yiwen , Pan Qi , Cai Tengda , Ye Yunyan , Liu Jianhui , Zhou Yang , Shao Yongqing , Yi Quanyong , Lu Zen Haut , Chen Lie , McKay Gareth , Rankin Richard , Meng Weihua 
Published: September 2024

AbstractThe human retina has a remarkable diversity of cell types, which is crucial for understanding the mechanisms underpinning visual development and function. While single-cell RNA sequencing (scRNA-seq) has advanced our understanding of retinal biology, most studies have relied on postmortem or frozen samples, potentially missing important transcriptional information. The aim of this study was to create the first comprehensive scRNA-seq atlas of fresh human retinal samples from living donors and recently deceased individuals using scRNA-seq technology. A total of 106,829 cells were analyzed, which were collected from nine retinal samples using standardized scRNA-seq workflow. Our findings identified several novel subtypes of known retinal cells, including new subgroups of cones and amacrine cells (ACs), each characterized by distinct gene expression profiles. Notably, we discovered a novel cone subtype, the ELF1-Cone, which shows a clear developmental trajectory from mlCone precursors. This subtype exhibits unique functional properties and metabolic profiles, regulated by key transcription factors ELF1 and PRKAA1. We also identified five distinct AC subtypes, including three GABAergic ACs, each with unique gene expression profiles and functional characteristics. Our study highlights the critical importance of using fresh human retinal tissue for accurate cellular mapping and trajectory inference. Significant differences were observed between fresh and postmortem retinal samples in terms of pseudo time analysis such as RNA velocity. We also performed a comparative analysis of diabetic without retinopathy, diabetic retinopathy, and non-diabetic samples, suggesting diabetes-related transcriptional variation. In conclusion, we present a comprehensive human retina atlas using fresh samples that contribute to existing knowledge of retinal cell diversity, function, and transcriptional profiles. Our study is a milestone for future studies that will improve understanding of retinal biology and disease mechanisms.
A thiol–ene click-based strategy to customize injectable polymer–nanoparticle hydrogel properties for therapeutic delivery
Authors: Bailey Sophia J. , Eckman Noah , Brunel Elisa S. , Jons Carolyn K. , Sen Samya , Appel Eric A. 
Published: September 2024

AbstractPolymer–nanoparticle (PNP) hydrogels are a promising injectable biomaterial platform that has been used for a wide range of biomedical applications including adhesion prevention, adoptive cell delivery, and controlled drug release. By tuning the chemical, mechanical, and erosion properties of injected hydrogel depots, additional control over cell compatibility and pharmaceutical release kinetics may be realized. Here, we employ thiol–ene click chemistry to prepare a library of modified hydroxypropylmethylcellulose (HPMC) derivatives for subsequent use in PNP hydrogel applications. When combined with poly(ethylene glycol)-b-poly(lactic acid) nanoparticles, we demonstrate that systematically altering the hydrophobic, steric, or pi stacking character of HPMC modifications can readily tailor the mechanical properties of PNP hydrogels. Additionally, we highlight the compatibility of the synthetic platform for the incorporation of cysteine-bearing peptides to access PNP hydrogels with improved bioactivity. Finally, through leveraging the tunable physical properties afforded by this method, we show hydrogel retention timein vivocan be dramatically altered without sacrificing mesh size or cargo diffusion rates. This work offers a route to optimize PNP hydrogels for a variety of translational applications and holds promise in the highly tunable delivery of pharmaceuticals and adoptive cells.
Biocontrol of bacterial wilt disease using plant-associated bacterial communities in tomato
Authors: Tanaka Eriko , Umeki Daisuke , Kido Shota , Makishima Rikako , Tamaki Yuko , Murakami Takumi , Fujiwara Masayuki , Saijo Yusuke 
Published: September 2024

ABSTRACTHost-protective or disease-suppressive microorganisms are anticipated as sustainable controls for crop diseases, such as bacterial wilt. However, the efficacy of biocontrol strategies is often limited by a lack of resilience under varying environmental conditions and interactions with native microbial communities in the field. In this study, we assembled a bacterial wilt-suppressive synthetic community (SynCom) in tomato, consisting of bacterial isolates derived from co-cultured microbial complexes associated with the plant. This SynCom demonstrates significant disease-suppressive effects againstRalstonia solanacearumin tomato seedlings under both axenic and soil conditions. Additionally, our findings suggest the existence of an optimal level of SynCom colonization in plants, which is critical for effective disease control. Furthermore, the SynCom exhibits direct antibiotic activity and immunogenic properties that enhance the production of defense-related secondary metabolites, thereby influencing the plant-associated microbiome. Our results provide an effective approach to constructing SynComs that exert disease-suppressive effects within microbial community contexts.
Genetic associations between SGLT2 inhibition, DPP4 inhibition or GLP1R agonism and prostate cancer risk: a two-sample Mendelian randomisation study
Authors: Shen Lin , Yang Yifan , Lu Lei , Chou Oscar Hou In , Lee Quinncy , Liu Tong , Li Guoliang , Cheng Shuk Han , Tse Gary , Zhou Jiandong 
Published: September 2024

AbstractBackgroundEpidemiological studies have linked the use of the anti-diabetic medications, sodium-glucose co-transporter-2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) and glucagon-like peptide-1 receptor agonists (GLP1RA), with prostate cancer risk. However, these studies cannot infer causality.MethodsThis was a two-sample Mendelian randomization (MR) using genome-wide association study data designed to identify causal relationships between SGLT2I, DPP4I or GLP1RA and prostate cancer. Genetic associations with HbA1c and risk of prostate cancer were extracted from IEU Open-GWAS Project database with GWAS id ukb-d-30750_irnt (UK Biobank cohort) and ebi-a-GCST006085 (European Molecular Biology Laboratory’s European Bioinformatics Institute cohort), respectively. The two GWAS datasets chosen were obtained from individuals of European ancestry to minimise potential bias from population stratification. The encoding genes targeted by SGLT2I, DPP4I and GLP1RA were SGC5A2, DPP4 and GLP1R, located in Chr16: 31494323-31502181, Chr2: 162848755-162930904 and Chr6: 39016557-39059079, respectively.ResultsA total of 31, 2 and 5 single nucleotide variants (SNVs) were used for SGC5A2, DPP4 and GLP1R. Our MR analysis results supported a causal relationship between genetic variation in SLC5A2 and DPP4 and reduced risk of prostate cancer at the Bonferroni-corrected threshold, with odds ratios (OR) [95% confidence intervals] of 0.47 [0.38-0.58] and 0.35 [0.24-0.53], but not for GLP1R (OR: 1.39 [0.93-2.07]). Sensitivity analyses by the leave-one-out method did not significantly alter the OR for SGLT2I.ConclusionsThe two-sample MR analysis found that SGLT2 and DPP4 inhibition, but not GLP1R agonism, was associated with lower risks of developing prostate cancer.
Comparing Client and Provider Preferences for HIV Care Coordination Program Features using Discrete Choice Experiments
Authors: Zimba Rebecca , Fong Chunki , Conte Madellena , Guarino Honoria , Avoundjian Tigran , Carmona Jennifer , Herndon Grace , Gambone Gina , Irvine Mary , Nash Denis 
Published: September 2024

ABSTRACTIntroductionThe New York City (NYC) HIV Care Coordination Program (CCP) is designed to promote care engagement and treatment adherence among the people with HIV (PWH) who struggle the most with these key components of managing their health. We assessed preferences for CCP components among PWH enrolled in the program (“clients”) and among providers of CCP services. In this report we compare the preferences between clients and providers, previously analyzed separately.MethodsWe used a discrete choice experiment to assess preferences for four CCP features (“attributes”): Help with Adherence to Antiretroviral Therapy (ART), Help with Primary Care Appointments, Help with Issues other than Primary Care, and Where Program Visits Happen. Each of these attributes had three to four variants (“levels”). In the original surveys, levels within Where Program Visits Happen varied by participant type (client versus provider). We re-coded the levels by visit location (VL) or by travel time (TT) to make them comparable, and report results from both approaches. Preferences were quantified using the relative importance of the attributes and utility of the levels.ResultsJanuary 2020 to March 2021, 152 providers and 181 clients completed the survey. In both the VL and TT analyses, clients were most influenced by Help with Adherence to ART, preferring medication reminders via phone or text, and Where Program Visits Happen, preferring visits via phone or video chat. In the VL analysis, providers were most influenced by Help with Adherence to ART, valuing directly observed therapy most highly, and Help with Issues other than Primary Care, valuing helping clients with connections to specialty medical care. In the TT analysis, providers were most influenced by Where Program Visits Happen, preferring to meet at clients’ homes, and Help with Issues other than Primary Care, again preferring helping clients make connections to specialty medical care.ConclusionsClient and provider preferences clearly diverged with regard to CCP service intensity: in the aggregate, clients tended to prefer lower-intensity services, whereas providers endorsed higher-intensity services. These results highlight the importance of engaging clients as partners in decisions about program services so that they are aligned with client values.
Efficacy and Safety of Nicorandil for Prevention of Contrast-Induced Nephropathy in Patients Undergoing Coronary Procedures: A Systematic Review and Meta-Analysis
Authors: Butt Ayesha Imran , Afzal Fazila , Raza Sukaina , Namal FNU , Ahmed Dawood , Abid Hassaan , Hudaib Muhammad , Sarwar Zainab Safdar Ali , Bashir Soha , Khalid Asadullah , Hassan Umer , Ebad Ur Rehman Mohammad , Cheema Huzaifa Ahmad , Husnain Ali , Anwar Usama , Tahir Muhammad Mohid , Ahmad Adeel , Rehman Wajeeh Ur , Ahmed Raheel 
Published: September 2024

AbstractBackgroundContrast-induced nephropathy (CIN) is a potentially serious complication of intravenous or intra-arterial contrast administration during angiographic procedures that results in renal dysfunction. This meta-analysis assesses the efficacy and safety of nicorandil for the prevention of CIN in patients undergoing percutaneous coronary intervention (PCI) or coronary angiography (CAG).MethodsCochrane Central Register of Controlled Trials, MEDLINE, Embase, andClinicalTrials.govwere used to perform a thorough literature search from their inception to July 2024. A random-effects meta-analysis was performed on RevMan and pooled estimates were presented as forest plots. The Mantel-Haenszel method was used for dichotomous outcomes and risk ratios (RRs) were calculated along with 95% confidence intervals (95% CI).ResultsThis meta-analysis included 12 RCTs consisting of 2787 participants (nicorandil: 1418, control: 1394). The use of nicorandil was protective against CIN (RR 0.38, 95% CI 0.29-0.50). The incidence of major adverse events was comparable in both groups (RR 0.77, 95% CI 0.52-1.13, p=0.18). Similarly, the use of nicorandil did not affect the risk of developing stroke (RR 1.05), myocardial infarction (RR 0.90), heart failure (RR 0.81), cardiac death (RR 0.90), and dialysis (RR 0.70).ConclusionThis study revealed that nicorandil effectively reduced the risk of developing CIN in patients undergoing angiographic procedures like PCI or coronary angiography. However, more RCTs should be conducted for a more definitive conclusion.
The lack of trade-off between conformational stability and binding affinity in a nanobody with therapeutic potential for a misfolding disease
Authors: Gómez-Mulas Atanasio , Naganathan Athi N. , Pey Angel L. 
Published: September 2024

AbstractTo improve protein pharmaceuticals, we need to balance protein stability and binding affinity within vivoefficiency. We have recently developed a nanobody (NB-AGT-2) against the alanine:glyoxylate aminotransferase with high stability (Tm∼85°C) that may be useful to treat a misfolding disease called primary hyperoxaluria type 1. In this work, we characterize the relationships between protein stability and binding affinity in NB-AGT-2 by generating single and double cavity-creating mutants in its hydrophobic core. These mutations decrease thermal stability by 10-20 °C, reflecting changes in thermodynamic stability of up to 8 kcal·mol-1, hardly affecting their binding affinity for its target. Our results thus show that NB stability can be challenged without an effect on its binding.
Leveraging weighted quartet distributions for enhanced species tree inference from genome-wide data
Authors: Hasan Navid Bin , Biswas Avijit , Wahab Zahin , Mahbub Mahim , Reaz Rezwana , Bayzid Md Shamsuzzoha 
Published: September 2024

AbstractSpecies tree estimation from genes sampled from throughout the whole genome is challeng-ing in the presence of gene tree discordance, often caused by incomplete lineage sorting (ILS), where alleles can coexist in populations for periods that may span several speciation events. Quartet-based summary methods for estimating species trees from a collection of gene trees are becoming popular due to their high accuracy and theoretical guarantees of robustness to arbitrarily high amounts of ILS. ASTRAL, the most widely used quartet-based method, aims to infer species trees by maximizing the number of quartets in the gene trees that are consistent with the species tree. An alternative approach (as in wQFM) is to infer quartets for all subsets of four species and amalgamate them into a coherent species tree. While summary methods can be highly sensitive to gene tree estimation errors–especially when gene trees are derived from short alignments–quartet amalgamation offers an advantage by potentially bypassing the need for gene tree estimation. However, greatly understudied is the choice of weighted quar-tet inference method and downstream effects on species tree estimations under realistic model conditions. In this study, we investigated a broad range of methods for generating weighted quartets and critically assessed their impact on species tree inference. Our results on a collec-tion of simulated and empirical datasets suggest that amalgamating quartets weighted based on gene tree frequencies (GTF) typically produces more accurate trees than leading quartet-based methods like ASTRAL and SVDquartets. Further enhancements in GTF-based weighted quar-tet estimation were achieved by accounting for gene tree uncertainty, through the utilization of a distribution of trees for each gene (instead of a single tree), by employing traditional nonpara-metric bootstrapping methods or Bayesian MCMC sampling. Our study provides evidence that the careful generation and amalgamation of weighted quartets, as implemented in methods like wQFM, can lead to significantly more accurate trees compared to widely employed methods like ASTRAL, especially in the face of gene tree estimation errors.
De novoassembly of the selfishtsupergene reveals a deleterious evolutionary trajectory
Authors: Runge Jan-Niklas , Ullrich Kristian , Lindholm Anna K. 
Published: September 2024

AbstractSupergenes are linked clusters of DNA that are transmitted together due to rare or absent recombination. They undergo co-adaptation, allowing evolution to work on several genes to refine complex phenotypes, giving supergenes a competitive edge. Yet, due to their lack of recombination, supergenes are susceptible to deterioration as they cannot efficiently purge deleterious DNA. Few examples outside of sex chromosomes have been available for study. Here, we present the first assembly of thethaplotype, a 33.4 Mb supergene in house mice that ‘selfishly’ transmits itself at non-Mendelian frequencies. We characterize the four large non-overlapping inversions that make up thethaplotype. We compare in at/tindividual two differenttvariants with different recessive lethal phenotypes (age at death). Despite that difference, they differ much less from each other than the rest of the chromosome. However, the differences that they have were much more likely to be deleterious than the differences between the two variants of the rest of the chromosome. We interpret this marked difference as evidence of the accumulation of deleterious variants, a hallmark of deterioration. Thetregion of chromosome 17 is more distant to the reference than the rest of the chromosome, and has a higher fraction of impactful differences here as well. Thus, we conclude that thetappears as a quickly spreading and deteriorating selfish supergene, a rare example of Muller’s ratchet outside of sex chromosomes. Furthermore, we aim for our assembly to provide a resource for comparative work on thethaplotype, such as its evolutionary history.
Ecotype formation in the European anchovy fuelled by structural variants of different origins and genetic interactions with a southern lineage
Authors: Meyer Laura , Barry Pierre , Arbiol Christine , Castilho Rita , Van der Lingen Carl , Chlaïda Malika , McKeown Niall J , Ernande Bruno , Le Moan Alan , Bonhomme François , Gagnaire Pierre-Alexandre , Guinand Bruno 
Published: September 2024

AbstractThe speciation of ecotypes can unfold in diverse ways and likely depends on multiple processes. The variants involved in ecotype divergence can include new mutations as well as older allelic variation that evolved in different contexts. Among the different types of variants that can contribute to reproductive isolation between ecotypes, structural variants (SVs) represent likely candidates due to their ability to protect divergent haplotypes from recombination and gene flow. The European anchovy (Engraulis encrasicolus) is known to be subdivided into marine and coastal ecotypes, and their divergence shows patterns that are consistent with SVs. Here, we present the first genome-scale study investigating genetic structure in theE. encrasicolusspecies complex. We generated a reference genome and produced whole-genome resequencing data for anchovies from the North-East Atlantic and Mediterranean Sea, as well as from South Africa. We complemented this approach with the analysis of RAD-seq data in order to study ecotypic structure across the entire distribution range. We found that genetic diversity is not only characterised by the presence of two genetic clusters, namely the marine and coastal ecotypes, but also by a third ancestry which corresponds to a southern Atlantic lineage. This lineage occurs off South Africa but also in southern Morocco and the Canary Islands, and shows a gradient of admixture with northern populations nearing the Atlantic-Mediterranean transition zone. Genomic landscapes of differentiation showed evidence for large regions of high linkage disequilibrium, likely representing SVs that differentiate the three anchovy lineages. We found evidence that three of the SVs contributing to the gene flow barrier between ecotypes originated in the southern lineage, suggesting that the coastal and southern lineages have a partly shared evolutionary history. In addition to these barriers, three other SVs contributing to ecotype differentiation appear to have evolvedin situ. Anchovies thus present an interesting case for the study of ecotype speciation, since the barriers involved in reproductive isolation have different origins and have partly diverged in geographic isolation.
Sex-, development-, and nutrition-dependent expression of a major age-at-maturity gene in Atlantic salmon
Authors: Åsheim Eirik Ryvoll , Debes Paul Vincent , House Andrew , Liljeström Petra , Ruokolainen Annukka , Frapin Morgane , Donner Iikki , Ahi Ehsan Pashay , Erkinaro Jaakko , Verta Jukka-Pekka , Primmer Craig R 
Published: September 2024

ABSTRACTSexual maturation is a key process in the life history of an organism and is influenced by both genetic and environmental factors. In Atlantic salmon (Salmo salar), alternative alleles at the gene vgll3 have been found to associate with a large proportion of the variation in maturation age, yet the molecular and physiological mechanisms of this association are still largely unknown. Here, we investigated the mechanisms by which genetic variation in this major age-at-maturity gene translated into phenotypic variation. We established a time series of gonadal vgll3 mRNA expression in male and female Atlantic salmon in a common garden setting, starting at the prepubertal stage and spanning multiple spawning seasons. We found that vgll3 mRNA expression is reduced in early-maturing males and females. However, for the second spawning season, vgll3 expression increased with gonadal development in males, but eventually decreased in females. Expression of vgll3 had context-dependent correlations with expression of amh and lhr. We also found signs of reduced testicular vgll3 expression in a low-fat feed treatment. By significantly widening the scope of our knowledge on temporal vgll3 expression dynamics, our results exemplify that major-effect genes may use different pathways in sexes but achieve similar outcomes.