bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent adaptation in an imperiled salmonid revealed by museum genomics
Authors: Sharo Andrew G. , Supple Megan A. , Cabrera Randy , Seligmann William E. , Sacco Samuel , Columbus Cassondra D. , Pearse Devon E. , Shapiro Beth , Garza John Carlos 
Published: April 2024

AbstractSteelhead/rainbow trout (Oncorhynchus mykiss) is an imperiled salmonid with two main life history strategies: migrate to the ocean or remain in freshwater. Domesticated hatchery forms of this species have been stocked into almost all California waterbodies, possibly resulting in introgression into natural populations and altered population structure.We compared whole-genome sequence data from contemporary populations against a set of museum population samples of steelhead from the same locations that were collected prior to most hatchery stocking.We observed minimal introgression and few steelhead-hatchery trout hybrids despite a century of extensive stocking. Our historical data show signals of introgression with a sister species and indications of an early hatchery facility. Finally, we found that migration-associated haplotypes have become less frequent over time, a likely adaptation to decreased opportunities for migration. Since contemporary migration-associated haplotype frequencies have been used to guide species management, we consider this to be a rare example of shifting baseline syndrome that has been validated with historical data.We suggest cautious optimism that a century of hatchery stocking has had minimal impact on California steelhead population genetic structure, but we note that continued shifts in life history may lead to further declines in the ocean-going form of the species.
Resource competition affects the developmental outcome of the acoustic parasitoid flyOrmia ochracea
Authors: Dominguez Jimena A. , Latham Brendan , Mongui Laura C. , Rossinow Addie , Xiong Yeng , Schmidt Briella V. , Vu Quang , Torres-Lopez Blanca L. , Henderson Parker A. , Mason Andrew C. , Lee Norman 
Published: April 2024

AbstractOrmia ochraceais an acoustic parasitoid fly where the adults are free-living, but their larval young depend on nutritional resources within host crickets for growth and development. In nature, gravid female flies rely on their ability to recognize and localize cricket calling songs to find suitable host species to parasitize. In depth investigations of fly behavior and the mechanistic bases of auditory perception require a reliable approach to propagate stable fly colonies in the laboratory. Previous work has demonstrated that flies can be propagated using a number of natural host cricket species, as well as cricket species that flies do not parasitize in nature. However, we lack a complete understanding of fly developmental outcomes when non-host cricket species are utilized to propagate fly colonies. In this study, we document the feasibility of using commercially suppliedAcheta domesticusas a host species. We specifically test the hypothesis that host size and resource competition can affect developmental outcomes ofO. ochracea. We performed manual parasitizations on crickets that varied in size, and resource competition was varied by manipulating the number of larvae used to parasitize a host cricket. A series of morphometric analyses were conducted on host crickets, and developmental outcomes were measured in terms of pupation success and eclosion success, pupal width, and eclosed adult fly size. In the absence of resource competition, we found that host cricket size did not affect pupation or eclosion success. In the presence of resource competition between two developing larvae within a host cricket, pupation and eclosion successes were impacted negatively, and the developing pupae were more likely to be smaller. These results confirm that resource competition among developing parasitoids can negatively affect developmental outcomes, andAcheta domesticuscan be used effectively to propagate colonies ofO. ochraceain the laboratory.HighlightsThe acoustic parasitoid flyOrmia ochraceacan successfully develop within the house cricketAcheta domesticus.Pupal size and eclosed adult fly size varies positively with the size of host cricket.Resource competition negatively affects pupation and eclosion success.Resource competition resulted in smaller fly pupae that were less likely to eclose.Graphical Abstract
Genome sequence and characterization of a hypervirulent BI/NAP1/027Clostridioides difficile(CDC20121308)
Authors: Español Laureano A. , Palumbo Miranda C. , Barbero Angela M. , Palma Sabina , Serral Federico , Ruggeri Diego , Martí Marcelo A. , Fernández Do Porto Darío , Hernández Del Pino Rodrigo E. , Pasquinelli Virginia 
Published: April 2024

AbstractClostridioides difficileis a gram-positive bacterium implicated in antibiotic-associated diarrhea. The use of antibiotics alters the gut microbiota, rendering the host susceptible to infection byC. difficile.This pathogen colonizes the large intestine of humans and animals leading to asymptomatic carriage or clinical manifestations such as toxic megacolon and fulminant colitis depending on a wide range of pathogen and host factors. The emergence of BI/NAP1/027 strains in North America and the spread of these hypervirulent ribotypes worldwide have been linked to the increase in incidence and severity ofC. difficileinfections (CDI) over the last decade. In this work, we aimed to characterize the BI/NAP1/027C. difficilecommercial strain CDC20121308 widely employed in the study of host-pathogen interactions.The genome sequence was obtained using a whole-genome shotgun strategy. A total of 3,717 coding sequences (CDS) and 45 tRNAs were predicted. The annotation of the CDC20121308 strain identified 26% of CDS into RAST subsystems. We also detected the presence of RT 027 lineage markers such asthyA, cdtA, cdtB and tcdC 18bp-deletion. Moreover, the genome of CDC20121308 had 11 genes devoted to resistance to toxic compounds, antibiotics (e.g. Tetracycline (Tet) and Vancomycin (Van)) and disinfecting agents as predicted using CARD.C. difficileCDC20121308 resistance to Van and Tet was confirmed by broth microdilution assay. Crystal violet staining demonstrated biofilm formation, which could be associated with antibiotic resistance and pathogenicity. Additionally, we observed a spreading diffuse growth in soft agar tubes, suggesting a motile phenotype. Lastly, a genomic region containing Type 4 Secretory System components such as virD4, virB4, and virB6 was identified.In conclusion, our results allowed a genomic and functional characterization of the BI/NAP1/027C. difficileCDC20121308 strain. We demonstrated the presence of several genes associated with pathogenesis that were validated by experimental assays. This study provides additional data for the use of this highly virulence commercial strain of epidemiological relevance in research works involvingin vitroandin vivoapproaches.
Perturbation-Specific Transcriptional Mapping for unbiased target elucidation of antibiotics
Authors: Romano Keith P , Bagnall Josephine , Warrier Thulasi , Sullivan Jaryd , Ferrara Kristina , Orzechowski Marek , Nguyen Phuong H , Raines Kyra , Livny Jonathan , Shoresh Noam , Hung Deborah T 
Published: April 2024

AbstractThe rising prevalence of antibiotic resistance threatens human health. While more sophisticated strategies for antibiotic discovery are being developed, target elucidation of new chemical entities remains challenging. In the post-genomic era, expression profiling can play an important role in mechanism-of-action (MOA) prediction by reporting on the cellular response to perturbation. However, the broad application of transcriptomics has yet to fulfill its promise of transforming target elucidation due to challenges in identifying the most relevant, direct responses to target inhibition. We developed an unbiased strategy for MOA prediction, called Perturbation-Specific Transcriptional Mapping (PerSpecTM), in which large-throughput expression profiling of wildtype or hypomorphic mutants, depleted for essential targets, enables a computational strategy to address this challenge. We applied PerSpecTM to perform reference-based MOA prediction based on the principle that similar perturbations, whether chemical or genetic, will elicit similar transcriptional responses. Using this approach, we elucidated the MOAs of three new molecules with activity againstPseudomonas aeruginosaby comparing their expression profiles to those of a reference set of antimicrobial compounds with known MOAs. We also show that transcriptional responses to small molecule inhibition resemble those resulting from genetic depletion of essential targets by CRISPRi by PerSpecTM, demonstrating proof-of-concept that correlations between expression profiles of small molecule and genetic perturbations can facilitate MOA prediction when no chemical entities exist to serve as a reference. Empowered by PerSpecTM, this work lays the foundation for an unbiased, readily scalable, systematic reference-based strategy for MOA elucidation that could transform antibiotic discovery efforts.Significance StatementNew antibiotics are critically needed in the face of increasing antibiotic resistance. However, mechanism-of-action (MOA) elucidation remains challenging and imposes a major bottleneck in antibiotic discovery and development. Building on the principle that molecules with similar MOAs elicit similar transcriptional responses, we have developed a highly scalable strategy for MOA prediction in the important bacterial pathogenPseudomonas aeruginosabased on correlations between the expression profiles of new molecules and known perturbations, either small molecule inhibition by known antibiotics or transcriptional repression of essential targets by CRISPRi. By rapidly assigning MOAs to three new molecules with anti-pseudomonal activity, we provide proof-of-concept for a rapid, comprehensive, systematic, reference-based approach to MOA prediction with the potential to transform antibiotic discovery efforts.
Missing cell types in single-cell references impact deconvolution of bulk data but are detectable
Authors: Ivich Adriana , Davidson Natalie R. , Grieshober Laurie , Li Weishan , Hicks Stephanie C. , Doherty Jennifer A. , Greene Casey S. 
Published: April 2024

AbstractAdvancements in RNA-sequencing have dramatically expanded our ability to study gene expression profiles of biological samples in bulk tissue and single cells. Deconvolution of bulk data with single-cell references provides the ability to study relative cell-type proportions, but most methods assume a reference is present for every cell type in bulk data. This is not true in all circumstances--cell types can be missing in single-cell profiles for many reasons. In this study, we examine the impact of missing cell types on deconvolution methods. Our experimental designs are simulation-based, using paired single-cell and single-nucleus data, since single-nucleus RNA-sequencing is able to preserve the nucleus of cell types that would otherwise be missing in a single-cell counterpart. These datasets allow us to examine the missing-cell-type phenomenon in deconvolution with realistic proportions. We apply three deconvolution methods that vary from straightforward to state-of-the-art: non-negative least squares, BayesPrism, and CIBERSORTx. We find that the performance of deconvolution methods is influenced by both the number and the similarity of missing cell types, consistent with prior results. Additionally, we find that missing cell-type profiles can be recovered from residuals using a simple non-negative matrix factorization strategy. We expect our simulation strategies and results to provide a starting point for those developing new deconvolution methods and help improve their to better account for the presence of missing cell types. Building off of our findings on simulated data, we then analyzed data from high-grade serous ovarian cancer; a tumor that has regions of highly variable levels of adipocytes dependent on the region from which it is sampled. We observe results consistent with simulation, namely that expression patterns from cell types likely to be missing appear present in residuals. Our results suggests that deconvolution methods should consider the possibility of missing cell types and provide a starting point to address this. Our source code for data simulation and analysis is freely available athttps://github.com/greenelab/pred_missing_celltypes.
CAIM: Coverage-based Analysis for Identification of Microbiome
Authors: Acheampong Daniel A. , Jenjaroenpun Piroon , Wongsurawat Thidathip , Krulilung Alongkorn , Pomyen Yotsawat , Kandel Sangam , Kunadirek Pattapon , Chuaypen Natthaya , Kusonmano Kanthida , Nookaew Intawat 
Published: April 2024

ABSTRACTAccurate taxonomic profiling of microbial taxa in a metagenomic sample is vital to gain insights into microbial ecology. Recent advancements in sequencing technologies have contributed tremendously toward understanding these microbes at species resolution through a whole shotgun metagenomic (WMS) approach. In this study, we developed a new bioinformatics tool, CAIM, for accurate taxonomic classification and quantification within both long- and short-read metagenomic samples using an alignment-based method. CAIM depends on two different containment techniques to identify species in metagenomic samples using their genome coverage information to filter out false positives rather than the traditional approach of relative abundance. In addition, we propose a nucleotide-count based abundance estimation, which yield lesser root mean square error than the traditional read-count approach. We evaluated the performance of CAIM on 28 metagenomic mock communities and 2 synthetic datasets by comparing it with other top-performing tools. CAIM maintained a consitently good performance across datasets in identifying microbial taxa and in estimating relative abundances than other tools. CAIM was then applied to a real dataset sequenced on both Nanopore (with and without amplification) and Illumina sequencing platforms and found high similality of taxonomic profiles between the sequencing platforms. Lastly, CAIM was applied to fecal shotgun metagenomic datasets of 232 colorectal cancer patients and 229 controls obtained from 4 different countries and primary 44 liver cancer patients and 76 controls. The predictive performance of models using the genome-coverage cutoff was better than those using the relative-abundance cutoffs in discriminating colorectal cancer and primary liver cancer patients from healthy controls with a highly confident species markers.Key Points-Metagenomic coverage is an important index to obtain highly accurate species identification by reducing false positives from whole shotgun metagenomic data.-Comparative analyses of CAIM and other bioinformatics tools for species identification on many mock community whole shotgun metagenomic datasets generated by short-read and long-read sequencing and synthetic datasets were performed, showing that CAIM has a very good performance compared with the other tools.-Using the metagenomic coverage approach through CAIM improves the predictive power of species biomarkers identified from in stool samples of colorectal cancer and primary liver datasets.
ACTN3genotype influences androgen response in skeletal muscle
Authors: Roeszler Kelly N. , See Michael , Meehan Lyra R. , Lima Giscard , Kolliari-Turner Alexander , Alexander Sarah E. , Landen Shanie , Wood Harrison D. , Tiong Chrystal F. , Chen Weiyi , Mustafa Tomris , Houweling Peter J. , Eynon Nir , Lamon Severine , Pitsiladis Yannis , Handelsman David J. , Rossello Fernando J. , Ramialison Mirana , North Kathryn N. , Seto Jane T. 
Published: April 2024

AbstractAndrogens are vital for the maintenance of muscle mass and their anabolic effects are primarily exerted through the androgen receptor (AR). Accumulating evidence in humans and mice suggests that circulating androgens, AR and androgen response are influenced byACTN3 (α- actinin-3), also known as “the gene for speed”. One in 5 people worldwide are α-actinin-3 deficient due to homozygous inheritance of a common null polymorphism (577X) inACTN3. In this study, we show that α-actinin-3 deficiency decreases baseline AR in skeletal muscles of mice and humans, in both males and females, and that AR expression directly correlates withACTN3in a dosage dependent manner. We further demonstrate inActn3knockout mice that α- actinin-3 deficiency increases muscle wasting induced by androgen deprivation and reduces the muscle hypertrophic response to dihydrotestosterone and this is mediated by differential activation of pathways regulating amino acid metabolism, intracellular transport, MAPK signalling, autophagy, mitochondrial activity and calcineurin signalling. Gene set enrichment and protein analyses indicate that the absence of α-actinin-3 results in a failure to coactivate many of these pathways in response to changes in androgens, and relies on leveraging mitochondrial remodelling and calcineurin signalling to restore muscle homeostasis. We further identified 7 genes that are androgen sensitive and α-actinin-3-dependent in expression, and whose functions correspond to these processes. Our results highlight the pivotal role of α- actinin-3 in various processes associated with the regulation of protein turnover and muscle mass, and suggest thatACTN3genotype is a genetic modifier of androgen action in skeletal muscle.
Limosilactobacillus fermentumATG-V5 stimulates the immune response by enhancing gut microbiome and metabolite in a cyclophosphamide-induced immunosuppression mouse model
Authors: Park Arum , Park Yeon-Hwa , Kang Yewon , Park Juyi , Park Gun-Seok , Ju Yo-Han , Hwang Won , Kang Jihee 
Published: April 2024

AbstractLimosilactobacillus fermentumis known to exert immunomodulatory effects. In this study, we elucidated the immunoenhancing effects and mechanisms of a novel strain ofLimosilactobacillus fermentumATG-V5. Our findings demonstrate that ATG-V5 regulates the activation and proliferation of natural killer (NK) and T cells. It induced activation effects such as increased nitric oxide (NO) production, phagocytic capacity, and cytokine generation in Raw264.7 cells, which were confirmed to occur through the ERK and pp65 pathways. Furthermore, using a cyclophosphamide (CPP) mouse model, we demonstrated the immunomodulatory efficacy of ATG-V5, including enhanced activation of NK cells, increased levels of antibodies and cytokine secretion, in mice with immunosuppression induced by CPP. Additionally, by analyzing the gut bacterial community in the mouse model, we confirmed the ability of ATG-V5 consumption to regulate the gut microbiota, thereby substantiating the potential of this strain as a promising immunoenhancing agent.
Birth of protein-coding exons by ancient domestication of LINE retrotransposon
Authors: Kitao Koichi , Ichiyanagi Kenji , Nakagawa So 
Published: April 2024

AbstractTransposons, occasionally domesticated as novel host protein-coding genes, are responsible for the lineage-specific functions in vertebrates. LINE-1 (L1) is one of the most active transposons in the vertebrate genomes. Despite its abundance, the contribution of L1 to the birth of vertebrate proteins remains unelucidated. Here, we present a novel mechanism for the origination ofde novoproteins, in which the L1 retrotransposons are incorporated into host genes as protein-coding exons by alternative splicing. L1 ORF1 protein (ORF1p) is an RNA-binding protein that binds to L1 RNA and is required for retrotransposition by acting as an RNA chaperone. We identified a splicing variant ofmyosin light chain 4(MYL4) containing an L1 ORF1-derived exon and encoding a chimeric protein of L1 ORF1p and MYL4, named Lyosin. Molecular evolutionary analysis revealed that Lyosin was acquired in the common ancestor of reptiles and birds during the Paleozoic era. The amino acid sequence of Lyosin had undergone purifying selection although it was lost in some lineages, including the Neognathae birds and snakes. The transcripts encoding Lyosin were expressed in the testes of two lizard species, suggesting that its function is different from that of the canonical MYL4 expressed specifically in the heart. Furthermore, sequence searches revealed other evolutionarily conserved chimeric isoforms fused to the L1 ORF1p in three genes in vertebrates. Our findings suggest a novel evolutionary mechanism for the birth of lineage-specific proteins derived from transposons and implicate the previously unrecognized adaptive functions of L1 ORF1p.
Genome of tropical bed bugCimex hemipterus(Cimicidae, Hemiptera) reveals tetraspanin expanded in bed bug ancestor
Authors: Law Sean Tsz Sum , Nong Wenyan , Li Chade , Chong Tze Kiu , Yip Ho Yin , Swale Thomas , Chiu Siu Wai , Chung Roger Yat-Nork , Lam Hon-Ming , Wong Samuel Y.S. , Wong Hung , Hui Jerome H.L. 
Published: April 2024

AbstractCimexspecies are ectoparasites that exclusively feed on warm-blooded animals such as birds and mammals. Three cimicid species are known to be persistent pests for humans, including the tropical bed bugC. hemipterus, common bed bugC. lectularius, and Eastern bat bugLeptocimex boueti. To date, genomic information is restricted to the common bed bugC. lectularius, which limits understand their biology and to provide controls of bed bug infestations. Here, a chromosomal-level genome assembly ofC. hemipterus(495 Mb) containing on 16 pseudochromosomes (scaffold N50 = 34 Mb), together with 9 messenger RNA and small RNA transcriptomes were obtained. Comparison between hemipteran genomes, we found that the tetraspanin superfamily were expanded in theCimexancestor. This study provides the first genome assembly for the tropical bed bugC. hemipterus, and offers an unprecedented opportunity to address to questions relating to bed bug infestations, as well as genomic evolution to hemipterans more widely.