bluuebunny/crossref_metadata_2025_split huggingface dataset:
<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">Staphylococcus aureus&#160; associated with post-operative wound infections in Western Kenya reveals genomic hotspots for pathogen evolution
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Authors: MOGOI NICHOLAS NYABERA , Sifuna Anthony Wawire , Okoth Patrick Kirsteen , Reva Oleg , Malaba Rose , Negesa Ruth , Nyongesa Peter Kuloba , Osoro Ezra Kombo , Welch Martin 
Published: May 2024

Objectives. Staphylococcus aureus is one of the most common pathogens attributed to hospital infections. Although S. aureus infections have been well studied in developed countries, far less is known about the biology of the pathogen in sub-Saharan Africa.
Methods. Here, we report on the isolation, antibiotic resistance profiling, whole genome sequencing, and genome comparison of six multi-drug resistant isolates of S. aureus obtained from a referral hospital in Kakamega, Western Kenya.
Results. Five of the six isolates contained a 20.7-kb circular plasmid carrying blaZ (associated with resistance to b-lactam antibiotics). These five strains all belonged to the same sequence type, ST152. Despite the similarity of the plasmid these isolates, whole genome sequencing revealed that the strains differed, depending on whether they were associated with hospital-acquired or community-acquired infections.
Conclusion. The intriguing finding is that the hospital acquired and the community acquired isolates of S. aureusbelonging to the same genotype ST152 formed two separate sub-clusters in the phylogenetic tree and differed by the repertoire of accessory virulence genes suggesting an ongoing adaptive evolution and significant genomic plasticity.
Gordonia prachuapensis sp. nov. and Gordonia sesuvii sp. nov., two novel actinobacteria isolated from mangrove sediments and leaves of halophyte Sesuvium portulacastrum in Thailand
Authors: Suphannarot Aekasit , Butdee Waranya , Suriyachadkun Chanwit , Duangmal Kannika , Mingma Ratchanee 
Published: May 2024

A polyphasic approach was used to characterize two novel actinobacterial strains, designated PKS22-38T and LSe1-13T, which were isolated from mangrove soils and leaves of halophyte Sesuvium portulacastrum (L.), respectively. Phylogenetic analyses based on 16S rRNA gene sequences showed that they belonged to the genus Gordonia and were most closely related to three validly published species with similarities ranging from 98.6 to 98.1 %. The genomic DNA G+C contents of strains PKS22-38T and LSe1-13T were 67.3 and 67.2 mol%, respectively. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between the two strains were 93.3 and 54.9 %, respectively, revealing that they are independent species. Meanwhile, the ANI and dDDH values between the two novel strains and closely related type strains were below 80.5 and 24.0 %, respectively. Strains PKS22-38T and LSe1-13T contained C16 : 0, C18 : 1
ω9c and C18 : 0 10-methyl (TBSA) as the major fatty acids and diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol as the main phospholipids. The predominant menaquinone was MK-9(H2). Based on phenotypic, chemotaxonomic, phylogenetic and genomic data, strains PKS22-38T and LSe1-13T are considered to represent two novel species within the genus Gordonia, for which the names Gordonia prachuapensis sp. nov. and Gordonia sesuvii sp. nov. are proposed, with strain PKS22-38T (=TBRC 17540T=NBRC 116256T) and strain LSe1-13T (=TBRC 17706T=NBRC 116396T) as the type strains, respectively.
Natural killer cells associate with epithelial cells in the pancreatic ductal adenocarcinoma tumor microenvironment
Authors: Malchiodi Zoe X. , Suter Robert K. , Deshpande Atul , Peran Ivana , Harris Brent T. , Duttargi Anju , Chien Min-Ju , Hariharan Samika , Wetherill Lucia , Jablonski Sandra A. , Ho Won Jin , Fertig Elana J. , Weiner Louis M. 
Published: May 2024

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. PDAC’s poor prognosis and resistance to immunotherapy are attributed in part to its dense, fibrotic tumor microenvironment (TME), which is known to inhibit immune cell infiltration. We recently demonstrated that PDAC patients with higher natural killer (NK) cell content and activation have better survival rates. However, NK cell interactions in the PDAC TME have yet to be deeply studied. We show here that NK cells are present and active in the human PDAC TME.MethodsWe used imaging mass cytometry (IMC) to assess NK cell content, function, and spatial localization in human PDAC samples. Then, we used CellChat, a tool to infer ligand-receptor interactions, on a human PDAC scRNAseq dataset to further define NK cell interactions in PDAC.ResultsSpatial analyses showed for the first time that active NK cells are present in the PDAC TME, and both associate and interact with malignant epithelial cell ducts. We also found that fibroblast-rich, desmoplastic regions limit NK cell infiltration in the PDAC TME. CellChat analysis identified that the CD44 receptor on NK cells interacts with PDAC extracellular matrix (ECM) components such as collagen, fibronectin and laminin expressed by fibroblasts and malignant epithelial cells. This led us to hypothesize that these interactions play roles in regulating NK cell motility in desmoplastic PDAC TMEs. Using 2D and 3Din vitroassays, we found that CD44 neutralization significantly increased NK cell invasion through matrix.ConclusionsTargeting ECM-immune cell interactions may increase NK cell invasion into the PDAC TME.Graphical Abstract
Supersize me: torpor assists pre-hibernation fattening in a boreal bat
Authors: Fjelldal Mari A. , Fritzén Niclas R. , Suominen Kati M. , Lilley Thomas M. 
Published: May 2024

AbstractHibernators face an energetic dilemma in the autumn at northern latitudes; while temperatures and food availability decrease, hibernating species need to build fat deposits to survive the winter. During this critical fattening phase, insectivorous boreal bats use torpor to build and conserve their reserves. However, we still know little about temporal variability in torpor use employed by bats in autumn and how decreasing temperatures and food availability in combination with increasing individual body mass impact this. Here we present two general hypotheses for explaining temporal torpor patterns observed in a boreal bat (Eptesicus nilssonii), in which torpor use I) facilitates rapid mass gain or II) conserves stored body mass. Although temporally separated in our dataset, temperature, insect abundance and body mass throughout autumn in the study system indicate thatE. nilssoniireaches a majority of its overwintering mass before the onset of increasing daily and nightly torpor use. In combination with generally low food availability by this point in time, these observations suggest that torpor expression might be intended to conserve gained reserves. Our study is intended as a first proof-of-concept for disentangling temporal drivers of torpor in bats during the pre-hibernation fattening phase.
Gene regulatory activity associated with PCOS revealedDENND1A-dependent testosterone production
Authors: Sankaranarayanan Laavanya , Brewer Kelly J , Johnson Graham D , Barrera Alejandro , Venukuttan Revathy , Sisk Ryan , Dunaif Andrea , Reddy Timothy E 
Published: May 2024

AbstractPolycystic ovary syndrome (PCOS) is among the most common disorders affecting up to 15% of the menstruating population globally. It is the leading cause of anovulatory infertility and a major risk factor for type 2 diabetes. Elevated testosterone levels are a core endophenotype. Despite that prevalence, the underlying causes remain unknown. PCOS genome-wide association studies (GWAS) have reproducibly mapped a number of susceptibility loci, including one encompassing a gene regulating androgen biosynthesis, DENND1A. Identifying the causal variants within these loci will provide fundamental insight into the precise biological pathways that are disrupted in PCOS. We report the discovery of gene regulatory mechanisms that help explain genetic association with PCOS in the GATA4, FSHB and DENND1A loci using a combination of high throughput reporter assays, CRISPR-based epigenome editing, and genetic association analysis from PCOS case and control populations. In addition, we found that increased endogenous DENND1A expression causes elevated testosterone levels in an adrenal cell model, specifically by perturbing candidate regulatory elements. These results further highlight the potential for combining genetic variant analyses with experimental approaches to fine map genetic associations with disease risk.
Modeling the Impact of Seasonality on Mosquito Population Dynamics: Insights for Vector Control Strategies
Authors: Baafi Joseph , Hurford Amy 
Published: May 2024

AbstractMosquitoes are important vectors for the transmission of some major infectious diseases of humans, i.e., malaria, dengue, West Nile Virus and Zika virus. The burden of these diseases is different for different regions, being highest in tropical and subtropical areas, which have high annual rainfall, warm temperatures, and less pronounced seasonality. The life cycle of mosquitoes consists of four distinct stages: eggs, larvae, pupae, and adults. These life stages have different mortality rates and only adults can reproduce. Seasonal weather may affect the population dynamics of mosquitoes, and the relative abundance of different mosquito stages. We developed a stage-structured model that considers laboratory experiments describing how temperature and rainfall affects the reproduction, maturation and survival of different Anopheles mosquito stages, the species that transmits the parasite that causes malaria. We consider seasonal temperature and rainfall patterns and describe the stage-structured population dynamics of the Anopheles mosquito in Ain Mahbel, Algeria, Cape Town, South Africa, Nairobi, Kenya and Kumasi, Ghana. We find that neglecting seasonality leads to significant overestimation or underestimation of mosquito abundance. We find that depending on the region, mosquito abundance: peaks one, two or four times a year, periods of low abundance are predicted to occur for durations ranging from six months (Ain Mahbel) to not at all (Nairobi); and seasonal patterns of relative abundance of stages are sub-stantially different. The region with warmer temperatures and higher rainfall across the year, Kumasi, Ghana, is predicted to have higher mosquito abundance, which is broadly consistent with reported malaria deaths relative to the other countries considered by our study. Our analysis reveals distinct patterns in mosquito abundance across different months and regions. Control strategies often target one specific life stage, for example, applying larvicides to kill mosquito larvae, or spraying insecticides to kill adult mosquitoes. Our findings suggest that differences in seasonal weather affect mosquito stage structure, and that the best approaches to vector control may differ between regions in timing, duration, and efficacy.
LotOfCells: data visualization and statistics of single cell metadata
Authors: González-Velasco Óscar 
Published: May 2024

AbstractSingle-cell sequencing unveils a treasure trove into the biological and molecular characteristics of samples. Yet, within this flood of data, the challenge to draw meaningful conclusions sometimes can be time consuming and a tortuous process.Here we introduce LotOfCells: a simple R package designed to explore the intricate landscape of phenotypic data within single-cell studies. Normally, we are interested in visualizing and measuring if the differences in the proportion of number of cells across various covariates is significant or biologically relevant. As an example, one of the most common questions is the proportion of different cell types across conditions in our experiment, or the cluster composition before and after treatment (e.g.: difference in cell type proportions between wild type and mutant). LotOfCells helps with the interpretation and visualization of meta-data of these recurrent scenarios, including the test of proportion changes across multiple ordered stages. Additionally, it computes a symmetric divergence score to measure global deregulation of cell proportions due to a condition.Code repositoryR package, manual and relevant examples can be accessed on the GitHub repository:https://github.com/OscarGVelasco/LotOfCells
Bispecific GD2 x B7-H3 Antibody Improves Tumor Targeting and Reduces Toxicity while Maintaining Efficacy for Neuroblastoma
Authors: Erbe Amy K. , Feils Arika S. , Hampton Alina , Rosenkrans Zachary T , Felder Mildred , Wiwczar Jessica , Gerhardt Daniel J. , Bercher Mark , Wenke Belinda , Haertle Callie , Heck Mackenzie , VandenHeuvel Sabrina N. , Frankel Lizzie , Nielsen Megan , Spiegelman Dan , Tsarovsky Noah , Zaborek Jen , Rakhmilevich Alexander L. , Hank Jacquelyn A. , Aluicio-Sarduy Eduardo , Engle Jonathan W. , Davis Jonathan H. , Glaser Bryan , Subbotin Vladimir , Green Roland , Hernandez Reinier , Hammer Bonnie , Sondel Paul M. 
Published: May 2024

AbstractThe current treatment for neuroblastoma involves an immunotherapy regimen that includes a monoclonal antibody that recognizes disialoganglioside (GD2), expressed at high levels on neuroblastoma. GD2 is not present on most normal tissues but is expressed on nerves. Thus, anti-GD2 treatment causes substantial, dose-limiting, neuropathic pain. B7-H3 is overexpressed on multiple tumor types, including neuroblastoma, with minimal normal cell expression and is absent on nerves. We designed a bispecific antibody (bsAb) that requires simultaneous binding of these two tumor antigens to achieve tight-binding of tumor cells. Our preclinical research shows that when compared to an anti-GD2 monospecific antibody, the GD2xB7-H3 bsAb has improved tumor specificity with similar efficacy and reduced toxicity. Since this bsAb does not bind to nerves, it may be possible to administer increased or additional doses beyond the tolerable dose of monospecific anti-GD2 antibodies, which could improve therapeutic efficacy and quality of life for patients with neuroblastoma.
Structure-activity relationships and crucial mechanisms of the coumarin family as germination inhibitors
Authors: Fukuda Kazuma , Hyakutake Sota , Oishi Taiga , Yoshida Michinari , Koga Mizuho , Egami Chisato , Matsura Hyuga , Ito Ryusei , Tsukahara Kosei , Noda Mitsuki , Yoshida Takako , Ryuda Noriko , Nagano Yukio , Matsutaka Kazuhide 
Published: May 2024

AbstractMembers of the coumarin family, including coumarin and its derivatives, are molecules produced by various higher plants, such as cherry trees, and are noted for their diverse physiological activities. Notably, these compounds serve as germination inhibitors, which is considered their primary role. However, the structural basis underpinning the germination-inhibitory effects of the coumarin family is not well understood. Our research investigated the structure-activity relationships using coumarin analogs and revealed that the benzene ring and ester bond within the coumarin skeleton play a crucial role in germination inhibition. We also identified a correlation between the topological polar surface area (TPSA) and the inhibitory effects on germination. Furthermore, while the physiological effects of coumarin on seeds prior to germination have been reported variably, the mechanisms of germination inhibition remain largely unknown. Using RNA-Seq analysis, we have discovered a novel mechanism that is pivotal for germination inhibition, where coumarin suppresses the expression of genes associated with cellulose fiber reassembly. This study holds significant importance in understanding how the coumarin family contributes to plant competition in nature and promises future contributions to the agricultural field through the development of novel growth regulation methods.
Community Collaboration in Public Health Genetic Literacy: Co-Designing Educational Resources for Equitable Genomics Research and Practice
Authors: Salunke Juhi , Byfield Grace , Powell Sabrina N. , Torres Daniel , Leon-Lozano Grace , Jackson Jahnelle , Orphanides Andreas K. , Shaw Jonathan , Owens Thomas , Berg Jonathan S. , Branch Elizabeth , Caro Lennin , Giric Stefanija , O’Daniel Julianne M. , Powell Bradford C. , Ray Ken , Roberts Megan C. , Robinson Carla , Schilling Samantha , Shaw Nicole , Song Erin , Waltz Margaret , Foreman Ann Katherine M. , Foss Kimberly , Milko Laura V. 
Published: May 2024

AbstractIntroductionUnequal representation in genetic and genomic research is due to various factors including historically inequitable and unjust institutional research practices, potential mistrust of biomedical research among underrepresented populations, and lack of access to or awareness of research opportunities. Facilitating sustainable dialogue between diverse communities and genetic researchers can cultivate trusting, bidirectional relationships, potentially encouraging greater participation in research. Herein, we describe the co-creation of public health educational materials and dissemination plans.MethodsWe describe co-creation by genetics clinicians, researchers, and community members of Genetics and Genomics Educational modules. These modules are aimed at enhancing genetic literacy with a goal to facilitate informed decision-making regarding genetic research and health services. We used Designing for Dissemination and Sustainability, which is grounded in Dissemination and Implementation science, and the Fit to Context process framework to guide the process. This approach ensures the public health context and diverse audience for the modules are considered throughout their development. Additionally, it ensures that broader goals such as dissemination, equity, and sustainability are integrated from the outset, fostering long-term impact and effectiveness.ConclusionThis article offers an evidence-based template for adoption or adaptation by other community-engaged groups, aimed at bolstering equity and sustainability in the development of health care interventions, with an emphasis on accessible public health literacy. The co-creation of both materials and dissemination plans between researchers and community members may improve the cultural appropriateness and relevance of public health genetics campaigns. Ongoing research is needed to assess the impact on receptiveness and participation.
Repetitive mild closed-head injury induced synapse loss and increased local BOLD-fMRI signal homogeneity
Authors: Markicevic Marija , Mandino Francesca , Toyonaga Takuya , Cai Zhengxin , Fesharaki-Zadeh Arman , Shen Xilin , Strittmatter Stephen M. , Lake Evelyn 
Published: May 2024

AbstractRepeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries, requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild closed-head injury (rmTBI) and chronic variable stress (CVS) mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [18F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespreaddecreasesin synaptic density coupled with an increasein local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions withhighersynapse density showed agreater increasein fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.
Cdbgtricks: Strategies to update a compacted de Bruijn graph
Authors: Hannoush Khodor , Marchet Camille , Peterlongo Pierre 
Published: May 2024

AbstractWe proposeCdbgtricks, a new method for updating a compacted de Bruijn graph when adding novel sequences, such as full genomes. Our method indexes the graph, enabling to identify in constant time the location (unitig and offset) of anyk-mer. The update operation that we propose also updates the index. Our results show thatCdbgtricksis faster thanBifrostandGGCAT. We benefit from the index of the graph to provide new functionalities, such as reporting the subgraph that shares a desired percentage ofk-mers with a query sequence with the ability to query a set of reads. The open-sourceCdbgtrickssoftware is available athttps://github.com/khodor14/Cdbgtricks.
Comprehensive multi-site profiling of the malignant pleural mesothelioma micro-environment identifies candidate molecular determinants of histopathologic type
Authors: Severson David T , Freyaldenhoven Samuel , Wadowski Benjamin , Hughes Travis , Hung Yin P , Chirieac Lucien , Jensen Roderick V , Richards William G , Sadek Ahmed A , Gustafson Corinne E , Vermilya Kimberly , Inoccenti Simona , Korle Stephani , Barlow Julianne S , Couger Matthew B , Anderson Jamie , Meyerovitz Jason , Wang Vivian , Dao Mary N. , Shalek Alex K. , De Rienzo Assunta , Bueno Raphael 
Published: May 2024

ABSTRACTPleural mesothelioma (PM) comprises sarcomatoid, epithelioid and biphasic histologic subtypes. Bulk PM RNA-sequencing identifies a histology-associated molecular gradient with features of epithelial-mesenchymal (EM) transition but cannot parse malignant, stromal, and immune tumor components. The mechanisms driving PM malignant cell phenotype and associated histology is not well-characterized. Here, we use single-cell RNA-sequencing (scRNA-seq) paired with exome, bulk RNA-sequencing, and histologic analysis of adjacent samples to characterize malignant cell EM state, parse the tumor microenvironment (TME), and identify candidate drivers of PM cell fate. We observe EM variation in malignant cells analogous to bulk samples. We characterize epithelioid and sarcomatoid malignant cell programs and identify a new uncommitted malignant cell EM phenotype enriched in biphasic histology samples. Using inferred CNVs we observe that single individual PM clones consist of cells exhibiting all three EM cell states. We find that distinct non-malignant microenvironments associated with tumors consisting of mostly cells in each state, and identifyWNTinhibition,GAS6-AXL, andHBEGF-EGFRsignaling as pathways associated with distinct EM cell states. These findings provide deeper insight into the molecular drivers of PM malignant cells and identify non-malignant cell signals as potential EMT and growth drivers in PM.
GRanges: A Rust Library for Genomic Range Data
Authors: Buffalo Vince 
Published: May 2024

AbstractMotivationThe Rust programming language is a fast, memory-safe language that is increasingly used in computational genomics and bioinformatics software development. However, it can have a steep learning curve, which can make writing specialized, high performance bioinformatics software difficult.ResultsGRanges is a Rust library that provides an easy-to-use and expressive way to load genomic range data into memory, compute and process overlapping ranges, and summarize data in a tidy way. The GRanges library outperforms established tools like plyranges and bedtools.AvailabilityThe GRanges library is available athttps://github.com/vsbuffalo/grangesandhttps://crates.io/crates/granges.