bluuebunny/crossref_metadata_2025_split huggingface dataset:
PfCAP-H is essential for assembly of condensin I complex and karyokinesis during asexual proliferation ofPlasmodium falciparum
Authors: Gurung Pratima , McGee James P. , Dvorin Jeffrey D. 
Published: March 2024

AbstractCondensin I is a pentameric complex that regulates the mitotic chromosome assembly in eukaryotes. The kleisin subunit CAP-H of the condensin I complex acts as a linchpin to maintain the structural integrity and loading of this complex on mitotic chromosomes. This complex is present in all eukaryotes and has recently been identified inPlasmodium spp. However, how this complex is assembled and whether the kleisin subunit is critical for this complex in these parasites is yet to be explored. To examine the role of PfCAP-H during cell division within erythrocytes, we generated an inducible PfCAP-H knockout parasite. We find that PfCAP-H is dynamically expressed during mitosis with the peak expression at the metaphase plate. PfCAP-H interacts with PfCAP-G and is a non-SMC member of the condensin I complex. Notably, the absence of PfCAP-H does not alter the expression of PfCAP-G but affects its localization at the mitotic chromosomes. While mitotic spindle assembly is intact in PfCAP-H deficient parasites, duplicated centrosomes remain clustered over the mass of unsegmented nuclei with failed karyokinesis. This failure leads to the formation of an abnormal nuclear mass, while cytokinesis occurs normally. Altogether, our data suggest that PfCAP-H plays a crucial role in maintaining the structural integrity of the condensin I complex on the mitotic chromosomes and is essential for the asexual development of malarial parasites.ImportanceMitosis is a fundamental process forPlasmodiumparasites, which plays a vital role in their survival within two distinct hosts - human andAnophelesmosquitoes. Despite its great significance, our comprehension of mitosis and its regulation remains limited. In eukaryotes, mitosis is regulated by one of the pivotal complexes known as condensin complexes. The condensin complexes are responsible for chromosome condensation, ensuring the faithful distribution of genetic material to daughter cells. While condensin complexes have recently been identified inPlasmodium spp, our understanding of how this complex is assembled and their precise functions during the blood stage development ofPlasmodium falciparumremains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development ofP. falciparum. Our findings reveal that PfCAP-H is essential and plays a pivotal role in upholding the structure of condensin I and facilitating karyokinesis.
Prenatal Exposure to Environmentally Relevant Low Dosage Dibutyl Phthalate Reduces Placental Efficiency in CD-1 Mice
Authors: Pontifex Tasha , Yang Xinran , Tracy Ayna , Burns Kimberlie , Craig Zelieann , Zhou Chi 
Published: March 2024

AbstractIntroductionDibutyl phthalate (DBP), a phthalate congener, is widely utilized in consumer products and medication coatings. Women of reproductive age have a significant burden of DBP exposure through consumer products, occupational exposure, and medication. Prenatal DBP exposure is associated with adverse pregnancy/fetal outcomes and cardiovascular diseases in the offspring. However, the role of fetal sex and the general mechanisms underlying DBP exposure-associated adverse pregnancy outcomes are unclear. Wehypothesizethat prenatal DBP exposure at an environmentally relevant low dosage adversely affects fetal-placental development and function during pregnancy in a fetal sex-specific manner.MethodsAdult female CD-1 mice (8-10wks) were orally treated with vehicle (control) or with environmentally relevant low DBP dosages at 0.1 μg/kg/day (refer as DBP0.1) daily from 30 days before pregnancy through gestational day (GD) 18.5. Dam body mass composition was measured non-invasively using the echo-magnetic resonance imaging system. Lipid disposition in fetal labyrinth and maternal decidual area of placentas was examined using Oil Red O staining.ResultsDBP0.1 exposure did not significantly affect the body weight and adiposity of non-pregnant adult female mice nor the maternal weight gain pattern and adiposity during pregnancy in adult female mice. DBP0.1 exposure does not affect fetal weight but significantly increased the placental weight at GD18.5 (indicative of decreased placental efficiency) in a fetal sex-specific manner. We further observed that DBP0.1 significantly decreased lipid disposition in fetal labyrinth of female, but not male placentas, while it did not affect lipid disposition in maternal decidual.ConclusionsPrenatal exposure to environmentally relevant low-dosage DBP adversely impacts the fetal-placental efficiency and lipid disposition in a fetal sex-specific manner.
Rare and Common Variants Associated with Alcohol Consumption Identify a Conserved Molecular Network
Authors: Leger Brittany S. , Meredith John J. , Ideker Trey , Sanchez-Roige Sandra , Palmer Abraham A. 
Published: March 2024

AbstractGenome-wide association studies (GWAS) have identified hundreds of common variants associated with alcohol consumption. In contrast, rare variants have only begun to be studied for their role in alcohol consumption. No studies have examined whether common and rare variants implicate the same genes and molecular networks. To address this knowledge gap, we used publicly available alcohol consumption GWAS summary statistics (GSCAN, N=666,978) and whole exome sequencing data (Genebass, N=393,099) to identify a set of common and rare variants for alcohol consumption. Gene-based analysis of each dataset have implicated 294 (common variants) and 35 (rare variants) genes, including ethanol metabolizing genesADH1BandADH1C, which were identified by both analyses, andANKRD12, GIGYF1, KIF21B, andSTK31, which were identified only by rare variant analysis, but have been associated with related psychiatric traits. We then used a network colocalization procedure to propagate the common and rare gene sets onto a shared molecular network, revealing significant overlap. The shared network identified gene families that function in alcohol metabolism, includingADH, ALDH, CYP, andUGT. 74 of the genes in the network were previously implicated in comorbid psychiatric or substance use disorders, but had not previously been identified for alcohol-related behaviors, includingEXOC2, EPM2A, CACNB3, andCACNG4. Differential gene expression analysis showed enrichment in the liver and several brain regions supporting the role of network genes in alcohol consumption. Thus, genes implicated by common and rare variants identify shared functions relevant to alcohol consumption, which also underlie psychiatric traits and substance use disorders that are comorbid with alcohol use.
Resistance Gene Association and Inference Network (ReGAIN): A Bioinformatics Pipeline for Assessing Probabilistic Co-Occurrence Between Resistance Genes in Bacterial Pathogens
Authors: Bring Horvath Elijah R. , Stein Mathew G. , Mulvey Matthew A. , Hernandez Edgar J. , Winter Jaclyn M. 
Published: March 2024

AbstractThe rampant rise of multidrug resistant (MDR) bacterial pathogens poses a severe health threat, necessitating innovative tools to unravel the complex genetic underpinnings of antimicrobial resistance. Despite significant strides in developing genomic tools for detecting resistance genes, a gap remains in analyzing organism-specific patterns of resistance gene co-occurrence. Addressing this deficiency, we developed the Resistance Gene Association and Inference Network (ReGAIN), a novel web-based and command line genomic platform that uses Bayesian network structure learning to identify and map resistance gene networks in bacterial pathogens. ReGAIN not only detects resistance genes using well- established methods, but also elucidates their complex interplay, critical for understanding MDR phenotypes. Focusing on ESKAPE pathogens, ReGAIN yielded a queryable database for investigating resistance gene co-occurrence, enriching resistome analyses, and providing new insights into the dynamics of antimicrobial resistance. Furthermore, the versatility of ReGAIN extends beyond antibiotic resistance genes to include assessment of co-occurrence patterns among heavy metal resistance and virulence determinants, providing a comprehensive overview of key gene relationships impacting both disease progression and treatment outcomes.Graphical Abstract
Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy
Authors: Yoon Joonho , Liu Zhenan , Alaba Mathew , Bruggeman Leslie A. , Janmey Paul A. , Arana Carlos A. , Ayenuyo Oluwatoyosi , Medeiros Isabela , Eddy Sean , Kretzler Matthias , Henderson Joel M. , Nair Viji , Naik Abhijit S. , Chang Audrey N. , Miller R. Tyler 
Published: March 2024

AbstractObjectivesTo understand the early stages if Alport nephropathy, we characterize the structural, functional, and biophysical properties of glomerular capillaries and podocytes inCol4α3-/-mice, analyze kidney cortex transcriptional profiles at three time points, and investigate the effects of the ER stress mitigation by TUDCA on these parameters. We use human FSGS associated genes to identify molecular pathways rescued by TUDCA.FindingsWe define a disease progression timeline inCol4α3-/-mice. Podocyte injury is evident by 3 months, with glomeruli reaching maximum deformability at 4 months, associated with 40% podocytes loss, followed by progressive capillary stiffening, increasing proteinuria, reduced renal function, inflammatory infiltrates, and fibrosis from months 4 to 7. RNA sequencing at 2, 4, and 7 months reveals increased cytokine and chemokine signaling, matrix and cell injury, and activation of the TNF pathway genes by 7 months, similar to NEPTUNE FSGS cohorts. These features are suppressed by TUDCA.ConclusionsWe define two phases ofCol4α3-/-nephropathy. The first is characterized by podocytopathy, increased glomerular capillary deformability and accelerated podocyte loss, and the second by increased capillary wall stiffening and renal inflammatory and profibrotic pathway activation. Disease suppression by TUDCA treatment identifies potential therapeutic targets for treating Alport and related nephropathies.
Digesting the data: Proper validation in ancient metagenomic studies is essential
Authors: Pach Aleksandra Laura , Lanigan Liam T , Niemann Jonas , Pedersen Mikkel Winther , Schroeder Hannes 
Published: March 2024

In a recent publication in this journal, Reynoso-García et al. [1] used shotgun sequencing to analyze human coprolites (paleofeces) from two pre-Columbian contexts in Puerto Rico to reconstruct the diet of the island’s Indigenous population before the arrival of Europeans. Based on the results, the team claim to have identified various edible New World plant species, including maize (Zea mays), sweet potato (Ipomoea batatas), chili pepper (Capsicum annuum), peanut (Arachis spp.), papaya (Carica papaya), and tomato (Solanum lycopersicum), as well as other cultivars such as cotton (Gossypium barbadense) and tobacco (Nicotiana sylvestris) [1]. Reynoso-García et al. [1] also claim to have identified edible fungi, includingUstilago spp., which according to the authors, further supports their findings and points to the consumption ofhuitlacocheor corn smut, a known delicacy in Mexico today that is believed to have originated in Aztec times [2].Shotgun DNA sequencing of archaeological samples, such as dental calculus or coprolites, provides a powerful tool to reconstruct ancient microbial communities and to study the evolution of the human microbiome [e.g. 3,4–6]. In some instances, shotgun sequencing results can also provide insights into the diet and subsistence strategies of past communities [e.g. 7,8]. However, identifying DNA from dietary sources in complex shotgun metagenomic datasets is far from straightforward. As has been discussed previously [9,10], and as we demonstrate below, one of the main challenges is the risk of false positives. Any potential dietary signals should, therefore, be carefully assessed. Unfortunately, we feel that Reynoso-García et al.’s study [1] falls short in that regard and we conclude that while it is entirely possible (and even likely, based on other evidence [e.g. 11,12]) that the Indigenous inhabitants of Puerto Rico subsisted on a diet that included some, or even all of the edible plant taxa the team identified, the DNA results they present do not, in and of themselves, support that claim.
Nosemosis negatively affects honeybee survival: experimental and meta-analytic evidence
Authors: Ostap-Chec M. , Cait J. , Scott R. W. , Arct A. , Moroń D. , Rapacz M. , Miler K. 
Published: March 2024

AbstractNosemosis, caused by microsporidian parasites of the genusNosema, is considered a significant health concern for insect pollinators, including the economically important honeybee (Apis mellifera). Despite its acknowledged importance, the impact of this disease on honeybee survivorship remains unclear. Here, a standard laboratory cage trial was used to compare mortality rates between healthy andNosema-infected honeybees. Additionally, a systematic review and meta-analysis of existing literature were conducted to explore how nosemosis contributes to increased mortality in honeybees tested under standard conditions. The review and meta-analysis included 50 studies that reported relevant experiments involving healthy andNosema-infected individuals. Studies lacking survivorship curves or information on potential moderators, such as spore inoculation dose, age of inoculated bees, or factors that may impact energy expenditure, were excluded. Both the experimental results and meta-analysis revealed a consistent, robust effect of infection, indicating a threefold increase in mortality among the infected group of honeybee workers (hazard ratio for infected individuals = 3.16 [1.97, 5.07] and 2.99 [2.36, 3.79] in the experiment and meta-analysis, respectively). However, the meta-analysis also indicated high heterogeneity in the effect magnitude, which was not explained by our moderators. Furthermore, there was a serious risk of bias within studies and potential publication bias across studies. The findings underscore knowledge gaps in the literature. It is stressed that laboratory cage trials should be viewed as an initial step in evaluating the impact ofNosemaon mortality and that complementary field and apiary studies are essential for identifying effective treatments to preserve honeybee populations.
Inferring fungal growth rates from optical density data
Authors: Hameed Tara , Motsi Natasha , Bignell Elaine , Tanaka Reiko J. 
Published: March 2024

AbstractQuantifying fungal growth underpins our ability to effectively treat severe fungal infections. Current methods quantify fungal growth rates from time-course morphology-specific data, such as hyphal length data. However, automated large-scale collection of such data lies beyond the scope of most clinical microbiology laboratories. In this paper, we propose a mathematical model of fungal growth to estimate morphology-specific growth rates from easy-to-collect, but indirect, optical density (OD600) data ofAspergillus fumigatusgrowth (filamentous fungus). Our method accounts for OD600being an indirect measure by explicitly including the relationship between the indirect OD600measurements and the calibrating true fungal growth in the model. Therefore, the method does not requirede novogeneration of calibration data. Our model outperformed reference models at fitting to and predicting OD600growth curves and overcame observed discrepancies between morphology-specific rates inferred from OD600versus directly measured data in reference models that did not include calibration.Author summaryQuantifying fungal growth is essential for antifungal drug discovery and monitoring antifungal resistance. As fungal growth is complex, with fungal morphology (shape) dynamically changing over time, previous studies have quantified fungal growth by estimating growth rates during specific fungal morphologies (morphology-specific growth rates) or by mathematically modelling fungal growth. However, collecting time-series data that captures the morphological information required for mathematical model fitting or estimating morphology-specific growth rates is prohibitively time consuming for large-scale drug testing in most microbiology laboratories. Alternatively, fungal growth can be quickly, although indirectly, quantified by measuring the optical density (OD) of a broth culture. However, changes in OD are not always reflective of true changes in fungal growth because OD is an indirect measure. This paper proposes a method to model fungal growth and estimate a morphology-specific growth rate from indirect OD600measurements of the major mould pathogen,Aspergillus fumigatus. We explicitly model the relationship between measured indirect OD600data and true fungal growth (calibration). The presented work serves as the much-needed foundation for estimating and comparing morphology-specific fungal growth rates in varying antifungal drug concentrations using only OD600data.
Improved prediction of site-rates from structure with averaging across homologs
Authors: Norn Christoffer , Oliveira Fábio , André Ingemar 
Published: March 2024

ABSTRACTVariation in mutation rates at sites in proteins can largely be understood by the constraint that proteins must fold into stable structures. Models that calculate site-specific rates based on protein structure and a thermodynamic stability model have shown a significant but modest ability to predict empirical site-specific rates calculated from sequence. Models that use detailed atomistic models of protein energetics do not outperform simpler approaches using packing density. We demonstrate that a fundamental reason for this is that empirical site-specific rates are the result of the average effect of many different microenvironments in a phylogeny. By analyzing the results of evolutionary dynamics simulations, we show how averaging site-specific rates across many extant protein structures can lead to correct recovery of site-rate prediction. This result is also demonstrated in natural protein sequences and experimental structures. Using predicted structures, we demonstrate that atomistic models can improve upon contact density metrics in predicting site-specific rates from a structure. The results give fundamental insights into the factors governing the distribution of site-specific rates in protein families.
Beta-hydroxybutyrate promotes basal insulin secretion while decreasing glucagon secretion in mouse and human islets
Authors: Banerjee Risha , Zhu Ying , Brownrigg George P. , Moravcova Renata , Rogalski Jason C. , Foster Leonard J. , Johnson James D. , Kolic Jelena 
Published: March 2024

ABSTRACTDietary carbohydrates raise blood glucose and limiting carbohydrate intake improves glycemia in patients with type 2 diabetes. Low carbohydrate intake (< 25 g) allows the body to utilize fat as its primary fuel. As a consequence of increased fatty acid oxidation, the liver produces ketones to serve as an alternative energy source. β-Hydroxybutyrate (βHB) is the most abundant ketone. While βHB has a wide range of functions outside of the pancreas, its direct effects on islet cell function remain understudied. We examined human islet secretory response to acute racemic βHB treatment and observed increased insulin secretion at low glucose concentrations (3 mM glucose). Because βHB is a chiral molecule, existing as both R and S forms, we further studied insulin and glucagon secretion following acute treatment with individual βHB enantiomers in human and C57BL6/J mouse islets. We found that acute treatment with R-βHB increased insulin secretion and decreased glucagon secretion at physiological glucose concentrations in both human and mouse islets. Proteomic analysis of human islets treated with R-βHB over 72 h showed altered abundance of proteins that may promote islet cell health and survival. Collectively, our data show that physiological concentrations of βHB influence hormone secretion and signaling within pancreatic islets.
Dynamic role of monocytes and meningeal macrophages in bacterial meningoencephalitis
Authors: Gres Vitka , Lohrmann Florens , Fuchs Vidmante , Bosch Lance Fredrick Pahutan , Lösslein Anne , Neuber Jana , Moghadam Zohreh Mansoori , Martins Tiago , Baasch Sebastian , Henschel Julia , Freudenhammer Mirjam , Prinz Marco , Kierdorf Katrin , Kolter Julia , Erny Daniel , Henneke Philipp 
Published: March 2024

1.AbstractMacrophages in the dura mater are substantial contributors to the immune defense of the brain, however, their site-specific origin and function in bacterial infections of the central nervous system are incompletely understood.In a natural model of streptococcal meningoencephalitis, where bacteria systemically spread via the bloodstream to the brain, we found streptococci to be largely restricted in the meninges. Further sporadic spread of bacteria to the underlying brain parenchyma caused a region-restricted microglia activation. Invasion of monocytes, but not granulocytes into brain and leptomeninges correlated to the disease severity. Inflammation in the dura was accompanied by activation and loss of dural macrophages, and by the rapid engraftment of highly activated monocytes. In addition, monocyte progenitors in the skull marrow underwent drastic changes and acquired a more immature phenotype likely due to infection-induced emergency myelopoiesis. Notably, while dural monocytes were derived from adjacent skull marrow in a CCR2-independent fashion, the high demand for dural monocytes in streptococcal meningoencephalitis required intact CCR2 signalling and involved the long bone marrow, indicating heterogeneity in monocyte recruitment. Furthermore, meningoencephalitis increased monocyte progeny from monocyte-dendritic cell progenitors compared to the homeostatic, granulocyte-monocyte progenitor-dominated origin. Accordingly, monocytes in the dura, recruited from distinct reservoirs depending on disease-inherent needs, are intertwined with the disease course and may thus offer opportunities for therapeutic interventions.
doubletrouble:an R/Bioconductor package for the identification, classification, and analysis of gene and genome duplications
Authors: Almeida-Silva Fabricio , Van de Peer Yves 
Published: March 2024

AbstractGene and genome duplications are major evolutionary forces that shape the diversity and complexity of life. However, different duplication modes have distinct impacts on gene function, expression, and regulation. Existing tools for identifying and classifying duplicated genes are either outdated or not user-friendly. Here, we presentdoubletrouble, an R/Bioconductor package that provides a comprehensive and robust framework for analyzing duplicated genes from genomic data.doubletroublecan detect and classify gene pairs as derived from six duplication modes (segmental, tandem, proximal, retrotransposon-derived, DNA transposon-derived, and dispersed duplications), calculate substitution rates, detect signatures of putative whole-genome duplication events, and visualize results as publication-ready figures. We applieddoubletroubleto classify the duplicated gene repertoire in 822 eukaryotic genomes, which we made available through a user-friendly web interface (available athttps://almeidasilvaf.github.io/doubletroubledb).doubletroubleis freely accessible from Bioconductor (https://bioconductor.org/packages/doubletrouble), and it provides a valuable resource to study the evolutionary consequences of gene and genome duplications.