bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracing the genetic diversity of the bread wheat D genome
Authors: Wang Zihao , Wang Wenxi , He Yachao , Xie Xiaoming , Yang Zhengzhao , Zhang Xiaoyu , Niu Jianxia , Peng Huiru , Yao Yingyin , Xie Chaojie , Xin Mingming , Hu Zhaorong , Sun Qixin , Ni Zhongfu , Guo Weilong 
Published: August 2024

AbstractBread wheat (Triticum aestivum) became a globally dominant crop after incorporating the D genome from donor speciesAegilops tauschii, while evolutionary history shaping the D genome during this process remains elusive. Here, we proposed a renewed evolutionary model linkingAe. tauschiiand hexaploid wheat D genome, based on an ancestral haplotype map covering a total of 762Ae. tauschiiand hexaploid wheat accessions. We dissected the evolutionary process ofAe. tauschiilineages and clarified L3 as the most ancient lineage. A few independent intermediate accessions were reported, demonstrating the low-frequent inter-sublineage geneflow enriched the diversity ofAe. tauschii. We discovered that the D genome of hexaploid wheat inherited from a unified ancestral template, but with a mosaic composition that is highly mixed by threeAe. tauschiiL2 sublineages located in the Caspian coastal region, suggesting the early agricultural activities facilitate the innovation of D genome compositions that finalized the success of hexaploidization. We further found that the majority (65.6%) of polymorphisms were attributed to novel mutations absent during the spreading of bread wheat, and also identified largeAe. tauschiiintrogressions from wildAegilopslineages, expanding the diversity of wheat D genome and introducing beneficial alleles. This work decoded the mystery of the wheat hexaploidization process and the evolutionary significance of the multi-layered origins of the genetic diversity of the bread wheat D genome.
Climate drives geographic variation in individualPeromyscus leucopusimmunity against zoonotic disease
Authors: Assis Vania R. , McCain Kailey , Munds Rachel A. , Brehm Allison M. , Orrock John L. , Martin Lynn B. 
Published: August 2024

AbstractGeographic variation in host immunity could have major influences on disease dynamics, including zoonotic forms that affect humans. Such variation in immunity could be driven by variation in climate, either directly or, more likely, indirectly via resource availability. We compared the immune gene expression of wildPeromyscus leucopusmice, the primary reservoir for the bacterium that causes Lyme disease,Borrelia burgdorferi, among eight sites spanning 1,400 km of the northeastern United States. We discovered that climate conditions at sites strongly predicted immunity to the most common zoonotic pathogen in the U.S.: mice from warmer, wetter sites were more prepared to resistB. burgdorferiinfections. Our results reveal a novel pathway by which climate change could affect pathogen spillover or zoonotic epidemics generally.
Infection characteristics amongSerratia marcescenscapsule lineages
Authors: Anderson Mark T. , Himpsl Stephanie D. , Kingsley Leandra G. , Smith Sara N. , Bachman Michael A. , Mobley Harry L. T. 
Published: August 2024

ABSTRACTSerratia marcescensis a healthcare-associated pathogen that causes bloodstream infections, pneumonia, and urinary tract infections. The capsule polysaccharide ofS. marcescensis a critical fitness determinant during infection and recent work established the relationship between capsule locus (KL) genetic sequences within the species. Strains belonging to KL1 and KL2 capsule clades produce sialylated polysaccharides and represent the largest subpopulation of isolates from clinical origin while theS. marcescenstype strain and other environmental isolates were classified as KL5. In this work, the contribution of these and other capsules to pathogenesis in multiple infection models was determined. Using a murine tail vein injection model of bacteremia, clinical strains demonstrated capsule-dependent colonization of spleen, liver, and kidney following inoculation. The KL5 strain, in contrast, exhibited no loss of survival in this model when capsule genes were deleted. Furthermore, the wild-type KL5 strain was cleared more rapidly from both the spleen and liver compared to a KL1 strain. Similar results were observed in a bacteremic pneumonia model in that all tested strains of clinical origin demonstrated a requirement for capsule in both the primary lung infection site and for bloodstream dissemination to other organs. Finally, strains from each KL clade were tested for the role of capsule in internalization by bone marrow-derived macrophages. Only the sialylated KL1 and KL2 clade strains, representing the majority of clinical isolates, exhibited capsule-dependent inhibition of internalization, suggesting that capsule-mediated resistance to macrophage phagocytosis may enhance survival and antibacterial defenses during infection.IMPORTANCEBacterial bloodstream infections result from evasion of the host innate immune system and stable colonization following an initial inoculation event from either an internal or external source. Capsule polysaccharides play a protective role forSerratia marcescensduring bacteremia but there is abundant genetic diversity at the capsule-encoding locus within the species. This study compares the infection characteristics ofS. marcescensisolates belonging to five different capsule types and defines the contributions to infection fitness for each type. By characterizing the differences in capsule dependence and infection potential betweenS. marcescensstrains, efforts to combat these life-threatening infections can be focused toward identifying strategies that target the most critical genetic lineages of this important opportunistic pathogen.
Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks
Authors: Mojumdar Aditya , Granger Courtney , Cobb Jennifer A. 
Published: August 2024

SUMMARYDNA double-strand breaks (DSBs) are highly detrimental to cells, as improper repair can result in inheritable genetic rearrangements or cell death. The role of RNA:DNA hybrids (RDHs) in DSB repair remains poorly understood, but their transient accumulation and subsequent resolution are crucial for accurate repair. The absence of the end-joining factor Nej1 at DSBs significantly reduced RDH levels, which was linked to increased activity of the Dna2 nuclease. Dna2 limits the accumulation of hybrids at DSBs, with levels rising in the presence of a nuclease-dead Dna2 andRNH201deletion. Dna2 has a heightened preference for resolving RDHs with 5’ RNA overhangs compared to duplex substrates with 5’ DNA overhangs. This selective resolution by Dna2 helps restrict hybrid accumulation at DSBs and promotes resection, a function not shared by Exo1. This study underscores the multifunctional roles of canonical repair factors in ensuring efficient homology-directed repair.Graphical Abstract
The physical chemistry of interphase loop extrusion
Authors: Tortora Maxime M.C. , Fudenberg Geoffrey 
Published: August 2024

AbstractLoop extrusion constitutes a universal mechanism of genome organization, whereby structural maintenance of chromosomes (SMC) protein complexes load onto the chromatin fiber and generate DNA loops of increasingly-larger sizes until their eventual release. In mammalian interphase cells, loop extrusion is mediated by the cohesin complex, which is dynamically regulated by the interchange of multiple accessory proteins. Although these regulators bind the core cohesin complex only transiently, their disruption can dramatically alter cohesin dynamics, gene expression, chromosome morphology and contact patterns. Still, a theory of how cohesin regulators and their molecular interplay with the core complex modulate genome folding remains at large. Here we derive a model of cohesin loop extrusion from first principles, based onin vivomeasurements of the abundance and dynamics of cohesin regulators. We systematically evaluate potential chemical reaction networks that describe the association of cohesin with its regulators and with the chromatin fiber. Remarkably, experimental observations are consistent with only a single biochemical reaction cycle, which results in a unique minimal model that may be fully parameterized by quantitative protein measurements. We demonstrate how distinct roles for cohesin regulators emerge simply from the structure of the reaction network, and how their dynamic exchange can regulate loop extrusion kinetics over time-scales that far exceed their own chromatin residence times. By embedding our cohesin biochemical reaction network within biophysical chromatin simulations, we evidence how variations in regulatory protein abundance can alter chromatin architecture across multiple length- and time-scales. Predictions from our model are corroborated by biophysical and biochemical assays, optical microscopy observations, and Hi-C conformation capture techniques. More broadly, our theoretical and numerical framework bridges the gap betweenin vitroobservations of extrusion motor dynamics at the molecular scale and their structural consequences at the genome-wide level.
Oxytocin and vasopressin 1a receptor alterations in the superior temporal sulcus and hypothalamus in schizophrenia
Authors: Snowden Ariel W. , Schwartz Sarah E. , Smith Aaron L. , Goodman Mark M. , Freeman Sara M. 
Published: August 2024

AbstractSchizophrenia is a chronic, severe psychiatric condition characterized in part by social impairments. As social cognitive functioning is a major predictor of successful life outcomes in schizophrenia, there is a critical need to determine the neurobiological basis of social impairments in schizophrenia. The current study used receptor autoradiography to examine vasopressin 1a (AVPR1a) and oxytocin receptor (OXTR) densities in the postmortem brain tissue of individuals who had schizophrenia (N=23) relative to unaffected matched controls (N=18). We analyzed the superior temporal sulcus, a brain region that is highly implicated in social perception and shows aberrant functioning in schizophrenia. GreaterAVPR1a binding densities were observed relative to OXTR. Increases in AVPR1a densities with advanced age in females who had schizophrenia were also observed. This finding in the superior temporal sulcus may explain a shift in positive symptom severity(paranoia/suspiciousness) that has been observed with advanced age in women with schizophrenia. In addition, increased OXTR and a trend toward increased AVPR1a densities were observed in the hypothalamus in schizophrenia. The hypothalamus synthesizes oxytocin and vasopressin in the brain and is the initiator of the hypothalamic-pituitary-adrenal axis, which facilitates the fight or flight stress response. These receptor systems may be upregulated to compensate for possibly low exogenous oxytocin and vasopressin release from the hypothalamus in schizophrenia. Our findings show age- and sex-dependent effects on nonapeptide receptor binding that shed light onto the neurobiology of the social brain in the progression of schizophrenia.
Clostridium scindens: an endocrine keystone species in the mammalian gut
Authors: Daniel Steven L. , Ridlon Jason M. 
Published: August 2024

AbstractClostridium scindensis a keystone human gut microbial taxonomic group that, while low in abundance, has a disproportionate effect on bile acid and steroid metabolism in the mammalian gut. Numerous studies indicate that the two most studied strains ofC. scindens(i.e., ATCC 35704 and VPI 12708) are important for a myriad of physiological processes in the host. We focus on both historical and current microbiological and molecular biology work on the Hylemon-Björkhem pathway and the steroid-17,20-desmolase pathway that were first discovered inC. scindens.Our most recent analysis now calls into question whether strains currently defined asC. scindensrepresent two separate taxonomic groups. Future directions include developing genetic tools to further explore the physiological role bile acid and steroid metabolism by strains ofC. scindens, and the causal role of these pathways in host physiology and disease.
Recontextualizing Eukaryogenesis via Computational Analysis of RNA Processing in 16,449 Archaeal Genomes
Authors: Kannan Srinivasan 
Published: August 2024

AbstractThe analysis of proteins related to RNA processing reveals intriguing aspects of the evolutionary transition from archaea to eukaryotes. Eukaryagenesis is the process in which the first eukaryote came into existence, with multiple hypotheses on the order of events. These hypothesis often focus on the mitochondria and cell skeletal structure, without much discussion on eukaryotic signature proteins(ESP). ESP is integral in increasing the longevity of RNA and for the increase in the variety of proteins able to be produced which ultimately increases fitness of eukaryotes. 16,449 genomes and 10 proteins were acquired and BLAST was run for each superclass for each protein. BLAST scores were compared between superclasses and analyzed. Results for proteins such as Prp9, Rex3, Histone H2A, H2B, and Histone 3 indicate that there is no substantial difference between BLAST results implying a transitional state consistent withE3model. The results for Smd3 and Ceg1 highlight that a group of Asgardarchaeota and Diaforarchaearchaea were different to other types of archaea. These groups likely underwent similar environmental pressures giving organisms with these genes higher fitness. These early genes evolved into their eukaryotic versions, while other genes like Histone 4, Abd1, and Lsm2 may have had ancestral prototypes present across archaea. Gene prototypes likely served different purposes, but the presence of such prototypes imply that evolution of the nucleus was likely independent from the presence of the mitochondria.
Heterologous Surface Display Reveals Conserved Complement Inhibition and Functional Diversification ofBorrelia burgdorferiElp Proteins
Authors: Hill Nathan , Matulina Lara M. , MacIntyre Cameron , Hassani M. Amine , Thomas Sheila , Luban Matteo , Ward Isabelle , Abdalla Amina , Leong John M. , Garcia Brandon L. , Lemieux Jacob E. 
Published: August 2024

AbstractLyme disease is a tick-borne spirochetosis with diverse clinical manifestations. Phenotypic variation amongBorrelia burgdorferistrains correlates with variable manifestations of Lyme disease in humans; this diversity is attributed in part to variation in surface-exposed lipoproteins, which are targets of the human antibody response and contribute to tissue adhesion, immune evasion, and other host interactions. ManyB. burgdorferilipoproteins are encoded as multi-copy gene families including the OspE/F- like leader peptide (Elp) protein family. To characterize Elp allelic variants, we adapted thePseudomonas syringaeice nucleation protein (INP) system to presentB. burgdorferilipoproteins on the surface ofEscherichia coli. We identified interactions with classical complement proteins and mapped binding regions in theE. colisystem. We validated interactions using recombinant proteins andB. burgdorferisurface display. By assessing potential interactions with extracellular matrix components, we identified a novel interaction between Elp proteins and perlecan, a component of mammalian basement membranes, and revealed the bifunctional nature of Elps. Our findings reveal that Elps have undergone functional diversification while maintaining classical complement inhibition mediated by potent and conserved C1s binding and demonstrate thatE. colisurface display offers an efficient, cost-effective, and relatively high throughput approach to characterizeB. burgdorferilipoproteins.
Deep mutational scanning of EccD3reveals the molecular basis of its essentiality in the mycobacterium ESX secretion system
Authors: Trinidad Donovan D. , Macdonald Christian B. , Rosenberg Oren S. , Fraser James S. , Coyote-Maestas Willow 
Published: August 2024

AbstractTuberculosis remains the deadliest infectious disease in the world and requires novel therapeutic targets. The ESX-3 secretion system, which is essential for iron and zinc homeostasis and thusM. tuberculosissurvival, is a promising target. In this study, we perform a deep mutational scan on the ESX-3 core protein EccD3in the model organismM. smegmatis. We systematically investigated the functional roles of 145 residues across the soluble ubiquitin-like domain, the conformationally distinct flexible linker, and selected transmembrane helices of EccD3. Our data combined with structural comparisons to ESX-5 complexes support a model where EccD3stabilizes the complex, with the hinge motif within the linker being particularly sensitive to disruption. Our study is the first deep mutational scan in mycobacteria, which could help guide drug development toward novel treatment of tuberculosis. This study underscores the importance of context-specific mutational analyses for discovering essential protein interactions within mycobacterial systems.
Patient mutations in DRP1 perturb synaptic maturation of cortical neurons
Authors: Baum TB , Bodnya C , Costanzo J , Gama V 
Published: August 2024

AbstractWith the advent of exome sequencing, a growing number of children are being identified withde novoloss of function mutations in the dynamin 1 like (DNM1L)gene encoding the large GTPase essential for mitochondrial fission, dynamin-related protein 1 (DRP1); these mutations result in severe neurodevelopmental phenotypes, such as developmental delay, optic atrophy, and epileptic encephalopathies. Though it is established that mitochondrial fission is an essential precursor to the rapidly changing metabolic needs of the developing cortex, it is not understood how identified mutations in different domains of DRP1 uniquely disrupt cortical development and synaptic maturation. We leveraged the power of induced pluripotent stem cells (iPSCs) harboring DRP1 mutations in either the GTPase or stalk domains to model early stages of cortical developmentin vitro. High-resolution time-lapse imaging of axonal transport in mutant DRP1 cortical neurons reveals mutation-specific changes in mitochondrial motility of severely hyperfused mitochondrial structures. Transcriptional profiling of mutant DRP1 cortical neurons during maturation also implicates mutation dependent alterations in synaptic development and calcium regulation gene expression. Disruptions in calcium dynamics were confirmed using live functional recordings of 100 DIV (days in vitro) mutant DRP1 cortical neurons. These findings and deficits in pre- and post-synaptic marker colocalization using super resolution microscopy, strongly suggest that altered mitochondrial morphology of DRP1 mutant neurons leads to pathogenic dysregulation of synaptic development and activity.
Methanol chemoreceptor MtpA- and flagellin protein FliC-dependent methylotaxis determines the spaciotemporal colonization of PPFM in the phyllosphere
Authors: Katayama Shiori , Shiraishi Kosuke , Kaji Kanae , Kawabata Kazuya , Tamura Naoki , Tani Akio , Yurimoto Hiroya , Sakai Yasuyoshi 
Published: August 2024

AbstractPink-pigmented facultative methylotrophs (PPFMs) capable of growth on methanol are dominant and versatile phyllosphere bacteria that provide positive effects on plant growth through symbiosis. However, the spatiotemporal behavior of PPFMs on plant surfaces and its molecular basis are unknown. Here we show thatMethylobacteriumsp. strain OR01 inoculated onto red perilla seeds colonized across the entire plant surface in the phyllosphere concomitant with the plant growth. FliC flagellin proteins required for motility were necessary for distributed colonization on plant leaves, but not for colonization at the leaf periphery. Methanol-sensing chemoreceptor MtpA-dependent chemotaxis (methylotaxis; chemotaxis toward methanol) facilitated the bacterial movement from the peripheral to the inner part of leaves and further entry into the stomatal cavity, indicating that methanol functions as a volatile messenger attracting PPFMs to particular leaf locations possibly to support with photosynthesis and to afford protection from pathogenic invasion.
Factors affecting user intention to use social commerce continuously from a habit perspective
Authors: Handarkho Yonathan Dri 
Published: August 2024

PurposeThis study proposes a theoretical model to explain user intention to continue engaging with Social Commerce (SC) from a habit perspective. The research uses social impact theory, user personal traits, and SC quality to explain how user habits are formed in SC, leading to continued usage.Design/methodology/approachThe study collected data from 868 Indonesian respondents using a cross-sectional field design. SEM analysis confirmed the proposed theoretical model, calculating direct, indirect, and moderating effects.FindingsThe results showed that the social aspect is the dominant construct influencing users’ habit of using SC. Further, the outcome indicates that habit significantly predicts Continuity usage. Profoundly, subjective norms are the most significant predictors of habit, followed by self-efficacy, content quality, and herd behavior. Meanwhile, Trust and Social Support only indirectly affect Habit through self-efficacy and content quality, respectively, as mediators. Additionally, the moderating effect analysis revealed that age and gender play a role in habit formation.Originality/valueThis study specifically explores the factors affecting the development of habits in SC usage, leading to repeated behaviors. This area has not been thoroughly examined in previous research. Therefore, this study seeks to address this gap by investigating how habits are formed through social interactions on SC platforms. Understanding habit formation provides an alternative way of comprehending the continued use of SC, as it is considered a significant factor that leads to continued intention.
The macroeconomic overview of the alcohol industry: a perspective from the emerging market of Asia
Authors: Dsouza Sarah Lucia , Chopra Rita Rani , Nayak Raghavendra 
Published: August 2024

Purpose
This study aims to analyze the relationship between the alcohol brewing industry and the macroeconomic variables of the emerging market of Asia.

Design/methodology/approach
The study uses secondary data for the period of 32 years and applies the autoregressive distributed lag-error correction method (ARDL-ECM) approach to understand short- and long-run dynamics in the alcohol industry by considering macroeconomic variables.

Findings
The findings of the study confirm the existence of a long-run relationship between the alcohol brewing industry and the macroeconomic variables considered for this study.

Research limitations/implications
The authors present a few limitations of this study. First, this study uses secondary data originating from one of the emerging markets of Asia. Second, the study is solely conducted from an economic perspective rather than from a social or health perspective. Finally, the study considers the data originating from the organized sector of the alcohol industry of India.

Practical implications
The study will be helpful to the researchers in guiding the future course of research in the area of the alcohol industry. This study can be helpful to the policymakers in framing the National Alcohol and taxation Policy. This study also helps both the producers and exporters to strategize sustainable production and trade of alcoholic beverages.

Originality/value
To the best of the authors’ knowledge, this study is the first of its kind to analyze the alcohol industry from the macroeconomic perspective through the ARDL-ECM approach.