bluuebunny/crossref_metadata_2025_split huggingface dataset:
PM2.5 from Automobile Exhaust Induces Apoptosis in Male Rat Germ Cellsviathe ROS-UPRmtSignaling Pathway
Authors: Wang Cao , Zhao Yingchi , Liu Bin , Luo Zhen , Zhou Guangxu , Mao Kaiyi 
Published: November 2024

AbstractObjectiveTo explore the underlying mechanism behind the fine particulate matter’s (PM2.5)-mediated regulation of reproductive function in male rats, and to determine the role of vitamins in this process.MethodsIn all, 32 male SD rats were randomized to a control cohort (normal saline), a Vit cohort (vitamin C at 100 mg/kg + vitamin E at 50 mg/kg), a PM2.5 cohort (PM2.5 10 mg/kg), and a PM2.5+Vit cohort (PM2.5 exposure + vitamin C at 100 mg/kg + vitamin E at 50 mg/kg), with eight rats in each cohort. After four weeks of exposure, mating experiments were carried out. Thereafter, rats were euthanized, and the testis and epididymis tissues were excised for hematoxylin-eosin (HE) staining and sperm quality analysis. Apoptosis of testis tissues was quantified via a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the testicular oxidative stress (OS)-, apoptosis- and mitochondrial unfolded protein response (UPRmt)-related essential protein expressions were measured via western blotting (WB).ResultsAfter PM2.5 exposure, the sperm count and motility decreased, while sperm abnormality and the apoptosis index increased. HE staining showed that the number of spermatogenic cells decreased. WB showed that the PM2.5 group had decreased expressions of superoxide dismutase (SOD), nuclear factor E2-related factor 2 (Nrf2), and B-cell lymphoma-2 (Bcl-2) (p< 0.05), increased expressions of malondialdehyde (MDA), Bcl-2 associated X protein (Bax), and Caspase3 (p< 0.05), and downregulated expressions of C/EBP homologous protein (CHOP), heat shock protein 60 (HSP60), and activating transcription factor 5 (ATF5) (p< 0.05). These were all reversed by vitamin intervention.ConclusionPM2.5 from automobile exhaust disrupts male reproductive function. A combination of vitamins may protect reproductive function via the reactive oxygen species (ROS)-UPRmtsignaling pathway.HighlightsPM2.5 from vehicle exhaust can cause apoptosis of male germ cells.PM2.5 from vehicle exhaust induces germ cell apoptosis through the ROS-UPRmt signaling pathway.Combined vitamin C and E can enhance UPRmt activity to alleviate the germ cell apoptosis caused by PM2.5 from vehicle exhaust.Graphical abstract
Cross-Kingdom Genomic Conservation of Human Sleep-Related Gene Orthologs: Phylogenomic Evidence fromChlamydomonas reinhardtii
Authors: Pandi-Perumal Seithikurippu R , Saravanan Konda Mani , Paul Sayan , Abraham George C. , Spence David Warren , Chidambaram Saravana Babu 
Published: November 2024

AbstractSleep is a widespread and evolutionarily conserved process observed in diverse organisms, from jellyfish to mammals, hinting at its origin as a life-supporting mechanism over 500 million years ago. Although its fundamental purpose and mechanisms remain unclear, the evolution and adaptive significance of sleep continue to be debated. This study explores the evolutionary origins of sleep using Chlamydomonas reinhardtii as a model organism, identifying 145 orthologs analogous to known sleep-related genes across species, highlighting the evolutionary conservation of sleep-regulating pathways. Additionally, discovering uncharacterized proteins with high sequence similarity and significant e-values suggests unexplored roles in sleep regulation, underscoring the potential of C. reinhardtii to reveal new insights into the molecular basis of sleep. This work provides a foundation for identifying previously unknown sleep-associated proteins, particularly within single-celled organisms, which may offer novel perspectives on the biological role of sleep. The study demonstrates that phylogenomic analysis of diverse model organisms can expand our understanding of the evolutionary trajectory of sleep and its fundamental function, paving the way for further research in sleep biology and its health implications. Overall, the fundamental functions of sleep observed in higher animal phyla originated from its primordial activities, demonstrating an evolutionary continuum wherein more specialized tasks were integrated with sleep’s essential restorative properties.
GenoSiS: A Biobank-Scale Genotype Similarity Search Architecture for Creating Dynamic Patient-Match Cohorts
Authors: Schneider Kristen , Chowdhury Murad , Tepper Mariano , Khan Jawad ,   Colorado Center for Personalized Medicine, Shortt Jonathan A. , Gignoux Chris , Layer Ryan 
Published: November 2024

ABSTRACTMany patients do not experience optimal benefits from medical advances because clinical research does not adequately represent them. While the diversity of biomedical research cohorts is improving, ensuring that individual patients are adequately represented remains challenging. We propose a new approach, GenoSiS, which leverages machine learning-based similarity search to dynamically find patient-matched cohorts across different populations quickly. These cohorts could serve as reference cohorts to improve a range of clinical analyses, including disease risk score calculations and dosage decisions. While GenoSiS focuses on finding genetic similarity within a biobank, our similarity search architecture can be extended to represent other medically relevant patient characteristics and search other biobanks.
AnnSQL: A Python SQL-based package for large-scale single-cell genomics analysis on a laptop
Authors: Pavan Kenny , Saunders Arpiar 
Published: November 2024

AbstractAs single-cell genomics technologies continue to accelerate biological discovery, software tools that use elegant syntax and minimal computational resources to analyze atlas-scale datasets are increasingly needed. Here we introduce AnnSQL, a Python package that constructs an AnnData-inspired database using the in-process DuckDb engine, enabling orders-of-magnitude performance enhancements for parsing single-cell genomics datasets with the ease of SQL. We highlight AnnSQL functionality and demonstrate transformative runtime improvements by comparing AnnData or AnnSQL operations on a 4.4 million cell single-nucleus RNA-seq dataset: AnnSQL-based operations were executed in minutes on a laptop for which equivalent AnnData operations largely failed (or were ∼700x slower) on a high-performance computing cluster. AnnSQL lowers computational barriers for large-scale single-cell/nucleus RNA-seq analysis on a personal computer, while demonstrating a promising computational infrastructure extendable for complete single-cell workflows across various genome-wide measurements.Availability and ImplementationAnnSQL is a pip installable package that can be accessed with usage documentation at:https://github.com/ArpiarSaundersLab/annsql.
Two ways to learn in visuomotor adaptation
Authors: Zhang Yifan , Jayaswal Sana , Schweighofer Nicolas 
Published: November 2024

AbstractPrevious research has demonstrated significant inter-individual variability in the recruitment of the fast-explicit and slow-implicit processes during motor adaptation. In addition, we previously identified qualitative individual differences in adaptation linked to the formation and updating of new memory processes. Here, we investigated quantitative and qualitative differences in visuomotor adaptation with a design incorporating repeated learning and forgetting blocks, allowing for precise estimation of individual learning and forgetting rates in fast-slow adaptation models. Participants engaged in a two-day online visuomotor adaptation task. They first adapted to a 30-degree perturbation to eight targets in three blocks separated by short blocks of no feedback trials. Approximately 24 hours later, they performed a no-feedback retention block and a relearning block. We clustered the participants into strong and weak learners based on adaptation levels at the end of day one and fitted a fast-slow system to the adaptation data. Strong learners exhibited a strong negative correlation between the estimated slow and fast processes, which predicted 24-hour retention and savings, respectively, supporting the engagement of a fast-slow system. The pronounced individual differences in the recruitment of the two processes were attributed to wide ranges of estimated learning rates. Conversely, weak learners exhibited a positive correlation between the two estimated processes, as well as retention but no savings, supporting the engagement of a single slow system. Finally, both during baseline and adaptation, reaction times were shorter for weak learners. Our findings thus revealed two distinct ways to learn in visuomotor adaptation and highlight the necessity of considering both quantitative and qualitative individual differences in studies of motor learning.
Island population demography: Breeding dynamics and drivers of Gotland’s iconic Golden Eagles
Authors: Singh Navinder J , Olofsson Robin , van der Meiden Aemilius Johannes , Lopez-Painado Andres , Månsson Johan 
Published: November 2024

AbstractRaptor populations on islands are limited by resource availability and the dispersal possibilities for young birds, which are often determined by the size of the island. This leads to differences in population dynamics and viability compared to mainland populations. Human land use modifications on islands—such as agriculture, forestry, excessive hunting, and urban infrastructure development—may affect resource availability and increase risks to these populations, ultimately threatening their survival. Consequently, many island raptor populations have been dramatically reduced or driven to extinction and have never fully recovered. The conditions necessary for their long-term persistence remain uncertain.Gotland, a large, human-dominated island located in the Baltic Sea, is home to one of the densest populations of Golden Eagles (Aquila chrysaetos) in the world. However, the drivers of population dynamics remain unknown, and many speculations exist that require empirical testing.Approximately 86 Golden Eagle territories were identified and surveyed across Gotland, an island spanning approximately 3,200 km² (152 km long, 52 km wide, with an 800 km coastline). We investigated the spatial drivers of breeding dynamics in this eagle population, evaluating the effects of territorial habitat composition, overlap with White-tailed Eagles, prey density, and neighborhood effects on territorial productivity.The average productivity was 0.41 fledglings per pair, which varied annually, with approximately 72% of territories occupied and 32% being successful. Despite significant variation in habitat composition across territories, spatial differences in productivity were primarily influenced by the proportion of coniferous forest (nesting habitat), access to coastal areas (greater prey diversity), the density of the main prey species (roe deer,Capreolus capreolus), and the reproductive status of neighboring territories in a year.Several novel findings emerged: the role of roe deer as a potential prey species had been previously underappreciated, proximity to the coast was associated with increased productivity, and the variation in spatio-temporal reproductive dynamics across neighboring territories appears to influence overall population dynamics. This relationship warrants further study. We discuss the implications of these findings for the long-term conservation and persistence of this iconic island population and similar populations worldwide.
Single-cell DNA methylome and 3D genome atlas of the human subcutaneous adipose tissue
Authors: Chen Zeyuan Johnson , Das Sankha Subhra , Kar Asha , Lee Seung Hyuk T. , Abuhanna Kevin D. , Alvarez Marcus , Sukhatme Mihir G. , Gelev Kyla Z. , Heffel Matthew G. , Zhang Yi , Avram Oren , Rahmani Elior , Sankararaman Sriram , Heinonen Sini , Peltoniemi Hilkka , Halperin Eran , Pietiläinen Kirsi H. , Luo Chongyuan , Pajukanta Päivi 
Published: November 2024

AbstractHuman subcutaneous adipose tissue (SAT) contains a diverse array of cell-types; however, the epigenomic landscape among the SAT cell-types has remained elusive. Our integrative analysis of single-cell resolution DNA methylation and chromatin conformation profiles (snm3C-seq), coupled with matching RNA expression (snRNA-seq), systematically cataloged the epigenomic, 3D topology, and transcriptomic dynamics across the SAT cell-types. We discovered that the SAT CG methylation (mCG) landscape is characterized by pronounced hyper-methylation in myeloid cells and hypo-methylation in adipocytes and adipose stem and progenitor cells (ASPCs), driving nearly half of the 705,063 detected differentially methylated regions (DMRs). In addition to the enriched cell-type-specific transcription factor binding motifs, we identifiedTET1andDNMT3Aas plausible candidates for regulating cell-type level mCG profiles. Furthermore, we observed that global mCG profiles closely correspond to SAT lineage, which is also reflected in cell-type-specific chromosome compartmentalization. Adipocytes, in particular, display significantly more short-range chromosomal interactions, facilitating the formation of complex local 3D genomic structures that regulate downstream transcriptomic activity, including those associated with adipogenesis. Finally, we discovered that variants in cell-type level DMRs and A compartments significantly predict and are enriched for variance explained in abdominal obesity. Together, our multimodal study characterizes human SAT epigenomic landscape at the cell-type resolution and links partitioned polygenic risk of abdominal obesity to SAT epigenome.
Spatiotemporally restricted Hippo signalings instruct the fate and maturation of hepatobiliary cells
Authors: Wang Yebin , Zhong Zhenxing , Wang Yu , Zhu Ying , Guan Kun-Liang , Yu Fa-Xing 
Published: November 2024

ABSTRACTThe Hippo pathway is an evolutionary conserved signaling cascade involved in organ size control and tumorigenesis, but its cellular functions and regulatory mechanisms are not fully understood. Recently, we have defined two independent modules (HPO1 and HPO2) in the Hippo signaling network. Here, by using spatially resolved transcriptomic and imaging analysis of mouse livers with defective Hippo signaling, we show that HPO1 and HPO2 operate in distinct cells at different developmental stages to regulate the fate and maturation of liver parenchymal cells. HPO1 controls the maturation of hepatocytes postnatally, and its perturbation leads to the expansion of immature hepatocytes (imHep). HPO2, on the other hand, regulates the maturation of cholangiocytes perinatally, and its ablation results in the accumulation of immature cholangiocytes (imCho2) identical to developing ductal plate cells. Moreover, the inactivation of HPO1 or HPO2 causes the conversion of hepatocytes into immature cholangiocytes (imCho1). These immature cells are also observed in regenerating livers following different damages. In contrast, deletion ofYap/Tazencoding downstream effectors of the Hippo pathway accelerates liver maturation and promotes cell death. These findings suggest that the spatiotemporally restricted Hippo signaling modules act as checkpoints in liver development and may coordinate cell proliferation and maturation to ensure proper liver size and function.
Investigate c-Fos changes in genetically identified amygdala neurons after mild footshock stress
Authors: Dong Hallie , Schlüter Oliver M. , Huang Xiaojie 
Published: November 2024

SummaryThe amygdala is a key brain region that processes stress-related inputs to reshape future behaviors. The lateral amygdala (LA), basolateral amygdala (BLA), and central amygdala (CeA) are important subregions that mediate different aspects of stress experiences from receiving sensory input to memory formation and behavioral responding. The principal neurons in these regions are glutamatergic pyramidal neurons, which are genetically separable into two subpopulations, protein phosphatase 1 regulatory subunit 1B-positive (Ppp1r1b, also known as DARPP-32) parvocellular neurons and R-spondin2-positive (Rspo2) magnocellular neurons. Recent studies show that these two subpopulations of amygdala neurons differentially regulate appetitive versus aversive behaviors. The research goal of this study is to explore whether amygdala Ppp1r1b and Rspo2 neurons are transcriptionally activated by moderate stress experience, such that persistent cellular changes are made to influence future functional output of these two subtypes of neurons. To test transcriptional activation, we focused on c-Fos, one of the early genes that are transiently expressed in response to cellular stimulations to regulate downstream gene transcription. Moderate stress was introduced through brief footshocks, with mice without footshock as controls. Between shocked and control mice, we observed similar numbers of Ppp1r1b or Rspo2 neurons per unit area that expressed c-Fos, which was consistent across LA-BLA and CeA. Moreover, in LA-BLA, Ppp1r1b/c-Fos cells consistently outnumber Rspo2/c-Fos cells across treatment conditions, and the reverse is true in CeA. These results suggest that moderate stress experience is not sufficient to induce robust transcriptional alterations in the two key subpopulations of amygdala neurons, and Ppp1r1b versus Rspo2 neuron activities, as measured by c-Fos expression levels, show differential dominance in amygdala subregions.
Prolonged low flows and non-native fish operate additively to alter insect emergence in mountain streams
Authors: Evangelista Charlotte , Buoro Mathieu , Leathers Kyle , Tronel Tatiana , Carlson Stephanie M. , Ruhi Albert 
Published: November 2024

AbstractClimate-induced flow alteration is subjecting mountain streams to more frequent and severe low-flow periods due to lower snowpack and earlier snowmelt. Yet, anticipating how stream ecosystems respond to prolonged low flows remains challenging because trophic levels can respond differently, and non-native predators could dampen or amplify responses. Here, we conducted a large-scale experiment to examine how early, prolonged low flows projected by the end of the century in California’s Sierra Nevada will alter mountain stream food webs and emerging insect flux—a critical stream-to-land cross-ecosystem linkage. Additionally, we tested whether Brown trout (Salmo trutta), a widespread non-native top predator, would change food-web responses to low-flow conditions. We found that early low flows and non-native fish effects were additive rather than synergistic or antagonistic. Early low flows did not alter the overall rate of emerging insects but they did shift community structure and reduce the prevalence of small-sized individuals—possibly reflecting larger size at emergence and faster growth rates due to warming. In contrast, non-native fish presence increased seasonally-aggregated abundance of stream insects up to 12%, mainly by increasing abundance of Chironomidae and small-sized Ephemeroptera and Trichoptera. In channels with fish, benthic algal biomass doubled and scraper-grazer and collector-gatherer insects emerged 60% and 55% more than channels without fish, likely benefiting from trout keeping mesopredators at bay. This experiment illustrates that prolonged low flows and invasions can profoundly alter mountain river food webs even when operating additively; and shows how mesocosm-based research may help understand global-change driven disruption of cross-ecosystem linkages.
Synchronous activation of striatal cholinergic interneurons induces local serotonin release
Authors: Matityahu Lior , Hobel Zachary B. , Berkowitz Noa , Malgady Jeffrey M. , Gilin Naomi , Plotkin Joshua L. , Goldberg Joshua A. 
Published: November 2024

AbstractStriatal cholinergic interneurons (CINs) activate nicotinic acetylcholine receptors on dopamine axons to extend the range of dopamine release. Here we show that synchronous activation of CINs induces and extends the range of local serotonin release via a similar mechanism. This process is exaggerated in the hypercholinergic striatum of a mouse model of OCD-like behavior, implicating CINs as critical regulators of serotonin levels in the healthy and pathological striatum.
Assessing the Biosecurity Risk of Footwear as a Fomite for Transmission of Adventitious Infectious Agents to Mice
Authors: Palillo Michael B , Mishkin Noah , Atmane Mohamad , Palillo Jack A , Carrasco Sebastian , Woods Cheryl , Henderson Kenneth S. , Lipman Neil S , Arbona Rodolfo J Ricart 
Published: November 2024

AbstractThe soles of staff shoes accessing vivaria can become contaminated on urban streets, potentially serving as a source of fomite-mediated transmission of adventitious agents to laboratory rodents. While shoe covers may mitigate this risk, donning them can lead to hand contamination. Staff accessing our vivaria use motor-driven shoe cleaners hundreds of times daily to remove and collect particulates via a vacuum collection system from the top, sole, and sides of shoes instead of shoe covers. Shoe cleaner debris (SCD) and contact media (CM) exposed to SCD from shoe cleaners in 5 vivaria were assessed by PCR for 84 adventitious agents. SCD and CM samples tested positive for 33 and 37 agents, respectively, and a combined 39 agents total. To assess SCD infectivity, NSG and Swiss outbred mice were housed for 7 days in direct contact with SCD and oronasally inoculated with a suspension created from SCD collected from each of the 5 vivaria. Mice were tested by PCR and serology 3-, 7-, 14- and 63-days post-inoculation. All mice remained healthy until the study’s end and tested negative for all agents found in SCD/CM except murine astrovirus 1,Staphyloccocus xylosusandCandidatus Savagella, agents known to be enzootic in the experimental mouse source colony. In a follow-up study, the soles of 27 staff street shoes were directly sampled using CM. Half of CM was used for PCR, while the other half was added as bedding material to a cage containing NSG and Swiss outbred mice. While CM tested positive for 11 agents, all mice were healthy 63 days post-exposure and again positive for only enzootic agents. These results suggest that shoe debris might not be a significant biosecurity risk to laboratory mice, questioning the need for shoe covers or cleaners when entering experimental barrier vivaria.
Planning and movement activities co-adapt in a motor-reference frame during 3D BCI-controlled reach adaptation in monkey frontal and parietal cortices
Authors: Ferrea E. , Morel P. , Gail A. 
Published: November 2024

AbstractPerturbing visual feedback is a powerful tool for studying visuomotor adaptation. However, unperturbed proprioceptive signals in common paradigms inherently co-varies with physical movements and causes incongruency with the visual input. This can create challenges when interpreting underlying neurophysiological mechanisms. We employed a brain-computer interface (BCI) in rhesus monkeys to investigate spatial encoding in frontal and parietal areas during a 3D visuomotor rotation task where only visual feedback was movement-contingent. We found that both brain regions better reflected the adapted motor commands than the perturbed visual feedback during movement preparation and execution. This adaptive response was observed in both local and remote neurons, even when they did not directly contribute to the BCI input signals. The transfer of adaptive changes in planning activity to corresponding movement corrections was stronger in the frontal than in the parietal cortex. Our results suggest an integrated large-scale visuomotor adaptation mechanism in a motor-reference frame spanning across frontoparietal cortices.