bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational functions of precisely balanced neuronal assemblies in an olfactory memory network
Authors: Meissner-Bernard Claire , Jenkins Bethan , Rupprecht Peter , Bouldoires Estelle Arn , Zenke Friedemann , Friedrich Rainer W. , Frank Thomas 
Published: April 2024

ABSTRACTStructured connectivity in the brain organizes information by constraining neuronal dynamics. Theoretical models predict that memories are represented by balanced assemblies of excitatory and inhibitory neurons, but the existence and functions of such EI assemblies are difficult to explore. We addressed these issues in telencephalic area Dp of adult zebrafish, the homolog of piriform cortex, using computational modeling, population activity measurements, and optogenetic perturbations. Modeling revealed that precise balance of EI assemblies is important to prevent not only excessive firing rates (“runaway activity”) but also the stochastic occurrence of high pattern correlations (“runaway correlations”). Consistent with model-derived predictions, runaway correlations emerged in Dp when synaptic balance was perturbed by optogenetic manipulations of fast-spiking feedback interneurons. Moreover, runaway correlations were driven by sparse subsets of strongly active neurons, rather than by a general broadening of tuning curves. These results reveal novel computational functions of EI assemblies in an autoassociative olfactory memory network and support the hypothesis that EI assemblies organize information on continuous representational manifolds rather than discrete attractor landscapes.
RummaGEO: Automatic Mining of Human and Mouse Gene Sets from GEO
Authors: Marino Giacomo B. , Clarke Daniel J. B. , Deng Eden Z. , Ma’ayan Avi 
Published: April 2024

AbstractThe Gene Expression Omnibus (GEO) is a major open biomedical research repository for transcriptomics and other omics datasets. It currently contains millions of gene expression samples from tens of thousands of studies collected by many biomedical research laboratories from around the world. While users of the GEO repository can search the metadata describing studies for locating relevant datasets, there are currently no methods or resources that facilitate global search of GEO at the data level. To address this shortcoming, we developed RummaGEO, a webserver application that enables gene expression signature search of a large collection of human and mouse RNA-seq studies deposited into GEO. To develop the search engine, we performed offline automatic identification of sample conditions from the uniformly aligned GEO studies available from ARCHS4. We then computed differential expression signatures to extract gene sets from these studies. In total, RummaGEO currently contains 135,264 human and 158,062 mouse gene sets extracted from 23,395 GEO studies. Next, we analyzed the contents of the RummaGEO database to identify statistical patterns and perform various global analyses. The contents of the RummaGEO database are provided as a web-server search engine with signature search, PubMed search, and metadata search functionalities. Overall, RummaGEO provides an unprecedented resource for the biomedical research community enabling hypothesis generation for many future studies. The RummaGEO search engine is available from:https://rummageo.com/.
The chromatin conformation landscape of Alzheimer’s disease
Authors: Nativio R , Lan Y , Donahue G , Shcherbakova O , Barnett N , Titus KR , Chandrashekar H , Phillips-Cremins JE , Bonini NM , Berger SL 
Published: April 2024

ABSTRACTWe have been investigating epigenetic alterations in the brain during human aging and Alzheimer’s disease (AD), and have evidence for histone acetylation both protecting the aging epigenome and driving AD. Here we extend our studies to chromatin architecture via looping studies, and with binding studies of key proteins required for looping: CTCF and RAD21. We detected changes in CTCF and RAD21 levels and localization, finding major changes in CTCF in AD compared to fewer changes in healthy aging. In our study of 3D genome conformation changes, we identified stable topological associating domains (TADs) in Old and AD; in contrast, in AD, there is loss of interaction at genomic sites/loops within TADs, likely reflecting the loss of CTCF. We identified genes and potential transcription factor binding at the loops that are lost in AD. in addition, we found enrichment of CTCF peak losses for AD eQTLs, suggesting that architectural dysfunction has a role in Alzheimer’s. Functional experiments lowering the homologues of several key genes in aDrosophilamodel of Aβ42 toxicity exacerbate neurodegeneration. Taken together, these data indicate both functional protections and losses occur in the Alzheimer’s brain genome compared to normal aging.
Scribbleknockdown induced metastasis tracking, identification of its associated novel molecular candidates through Proteome andin silicostudies
Authors: Singh Jyotsna , Srikrishna Saripella 
Published: April 2024

AbstractMetastasis is the primary cause of cancer associated death globally. Loss of function ofScribble, a cell polarity regulator/tumor suppressor gene, is associated with many forms of human cancer but its role in cell proliferation and metastasis remains unknown. We generated metastatic cancer inDrosophilausing UAS-GAL4 system, through knockdown ofScribblein the wing imaginal discs and tracked metastasis events from 0hr early pupae to 84hrs late pupae using fluorescence microscope. Here, we report, for the first time, that knockdown ofScribblealone could lead to the development of primary tumor in the wing imaginal discs, which is capable of establishing metastasis, leading to secondary tumor formation, eventually resulting in absolute pupal lethality. Further, we checked a metastasis biomarker, MMP1 levels during pre-and post-metastatic phases inDrosophilapupae using qRT-PCR and Western blot analysis. In addition, we analyzed the proteome ofScribbleknockdown induced tumor-bearing pupae by 2-D gel electrophoresis followed by MALDI-TOF MS to identify novel proteins involved in the process of tumorigenesis and metastasis. We identified six differentially expressed proteins, Obp 99b, Fer2LCH,CG13492, Hsp23, Ubiquitin and Colt inScribknockdown pupae compared to wild-type and validated their expression at the transcriptional level using qRT-PCR.In-silicostudies show these novel protein interaction withScrib. Thus, our results suggested that loss ofScribalone causes metastasis, without the need for cooperative interaction with oncogenicRas.The newly identified Fer2LCH (ferritin) and colt proteins could be important candidates for therapeutic target againstScribassociated cell proliferation and metastasis.
Bioinformatics analysis and validation of differentially expressed miRNA in the sperm of partners of patients with unexplained recurrent miscarriages
Authors: Tian Hui , Zhao Xiao-Xi 
Published: April 2024

ABSTRACTBackgroundRecurrent miscarriage is a common multifactorial disease, and even after systematic examination, the cause of the miscarriages cannot be determined in approximately 50% of patients. However, currently, few examinations are conducted for partners of patients with recurrent miscarriages. The contribution of spermatozoa to new individuals is not limited to half of the diploid genome. Recent studies have shown that spermatozoa add several components to oocytes, including a complex RNA population that plays an important role in paternal chromatin packaging, sperm maturation and empowerment, fertilisation, early embryogenesis, and developmental maintenance. In view of this, we constructed a sperm miRNA expression profile of partners of patients with unexplained recurrent miscarriages and explored the relationship between unexplained recurrent miscarriages and differential miRNA expression in sperm.MethodsSemen samples were obtained from the partners of patients with unexplained recurrent miscarriages treated at the affiliated hospital of Inner Mongolia Medical University, as well as healthy men who underwent physical examinations between July 2021 and February 2023. The miRNA expression profiles of the sperm in the two groups were detected using high-throughput sequencing. Bioinformatics analysis of differentially expressed miRNAs was performed to predict target genes and their action pathways and verify the expression levels of paternal miRNAs in known embryos in the study and control groups through RT-PCR technology.ResultA total of 83 differentially expressed miRNAs were detected between the two groups, of which 39 were significantly upregulated and 44 were significantly downregulated. The results showed that spermatic hsa-miR-34c-5p, hsa-miR-1285-3p, hsa-miR-486-3p, and hsa-miR-146b-3p may regulate the occurrence of unexplained recurrence through the Ras, PI3K-Akt, and MAPK signalling pathways in the bioinformatics analysis. The expression of hsa-miR-34c-5 in spouses of patients with unexplained miscarriage recurrence was downregulated (p < 0.001). Binary logistic regression analysis showed that low expression of hsa-miR-34c-5p was a high-risk factor for recurrent miscarriage (odds ratio [OR] = 4.344; 95% confidence interval [CI], 1.119–16.857; p < 0.05).ConclusionThe occurrence of unexplained recurrent miscarriages is associated with the differential expression of key miRNAs in the sperms of patients’ spouses.
Development of a recombineering system for the acetogenEubacterium limosumwith Cas9 counterselection for markerless genome engineering
Authors: Sanford Patrick A. , Woolston Benjamin M. 
Published: April 2024

AbstractEubacterium limosumis a Clostridial acetogen that efficiently utilizes a wide range of single-carbon substrates and contributes to metabolism of health-associated compounds in the human gut microbiota. These traits have led to interest in developing it as a platform for sustainable CO2-based biofuel production to combat carbon emissions, and for exploring the importance of the microbiota in human health. However, synthetic biology and metabolic engineering inE. limosumhave been hindered by the inability to rapidly make precise genomic modifications. Here, we screened a diverse library of recombinase proteins to develop a highly efficient oligonucleotide-based recombineering system based on the viral recombinase RecT. Following optimization, the system is capable of catalyzing ssDNA recombination at an efficiency of up to 2%. Addition of a Cas9 counterselection system allows recombination to reach an efficiency of up to 100%, enabling creation of genomic point mutations in a scarless and markerless manner. We deployed this system to create a clean knockout of the extracellular polymeric substance (EPS) gene cluster, generating a strain incapable of biofilm formation. This approach is rapid and simple, not requiring laborious homology arm cloning, and can readily be retargeted to almost any genomic locus. This work overcomes a major bottleneckEubacterium limosumgenetic engineering by enabling precise genomic modifications, and provides both a roadmap and associated recombinase plasmid library for developing similar systems in other Clostridia of interest.Graphical Abstract
HIV-1 controllers possess a unique CD8+ T-cell activation phenotype and loss of control is associated with increased expression of exhaustion markers
Authors: Jones Amber D , Capriotti Zachary , Santos Erin , Lin Angel , Duyne Rachel Van , Smith Stephen , Klase Zachary 
Published: April 2024

ABSTRACTHIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. These controllers can be categorized based on the level and mechanism of control. Understanding the mechanisms by which controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. We explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control by examining immune characteristics of HIV-1 controllers and controllers who lost control within the duration of the study. Previous work revealed the ability of CD8+ T-cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T-cellsex vivo. Using flow cytometry, we analyzed exhaustion marker expression on CD8+ T-cells from these controllers and determined that they maintain a unique exhaustion profile as compared to HIV-negative individuals and standard progressors. The low level of T-cell exhaustion seen in controllers was reversed when these individuals lost control and showed increased viral loads. Immune checkpoint blockade targeting exhaustion markers was able to restoreex vivocontrol by CD8+ T-cells from former controllers. These results suggest that CD8+ T cell exhaustion compromises the ability to control viral replication in HIV-1 controllers.AUTHOR SUMMARYDespite the use of antiretroviral therapy, HIV continues to be a major public health issue that affects the lives of millions of people. Some infected people can control viral infection without therapy. The mechanism by which some people can control HIV infection at low, but detectable levels is unknown. In this study we examined the state of cytotoxic CD8+ T-cells in a group of HIV controllers and found that controllers maintain low levels of markers for a chronic state of activation called exhaustion. Loss of control correlated with increase in exhausted T-cells and for individuals who had recently lost control of infection we could restore protection in the cell culture dish by using immune checkpoint blockade drugs that affect exhaustion.
Impact of Prescribed Fire on Soil Microbial Communities in a Southern Appalachian Forest Clearcut
Authors: Rafie S.A.A , Blentlinger L. , Putt A. D. , Williams D. E. , Joyner D. C. , Campa M. F. , Schubert M. J. , Hoyt K. P. , Horn S. P. , Franklin J. A. , Hazen T. C. 
Published: April 2024

AbstractEscalating wildfire frequency and severity, exacerbated by shifting climate patterns, pose significant ecological and economic challenges. Prescribed burns, a common forest management tool, aim to mitigate wildfire risks and protect biodiversity. Nevertheless, understanding the impact of prescribed burns on soil and microbial communities in temperate mixed forests, considering temporal dynamics and slash fuel types, remains crucial. Our study, conducted at the University of Tennessee Forest Resources AgResearch and Education Center in Oak Ridge, TN, employed controlled burns across various treatments, and the findings indicate that low-intensity prescribed burns have none or minimal short-term effects on soil parameters but may alter soil nutrient concentrations, as evidenced by significant changes in porewater acetate, formate, and nitrate concentrations. These burns also induce shifts in microbial community structure and diversity, with Proteobacteria and Acidobacteria increasing significantly post-fire, possibly aiding soil recovery. In contrast, Verrucomicrobia showed a notable decrease over time, and other specific microbial taxa correlated with soil pH, porewater nitrate, ammonium, and phosphate concentrations. Our research contributes to understanding the intricate relationships between prescribed fire, soil dynamics, and microbial responses in temperate mixed forests in the Southern Appalachian Region, which is valuable for informed land management practices in the face of evolving environmental challenges.
A Novel Magnetic Field Device: Effects of Magnetic Fields on Planktonic Yeasts and Fungal Mats
Authors: Bandara Akila , Li Enoki , Charlebois Daniel A. 
Published: April 2024

AbstractMicroorganisms evolved within the geomagnetic field and can be affected by magnetic field exposure. However, the mechanisms underlying many magnetic phenomena in microbes remain to be elucidated. We develop a 3D-printed magnetic field exposure device to perform experiments on microbes. This device is designed in AutoCAD, modeled in COMSOL, and validated using a Gaussmeter. Using the magnetic field exposure device, we perform static magnetic field experiments on different strains of the budding yeastSaccharomyces cerevisiae. We find that static magnetic field exposure slows the spatially-structured expansion of yeast mats that expands in two dimensions, but not yeast mats that expand in three dimensions, across the surface of semi-solid media. We also find that magnetic fields do not affect the growth of yeast cells in well-mixed liquid media. This study provides a novel device for magnetic field exposure experiments on microorganisms and advances our understanding of the effects of magnetic fields on fungi.Why it mattersMicroorganisms have evolved to function, survive, and reproduce in Earth’s magnetic field. However, the mechanisms underlying magnetic phenomena in microorganisms are unknown. This is especially true for fungi, which are important microorganisms for microbiological research, industrial application, and infectious disease. To elucidate mechanisms driving magnetic phenomena, we need devices to perform controlled experiments in a variety of conditions. We develop a 3D-printed magnetic field exposure device using computer-aided design, physics modeling software, and a magnetometer. Using this novel magnetic field device, we discover that magnetic fields can slow the growth of yeast on agar plates, but that magnetic fields do not affect the growth of yeast in liquid media.
Impact of Obesity on the CCR6-CCL20 Axis in Epidermal γδ T Cells and IL-17A Production in Murine Wound Healing and Psoriasis
Authors: Lawler William , Castellanos Tanya , Engel Emma , Alvizo Cristian R. , Kasler Antolette , Bshara-Corson Savannah , Jameson Julie M. 
Published: April 2024

AbstractObesity is associated with comorbidities including type 2 diabetes, chronic nonhealing wounds and psoriasis. Normally skin homeostasis and repair is regulated through the production of cytokines and growth factors derived from skin-resident cells including epidermal γδ T cells. However epidermal γδ T cells exhibit reduced proliferation and defective growth factor and cytokine production during obesity and type 2 diabetes. One of the genes modulated in epidermal γδ T cells during obesity and type 2 diabetes is CCR6, which is the receptor for CCL20. CCL20 is elevated in the skin during obesity and type 2 diabetes. Here we identify a subset of murine epidermal γδ T cells that expresses CCR6 in response to activationin vitroand post-wounding or psoriasis induction with imiquimodin vivo. We show that CCL20 stimulates epidermal γδ T cells to produce IL-17 suggesting CCR6 regulates the IL-17 axis as in dermal γδ T cells. Further, epidermal γδ T cells upregulate CCR6 and produce IL-17 during murine models of wound repair and psoriasis. Obesity increases CCR6 and IL-17 expression by epidermal γδ T cells during wound repair but has less of an effect during psoriasis. These findings have novel implications for the regulation of a specific population of IL-17-producing epidermal γδ T cells during skin damage and inflammation.
Coral long-term recovery after bleaching: implications for sexual reproduction and physiology
Authors: Padilla-Gamiño JL , Timmins-Schiffman E , Lenz EA , White SJ , Axworthy J , Potter A , Lopez J , Wang F 
Published: April 2024

ABSTRACTThis study examined the long-term impacts of coral bleaching on the reproduction and physiology ofMontipora capitata, a dominant reef-building coral in Hawaiʻi. We monitored bleached and non-bleached colonies during and after a natural coral bleaching event in 2014 and analyzed reproductive traits and transcriptomic signatures eight months later. Our study shows that non-bleached and bleached colonies successfully produced gametes. Colonies that bleached had smaller oocytes, and development was slower than in colonies that did not bleach. Corals with different vulnerabilities to bleaching exhibited distinct transcriptomic responses eight months after a bleaching event. Those more prone to bleaching showed suppression of transcripts associated with sperm motility, calcification, and immunity. We found distinct transcriptomic signatures between fringing and patch reefs, suggesting local adaptation and/or acclimatization. To conserve coral reefs and better understand how they will be affected by future heat stress, we need to track which colonies survive and examine how their physiological and reproductive processes are impacted in the short- and long-term. This is critical as consecutive bleaching events become more frequent, and corals have less time to recover. Our study provides valuable molecular and reproductive data that can be used for conservation and management purposes. This information can help us identify signs of coral vulnerability and resilience to bleaching, project how future bleaching events will affect coral reproduction, determine which traits are most at risk, and assess which sites are more likely to be compromised.
Breaking Down the Bottlebrush: Atomically-Detailed Structural Dynamics of Mucins
Authors: Kearns Fiona L. , Rosenfeld Mia A. , Amaro Rommie E. 
Published: April 2024

AbstractMucins, the biomolecular components of mucus, are glycoproteins that form a thick physical barrier at all tissue-air interfaces, forming a first line of defense against pathogens. Structural features of mucins and their interactions with other biomolecules remain largely unexplored due to challenges associated with their high-resolution characterization. Combining limited mass spectrometry glycomics and protein sequencing data, we present all-atom, explicitly solvated molecular dynamics simulations of a major respiratory mucin, MUC5B. We detail key forces and degrees of freedom imposed by the extensive O-glycosylation, which imbue the canonically observed bottlebrush-like structures to these otherwise intrinsically disordered protein backbones. We compare our simulation results to static structures observed in recent scanning tunneling microscopy experiments, as well as other published experimental efforts. Our work presents a generalizable framework for investigating the dynamics and interactions of mucins, which can inform on structural details currently inaccessible to experimental techniques.