bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation
Authors: Caetano-Silva Maria Elisa , Shrestha Akriti , Duff Audrey F. , Kontic Danica , Brewster Patricia C. , Kasperek Mikaela C. , Lin Chia-Hao , Wainwright Derek A. , Hernandez-Saavedra Diego , Woods Jeffrey A. , Bailey Michael T. , Buford Thomas W. , Allen Jacob M. 
Published: March 2024

ABSTRACTAging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin.Ex vivoimmunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonicIl6, Tnf, Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation inEscherichia(Proteobacteria)and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.
Elucidating the sustainability of 700 years of Inuvialuit beluga whale hunting in the Mackenzie River Delta, Northwest Territories, Canada
Authors: Skovrind Mikkel , Louis Marie , Ferguson Steven H. , Glazov Dmitry M. , Litovka Dennis I. , Loseto Lisa , Meschersky Ilya G. , Miller Mariah M. , Postma Lianne , Rozhnov Viatcheslav V. , Scott Michael , Westbury Michael V. , Szpak Paul , Friesen T. Max , Lorenzen Eline D. 
Published: March 2024

AbstractBeluga whales play a critical role in the subsistence economies and cultural heritage of Indigenous communities across the Arctic, yet the effects of Indigenous hunting on beluga whales remains unknown. Here, we integrate paleogenomics and stableδ13C andδ15N isotope analysis to investigate 700 years of beluga subsistence hunting in the Mackenzie Delta area of northwestern Canada. Genetic identification of the zooarchaeological remains, which based on radiocarbon dating span three time periods (1290-1440 CE; 1450-1650 CE; 1800-1870 CE), indicate shifts across time in the sex ratio of the harvested belugas. The equal number of females and males harvested in 1450-1650 CEversusmore males harvested in the two other time periods may reflect changes in hunting practices or temporal shifts in beluga availability. We find temporal shifts and sex-based differences in δ13C of the harvested belugas across time, suggesting historical adaptability in the foraging ecology of the whales. Although we uncovered novel mitochondrial diversity in the Mackenzie Delta belugas, we found no changes in nuclear genomic diversity nor any substructuring across time. Our findings indicate the genomic stability and continuity of the Mackenzie Delta beluga population across the 700 years surveyed, indicating the impact of Inuvialuit subsistence harvests on the genetic diversity of contemporary beluga individuals has been negligible.Significance StatementSince colonizing the Mackenzie Delta in northwestern Canada ∼1200 CE, Inuvialuit have been heavily reliant on belugas for their livelihoods and cultural heritage. However, little is known of the impact of centuries of sustained Inuvialuit subsistence hunting on the beluga population inhabiting the Mackenzie Delta. Using palaeogenomic and stable isotope analysis of zooarchaeological remains, and comparing the findings with contemporary data, we investigate temporal changes in beluga diversity, structuring, and foraging ecology. We show Inuvialuit harvests had a negligible impact on the genetic diversity of contemporary Mackenzie belugas, and highlight the applicability of combining genomic sexing and isotope analysis of zooarchaeological remains for advancing our understanding of past hunting practices and faunal ecologies.
DUAL ACTION ELECTROCHEMICAL BANDAGE OPERATED by a PROGRAMMABLE MULTIMODAL WEARABLE POTENTIOSTAT
Authors: Bozyel Ibrahim , Fleming Derek , Kim Won-Jun , Rosen Peter F. , Gelston Suzanne , Ozdemir Dilara , Ay Suat U. , Patel Robin , Beyenal Haluk 
Published: March 2024

ABSTRACTElectrochemical bandages (e-bandages) can be applied to biofilm-infected wounds to generate reactive oxygen species, such as hypochlorous acid (HOCl) or hydrogen peroxide (H2O2). The e-bandage-generated HOCl or H2O2kills biofilmsin vitroand in infected wounds on mice. The HOCl-generating e-bandage is more active against biofilmsin vitro, although this distinction is less apparentin vivo. The H2O2-generating e-bandage, more than the HOCl-generating e-bandage, is associated with improved healing of infected wounds. A strategy in which H2O2and HOCl are generated alternately—for dual action—was explored. The goal was to develop a programmable multimodal wearable potentiostat (PMWP) that could be programmed to generate HOCl or H2O2, as needed. An ultralow-power microcontroller unit managed operation of the PMWP. The system was operated with a 260-mAh capacity coin battery and weighed 4.6 grams, making it suitable for small animal experiments or human use. The overall cost of a single wearable potentiostat was $6.50 (USD). The device was verified using established electrochemical systems and functioned comparably to a commercial potentiostat. To determine antimicrobial effectiveness, PMWP-controlled e-bandages were tested against clinical isolates of four prevalent chronic wound bacterial pathogens, methicillin-resistantStaphylococcus aureus(MRSA),Pseudomonas aeruginosa, Acinetobacter baumannii, andEnterococcus faecium, and one fungal pathogen of emerging concern,Candida auris. PMWP-controlled e-bandages exhibited broad-spectrum activity against biofilms of all study isolates tested when programmed to deliver HOCl followed by H2O2. These results show that the PMWP operates effectively and is suitable for animal testing.
Intracellular pH regulates β-catenin with low pHi increasing adhesion and signaling functions
Authors: Czowski Brandon J. , White Katharine A. 
Published: March 2024

AbstractIntracellular pH (pHi) dynamics are linked to cell processes including proliferation, migration, and differentiation. The adherens junction (AJ) and signaling protein β-catenin has decreased abundance at high pHi due to increased proteasomal-mediated degradation. However, the effects of low pHi on β-catenin abundance and functions have not been characterized. Here, we show that low pHi stabilizes β-catenin in epithelial cells using population-level and single-cell assays. β-catenin abundance is increased at low pHi and decreased at high pHi. We also assay single-cell protein degradation rates to show that β-catenin half-life is longer at low compared to high pHi. Importantly, we show that AJs are not disrupted by β-catenin loss at high pHi due to rescue by plakoglobin. Finally, we show that low pHi increases β-catenin transcriptional activity in single cells and is indistinguishable from a Wnt-on state. This work characterizes pHi as a rheostat regulating β-catenin abundance, stability, and funcion and implicates β-catenin as a molecular mediator of pHi-dependent cell processes.SummaryIntracellular pH (pHi) regulates the degradation rate of the pH sensor β-catenin, altering protein abundance, localization, and function in epithelial cells. This work shows pHi acts as a rheostat to alter both adhesion and signaling functions of β-catenin.
Deep Learning and GBLUP Integration: An Approach that Identifies Nonlinear Genetic Relationships Between Traits
Authors: Shokor Fatima , Croiseau Pascal , Gangloff Hugo , Saintilan Romain , Tribout Thierry , Mary-Huard Tristan , C.D. Cuyabano Beatriz 
Published: March 2024

AbstractBackgroundGenomic prediction aims to predict the breeding values of multiple complex traits, usually assumed to be normally distributed by the largely used statistical methods, thus imposing linear genetic correlations between traits. While statistical methods are of great value for genomic prediction, these methods do not account for nonlinear genetic relationships between traits. If such relationships exist, although statistical models do perform a fair linear approximation, their prediction accuracy is limited due to the nonlinearity. Deep learning (DL) is a promising methodology for predicting multiple complex traits, in scenarios where nonlinear genetic relationships are present, due to its capacity to capture complex and nonlinear patterns in large data. We proposed a novel hybrid DLGBLUP model which uses the output of the traditional GBLUP, and enhances its PGV by accounting for nonlinear genetic relationships between traits using DL. Using simulated data, we compared the accuracy of the PGV obtained with the proposed hybrid DLGBLUP model, a DL model, and the traditional GBLUP model – the latter being our baseline reference.ResultsWe found that both DL and DLGBLUP models either outperformed GBLUP, or presented equally accurate PGV, with a particular greater accuracy for traits presenting a strongly characterized nonlinear genetic relationship. Overall, DLGBLUP presented the highest prediction accuracy, up to 0.2 points higher than GBLUP, and smallest mean squared error of the PGV for all traits. Additionally, we evolved a base population over seven generations and compared the genetic progress when selecting individuals based on the additive PGV obtained by either DL, DLGBLUP or GBLUP. For all traits with a nonlinear genetic relationship, after the fourth generation, the observed genetic gain when selection was based on the additive PGV from GBLUP was always inferior to the one achieved from either DL or DLGBLUP.ConclusionsThe integration of DL into genomic prediction enables the possibility of modeling nonlinear relationships between traits. Moreover, by identifying these nonlinear genetic relationships, our DL and DLGBLUP models improved prediction accuracy, when compared to GBLUP. The possibility of nonlinear relationships between traits offers a different perspective into multi-trait evaluations and prediction, as well as into the traits’ evolution over generations, with potential to further improve selection strategies in commercial livestock breeding programs. Moreover, DLGBLUP shows that DL can be used as a complement to statistical methods, by enhancing their performance.
STING-Activating Polymer-Drug Conjugates for Cancer Immunotherapy
Authors: Sheehy Taylor L. , Kwiatkowski Alexander J. , Arora Karan , Kimmel Blaise R. , Schulman Jacob A. , Gibson-Corley Katherine N. , Wilson John T. 
Published: March 2024

AbstractThe stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity and therefore plays an important role in cancer immune surveillance. This has prompted widespread development of STING agonists for cancer immunotherapy, but pharmacological barriers continue to limit the clinical impact of STING agonists and motivate the development of drug delivery systems to improve their efficacy and/or safety. To address these challenges, we developed SAPCon, a STING-activating polymer-drug conjugate platform based on strain-promoted azide-alkyne cycloaddition of dimeric-amidobenzimidazole (diABZI) STING agonists to hydrophilic polymer chains through an enzyme-responsive chemical linker. To synthesize a first-generation SAPCon, we designed a diABZI prodrug modified with a DBCO reactive handle with a cathepsin B-cleavable spacer for intracellular drug release and conjugated this to pendant azide groups on a 100kDa poly(dimethyla acrylamide-co-azide methacrylate) copolymer backbone to increase circulation time and enable passive tumor accumulation. We found that intravenously administered SAPCon accumulated at tumor sites, where it was endocytosed by tumor-associated myeloid cells, resulting in increased STING activation in tumor tissue. Consequently, SAPCon promoted an immunogenic tumor microenvironment, characterized by increased frequency of activated macrophages and dendritic cells and improved infiltration of CD8+T cells, resulting in inhibition of tumor growth, prolonged survival, and enhanced response to anti-PD-1 immune checkpoint blockade in orthotopic breast cancer models. Collectively, these studies position SAPCon as a modular and programmable platform for improving the efficacy of systemically administered STING agonists for cancer immunotherapy.
Compromised retinoic acid receptor beta (RARβ) accelerates the onset of motor, cellular and molecular abnormalities in mouse model of Huntington’s disease
Authors: Zinter Nicolas , Ye Tao , Fraulob Valerie , Plassard Damien , Krezel Wojciech 
Published: March 2024

ABSTRACTThe mechanisms underlying detrimental effects of mutant huntingtin on striatal dysfunction in Huntington’s disease (HD) are not well understood. Although retinoic acid receptor beta (RARβ) emerged recently as one of the top regulators of transcriptionally downregulated genes in the striatum of HD patients and mouse models of HD its involvement in disease progression remains elusive. We report that genetically compromised RARβ signaling accelerates onset of motor abnormalities in R6/1 mouse model of HD. Transcriptional profiling revealed that downregulation of RARβ expression inRarβ+/-; R6/1 mice also accelerates transcriptional signature of disease progression by emergence of upregulated cluster of genes related to cell-cycle, stem cell maintenance and telencephalon development with concomitant downregulation of striatal cell-identity genes. The reactivation of proliferative activity demonstrated in the neurogenic niche and development-related transcriptional programs in the striatum prompt an attempt of lineage infidelity in HD striatum which may lead in consequence to disease-driving energy crisis as suggested by concomitant downregulation of transcripts essential for oxidative phosphorylation, a well-accepted correlate of HD physiopathology, and a metabolic change required for maintenance of proliferative activity and differentiation but not compatible with high energetic demand of differentiated and active neurons.HighlightsCompromising RARβ expression in R6/1 mouse model of HD accelerates onset of HD-like motor abnormalitiesCompromised RARβ signaling contributes to the progression of disease-related transcriptional changes in R6/1 miceRARβ supports cell-identity maintenance in HD mouse model
Investigating Cryopreserved PBMC Functionality in an Antigen-Induced Model of Sarcoidosis Granuloma Formation
Authors: Seman Sarah G. , Bicer Sabahattin , Julian Mark W. , Kramer Patrick J. , Mitchell Jonah R. , Crouser Elliott D. , Locke Landon W. 
Published: March 2024

AbstractSarcoidosis, a systemic inflammatory disease, poses challenges in understanding its etiology and variable clinical courses. Despite ongoing uncertainty about causative agents and genetic predisposition, granuloma formation remains its hallmark feature. To address this complexity, we developed a validated in vitro human granuloma model using peripheral blood mononuclear cells (PBMCs), providing a dynamic platform for studying sarcoidosis pathogenesis. While cryopreservation is a common method for long-term sample preservation, the biological effects of freezing and thawing PBMCs on granuloma formation remain unclear. This study aimed to assess the viability and functionality of cryopreserved sarcoidosis PBMCs within the granuloma model, revealing similar granulomatous responses to fresh cells and highlighting the potential of cryopreserved PBMCs as a valuable tool for studying sarcoidosis and related diseases.
Initiation and Formation of Stereocilia during the Development of Mouse Cochlear Hair Cells
Authors: Chakravarthy Suraj Ranganath , van Zanten Thomas S. , Ladher Raj K 
Published: March 2024

ABSTRACTStereocilia are apically located actin-protrusions found on the hair cells of the inner ear. At least three rows of stereocilia are arranged in a graded staircase pattern, which is vital for mechanosensation. Stereocilia form soon after the specification of hair cells. While these steps have been well-characterized in the avian auditory epithelium, the equivalent information in mice is lacking. Using scanning electron microscopy and super-resolution microscopy, we investigate stereocilia formation from hair cell specification stages in the mouse organ of Corti. Even before differentiation, we find that sensory progenitors, which will give rise to both hair cells and support cells, have a dense lawn of microvilli. Hair cell specialisation is first apparent as an enrichment in junctional actin, followed by the relocalisation of kinocilium into an eccentric position and the thickening of hair cell microvilli closest to the kinocilium. To determine actin signatures associated with hair cell development, we use a new analytical method to map cellular actin filament distribution during development. By nomalising relative actin filament density, we obtain insights into cuticular plate development and actin redistribution during the earliest phases of hair cell specialisation.
TreeCompR: Tree competition indices for inventory data and 3D point clouds
Authors: Rieder Julia S. , Link Roman M. , Köthe Konstantin , Seidel Dominik , Ullmann Tobias , Žmegač Anja , Zang Christian , Schuldt Bernhard 
Published: March 2024

AbstractIn times of more frequent global-change-type droughts and associated tree mortality events, competition release is one silvicultural measure discussed to have an impact on the resilience of managed forest stands. Understanding how trees compete with each other is therefore crucial, but different measurement options and competition indices leave users with the agony of choice, as no single competition index has proven universally superior.To help users with the choice and computation of appropriate indices, we present the open-sourceTreeCompRpackage, which can handle 3D point clouds in various formats as well as classical forest inventory data and serves as a centralized platform for exploring and comparing different competition indices (CIs). Within a common interface, users can efficiently select the most suitable CI for their specific research questions. The package facilitates the integration of both traditional distance-dependent and novel point cloud-based indices.To evaluate the package, we usedTreeCompRto quantify the competition situation of 308 European beech trees from 13 sites in Central Europe. Based on this dataset, we discuss the interpretation, comparability and sensitivity of the different indices to their parameterization and identify possible sources of uncertainty and ways to minimize them.The compatibility ofTreeCompRwith different data formats and different data collection methods makes it accessible and useful for a wide range of users, specifically ecologists and foresters. Due to the flexibility in the choice of input formats as well as the emphasis on tidy, well-structured output, our package can easily be integrated into existing data-analysis workflows both for 3D point cloud and classical forest inventory data.
No Evidence of Altered Language Laterality in People Who Stutter across Different Brain Imaging Studies of Speech and Language
Authors: Demirel Birtan , Chesters Jennifer , Connally Emily , Gough Patricia , Ward David , Howell Peter , Watkins Kate E. 
Published: March 2024

AbstractA long-standing neurobiological explanation of stuttering is the incomplete cerebral dominance theory, which refers to competition between two hemispheres for “dominance” over handedness and speech, causing altered language lateralisation. Renewed interest in these ideas came from brain imaging findings in people who stutter (PWS) of increased activity in the right hemisphere during speech production or of shifts in activity from right to left when fluency increased. Here, we revisited this theory using functional MRI data from children and adults who stutter, and typically fluent speakers (119 participants in total) during four different speech and language tasks: overt sentence reading, overt picture description, covert sentence reading and covert auditory naming. Laterality indices (LIs) were calculated for the frontal and temporal lobes using the LI toolbox running in Statistical Parametric Mapping. We also repeated the analyses with more specific language regions, namely the pars opercularis (Brodmann Area 44) and pars triangularis (Brodmann Area 45). Laterality indices in PWS and typically fluent speakers (TFS) did not differ and Bayesian analyses provided moderate to anecdotal levels of support for the null hypothesis (i.e., no differences in laterality in PWS compared with TFS). The proportions of the PWS and TFS who were left lateralised or had atypical rightwards or bilateral lateralisation did not differ. We found no support for the theory that language laterality is reduced or differs in PWS compared with TFS.
Diversity and abundance of tree microhabitats in the tropical forests of southern Western Ghats, India
Authors: Patel Bharati , Sivaraman Sreejith , Hrideek T.K. , Balakrishnan Peroth 
Published: March 2024

AbstractTree microhabitats (TMHs) are proven tools for assessing and monitoring diversity. These structures on trees are potential indicators of biota, but there is a huge gap in TMH-related knowledge from the tropical regions, the cradles of biodiversity. Thus, an inventory was made to document the TMHs in the tropical forests of southern Western Ghats, India. In evergreen forests, 3,637 TMH host and 450 cavity host trees were identified from the 6,363 trees sampled. The density of TMHs was 972.57±341.25 ha-1and cavity density was 63.13±11.91 ha-1. In moist deciduous forests, out of 1,545 trees sampled, 1,108 hosted TMHs and 212 trees hosted cavities. The density of TMHs was 493.67±133.28 ha-1and cavity density was 42.00±15.01 ha-1. TMHs were categorised into nine categories and 33 sub-categories. The TMH and cavity occurrences were significantly influenced by species richness, stand density, basal area, diameter and height of trees, and density of healthy, unhealthy and dead trees. Dominant and codominant individuals hosted more TMHs and cavities in the deciduous stands while in evergreen, intermediate and overtopped trees had more TMHs and intermediate and codominant had more cavities. In both the habitats the important species of the habitat were also major hosts for TMHs and cavities.HighlightsPrimary inventory of diversity of TMHs and their host trees in tropical forestsTMH and cavity occurrences are significantly influenced by stand characteristicsKey species in the habitats also form major hosts for TMHs and cavitiesDominant and codominant individuals host more TMHs and cavities in deciduous standsIntermediate and overtopped trees host more TMHs, intermediate and codominant host more cavities in evergreen