bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embedding bioprinting of low viscous, photopolymerizable blood-based bioinks in a self-healing transparent supporting bath
Authors: Decarli Monize Caiado , Ferreira Helena P. , Sobreiro-Almeida Rita , Teixeira Filipa C. , Correia Tiago R. , Babilotte Joanna , Olijve Jos , Custódio Catarina A. , Gonçalves Inês C. , Mota Carlos , Mano João F. , Moroni Lorenzo 
Published: June 2024

AbstractProtein-based hydrogels have great potential to be used as bioinks for biofabrication-driven tissue regeneration strategies due to their innate bioactivity. Nevertheless, their use as bioinks in conventional 3D bioprinting is impaired due to their intrinsic low viscosity. Using embedding bioprinting, a liquid bioink is printed whithin a support that physically holds the patterned filament. Inspired by the recognized microencapsulation technique complex coacervation, we introduce crystal self-healing embedding bioprinting (CLADDING) based on a highly transparent crystal supporting bath. The suitability of distinct classes of gelatins was evaluated (i.e., molecular weight distribution, isoelectric point and ionic content), as well as the formation of gelatin-gum arabic microparticles as a function of pH, temperature, solvent and mass ratios. Characterizing and controlling this parametric window resulted in high yields of support bath with ideal self-healing properties for interaction with protein-based bioinks during bioprinting. This support bath achieved transparency, which boosted light permeation within the bath. CLADDING bioprinted constructs fully composed of platelet lysates encapsulating a co-culture of human mesenchymal stem cells and endothelial cells were obtained, demonstrating high-dense cellular network with excellent cell viability and stability over a month. CLADDING broadens the spectrum of photocrosslinkable materials with extremely low viscosity that can now be bioprinted with sensitive cells using embedding bioprinting without any additional support.
Multicompartmentalized microvascularized tumor-on-a-chip to study tumor-stroma interactions and drug resistance in ovarian cancer
Authors: Plesselova Simona , Calar Kristin , Axemaker Hailey , Sahly Emma , de la Puente Pilar 
Published: June 2024

AbstractIntroductionThe majority of ovarian cancer (OC) patients receiving standard of care chemotherapy develop chemoresistance within 5 years. The tumor microenvironment (TME) is a dynamic and influential player in disease progression and therapeutic response. However, there is a lack of models that allow us to elucidate the compartmentalized nature of TME in a controllable, yet physiologically relevant manner and its critical role in modulating drug resistance.MethodsWe developed a 3D microvascularized multiniche tumor-on-a-chip formed by five chambers (central cancer chamber, flanked by two lateral stromal chambers and two external circulation chambers) to recapitulate OC-TME compartmentalization and study its influence on drug resistance. Stromal chambers included endothelial cells alone or cocultured with normal fibroblasts or cancer-associated fibroblasts (CAF).ResultsThe tumor-on-a-chip recapitulated spatial TME compartmentalization including vessel-like structure, stromal-mediated extracellular matrix (ECM) remodeling, generation of oxygen gradients, and delayed drug diffusion/penetration from the circulation chamber towards the cancer chamber. The cancer chamber mimicked metastasis-like migration and increased drug resistance to carboplatin/paclitaxel treatment in the presence of CAF when compared to normal fibroblasts. CAF-mediated drug resistance was rescued by ECM targeted therapy. Critically, these results demonstrate that cellular crosstalk recreation and spatial organization through compartmentalization are essential to determining the effect of the compartmentalized OC-TME on drug resistance.ConclusionsOur results present a functionally characterized microvascularized multiniche tumor-on-a-chip able to recapitulate TME compartmentalization influencing drug resistance. This technology holds the potential to guide the design of more effective and targeted therapeutic strategies to overcome chemoresistance in OC.
Widespread temporal niche partitioning in an adaptive radiation of cichlid fishes
Authors: Nichols Annika L. A. , Shafer Maxwell E. R. , Indermaur Adrian , Rüegg Attila , Gonzalez-Dominguez Rita , Malinsky Milan , Sommer-Trembo Carolin , Fritschi Laura , Salzburger Walter , Schier Alexander F. 
Published: June 2024

AbstractThe partitioning of ecological niches is a fundamental component of species diversification in adaptive radiations. However, it is presently unknown if and how such bursts of organismal diversity are influenced by temporal niche partitioning, wherein species avoid competition by being active during different time windows. Here, we address this question through profiling temporal activity patterns in the exceptionally diverse fauna of cichlid fishes from African Lake Tanganyika. By integrating week-long longitudinal behavioural recordings of over 500 individuals from 60 species with eco-morphological and genomic information, we provide two lines of evidence that temporal niche partitioning facilitated this massive adaptive radiation. First, Tanganyikan cichlids exhibit all known circadian temporal activity patterns (diurnal, nocturnal, crepuscular, and cathemeral) and display substantial inter-specific variation in daily amounts of locomotion. Second, many species with similar habitat and diet niches occupy distinct temporal niches. Moreover, our results suggest that shifts between diurnal and nocturnal activity patterns are facilitated by a crepuscular intermediate state. In addition, genome-wide association studies indicate that the genetics underlying activity patterns is complex, with different clades associated with different combinations of variants. The identified variants were not associated with core circadian clock genes but with genes implicated in synapse function. These observations indicate that temporal niche partitioning contributed to adaptive radiation in cichlids and that many genes are associated with the diversity and evolution of temporal activity patterns.
Complement Biosensors Identify a Classical Pathway Stimulus in Complement-Mediated Hemolytic Uremic Syndrome
Authors: Cole Michael A. , Ranjan Nikhil , Gerber Gloria F. , Pan Xiang-Zuo , Flores-Guerrero Daniel , Chaturvedi Shruti , Sperati C. John , McCrae Keith R. , Brodsky Robert A. 
Published: June 2024

AbstractComplement-mediated hemolytic uremic syndrome (CM-HUS) is a thrombotic microangiopathy characterized by germline variants or acquired antibodies to complement proteins and regulators. Building upon our prior experience with the modified Ham (mHam) assay for ex vivo diagnosis of complementopathies, we have developed an array of cell-based complement “biosensors’’ by selective removal of complement regulatory proteins (CD55 and CD59, CD46, or a combination thereof) in an autonomously bioluminescent HEK293 cell line. These biosensors can be used as a sensitive method for diagnosing CM-HUS and monitoring therapeutic complement blockade. Using specific complement pathway inhibitors, this model identifies IgM-driven classical pathway stimulus during both acute disease and in many patients during clinical remission. This provides a potential explanation for ~50% of CM-HUS patients who lack an alternative pathway “driving” variant and suggests at least a subset of CM-HUS is characterized by a breakdown of IgM immunologic tolerance.Key PointsCM-HUS has a CP stimulus driven by polyreactive IgM, addressing the mystery of why 40% of CM-HUS lack complement specific variantsComplement biosensors and the bioluminescent mHam can be used to aid in diagnosis of CM-HUS and monitor complement inhibitor therapy
Analysis of gene expression profiles to elucidate racial differences in African American and White patients with Triple-negative breast cancer
Authors: McAndrew Hailey , Rigler Jessica , Yeguvapalli Suneetha , Chitrala Kumaraswamy Naidu 
Published: June 2024

AbstractTriple-negative breast cancer (TNBC) is the second most diagnosed subtype of breast cancer. It is known to be the most aggressive one that lacks known targetable receptors. One of the concerns in TNBC is the disparities in its prevalence and tumor pathogenesis among women with non-Hispanic African American backgrounds. Despite extensive research, the genetic underpinnings that lead to these disparities remain elusive. The current study aims to provide initiative for further clinical research in the development of targeted therapy for TNBC. Gene expression profiles from African American (AA) and European American (EA) patients with TNBC were collected from Gene Expression Omnibus and performed differential gene expression (DEG)analysis. Candidate genes for a significant correlation between expression and survival rates for breast invasive carcinoma were analyzed using UALCAN. The DAVID annotation tool, Enrichr web server, KEGG database, and Gene Ontology (GO) database were used for functional enrichment analysis of target genes. The Network Analyst server was used to identify ligands with strong affinities, SeamDock server for molecular docking between the biomarkers/associated ligands and examined protein-protein interactions (PPI) from the STRING server. Data from public breast cancer cohorts was utilized to identify expression patterns associated with poor survival outcomes of AA patients with TNBC. Our results showed three genes of interest (CCT3,LSM2, andMRPS16) and potential ligands for molecular docking. Molecular docking was performed for the ICG001 ligand toCCT3(binding affinities of -9.3 kcal/mol and -8.9 kcal/mol) and other interacting proteins (CDC20andPPP2CA) with high degrees of connectivity. The results determined molecular docking of ICG001 to theCDC20protein resulted in the highest binding affinity. Our results demonstrated thatCCT3and its interacting partners could serve as potential biomarkers due to their association with the survival outcome of AA patients with TNBC and ICG 001 could be the therapeutic lead for these biomarkers.
Cardiac acetylcholinesterase and butyrylcholinesterase have distinct localization and function
Authors: Dingová Dominika , Kučera Matej , Hodbod Tibor , Fischmeister Rodolphe , Krejci Eric , Hrabovská Anna 
Published: June 2024

AbstractCholinesterase (ChE) inhibitors are under consideration to be used in the treatment of cardiovascular pathologies. A prerequisite to advancing ChE inhibitors into the clinic is their thorough characterization in the heart. The aim here was to provide a detailed analysis of cardiac ChE to understand their molecular composition, localization, and physiological functions. A battery of biochemical, microscopic, and physiological experiments was used to analyze two known ChE, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), in hearts of mutant mice lacking different ChE molecular forms. Overall, AChE activity was exceeded by BChE, while it was localized mainly in the atria and the ventricular epicardium of the heart base. AChE was anchored by ColQ in the basal lamina or by PRiMA at the plasma membrane and co-localized with the neuronal marker TUJ1. In absence of anchored AChE, heart rate was unresponsive to a ChE inhibitor. BChE, the major ChE in heart, was detected predominantly in ventricles, presumably as a precursor (soluble monomers/dimers). Mice lacking BChE were more sensitive to a ChE inhibitor. Nevertheless, the overall impact on heart physiology was subtle, showing mainly a role in cholinergic antagonism to the positive inotropic effect of β-adrenergic stimulation. Our results help to unravel the mechanisms of ChE in cardiovascular pathologies and provide a foundation to facilitate the design of a novel, more effective pharmacotherapies, which may reduce morbidity and mortality of patients with various heart diseases.Abstract figure legendAcetylcholinesterase (AChE) has the highest activity in the atria. It is present in the heart in molecular forms anchored by a proline-rich membrane anchor (PRiMA) and by collagen Q (ColQ) and hydrolyzes acetylcholine of neuronal origin (neuronal ACh). Butyrylcholinesterase (BChE) is predominant in the ventricles. It is secreted in the form of a soluble tetramer and hydrolyzes acetylcholine originating from cardiomyocytes (non-neuronal ACh).Key pointsInhibition of cholinesterases has therapeutic potential in cardiovascular pathologiesBoth known cholinesterases are present in heartEach cholinesterase has distinct localization patterns in the heart and functions in cardiac physiologySelective inhibition of acetylcholinesterase or butyrylcholinesterase may be used to alter specific cardiac functionsButyrylcholinesterase polymorphism may have an impact on the outcome of the cholinesterase inhibitor treatment
Evaluating methods for B-cell clonal family assignment
Authors: Voss Katalin , Kaur Katrina M. , Banerjee Rituparna , Breden Felix , Pennell Matt 
Published: June 2024

AbstractThe adaptive immune response relies on a diverse repertoire of B-cell receptors, each of which is characterized by a distinct sequence resulting from VDJ-recombination. Upon binding to an antigen, B-cells undergo clonal expansion and in a process unique to B-cells the overall binding affinity of the repertoire is further enhanced by somatic hypermutations in the receptor sequence. For B-cell repertoires it is therefore particularly important to analyze the dynamics of clonal expansion and patterns of somatic hypermutations and thus it is necessary to group the sequences into distinct clones to determine the number and identity of expanding clonal families responding to an antigen. Multiple methods are currently used to identify clones from sequences, employing distinct approaches to the problem. Until now there has not been an extensive comparison of how well these methods perform under the same conditions. Furthermore, since this is fundamentally a phylogenetics problem, we speculated that the mPTP method, which delimits species based on an analysis of changes in the underlying process of diversification, might perform as well as or better than existing methods. Here we conducted extensive simulations of B-cell repertoires under a diverse set of conditions and studied errors in clonal assignment and in downstream ancestral state reconstruction. We demonstrated that SCOPer-H consistently yielded superior results across parameters. However, this approach relies on a good reference assembly for the germline immunoglobulin genes which is lacking for many species. Using mPTP had lower error rates than tailor-made immunogenetic methods and should therefore be considered by researchers studying antibody evolution in non-model organisms without a reference genome.
Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with Multiple Sclerosis
Authors: Smith Katie J , Lim Zachary , Vermeren Sonja , Miron Veronique E. , Dimeloe Sarah , Davidson Donald J , Williams Anna , Findlay Emily Gwyer 
Published: June 2024

AbstractMultiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterised. Here we focused on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences. In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular over-abundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells. Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.
Assessing the Sustainability of Pacific Walrus Harvest in a Changing Environment
Authors: Johnson Devin L. , Eisaguirre Joseph M. , Taylor Rebecca L. , Andersen Erik M. , Garlich-Miller Joel L. 
Published: June 2024

ABSTRACTHarvest sustainability is a primary goal of wildlife management and conservation, and in a changing world it is increasingly important to consider environmental drivers of population dynamics alongside harvest in cohesive management plans. This is particularly pertinent for harvested species that are acutely experiencing effects of climate change. The Pacific walrus (Odobenus rosmarus divergens), a critical traditional subsistence resource for indigenous communities, is simultaneously subject to rapid habitat loss associated with diminishing sea ice and an increasing anthropogenic footprint in the Arctic. We developed a theta-logistic population modeling-management framework to evaluate various harvest scenarios combined with four potential climate/disturbance scenarios (ranging from optimistic–pessimistic) which simulates Pacific walrus population dynamics to the end of the 21stcentury. We considered two types of harvest strategies: (1) adaptive harvest scenarios wherein harvest is calculated as a percentage of the population and annual harvests are updated at set intervals as the population is reassessed, and (2) non-adaptive harvest scenarios wherein annual harvest remains constant. All climate/disturbance scenarios indicated declines of varying severity in Pacific walrus abundance to the end of the 21stcentury, even in the absence of harvest. However, we found that an adaptive annual harvest of 1.23% of the independent-aged female subset of the population (e.g., 1,280 independent-aged females harvested in 2020, representing contemporary harvest levels) met our criterion for sustainability (>70% probability of maintaining population abundance above maximum net productivity level) under all climate/disturbance scenarios, accepting a medium risk tolerance level of 25%. This suggests that the present rate of Pacific walrus harvest is sustainable and will continue to be—provided the harvest adapts to match changes in population dynamics. Our simulations suggest that a sustainable non-adaptive harvest is also possible, but only at low levels if the population declines as expected. Applying a constant annual harvest of 1,280 independent-aged females (equivalent to contemporary harvest levels of 1.23) exceeded our criterion for sustainability and resulted in a >5% chance of quasi-extinction by the end of the 21stcentury under three of the four climate/disturbance scenarios we evaluated. Our results highlight the importance of adaptive co-management strategies, and we suggest such modeling frameworks are useful for managing for harvest sustainability in a changing climate.
Rapid Changes in Chromosome Counts in Fishes from the Spiral Egg Clade within the Gourami Family (Osphronemidae)
Authors: Mobley Brendan , Anderson Andrew P. 
Published: June 2024

AbstractIdentifying clades with numerous and noticeable changes in chromosome counts is an important step in unraveling the evolutionary mechanisms that shape cytogenetic processes. Here, we describe low chromosome counts in a group of teleost fishes delimited by their unique spiral egg structure and with a species with a known low chromosome count within the labyrinthine clade (Osphronemidae). We sampled seven of nine known species within this spiral egg clade, reporting novel chromosome counts for five species and confirming two others. Overall, we find high variability in both chromosome count and arm number, which suggests a rapid loss of chromosomes during the emergence of the clade and numerous large-scale mutations occurring across evolutionary time. Lastly, we offer some possible explanations for these changes based on current and ongoing empirical and theoretical research. These data provide important information in cataloguing rapid chromosomal shifts in teleost fishes and highlights this group for further study in chromosomal and genomic evolution due to their karyotypic heterogeneity.
Chromatin Capture Upsampling Toolbox - CCUT: A Versatile and unified Framework to Train Your Chromatin Capture Deep Learning Models
Authors: Sys Stanislav , Ceron-Noriega Alejandro , Kerber Anne , Weißbach Stephan , Schweiger Susann , Wand Michael , Everschor-Sitte Karin , Gerber Susanne 
Published: June 2024

AbstractChromatin Capture Experiments such as Hi-C and Micro-C have become popular methods for genome architecture exploration. Recently, also a protocol for long read sequencing, Pore-C, was introduced, allowing the characterization of three-dimensional chromatin structures using Oxford Nanopore Sequencing Technology. Here, we present a framework that focuses on the efficient reconstruction of low-resolution Pore-C data but can also process all other 3C data, such as Hi-C and Micro-C matrices, using models that can be trained on a consumer GPU. Furthermore, we integrate building blocks of popular super-resolution methods such as SWIN-Transformer or residual-in-residual-blocks to modify or build customized networks on the fly. Pre-built models were trained and evaluated on multiple publicly available gold-standard Micro-C and Pore-C datasets, allowing for fine-scale structure prediction. Our work aims to overcome the drawback of high sequencing costs to construct high resolution contact matrices, as well as the problem of mapping low-coverage libraries to high-resolution structures in the genome. Although there have been major breakthroughs regarding NGS-based methods for the reconstruction of high-resolution chromatin interaction matrices from low-resolution data, for data obtained by long-read sequencing, there is currently no solution to reconstruct missing and sparse information and to improve the quality.AvailabilityThe tool is available at (https://github.com/stasys-hub/CCUT)