bluuebunny/crossref_metadata_2025_split huggingface dataset:
Particulate Contamination of Human Placenta: Plastic and non-plastic
Authors: Zurub Rewa , Bainbridge Shannon , Rahman Luna , Halappanavar Sabina , Wade Michael G. 
Published: March 2024

AbstractRecent evidence indicates that the human womb is contaminated with a variety of particulate contaminants. Microplastics (MPs, tiny plastic particles (<5 mm) generated by the breakdown of larger plastic products in the environment) accumulation in human placenta has recently been described. In addition, recent evidence has correlated the number of air pollution particulates in term placentas to the loading of these particles in dust from the gestational parent home. The current study sought to characterize the accumulation of plastic and non-plastic particles (NPP) within the term human placenta. Placenta tissues were collected from healthy, singleton pregnancies following vaginal (n=5) and caesarean section (n=5) deliveries at a tertiary care centre located in an urban Canadian city (Ottawa, ON), with particles detected and characterized by Raman micro-spectroscopy. Both plastic and non-plastic particles were identified in all placentas examined, with an average of 1 ± 1.2 MPs /g and 4 ± 2.9 NPP /g of tissue. Similar tissue concentrations of MPs and NNP were identified in all regions of the placenta (basal plate, chorionic villous, chorionic plate), and did not differ according to mode of delivery. MPs ranged in size (2 - 60 μm), with the most abundant MPs being polyethylene (PE), polypropylene (PP), polystyrene (PS) and polyvinyl chloride (PVC). The most abundantly identified NPP were carbon, graphite, and lead oxide. Collectively, these results demonstrate the accumulation of foreign particles, including MPs, throughout the human placenta. Given the vital functions of the placenta in supporting fetal growth and development, and a potential for MPs to induce toxicity, further investigations into the potential harmful effects of these environmental toxicants on maternal and fetal health is warranted.Graphical AbstractHighlightsBoth plastic and non-plastic foreign particles were observed in term placentas from Canadian womenPlacenta contamination with most of the non-plastic particle types observed has not previously been reported.Particles were observed in similar frequency in placenta regions corresponding to maternal or fetal circulation suggesting that particles pass unhindered through the placenta.
Circadian Rhythms in Murine Ocular Tissues including Sclera are affected by Neurobasal A Medium Preincubation, Mouse Strain, but not Sex
Authors: Milićević Nemanja , Sandu Cristina , Challet Etienne , Ihalainen Teemu O. , Nymark Soile , Felder-Schmittbuhl Marie-Paule 
Published: March 2024

AbstractPurposeOur understanding of ocular clocks has been profoundly advanced by the development of real-time recording of bioluminescence of PER2::LUC knock-in mouse explants. However, the effect of sex, mouse strain and culturing conditions on ocular clocks remains unknown. Here, we studied the role these variables play on PER2::LUC bioluminescence rhythms of ocular tissues: retinas, corneas and posterior eye cups (PEC). We also tested the hypothesis that the sclera contains a circadian oscillator by using scraped PEC as a proxy.MethodsRetinas, corneas, intact and scraped PECs were obtained from male and female PER2::LUC knock-in mice maintained on either a pigmented C57BL/6J or albino RjOrl:SWISS background. PER2::LUC bioluminescence rhythms in ocular tissues were measured using a Lumicycle®.ResultsWe compared PER2::LUC bioluminescence rhythms between ocular tissues and found that all ocular tissues oscillated, including the scraped PEC, which was previously not known to oscillate. The rhythms in scraped PECs had lower amplitudes, longer periods and distinct acrophases compared to other ocular tissues. Ocular tissues of RjOrl:SWISS mice oscillated with higher amplitudes compared to the ones of C57BL/6J, with corneal rhythms being most affected by mouse strain. A 24h preincubation with Neurobasal A medium enhanced rhythms of ocular tissues, whereas sex differences were not detected for these rhythms.ConclusionsWe discovered a novel oscillator in the sclera. PER2::LUC bioluminescence rhythms in murine ocular tissues are enhanced by Neurobasal A medium preincubation, mouse strain but not sex.
CHEMOKINE SIGNALING IN BREAST CANCER: FOCUS ON CC-MOTIF CHEMOKINE LIGANDS
Authors: Kacar Sedat 
Published: March 2024

AbstractBased on 2020 data from GLOBOCAN, breast cancer holds the highest incidence rate in the majority of countries (159 out of 185 countries) and is the leading cause of mortality in 110 countries Chemokines are 8-10 kDa proteins activating through transmembrane G-coupled receptors (GPCRs) with 24 CC-motif type known human cytokines and 10 respective receptors. Chemokines and chemokines receptors have the potential for new breast cancer therapeutics modalities. In the complex chemokine world, not only one chemokine can bind to multiple receptors but also one receptor can be activated by several chemokine ligands. The fact that immune cells possess the potential to express multiple receptors and also secrete a diverse number of chemokines further intensifies the intricate and challenging to grasp chemokines interaction with receptors and microenvironment. In addition, the implication of chemokines in the malignant activation of tumor cells makes them indispensable contributors to the cancer microenvironment and influences the fate of tumor cells and the overall survival of the patients. Therefore, herein, we aimed in this study at attracting the researchers’ attention to the particular function of all known CC-motif chemokines and to-date findings, their expressional changes in normal, tumor and tumor adjacent tissues, important key effects in breast cancer and more importantly, we analyzed the breast tumor samples’ expression data retrieved from TCGA, Xena UCSC as well as UALCAN database regarding to showing any potential to be a general, subclass-specific or stage-specific marker as well as effects of overall survival of the patients and their correlation with literature findings. Basically, we desire this study to be a sort of reference insights for effects of human CC-motif chemokines in breast cancer or provide ready-to-use source and insights for researchers with the graphs and analyzes from different databases.
An immune signature of postoperative cognitive decline in elderly patients
Authors: Verdonk Franck , Cambriel Amélie , Hedou Julien , Ganio Ed , Bellan Grégoire , Gaudilliere Dyani , Einhaus Jakob , Sabayev Maximilian , Stelzer Ina A. , Feyaerts Dorien , Bonham Adam T. , Ando Kazuo , Choisy Benjamin , Drover David , Heifets Boris , Chretien Fabrice , Aghaeepour Nima , Angst Martin S. , Molliex Serge , Sharshar Tarek , Gaillard Raphael , Gaudilliere Brice 
Published: March 2024

AbstractPostoperative cognitive decline (POCD) is the predominant complication affecting elderly patients following major surgery, yet its prediction and prevention remain challenging. Understanding biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This longitudinal study involving 26 elderly patients undergoing orthopedic surgery aimed to characterize the impact of peripheral immune cell responses to surgical trauma on POCD. Trajectory analyses of single-cell mass cytometry data highlighted early JAK/STAT signaling exacerbation and diminished MyD88 signaling post-surgery in patients who developed POCD. Further analyses integrating single-cell and plasma proteomic data collected before surgery with clinical variables yielded a sparse predictive model that accurately identified patients who would develop POCD (AUC = 0.80). The resulting POCD immune signature included one plasma protein and ten immune cell features, offering a concise list of biomarker candidates for developing point-of-care prognostic tests to personalize perioperative management of at-risk patients. The code and the data are documented and available athttps://github.com/gregbellan/POCD.TeaserModeling immune cell responses and plasma proteomic data predicts postoperative cognitive decline.
Chromatin packing domains persist after RAD21 depletion in 3D
Authors: Li Wing Shun , Carter Lucas M , Almassalha Luay Matthew , Pujadas-Liwag Emily M. , Kuo Tiffany , MacQuarrie Kyle L , Carignano Marcelo , Dravid Vinayak , Kanemaki Masato T. , Szleifer Igal , Backman Vadim 
Published: March 2024

AbstractUnderstanding chromatin organization requires integrating measurements of genome connectivity and physical structure. Prior work demonstrates that RAD21 depletion results in the complete loss of topologically associated and loop domains on Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with Hi-C, we study the role of cohesin in regulating the spatially resolved, conformationally defined chromatin packing domains. We find that only 20% of packing domains are lost on electron microscopy upon RAD21 depletion with the effect primarily on small, poorly packed (nascent) domains. Overall, this contrasts with the prevailing understanding of genome regulation, indicating that while cohesin influences domain formation, non-cohesin mediated mechanisms predominantly regulate the 3D genomic physical structure.
Characterization of Composite Agarose-Collagen Hydrogels for Chondrocyte Culture
Authors: Zigan Clarisse , Alston Claudia Benito , Chatterjee Aritra , Solorio Luis , Chan Deva D. 
Published: March 2024

ABSTRACTTo elucidate the mechanisms of cellular mechanotransduction, it is necessary to employ biomaterials that effectively merge biofunctionality with appropriate mechanical characteristics. Agarose and collagen separately are common biopolymers used in cartilage mechanobiology and mechanotransduction studies but lack features that make them ideal for functional engineered cartilage. In this study, agarose (8% w/v and 4% w/v) is blended with collagen type I (4mg/mL) to create composites. We hypothesized that a higher stiffness, composite hydrogel would promote native cartilage-like conditions. To address these questions, acellular and cell-laden studies were completed to assess rheologic and compressive properties, contraction, and structural homogeneity in addition to matrix mechanics, cell proliferation, and glycosaminoglycan production. Over 21 days in culture, cellular 4% agarose – 2mg/mL collagen I hydrogels displayed good structural and bulk mechanical properties, cell proliferation, and continual glycosaminoglycan production, indicating promise towards the development of an effective hydrogel for chondrocyte mechanotransduction and mechanobiology studies.Graphical Abstract
Chrom-pro: A User-Friendly Toolkit for De-novo Chromosome Assembly and Genomic Analysis
Authors: Song Wei , Ye Tianrui , Liu Shaobo , Shen Dawei , Du Yuhui , Yang Yuening , Lu Yanming , Jin Hulin , Huo Yixin , Piao Weilan , Jin Hua 
Published: March 2024

AbstractChromosome-level genome assembly is fundamental to current genomic and post-genomic research, however, the process remains complicated and challenging due to the lack of a standardized automatic workflow. The frequently-used method for high-quality genome assembly generally employs second-generation sequencing (SGS) low error reads, third-generation sequencing (TGS) long reads and Hi-C reads. In this study, we developed a multifunctional toolkit called Chrom-pro that integrated commonly-used algorithms for de novo chromosome-level genome assembly with above three data sets into a user-friendly, automatic workflow. Besides chromosome assembly, Chrom-pro also encompasses multiple functionalities for genome quality assessment, comparative genomic analysis, and structural variant detection, which offers substantial support for downstream research. To evaluate the performance of Chrom-pro software, we tested the software with publicly available sequencing data of mango, pufferfish, and plum, and the excellence was confirmed by achieving a BUSCO completeness score of over 95% as well as high collinearity with the reference genome. Furthermore, we applied Chrom-pro to investigating the impact of different internal algorithm options on the accuracy of chromosome assembly, providing guidance for advancing relevant research in the future. Overall, the development of Chrom-pro will significantly improve the efficiency and quality of chromosome assembly and contributing to the advancement of genomic research.
The CCR4/CCL17 axis drives intestinal acute Graft versus Host disease after allogeneic bone marrow transplantation
Authors: Schlaweck Sebastian , Klesse Michelle , Schanz Oliver , Jorch Selina K. , Kristiansen Glen , Toma Marieta , Flores Chrystel , Becker-Gotot Janine , Kurts Christian , Brossart Peter , Wolf Dominik , Heine Annkristin 
Published: March 2024

AbstractAcute-Graft-versus-Host disease (aGvHD) is a life-threatening complication after allogeneic stem-cell-transplantation. It is mediated by alloreactive T cells whose trafficking to aGvHD target organs is orchestrated by chemokines.We here asked whether CCL17 and its corresponding receptor CCR4 are involved in aGvHD development and severity. We applied an experimental mouse model of aGvHD in CCR4/CCL17 knockout mice and analyzed gut biopsies of GvHD patients.We show that the absence of CCR4 in transplanted T cells induced significantly less severe aGvHD. This was accompanied by reduced expression of Gata3. Mechanistically, only CD4+, but not CD8+CCR4-/-T cells protected from aGvHD. We next identified dendritic cells in the small intestine to produce CCL17, which selectively recruited CD4+T cells. IL-4 production by intestinal CD4+T cells promoted proliferation of CD8+T cells. In line, we detected an upregulation of CCL17 andGata3in human aGvHD samples.Our results indicate that local CCL17 production in aGvHD target organs recruits T cells, reinforcing local tissue damage and immune cell recruitment. We identified the JAK1/2-inhibitor ruxolitinib to dampen CCL17-expression, thereby reducing GvHD severity.We here dissect a to date unknown role of the CCL17-CCR4 axis in aGvHD, which might help to develop novel therapeutic strategies.
Examination of the role of mutualism in immune evasion
Authors: Gourmet Lucie , Walker-Samuel Simon , Mallick Parag 
Published: March 2024

AbstractThough the earliest stages of oncogenesis, post initiation, are not well understood, it is generally appreciated that a successful transition from a collection of dysregulated cells to an aggressive tumor requires complex ecological interactions between cancer cells and their environment. One key component of tumorigenesis is immune evasion. To investigate the interplay amongst the ecological behaviour of mutualism and immune evasion, we used a computational simulation framework. Sensitivity analyses of the growth of a virtual tumor implemented as a 2D-hexagonal lattice model suggests tumor survival depends on the interplay between growth rates, mutualism and immune evasion. In 60% of simulations, cancer clones with low growth rates, but exhibiting mutualism were able to evade the immune system and continue progressing suggesting that tumors with equivalent growth rates and no mutualism are more likely to be eliminated than tumors with mutualism. Tumors with faster growth rates showed a lower dependence upon mutualism for progression. Geostatistical analysis showed decreased spatial heterogeneity over time for polyclonal tumours with a high division rate. Overall, these results suggest that in slow growing tumors, mutualism is critical for early tumorigenesis.
Variety is the spice of life: nongenetic variation in life histories influences population growth and evolvability
Authors: Forsythe Amy B. , Otto Sarah P. , Nelson William A. , Day Troy 
Published: March 2024

AbstractIndividual vital rates are key determinants of lifetime reproductive success, and variability in these rates shapes population dynamics. Previous studies have found that this vital rate hetero-geneity can influence demographic properties including population growth rates, however, the explicit effects of the amount of variation within and the covariance between vital rates that can also vary throughout the lifespan on population growth remains unknown. Here, we explore the analytical consequences of nongenetic heterogeneity on long-term population growth rates and rates of evolution by modifying traditional age-structured population projection matrices to incorporate variation among individual vital rates. The model allows vital rates to be permanent throughout life (“fixed condition”) or to change over the lifespan (“dynamic condition”). We reduce the complexity associated with adding individual heterogeneity to age-structured models through a novel application of matrix collapsing (“phenotypic collapsing”), showing how to collapse in a manner that preserves the asymptotic and transient dynamics of the original matrix. The main conclusion is that nongenetic individual heterogeneity can strongly impact the longterm growth rate and rates of evolution. The magnitude and sign of this impact depends heavily on how the heterogeneity covaries across the lifespan of an organism. Our results emphasize that nongenetic variation cannot simply be viewed as random noise, but rather that it has consistent, predictable effects on fitness and evolvability.
Evolved and plastic gene expression in adaptation to a novel niche
Authors: Steward Rachel A , Ortega Giménez Jesús , Choudhary Shruti , Yi Su , Aken Olivier Van , Runemark Anna 
Published: March 2024

AbstractGene expression, resulting from complex regulatory interactions, plays an important role in adaptation and speciation. While gene expression historically has been studied in the context of reproductive isolation in speciation research, a role for evolved differences in gene expression in adaptation to novel niches is increasingly appreciated. How gene expression evolves and enables divergent ecological adaptation, and how changes in gene expression relate to genomic architecture and genetic divergence are pressing questions in understanding the processes of adaptation and ecological speciation. Further, how plasticity in gene expression can both contribute to and be affected by the process of ecological adaptation is a crucial component in understanding gene expression evolution. To address these questions, we investigate the role of evolved and plastic gene expression differences in adaptation leveraging an established host plant shift in the peacock flyTephritis conura. Using a cross-fostering design where larvae feed on either natal or alternate host plants, we uncover extensive evolved differences in gene expression between the ecotypes, strikingly in genes associated with processing of host plant chemicals. We find limited evidence for plasticity, with some indications of higher plasticity in the ancestral ecotype where the expression of three gene coexpression modules is altered when larvae are cross-fostered to the derived host plant. Interestingly, we find an enrichment of differentially expressed genes within a large, ecotype-specific inversion in theT. conuragenome. This finding adds to evidence that inversions are important for enabling diversification in the face of gene flow and underscores that effects on gene expression may be key to understanding the role of inversions.
Harnessing Transformers to Generate Protein Sequences Prone to Liquid Liquid Phase Separation
Authors: Wasim Abdul , Pramanik Ushasi , Das Anirban , Latua Pikaso , Rudra Jai S. , Mondal Jagannath 
Published: March 2024

AbstractUnderstanding the molecular grammar that governs protein phase separation is essential for advancements in bioinformatics and protein engineering. This study leverages Generative Pre-trained Transformer (GPT)-based Protein Language Models (PLMs) to decode the complex grammar of proteins prone to liquid-liquid phase separation (LLPS). We trained three distinct GPT models on datasets comprising amino acid sequences with varying LLPS propensities: highly predisposed (LLPS+ GPT), moderate (LLPS-GPT), and resistant (PDB* GPT). As training progressed, the LLPS-prone model began to learn embeddings that were distinct from those in LLPS-resistant sequences. These models generated 18,000 protein sequences ranging from 20 to 200 amino acids, which exhibited low similarity to known sequences in the SwissProt database. Statistical analysis revealed subtle but significant differences in amino acid occurrence probabilities between sequences from LLPS-prone and LLPS-resistant models, suggesting distinct molecular grammar underlying their phase separation abilities. Notably, sequences from LLPS+ GPT showed fewer aromatic residues and a higher fraction of charge decoration. Short peptides (20-25 amino acids) generated from LLPS+ GPT underwent computational and wet-lab validation, demonstrating their ability to form phase-separated states in vitro. The generated sequences enriched the existing database and enabled the development of a robust classifier that accurately distinguishes LLPS-prone from non-LLPS sequences. This research marks a significant advancement in using computational models to explore and engineer the vast protein sequence space associated with LLPS-prone proteins.
Crimean-Congo Hemorrhagic Fever Survivors Elicit Protective Non-Neutralizing Antibodies that Target 11 Overlapping Regions on Viral Glycoprotein GP38
Authors: Shin Olivia S. , Monticelli Stephanie R. , Hjorth Christy K. , Hornet Vladlena , Doyle Michael , Abelson Dafna , Kuehne Ana I. , Wang Albert , Bakken Russell R. , Mishra Akaash , Middlecamp Marissa , Champney Elizabeth , Stuart Lauran , Maurer Daniel P. , Li Jiannan , Berrigan Jacob , Barajas Jennifer , Balinandi Stephen , Lutwama Julius J. , Lobel Leslie , Zeitlin Larry , Walker Laura M. , Dye John M. , Chandran Kartik , Herbert Andrew S. , Pauli Noel T. , McLellan Jason S. 
Published: March 2024

SUMMARYCrimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, unique toNairoviridae, is a target of protective antibodies, but extensive mapping of the human antibody response to GP38 has not been previously performed. Here, we isolated 188 GP38-specific antibodies from human survivors of infection. Competition experiments showed that these antibodies bind across five distinct antigenic sites, encompassing eleven overlapping regions. Additionally, we reveal structures of GP38 bound with nine of these antibodies targeting different antigenic sites. Although GP38-specific antibodies were non-neutralizing, several antibodies were found to have protection equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and inform the development of broadly effective CCHFV antibody therapeutics.