bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tunable bicontinuous macroporous cell culture scaffolds via kinetically controlled phase separation
Authors: Dudaryeva Oksana Y. , Cousin Lucien , Krajnovic Leila , Gröbli Gian , Sapkota Virbin , Ritter Lauritz , Deshmukh Dhananjay , Style Robert W. , Levato Riccardo , Labouesse Céline , Tibbitt Mark W. 
Published: July 2024

AbstractThree-dimensional (3D) scaffolds enable biological investigations with a more natural cell conformation. However, the porosity of synthetic hydrogels is often limited to the nanometer scale, which confines the movement of 3D encapsulated cells and restricts dynamic cell processes. Precise control of hydrogel porosity across length scales remains a challenge and the development of porous materials that allow cell infiltration, spreading, and migration in a manner more similar to natural ECM environments is desirable. Here, we present a straightforward and reliable method for generating kinetically-controlled macroporous systems using liquid–liquid phase separation between poly(ethylene glycol) (PEG) and dextran. Photopolymerization-induced phase separation resulted in macroporous hydrogels with tunable pore size. Varying light intensity and hydrogel composition controlled polymerization kinetics, time to percolation, and complete gelation, which defined the average pore diameter (Ø = 1– 300 μm) and final gel stiffness of the formed hydrogels. Critically, for biological applications, macroporous hydrogels were prepared from aqueous polymer solutions at physiological pH and temperature using visible light, allowing for direct cell encapsulation. We encapsulated human dermal fibroblasts in a range of macroporous gels with different pore sizes. Porosity improved cell spreading with respect to bulk gels and allowed migration in the porous systems.
MR Corge: Sensitivity analysis of Mendelian randomization based on the core gene hypothesis for polygenic exposures
Authors: Zhang Wenmin , Su Chen-Yang , Yoshiji Satoshi , Lu Tianyuan 
Published: July 2024

AbstractSummaryMendelian randomization is being utilized to assess causal effects of polygenic exposures, where many genetic instruments are subject to horizontal pleiotropy. Existing methods for detecting and correcting for horizontal pleiotropy have important assumptions that may not be fulfilled. Built upon the core gene hypothesis, we developed MR Corge for performing sensitivity analysis of Mendelian randomization. MR Corge identifies a small number of putative core instruments that are more likely to affect genes with a direct biological role in an exposure and obtains causal effect estimates based on these instruments, thereby reducing the risk of horizontal pleiotropy. Using positive and negative controls, we demonstrated that MR Corge estimates aligned with established biomedical knowledge and the results of randomized controlled trials. MR Corge may be widely applied to investigate polygenic exposure-outcome relationships.Availability and ImplementationAn open-sourced R package is available athttps://github.com/zhwm/MRCorge.
IL-4 receptor alpha blockade in mice reduces skin inflammation, systemic response and the atopic march
Authors: Leyva-Castillo Juan-Manuel , Wong Daniel Sen Hoi , Geha Raif S 
Published: July 2024

AbstractAtopic dermatitis (AD) commonly precedes food allergy and asthma in the atopic march. Epicutaneous (EC) sensitization in mice with ovalbumin (OVA) results in allergic skin inflammation that mimics AD and promotes food anaphylaxis or asthma following a gastric or intranasal challenge with OVA, respectively. Using our mouse model of EC sensitization with OVA we evaluate whether anti-IL-4Rα blocking antibody improve allergic skin inflammation and impact the atopic march. IL-4Rα blockade at the end of EC sensitization decreased allergic skin inflammation in OVA-sensitized mice, evidenced by significantly decreased eosinophil infiltration, decrease production of IL-4, IL-13 by OVA- restimulated splenocytes and reduced serum levels OVA-specific IgE. However, late IL- 4Rα blockade did not affect food anaphylaxis or airway inflammation in EC sensitized mice following an oral or intranasal challenge with OVA. IL-4Rα blockade at the beginning of EC sensitization not only impact allergic skin inflammation and systemic response to the antigen, but also decreased food anaphylaxis or airway inflammation following OVA challenge. These results suggest that the blockade of sensitization through the skin by IL-4Rα blockade could impact the atopic march.
A pan-cancer gamma delta T cell repertoire
Authors: Yu Xiaoqing , Song Li , Cen Ling , Cao Biwei , Tao Ranran , Shen Yuanyuan , Daga Daniel Abate- , Rodriguez Paulo C. , Conejo-Garcia Jose R. , Wang Xuefeng 
Published: July 2024

SUMMARYThis report presents the largest collection of gamma-delta T cell receptor (γδ TCR) reads in human cancer to date, analyzing about 11,000 patient tumor samples across 33 cancer types using the TRUST4 algorithm. Despite γδ T cells being a small fraction of the T cell population, they play a key role in both innate and adaptive immunity. Our comprehensive analysis reveals their significant presence across all cancer types, specifically highlighting the diverse spectrum and clonality patterns of their γδ receptors. This research highlights the complex roles of γδ T cells in tumor tissues and their potential as prognostic biomarkers. We also demonstrate the utility of T cell receptor gamma (TRG) and delta (TRD) gene expression values from standard RNA-seq data. Ultimately, our work establishes a fundamental resource for future tumor-infiltrating γδ T cell research and may facilitate the development of novel γδ-T-cell-based therapeutic strategies. Together, we demonstrate the strong diversity and prognostic potential of γδ T cells in multiple cancer types.HighlightsComprehensive analysis of γδ TCRs from 11,473 tumor samplesSignificant variability and overall consistency in γδ gene expression and clonotypeγδ TCR expression and diversity as prognostic biomarkers across multiple cancersCentralized γδ TCR repertoire database for future therapeutic discovery
Effects of Age and Diet on Triglyceride Metabolism in Mice
Authors: Spitler Kathryn M. , Shetty Shwetha K. , Davies Brandon S.J. 
Published: July 2024

ABSTRACTBackgroundBoth age and diet can contribute to alterations in triglyceride metabolism and subsequent metabolic disease. In humans, plasma triglyceride levels increase with age. Diets high in saturated fats can increase triglyceride levels while diets high in omega-3 fatty acids decrease triglyceride levels. Here we asked how age and long-term diet effected triglyceride metabolism in mice.MethodsWe fed male and female mice a low-fat diet, a western diet, or a diet high in polyunsaturated and omega-3 (n-3) fatty acids for up to 2 years. We measured survival, body composition, plasma triglyceride levels, chylomicron clearance, and oral fat, glucose, and insulin tolerance.ResultsTriglyceride levels in mice did not increase with age, regardless of diet. Oral fat tolerance increased with age, while chylomicron clearance remained unchanged. Mice fed western diet had decreased survival. Interestingly, mice fed the n-3 diet gained more lean mass, and had lower insulin levels than mice fed either low-fat or western diet. Moreover, triglyceride uptake into the hearts of mice fed the n-3 diet was strikingly higher than in other groups.ConclusionsIn mice, age-induced changes in triglyceride metabolism did not match those in humans. Our data suggested that mice, like humans, had decreased fat absorption with age, but plasma triglyceride clearance did not decrease with age in mice, resulting in lower plasma triglyceride levels and improved oral fat tolerance with age. A chronic diet high in n-3 fatty acids increased insulin sensitivity and uptake of triglycerides specifically into the heart but how these observations are connected is unclear.Research PerspectivesThe changes in triglyceride metabolism that occur with age in humans are not reflected in a mouse model, thus mice are likely not an ideal model for understanding how age impacts lipid metabolism and subsequent metabolic disease.A fish-oil based high-fat diet high in omega-3 fatty acids significantly increases fatty acid uptake in the heart while at the same time decreases fasting insulin levels.In future studies it will be important to understand how the omega-3 fatty acid induced increase in fatty acid uptake affects cardiac function and how it is related to other phenotypes induced by omega-3 fatty acids.
A Novel Whole Tissue Explant Model of Hidradenitis Suppurativa
Authors: Leboit PE , Patel DU , Cohen JN , Moss MI , Naik HB , Yates AE , Harris HW , Klufas DM , Kim EA , Neuhaus IM , Hansen SL , Kyle RL , Kelly M , Rosenblum MD , Lowe MM 
Published: July 2024

ABSTRACTHidradenitis Suppurativa (HS) is a relatively common and highly morbid inflammatory skin disease. Due to our relatively limited understanding of HS’s pathogenesis, there are currently insufficient treatment options available, and many patients’ medical needs are not being met. This is partly due to a scarcity of ex vivo human assays and animal models that accurately recapitulate the disease. To address this deficit, we have developed a whole-tissue explant model of HS to examine its pathogenic mechanisms and the efficacy of potential treatments within intact human tissue. We measured cytokine protein and RNA within whole tissue maintained in an agar-media solution, finding that IL-6 and IL-8 concentrations trended upwards in both HS explants and healthy controls, while IL-17A, IL-1β, and TNF-α exhibited increases in HS tissue alone. We also show that the explants were responsive to treatment with both dexamethasone and IL-2. Not only do our results show that this model effectively delivers treatments throughout the explants, but they also elucidate which cytokines are related to the explant process regardless of tissue state and which are related to HS tissue specifically, laying the groundwork for future implementations of this model.
Uncovering the Neural Correlates of the Urge-to-Blink: A Study Utilising Subjective Urge Ratings and Paradigm Free Mapping
Authors: Houlgreave Mairi S. , Uruñuela Eneko , Caballero-Gaudes César , Gowland Penny , Dyke Katherine , Brandt Valerie , Mohammed Imaan , Panchuelo Rosa Sanchez , Jackson Stephen 
Published: July 2024

AbstractNeuroimaging plays a significant role in understanding the neurophysiology of Tourette syndrome (TS), in particular the main symptom, tics, and the urges associated with them. Premonitory urge is thought to be a negative reinforcer of tic expression in TS. Tic expression during neuroimaging is most often required as an overt marker of increased urge-to-tic, which can lead to considerable head movement, and thus data loss. This study aims to identify the brain regions involved in urge in healthy subjects using multi-echo functional MRI and a timing- free approach to localise the BOLD response associated with the urge-to-act without information of when these events occur. Blink suppression is an analogous behaviour that can be expressed overtly in the MRI scanner which gives rise to an urge like those described by individuals with TS.We examined the urge-to-blink in 20 healthy volunteers with an experimental paradigm including two conditions, “Okay to blink” and “Suppress blinking”, to identify brain regions involved in blink suppression. Multi-echo functional MRI data was analysed using a novel approach to investigate the BOLD signal correlated with the build-up of the urge-to-blink that participants continuously reported using a rollerball device. In addition, we used the method of multi-echo paradigm free mapping (MESPFM) to identify these regions without prior specification of task timings.Subjective urge scores were correlated with activity in the right posterior and ventral-anterior insula as well as the mid-cingulate and occipital cortices. Furthermore, blink suppression was associated with activation in the dorsolateral prefrontal cortex, cerebellum, right dorsal-anterior insula, mid-cingulate cortex and thalamus. These findings illustrate that different insula subregions contribute to the urge-for-action and suppression networks. The MESPFM approach showed co-activation of the right insula and cingulate cortex. The MESPFM activation maps showed the highest overlap with activation associated with blink suppression, as identified using general linear model analysis, demonstrating that activity associated with suppression can be determined without prior knowledge of task timings.
A novel method (RIM-Deep) for enhancing imaging depth and resolution stability of deep cleared tissue in inverted confocal microscopy
Authors: Liu Yisi , Wang Pu , Zou Junjie , Zhou Hongwei 
Published: July 2024

AbstractThe increasing use of tissue clearing techniques underscores the urgent need for cost-effective and simplified deep imaging methods. While traditional inverted confocal microscopes excel in high-resolution imaging of tissue sections and cultured cells, they face limitations in deep imaging of cleared tissues due to refractive index mismatches between the immersion media of objectives and sample container. To overcome these challenges, the RIM-Deep was developed to significantly improve deep imaging capabilities without compromising the normal function of the confocal microscope. This system facilitates deep immunofluorescence imaging of the prefrontal cortex in cleared macaque tissue, extending imaging depth from 2 mm to 5 mm. Applied to an intact and cleared Thy1-EGFP mouse brain, the system allowed for clear axonal visualization at high imaging depth. Moreover, this advancement enables large-scale, deep 3D imaging of intact tissues. In principle, this concept can be extended to any imaging modality, including existing inverted wide-field, confocal, and two-photon microscopy. This would significantly upgrade traditional laboratory configurations and facilitate the study of connectomics in the brain and other tissues.
An application of the MR-Horse method to reduce selection bias in genome-wide association studies of disease progression
Authors: Donovan Killian , Torres Jason , Zhu Doreen , Herrington William G , Staplin Natalie 
Published: July 2024

AbstractGenome-wide association studies (GWAS) of disease progression are vulnerable to collider bias caused by selection of participants with disease at study entry. This bias introduces spurious associations between disease progression and genetic variants that are truly only associated with disease incidence. Methods of statistical adjustment to reduce this bias have been published, but rely on assumptions regarding the genetic correlation of disease incidence and disease progression which are likely to be violated in many human diseases.MR-Horse is a recently published Bayesian method to estimate the parameters of a general model of genetic pleiotropy in the setting of Mendelian Randomisation. We adapted this method to provide bias-reduced GWAS estimates of associations with disease progression, robust to the genetic correlation of disease incidence and disease progression and robust to the presence of pleiotropic variants with effects on both incidence and progression.We applied this adapted method to simulated GWAS of disease incidence and progression with pleiotropic variants and varying degrees of genetic correlation. When significant genetic correlation was present, the MR-Horse method produced less biased estimates than unadjusted analyses or analyses adjusted using other existing methods. Type 1 error rates with the MR-Horse method were consistently below the nominal 5% level, at the expense of a modest reduction in power. We then applied this method to summary statistics from the CKDGen consortium GWAS of kidney function decline. MR-Horse attenuated the effects of variants with known likely biased effects in the CKDGen GWAS, whilst preserving effects at loci with likely true effects.
Cell cycle expression heterogeneity predicts degree of differentiation
Authors: Noller Kathleen , Cahan Patrick 
Published: July 2024

ABSTRACTMethods that predict fate potential or degree of differentiation from transcriptomic data have identified rare progenitor populations and uncovered developmental regulatory mechanisms. However, some state-of-the-art methods are too computationally burdensome for emerging large-scale data and all methods make inaccurate predictions in certain biological systems. We developed a method in R (stemFinder) that predicts single cell differentiation time based on heterogeneity in cell cycle gene expression. Our method is computationally tractable and is as good as or superior to competitors. As part of our benchmarking, we implemented four different performance metrics to assist potential users in selecting the tool that is most apt for their application. Finally, we explore the relationship between differentiation time and cell fate potential by analyzing a lineage tracing dataset with clonally labelled hematopoietic cells, revealing that metrics of differentiation time are correlated with the number of downstream lineages.
Structural diversity of mitochondria in the neuromuscular system across development
Authors: Bae J. Alexander , Choi Myung-kyu , Ahn Soungyub , Ko Gwanho , Choe Daniel T. , Yim Hyunsoo , Nguyen Ken C. , Kim Jinseop S. , Hall David H. , Lee Junho 
Published: July 2024

AbstractAs an animal matures, its neural circuit undergoes alterations, yet the developmental changes in intracellular organelles to facilitate these changes is less understood. Using 3D electron microscopy and deep learning, we developed semi-automated methods for reconstructing mitochondria inC.elegansand collected mitochondria reconstructions from normal reproductive stages and dauer, enabling comparative study on mitochondria structure within the neuromuscular system. We found that various mitochondria structural properties in neurons correlate with synaptic connections and these properties are preserved across development in different neural circuits. To test the necessity of these universal mitochondria properties, we examined the behavior indrp-1mutants with impaired mitochondria fission and discovered that it caused behavioral deficits. Moreover, we observed that dauer neurons display distinctive mitochondrial features, and mitochondria in dauer muscles exhibit unique reticulum-like structure. We propose that this specialized mitochondria structure may serve as an adaptive mechanism to support stage-specific behavioral and physiological needs.
Dads on duty: First account of nest sitting in barnacle ganders
Authors: Scheiber Isabella B. R. , Slettenhaar Annabel J. , Loonen M. J. J. E. , de Jong Margje E. 
Published: July 2024

AbstractIn most Anseriformes (ducks, geese and swans) only females are known to incubate. Here we scientifically describe, indicidents of male nest sitting in barnacle geese (Branta leucopsis) as a form of paternal care of nest attendance. Based on pictures from wildlife cameras we identified males, which sat on their nests when their mates took incubation recesses. Wildlife cameras were placed at nests of which either the male or female was fitted with a GPS neck collar in the year prior, which aided with identifying individual birds on the nest. To attach transmitters, some geese were caught while defending their nests, thus we may have unintentionally selected bolder males which defended their nests more aggressively and were easier to catch. Nest sitting occurred relatively frequent,i.e. in 6/15 individuals. Our results show that males with collars were more likely to nest sit, but this does not deflect from the fact this behaviour exists in geese. In the course of this finding we discuss several possible functions of this behaviour,i.e. against raiding of nests by aerial predators, thermal control of nest temperature, and intraspecific brood parasitism. At this time we cannot demonstrate a possible function, as chances of successful hatching were not increased in nest-sitting males and we lack sample size for more in depth analyses. Lastly, we argue that ‘male incubation’ is misleading in the waterfowl literature, as it is truly justified for only two species, the black swan (Cygnus atratus)and black-bellied whistling duck (Dendrocygna autumnalis).
Diversity and functional specialization of oyster immune cells uncovered by integrative single cell level investigations
Authors: Divonne Sébastien de La Forest , Pouzadoux Juliette , Romatif Océane , Montagnani Caroline , Mitta Guillaume , Destoumieux-Garzon Delphine , Gourbal Benjamin , Charrière Guillaume M. , Vignal Emmanuel 
Published: July 2024

AbstractMollusks are a major component of animal biodiversity and play a critical role in ecosystems and global food security. The Pacific oyster,Crassostrea (Magallana) gigas, is the most farmed bivalve mollusk in the world and is becoming a model species for invertebrate biology. Despite the extensive research on hemocytes, the immune cells of bivalves, their characterization remains elusive. Here we were able to extensively characterize the diverse hemocytes and identified at least seven functionally distinct cell types and three hematopoietic lineages. A combination of single-cell RNA sequencing, quantitative cytology, cell sorting, functional assays and pseudo-time analyses was used to deliver a comprehensive view of the distinct hemocyte types. This integrative analysis enabled us to reconcile molecular and cellular data and identify distinct cell types performing specialized immune functions, such as phagocytosis, reactive oxygen species production, copper accumulation, and expression of antimicrobial peptides. This study emphasized the need for more in depth studies of cellular immunity in mollusks and non-model invertebrates and set the ground for further comparative immunology studies at the cellular level.
Spiking neural network models of sound localisation via a massively collaborative process
Authors: Ghosh Marcus , Habashy Karim G. , De Santis Francesco , Fiers Tomas , Erçelik Dilay Fidan , Mészáros Balázs , Friedenberger Zachary , Béna Gabriel , Hong Mingxuan , Abubacar Umar , Byrne Rory T. , Riquelme Juan Luis , Liu Yuhan Helena , Aizenbud Ido , Bicknell Brendan A. , Bormuth Volker , Antonietti Alberto , Goodman Dan F. M. 
Published: July 2024

AbstractNeuroscientists are increasingly initiating large-scale collaborations which bring together tens to hundreds of researchers. However, while these projects represent a step-change in scale, they retain a traditional structure with centralised funding, participating laboratories and data sharing on publication. Inspired by an open-source project in pure mathematics, we set out to test the feasibility of an alternative structure by running a grassroots, massively collaborative project in computational neuroscience. To do so, we launched a public Git repository, with code for training spiking neural networks to solve a sound localisation task via surrogate gradient descent. We then invited anyone, anywhere to use this code as a springboard for exploring questions of interest to them, and encouraged participants to share their work both asynchro-nously through Git and synchronously at monthly online workshops. At a scientific level, our work investigated how a range of biologically-relevant parameters, from time delays to mem-brane time constants and levels of inhibition, could impact sound localisation in networks of spiking units. At a more macro-level, our project brought together 31 researchers from multiple countries, provided hands-on research experience to early career participants, and opportunities for supervision and teaching to later career participants. Looking ahead, our project provides a glimpse of what open, collaborative science could look like and provides a necessary, tentative step towards it.