bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCDC78: unveiling the function of a novel gene associated to hereditary myopathy
Authors: Lopergolo Diego , Gallus Gian Nicola , Pieraccini Giuseppe , Boscaro Francesca , Berti Gianna , Serni Giovanni , Volpi Nila , Formichi Patrizia , Bianchi Silvia , Cassandrini Denise , Sorrentino Vincenzo , Rossi Daniela , Santorelli Filippo Maria , De Stefano Nicola , Malandrini Alessandro 
Published: December 2023

AbstractCCDC78was indicated about ten years ago as novel candidate gene for the autosomal dominant centronuclear myopathy-4 (CNM4). However, to date, only one family has been described and CCDC78 function remains unclear. Here we deeply analyze for the first time a family harbouring aCCDC78nonsense mutation. Histopathological features included, as novel histological hallmark, peculiar sarcoplasmic reticulum (SR) abnormalities. We provided evidence of nonsense mediated mRNA decay, defined novelCCDC78transcripts and, through transcriptome profiling, detected 1035 muscular differentially expressed genes including a series of genes involved in SR. Through coimmunoprecipitation assay and mass spectrometry studies we demonstrated that CCDC78 interacts with two pivotal SR proteins: SERCA1 and CASQ1. We also found an interaction with MYH1, ACTN2 and ACTA1. Our findings shed light on interactors and possible role of CCDC78 in skeletal muscle, thus allowing us to locate the protein in SR and to considerCCDC78as CNM4 causative gene.
Bacteroidia and Clostridia genomes collectively encode for a progressive cascade of marine polysaccharide degradation along the hindgut of the herbivorous fishKyphosus sydneyanus
Authors: Facimoto Cesar T. , Clements Kendall D. , Lindsey White W. , Handley Kim M. 
Published: December 2023

ABSTRACTThe gut microbiota of the marine herbivorous fishKyphosus sydneyanusare thought to play an important role in host nutrition by supplying short-chain fatty acids (SCFA) through fermentation of dietary macroalgae. Here, we assembled 645 metagenome-assembled genomes (MAGs) from wild fish to determine the capacity of different bacterial taxa to degrade seaweed carbohydrates along the gut. Most bacteria (99%) were unclassified at the species level, highlighting taxonomic novelty dominated by Bacteroidia and Clostridia within the gut community. The presence of genes encoding endo-acting CAZymes in both phyla suggest they have a role in initiating glycan depolymerization. Bacteroidia also contributed the most to CAZyme-related gene expression in the distal hindgut, and encoded the highest densities of CAZymes within the community. In particular, the enrichment of CAZyme gene clusters (CGCs) within the Bacteroidia genusAlistipes(n = 73 versus just 59 distributed across all other taxa) points to an enhanced capacity for macroalgal polysaccharide utilization (e.g., alginate, laminarin and sulfated polysaccharides). Pairwise correlations of MAG relative abundances and encoded CAZyme compositions provide evidence of potential inter-species collaborations, whereby co-abundant MAGs exhibited complementary degradative capacities for specific substrates. Results indicated flexibility across these co-abundant groups in their capacity to source carbon (e.g., glucose or galactose-rich glycans), which possibly facilitates coexistence via niche partitioning. Our results indicate the potential for collaborative microbial carbohydrate metabolism in the gut ofK. sydneyanusby Bacteroidia and Clostridia, and suggest that members of the genusAlistipesare a metabolically and taxonomically diverse group of specialized macroalgae biomass degraders.
Combinatory differentiation of human induced pluripotent stem cells generates thymic epithelium that supports thymic crosstalk and directs dendritic- and CD4/CD8 T-cell full development
Authors: Provin Nathan , d’Arco Manon , Kervagoret Erwan , Bruneau Alexandre , Brusselle Lucas , Fourgeux Cynthia , Poschmann Jérémie , Saulquin Xavier , Guillonneau Carole , David Laurent , Giraud Matthieu 
Published: December 2023

AbstractThe thymus is a primary lymphoid organ playing a crucial role in immune tolerance, by educating thymocytes through a selection mediated by thymic epithelial cells (TEC). Recent advances in gene editing and immunotherapies have made in vitro generation of iPSC-derived T cells a crucial issue with promising therapeutic applications. Current state-of-the-art approaches often fail to accurately replicate the thymic niche, resulting in impaired T cell generation, particularly for CD4+ T cells. Here we address the production of functional mature iPSc-derived TECs that are able to support in vitro T cell generation. We designed a protocol allowing iPSc differentiation into thymic epithelial progenitors (TEP) through an unbiased multifactorial method based on optimal experimental design. Modulation of signaling pathways known to regulate embryonic thymus organogenesis resulted in the obtention of TEPs expressing typical thymic markers. We achieved TEP maturation into medullary and cortical TECs by setting up a hydrogel-based 3D culture supplemented in RANK ligand, resulting in the formation of thymic organoids. To assess the functionality of the generated TECs, primary hematopoietic progenitors were co-cultured in the organoids and showed significantly improved maturation in single-positive CD4 or CD8 T cells. Remarkably, our thymic organoid model shows multilineage differentiation potential, with generation of distinct dendritic cells populations in addition to the T lineages. Thus, generation of functional TECs and thymic organoids offers a practical platform for the study of thymic cellular interactions and paves the road to future cellular therapies by producing mature thymic immune cells of clinical interest.
Active shape programming drivesDrosophilawing disc eversion
Authors: Fuhrmann Jana F. , Krishna Abhijeet , Paijmans Joris , Duclut Charlie , Eaton Suzanne , Popović Marko , Jülicher Frank , Modes Carl D. , Dye Natalie A. 
Published: December 2023

AbstractHow complex 3D tissue shape emerges during animal development remains an important open question in biology and biophysics. In this work, we study eversion of theDrosophilawing disc pouch, a 3D morphogenesis step when the epithelium transforms from a radially symmetric dome into a curved fold shape via an unknown mechanism. To explain this morphogenesis, we take inspiration from inanimate “shape-programmable” materials, which are capable of undergoing blueprinted 3D shape transformations arising from in-plane gradients of spontaneous strains. Here, we show that active, in-plane cellular behaviors can similarly create spontaneous strains that drive 3D tissue shape change and that the wing disc pouch is shaped in this way. We map cellular behaviors in the wing disc pouch by developing a method for quantifying spatial patterns of cell behaviors on arbitrary 3D tissue surfaces using cellular topology. We use a physical shape-programmability model to show that spontaneous strains arising from measured active cell behaviors create the tissue shape changes observed during eversion. We validate our findings using a knockdown of the mechanosensitive molecular motor MyoVI, which we find to reduce active cell rearrangements and disrupt wing pouch eversion. This work shows that shape programming is a mechanism for animal tissue morphogenesis and suggests that there exist intricate patterns in nature that could present novel designs for shape-programmable materials.
T cell exhaustion dynamics in systemic autoimmune disease
Authors: Turner Christi N. , Camilo Sanchez Arcila Juan , Huerta Noah , Quiguoe Avi Rae , Jensen Kirk D.C. , Hoyer Katrina K. 
Published: December 2023

AbstractUnlike in infection and cancer, T cell exhaustion in autoimmune disease has not been clearly defined. Here we set out to understand inhibitory protein (PD-1, Tim3, CTLA4, Lag3) expression in CXCR5- and CXCR5+ CD8 and CD4 T cells in systemic lupus erythematosus. CXCR5+ CD8 and CD4 T cells express PD-1 and engage B cells in germinal center reactions, leading to autoantibody formation in autoimmunity. We hypothesized that CXCR5+ CD8 T cells develop an exhausted phenotype as SLE autoimmunity expands from initial to chronic, self-perpetuating disease due to chronic self-antigen exposure. Our results indicate that there is no exhaustion frequency differences between sexes, although disease kinetics vary by sex. CXCR5+ CD8 T cells express primarily IFNγ, known to promote autoimmune disease development, whereas CXCR5-CD8 T cells express TNFα and IFNγ as disease progresses from 2-6 months. Tim3 is the highest expressed inhibitory marker for all CD4 and CD8 T cell populations demonstrating potential for terminally exhausted populations. CTLA4 expression on CD4 T cells suggests potential tolerance induction in these cells. We identified exhaustion phenotypes within autoimmune disease that progress with increasing lupus erythematosus severity and possibly provide a feedback mechanism for immunological tolerance.HighlightsCXCR5- and CXCR5+ CD8 T cells expand with rate of disease in SLE mouse model.CXCR5+ CD8 T cells are low contributors to TNFα disease progression unlike CXCR5-CD8 T cells but may increase disease mechanisms through high IFNγ production.Inhibitory markers upregulate in frequency with the highest amounts seen in Tim3+ populations. Tim3+Lag3+ expression may be an indicator of terminal differentiation for all populations.Inhibitory marker expression frequency was unrelated to sex.
Aggregation of the Amyloid-β Peptide (Aβ40) within Condensates Generated through Liquid-Liquid Phase Separation
Authors: Morris Owen M. , Toprakcioglu Zenon , Röntgen Alexander , Cali Mariana , Knowles Tuomas P. J. , Vendruscolo Michele 
Published: December 2023

AbstractThe deposition of the Aβ peptide into amyloid fibrils is characteristic of Alzheimer’s disease. As it has been recently observed that the process of amyloid aggregation can take place within an intermediate liquid-like condensed phase, we investigated whether Aβ could undergo liquid-liquid phase separation, and whether Aβ amyloid aggregation could take place within Aβ liquid condensates. By using a microfluidic protocol, we observed that the 40-residue form of Aβ (Aβ40) can undergo liquid-liquid phase separation, and that accessing a liquid intermediate state enhances primary nucleation and enables Aβ40 to readily self-assemble into amyloid fibrils. These results prompt further studies to investigate the possible role of Aβ condensates in the aggregation of this peptide in Alzheimer’s disease.
Rapid body colouration change inOryzias celebensisas a social signal for intraspecific competition
Authors: Ueda Ryutaro , Ansai Satoshi , Takeuchi Hideaki 
Published: December 2023

AbstractIn some species, such as chameleon and cichlid fish, rapid body colouration changes (within seconds or minutes) serve as visual social signals in male-male competition. This study investigated the relationship between aggressive behaviour and body colouration changes inOryzias celebensis, an Indonesian medaka fish. We analysed aggressive behaviours and corresponding body colouration changes during attack events in a controlled laboratory setting using groups of 3 adult fish in a small tank. In a triadic relationship consisting of 2 males and a female, males with blackened markings attacked more frequently than males without blackened markings and females. Additionally, we observed that the males with blackened markings were seldom attacked by males without blackened markings and females. These tendencies persisted even in groups consisting of 3 males. Our results suggest that the blackened markings in maleO. celebensisnot only indicate the level of aggression but also serve as a social signal to suppress attacks by other individuals.
Analysis of Metabolomics and Transcriptomics Data to Assess Interactions in Microalgal Co-culture ofSkeletonema marinoiandPrymnesium parvum
Authors: Zulfiqar Mahnoor , Abel Anne-Susann , Barth Emanuel , Syhapanha Kristy , Poulin Remington Xavier , Dehiwalage Sassrika Nethmini Costa Warnakulasu , Pohnert Georg , Steinbeck Christoph , Peters Kristian , Sorokina Maria 
Published: December 2023

AbstractIn marine ecosystems, microbial communities often interact using specialised metabolites, which play a central role in shaping the dynamics of the ecological networks and maintaining the balance of the ecosystem. With metabolomics and transcriptomics analyses, this study explores the interactions between two marine microalgae,Skeletonema marinoiandPrymnesium parvum, grown in mono-cultures and non-contact co-cultures. As a growth indicator, the photosynthetic potential, measured via fluorescence, suggested chemical interaction betweenS. marinoiandP. parvum. Using Liquid Chromatography-Mass Spectrometry (LC-MS) data, we identified 346 and 521 differentially produced features in the endo- and exometabolome ofS. marinoiandP. parvum, respectively. Despite limited tandem mass spectrometry data (MS2) for these features, we structurally annotated 14 compounds, most of which were previously under-studied specialised metabolites. Differential gene expression analysis was then performed on the transcriptomes of the microalgae, which uncovered differentially expressed genes involved in energy metabolism and cellular repair for both species. These metabolic and transcriptomics changes depict the adaptation of both species in the co-culture. However, further data acquisition and investigation will be necessary to confirm the type of interaction and the underlying mechanisms.ImportanceMarine microalgae have great ecological importance and biochemical potential. Among these microbes are the diatomSkeletonema marinoi, known for its marine biogeochemical cycling, and the haptophytePrymnesium parvum, which poses adverse environmental consequences. Given these opposing roles for the two cosmopolitan microalgae, we designed a study using untargeted metabolomics and transcriptomics to acquire a comprehensive snapshot of their interactions, grown as mono-cultures and co-cultures. The statistical analysis of the chlorophyllafluorescence levels, and the metabolomics and transcriptomics dataset revealed metabolic communication occurring among the two species via specialised metabolites and activated cellular repair mechanisms. These findings reveal the complexity of the interactions within marine microbial ecosystems, offering a foundation for future research to understand and harness marine ecological systems.
IST-editing: Infinite spatial transcriptomic editing in a generated gigapixel mouse pup
Authors: Wu Jiqing , Berg Ingrid , Koelzer Viktor H. 
Published: December 2023

ABSTRACTAdvanced spatial transcriptomics (ST) techniques provide comprehensive insights into complex living systems across multiple scales, while simultaneously posing challenges in bioimage analysis. The spatial co-profiling of biological tissues by gigapixel whole slide images (WSI) and gene expression arrays motivates the development of innovative and efficient algorithmic approaches. Using Generative Adversarial Nets (GAN), we introduceInfiniteSpatialTranscriptomicediting (IST-editing) and establish gene expression-guided editing in a generated gigapixel mouse pup. Trained with patch-wise high-plex gene expression (input) and matched image data (output), IST-editing enables the synthesis of arbitrarily large bioimages at inference,e.g., with a 106496×53248 resolution. After feeding edited gene expressions to the trained network, we model cell-, tissue- and animal-level morphological transitions in the generated mouse pup. Lastly, we discuss and evaluate editing effects on interpretable morphological features. The generated WSIs of the mouse pup and code are publicly released and accessible viahttps://github.com/CTPLab/IST-editing.
Discerning state estimation and sensory gating, two presumptive predictive signals in mouse barrel cortex
Authors: Gupta Kalpana , Chowdhury Ritu Roy , Chakrabarti Shubhodeep , Schwarz Cornelius 
Published: December 2023

AbstractThe brain is assumed to contain distinctive predictive systems ranging from sensorimotor to cognitive functions. Here we report the successful functional delineation of two different presumptive predictive systems on the neuronal level, state estimation (SE) and sensory gating (SG), which both attenuate sensory flow during movement. Studying neuronal sensorimotor responses throughout the depth of primary somatosensory cortex in mice trained on a whisker reach task, SE appeared as a learned attenuation of tactile signal flow, due to a suppressive predictive signal, precisely at the time of an experimental sensory consequence. In contrast, SG was observable during a much longer interval after onset of the motor command. Both phenomena are internal, presumptively predictive signals, as blockade of the reafference did not affect them. We speculate that SG may be related to cognitive signals monitoring goals of movements, while SE likely is the expression of the classical notion of the reafference principle.
Role ofStaphylococcus aureus’s Buoyant Density in the Development of Biofilm Associated Antibiotic Resistance
Authors: Kispert Sarah , Liguori Madison , Valikaneye Cody , Qiu Chong , Wang Shue , Zhang Nan , Gu Huan 
Published: December 2023

AbstractBacterial biofilms are clusters of bacterial cells that form at various interfaces, including those between air and liquid or liquid and solid. Due to their roles in enhancing wastewater treatment processes, and their unfortunate propensity to cause persistent human infections through high antibiotic resistance, understanding and managing bacterial biofilms is of paramount importance. A pivotal stage in biofilm development is the initial bacterial attachment to these interfaces. However, the determinants of bacterial cell choice in colonizing an interface first and heterogeneity in bacterial adhesion remain elusive. Recent research has unveiled variations in the buoyant density ofStaphylococcus aureuscells, irrespective of their growth phase. Cells with a low cell buoyant density, characterized by fewer cell contents, exhibited greater resistance to antibiotic treatments (100 μg/mL vancomycin) and favored biofilm formation at air-liquid interfaces. In contrast, cells with higher buoyant cell density, which have richer cell contents, were more vulnerable to antibiotics and predominantly formed biofilms on liquid-solid interfaces when contained upright. In essence,S. aureuscells with higher buoyant cell density are more inclined to adhere to upright substrates.
Transcriptomic analysis of melanoma cells reveals an association of α-synuclein with regulation of the inflammatory response
Authors: Rajasekaran Santhanasabapathy , Cheng Siyuan , Gajendran Nithya , Shekoohi Sahar , Chesnokova Liudmila , Yu Xiuping , Witt Stephan N. 
Published: December 2023

AbstractThe Parkinson’s disease protein, alpha-synuclein (α-syn/SNCA), is highly expressed in neurons and melanomas. The goal of this study was to reveal the mechanism(s) of α-syn’s involvement in melanoma pathogenesis. To decipher the genes and pathways affected by α-syn, we conducted an RNA sequencing analysis of human SK-MEL-28 cells and several SK-MEL-28SNCA-KO clones. We identified 1098 significantly up-regulated genes and 660 significantly down-regulated genes. Several of the upregulated genes are related to the immune system, i.e., the inflammatory response and the matrisome. We validated five upregulated genes (IL-1ý, SAA1, IGFBP5, CXCL8, and CXCL10) by RT-qPCR and detected IGFBP5 and IL-1ý in spent media of control andSNCA-KO cells. The levels of each of these secreted proteins were significantly higher in the spent media of theSNCA-KO clones than control cells. We suggest that the loss of α-syn expression unleashes chemokine/cytokine secretion, which could help melanoma cells evade the immune system.
EnhancerTracker: Comparing cell-type-specific enhancer activity of DNA sequence triplets via an ensemble of deep convolutional neural networks
Authors: Garza Anthony B. , Garcia Rolando , Solis Luis M. , Halfon Marc S. , Girgis Hani Z. 
Published: December 2023

AbstractMotivationTranscriptional enhancers — unlike promoters — are unrestrained by distance or strand orientation with respect to their target genes, making their computational identification a challenge. Further, there are insufficient numbers of confirmed enhancers for many cell types, preventing robust training of machine-learning-based models for enhancer prediction for such cell types.ResultsWe presentEnhancerTracker, a novel tool that leverages an ensemble of deep separable convolutional neural networks to identify cell-type-specific enhancers with the need of only two confirmed enhancers.EnhancerTrackeris trained, validated, and tested on 52,789 putative enhancers obtained from the FANTOM5 Project and control sequences derived from the human genome. Unlike available tools, which accept one sequence at a time, the input to our tool is three sequences; the first two are enhancers active in the same cell type.EnhancerTrackeroutputs 1 if the third sequence is an enhancer active in the same cell type(s) where the first two enhancers are active. It outputs 0 otherwise. On a held-out set (15%),EnhancerTrackerachieved an accuracy of 64%, a specificity of 93%, a recall of 35%, a precision of 84%, and an F1 score of 49%.Availability and implementationhttps://github.com/BioinformaticsToolsmith/EnhancerTrackerContacthani.girgis@tamuk.edu
Senescent cells inhibit muscle differentiation via the SASP-lipid 15d-PGJ2mediated modification and control of HRas
Authors: Pundlik Swarang Sachin , Barik Alok , Venkateshvaran Ashwin , Sahoo Snehasudha Subhadarshini , Jaysingh Mahapatra Anshuman , Math Raviswamy G H , Ramanathan Arvind 
Published: December 2023

AbstractSenescent cells, which are characterized by multiple features such as increased expression of Senescence-Associated β-galactosidase activity (SA β-gal) and cell cycle inhibitors such as p21 or p16, accumulate with tissue damage and dysregulate tissue homeostasis. In the context of skeletal muscle, it is known that agents used for chemotherapy such as Doxorubicin cause buildup of senescent cells, leading to the inhibition of tissue regeneration. Senescent cells influence the neighboring cells via numerous secreted factors which form the senescence-associated secreted phenotype (SASP). Lipids are emerging as a key component of SASP that can control tissue homeostasis. Arachidonic acid-derived lipids have been shown to accumulate within senescent cells, specifically 15d-PGJ2, which is an electrophilic lipid produced by the non-enzymatic dehydration of the prostaglandin PGD2. In this study, we show that 15d-PGJ2is also released by Doxorubicin-induced senescent cells as a SASP factor. Treatment of skeletal muscle myoblasts with the conditioned medium from these senescent cells inhibits myoblast fusion during differentiation. Inhibition of L-PTGDS, the enzyme that synthesizes PGD2, diminishes the release of 15d-PGJ2by senescent cells and restores muscle differentiation. We further show that this lipid post-translationally modifies Cys184 of HRas in skeletal muscle cells, causing a reduction in the localization of HRas to the Golgi, increased HRas binding to RAF RBD, and activation of cellular MAPK-Erk signaling (but not the Akt signaling). Mutating C184 of HRas prevents the ability of 15d- PGJ2to inhibit the differentiation of muscle cells and control the activity of HRas. This work shows that 15d-PGJ2released from senescent cells could be targeted to restore muscle homeostasis after chemotherapy.