bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRE1-dependent GOLIM4 expression controls protein secretion to modulate glioblastoma cell adhesion and migration
Authors: Bakambamba Ketsia , Nivet Manon , Sauzay Chloé , Martin Sophie , Lafont Elodie , Négroni Luc , Chevet Eric , Avril Tony 
Published: October 2024

AbstractOne of the main glioblastoma (GB) features is the diffuse migration of the tumor cells within the surrounding brain parenchyma, rendering almost impossible the complete tumor resection and irradiation, leading to inexorable lethal relapse of the disease. In the past years, we demonstrated that IRE1α (hereafter IRE1), one of the Endoplasmic Reticulum (ER) stress sensors, plays a key role in GB biology by impacting on immune infiltration, angiogenesis and tumor cell migration/invasion, all these features being linked to an alteration of protein secretion. In the present study, we investigated if and how IRE1 could regulate the functionality of the secretory machinery in GB cells and identified GOLIM4, a Golgi-associated molecule whose expression is regulated downstream of IRE1 through the transcription of XBP1s. Interestingly, GOLIM4 silencing led to decreased surface expression of multiple molecules including MHC class I molecules, growth factor receptors (PDGFRA and IL13RA2) and proteins involved in cell-cell adhesion (CD44, CD54, NCAM1), adhesion to matrix (ITGB1) or cell migration (CD90) without alteration of their encoding transcripts’ expression levels. Moreover, GOLIM4 silencing phenotypically affected GB cell-cell adhesion and cell migration in multiple models. Overall, we have described a novel IRE1/XBP1s/GOLIM4 operon that controls the secretion of specific proteins and impacts the tumor aggressiveness.Graphical abstract
Cannabidiol Toxicity Driven by Hydroxyquinone Formation
Authors: Montero Metzli I. , Rajaram Pravien S. , Alvarado Jose E. Zamora , McCloskey Kara E. , Baxter Ryan D. , Eguiluz Roberto C. Andresen 
Published: October 2024

ABSTRACTOxidative byproducts of cannabidiol (CBD) are known to be cytotoxic. However, CBD susceptibility to oxidation and resulting toxicity dissolved in two common solvents, ethanol (EtOH) and dimethyl sulfoxide (DMSO), is seldom discussed. Furthermore, CBD products contain a wide range of concentrations, making it challenging to link general health risks associated with CBD cytotoxicity. Here, we report on the effect of CBD and CBD analogs dissolved in EtOH or DMSO at various concentrations. The cells used in these studies were human umbilical vascular endothelial cells (HUVECs). Our findings show that significant CBD oxidation of CBD to form cannabidiol-quinone (CBD-Q) and subsequent cytotoxicity, occurring at 10 µM concentration regardless of the solution delivery vehicle. Moreover, a new analog of CBD, cannabidiol-diacetate (CBD-DA), exhibits significantly more stability and reduced toxicity compared with CBD or CBD-Q. This knowledge is important for determining concentration-dependent health risks of complex cannabinoid mixtures and establishing legal limits.
Cooperation maximizes biodiversity
Authors: Godoy Oscar , Soler-Toscano Fernando , Portillo José R. , Suárez Antonio , Langa José A. 
Published: October 2024

AbstractCooperation, the mutual benefit that individuals of different species obtain when they interact together, is ubiquitous in nature. Despite their importance, most of all current ecological theories have been formalized focusing on negative interactions such as competition or predation. The role of cooperation, or other types of positive interactions including facilitation and mutualism, has not been fully addressed, or, if so, always in combination with negative interactions. This fact limits our understanding of the unique features by which cooperation as opposed to competition promotes biodiversity. To address this gap, we introduce here cooperation into structural stability, a general framework to understand how species interactions and environmental variability determine the long-term persistence of species within communities. Compared to a pure competitive case, cooperation promotes three distinctive features. First, cooperation increases the opportunities for species to coexist. This feature increases the persistence of species with contrasted phylogenetic, functional, and demographic strategies that the environment would otherwise filter. Second, cooperation creates intertwined biodiversity where the existence of some species begets the presence of others. Third, cooperation promotes multistability by changing the dynamics of community assembly due to variations in environmental conditions. In conclusion, we present a fully operational framework to understand the unique ecological roles of cooperation in nature. It indicates that cooperation as opposed to competition maximizes the maintenance of biodiversity.
Equi-Under-Dispersed Possion Distribution (EUPoisson)
Authors: Hassan Mohamed Y. 
Published: October 2024

AbstractIn this study, we propose an Equi-Under-dispersed Poisson distribution derived from a finite mixture of weighted Poisson distributions. This probability distribution is a simple, parsimonious, and flexible option suitable for modeling under-dispersed count data. It aims to overcome some of the weaknesses of existing methods in modeling Equi-Under-dispersed count data. Explicit expressions for the moment-generating function, mean, variance, and index of dispersion are derived. Real count data are used to compare its performance with that of the zero-inflated Poisson distribution and the finite mixture of Poisson distributions. Maximum likelihood estimation is implemented to estimate the parameters of the distribution, and goodness-of-fit statistical techniques are used to compare the fit of the competing distributions.
Adult diet strongly affects cuticle thickness and its injury resistance in the insectNarnia femorata(Hemiptera: Coreidae)
Authors: Greenway EV(Ginny) , Woodman Tamsin , Emberts Zachary , Chen Simon , Federle Walter , Miller Christine W. 
Published: October 2024

AbstractArthropods are the most diverse phylum on earth, accounting for up to 90% of animal species. The cuticular exoskeleton has played a vital role in their evolutionary success, but we know surprisingly little about the factors influencing its development, structure, and biomechanical properties. In this study, we examined whether and how nutrition affects the cuticle after an insect has completed its final molt into the adult stage. We found that a high-quality adult diet provided to the leaf-footed cactus bug,Narnia femorata(Hemiptera: Coreidae), over three weeks led to 4.1-times thicker cuticle with 3.7-times greater injury resistance relative to those that consumed a poor, but still ecologically relevant, diet. We further discovered that a high-quality adult diet allowed compensation for a sub-optimal juvenile diet. The cuticle of males was more injury resistant than that of females, as expected due to the aggressive male competition in this species. Altogether, our results show that, even after the final molt, nutrition can strongly influence the development and properties of the arthropod cuticle, a phenomenon that likely has drastic fitness-related consequences for locomotion, predator-prey interactions, and resource acquisition.
The maintenance of multiple ecDNA types in single cancer cells
Authors: Scanu Elisa , Werner Benjamin , Huang Weini 
Published: October 2024

AbstractExtrachromosomal DNA (ecDNA) emerges as a crucial promoter of rapid intra-tumour heterogeneity and oncogene amplification, contributing to tumour progression and adaptability to resistance. Multiple types of ecDNA are often observed within the same cancer cell, promoting high levels of complexity. While the study of multiple ecDNA types is still in its early stages with exciting new clinical and experimental studies in human cancers, few theoretical models have been proposed to understand the mechanisms enabling the maintenance of multiple ecDNA types (mix cells). Here, based on our general framework of modeling multiple ecDNA types, we explore the conditions that allow for a stable coexistence of multiple ecDNA types within single cancer cells. We study how genetic mutations or phenotypic switching among different ecDNA types contribute to the maintenance of ecDNA diversity under different fitness regimes. We show that either positive epistasis or switching is required to stably maintain mix cell populations. Counter-intuitively, intermediate rather than high switching rates lead to the highest fraction of mix cells, which is further confirmed by our analysis of sub-population compositions, transition probabilities between pure and mix states as well as single-cell Shannon indices.
Discovery of Novel Targets for Important Human and Plant Fungal Pathogens via Automated Computational Pipeline HitList
Authors: Condon David E. , Schroeder Brenda K. , Rowley Paul A. , Ytreberg F. Marty 
Published: October 2024

AbstractFungi are a major threat to human health and agricultural productivity, causing 1.7 million human deaths and billions of dollars in crop losses and spoilage annually. While various antifungal compounds have been developed to combat these fungi in medical and agricultural settings, but there are concerns that treatment effectiveness is waning due to the emergence of acquired drug resistance and to novel pathogens. Effectiveness is further hampered due to the limited number of modes of action for available antifungal compounds.To develop new strategies for the control and mitigation of fungal disease and spoilage, new antifungals are needed with novel fungal-specific protein targets that can overcome resistance and prevent host toxicity. New antifungals can add new methods of targeting fungi that have no effective control measures. The increasing availability of complete genomes of pathogenic and spoilage fungi has enabled identification of novel protein and RNA targets essential for viability and not found in host plants or humans. In this study, an automated bioinformatics pipeline utilizing BLAST, ClustalΩ, and subtractive genomics was created and used to identify potential new targets for any system of hosts and pathogens with available genomic or proteomic data. This pipeline called HitList allowsin silicoscreening of thousands of possible targets. HitList was then used to generate a list of potential antifungal targets for the World Health Organization fungal priority pathogens list and the top 10 agricultural fungal pathogens. Known antifungal targets were found, validating the approach, and an additional eight novel protein targets were discovered that could be used for the rational design of antifungal compounds.
Heterogeneity Assessment and Protein Pathway Prediction via Spatial Lipidomic and Proteomic Correlation: Advancing Dry Proteomics concept for Human Glioblastoma Prognosis
Authors: Lagache Laurine , Zirem Yanis , Rhun Émilie Le , Fournier Isabelle , Salzet Michel 
Published: October 2024

ABSTRACTPrediction of proteins and associated biological pathways from lipid analyses via MALDI MSI is a pressing challenge. We introduced “dry proteomics,” using MALDI MSI to validate spatial localization of identified optimal clusters in lipid or protein imaging. Consistent cluster appearance across omics images suggests association with specific lipid and protein pathways, forming the basis of dry proteomics. The methodology was refined using rat brain tissue as a model, then applied to human glioblastoma, a highly heterogeneous cancer. Sequential tissue sections underwent omics MALDI MSI and unsupervised clustering. Differentiated lipid and protein clusters, with distinct spatial locations, were identified. Spatial omics analysis facilitated lipid and protein characterization, leading to a predictive model identifying clusters in any tissue based on unique lipid signatures and predicting associated protein pathways. Application to rat brain slices revealed diverse tissue subpopulations, including successfully predicted cerebellum areas. Similar analysis on 50 glioblastoma patients confirmed lipid-protein associations, correlating with patient prognosis.GRAPHICAL ABSTRACT
Functional yeast promoter sequence design using temporal convolutional generative language models
Authors: Alsaggaf Ibrahim , Wan Cen 
Published: October 2024

AbstractPromoter sequence design is the key to accurately control gene expression processes that play a crucial role in biological systems. Thanks to the recent community effort, we are now able to elucidate the associations between yeast promoter sequences and their corresponding expression levels using advanced deep learning methods. This milestone boosts the further development of many downstream biological sequence research tasks like synthetic DNA design. In this work, we propose a novel synthetic promoter sequence design method, namely Gen-DNA-TCN, which exploits a pre-trained sequence-to-expression predictive model to facilitate its temporal convolutional neural networks-based generative model training. A large-scale evaluation suggests that Gen-DNA-TCN successfully generated diverse synthetic promoter sequences that also encode similar distributions of transcription factor binding sites to real promoter sequences.
Annexin A6 modulates the secretion of pro-inflammatory cytokines and exosomes via interaction with SNAP23 in triple negative breast cancer cells
Authors: Sakwe Nobelle I. , Vuong Ngoc B. , Black Perrin J. , Ball Destiny D. , Thomas Portia , Beasley Heather K. , Hinton Antentor , Ochieng Josiah , Sakwe Amos M. 
Published: October 2024

AbstractPro-inflammatory cytokines are secreted via the classical pathway from secretory vesicles or the non-classical pathway via extracellular vesicles (EVs), that together, play critical roles in triple-negative breast cancer (TNBC) progression. Annexin A6 (AnxA6) is a Ca2+-dependent membrane-binding protein that in TNBC is implicated in cell growth and invasiveness. AnxA6 is associated with EVs, but whether it affects the secretion of proinflammatory cytokines and/or EVs remains to be fully elucidated. To assess if AnxA6 influences the secretion of cytokines and extracellular vesicles, we used cytokine arrays to analyze secreted factors in cleared culture supernatants from control AnxA6 expressing and AnxA6 downregulated MDA-MB-468 TNBC cells. This revealed the diminished secretion of monocyte chemoattractant protein 1 (MCP-1/CCL2), interleukin 8 (IL-8), dickkopf1 (DKK1), throbospondin-1 (TSP-1), and osteopontin (OPN) following AnxA6 downregulation. We also show that the secretion of small EVs is strongly reduced in AnxA6 downregulated cells and that upregulation of AnxA6 promoted the secretion of treatment was also associated with increased EVs associated Rab7, cholesterol, and MCP-1 levels. Moreover, cholesterol content in EVs was significantly higher in AnxA6-expressing cells than in AnxA6 downregulated cells and following chronic lapatinib induced upregulation of AnxA6. Mechanistically, we demonstrate that the secretion of MCP-1 and/or EVs is AnxA6 dependent and that this requires the translocation of AnxA6 to cellular membranes and its interaction with SNAP23. AnxA6 neutralizing antibodies strongly diminished the survival of AnxA6 low TNBC cells but had minimal effects on the survival of TNBC cells expressing relatively high levels of the protein. Together, these data suggest that AnxA6 facilitates the secretion of EVs and proinflammatory cytokines that may be critical for TNBC progression.
CXADR is a Human IgG Fc Receptor
Authors: Emig Christopher J. , Vitug Adela A. 
Published: October 2024

AbstractCXADR is a membrane protein present in epithelial tight junctions and other tissues with a variety of known functions, in addition to its role as entry receptor for coxsackie B virus and adenovirus 2 and 5. We identified a previously unknown function of CXADR as a binding partner for human IgG but not IgA, IgE, IgM, or ScFv in a non paratope specific manner. Binding was specific to human and rabbit IgG, and not observed for mouse, rat, donkey, or goat IgG. Binding of Ig to CXADR is inhibited by FcBlock (BD), and is competitive with anti-Fc binding secondary antibodies, but not anti-Fab secondary antibodies, indicating that CXADR binds the Fc portion of IgG. CXADR, being a member of the immune superfamily of proteins, has similar structural homology to other Ig binding proteins, including Fc receptors. We conclude that CXADR has a previously unknown function as a human Fc receptor, serving as a direct link between the humoral adaptive immune system and many cell types in the human body previously unknown to express FcR.
Identification of immunogenic and cross-reactive chikungunya virus-specific CD4+T cell epitopes in chronic chikungunya viral arthritic disease in humans
Authors: Agarwal Rimjhim , Ha Calvin , Cortes Fernanda H. , Lee Yeji , Martínez-Pérez Amparo , Gálvez Rosa Isela , Castillo Izabella N. , Balmaseda Angel , Harris Eva , Romero-Vivas Claudia M , Premkumar Lakshmanane , Falconar Andrew K , Grifoni Alba , Sette Alessandro , Weiskopf Daniela 
Published: October 2024

ABSTRACTChikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic chikungunya virus disease (CHIKVD) marked by persistent debilitating arthralgia. At present, the exact cause of chronic CHIKVD is not understood, and in humans, the targets of CD4+T cells in CHIKV are currently unknown. Here, by stimulating peripheral blood mononuclear cells (PBMCs) collected from patients suffering from chronic CHIKVD with peptides spanning the entire CHIKV genome, we provide a comprehensive landscape of CHIKV CD4+T cell epitopes. We identified 123 novel CD4+T cell epitopes and three immunodominant regions in E1, nsP1 and CP proteins. The immunodominance of these E1, nsP1 and CP regions was mapped to optimal epitopes, characterized by the capacity to bind to many common HLA class II allelic variants. In addition, we designed and validated a new CHIKV-specific CD4+T cell epitope megapool, spanning both structural and non-structural proteins, which can be a useful tool to study CHIKV-specific T cell responses in small blood volumes, typically available in pediatric or clinical samples. Finally, byin silicoassessment of the conservation of the CHIKV proteome in a diverse set of alphaviruses, we defined CHIKV epitopes conserved across arthritogenic and encephalitic viruses. Overall, our work is the first to identify CD4+T cell targets of CHIKV in humans, expanding our capacity to study the role of T cells in CHIKV pathogenesis and mapping targets of alphaviruses for vaccine design.
Universal function of WRI1 involved in integrated regulation of multiple latex metabolism pathways inHevea brasiliensisandTaraxacum kok-saghyz
Authors: Fan Ruisheng , wan Jiong , Yang Wenfeng , Wei Fang , Gao Honghua , Qu Peng , Du Huabo , Qiu Jian 
Published: October 2024

AbstractHevea brasiliensisandTaraxacum kok-saghyzare sources of nature rubber (NR) and recent research has focused on finding a method to increase NR quality and production. NR consists mainly ofcis-1,4-polyisoprene, which is synthesized from sucrose by a series of reactions during carbon metabolism. WRINKLED1 (WRI1) is a transcription factor (TF) that coordinates many genes involved in carbon metabolism and lipid biosynthesis. Here, we isolated and characterized two orthologues ofWRIin rubber-producing plantsH. brasiliensisa andT. kok-saghyz, which are highly expressed in their latex. Subcellular localization and ectopic expression inArabidopsis thalianaindicated that the TFs,HbWRI1andTkWRI1, are involved in lipid accumulation. Overexpression ofHbWRI1andTkWRI1inT. kok-saghyzsubstantially enhanced NR quality and production, including dry rubber content, molecular weight, and the diameter of rubber particles in the latex. Conversely, they were decreased inTkWRI1repression. Furthermore, based on the activated expression in transgenicT. kok-saghyzlatex and the existence of AW-box element in the promoter regions, 16 direct downstream genes of HbWRI1 and TkWRI1 were identified by a dual-luciferase reporter assay and yeast one-hybrid assay, and their products were responsible for both NR biosynthesis and lipid metabolism. These results reveal a regulatory module that HbWRI1 and TkWRI1 TFs can positively regulate NR quality and production inT. kok-saghyzlatex by synergistically regulating the entire NR biosynthesis. This module is expected to be utilized to develop superior varieties to enhance NR quality and production.
A near-complete telomere-to-telomere genome assembly forBatrachochytrium dendrobatidisGPL JEL423 reveals a CBM18 gene family expansion and a M36 metalloprotease gene family contraction
Authors: Helmstetter Nicolas , Harrison Keith , Greggory Jack , Harrison Jamie , Ballou Elizabeth , Farrer Rhys A. 
Published: October 2024

AbstractBatrachochytrium dendrobatidis(Bd) is responsible for mass extinctions and extirpations of amphibians, mainly driven by the Global Panzootic Lineage (BdGPL).BdGPL isolate JEL423 is a commonly used reference strain in studies exploring the evolution, epidemiology and pathogenicity of chytrid pathogens. These studies have been hampered by the fragmented, erroneous and incompleteB. dendrobatidisJEL423 genome assembly, which includes long stretches of ambiguous positions, and poorly resolved telomeric regions. Here we present and describe a substantially improved, near telomere-to-telomere genome assembly and gene annotation forB. dendrobatidisJEL423. Our new assembly is 24.5 Mb in length, ∼800 kb longer than the previously published assembly for this organism, comprising 18 nuclear scaffolds and 2 mitochondrial scaffolds and including an extra 839 kb of repetitive sequence. We discovered that the patterns of aneuploidy inB. dendrobatidisJEL423 have remained stable over approximately 5 years. We found that our updated assembly encodes fewer than half the number of M36 metalloprotease genes predicted in the previous assembly. In contrast, members of the crinkling and necrosis gene family were found in similar numbers to the previous assembly. We also identified a more extensive carbohydrate binding module 18 gene family than previously observed. We anticipate our findings, and the updated genome assembly will be a useful tool for further investigation of the genome evolution of the pathogenic chytrids.Author SummaryB. dendrobatidisis a fungus that has been implicated in the extinctions and declines of dozens of amphibians globally. Here we describe a new genome assembly for the commonly usedB. dendrobatidisisolate JEL423, which is a substantial improvement from the previously used assembly. Compared with the previous assembly, we reveal that some gene families (such as carbohydrate binding module 18 genes) are more expanded than previously recognised, while others (such as the M36 metalloproteases) are more contracted than previously recognised. Our new genome assembly will be useful for future work exploring the pathogenicity, epidemiology and evolution of chytrid fungi.
MEDIAL FRONTAL THETA (MFT) AS A PREDICTOR OF ANXIETY SENSITIVITY TREATMENT RESPONSE
Authors: Ellis Jessica , Mello Glenda , Butler Devin , Schmidt N. B. , Bernat Edward 
Published: October 2024

AbstractDespite various interventions for anxiety disorders, effects can take months and many individuals do not respond. Activity in the anterior cingulate cortex is a consistent predictor of treatment outcomes, and can be measured by medial frontal theta (MFT) event-related potentials. This study used task-based electroencephalography and MFT to predict anxiety sensitivity treatment response at mid-treatment, 1-week post-treatment, and 6 months post-treatment. Results indicated that lower medial to lateral prefrontal theta phase synchrony was associated with greater symptom improvement. This work represents a novel finding that may contribute to the improvement in treatment efficacy by serving as a target for future interventions and individualized treatment selection.