Ontology highlight
ABSTRACT:
PROVIDER: PRJNA975438 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24696360_1.fastq.gz | Fastqsanger.gz | |||
| SRR24696360_2.fastq.gz | Fastqsanger.gz | |||
| SRR24696361_1.fastq.gz | Fastqsanger.gz | |||
| SRR24696361_2.fastq.gz | Fastqsanger.gz | |||
| SRR24696362_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Experimental evidence for cancer resistance in a bat species
| PRJNA975353 | ENA
Project description:Bats are remarkably long-lived for their size with many species living more than 20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigated requirements for malignant transformation in primary bat fibroblasts in four bat species - little brown bat (Myotis lucifugus), big brown bat (Eptesicus fuscus), cave nectar bat (Eonycteris spelaea) and Jamaican fruit bat (Artibeus jamaicensis) – spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence and express active telomerase. Bat cells displayed attenuated stress induced premature senescence with a dampened secretory phenotype. Unexpectedly, we discovered that bat cells could be readily transformed by only two oncogenic perturbations or “hits”: inactivation of either p53 or pRb and activation of oncogenic RASV12. This was surprising because other long-lived mammalian species require up to five hits for malignant transformation. Additionally, bat fibroblasts exhibited increased p53 and MDM2 transcript levels, and elevated p53-dependent apoptosis. The little brown bat showed a genomic duplication of the p53 gene. We hypothesize that bats evolved enhanced p53 activity through gene duplications and transcriptional upregulation as an additional anti-cancer strategy, similar to elephants. In summary, active telomerase and the small number of oncogenic hits sufficient to malignantly transform bat cells suggest that in vivo bats rely heavily on non-cell autonomous mechanisms of tumor suppression.
2025-02-21 | GSE262772 | GEO
Project description:Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances by its ability to dissipate energy excess. In the current study, we analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR-Retn versus nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR-Retn transgenic rats when compared to SHR controls showed a lower relative weight, significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids, and significantly decreased palmitate oxidation and glucose oxidation. In addition, in vivo microPET imaging revealed significantly reduced 18F-FDG uptake in BAT induced by exposure to cold in SHR-Retn versus control SHR. Gene expression profiles identified differentially expressed genes involved in skeletal muscle and connective tissue developmental and inflammation, as well as MAPK and insulin signaling. These results provide compelling evidence that autocrine effects of resisitin in BAT play an important role in the pathogenesis of insulin resistance in the rat.
2016-07-03 | E-MTAB-3787 | biostudies-arrayexpress
Project description:Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), entitled Bipolar Androgen Therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill-defined. Here we show that growth inhibition of prostate cancer models by SPA requires high androgen receptor (AR) activity and is driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pre-treatment AR activity predicts downregulation of MYC, clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance can be overcome by alternating SPA with the AR inhibitor enzalutamide, which induces adaptive upregulation of AR and re-sensitizes prostate cancer to SPA. This work identifies high AR activity score as a predictive biomarker of response to BAT and supports a new treatment paradigm for prostate cancer involving alternating between AR inhibition and activation
2022-11-01 | GSE213437 | GEO
Project description:Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection. Here, we test whether such transcriptional patterns occur in Egyptian fruit bat tissues through single-cell and spatial transcriptomics of gut, lung and blood cells, comparing gene expression between bat, mouse and human. Despite numerous recent loss and expansion events of interferons in the bat genome, interferon expression and induction are remarkably similar to that of mouse. In contrast, central complement system genes are highly and uniquely expressed in key regions in bat lung and gut epithelium, unlike in human and mouse. These genes also evolve rapidly in their coding sequence across the bat lineage. Finally, the bat complement system displays strong hemolytic and inhibitory activities. Together, these results indicate a distinctive transcriptional divergence of the complement system, which may be linked to bat resistance, and highlight the intricate evolutionary landscape of bat immunity.
2024-11-18 | PXD058003 | Pride
Project description:The Global Burden of Disease implicates air pollution in mediating as much as 20% of Type 2 Diabetes mellitus globally. This profound impact of air pollution is supported by experimental studies suggesting effects on whole body metabolism and insulin resistance. We explored the effect of chronic inhalational air pollution exposure for 12 weeks, using a whole body inhalation device in mice that allows for daily exposure to concentrated ambient particulate matter <2.5 microns (6 hours/day, 5 days a week) on whole body metabolism and brown adipose tissue (BAT) function, with detailed investigation of differentially methylated regions (DMRs), chromatin accessibility (differential accessible regions or DARs), and differential gene expression (DEGs) levels using a combination of whole genome bisulfite sequencing, ATAC-sequencing, and RNA-sequencing respectively. A significant impact of chronic PM2.5 exposure on BAT function and whole-body metabolism through alterations in key BAT transcriptional programs resulting in increased redox stress, lipid deposition, fibrosis and reduced thermogenic function of BAT was observed. Significant differential methylation with evidence for both hypomethylation and hypermethylation involving target regions corresponding to both circadian and Nrf2 target genes including sites enriched for transcription factor binding sites implicated in redox stress, insulin resistance and BAT function in response to PM2.5. ATAC sequencing revealed widespread chromatin remodeling involving intronic regions and enhancer elements and loss of DARs in Ucp1 and Gclc major regulatory genes associated with thermogenesis and glutathione synthesis. DARs-DEGs interaction analysis pointed to functional pathways linked to diabetes development, fatty acid biosynthesis activation and activation of JAK-STAT, and MAPK in PM-exposed mice. Integrated analysis of DARs, DEGs and DMRs uncovered the Histone de-acetylase Hdac9 and Kdm2b, a Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3. ChiP studies demonstrated that Hdac9 physically interacts with the BAT transcription factor Prdm16 and rorα in BAT decreasing their expression and providing at least one direct mechanism for our observations. Collectively our results results link DNA methylation with control of chromatin accessibility and gene expression changes involved in the alteration of brown fat metabolism linking chronic air pollution exposure with alterations in BAT and whole-body metabolism
2025-07-30 | GSE255961 | GEO
Project description:Brown adipose tissue (BAT) is best known for thermogenesis. Whereas numerous studies in rodents found tight associations between the metabolic benefits of BAT and enhanced wholebody energy expenditure, emerging evidence in humans suggests that BAT is protective against Type 2 diabetes independent of body-weight. The underlying mechanism for this dissociation remained unclear. Here, we report that impaired mitochondrial flux of branched-chain amino acids (BCAA) in BAT, by deleting mitochondrial BCAA carrier (MBC, encoded by Slc25a44), was sufficient to cause systemic insulin resistance without affecting whole-body energy expenditure or body-weight. We found that brown adipocytes catabolized BCAAs in the mitochondria as essential nitrogen donors for the biosynthesis of glutamate, N-acetylated amino acids, and one of the products, glutathione. BAT-selective impairment in mitochondrial BCAA flux led to elevated oxidative stress and insulin resistance in the liver, accompanied by reduced levels of BCAA-derived metabolites in the circulation. In turn, supplementation of glutathione restored insulin sensitivity of BAT-specific MBC knockout mice. Notably, a high-fat diet rapidly impaired BCAA catabolism and the synthesis of BCAA-nitrogen derived metabolites in the BAT, while cold-induced BAT activity is coupled with an active synthesis of these metabolites. Together, the present work uncovers a mechanism through which brown fat controls metabolic health independent of thermogenesis via BCAA-derived nitrogen carriers acting on the liver.
2024-03-05 | PXD043813 | JPOST Repository
Project description:Bat adenoviruses are a group of recently identified adenoviruses (AdVs) which are highly prevalent in bats yet share low similarity to known AdVs from other species. In this study, deep RNA sequencing was used to analyze the transcriptome at five time points following the infection of a bat AdV in a kidney cell line derived from a myotis bat species. Evidence of AdV replication was observed with the proportion of viral RNAs ranging from 0.01% at 6 h to 1.3% at 18 h. Further analysis of viral temporal gene expression revealed three replication stages; the early stage genes encoding mainly for host interaction proteins, the intermediate stage genes for the DNA replication and assembly proteins, and the late stage genes for most structural proteins. Several bat AdV genes were expressed at stages that differed from their counterpart genes previously reported for human AdV. In addition, single-base resolution splice sites of several genes and promoter regions of all 30 viral genes were fully determined. Simultaneously, the temporal cellular gene expression profiles were identified. The most overrepresented functional categories of the differentially expressed genes were related to cellular immune response, transcription, translation, and DNA replication and repair. Taken together, the deep RNA sequencing provided a global, transcriptional profile of the novel BtAdV and the virus-host interactions, which will be useful for the understanding and investigation of AdV replication, pathogenesis and specific virus-bat interactions in future research. Deep RNA sequencing was used to analyze the transcriptome at five time points(0h,6h,8h, 12h 18h) following the infection of a bat AdV in a bat kidney cell.
2013-02-06 | E-GEOD-41275 | biostudies-arrayexpress
Project description:The bat offers an alternative paradigm to the standard mouse and chick model of limb development as it has extremely divergent forelimbs (long digits supporting a wing) and hindlimbs (short digits and claws) due the distinct requirements of both aerial and terrestrial locomotion. We used a cross-species microarray approach to identify differentially expressed (DE) genes between the bat (Minniopterus natalensis) forelimb and hindlimb autopods at Carollia developmental stages (CS) 16 and CS17, and between the bat (CS17) and mouse (E13.5) forelimb autopods. Several DE genes were identified, including two homeobox genes, Meis2, a proximal limb-patterning gene, and Hoxd11, a gene involved in digit elongation. Both genes are significantly over-expressed in the developing bat forelimb as compared to the hindlimb and equivalently staged mouse forelimbs. A reference design was used in this microarray experiment. A pool of left and right mouse forelimb autopods from 24 embryos was used as the reference sample. This sample was directly compared to individual CS16 and CS17 bat fore- and hindlimbs (left and right of one individual pooled) that were classified as the test conditions. Four experimental sessions were performed using an independently amplified mouse reference pool and 4 biological repeats for the bat limbs. These samples were co-hybridised to OPERON Mouse OpArray (ver. 4.0) spotted oligonucleotide slides to perform a competitive Cross-Species Hybridisation experiment. The bat aRNA (test) samples were labelled with Cy3 dye (green signal), the mouse aRNA (reference) sample was labelled with Cy5 dye (red signal).
2014-02-15 | E-GEOD-51042 | biostudies-arrayexpress