Vascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the progressive loss of VSMC in the Notch3-/- mouse on blood vessel integrity in the central nervous system
Notch3 is necessary for blood vessel integrity in the central nervous system.
Age, Specimen part
View SamplesMost commonly used models of non-alcoholic steatohepatitis (NASH) are diets based on specific gene knockouts or represent extreme manipulations of diet. We have examined the effects of modest increased caloric intake and high dietary unsaturated fat content on the development of NASH in male rats using a model in which overfeeding is accomplished via intragastric infusion of liquid diets as a part of total enteral nutrition. Male Sprague dawley rats were fed diets 5% corn oil containing diets at 187 Kcal/kg3/4/d or fed 70% corn oil containing diets at 220 Kcal/kg3/4/d for a period of 3 weeks. Hepatic gene expression were assessed at the end of the study. Our results indicate that overfeeding of high unsaturated fat diets leads to pathological, endocrine and metabolic changes characteristic of NASH patients and is associated with increased oxidative stress and TNF-a.
A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet.
No sample metadata fields
View SamplesSoy foods have been suggested to have both positive health benefits and potentially adverse effects largely as a result of their content of isoflavone phytoestrogens. Since soy protein isolate (SPI) contains isoflavones, in addition to purported health benefits, safety concerns have been raised regarding the use of SPI and soy formulas, because of potential estrogenic actions during the neonatal period, including the potential for reproductive toxicity, infertility, and the possibility of increased risk for development and recurrence of estrogen sensitive cancers such as breast cancer. In the current study, we used a rat model to compare the effects of SPI with those of 17b-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were either fed AIN-93G diets containing casein (CAS) or SPI beginning on postnatal day (PND) 30.
Mammary gland morphology and gene expression differ in female rats treated with 17β-estradiol or fed soy protein isolate.
Sex
View SamplesIncreased miR-135a levels are observed in human patients with temporal lobe Epilepsy (TLE) and in experimental animal models. Upon targeting the increased miR-135a levels in vivo using antagomirs in kainic acid induced status epilepticus mouse model of TLE, we observed a strong reduction of spontaneous recurrent seizures. To understand this further and to find target mRNAs that potentially mediate the seizure suppressive function of miR-135a, we performed immunoprecipitation using biotin tagged miRNA mimics, followed by RNAsequencing (RNAseq). We found several novel neuronal targets of miRNA-135a and identified Mef2a as a key target in this study. Here we report the total RNAseq data. Overall design: N2A cells were transfected with biotin tagged miRNA mimics for miR-135a and negative control and immunoprecipitations were performed. N = 3 replicates of IP and input samples for each condition were generated and sequenced on illumina platform for total RNA for identification of novel targets of miR-135a.
Antagonizing Increased <i>miR-135a</i> Levels at the Chronic Stage of Experimental TLE Reduces Spontaneous Recurrent Seizures.
Cell line, Subject
View SamplesThe current study was designed to determine if dietary fatty acid concentration and composition affects the development and progression of nonalcoholic fatty liver disease. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated), or corn oil (polyunsaturated). Overfeeding 5% corn oil produced little steatosis relative to feeding 5% olive oil. This was associated with lower fatty acid synthesis and reduced SREBP-c signaling in the 5% corn oil group. Overfeeding 70% fat diets increased steatosis and lead to increased liver necrosis in the 70% corn oil but not olive oil group. Increased injury after feeding polyunsaturated fat diets was linked to peroxidizability of hepatic free fatty acids and triglycerides and appearance of peroxidaized lipid products HETES and HODES previously linked to clinical nonalcoholic steatohepatitis.
Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition.
Sex
View SamplesIn order to properly understand whether xenoestrogens act as estrogens, it is essential to possess a solid portrait of the physiological effects of exogenous estradiol. Because the estrogen-dependent gene expression is one of the primary biomarkers of estrogenic action, we have assessed effects of three doses of exogenous estradiol (0.1, 1.0 and 10 g/kg of body weight/day) on the mammary gland morphology and gene expression profiles by microarray analysis of prepubertal male and female rats of both sexes compared to untreated controls. Estradiol was administered subcutaneously with minipumps from weaning at PND21 to the end of the experiment at PND33. The data suggest that the male mammary is a sensitive tissue for estrogenicity assessment.
Mammary gland morphology and gene expression signature of weanling male and female rats following exposure to exogenous estradiol.
Sex
View SamplesIn order to study the transcriptional response of the fly brain to sugar and complete starvation, we first confirmed that 24 hours of sugar and complete starvation in flies is sufficient to elicit a homeostatic response. Subsequently, we used holidic medium to study effects of deficiency of a specfic macronutrient- cabohydrate in the food. To do so , we generated RNA- seq libraries from brains of 5 day old mated adult male flies maintained on different feeding regimes and used the sequencing data to identify diffrentially expressed genes in the brain under different feeding regimes. Overall design: For each condition, we used RNA prepared from 120-130 manually dissected adult fly brains maintained under complete starvation or sugar starvation regime for 24 hours.
Sugar Promotes Feeding in Flies via the Serine Protease Homolog scarface.
Sex, Specimen part, Cell line, Subject
View SamplesWhile the existence of intestinal epithelial stem cells (IESCs) has been well established, their study has been limited due to the inability to isolate them. Previous work has utilized side population (SP) sorting of the murine small intestinal mucosa to isolate a viable fraction of cells enriched for putative IESCs. We have used microarray analyses to characterize the molecular features of this potential stem cell population.
Molecular properties of side population-sorted cells from mouse small intestine.
No sample metadata fields
View SamplesWe applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80mM or 150mM NaCl after digestion contain predominantly mononucleosomes and represent calssical 'active' chromatin. Profiles of these low-salt-soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of RNA polymerase II. Nearly quantitative recovery of chromatin is obtained with 600mM NaCl, however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and unbound intermediates in active processes, thus providing a simple, powerful strategy for mapping epigenome dynamics.
Genome-wide profiling of salt fractions maps physical properties of chromatin.
Specimen part
View SamplesWorldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe thread to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC). The OPCs had previously been obtained from a hydro-ethanolic (1:1) extract from the leaves of Combretum mucronatum, a plant which is traditionally used in West Africa for the treatment of helminthiasis, therefore, also the crude extract was included in the study. Significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms defense against tannins. For example, T22D1.2, an orthologue of human basic salivary proline-rich protein (PRB) 2, and numr-1 (nuclear localized metal responsive) were found to be strongly up-regulated. Down-regulated genes were mainly associated with lysosomal activity, glycoside hydrolysis or the worms innate immune response. No major differences were found between the groups treated with purified OPCs versus the crude extract. Investigations using GFP reporter gene constructs of T22D1.2 and numr-1 corroborated the intestine as the predominant site of the anthelmintic activity.
Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.
Specimen part, Treatment
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