Ontology highlight
ABSTRACT:
PROVIDER: PRJNA846357 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: ATAC-seq was performed on preterm lambs that were ventilated by invasive mechanical ventilation or noninvasive respiratory support utilizing a mask and compared to gestation-age-matched preterm lambs that were not ventilated and naturally delivered term lambs. Methods: Lung chromatin access profiles were generated for: 1) Unventilated preterm lamb, 2) preterm lambs delivered at gd131 and intubated and mechanically ventilated for 3 days, 3) preterm lambs delivered at gd131 and not intubated and resuscitated by placing a face mask over the nose and mouth and controlling O2 delivery via a computer-controlled electronic blower device, 4) unventilated naturally delivered full-term lambs. Results: Using an optimized data analysis workflow, we mapped between 76 and 96 million sequence reads per sample to the sheep genome Conclusions: Our study represents the first detailed analysis of ventilated preterm lung chromatin access, with biologic replicates, generated by ATAC-seq
2021-06-30 | GSE163807 | GEO
Project description:In this study, we studied the fibrolytic potential of the rumen microbiota in the rumen of 6 lambs separated from their dams from 12h of age and artificially fed with milk replacer (MR) and starter feed from d8, in absence (3 lambs) or presence (3 lambs) of a combination of the live yeast Saccharomyces cerevisiae CNCM I-1077 and selected yeast metabolites. The fibrolytic potential of the rumen microbiota of the lambs at 56 days of age was analyzed with a DNA microarray (FibroChip) targeting genes coding for 8 glycoside hydrolase (GH) families.
2019-10-01 | GSE122256 | GEO
Project description:Pompe disease (PD) is a neuromuscular disorder caused by deficiency of acid-alpha-glucosidase (GAA), leading to motor and respiratory dysfunctions. Available Gaa knock-out (KO) mouse models do not accurately mimic PD, particularly the highly impaired respiratory phenotype. Methods. Here we developed a new mouse model of PD crossing Gaa KO B6;129 with DBA2/J mice. Findings. Male Gaa KODBA2/J presents most of the key features of the human disease, including early lethality, severe respiratory impairment, cardiac hypertrophy and muscle weakness. Transcriptome analyses of Gaa KODBA2/J, compared to the parental Gaa KOB6;129 mice, revealed a profoundly impaired gene signature in the spinal cord and a similarly deregulated gene expression in skeletal muscle. Muscle and spinal cord transcriptome changes in Gaa KODBA2/J, were significantly improved upon gene therapy with AAV vectors expressing a secreted GAA enzyme.
2020-10-22 | GSE156230 | GEO
Project description:Cistus ladanifer L. is a common shrub endemic to the Mediterranean that is highly concentrated in condensed tannins (CT). CT form complexes with dietary protein that resist microbial degradation in the rumen, which enhances dietary protein utilization in ruminant diets. The objective of this study was to evaluate the utilization of CT in the diet of lambs on the proteomes of muscle, hepatic and adipose tissues. Twenty-four white merino ram lambs were divided in three groups (n=8) fed on different diets: control (16% crude protein - CP), reduced protein (12% CP) and reduced protein treated with CT extract. At the end of the trial, lambs were slaughtered and the longissimus lumborum muscle, hepatic and peri-renal adipose tissues sampled. A two-way approach was used for shotgun proteomic analysis: 2D-DIGE (gel-based) and nanoLC-MS (gel-free). In the muscle, control lambs had lower abundance proteins that partake in the glycolysis pathway. With dietary 12 % CP, lambs had higher abundance of Fe-carrying proteins in the hepatic tissue. Lambs with dietary CT had higher abundance of hepatic flavin reductase. In the adipose tissue, control lambs had lower abundance of fatty-acid synthase. In conclusion, CT inclusion influences specific pathways in lamb tissues.
2021-02-16 | PXD015689 | Pride
Project description:Pompe disease is a neuromuscular disorder caused by mutations in the gene encoding for the lysosomal enzyme acid α-glucosidase (GAA). GAA converts lysosomal glycogen to glucose, and its deficiency leads to pathologic glycogen accumulation. Enzyme replacement therapy (ERT) is the only available treatment for Pompe disease at the moment with several shortcomings. We have shown that liver expression of secGAA has better therapeutic efficacy than non-engineered GAA after long-term treatment of four months old Gaa-/- mice with low vector doses. Based on those results, we have treated severely affected nine months old Gaa-/- mice with the AAV-secGAA vector and followed the animals for nine months thereafter. At the end of the study, AAV-treated Gaa-/- mice showed complete rescue of the Pompe phenotype. Transcriptomic profiling of skeletal muscle highlighted mitochondrial bioenergetics defects, supported by electron microscopy, western blotting and biochemical findings, which were partially corrected after AAV treatment. Together, these results provide insight into the reversibility of advanced Pompe disease in the Gaa-/- mouse model via liver gene transfer of secGAA.
2021-04-26 | GSE150935 | GEO
Project description:Expansion of triplex-forming GAA/TTC repeats in the first intron of FRDA gene is known to cause Friedreich’s ataxia. Besides FRDA, there are a number of other highly polymorphic GAA/TTC loci in the human genome where the size variations so far were considered to be a neutral event. Using yeast as a model system, we demonstrate that expanded GAA/TTC repeats represent a threat to eukaryotic genome integrity by triggering double-strand breaks and gross chromosomal rearrangements. The fragility potential strongly depends on the length of the track and orientation of the repeats relative to the replication origin which correlates with their propensity to adopt secondary structure and to block replication progression. We show that fragility is mediated by mismatch repair machinery and requires the MutS(beta) and endonuclease activity of MutL(alpha). We suggest that the mechanism of GAA/TTC-induced chromosome aberrations defined in yeast can also operate in human carriers with expanded tracks. Keywords: CGH-array
2008-05-14 | GSE11425 | GEO
Project description:Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study’s objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106-107 days), control late pre-term (127 days), and experimental lambs who were born pre-term and supported on EXTEND until late pre-term age (125-128 days). Bioinformatic analysis determined differential gene expression among the three cohorts and across four different brain tissue sections: basal ganglia, cerebellum, hippocampus, and motor cortex. There were no clinically relevant histological differences between the control late pre-term and EXTEND ovine brain tissues. RNA-sequencing demonstrated that there was greater differential gene expression between the control pre-term lambs and EXTEND lambs than between the control late pre-term lambs and EXTEND lambs. Our study demonstrates that the use of EXTEND to support pre-term lambs until they reach late pre-term gestational age results in brain tissue gene expression that more closely resembles that of the lambs who reached late pre-term gestation within their maternal sheep’s womb than that of the lambs who were born prematurely.
2024-11-21 | GSE275228 | GEO
Project description:The common practise of artificially rearing some lambs from prolific meat breeds of sheep constitutes a welfare issue due to increased mortality rates and negative health issues. In this multidisciplinary study, we investigated the possible short and mid-term advantages of artificially feeding fresh ewe’s milk instead of commercial milk replacer on lambs’ growth, health and welfare. Romane lambs were either separated from their mothers on D3 and fed with Lacaune ewes’ milk (LAC, n=13) or milk replacer (REP, N=15), or they were reared by their mothers (MOT, n=15). On D45, they were weaned, gathered in single sex groups until the end of the study on D150. Lamb performance and biomarkers of overall health were assessed by measuring: growth, dirtiness of the perianal area, enteric pathogens in the faeces, total antioxidant status and redox status assessed by plasma reduced (GSH)/oxidized (GSSG) glutathione ratio, and immune response after vaccination against chlamydiosis. As an exploratory approach, blood cell transcriptomic profiles were also investigated. Last, Qualitative Behaviour Assessment was performed as an integrated welfare criteria. LAC and REP never differed in their average daily gain but grew less than MOT lambs in the early suckling period and just after weaning. No effect was detected afterwards. On D30, LAC and REP lambs had lower total antioxidant and higher redox status than MOT lambs but did not differ among themselves. LAC and MOT had a cleaner perianal area than REP lambs on D21, while faecal pathogen infection did not vary between the treatment groups. After vaccination, LAC also had a stronger immune response on D90 compared to REP lambs. Transcriptome analysis performed on D150 showed differential gene expression, mainly in relation to inflammatory, immune and cell cycle response, between male lambs of the LAC group and those of the MOT and REP groups. Based on Qualitative Behaviour Assessment, LAC lambs never differed from MOT lambs in their general activity and varied from REP only on D21; REP lambs were always more agitated than MOT lambs. In conclusion, artificial milk feeding impaired early growth rate, health, and emotional state mainly during the milk feeding period and at weaning. Feeding artificially reared lambs with fresh ewe's milk partly mitigated some of the negative effects induced by milk replacer but without achieving the full benefit of being reared by the mother.
2020-11-23 | GSE131763 | GEO