This dataset is a time series (1 hour [h], 4 hours, 24 hours, 48 hours, 1 week [w], and 8 weeks) intended to compare normal functioning left ventricles [lv + lv2] with infarcted [ilv] and non-infarcted left ventricles [nilv]. Ilv samples are taken from the region between the LAD artery and the apex on a mouse with myocardial infarction. Lv2 samples are from the same region in a sham operated mouse. Nilv samples are taken from the region above the infartion and the left ventricle [lv] samples mimic that region in a sham mouse. The lv and lv2 samples can be compared as both are from normal functioning hearts. For more information visit http://cardiogenomics.med.harvard.edu/groups/proj1/pages/mi_home.html
Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies.
No sample metadata fields
View SamplesAn important event in the pathogenesis of heart failure is the development of pathological cardiac hypertrophy. In cultured cardiac cardiomyocytes, the transcription factor Gata4 is required for agonist-induced cardiomyocyte hypertrophy. We hypothesized that in the intact organism Gata4 is an important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress. To test this hypothesis, we studied mice heterozygous for deletion of the second exon of Gata4 (G4D). At baseline, G4D mice had mild systolic and diastolic dysfunction associated with reduced heart weight and decreased cardiomyocyte number. After transverse aortic constriction (TAC), G4D mice developed overt heart failure and eccentric cardiac hypertrophy, associated with significantly increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced heart failure in G4D mice. Unlike WT-TAC controls, G4D-TAC cardiomyocytes hypertrophied by increasing in length more than width. Gene expression profiling revealed upregulation of genes associated with apoptosis and
Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure.
No sample metadata fields
View SamplesIGF1 and IGF1 receptors (IGF1R) are present in the adult heart and have been shown to be essential for myocardial performance. Insulin-like growth factor 1 (IGF1) is produced in numerous tissues particularly by the liver in response to growth hormone stimulation and is an important factor in the regulation of post-natal growth and development. We have generated and characterized transgenic mice over-expressing the IGF1R. We crossed IGF1R transgenic mice with dominant negative (dn)PI3K (p110) and with constitutively active (ca)PI3K(p110) transgenic mice. Expression profiling was performed on the ventricles of IGF1R, IGF1R-caPI3K, IGF1R-dnPI3K, caPI3K, dnPI3K transgenic female mice at 3 months of age. Non-transgenic littermates were used as controls.
The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway.
No sample metadata fields
View SamplesHumoral responses of mice specifically deleted for Moz (a histone acetyltransferase) or c-Myb (a transcription factor) in B cells were aberrant. RNA-sequencing analysis was performed to assess gene expression differences compared to wild-type controls in germinal center B cells or plasmablasts. Overall design: Moz f/f Aicda1-Cre, Aicda1-Cre, Myb f/f Cd23-Cre, Mybf/f (no cre) mice were immunized with NP-KLH precipitated in alum and germinal center B cells were sort-purified. Secondary plasmablasts were sort-purified from immunized mice boosted with NP-KLH in PBS (Myb experiment). Two independent experiments were conducted.
Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ.
Specimen part, Subject
View SamplesThe study has been described in the following paper: Gianni Parise, Stuart M. Phillips, Jan J. Kaczor and Mark A. Tarnopolsky (2005). Antioxidant enzyme activity is up-regulated after unilateral resistance exercise training in older adults. Free Radical Biology and Medicine, Volume 39, Issue 2, 15 July 2005, Pages 289-295 We cite the following three paragraphs from this paper: "MATERIALS AND METHODS Subjects Twelve men (71.2 ± 6.5 y) volunteered to participate in a 12 week uni-lateral leg resistance training program (Table 1). All subjects underwent a thorough screening process before being admitted into the study. Subjects were first screened by telephone, and were then subject to a medical evaluation. Consent from their family physician was required, and then all potential subjects underwent a resting electrocardiogram, and a sub-maximal graded exercise test on a bicycle ergometer witih a 12-lead ECG. Exclusion criteria included: evidence of coronary hear disease; congestive heart failure; uncontrolled hypertension; chronic obstructive pulmonary disease; diabetes mellitus; renal failure; major orthopaedic disability; and smoking. None of the subjects had ever participated in a structured exercise program. After subjects were advised of the benefits and risks of participation, subjects gave their written informed consent. The study was approved by the McMaster University and Hamilton Health Sciences Research Ethics Board and conferred to the principles of the declaration of Helsinki. Exercise Training Resistance training was performed three times weekly on non-consecutive days (Monday, Wednesday, and Friday) for 12 weeks, under strict supervision. Prior to and after each training session subjects were required to perform passive stretching. Resistance exercise for each session consisted of 3 sets of 10 repetitions for each of leg press and leg extension. Training progressed from one set of each exercise at 50% of the initial 1 repetition maximum (1RM) to 3 sets at 80% of 1RM over the training period. Training logs were kept to record the volume and intensity of each session. The 1RM was re-evaluated every 2 weeks, and the training load was adjusted accordingly. All exercises were performed on universal strength training equipment (Universal Gym Equipment, Inc., Cedar Rapids, Iowa). Muscle Biopsy A muscle biopsy was taken from the vastus lateralis muscle of both legs before as well as after the training period, 20 cm proximal to the knee joint using a modified Bergström needle (5 mm diameter) with suction modification. The biopsy specimen was dissected of fat and connective tissue and immediately frozen in liquid nitrogen. All samples were stored at -80 °C for subsequent analysis. All subjects were required to abstain from strenuous physical activity for 48 hours prior to the testing session. The non-trained leg performed an acute bout of exercise at the same relative intensity of the training leg to allow for the determination of the effect of training and the effect of acute resistance exercise." Additional Notes: 1) The samples of 8 out 12 were used in the gene expression study. 2) The 2 factors in this study are: 2.1) Leg - Left or Right 2.2) Training - Baseline: samples taken on each leg before exercise - Resistance Training: one of the legs was subject to resistance training followed by acute exercise - Acute Exercise: the other leg had only the acute exercise 3) The baseline samples will be used for right versus left leg comparison to see variance between legs for human experimentation technical issues. The samples from Resistance or Acute Exercise will be compared to corresponding baseline samples to evaluate the effect of both exercise programs on gene expression.
Gene expression, fiber type, and strength are similar between left and right legs in older adults.
Sex, Age, Specimen part, Subject
View SamplesWe used the CRISPR/Cas9 technique to construct nbr1-KO lines (KO1 and KO3) in order to test the effects of AtNBR1 depletion. Reduced expression of several ABA-up regulated genes were observed in shoots of the two KO lines.
A selective autophagy cargo receptor NBR1 modulates abscisic acid signalling in Arabidopsis thaliana.
Age, Specimen part
View SamplesC.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Treatment
View SamplesSpecific bile acids are potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis, and the microbiota. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis (Cyp7a1, Cyp8b1) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway and modifies the biliary bile acid composition. In contrast, loss-of-function studies using MafG(+/-) mice causes de-repression of the same genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR
MAFG is a transcriptional repressor of bile acid synthesis and metabolism.
Treatment
View Samplesassess the efficacy of Pimasertib to characterize its mechanism of action
Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas.
Cell line, Treatment, Time
View Samples