Regulation of metabolism by miR-378

The present invention provides a method of regulating fatty acid metabolism in a cell by contacting the cell with a modulator of miR-378 and/or miR-378* activity or expression. The present invention also provides a method of treating or preventing a metabolic disorder, such as obesity, diabetes, or metabolic syndrome, in a subject by administering to the subject an inhibitor of miR-378 and/or miR-378* expression or activity. Methods of treating or preventing pathologic cardiac hypertrophy, cardiac remodeling, myocardial infarction, or heart failure in a subject by inhibiting the expression or activity of miR-378 and/or miR-378* in a subject are also disclosed.Board of Regents, University of Texas Syste

Micro-RNAs of the miR-15 family modulate cardiomyocyte survival and cardiac repair

A family of microRNAs, called the miR-15 family, which includes miR-195, are shown to be up-regulated during pathological cardiac remodeling and repress the expression of mRNAs required for cell proliferation and survival, with consequent loss of cardiomyocytes. Strategies to block expression of the miR-15 family in the heart as a treatment for diverse cardiac disease are provided.Board of Regents, University of Texas Syste

Micro-RNAS that control myosin expression and myofiber identity

The present invention relates to the identification of two microRNAs, miR-499 and miR-208b, that repress fast skeletal muscle contractile protein genes. Expression of miR-499 and/or miR-208b can be used to repress fast fiber genes and activate slow fiber genes in the treatment of musculoskeletal disorders. Inhibition of miR-499 and/or miR-208b is proposed as a treatment for cardiac hypertrophy, myocardial infarction, and/or heart failure. Pharmaceutical compositions comprising antagonists and agonists of miR-499 and miR-208b function are also disclosed.Board of Regents, University of Texas Syste

Micro-RNA family that modulates fibrosis and uses thereof

The present invention relates to the identification of a microRNA family, designated miR-29a-c, that is a key regulator of fibrosis in cardiac tissue. The inventors show that members of the miR-29 family are down-regulated in the heart tissue in response to stress, and are up-regulated in heart tissue of mice that are resistant to both stress and fibrosis. Also provided are methods of modulating expression and activity of the miR-29 family of miRNAs as a treatment for fibrotic disease, including cardiac hypertrophy, skeletal muscle fibrosis other fibrosis related diseases and collagen loss-related disease.Board of Regents, University of Texas Syste

Reversible to Irreversible Flow Transition in Periodically Driven Vortices

We show that periodically driven superconducting vortices in the presence of quenched disorder exhibit a transition from reversible to irreversible flow under increasing vortex density or cycle period. This type of behavior has recently been observed for periodically sheared colloidal suspensions and we demonstrate that driven vortex systems exhibit remarkably similar behavior. We also provide evidence that the onset of irreversible behavior is a dynamical phase transition.Comment: 4 pages, 4 postscript figures. Version to appear in Physical Review Letter

ROCK2/rasHa cooperation induce malignant conversion via p53 loss, elevated NF-κβ and tenascin C-associated rigidity but p21 inhibits ROCK2/NF-κβ-mediated progression

To study ROCK2 activation in carcinogenesis, mice expressing 4-hydroxytamoxifen (4HT)- activated ROCK2 [K14.ROCKer] were crossed to mice expressing epidermal activated ras Ha [HK1.ras1205]. At 8 weeks, 4HT-treated K14.ROCKer-HK1.ras1205 cohorts exhibited papillomas similar to HK1.ras1205 controls; however, K14.ROCKer-HK1.ras1205 histotypes comprised a mixed papilloma/well-differentiated squamous cell carcinoma [wdSCC], exhibiting p53 loss, increased proliferation, and novel NF-κβ expression. By 12 weeks, K14.ROCKer-HK1.ras1205 wdSCCs exhibited increased NF-κβ and novel tenascin C, indicative of elevated rigidity; yet despite continued ROCK2 activities /p-Mypt1 inactivation, progression to SCC required loss of compensatory p21 expression. K14.ROCKer -HK1.ras1205 papillomatogenesis also required a wound-promotion stimulus, confirmed by breeding K14.ROCKer into promotion-insensitive HK1.ras1276 mice, suggesting a permissive K14.ROCKer-HK1.ras1205 papilloma context [wound-promoted/NF-κβ+ve/p53-ve/p21+ve] preceded K14.ROCKer-mediated [p-Mypt1/tenascin C/rigidity] malignant conversion. Malignancy depended on ROCKer/p-Mypt1 expression, as cessation of 4HT-treatment induced disorganised tissue architecture and p21-associated differentiation in wdSCCs; yet tenascin C retention in connective tissue ECM suggests the rigidity laid down for conversion persists. Novel papilloma outgrowths appeared expressing intense, basal-layer p21 which confined endogenous ROCK2/p-Mypt1/NF-κβ to supra-basal layers, and was paralleled by restored basal-layer p53. In later SCCs, 4HT-cessation became irrelevant as endogenous ROCK2 expression increased, driving progression via p21 loss, elevated NF-κβ expression and tenascin C-associated rigidity; with p-Mypt1 inactivation/actinomyosin-mediated contractility to facilitate invasion. However, p21-associated inhibition of early-stage malignant progression and the intense expression in papilloma outgrowths, identifies a novel, significant antagonism between p21 and ras Ha/ROCK2/NF-κβ signalling in skin 3 carcinogenesis. Collectively these data show that ROCK2 activation induces malignancy in rasHa-initiated/promoted papillomas in the context of p53 loss and novel NF-κβ expression;whilst increased tissue rigidity and cell motility/contractility help mediate tumour progression

Investigation of kilovolt ion sputtering second quarterly progress report

Kilovolt ion sputtering - electron beam focusing of cesium ion beam, radiation detection in copper atoms, ultrahigh vacuum system construction, and spectrometer pulse heigh