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 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-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-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

Dual targeting of MIR-208 and MIR-499 in the treatment of cardiac disorders

The present invention provides a method of treating or preventing cardiac disorders in a subject in need thereof by inhibiting the expression or function of both miR-499 and miR-208 in the heart cells of the subject. In particular, specific protocols for administering inhibitors of the two miRNAs that achieve efficient, long-term suppression are disclosed. In addition, the invention provides a method for treating or preventing musculoskeletal disorders in a subject in need thereof by increasing the expression or activity of both miR-208 and miR-499 in skeletal muscle cells of the subject.Board of Regents, University of Texas Syste

Continuous Data Assimilation with Stochastically Noisy Data

We analyze the performance of a data-assimilation algorithm based on a linear feedback control when used with observational data that contains measurement errors. Our model problem consists of dynamics governed by the two-dimension incompressible Navier-Stokes equations, observational measurements given by finite volume elements or nodal points of the velocity field and measurement errors which are represented by stochastic noise. Under these assumptions, the data-assimilation algorithm consists of a system of stochastically forced Navier-Stokes equations. The main result of this paper provides explicit conditions on the observation density (resolution) which guarantee explicit asymptotic bounds, as the time tends to infinity, on the error between the approximate solution and the actual solutions which is corresponding to these measurements, in terms of the variance of the noise in the measurements. Specifically, such bounds are given for the the limit supremum, as the time tends to infinity, of the expected value of the $L^2$-norm and of the $H^1$ Sobolev norm of the difference between the approximating solution and the actual solution. Moreover, results on the average time error in mean are stated

A Computational Study of a Data Assimilation Algorithm for the Two-dimensional Navier--Stokes Equations

We study the numerical performance of a continuous data assimilation (downscaling) algorithm, based on ideas from feedback control theory, in the context of the two-dimensional incompressible Navier--Stokes equations. Our model problem is to recover an unknown reference solution, asymptotically in time, by using continuous-in-time coarse-mesh nodal-point observational measurements of the velocity field of this reference solution (subsampling), as might be measured by an array of weather vane anemometers. Our calculations show that the required nodal observation density is remarkably less that what is suggested by the analytical study; and is in fact comparable to the {\it number of numerically determining Fourier modes}, which was reported in an earlier computational study by the authors. Thus, this method is computationally efficient and performs far better than the analytical estimates suggest