Myostatin promotes liver fat accumulation through activation of the mTOR-SREBP-1c pathway

Thesis (M.A.)--Boston UniversityMyostatin is a cytokine primarily expressed in skeletal muscle and heart muscle and acts as a negative regulator for muscle development. Inhibition of myostatin by genetic and pharmacological approaches improves metabolic health, which has been generally considered as secondary to the hypermuscularity and insulin hyper-sensitivity. Although the receptor for myostatin is ubiquitously expressed, whether and how myostatin interacts with other metabolically important cell types remain largely unknown. In this work, we provide multiple lines of evidence that myostatin directly interacts with hepatocytes. Furthermore, we show for the first time that myostatin enhances insulin signaling in both cultured hepatocytes and in mouse liver. Mice injected with adena-associated virus encoding myostatin propeptide, an endogenous myostatin inhibitor, were partially protected from diet-induced liver fat accumulation and reduced lipogenic gene expression. Consistent with the in vivo findings, increased lipid accumulation was found in cells treated with myostatin peptide or transfected with myostatin construct. Myostatin promotes the lipogenic effect of insulin by enhancing nuclear translocation of SREBP-1c, the master lipogenic transcription factor and increases expression of its downstream target genes. This effect was found to be associated with myostatin-related mTOR activation. Blocking mTOR activation by rapamycin prevents myostatinassociated increase of nuclear SREBP-1 c and its downstream lipogenic enzymes. In summary, this work identified liver as a direct target of myostatin, providing the first evidence that myostatin has opposite impacts on insulin signaling in muscle cells and hepatocytes. Our data also provided a novel mechanism for the long-term metabolic protection afforded by anti-myostatin treatments demonstrated in this work as well as elsewhere

Topological structure bifurcation of temperature field of deformable drop in Marangoni migration

AbstractThe unsteady processes of the Marangoni migration of deformable liquid drops are simulated numerically in a wider range of Marangoni number (up to Ma = 500) in the present work. A steady terminal state can always be reached, and the scaled terminal velocity is a monotonic function decreasing with increasing Marangoni number, which is generally in agreement with corresponding experimental data. The topological structure of flow field in the steady terminal state does not change as the Marangoni number increases, while bifurcation of the topological structure of temperature field occurs twice at two corresponding critical Marangoni numbers. A third critical value of Marangoni number also exists, beyond which the coldest point jumps from the rear stagnation to inside the drop though the topological structure of the temperature field does not change. It is found that the inner and outer thermal boundary layers may exist along the interface both inside and outside the drop if Ma > 70. But the thickness decreases with increasing Marangoni number more slowly than the prediction of potential flow at large Marangoni and Reynolds numbers

Expression and Clinical Significance of mTOR and PTEN in Non-small Cell Lung Cancer

Background and objective It has been proved that mTOR was an important signal transduction molecular and protein kinase regulating cell growth and proliferation, and mTOR could activate the downstream protein effector. PTEN could negatively regulate mTOR signal pathway and inhibit its activity. The aim of this study is to detect the mRNA expression levels of mTOR and PTEN gene, which are the key genes of mTOR signaling pathway in human non-small cell lung cancer (NSCLC) tissue. The relationship between mTOR signaling pathway and NSCLC is also explored. Methods Lung cancer tissue specimens were obtained from 65 patients. Adjacent-tumor non-small cell lung cancer tissues from the 30 patients were served as control. The RT-PCR technique was used to detect the mTOR and PTEN gene expression levels. Results The average mRNA expression levels of mTOR gene were significantly higher (0.23±0.16) in lung cancer than in adjacent-tumor tissue (0.12±0.09)(P < 0.01). The average mRNA expression levels of PTEN gene were (0.19±0.28) in lung cancer, while the mRNA expression levels of PTEN gene were (0.53±0.28) in adjacent-tumor tissue (P < 0.01). The levels of PTEN gene expression in non-small cell lung cancer were significantly lower than that in adjacent-tumor lung tissue. There are not significant relationship between mTOR and PTEN gene expression levels and patients’ age, gender, pathological type, differentiation, lymph node metastasis, except tumor size. Conclusion The expression of mTOR is activated in NSCLC. The expression of PTEN is absent or decreased. The mTOR activated in NSCLC may be correlate with the absent or decreased of PTEN. The absent or decreased expression of PTEN and the actived mTOR may play important roles in carcinogenesis and metastasis of NSCLC

A Continual Learning Paradigm for Non-differentiable Visual Programming Frameworks on Visual Reasoning Tasks

Recently, the visual programming framework (VisProg) has emerged as a significant framework for executing compositional visual tasks due to its interpretability and flexibility. However, the performance of VisProg on specific Visual Reasoning (VR) tasks is markedly inferior compared to well-trained task-specific models since its employed visual sub-modules have limited generalization capabilities. Due to the non-differentiability of VisProg, it is quite challenging to improve these visual sub-modules within VisProg for the specific VR task while maintaining their generalizability on the un-seen tasks. Attempt to overcome these difficulties, we propose CLVP, a Continuous Learning paradigm for VisProg across various visual reasoning tasks. Specifically, our CLVP distills the capabilities of well-trained task-specific models into the visual sub-modules in a stepwise and anti-forgetting manner. This can continually improve the performance of VisProg on multiple visual tasks while preserving the flexibility of VisProg. Extensive and comprehensive experimental results demonstrate that our CLVP obtains significant performance gains on specific VR benchmarks, i.e., GQA (+1.4%) and NLVRv2 (+5.6%), compared to the VisProg baseline, and also maintains a promising generalizability for VR on un-seen and previous learned tasks

Transient microscopic testing method based on deflectometry

The deflectometry provides an optical testing method with ultra-high dynamic range. In this paper, a microscopic testing method based on deflectometric technique is proposed to quantitatively evaluate the microstructures according to the wavefront aberration. To achieve the real-time and accurate wavefront testing for microstructure evaluation, a color-coded phase-shifting fringe pattern is applied to illuminate the test object. It avoids the sequential projection of multistep phase-shifting fringes in traditional deflectometry, enabling the transient wavefront testing. The feasibility of the proposed transient microscopic testing method is demonstrated by the experiment. The proposed method enables accurate and transient testing of microstructures with high dynamic range, minimizing the environmental disturbance.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]