-
Oneal Pham posted an update 1 week, 6 days ago
stantial institutional variation. Our study elucidates common clinical scenarios deemed rarely appropriate and clarifies the potential targets of quality improvement. Registration URL https//www.umin.ac.jp/ctr/index.htm. Unique identifier UMIN000020423.SIGNIFICANCE Regular contractile activity plays a critical role in maintaining skeletal muscle morphological integrity and physiological function. If the muscle is forced to stop contraction, such as during limb immobilization (IM), the IGF/Akt/mTOR signaling pathway that normally stimulates protein synthesis and inhibits proteolysis will be suppressed, whereas the FoxO-controlled catabolic pathways such as ubiquitin-proteolysis and autophagy/mitophagy will be activated and dominate, resulting in muscle fiber atrophy. Recent Advances. Mitochondria occupy a central position in regulating both protein synthesis and degradation via several redox-sensitive pathways including PGC-1α, mitochondrial fusion/fission proteins, mitophagy, and sirtuins. Prolonged IM downregulates PGC-1α due to AMPK and FoxO activation thus decreasing mitochondrial biogenesis and causing oxidative damage. Decline of mitochondrial inner membrane potential and increased mitochondrial fission can trigger cascades of mitophagy leading to loss of mitochondrial homeostasis (mitostasis), inflammation, and apoptosis. The phenotypic outcomes of these disorders are compromised muscle function and fiber atrophy. CRITICAL ISSUES Given the molecular mechanism of the pathogenesis, it is imperative that the integrity of intracellular signaling be restored to prevent the deterioration. selleckchem So far, overexpression of PGC-1α via transgene and in vivo DNA transfection has been found to be effective in ameliorating mitostasis and reduces IM-induced muscle atrophy. Nutritional supplementation of select amino acids and phytochemicals also provides mechanistic and practical insights into the prevention of muscle disuse atrophy. FUTURE DIRECTIONS In light of the importance of mitochondria in regulating the various critical signaling pathways, future work should focus on exploring new epigenetic strategies to restore mitostasis and redox balance.SIGNIFICANCE Senescence is an essential biological process that blocks tumorigenesis, limits tissue damage and aids embryonic development. However, once senescent cells accumulate in tissues during aging, they promote development of age-related disease and limit healthspan. It is therefore crucial to gain a better understanding of the mechanisms controlling cellular senescence. Recent Advances Cellular metabolism plays a significant role in regulation of various signaling process involved in cell senescence. In recent years, our understanding of the intimate relationship between cell metabolism, cell signaling, and cellular senescence has greatly improved. CRITICAL ISSUES In this review, we discuss metabolic pathways in senescent cells and the impact of these pathways on DNA damage response and senescence associated secretory phenotype (SASP). FUTURE DIRECTIONS Future research should elucidate metabolic mechanisms that promote specific alterations in senescent cell phenotype, with the final aim of developing new therapeutic strategies.New experimental technology and theoretical approaches have advanced battery research across length scales ranging from the molecular to the macroscopic. Direct observations of nanoscale phenomena and atomistic simulations have enhanced the understanding of the fundamental electrochemical processes that occur in battery materials. This vast and ever-growing pool of microscopic data brings with it the challenge of isolating crucial performance-decisive physical parameters, an effort that often requires the consideration of intricate interactions across very different length scales and timescales. Effective physics-based battery modeling emphasizes the cross-scale perspective, with the aim of showing how nanoscale physicochemical phenomena affect device performance. This review surveys the methods researchers have used to bridge the gap between the nanoscale and the macroscale. We highlight the modeling of properties or phenomena that have direct and considerable impact on battery performance metrics, such as open-circuit voltage and charge/discharge overpotentials. Particular emphasis is given to thermodynamically rigorous multiphysics models that incorporate coupling between materials’ mechanical and electrochemical states. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 11 is June 8, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Lipids are an important class of biomolecules with many roles within cells and tissue. As targets for study, they present several challenges. They are difficult to label, as many labels lack the specificity to the many different lipid species or the labels maybe larger than the lipids themselves, thus severely perturbing the natural chemical environment. Mass spectrometry provides exceptional specificity and is often used to examine lipid extracts from different samples. However, spatial information is lost during extraction. Of the different imaging mass spectrometry methods available, secondary ion mass spectrometry (SIMS) is unique in its ability to analyze very small features, with probe sizes less then 50 nm available. It also offers high surface sensitivity and 3D imaging capability on a subcellular scale. This article reviews the current capabilities and some remaining challenges associated with imaging the diverse lipids present in cell and tissue samples. We show how the technique has moved beyond show-and-tell, proof-of-principle analysis and is now being used to address real biological challenges. These include imaging the microenvironment of cancer tumors, probing the pathophysiology of traumatic brain injury, or tracking the lipid composition through bacterial membranes. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 13 is June 12, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.