Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a global pandemic that affects one-quarter of the world’s population. NAFLD includes a spectrum of progressive liver disease from steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis and can be complicated by hepatocellular carcinoma. It is strongly associated with metabolic syndromes, obesity, and type 2 diabetes, and it has been shown that metabolic dysregulation is central to its pathogenesis. Recently, it has been suggested that metabolic- (dysfunction) associated fatty liver disease (MAFLD) is a more appropriate term to describe the disease than NAFLD, which puts increased emphasis on the important role of metabolic dysfunction in its pathogenesis. There is strong evidence that mitochondrial dysfunction plays a significant role in the development and progression of NAFLD. Impaired mitochondrial fatty acid oxidation and, more recently, a reduction in mitochondrial quality, have been suggested to play a major role in NAFLD development and progression. In this review, we provide an overview of our current understanding of NAFLD and highlight how mitochondrial dysfunction contributes to its pathogenesis in both animal models and human subjects. Further we discuss evidence that the modification of mitochondrial function modulates NAFLD and that targeting mitochondria is a promising new avenue for drug development to treat NAFLD/NASH.     

Evolutionary Algorithms and Theirs Use in the Design of Sequential Logic Circuits

In this paper an approach based on an evolutionary algorithm to design synchronous sequential logic circuits with minimum number of logic gates is suggested. The proposed method consists of four main stages. The first stage is concerned with the use of genetic algorithms (GA) for the state assignment problem to compute optimal binary codes for each symbolic state and construct the state transition table of finite state machine (FSM). The second stage defines the subcircuits required to achieve the desired functionality. The third stage evaluates the subcircuits using extrinsic Evolvable Hardware (EHW). During the fourth stage, the final circuit is assembled. The obtained results compare favourably against those produced by manual methods and other methods based on heuristic techniques.     

A simplified design approach for high-speed wind tunnels. Part I: Table of inclination

Journal of Mechanical Science and Technology - This study aims to develop a simplified approach for the design of high-speed wind tunnels, operating within the range of Mach 1-4. The study is...     

Robust design of processes and products using the mathematics of the stochastic frontier (SF)

The International Journal of Advanced Manufacturing Technology - The paper discusses a generic procedure for the parameter design of product and process development using planned and non-planned...     

Chemical Coupled PEDOT:PSS/Si Electrode: Suppressed Electrolyte Consumption Enables Long‑Term Stability

Huge volume changes of Si during lithiation/delithiation lead to regeneration of solid-electrolyte interphase(SEI)and consume electrolyte.In this article,γ-glycidoxypropyl trimethoxysilane(GOPS)was incorporated in Si/PEDOT:PSS electrodes to construct a flexible and conductive artificial SEI,effectively suppressing the consumption of electrolyte.The optimized electrode can maintain 1000 mAh g^−1 for nearly 800 cycles under limited electrolyte compared with 40 cycles of the electrodes without GOPS.Also,the optimized electrode exhibits excellent rate capability.The use of GOPS greatly improves the interface compatibility between Si and PEDOT:PSS.XPS Ar+etching depth analysis proved that the addition of GOPS is conducive to forming a more stable SEI.A full battery assembled with NCM 523 cathode delivers a high energy density of 520 Wh kg^−1,offering good stability.     

Membrane Targeting and GTPase Activity of Rab7 Are Required for Its Ubiquitination by RNF167

Rab7 is a GTPase that controls late endosome and lysosome trafficking. Recent studies have demonstrated that Rab7 is ubiquitinated, a post-translational modification mediated by an enzymatic cascade. To date, only one ubiquitin E3 ligase and one deubiquitinase have been identified in regulating Rab7 ubiquitination. Here, we report that RNF167, a transmembrane endolysosomal ubiquitin ligase, can ubiquitinate Rab7. Using immunoprecipitation and in vitro ubiquitination assays, we demonstrate that Rab7 is a direct substrate of RNF167. Subcellular fractionation indicates that RNF167 activity maintains Rab7′s membrane localization. Epifluorescence microscopy in HeLa cells shows that Rab7-positive vesicles are larger under conditions enabling Rab7 ubiquitination by RNF167. Characterization of its ubiquitination reveals that Rab7 must be in its GTP-bound active form for membrane anchoring and, thus, accessible for RNF167-mediated ubiquitin attachment. Cellular distribution analyses of lysosome marker Lamp1 show that vesicle positioning is independent of Rab7 and RNF167 expression and that Rab7 endosomal localization is not affected by RNF167 knockdown. However, both Rab7 and RNF167 depletion affect each other’s lysosomal localization. Finally, this study demonstrates that the RNF167-mediated ubiquitination of Rab7 GTPase is impaired by variants of Charcot–Marie–Tooth Type 2B disease. This study identified RNF167 as a new ubiquitin ligase for Rab7 while expanding our knowledge of the mechanisms underlying the ubiquitination of Rab7.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.