Explore the vast range of titles available.

Calsequestrin (CASQ) was discovered in rabbit skeletal muscle tissues in 1971 and has been considered simply a passive Ca2+-buffering protein in the sarcoplasmic reticulum (SR) that provides Ca2+ ions for various Ca2+ signals. For the past three decades, physiologists, biochemists, and structural biologists have examined the roles of the skeletal muscle type of CASQ (CASQ1) in skeletal muscle and revealed that CASQ1 has various important functions as (1) a major Ca2+-buffering protein to maintain the SR with a suitable amount of Ca2+ at each moment, (2) a dynamic Ca2+ sensor in the SR that regulates Ca2+ release from the SR to the cytosol, (3) a structural regulator for the proper formation of terminal cisternae, (4) a reverse-directional regulator of extracellular Ca2+ entries, and (5) a cause of human skeletal muscle diseases. This review is focused on understanding these functions of CASQ1 in the physiological or pathophysiological status of skeletal muscle.Muscle function: Multiple roles for a muscle modulatorAlthough previously considered merely a passive regulator of calcium levels, the protein calsequestrin is now known to perform a range of physiological activities essential to skeletal muscle function. The process of muscle contraction depends on the release of calcium ions from an intracellular structure called the sarcoplasmic reticulum (SR). Calsequestrin was originally identified as a “buffering” factor that maintains adequate calcium reserves in the SR, but Eun Hui Lee and colleagues at the Catholic University of Korea review diverse functions that have since been ascribed to this protein. For example, calsequestrin also helps reinforce the structure of the SR, and actively regulates the flux of calcium ions into muscle cells. Perturbations in calsequestrin function also appear to contribute to a number of muscular disorders, including a potential link to Duchenne muscular dystrophy.

Osteoarthritis (OA) is the most common degenerative joint disease and is characterized by breakdown of joint cartilage. Coenzyme Q10 (CoQ10) exerts diverse biological effects on bone and cartilage; observational studies have suggested that CoQ10 may slow OA progression and inflammation. However, any effect of CoQ10 on OA remains unclear. Here, we investigated the therapeutic utility of CoQ10-micelles. Seven-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. CoQ10-micelles were administered orally to MIA-induced OA rats; celecoxib served as the positive control. Pain, tissue destruction, and inflammation were measured. The expression levels of catabolic and inflammatory cell death markers were assayed in CoQ10-micelle-treated chondrocytes. Oral supplementation with CoQ10-micelles attenuated OA symptoms remarkably, including pain, tissue destruction, and inflammation. The expression levels of the inflammatory cytokines IL-1[beta], IL-6, and MMP-13, and of the inflammatory cell death markers RIP1, RIP3, and pMLKL in synovial tissues were significantly reduced by CoQ10-micelle supplementation, suggesting that CoQ10-micelles might attenuate the synovitis of OA. CoQ10-micelle addition to cultured OA chondrocytes reduced the expression levels of catabolic and inflammatory cell death markers. CoQ10-micelles might usefully treat OA.

Considering that slow steaming requires low engine power, which impedes maneuverability under severe sea conditions, the International Maritime Organization (IMO) provides guidelines for the minimum propulsion power (MPP) required to maintain ship maneuverability in adverse conditions. This study focused on the characteristics of self-propulsion factors in the context of MPP assessment to enhance MPP prediction accuracy. Overload tests were conducted at low speeds of advance, considering added resistance in adverse conditions. Moreover, propeller open-water tests were conducted corresponding to propeller flow with low Reynolds numbers to investigate their effect on self-propulsion factors. In addition, computational fluid dynamics (CFD) simulations were conducted to analyze physical phenomena such as the flow field and pressure distribution under model test conditions. The results indicated that the thrust deduction factor was lower than that given in the guidelines, whereas the wake fraction was higher at the required forward speed of 2 knots. The MPP assessment in this study revealed that the required brake power was 4–5% lower than that given in the guidelines, indicating that the guidelines need reviewing for a more reliable assessment.

Submarines with pumpjet propulsors have recently been used in many countries to improve their propulsion and noise performance. The pumpjet has the advantage of improving noise and cavitation performance by increasing the pressure inside the duct, and it has good efficiency at a low advance ratio. This study analyzed the propulsive performance of a pumpjet propulsor affixed to a SUBOFF submarine as a function of variations in the design parameters using computational fluid dynamics analysis. The incidence angle and camber of the duct and the pitch angle of the stator were selected as the design parameters. To investigate the propulsion performance as a function of the design parameter variations, each case’s thrust, torque, and efficiency were compared, and the velocity and pressure fields of each case were analyzed. In addition, the efficiency was analyzed using the non-dimensional mass flow rate and area ratio difference for each case. The duct incidence angle contributed most dominantly to the dimensionless flow rate and the difference in area ratio, and these two factors resulted in high efficiency at certain values. It is expected that further research will be conducted in the near future that takes into account cavitation inception speed and cavitation.

Owing to environmental regulations, ships are equipped with a pre-swirl stator (PSS), which is one of the most effective energy-saving devices (ESDs) that is widely applied to various kinds of ships. It improves energy efficiency by recovering the rotational kinetic energy of the propeller with the aid of a PSS placed in front of the propeller. In this study, an asymmetric PSS system is applied to the 2500 TEU eco-friendly liquefied natural gas (LNG) fuel feeder container ship, aimed at optimizing the position of stator blades, using a potential-based program. Additionally, a parametric study was conducted for evaluating the optimum pitch angle and blade spacing. STAR-CCM+ was used for validating the efficiency of the final design. The Samsung towing tank and large cavitation tunnel were also utilized to verify the improvement in the performance of the proposed PSS. Although the efficiency gain is not largely affected by blade position optimization, the cavitation and pressure fluctuation issues are addressed by improving the in-flow to the propeller. Therefore, blade spacing optimization of the stator is important for container ships whose cavitation performance is very significant, especially the relatively high-speed commercial vessels.

Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) signaling adaptor that is essential for the type I interferon response to DNA pathogens. Aberrant activation of STING is linked to the pathology of autoimmune and autoinflammatory diseases. The rate-limiting step for the activation of STING is its translocation from the ER to the ER-Golgi intermediate compartment. Here, we found that deficiency in the Ca 2+ sensor stromal interaction molecule 1 (STIM1) caused spontaneous activation of STING and enhanced expression of type I interferons under resting conditions in mice and a patient with combined immunodeficiency. Mechanistically, STIM1 associated with STING to retain it in the ER membrane, and coexpression of full-length STIM1 or a STING-interacting fragment of STIM1 suppressed the function of dominant STING mutants that cause autoinflammatory diseases. Furthermore, deficiency in STIM1 strongly enhanced the expression of type I interferons after viral infection and prevented the lethality of infection with a DNA virus in vivo. This work delineates a STIM1-STING circuit that maintains the resting state of the STING pathway. STIM1 is a calcium sensor that is essential for functional lymphocyte responses. Gwack and colleagues demonstrate a calcium-independent role for STIM1 in macrophages that regulates their production of type I interferons.

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated Lactobacillus (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of Faecalibacterium which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA.

Ca 2+ release-activated Ca 2+ (CRAC) channels elevate cytoplasmic Ca 2+ concentration, which is essential for T cell activation, differentiation and effector functions. T cell receptor stimulation induces depletion of the endoplasmic reticulum (ER) Ca 2+ stores, which is sensed by stromal interaction molecule 1 (STIM1). STIM1 translocates to the ER-plasma membrane (PM) junctions to interact with ORAI1, the pore subunit of the CRAC channels. Here, we show that two members of the extended synaptotagmin (E-Syt) family, E-Syt1, and the short isoform of E-Syt2 (E-Syt2S), contribute to activation of CRAC channels in T cells. Knockdown or deletion of both ESYT1 and ESYT2 reduced store-operated Ca 2+ entry (SOCE) and ORAI1-STIM1 clustering in Jurkat T cells. Further, depletion of E-Syts in primary T cells decreased Ca 2+ entry and cytokine production. While the ER-PM junctions were reduced in both HeLa and Jurkat T cells deleted for ESYT1 and ESYT2 , SOCE was impaired only in Jurkat T cells, suggesting that the membrane-tethering function of E-Syts is distinct from their role in SOCE. Mechanistically, E-Syt2S, the predominant isoform of E-Syt2 in T cells, recruited STIM1 to the junctions via a direct interaction. This study demonstrates a membrane-tethering-independent role of E-Syts in activation of CRAC channels in T cells.

Background Graft- versus -host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD. Lactobacillus species are widely used supplements to induce production of antimicrobial and anti-inflammatory factors. Methods We determined the effect of the combination of Lactobacillus acidophilus and FK506 on GvHD following major histocompatibility complex-mismatched bone marrow transplantation. Results The combination treatment suppressed IFN-γ and IL-17-producing T cell differentiation, but increased Foxp3 + Treg differentiation and IL-10 production. Also, the combination treatment and combination treated-induced Treg cells modulated the proliferation of murine alloreactive T cells in vitro. Additionally, the combination treatment upregulated Treg-related genes— Nt5e , Foxp3 , Ikzf2 , Nrp1 and Itgb8 —in murine CD4 + -T cells. The combination treatment also alleviated GvHD clinically and histopathologically by controlling the effector T cell and Treg balance in vivo. Moreover, the combination treatment decreased Th17 differentiation significantly and significantly upregulated Foxp3 and IL-10 expression in peripheral blood mononuclear cells from healthy controls and liver transplantation (LT) patients. Conclusions Therefore, the combination of L . acidophilus and FK506 is effective and safe for patients undergoing allogeneic hematopoietic stem cell transplantation.

Tripartite motif-containing protein 32 (TRIM32) is a member of the tripartite motif family and is highly conserved from flies to humans. Via its E3 ubiquitin ligase activity, TRIM32 mediates and regulates many physiological and pathophysiological processes, such as growth, differentiation, muscle regeneration, immunity, and carcinogenesis. TRIM32 plays multifunctional roles in the maintenance of skeletal muscle. Genetic variations in the TRIM32 gene are associated with skeletal muscular dystrophies in humans, including limb–girdle muscular dystrophy type 2H (LGMD2H). LGMD2H-causing genetic variations of TRIM32 occur most frequently in the C-terminal NHL (ncl-1, HT2A, and lin-41) repeats of TRIM32. LGMD2H is characterized by skeletal muscle dystrophy, myopathy, and atrophy. Surprisingly, most patients with LGMD2H show minimal or no dysfunction in other tissues or organs, despite the broad expression of TRIM32 in various tissues. This suggests more prominent roles for TRIM32 in skeletal muscle than in other tissues or organs. This review is focused on understanding the physiological roles of TRIM32 in skeletal muscle, the pathophysiological mechanisms mediated by TRIM32 genetic variants in LGMD2H patients, and the correlations between TRIM32 and Duchenne muscular dystrophy (DMD).