Mutations in the dysferlin gene cause limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, and distal anterior compartment myopathy. Dysferlin mainly localizes to the sarcolemma in mature skeletal muscle where it is implicated in membrane fusion and repair. In different forms of muscular dystrophy, a predominantly cytoplasmic localization of dysferlin can be observed in regenerating myofibers, but the subcellular compartment responsible for this labeling pattern is not yet known. We have previously demonstrated an association of dysferlin with the developing T-tubule system in vitro. To investigate the role of dysferlin in adult skeletal muscle regeneration, we studied dysferlin localization at high resolution in a rat model of regeneration and found that the subcellular labeling of dysferlin colocalizes with the developing T-tubule system. Furthermore, ultrastructural analysis of dysferlin-deficient muscle revealed primary T-tubule anomalies similar to those seen in caveolin-3-deficient muscle. These findings indicate that dysferlin is necessary for correct T-tubule formation, and dysferlin-deficient skeletal muscle is characterized by abnormally configured T-tubules.

Skeletal muscle requires an efficient and active membrane repair system to overcome the rigours of frequent contraction. Dysferlin is a component of that system and absence of dysferlin causes muscular dystrophy (dysferlinopathy) characterized by adult onset muscle weakness, high serum creatine kinase levels and a prominent inflammatory infiltrate. We have observed that dysferlinopathy patient biopsies show an excess of immature fibres and therefore investigated the role of dysferlin in muscle regeneration. Using notexin-induced muscle damage, we have shown that regeneration is attenuated in a mouse model of dysferlinopathy, with delayed removal of necrotic fibres, an extended inflammatory phase and delayed functional recovery. Satellite cell activation and myoblast fusion appear normal, but there is a reduction in early neutrophil recruitment in regenerating and also needle wounded muscle in dysferlin-deficient mice. Primary mouse dysferlinopathy myoblast cultures show reduced cytokine release upon stimulation, indicating that the secretion of chemotactic molecules is impaired. We suggest an extension to the muscle membrane repair model, where in addition to fusing patch repair vesicles with the sarcolemma dysferlin is also involved in the release of chemotactic agents. Reduced neutrophil recruitment results in incomplete cycles of regeneration in dysferlinopathy which combines with the membrane repair deficit to ultimately trigger dystrophic pathology. This study reveals a novel pathomechanism affecting muscle regeneration and maintenance in dysferlinopathy and highlights enhancement of the neutrophil response as a potential therapeutic avenue in these disorders.

Objectives: Diabetic nephropathy (DN) is a major leading cause of kidney failure. Recent studies showed that serological microRNAs (miRs) could be utilized as biomarkers to identify disease pathogenesis; the DN-related miRs, however, remained to be explored. Methods: A prospective case-control study was conducted. The clinical significance of five potential miRs (miR-21, miR-29a, miR-29b, miR-29c and miR192) in type 2 Diabetes Mellitus (T2DM) patients who have existing diabetic retinopathy with differential Albumin:Creatinine Ratio (ACR) and estimated Glomerular Filtration Rate (eGFR) was performed using quantitative RT-PCR analysis. The subjects with diabetic retinopathy enrolled in Taipei City Hospital, Taiwan, were classified into groups of normal albuminuria (ACR<30mg/g; N=12); microalbuminuria (30mg/g300mg/g; N=21) as well as 18 low-eGFR (eGFR<60ml/min) and 32 high-eGFR (eGFR>60ml/min). The level of serum miRs was statistically correlated with age, Glucose AC, ACR, eGFR and DN progression. Results: The levels of miR-21, miR-29a and miR-192 were significantly enriched in the overt proteinuria group compared with microalbuminuria and/or overt proteinuria groups. It was shown that only miR-21 level was significantly up-regulated in low-eGFR group compared with high-eGFR patients. Interestingly, Pearson's correlation coefficient analysis demonstrated that DN progressors showed significantly greater levels of miR-21, miR-29a, miR-29b and miR-29c in comparison with non-progressors implying the clinical potential of DN associated miRs in monitoring and preventing disease advancement. Conclusion: Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression.

In recent years, the concept of the Internet of Things has been introduced. Information, communication, and network technology can be integrated, so that the unmanned aerial vehicle (UAV) from consumer leisure and entertainment toys can be utilized in high value commercial, agricultural, and defense field applications, and become a killer product. In this paper, a traceable and privacy-preserving authentication is proposed to integrate the elliptic curve cryptography (ECC), digital signature, hash function, and other cryptography mechanisms for UAV application. For sensitive areas, players must obtain flight approval from the ground control station before they can control the UAV in these areas. The traditional cryptography services such as integrity, confidentiality, anonymity, availability, privacy, non-repudiation, defense against DoS (Denial-of-Service) attack, and spoofing attack can be ensured. The feasibility of mutual authentication was proved by BAN logic. In addition, the computation cost and the communication cost of the proposed scheme were analyzed. The proposed scheme provides a novel application field.

Assessing access to healthcare for an entire healthcare system involves accounting for demand, supply, and geographic variation. In order to capture the interaction between healthcare services and populations, various measures of healthcare access have been utilized, including the popular two-step floating catchment area (2SFCA) method. However, despite the many advantages of 2SFCA, the problems, such as inappropriate assumption of healthcare demand and failure to capture cascading effects across the system have not been satisfactorily addressed. In this paper, a statistical model for evaluating flows of individuals was added to the 2SFCA method (hereafter we refer to it as F2SFCA) in order to overcome limitations associated with its current restriction. The proposed F2SFCA model can incorporate both spatial and nonspatial dimensions and thus synthesizes them into one framework. Moreover, the proposed F2SFCA model can be easily adapted to measure access for different types of individuals, over different service provider types, or with capacity constraints in a healthcare system. We implemented the proposed model in a case study assessing access to healthcare for the elderly in Taipei City, Taiwan, and compared the weaknesses and strengths to the 2SFCA method and its variations.

Dengue virus (DV) was detected early in infected mosquito

Chlorella is a type of unicellular fresh water algae. In an attempt to develop new agents for handling insulin resistance, Chlorella was employed to screen the effect on insulin resistance in rats induced by fructose-rich chow. A single oral administration of Chlorella for 90 min decreased the plasma glucose in a dose-dependent manner in rats receiving 4-week fructose-rich chow. In addition, chronic treatment with Chlorella for 15 days also lowered plasma glucose in the same manner. Then, the insulin action on glucose disposal rate was measured using the glucose-insulin index, values of the areas under the curves of glucose and insulin during the intraperitoneal glucose tolerance test (IPGTT). Oral administration (three times daily for 5 days) of Chlorella to rats receiving 4 weeks of fructose-rich chow abolished the elevated value of the glucose-insulin index, indicating that Chlorella has an ability to improve insulin resistance. An increase of insulin sensitivity by Chlorella was further evaluated using the plasma glucose lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Oral administration of Chlorella three times daily to STZ-diabetic rats increased the response to exogenous insulin 15 days later. The obtained results suggest that oral administration of Chlorella has the ability to improve insulin sensitivity, which may be used as an adjuvant therapy for patients with insulin resistance.

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