Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise

Myostatin is a TGFb family member and negative regulator of muscle size. Due to the complexity of the molecular pathway between myostatin mRNA/protein and changes in transcription, it has been difficult to understand whether myostatin plays a role in resistance exercise-induced skeletal muscle hypertrophy. To circumvent this problem, we determined the expression of a unique myostatin target gene, Mighty, following resistance exercise. Mighty mRNA increased by 6 h (82.9624.21%) and remained high out to 48 h (56.5619.67%) after resistance exercise. Further examination of the soleus, plantaris and tibialis anterior muscles showed that the change in Mighty mRNA at 6 h correlated with the increase in muscle size associated with this protocol (R2 = 0.9996). The increase in Mighty mRNA occurred both independent of Smad2 phosphorylation and in spite of an increase in myostatin mRNA (341.86147.14% at 3 h). The myostatin inhibitor SKI remained unchanged. However, activated Notch, another potential inhibitor of TGFb signaling, increased immediately following resistance exercise (83611.2%) and stayed elevated out to 6 h (78616.6%). Electroportion of the Notch intracellular domain into the tibialis anterior resulted in an increase in Mighty mRNA (63613.4%) that was equivalent to the canonical Notch target HES-1 (94.467.32%). These data suggest that acute resistance exercise decreases myostatin signaling through the activation of the TGFb inhibitor Notch resulting in a decrease in myostatin transcriptional activity that correlates well with muscle hypertrophy

<span style="font-size:14.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:HiddenHorzOCR; color:black;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">Optical and <span style="font-size:14.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; color:black;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">transport properties <span style="font-size:14.0pt; line-height:115%;font-family:"Times New Roman";mso-fareast-font-family:HiddenHorzOCR; color:black;mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language: HI" lang="EN-IN">of CdS_1-x Te_x <span style="font-size:14.0pt;line-height:115%;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";color:black; mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:HI" lang="EN-IN">alloyed thin <span style="font-size:14.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:HiddenHorzOCR;color:black; mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:HI" lang="EN-IN">films</span></span></span></span></span>

184-190A good deal of information regarding synthesis optical and electrical transport properties of the chemically grown CdS1-x Tex thin film structures is presented. Growth of these films depend upon various preparative parameters and deposition conditions such as temperature, pH, time, concentration, speed of the mechanical churning etc and the reaction kinetics suggests that the films grow in two different phases; an initial quasi -linear and second a saturation. The as-deposited films are crystalline over the whole range of the composition parameter and both CdS and CdTe are deposited as a mixture of the hexagonal wurtzite and cubic zinc blende structures (hexagonal being dominant). The solid solution is observed for hexagonal phase in the 0≤x ≤0.1 and 0.9≤ x≤ 1 regions. In the middle range (0.1 x < 0.9), separate phases of both CdS and CdTe have been detected. Optical absorption studies revealed a high absorption coefficient (104-105 cm-1) with a direct type of transition. The estimated bandgap decreased almost linearly with the composition parameter, x. The room temperature electrical conductivity is found to be increased initially with the composition parameter (0≤x ≤0.1) decreased for a further increased in x (0.1 x < 0.8) and again increased for higher Te content in CdS. The material exhibits both grain boundary scattering limited and a variable range hopping conduction mechanisms. The thermoelectric power is negative showing n-type behaviour of the samples. Both carrier concentration (n) and mobility (μ) were computed and found to be sensitive functions of temperature.</span

Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells

Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8+ terminal effector cells. PD-1 expression was elevated on CD8+ lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8+ effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.Barbara Withers, Emily Blyth, Leighton E. Clancy, Agnes Yong, Chris Fraser, Jane Burgess ... et al

The Ski proto-oncogene regulates body composition and suppresses lipogenesis

Objective: The Ski gene regulates skeletal muscle differentiation in vitro and and in vivo. In the c-Ski overexpression mouse model there occurs marked skeletal muscle hypertrophy with decreased adipose tissue mass. In this study, we have investigated the underlying molecular mechanisms responsible for the increased skeletal muscle and decreased adipose tissue mass in the c-Ski mouse