The role of glutathione depletion in skeletal muscle apoptotic signalling in young and old rats

There is substantial evidence that oxidative stress causes negative outcomes in many cell and tissue types. This is especially true of skeletal muscle, as it is continually subjected to various sources of reactive oxygen species (ROS). Oxidative stress in muscle has been linked to several disease states as well as to the normal aging process. Oxidative stress has also been associated with increased apoptotic signalling. Furthermore, elevated apoptosis is consistently observed in aged skeletal muscle and is thought to be one of the mechanisms of age-related muscle atrophy. Due to its post-mitotic nature, skeletal muscle may be more susceptible to the harmful effects of oxidative stress in light of its limited regenerative capacity. As a protective measure, a sophisticated antioxidant system exists in muscle consisting of both enzymatic (superoxide dismutases (SOD’s), catalase, glutathione peroxidase) and non-enzymatic elements (glutathione: GSH). GSH is a ubiquitously expressed tripeptide essential to maintenance of the redox status of the cell. Its role in skeletal muscle apoptosis, especially in different muscle types, is currently unclear. To elucidate the potential role of GSH in skeletal muscle apoptosis and oxidative stress, L-buthionine-[S,R]-sulfoximine (BSO) was used to deplete GSH in young (34.85 ± 0.68 wks) and old (69.11 ± 3.61 wks) male Sprague-Dawley rats. Thiol levels (GSH, GSSG), ROS production, 4-hydroxy-2-nonenal (4HNE) levels, DNA fragmentation and apoptosis-related protein expression were examined in soleus (SOL) and white gastrocnemius (WG) muscle. BSO led to significant GSH depletion (89% in SOL, 96% in WG) compared to age-matched controls. Catalase upregulation, in the absence of change in SOD levels, was evident as a result of BSO treatment and advancing age in both muscle tissues. BSO treatment also resulted in increased DNA fragmentation in WG and SOL, with elevated ROS production in SOL only; both of these effects were independent of age. Advancing age resulted in elevated caspase activity and Hsp70 protein content, with a concomitant decrease in anti-apoptotic ARC in SOL but not WG. Additionally, ROS production, 4HNE content, DNA fragmentation and ARC levels were all significantly elevated in SOL compared to WG. These data indicate that SOL may be subjected to a state of elevated cellular stress. There is also some evidence that GSH depletion increases DNA fragmentation while age contributes to a degradative loss of glycolytic muscle

A second reported malignancy in a patient with Morquio syndrome

Morquio syndrome is a rare lysosomal storage disease that affects multiple organ systems. However, it is rarely associated with malignancy. We present the case of a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma. This case also demonstrates two other findings that have not been previously described in patients with Morquio syndrome - malrotation of brainstem and cerebellum, without clinical neurologic deficit, and persistence of fetal lobulation in the kidney

A second reported malignancy in a patient with Morquio syndrome

Morquio syndrome is a rare lysosomal storage disease that affects multiple organ systems. However, it is rarely associated with malignancy. We present the case of a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma. This case also demonstrates two other findings that have not been previously described in patients with Morquio syndrome - malrotation of brainstem and cerebellum, without clinical neurologic deficit, and persistence of fetal lobulation in the kidney

Profiling Distributed File Systems with Computer Animation

Achieving performance, reliability, and scalability has proven difficult for distributed file systems. Placement of data, load distribution and other overheads are often the culprits. Profiling is a useful technique for understanding file system behavior, improving performance and debugging problems. Existing file system profiling methods often examine fine-grained system activity, such as the path of a single request. This makes understanding interactive relationships difficult. Also, current profiling techniques do not provide a way for users to easily view full system behavior, often relying on logs, statistics, or simple graphs. We present a distributed file system profiling method based on clear-box profiling and visualization of full system behavior. Our approach allows for portable, low-overhead profiling and provides users with real-time animation of system behavior. We present users with a visualization of the file system architecture and animate behaviors, such as load distribution, data location, and network traffic, under real workloads. This allows users to visually identify bottlenecks, latencies, characterize system state and I/O requests, and debug problems. We evaluate the overhead and effectiveness of our profiling method on the Ceph petabytescale, parallel file system and describe any problems our approach was able to identify. 1