Tumor necrosis factor-α and muscle wasting: a cellular perspective

Tumor necrosis factor-α (TNF-α) is a polypeptide cytokine that has been associated with muscle wasting and weakness in inflammatory disease. Despite its potential importance in muscle pathology, the direct effects of TNF-α on skeletal muscle have remained undefined until recently. Studies of cultured muscle cells indicate that TNF-α disrupts the differentiation process and can promote catabolism in mature cells. The latter response appears to be mediated by reactive oxygen species and nuclear factor-κB which upregulate ubiquitin/proteasome activity. This commentary outlines our current understanding of TNF-α effects on skeletal muscle and the mechanism of TNF-α action

MIP/MTMR14 and muscle aging

No abstract

Preliminary Performance of Lithium-ion Cell Designs for Ares I Upper Stage Applications

NASA's Ares I Crew Launch Vehicle (CLV) baselined lithium-ion technology for the Upper Stage (US). Under this effort, the NASA Glenn Research Center investigated three different aerospace lithium-ion cell suppliers to assess the performance of the various lithium-ion cell designs under acceptance and characterization testing. This paper describes the overall testing approaches associated with lithium-ion cells, their ampere-hour capacity as a function of temperature and discharge rates, as well as their performance limitations for use on the Ares I US vehicle

Improved Probability Method for Estimating Signal in the Presence of Background

A suggestion is made for improving the Feldman Cousins method of estimating signal counts in the presence of background. The method concentrates on finding essential information about the signal and ignoring extraneous information about background. An appropriate method is found which uses the condition that the number of background events obtained does not exceed the total number of events obtained. Several alternative approaches are explored.Comment: Modified 12/21 for singlespace to save trees, 9 pages, 1 figure. Modified 8/11/99 to add small modifications made for the Phys. Rev. articl

Laser-Induced Fluorescence of Singly-Charged Xenon in a 6-kW Hall Thruster Plume

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76708/1/AIAA-2008-5102-585.pd

Effects of dietary curcumin or N-acetylcysteine on NF-κB activity and contractile performance in ambulatory and unloaded murine soleus

BACKGROUND: Unloading of skeletal muscle causes atrophy and loss of contractile function. In part, this response is believed to be mediated by the transcription factor nuclear factor-kappa B (NF-κB). Both curcumin, a component of the spice turmeric, and N-acetylcysteine (NAC), an antioxidant, inhibit activation of NF-κB by inflammatory stimuli, albeit by different mechanisms. In the present study, we tested the hypothesis that dietary curcumin or NAC supplementation would inhibit unloading-induced NF-κB activity in skeletal muscle and thereby protect muscles against loss of mass and function caused by prolonged unloading. METHODS: We used hindlimb suspension to unload the hindlimb muscles of adult mice. Animals had free access to drinking water or drinking water supplemented with 1% NAC and to standard laboratory diet or diet supplemented with 1% curcumin. For 11 days, half the animals in each dietary group were suspended by the tail (unloaded) and half were allowed to ambulate freely. RESULTS: Unloading caused a 51–53% loss of soleus muscle weight and cross-sectional area relative to freely-ambulating controls. Unloading also decreased total force and force per cross-sectional area developed by soleus. Curcumin supplementation decreased NF-κB activity measured in peripheral tissues of ambulatory mice by gel shift analysis. In unloaded animals, curcumin supplementation did not inhibit NF-κB activity or blunt the loss of muscle mass in soleus. In contrast, NAC prevented the increase in NF-κB activity induced by unloading but did not prevent losses of muscle mass or function. CONCLUSION: In conclusion, neither dietary curcumin nor dietary NAC prevents unloading-induced skeletal muscle dysfunction and atrophy, although dietary NAC does prevent unloading induced NF-κB activation

Effects of dietary curcumin or N-acetylcysteine on NF-kappaB activity and contractile performance in ambulatory and unloaded murine soleus

BACKGROUND: Unloading of skeletal muscle causes atrophy and loss of contractile function. In part, this response is believed to be mediated by the transcription factor nuclear factor-kappa B (NF-kappaB). Both curcumin, a component of the spice turmeric, and N-acetylcysteine (NAC), an antioxidant, inhibit activation of NF-kappaB by inflammatory stimuli, albeit by different mechanisms. In the present study, we tested the hypothesis that dietary curcumin or NAC supplementation would inhibit unloading-induced NF-kappaB activity in skeletal muscle and thereby protect muscles against loss of mass and function caused by prolonged unloading. METHODS: We used hindlimb suspension to unload the hindlimb muscles of adult mice. Animals had free access to drinking water or drinking water supplemented with 1% NAC and to standard laboratory diet or diet supplemented with 1% curcumin. For 11 days, half the animals in each dietary group were suspended by the tail (unloaded) and half were allowed to ambulate freely. RESULTS: Unloading caused a 51-53% loss of soleus muscle weight and cross-sectional area relative to freely-ambulating controls. Unloading also decreased total force and force per cross-sectional area developed by soleus. Curcumin supplementation decreased NF-kappaB activity measured in peripheral tissues of ambulatory mice by gel shift analysis. In unloaded animals, curcumin supplementation did not inhibit NF-kappaB activity or blunt the loss of muscle mass in soleus. In contrast, NAC prevented the increase in NF-kappaB activity induced by unloading but did not prevent losses of muscle mass or function. CONCLUSION: In conclusion, neither dietary curcumin nor dietary NAC prevents unloading-induced skeletal muscle dysfunction and atrophy, although dietary NAC does prevent unloading induced NF-kappaB activation

Political economics, collective action and wicked socio-ecological problems: A practice story from the field

Empowering integrative, sustainable and equitable approaches to wicked socio-ecological problems requires multiple disciplines and ways of knowing. Following calls for greater attention to political economics in this transdisciplinary work, we offer a practitioner perspective on political economy and collective action and their influences on our community engagement practice and public policy. Our perspective is grounded in a pervasive wicked problem in Australia, invasive rabbits, and the emergence of the Victorian Rabbit Action Network. The network grew out of a publically funded research project to support community-led action in rabbit management. Victorian residents and workers affected by rabbits – public and private land managers, scientists, government officers and others – were invited to engage in a participatory planning process to generate sustainable strategies to address the rabbit problem. Each stage in the process, which involved interviews, a workshop and consultations, was designed to nurture the critical enquiry, listening and learning skills of participants, advance understandings of the problem from multiple perspectives, generate collective options to guide decision-making, and encourage community-led collective action. We reflect on our understanding of these processes using the language and lens of political economics and, in particular, the context of democratic professionalism. In so doing, we define terms and refer to information resources that have enabled us to bring a practical working knowledge of political economics to our professional practice. Our intent is to motivate academics, community members, government officials, and scientists alike, to draw on their knowledge and field experiences and to share practice stories through the lens of political economics and collective action. This is an opportunity to engage each other in small ‘p’ politics of how we understand and act on wicked problems, to negotiate and connect across disciplines, practical experiences and human difference, so that people may work more creatively and effectively together to address the challenging issues of our time. &nbsp

Advancing functional connectivity research from association to causation

Cognition and behavior emerge from brain network interactions, such that investigating causal interactions should be central to the study of brain function. Approaches that characterize statistical associations among neural time series-functional connectivity (FC) methods-are likely a good starting point for estimating brain network interactions. Yet only a subset of FC methods ('effective connectivity') is explicitly designed to infer causal interactions from statistical associations. Here we incorporate best practices from diverse areas of FC research to illustrate how FC methods can be refined to improve inferences about neural mechanisms, with properties of causal neural interactions as a common ontology to facilitate cumulative progress across FC approaches. We further demonstrate how the most common FC measures (correlation and coherence) reduce the set of likely causal models, facilitating causal inferences despite major limitations. Alternative FC measures are suggested to immediately start improving causal inferences beyond these common FC measures

Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma

Background: New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes.Methods: CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment.Results: Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients.Conclusions: Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment