A signaling role for dystrophin: Inhibiting skeletal muscle atrophy pathways

SummarySkeletal muscle atrophy is a common comorbidity of cancer. The cellular signaling mechanisms that regulate muscle size constitute a balance of the protein breakdown pathways upregulated during atrophy, and the protein synthesis pathways that are activated during skeletal muscle hypertrophy. In this issue of Cancer Cell, Acharyya et al. demonstrate a new and surprising regulatory axis that is centered around dystrophin, the protein that is mutated in settings of muscular dystrophy. These data reposition dystrophin as a signaling protein and connect an important cellular complex required for the structural integrity of muscle to the pathways that modulate muscle size

Treating cancer cachexia to treat cancer

Skeletal muscle wasting is a major component of cachectic states found in a variety of disease settings, including cancer. As increasing caloric intake often provides little benefit in combating muscle loss in cachectic patients, a major research focus has been to develop strategies stimulating muscle anabolic pathways - in an attempt to fight the catabolic pathways induced during cachexia. Two recent papers have reported the beneficial effects of blocking the myostatin/activin signalling pathway in mouse models of cancer cachexia. We discuss the implications of their findings both with respect to the role that this signalling pathway may play in the aetiology of cachexia and with respect to the prospects for targeting this pathway as a therapeutic strategy in patients with cachexia

Start Up of a Nb-1%Zr Potassium Heat Pipe From the Frozen State

The start up of a liquid metal heat pipe from the frozen state was evaluated experimentally with a Nb-1%Zr heat pipe with potassium as the working fluid. The heat pipe was fabricated and tested at Los Alamos National Laboratory. RF induction heating was used to heat 13 cm of the 1-m-long heat pipe. The heat pipe and test conditions are well characterized so that the test data may be used for comparison with numerical analyses. An attempt was made during steady state tests to calibrate the heat input so that the heat input would be known during the transient cases. The heat pipe was heated to 675 C with a throughput of 600 W and an input heat flux of 6 W/cm(exp 2). Steady state tests, start up from the frozen state, and transient variations from steady state were performed

Fabrication and Testing of Mo-Re Heat Pipes Embedded in Carbon/Carbon

Refractory-composite/heat-pipe-cooled wing an tail leading edges are being considered for use on hypersonic vehicles to limit maximum temperatures to values below material reuse limits and to eliminate the need to actively cool the leading edges. The development of a refractory-composite/heat-pipe-cooled leading edge has evolved from the design stage to the fabrication and testing of heat pipes embedded in carbon/carbon (C/C). A three-foot-long, molybdenum-rhenium heat pipe with a lithium working fluid was fabricated and tested at an operating temperature of 2460 F to verify the individual heat-pipe design. Following the fabrication of this heat pipe, three additional heat pipes were fabricated and embedded in C/C. The C/C heat-pipe test article was successfully tested using quartz lamps in a vacuum chamber in both a horizontal and vertical orientation. Start up and steady state data are presented for the C/C heat-pipe test article. Radiography and eddy current evaluations were performed on the test article

Development and validation of a bovine macrophage specific cDNA microarray

BACKGROUND: The response of macrophages to danger signals is an important early stage in the immune response. Our understanding of this complex event has been furthered by microarray analysis, which allows the simultaneous investigation of the expression of large numbers of genes. However, the microarray resources available to study these events in livestock animals are limited. RESULTS: Here we report the development of a bovine macrophage specific (BoMP) cDNA microarray. The BoMP microarray contains 5026 sequence elements (printed in duplicate) and numerous controls. The majority of the clones incorporated on the microarray were derived from the BoMP cDNA library generated from bovine myeloid cells subjected to various stimuli, including over 900 sequences unique to the library. Additional clones representing immunologically important genes have been included on the BoMP microarray. The microarray was validated by investigating the response of bovine monocytes to stimulation with interferon-γ and lipopolysaccharide using amplified RNA. At 2 and 16 hours post stimulation 695 genes exhibited statistically significant differential expression, including; 26 sequences unique to the BoMP library, interleukin 6, prion protein and toll-like receptor 4. CONCLUSION: A 5 K cDNA microarray has been successfully developed to investigate gene expression in bovine myeloid cells. The BoMP microarray is available from the ARK-Genomics Centre for Functional Genomics in Farm Animals, UK

Transpiration-Cooled Spacecraft-Insulation-Repair Fasteners

Transpiration-cooled fasteners are proposed that operate like an open-loop heat pipe (self-tapping screws, bolts, and spikes) for use in on-orbit repair of thermal- insulation of a space shuttle or other spacecraft. By limiting the temperature rise of such a fastener and of the adjacent repair material and thermal protection system, the transpiration cooling would contribute to the ability of the repair to retain its strength and integrity in the high-heat-flux, oxidizing environment of reentry into the atmosphere of the Earth. A typical fastener according to the proposal would include a hollow refractory-metal, refractory-composite, or ceramic screw or bolt, the central cavity of which would be occupied by a porous refractory- metal or ceramic plug that would act as both a reservoir and a wick for a transpirant liquid. The plug dimensions, the plug material, and the sizes of the pores would be chosen in conjunction with the transpirant liquid so that (1) capillary pumping could be relied upon to transport the liquid to the heated surface, where the liquid would be vaporized, and (2) the amount of liquid would suffice for protecting against the anticipated heat flux and integrated heat load

The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus.

Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level