PGC-1α4 gene expression is suppressed by the IL-6-MEK-ERK 1/2 MAPK signalling axis and altered by resistance exercise, obesity and muscle injury.

AIM: PGC-1α4 is a novel regulator of muscle hypertrophy; however, there is limited understanding of the regulation of its expression and role in many (patho)physiological conditions. Therefore, our purpose was to elicit signalling mechanisms regulating gene expression of Pgc1α4 and examine its response to (patho)physiological stimuli associated with altered muscle mass. METHODS: IL-6 knockout mice and pharmacological experiments in C2C12 myocytes were used to identify regulation of Pgc1α4 transcription. To examine Pgc1α4 gene expression in (patho)physiological conditions, obese and lean Zucker rats with/without resistance exercise (RE), ageing mice and muscle regeneration from injury were examined. RESULTS: In IL-6 knockout mice, Pgc1α4mRNA was ~sevenfold greater than wild type. In C2C12 cells, Pgc1α4mRNA was suppressed ~70% by IL-6. Suppression of Pgc1α4 by IL-6 was prevented by MEK-ERK-MAPK inhibition. RE led to ~260% greater Pgc1α4mRNA content in lean rats. However, obese Zucker rats exhibited ~270% greater Pgc1α4mRNA than lean, sedentary with no further augmentation by RE. No difference was seen in IL-6mRNA or ERK-MAPK phosphorylation in Zucker rats. Aged mice demonstrated ~50% lower Pgc1α4mRNA and ~fivefold greater ERK-MAPK phosphorylation than young despite unchanged Il-6mRNA. During muscle regeneration, Pgc1α4 content is ~30% and IL-6mRNA >threefold of uninjured controls 3 days following injury; at 5 days, Pgc1α4 was >twofold greater in injured mice with no difference in IL-6mRNA. CONCLUSION: Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL-6-ERK-MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions.

Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer.

During tumor initiation, oncogene-induced senescence (OIS) is proposed to limit the progression of preneoplasms to invasive carcinoma unless circumvented by the acquisition of certain tumor suppressor mutations. Using a variety of biomarkers, OIS has been previously reported in a wide range of human and murine precursor lesions, including the pancreas, lung, colon and skin. Here, we have characterized a panel of potential OIS biomarkers in human and murine pancreatic intraepithelial neoplasia (PanIN), and found that only senescence-associated ß-galactosidase (SAßgal) activity is specifically enriched in these precursors, compared with pancreatic ductal adenocarcinoma (PDA). Indeed, many of the other proposed OIS biomarkers are detected in actively proliferating PanIN epithelium and in cells within the microenvironment. Surprisingly, acinar to ductal metaplasia (ADM), a distinct preneoplasm that is potentially a precursor for PanIN, also exhibits SAßgal activity and contains a higher content of p21 and p53 than PanIN. Therefore, SAßgal activity is the only biomarker that accurately identifies a small and heterogeneous population of non-proliferating premalignant cells in the pancreas, and the concomitant expression of p53 and p21 in ADM supports the possibility that PanIN and ADM each exhibit discrete senescence blocks.

Surface-plasmon spatial light modulators based on liquid crystal.

The development of a new class of spatial light modulator (SLM), which uses modulation of lossy guided waves generated by surface-plasmon resonance, is described. The potential advantages of this technique are explained, including increased response uniformity and enhanced sensitivity and speed. An optically addressed SLM that is based on a nematic liquid crystal with a spatial resolution better than 10 line pairs/mm (at 50% modulation transfer function) is demonstrated. For the design of devices that are based on newer smectic liquid crystals the use of anisotropy-induced polarization mixing and the so-called pseudoplasmon modes are described. Such modes offer controllable sensitivity-spatial resolution characteristics in simple liquid-crystal SLM structures. Within a typical SLM resolution requirement of 10 line pairs/mm, for example, the sensitivity can be optimized to obtain a theoretical reflectivity modulation from 0 to 0.7 for a liquid-crystal director modulation of 5 degrees .

Percutaneous alternatives in nutritional support: a radiologic perspective.

As alternatives to per os feeding and nutritional support increase in number and complexity, the interventional radiologist has come to play a more significant role in the creation and maintenance of nutritional access. In very difficult access cases, the concerted effort of the nutritional surgeon and the radiologist is often required. We describe several such situations which have been successfully managed at our institution. The indications for and techniques of percutaneous reestablishment of surgically placed jejunostomy tubes, the percutaneous conversion of gastrostomy to jejunostomy tubes with retention of the gastrostomy tube, and percutaneous placement of an inferior vena caval Hickman catheter are all described in detail.

Plants with potential to enhance significant tumor growth.

Of 20,000 plant extracts submitted to the National Cancer Institute antitumor screens from 1960 to 1980, over 95% exhibited inadequate tumor-inhibiting activity or promoted tumor growth. Of these, 50 extracts representing 42 species showed significant levels of tumor growth enhancement compared to controls on the basis of tumor weights when the extracts were administered to test and control animals dosed equally on the basis of implanted tumor weights. Because of the continuing threat of environmentally induced or promoted cancer in the human population, the species identified in this report are deemed worthy of studies designed to quantitate the risks of contact by botanists, hikers, plant hobbyists, and field workers. Even more fundamental, studies of these plants could provide knowledge of new compounds under the influence of which tumor growth is enhanced. Further studies might also reveal the mechanisms of this tumor enhancement.