Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise

Muscle fibres have different properties with respect to force, contraction speed, endurance, oxidative/glycolytic capacity etc. Although adult muscle fibres are normally post-mitotic with little turnover of cells, the physiological properties of the pre-existing fibres can be changed in the adult animal upon changes in usage such as after exercise. The signal to change is mainly conveyed by alterations in the patterns of nerve-evoked electrical activity, and is to a large extent due to switches in the expression of genes. Thus, an excitation-transcription coupling must exist. It is suggested that changes in nerve-evoked muscle activity lead to a variety of activity correlates such as increases in free intracellular Ca2+ levels caused by influx across the cell membrane and/or release from the sarcoplasmatic reticulum, concentrations of metabolites such as lipids and ADP, hypoxia and mechanical stress. Such correlates are detected by sensors such as protein kinase C (PKC), calmodulin, AMP-activated kinase (AMPK), peroxisome proliferator-activated receptor δ (PPARδ), and oxygen dependent prolyl hydroxylases that trigger intracellular signaling cascades. These complex cascades involve several transcription factors such as nuclear factor of activated T-cells (NFAT), myocyte enhancer factor 2 (MEF2), myogenic differentiation factor (myoD), myogenin, PPARδ, and sine oculis homeobox 1/eyes absent 1 (Six1/Eya1). These factors might act indirectly by inducing gene products that act back on the cascade, or as ultimate transcription factors binding to and transactivating/repressing genes for the fast and slow isoforms of various contractile proteins and of metabolic enzymes. The determination of size and force is even more complex as this involves not only intracellular signaling within the muscle fibres, but also muscle stem cells called satellite cells. Intercellular signaling substances such as myostatin and insulin-like growth factor 1 (IGF-1) seem to act in a paracrine fashion. Induction of hypertrophy is accompanied by the satellite cells fusing to myofibres and thereby increasing the capacity for protein synthesis. These extra nuclei seem to remain part of the fibre even during subsequent atrophy as a form of muscle memory facilitating retraining. In addition to changes in myonuclear number during hypertrophy, changes in muscle fibre size seem to be caused by alterations in transcription, translation (per nucleus) and protein degradation

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Human chronic wounds treated with bioengineered skin: Histologic evidence of host-graft interactions

Bioengineered skin is being used to successfully treat a variety of wounds. Randomized controlled clinical trials have shown that a living bilayered skin construct (BSC), consisting of human neonatal keratinocytes and fibroblasts in a collagen matrix, was able to accelerate complete closure of both venous and diabetic ulcers. BSC was particularly effective in difficult-to-heal wounds of long duration. In patients treated with BSC, no obvious signs of gross clinical rejection were observed. Testing of these treated patients showed no BSC-specific immune response and no immune response to bovine collagen or alloantigens expressed on keratinocytes and fibroblasts. However, very little is known about the histologic changes that occur after BSC has been placed on human wounds. We report our preliminary histologic observations in this uncontrolled study of a cohort of 11 patients with 14 wounds treated with BSC in whom biopsy specimens of the grafted sites were obtained at least 2 weeks after application of the construct. The etiology of these ulcers varied from arterial or venous disease to an extensively and poorly healing burn wound. Histologically, thickening of the grafted bioengineered skin was seen in all samples where residual BSC could be identified. Mucin deposition was noted in the dermal layer of the wounds and BSC in 13 of the 14 specimens examined. Unexpectedly, and in spite of good clinical outcome, 4 of the 14 specimens exhibited a foreign body-like granulomatous response. There was no history of prior exposure to BSC in the 4 patients who had a granulomatous response. These early histologic observations suggest that stimulatory interactions develop between BSC and the wound. The consistently found deposition of mucin may point to a fetal pattern of wound repair associated with the neonatal cells in BSC. (J Am Acad Dermatol 2002;46:524-30.

Association of intercellular adhesion molecule-1 gene with type 1 diabetes

Intercellular adhesion molecule-1 (ICAM-1) functions via its ligands, the leucocyte integrins, in adhesion of immune cells to endothelial cells and in T cell activation. The third immunoglobulin-like extracellular domain binds integrin Mac-1 and contains a common non-conservative aminoacid polymorphism, G241R. Phenotypically, ICAM-1 has been associated with type 1 diabetes, a T-cell-mediated autoimmune disease. We assessed two independent datasets, and noted that R241 was associated with lower risk of type 1 diabetes than is G241 (3695 families, relative risk 0.91, p=0.03; 446 families, 0.60, p=0.006). Our data indicate an aetiological role for ICAM-1 in type 1 diabetes, which needs to be confirmed in future genetic and functional experiments