Curr Top Microbiol
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Activation of the PI3 kinase pathway can induce skeletal muscle hypertrophy, defined as an increase in skeletal muscle mass. In mammals, skeletal muscle hypertrophy occurs as a result of an increase in the size, as opposed to the number, of pre-existing skeletal muscle fibers. This pathway's effects on skeletal muscle have been implicated most prominently downstream of Insulin-like growth factor 1 signaling. ⋯ Blockade of RAPTOR also facilitates myostatin's inhibition of muscle differentiation. When added to post-differentiated myotubes, myostatin causes a decrease in their diameter - however, this does not happen through the normal "atrophy pathway." Rather than causing upregulation of the E3 ubiquitin ligases MuRF1 and MAFbx, previously shown to mediate skeletal muscle atrophy, myostatin decreases expression of these atrophy markers in differentiated myotubes, as well as other genes normally upregulated during differentiation, such as MyoD and myogenin. These findings show that myostatin signaling acts by blocking genes induced during differentiation, even in a myotube, as opposed to activating the distinct "atrophy program."
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Influenza vaccines are the mainstay of efforts to reduce the substantial health burden from seasonal influenza. Inactivated influenza vaccines have been available since the 1940s and are administered via intramuscular injection. Inactivated vaccines can be given to anyone six months of age or older. ⋯ Influenza vaccination is recommended in the United States for all children six months or older, all adults 50 years or older, all persons with chronic medical conditions, and pregnant women, and contacts of these persons, including healthcare workers. The global disease burden of influenza is substantial, and the World Health Organization has indicated that member states should evaluate the cost-effectiveness of introducing influenza vaccination into national immunization programs. More research is needed to develop more effective seasonal influenza vaccines that provide long-lasting immunity and broad protection against strains that differ antigenically from vaccine viruses.
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In the past decade, a growing number of evidence has implicated free radicals in a variety of pathophysiological conditions including aging, cancer, and coronary heart disease. Analyses of different aspects of multiple sclerosis (MS) pathology with respect to oxidative damage have also revealed evidence of free radical injury to the central nervous system (CNS), although attempts to protect the CNS using various antioxidants have met with only moderate success. Several recent studies have reported lower levels of uric acid (UA), a major scavenger of reactive nitrogen species, in MS patients, while other studies found no such correlation. Here, we discuss these studies as well as current efforts to manipulate serum UA levels in MS patients.
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The characterization of patients with recurrent inflammatory syndromes into distinct clinical phenotypes provided early clues to the mode of inheritance of these conditions and facilitated the subsequent identification of causative gene mutations. The prototype autoinflammatory syndrome, familial Mediterranean fever, is characterized by self-limiting episodes of localized inflammation. Hallmarks of the classical autoimmune response are largely absent. ⋯ The role of an established biochemical pathway in regulating inflammation was uncovered by the discovery that the hyperimmunoglobulin D with periodic fever syndrome (HIDS) results from mutations in MVK, which encodes an enzyme in the isoprenoid pathway. The discovery that mutations in the gene encoding tumor necrosis factor (TNF) receptor 1 (TNFR1) cause a proinflammatory phenotype was unanticipated, as it seemed more likely that such mutations would instead have resulted in an immunodeficiency pattern. This review describes the clinical phenotypes of autoinflammatory syndromes, the underlying gene mutations, and current concepts regarding their pathophysiology.
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Genetic variation of the host significantly contributes to dramatic differences in the outcomes of natural infection with virulent Mycobacterium tuberculosis (MTB) in humans, as well as in experimental animal models. Host resistance to tuberculosis is a complex multifactorial genetic trait in which many genetic polymorphisms contribute to the phenotype, while their individual contributions are influenced by gene-gene and gene-environment interactions. The most epidemiologically significant form of tuberculosis infection in humans is pulmonary tuberculosis. ⋯ The Ipr1 is an interferon-inducible nuclear protein that dynamically associates with other nuclear proteins in macrophages primed with interferons or infected with MTB. Several of the Ipr1-interacting proteins are known to participate in regulation of transcription, RNA processing, and apoptosis. Further biochemical analysis of the Ipr1-mediated pathway will help delineate a mechanism of innate immunity that is especially important for control of tuberculosis progression in the lungs.