The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Sub-kHz RF electrical linewidth from a 10GHz passively mode-locked quantum-dot laser diode

A packaged 10GHz monolithic two-section quantum-dot mode-locked laser is presented, with record narrow 500Hz RF electrical linewidth for passive mode-locking. Single sideband noise spectra show 147fs integrated timing jitter over the 4MHz-80MHz frequency range. © 2009 Optical Society of America

Intra-plant spatial distribution of Thaumastocoris peregrinus Carpintero & Dellapé (Hemiptera: Thaumastocoridae) on Eucalyptus grandis plants

The bronze bug Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae), which is native to Australia, damages eucalyptus plantations. In Brazil, this insect was recently introduced, but its distribution on eucalyptus plants remains to be studied. The best sample collection points of T. peregrinus are important to determine infestations of adults, nymphs and eggs on eucalyptus canopy. This study was conducted with Eucalyptus grandis (Myrtaceae). Ten leaves per branch of the prospected trees were collected and the number of T. peregrinus adults, nymphs and eggs on each was counted. Leaves sampled in the middle one-third of the canopy of E. grandis yielded representative data for the T. peregrinus biological cycle. This insect showed vertical intra-plant distribution of 58.28, 46.66 and 49.19 % of adults, nymphs and eggs, respectively, in this stratum. The horizontal distribution of T. peregrinus was 35, 46 and 41 % of adults, nymphs, and eggs in the east, west, and south quadrants, respectively. Thus, Thaumastocoris peregrinus should be sampled on leaves of the middle one-third part of E. grandis