In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades. OBJECTIVES: To investigate the contribution of these signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo. METHODS: We used the passive transfer mouse model. Mice were injected with IgG fractions of sera from a patient with PV, with or without pretreatment with inhibitors of proteins that mediate intracellular signalling cascades. RESULTS: Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in vivo. CONCLUSIONS: These observations strongly support the role of intracellular signalling cascades in the molecular mechanism of PV IgG-induced acantholysis

Characterisation of Perennial Ryegrass Parental Inbred Lines for Generating Recombinant Inbred Lines for Fine Mapping and Gene Cloning

Intermated recombinant inbred lines (IRIs) are a powerful tool for fine mapping and cloning of genes. Such population structures have been particularly helpful for cloning of genes in the model genetic plant Arabidopsis thaliana. IRIs or recombinant inbred lines (RILs) would be valuable for perennial ryegrass (Lolium perenne), but its allogamous character means that the construction of RILs is a difficult task. The international Lolium community would benefit from the development of such lines. The aims of the projects are to characterise the parental lines and initial generations at the (1) phenotypic, (2) molecular and (3) molecular cytogenetic level

S-SAP molecular marker-based detection of interspecific variability among grape cultivars

Genetska unutarsortna varijabilnost temelji se na pretpostavci da tijekom vremena dolazi do pojave spontanih mutacija u genomu sorte koje zbog vegetativnog načina razmnožavanja ostaju fiksirane. Svaka informacija o unutarsortnoj varijabilnosti može biti od velike važnosti prije odluke o tome koje trsove zadržati nakon provjere zdravstvenog statusa te može pružiti uvid u homogenost populacije i potencijal klonske selekcije. U ovom istraživanju korišten je sustav markera temeljen na retrotranspozonima – modificirana S-SAP metoda koja je u prijašnjim istraživanjima pokazala potencijal za razlikovanje klonova. Korišten biljni materijal vinove loze sastojao se od 22 primke dviju različitih sorti: Zlatarice blatske bijele i Glavinuše. S-SAP metoda provedena je sa 6 različitih kombinacija početnica. Ovom metodom uspješno su razlikovane obje sorte, a detektirane su i razlike među pojedinim jedinkama. Stupanj polimorfizma, iako analize nisu rađene na certificiranom klonskom materijalu, u skladu je sa sličnim istraživanjima rađenim na certificiranom materijalu. Početnica F100 je detektirala najviše razlika i može se preporučiti u daljnjim istraživanjima. Dobiveni rezultati pružaju smjernice prilikom daljnje propagacije i revitalizacije.Intra-varietal variability is based on the assumption that during the time spontaneous mutations occur in the varieties genome and stay fixed because of vegetative propagation. Any kind of information about intra-varietal variability could be of importance before making a decision which vines to keep after verification of their health status and could provide an insight into homogeneity of the population and into the potential of the clonal selection. In this study a retrotransposon based marker system was used – a modified SSAP method which, in previous studies, showed the potential for differentiating clones. Collected grapevine plant material consisted of 22 accessions representing two Croatian varieties: Zlatarica blatska bijela and Glavinuša. S-SAP method was performed using 6 different primer combinations. This method successfully differentiated both varieties and also detected some clonal differences among tested accessions. Although the analyses were not done on certified clonal material, level of polymorphism was similar to those in similar studies using certified clones. The use of universal retrotransposon primer F100 resulted in most observed polymorphism. Obtained results provide guidelines for further propagation and revitalization

Produção de biodiesel e geração de energia elétrica a partir de óleo de mamona em Quixeramobim, CE.

Introdução; Fase agrícola - produção de mamona; Fase industria l- extração de óleo e transesterificação; Fase final - geração de energia elétrica; Considerações finais.bitstream/CNPA/17471/1/DOC136.pd

Autoimmune and infectious skin diseases that target desmogleins

Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell–cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1–Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3−/− lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown