A Pathophysiologic Role for Epidermal Growth Factor Receptor in Pemphigus Acantholysis

The pemphigus family of autoimmune bullous disorders is characterized by autoantibody binding to desmoglein 1 and/or 3 (dsg1/dsg3). In this study we show that EGF receptor (EGFR) is activated following pemphigus vulgaris (PV) IgG treatment of primary human keratinocytes and that EGFR activation is downstream of p38 mitogen-activated protein kinase (p38). Inhibition of EGFR blocked PV IgG-triggered dsg3 endocytosis, keratin intermediate filament retraction, and loss of cell-cell adhesion in vitro. Significantly, inhibiting EGFR prevented PV IgG-induced blister formation in the passive transfer mouse model of pemphigus. These data demonstrate cross-talk between dsg3 and EGFR, that this cross-talk is regulated by p38, and that EGFR is a potential therapeutic target for pemphigus. Small-molecule inhibitors and monoclonal antibodies directed against EGFR are currently used to treat several types of solid tumors. This study provides the experimental rationale for investigating the use of EGFR inhibitors in pemphigus.     

Effect of melatonin on torsion and reperfusion induced pathogenesis of rat uterus

ABSTRACT

We investigated the use of melatonin to improve fertility and reduce uterine damage caused by torsion of the uterus in pregnant rats. We used 35 pregnant rats at gestational age 18 days. The animals were randomized into five groups. Group 1 was anesthetized only. Group 2 was subjected to experimental uterine torsion of 360° and the torsion was corrected after 6 h. Group 3 was subjected to uterine torsion of 360°, the torsion was corrected after 6 h and melatonin was administered at the time of correction. Group 4 rats were subjected to 360º uterine torsion and melatonin was administered 6 h later at the time of correction. Group 5 was administered melatonin followed by uterine torsion of 360 degrees followed by correction of torsion 6 h later. Samples were obtained from the uterine horns on the day 1 postpartum. We used Bax, Bcl-2 and caspase 3 staining to measure apoptosis in the uterine tissues. The mRNA levels of Rho-associated, coiled-coil containing protein kinases 1 (ROCK1), homeobox D10 (Hox4 HoxD10), TLR4, NFκB1, caveolin 1 (Cav1) heat shock protein 90 alpha (cytosolic), class B member 1 (Hsp90ab1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using quantitative real-time polymerase chain reaction analysis (qRT-PCR). Bax, Bcl-2 and caspase 3 were detected using immunohistochemistry. No difference was observed among groups with respect to abortion, neonatal mortality or congenital abnormalities. Compared to the control group, the mRNA levels of Rock1, Hox4, TLR4, NFκB1, Cav1 and Hsp90 genes were decreased significantly in the study groups; the decrease was greater in groups 3 and 4, which were treated with melatonin. The greatest amount of Bax staining was found in group 1 and the least amount of Bcl-2 staining was found in groups 4 and 5; the greatest amount of caspase 3 staining was found in group 2. Our findings indicate that melatonin reduced uterine torsion related tissue damage and that its application during torsion was more effective than application following removal of torsion.     

Scorzonera aksekiensis sp. nov. (Asteraceae) from south Anatolia,Turkey

Scorzonera aksekiensis A. Duran & M. Öztürk sp. nov. from the Akseki district (C3 Antalya province) in Turkey is described and illustrated. The diagnostic morphological characters of similar taxa are discussed. Scorzonera aksekiensis is related to S. semicana DC. from which it mainly differs in its habitus, indumentum, leaves, capitula and achenes. The ecology, biogeography and conservation status of the new species are also presented. The geographical distribution of S. aksekiensis and related species is mapped.     

GPCRs and EGFR – Cross-talk of membrane receptors in cancer

G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) are two important classes of cell surface receptors proven to be highly tractable as drug targets. Both receptor classes are involved in various complex (patho-) physiological processes in the human body including cellular growth and differentiation. More recently, accumulating data suggest that GPCR-induced activation of EGFR, the prototyp of RTKs represents a major mechanism in various cancers. The present review will focus on this cross-talk with particular emphasis on intracellular scaffold proteins regulating EGFR transactivation. It will give an overview about the current status of the research and future directions, highlight recent trends in the field, and discuss the potential of therapeutic strategies combining GPCR and EGFR targeting on the one hand and specific targeting of the cross-talk on the other hand in cancer therapy.     

Culturable bacterial microbiota of Plagiodera versicolora (L.) (Coleoptera: Chrysomelidae) and virulence of the isolated strains

Plagiodera versicolora (Laicharting, 1781) (Coleoptera: Chrysomelidae) is an important forest pest which damages many trees such as willow, poplar, and hazelnut. In order to find new microbes that can be utilized as a possible microbial control agent against this pest, we investigated the culturable bacterial flora of it and tested the isolated bacteria against P. versicolora larvae and adults. We were able to isolate nine bacteria from larvae and adults. The isolates were characterized using a combination of morphological, biochemical, and physiological methods. Additionally, we sequenced the partial sequence of the 16S rRNA gene to verify conventional identification results. Based on characterization studies, the isolates were identified as Staphylococcus sp. Pv1, Rahnella sp. Pv2, Rahnella sp. Pv3, Rahnella sp. Pv4, Rahnella sp. Pv5, Pantoea agglomerans Pv6, Staphylococcus sp. Pv7, Micrococcus luteus Pv8, and Rahnella sp. Pv9. The highest insecticidal activity against larvae and adults was obtained from M. luteus Pv8 with 50 and 40 % mortalities within 10 days after treatment, respectively. Extracellular enzyme activity of the bacterial isolates such as amylase, proteinase, lipase, cellulose, and chitinase was also determined. Consequently, our results show that M. luteus Pv8 might be a good candidate as a possible microbial control agent against P. versicolora and were discussed with respect to biocontrol potential of the bacterial isolates.     

cis-Regulatory elements for mesophyll-specific gene expression in the C4 plant Flaveria trinervia, the promoter of the C4 phosphoenolpyruvate carboxylase gene

C(4) photosynthesis depends on the strict compartmentalization of CO(2) assimilatory enzymes. cis-regulatory mechanisms are described that ensure mesophyll-specific expression of the gene encoding the C(4) isoform of phosphoenolpyruvate carboxylase (ppcA1) of the C(4) dicot Flaveria trinervia. To elucidate and understand the anatomy of the C(4) ppcA1 promoter, detailed promoter/reporter gene studies were performed in the closely related C(4) species F. bidentis, revealing that the C(4) promoter contains two regions, a proximal segment up to -570 and a distal part from -1566 to -2141, which are necessary but also sufficient for high mesophyll-specific expression of the beta-glucuronidase reporter gene. The distal region behaves as an enhancer-like expression module that can direct mesophyll-specific expression when inserted into the ppcA1 promoter of the C(3) plant F. pringlei. Mesophyll expression determinants were restricted to a 41-bp segment, referred to as mesophyll expression module 1 (Mem1). Evolutionary and functional studies identified the tetranucleotide sequence CACT as a key component of Mem1.