The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive) proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate cytokines, but also the loss of membrane receptors, adhesion molecules and T-cell cytokines that drive the aetiology of Buruli ulcer

Organic thin film transistors: Materials, process and devices

For the past ten years, organic materials have been extensively investigated as an electronic material for thin film transistor (TFT) devices. Organic materials offer strong promise in terms of properties, processing and cost effectiveness and they can be used in flat panel displays, imagers, smart cards, inventory tags and large area electronic applications. In this review, we summarize the current status of the organic thin film transistors including substrate materials, electrodes, semiconducting and dielectric layers; organic thin film preparation methods; morphological studies for organic thin films; electrical characterization of gate dielectric layers and semiconducting active layers; and characterization of the OTFTs. Future prospects and investigations required to improve the OTFT performance are also given.X1170sciescopuskc

Dielectric, thermally stimulated discharge current, pyroelectric and surface morphology of PMMA thin films prepared by isothermal immersion

Metal-Insulator-Metal. structure was used to investigate the dielectric, thermally stimulated discharge current (TSDC) and pyroelectric behavior of poly methyl methacrylate (PMMA) thin films prepared by isothermal immersion method. The surface morphology and the structure of the above said films were studied by using atomic force microscopy (AFW) and X-ray diffraction (CRD) respectively. The XRD spectrum of as grown and films annealed at 513 K indicated the amorphous nature. No pits and dendritic features were observed from the AFM spectrum. The only important topographic features observed is the hillocks of about 10-12 nm large with a peak to valley vertical distance of about 0.5-1 nm, Both as grown and films annealed at 513 K showed very smooth surface and amorphous nature. From the TSDC spectrum activation energy (E), capture cross-section (sigma), escape frequency (nu) and relaxation time (tau) were calculated. The observed amorphous phase, low loss, dielectric and thermal behavior imply the feasibility utilizing PMMA thin films as gate dielectric insulator layer in organic thin film transistors (OTFTs), which can find application in flat panel display.X1110sciescopu

Genetic and developmental disorders of the oral mucosa : epidemiology; molecular mechanisms; diagnostic criteria; management

A large number of disorders may affect the oral cavity, including genetic diseases, infections, cancers, blood diseases, skin diseases, endocrine and metabolic disorders, autoimmune and rheumatologic diseases, local lesions, to name a few. Oral mucosa shows a considerable variation in its normal structure and a wide range of conditions may affect it. Such conditions are often harmless or minor and could be primary or secondary to systemic disease. Several of them are quite rare and, hence, the diagnosis is not easy. Clinically, lesions may appear as ulcers, discoloration of the oral mucosa and alterations in size and configuration of oral anatomy. Genetic disorders have specific manifestations and can be caused by a derangement of one or more components of the tissue. Many of them follow the skin or systemic signs of the underlying genetic disease, but in a few cases oral signs could be the first manifestation of the disorder. Among them genodermatoses are prominent. They are inherited disorders characterized by a multisystem involvement. This review describes chondro-ectodermal dysplasia, dyskeratosis congenita, Ehlers-Danlos syndrome, hereditary benign intraepithelial dyskeratosis, keratosis follicularis, lipoid proteinosis, multiple hamartoma syndrome, pachyonychia congenita, Peutz-Jeghers syndrome, tuberous sclerosis and white sponge nevus. Other genetic disorders not included in the genodermatosis group and reported in the present review are: acanthosis nigricans, angio-osteo-hypertrophic syndrome, encephalotrigeminal angiomatosis, familial adenomatous polyposis, focal dermal hypoplasia, focal palmoplantar and oral mucosa hyperkeratosis syndrome, gingival fibromatosis, Maffucci's syndrome, neurofibromatosis (type 1) and oro-facial-digital syndrome (type 1). Disorders during embryonic development might lead to a wide range of abnormalities in the oral cavity; some of them are quite common but of negligible concern, whereas others are rare but serious, affecting not only the oral mucosa, but also other structures of the oral cavity (ie palate, tongue and gingiva). Fordyce's granules, leukoedema, cysts of the oral mucosa in newborns, retrocuspid papilla, geographic tongue, fissured tongue, median rhomboid glossitis, hairy tongue, lingual varices and lingual thyroid nodule are described. This review may help dentists, dental hygienists, but also general internists and pediatricians to diagnose different disorders of the oral mucosa, to understand the pathogenesis and to schedule a treatment plan