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Some cultured and natural pearls can be reliably distinguished by visual inspection and by the use of lens and microscope. However, assessing the origin of the pearls could be not straightforward since many different production techniques can now be found in the pearl market, for example in salt or freshwater environments, with or without a rigid nucleus. This wide range of products requires the use of new effective scientific techniques. Indeed, X-ray radiography has been used by gemologists since last century as the only safe and non-destructive way to visually inspect the interior of a pearl, and recently, also X-ray computed micro-tomography was used to better visualize the inner parts of the gems. In this study we analyzed samples of natural and cultured pearls by means of two non-destructive techniques: the X-ray Phase-Contrast Imaging (PCI) and the Neutron Imaging (NI). PCI and NI results will be combined for the first time, to better visualize the pearls internal morphology, thus giving relevant indications on the pearl formation process.

Systemic sclerosis is an autoimmune disease characterized by immunological abnormalities, vascular damage, and fibroblast proliferation. We have previously shown that a molecular mimicry mechanism links antibodies against the human-cytomegalovirus-derived protein UL94 to the pathogenesis of systemic sclerosis. The UL94 epitope shows homology with NAG-2, a surface molecule highly expressed on endothelial cells. Anti-UL94 peptide antibodies purified from patients' sera induce apoptosis of endothelial cells upon engagement of the NAG-2-integrin complex. We show here that NAG-2 is expressed on dermal fibroblasts and that anti-UL94 antibodies bind to fibroblasts. We have used the gene array strategy (Affimetrix oligonucleotide microarrays) to analyze the transcriptional profile in response to a 4-h and an 8-h treatment with antibodies against the UL94 peptide in endothelial cells and dermal fibroblasts. Exposure of endothelial cells to anti-UL94 antibodies had a profound impact on gene expression, resulting in the upregulation of 1,645 transcripts. Several gene clusters were upregulated including genes encoding adhesion molecules, chemokines, colony-stimulating factors (CSFs), growth factors, and molecules involved in apoptosis. Following antibody stimulation, dermal fibroblasts showed an upregulation of 989 transcripts and acquired a \"scleroderma-like\" phenotype. Indeed, genes involved in extracellular matrix deposition, growth factors, chemokines, and cytokines were upregulated. We confirmed the microarray results by real-time quantitative polymerase chain reaction and by measuring some of the corresponding proteins with ELISA and Western blotting. Our results show that anti-human-cytomegalovirus antibodies may be linked to the pathogenesis of systemic sclerosis not only by inducing endothelial cell activation and apoptosis but also by causing activation of fibroblasts, one of the hallmarks of the disease.

Systemic sclerosis is an autoimmune disease characterized by immunological and vascular abnormalities. Autoantibodies against intracellular antigens are associated with particular clinical features of the disease 1 , whereas autoantibodies against cell surface antigens may be pathogenic by inducing endothelial cell damage 2 , 3 , considered the primary event in the pathogenesis of the disease. Latent human cytomegalovirus infection may contribute to progression of systemic sclerosis through its ability to infect endothelial cells 4 ; however, direct links between human cytomegalovirus infection and systemic sclerosis are still lacking 5 . Molecular mimicry is one of the mechanisms that account for the link between infection and autoimmunity 6 , 7 , 8 . Here we have identified an immunodominant peptide using systemic sclerosis serum screening of a random peptide library; such peptide shares homology with autoantigens and with the human cytomegalovirus late protein UL94 (ref. 9 ). Immunoglobulin G antibodies against the peptide affinity-purified from the sera of patients with systemic sclerosis specifically recognized the viral product and autoantigens; moreover, such antibodies induced endothelial cell apoptosis through specific interaction with the cell surface integrin–NAG-2 protein complex 10 . Our results provide evidence that antibodies against human cytomegalovirus cause apoptosis of endothelial cells 11 , considered the initial pathogenic event of systemic sclerosis, and indicate a previously unknown mechanism for the etiological link between human cytomegalovirus infection and autoimmunity.

Cogan's syndrome is a chronic inflammatory disease of unknown origin, characterised by sensorineural hearing loss, episcleritis, and vasculitis. An autoimmune origin has been suggested but not proven. Our aim was to establish whether or not an autoimmune process is the cause of the disease. We used pooled IgG immunoglobulins derived from eight patients with Cogan's syndrome to screen a random peptide library to identify disease relevant autoantigen peptides. Among the identified peptides, one was recognised by all the patients’ sera. Antibodies against peptides were affinity purified from patients’ sera and used to characterise the autoantigen, to stain human cochlea, and to transfer the features of Cogan's disease into animals. We identified an immunodominant peptide that shows similarity with autoantigens such as SSA/Ro and with the reovirus III major core protein lambda 1. The peptide sequence shows similarity also with the cell-density enhanced protein tyrosine phosphatase-1 (DEP-1/CD148), which is expressed on the sensory epithelia of the inner ear and on endothelial cells. IgG antibodies against the peptide, purified from the patients’ sera, recognised autoantigens and DEP-1/CD148 protein, bound human cochlea, and inhibited proliferation of cells expressing DEP-1/CD148. The same antibodies bound connexin 26, gene mutations of which lead to congenital inner-ear deafness. Furthermore, these antibodies were able to induce the features of Cogan's disease in mice. Our results indicate that Cogan's syndrome is an autoimmune disease, characterised by the presence of autoantibodies able to induce tissue damage on binding of cell-surface molecules present on the sensory epithelia of the inner ear and on endothelial cells.

The biochemical role of the synovial-like membrane formed at the interface of eight aseptic failed total hip prosthesis has been investigated during in vitro mechanical loading. The study was carried out on four membranes from cemented prosthesis and four titanium alloy uncemented ones. Intermittent positive pressure leading to 20% deformation of the membrane (100 g/cm(2))was applied to the membrane fragments in cycles (300 cycles/15 min) repeated three times at thirty minutes intervals in which interleukin-6 (IL6), prostaglandin-E2 (PGE2) and interleukin-1beta (IL1beta) levels were quantified both in culture media and in tissue extracts. Histological, morphometrical and immunohistochemical studies were also carried out on the same membranes. Mechanical stress evidenced an increase in the release of the examined cytokines both in cemented and uncemented prosthesis tissues; particularly evident was IL6 trend of increase from cemented prosthesis and IL1beta result from uncemented ones. Histomorphological and immunohistochemical data revealed no differences between membranes obtained from cemented and uncemented prosthesis as to cell proliferation, fibrosis, macrophages lymphocytes B and T population, vessels and nervous fibers. The results indicate that mechanical stress plays a fundamental role in increasing membrane production and release of cytokines known as bone-resorbing agents. Furthermore, the histologic finding of synovial-like membrane with the same histomorphological and immunohistochemical findings but with different biochemical response to mechanical stimulation, suggests that cells involved in the production and release of the considered mediators might have different strain behavior by different development conditions (previous contact with PMMA).

Infections and autoimmunity have been implicated in the pathogenesis of atherosclerosis. Cytomegalovirus has been shown to contribute to the disease. Autoantibodies against human heat-shock protein (HSP) 60 are present in most atherosclerotic patients, and their titre correlates with disease severity, suggesting that anti-HSP60 might be implicated in disease pathogenesis. We postulated that cytomegalovirus infection might induce antibodies able to bind human HSP60 and to cause endothelial-cell damage. We studied 180 patients with coronary-artery disease, raised high sensitivity C-reactive protein concentrations, and presence or absence of traditional risk factors; 90 patients with coronary-artery disease, normal values for high sensitivity C-reactive protein, and no traditional risk factors; and 98 controls. Individual sera were used to define the relevant epitope of HSP60 by ELISA. Affinity purified IgGs were used to identify endothelial cell-surface ligands by western blot and to induce apoptotic cell death. We identified an 11 aminoacid sequence of HSP60 that was recognised by most patients with coronary-artery disease. This peptide shares homology with cytomegalovirus-derived proteins UL122 and US28. The same patients' sera recognised UL122-derived and US28-derived peptides. Purified IgGs against HSP60 and the viral peptides bound non-stressed human endothelial cells and induced endothelial-cell apoptosis by interaction with cell-surface molecules. During cytomegalovirus infection, antibodies against the virus can arise that are able to crossreact with human HSP60 and cause apoptosis of non-stressed endothelial cells, which is judged a primary event in the pathogenesis of atherosclerosis.

Cogan's syndrome is a chronic inflammatory disease of unknown origin, characterised by sensorineural hearing loss, episcleritis, and vasculitis. An autoimmune origin has been suggested but not proven. Used pooled IgG immunoglobulins derived from 8 patients with Cogan's syndrome to screen a random peptide library to identify disease relevant autoantigen peptides. Results indicate that Cogan's syndrome is an autoimmune disease, characterised by the presence of autoantibodies able to induce tissue damage on binding of cell-surface molecules present on the sensory epithelia of the inner ear and on endothelial cells. (Original abstract - amended)

Propionic acid (propionate) is a commercially valuable carboxylic acid produced through microbial fermentation. Propionic acid is mainly used in the food industry but has recently found applications in the cosmetic, plastics and pharmaceutical industries. Propionate can be produced via various metabolic pathways, which can be classified into three major groups: fermentative pathways, biosynthetic pathways, and amino acid catabolic pathways. The current review provides an in-depth description of the major metabolic routes for propionate production from an energy optimization perspective. Biological propionate production is limited by high downstream purification costs which can be addressed if the target yield, productivity and titre can be achieved. Genome shuffling combined with high throughput omics and metabolic engineering is providing new opportunities, and biological propionate production is likely to enter the market in the not so distant future. In order to realise the full potential of metabolic engineering and heterologous expression, however, a greater understanding of metabolic capabilities of the native producers, the fittest producers, is required.