SummaryType 1 diabetes (T1D) is caused by the selective destruction of the insulinproducing b cells of the pancreas by an autoimmune response. Due to ethical and practical difficulties, the features of the destructive process are known from a small number of observations, and transcriptomic data are remarkably missing. Here we report whole genome transcript analysis validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and correlated with immunohistological observations for four T1D pancreases (collected 5 days, 9 months, 8 and 10 years after diagnosis) and for purified islets from two of them. Collectively, the expression profile of immune response and inflammatory genes confirmed the current views on the immunopathogenesis of diabetes and showed similarities with other autoimmune diseases; for example, an interferon signature was detected. The data also supported the concept that the autoimmune process is maintained and balanced partially by regeneration and regulatory pathway activation, e.g. nonclassical class I human leucocyte antigen and leucocyte immunoglobulin-like receptor, subfamily B1 (LILRB1). Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms.
Aims/hypothesis Transmembrane protein 27 (TMEM27) is a membrane protein cleaved and shed by pancreatic beta cells that has been proposed as a beta cell mass biomarker. Despite reports of its possible role in insulin exocytosis and cell proliferation, its function in beta cells remains controversial. We aimed to characterise the function of TMEM27 in islets and its potential use as a beta cell mass biomarker. Methods To determine TMEM27 function, we studied TMEM27 gene expression and localisation in human healthy and diabetic islets, the correlation of its expression with cell cycle and insulin secretion genes in human islets, its expression in tungstate-treated rats, and the effects of its overproduction on insulin secretion and proliferation in a beta cell line and islets. To elucidate its utility as a beta cell mass biomarker, we studied TMEM27 cleavage in a beta cell line, islets and primary proximal tubular cells. Results TMEM27 mRNA levels in islets are lower in diabetic donors than in controls. Its gene expression correlates with that of insulin and SNAPIN in human islets. TMEM27 expression is downregulated in islets of tungstate-treated rats, which exhibit decreased insulin secretion and increased proliferation. TMEM27 overproduction in a beta cell line and islets significantly enhanced glucose-induced insulin secretion, with modest or no effects on proliferation. Finally, TMEM27 is cleaved and shed by renal proximal tubular cells and pancreatic islets.A. Barbera and R. Gomis contributed equally to this study. Electronic supplementary material The online version of this article
In order to profit from recycling sewage sludge through the soil‐plant system, it is necessary to know the amount of mineralizable organic‐N from sludge. The purpose of this study was to determine N‐mineralization of two sewage sludges in two different soils, comparing leached and nonleached incubation procedures. The cumulative N mineralized during successive incubation periods increased linearly with incubation time and sludge incorporation rate. The mineralization process was more influenced by soil type than by rate and kind of sludge applied. The amount of mineralized‐N was higher for the leaching procedure. This cumulative‐N expressed as the percentage of applied organic‐N was inversely dependent on sewage sludge rate added for the leached procedure and is independent of the rate for the nonleached. The N‐mineralization rate was 0.0202 ± 0.0011 and 0.0650 ± 0.0068 d−1, respectively, for leached and nonleached procedures. The potentially mineralizable N increased with the sludge rate applied and was higher for aerobic sludge and neutral soil. In general, the leached method gave twofold higher vlaues than the nonleached method. The net percentage of potentially mineralizable N vs. organic‐N added was 43.0 ± 7.8 and 27.7 ± 4.0, respectively, for leached and nonleached procedures.
Dietary lipids have a role in the aetiology of breast cancer, acting at several cellular levels. We investigated the effects of a high corn oil and a high extra virgin olive oil diet on the clinical and histopathological characteristics of rat dimethylbenz(α)anthracene-induced mammary carcinogenesis and on the expression of p21Ha-Ras, detected by immunohistochemistry, in one experimental series including a low-fat corn oil diet (LFCO) and two high-fat diet groups: HFCO(P), rich in corn oil, and HFOO(P), rich in extra virgin olive oil. Whereas the high corn oil diet tended to reduce latency time, to raise tumour incidence and to increase total tumour yield, the high extra virgin olive oil diet led to a latency time similar to that of LFCO and to a lower tumour incidence than HFCO(P) and lower total tumour yield, even than LFCO. HFCO(P) tumours displayed a higher histological grade and profile than LFCO tumours, while adenocarcinomas in HFOO(P) were similar to LFCO ones. Although no significant differences in p21Ha-Ras expression among dietary groups was found, we detected a significant p21Ha-Ras decreasing expression as grade increased, in groups LFCO and HFCO(P). HFOO(P) tumours exhibited a higher staining in high-grade carcinomas compared to the similar malignant tumours of the two other dietary groups. These data suggest that dietary lipids influence the clinical behaviour and the morphological malignancy of the experimental mammary carcinogenesis, according to the type of fat, without altering p21Ha-Ras expression. Nevertheless, this expression could be affected by the malignancy of tumours, probably through a post-translational event.
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