Large-scale radio morphology and nuclear accretion in FRII-low-excitation radio galaxies

Radio galaxies (RGs) are among the most energetic manifestation of the AGN phenomenon and, as such, are extraordinarily relevant to address important unknowns relating accretion and ejection, and to investigate the role of the surrounding environment in shaping the radio morphology. The best candidates for this pioneering study are the RGs classified as FRII-LERGs, since they show both a radio morphology typical of powerful RGs (expected to have a standard accretion disc) and have an inefficient engine, as suggested by their optical spectra. In this work we study the X-ray properties of all the FRII-LERGs of the 3CR sample at z<0.3 testing three possible scenarios: (i) FRII-LERGs are recently switched-off high-excitation RGs (HERGs) with efficient accretion disc; (ii) FRII-LERGs are strongly absorbed HERGs; (iii) FRII-LERGs are inefficient accretors and their large-scale radio emission is mainly determined by the environment. These results will be further supplemented by multi-wavelength observations, with particular attention to the radio band

Valutazione al SEM dell’assorbimento di fluoro nei tessuti duri dentari in seguito ad irraggiamento con laser ad Erbio e a Diodi.

Gli incoraggianti risultati ottenuti nel presente lavoro portano a indicare come il trattamento dell’ipersensibilità dentinale con gel al fluoro e sorgenti laser, utilizzate secondo i protocolli indicati, rappresenti oggi il miglior standard clinico disponibile per taleindicazione. L’interpretazione dei risultati ottenuti porta ad ipotizzare il trattamento con gel di fluoro e laser a Diodi comedi elezione per il trattamento dell’ipersensibilità dentinaleai colletti per il maggior assorbimento di fluoro ottenuto. Iltrattamento con gel di fluoro e laser ad Erbio comunque nonè trascurabile, e lascia spazio per ulteriori analisi a diversiparametri d’applicazione

Urinary MicroRNA Profiling in the Nephropathy of Type 1 Diabetes

Background: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. Methods and Findings: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. Conclusions: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes. © 2013 Argyropoulos et al

Restoration of Podocyte Structure and Improvement of Chronic Renal Disease in Transgenic Mice Overexpressing Renin

Proteinuria is a major marker of the decline of renal function and an important risk factor of coronary heart disease. Elevated proteinuria is associated to the disruption of slit-diaphragm and loss of podocyte foot processes, structural alterations that are considered irreversible. The objective of the present study was to investigate whether proteinuria can be reversed and to identify the structural modifications and the gene/protein regulation associated to this reversal.We used a novel transgenic strain of mouse (RenTg) that overexpresses renin at a constant high level. At the age of 12-month, RenTg mice showed established lesions typical of chronic renal disease such as peri-vascular and periglomerular inflammation, glomerular ischemia, glomerulosclerosis, mesangial expansion and tubular dilation. Ultrastructural analysis indicated abnormal heterogeneity of basement membrane thickness and disappearance of podocyte foot processes. These structural alterations were accompanied by decreased expressions of proteins specific of podocyte (nephrin, podocin), or tubular epithelial cell (E-cadherin and megalin) integrity. In addition, since TGFbeta is considered the major pro-fibrotic agent in renal disease and since exogenous administration of BMP7 is reported to antagonize the TGFbeta-induced phenotype changes in kidney, we have screened the expressions of several genes belonging in the TGFbeta/BMP superfamily. We found that the endogenous inhibitors of BMPs such as noggin and Usag-1 were several-fold activated inhibiting the action of BMPs and thus reinforcing the deleterious action of TGFbeta.Treatment with an AT1 receptor antagonist, at dose that did not decrease arterial pressure, gradually reduced albuminuria. This decrease was accompanied by re-expression of podocin, nephrin, E-cadherin and megalin, and reappearance of podocyte foot processes. In addition, expressions of noggin and Usag-1 were markedly decreased, permitting thus activation of the beneficial action of BMPs.These findings show that proteinuria and alterations in the expression of proteins involved in the integrity and function of glomerular and renal epithelial phenotype are reversible events when the local action of angiotensin II is blocked, and provide hope that chronic renal disease can be efficiently treated

PINCH1 Is Transcriptional Regulator in Podocytes That Interacts with WT1 and Represses Podocalyxin Expression

Background: PINCH1, an adaptor protein containing five LIM domains, plays an important role in regulating the integrin-mediated cell adhesion, migration and epithelial-mesenchymal transition. PINCH1 is induced in the fibrotic kidney after injury, and it primarily localizes at the sites of focal adhesion. Whether it can translocate to the nucleus and directly participate in gene regulation is completely unknown. Methodology/Principal Findings: Using cultured glomerular podocytes as a model system, we show that PINCH1 expression was induced by TGF-β1, a fibrogenic cytokine that promotes podocyte dysfunction. Interestingly, increased PINCH1 not only localized at the sites of focal adhesions, but also underwent nuclear translocation after TGF-β1 stimulation. This nuclear translocation of PINCH1 was apparently dependent on the putative nuclear export/localization signals (NES/NLS) at its C-terminus, as deletion or site-directed mutations abolished its nuclear shuttling. Co-immunoprecipitation and pull-down experiments revealed that PINCH1 interacted with Wilms tumor 1 protein (WT1), a nuclear transcription factor that is essential for regulating podocyte-specific gene expression in adult kidney. Interaction of PINCH1 and WT1 was mediated by the LIM1 domain of PINCH1 and C-terminal zinc-finger domain of WT1, which led to the suppression of the WT1-mediated podocalyxin expression in podocytes. PINCH1 also repressed podocalyxin gene transcription in a promoter-luciferase reporter assay. Conclusion/Significance: These results indicate that PINCH1 can shuttle into the nucleus from cytoplasm in podocytes, wherein it interacts with WT1 and suppresses podocyte-specific gene expression. Our studies reveal a previously unrecognized, novel function of PINCH1, in which it acts as a transcriptional regulator through controlling specific gene expression. © 2011 Wang et al

Mechanisms and consequences of TGF-ß overexpression by podocytes in progressive podocyte disease

In patients with progressive podocyte disease, such as focal segmental glomerulosclerosis (FSGS) and membranous nephropathy, upregulation of transforming growth factor-ß (TGF-ß) is observed in podocytes. Mechanical pressure or biomechanical strain in podocytopathies may cause overexpression of TGF-ß and angiotensin II (Ang II). Oxidative stress induced by Ang II may activate the latent TGF-ß, which then activates Smads and Ras/extracellular signal-regulated kinase (ERK) signaling pathways in podocytes. Enhanced TGF-ß activity in podocytes may lead to thickening of the glomerular basement membrane (GBM) by overproduction of GBM proteins and impaired GBM degradation in podocyte disease. It may also lead to podocyte apoptosis and detachment from the GBM, and epithelial-mesenchymal transition (EMT) of podocytes, initiating the development of glomerulosclerosis. Furthermore, activated TGF-ß/Smad signaling by podocytes may induce connective tissue growth factor and vascular endothelial growth factor overexpression, which could act as a paracrine effector mechanism on mesangial cells to stimulate mesangial matrix synthesis. In proliferative podocytopathies, such as cellular or collapsing FSGS, TGF-ß-induced ERK activation may play a role in podocyte proliferation, possibly via TGF-ß-induced EMT of podocytes. Collectively, these data bring new mechanistic insights into our understanding of the TGF-ß overexpression by podocytes in progressive podocyte disease

Key fibrogenic mediators: Old players. Renin-angiotensin system

Interstitial fibrosis represents the final common pathway of any form of progressive renal disease. The severity of tubular interstitial damage is highly correlated to the degree of decline of renal function, even better than the glomerular lesions do. Angiotensin II (Ang II), the main effector of the renin-angiotensin system, is a critical promoter of fibrogenesis. It represents a nexus among glomerular capillary hypertension, barrier dysfunction, and renal tubular injury caused by abnormally filtered proteins. Transforming growth factor (TGF)-\u3b21 and reactive oxygen species (ROS) are the key mediators of the pro-fibrotic effect of Ang II causing apoptosis and epithelial-to-mesenchymal transition of the renal tubular epithelium. Recent studies link fibrosis to changes of microRNA (miRNA) modulated by Ang II through TGF-\u3b21, unraveling that antifibrotic action of Ang II antagonism is attributable to epigenetic control of fibrosis-associated genes. Other mechanisms of Ang II-induced fibrosis include ROS-dependent activation of hypoxia-inducible factor-1. Finally, Ang II via angiotensin type 1 receptor regulates the activation and transdifferentiation of pericytes and fibrocytes into scar-forming myofibroblasts. Detachment and phenotypic changes of the former can lead to the loss of peritubular capillaries and also contribute to hypoxia-dependent fibrosis

A structural equation modelling approach to explore consumers’ attitude towards sustainable wine

This paper investigates how environmental and socio-economic beliefs affect consumers attitude towards sustainable wine, and the main drivers during wine purchase. Data were collected with online questionnaire in 2013 from 513 Italian wine drinkers. The results of a structural equation model show that attitude towards sustainable wine is driven by both environmental and quality beliefs of sustainable wine, while is not affected by the economic dimension. Attitudes and quality beliefs affect consumer’s importance of sustainable aspects during wine purchase. This paper suggests that communication strategies should focus on sustainable issues to meet the need of environmentally-conscious consumers