Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism

© 2015 Wiley Periodicals, Inc. Acknowledgement Grant sponsor: State of Lower Saxony-Israel Research Cooperation; Grant number: ZN2035; Grant sponsor:German Research Council; Grant number: SFB/TRR43 and FOR1336; Grant sponsor: Parkinson UK; Grant number: K-1001; Grant sponsor: ProFutura Program (University of Gottingen); Grant sponsor: Else Kroner Fresenius Stiftung;Grant number: A69/2010; Grant sponsor: DFG; Grant number: WE 3547/4–1; Grant sponsor: US National Multiple Sclerosis Society; Grant numbers: NMSS; PP 1660. The authors thank Elke Pralle, Susanne Kiecke and Caroline Jaß (University of Gottingen) for excellent technical assistance.Peer reviewedPostprin

Visualization and analysis of cellular & Twitter data using qgis

The study is to understand individual presence and movement in Friuli Venezia Giulia region. It is important for tourism planning, hazard management, business marketing, implementing government lifetime policies and benefit. The aim of this study is achieved by advanced web 2.0 applications. We need real time and geo-located data to monitor the inflow of tourist and to come up with effective promoting and benefiting plans for tourism, the evacuation and mitigation strategies during hazards to protect social life and environment with less infrastructure damage, marketing plans for advertising or selling of products. Despite wide spread success in predicting specific aspects of human behavior by social media information, a little attention is given to twitter and cell phone data. Accessibility to detailed human movements with fine spatial and temporal granularity is challenging due to confidentiality and safety reasons. With rapid development of web2.0 applications people can post about events, share opinion and emotions online. Using twitter data, how short term travelers, such as tourists, can be recognized and how their travel pattern can be analyzed. Study of finding tourist dynamics such as arriving and outgoing of tourist, sum of trips, sum of days and night spent, number of unique visitors, country of residence, main destination, secondary destination, transits pass through, repeat visits are achieved using CDR (call detail records) and DDR (data detail records)

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

Ultrasound findings of BK polyomavirus-associated nephropathy in renal transplant patients

none12BK polyomavirus (BKV) is an emerging pathogen in immunocompromised patients. BKV infection occurs in 1-9 % of renal transplants and causes chronic nephropathy or graft loss. Diagnosis of BKV-associated nephropathy (BKVAN) is based on detection of viruria then viremia and at least a tubule-interstitial nephritis at renal biopsy. This paper describes the ultrasound and color Doppler (US-CD) features of BKVAN. Seventeen patients affected by BKVAN were studied using a linear bandwidth 7-12 MHz probe. Ultrasound showed a widespread streak-like pattern with alternating normal echoic and hypoechoic streaks with irregular edges from the papilla to the cortex. Renal biopsy performed in hypoechoic areas highlighted the typical viral inclusions in tubular epithelial cells. Our experience suggests a possible role for US-CD in the non-invasive diagnosis of BKVAN when combined with blood and urine screening tests. US-CD must be performed with a high-frequency linear probe to highlight the streak-like pattern of the renal parenchyma.noneDugo, Mauro; Mangino, Margherita; Meola, Mario; Petrucci, Ilaria; Valente, Maria Luisa; Laurino, Licia; Stella, Mario; Mastrosimone, Stefania; Brunello, Anna; Virgilio, Bice; Rizzolo, Monica; Maresca, Maria CristinaDugo, Mauro; Mangino, Margherita; Meola, Mario; Petrucci, Ilaria; Valente, Maria Luisa; Laurino, Licia; Stella, Mario; Mastrosimone, Stefania; Brunello, Anna; Virgilio, Bice; Rizzolo, Monica; Maresca, Maria Cristin

MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner

Abstract Background Fibroblasts are crucial mediators of tumor-stroma cross-talk through synthesis and remodeling of the extracellular matrix and production of multiple soluble factors. Nonetheless, little is still known about specific determinants of fibroblast pro-tumorigenic activity in lung cancer. Here, we aimed at understanding the role of miRNAs, which are often altered in stromal cells, in reprogramming fibroblasts towards a tumor-supporting phenotype. Methods We employed a co-culture-based high-throughput screening to identify specific miRNAs modulating the pro-tumorigenic potential of lung fibroblasts. Multiplex assays and ELISA were instrumental to study the effect of miRNAs on the secretome of both primary and immortalized lung fibroblasts from lung cancer patients and to evaluate plasmatic levels of HGF in heavy smokers. Direct mRNA targeting by miRNAs was investigated through dual-luciferase reporter assay and western blot. Finally, the pro-tumorigenic activity of fibroblasts and their conditioned media was tested by employing in vitro migration experiments and mouse xenografts. Results We identified miR-16 as a master regulator of fibroblast secretome and showed that its upregulation reduces HGF secretion by fibroblasts, impairing their capacity to promote cancer cell migration. This effect is due to a pleiotropic activity of miR-16 which prevents HGF expression through direct inhibition of FGFR-1 signaling and targeting of HGF mRNA. Mechanistically, miR-16 targets FGFR-1 downstream mediator MEK1, thus reducing ERK1/2 activation. Consistently, chemical or genetic inhibition of FGFR-1 mimics miR-16 activity and prevents HGF production. Of note, we report that primary fibroblast cell lines derived from lungs of heavy smokers express reduced miR-16 levels compared to those from lungs not exposed to smoke and that HGF concentration in heavy smokers’ plasma correlates with levels of tobacco exposure. Finally, in vivo experiments confirmed that restoration of miR-16 expression in fibroblasts reduced their ability to promote tumor growth and that HGF plays a central role in the pro-tumorigenic activity of fibroblasts. Conclusions Overall, these results uncover a central role for miR-16 in regulating HGF production by lung fibroblasts, thus affecting their pro-tumorigenic potential. Correlation between smoking exposure and miR-16 levels could provide novel clues regarding the formation of a tumor-proficient milieu during the early phases of lung cancer development

Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy.

ABSTRACT Background. Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the 25 prevalence of the association has not been assessed yet. Methods. We screened 28 families with AD FSGS and identified eight INF2 mutations in 9 families (32 patients overall), 3 of which were new. Mutations were in all cases localized in the diaphanous-inhibitory domain (DID) of the protein. 30 Results. Clinical features associated with INF2 mutations in our patient cohort included mild proteinuria (1.55 g/L; range 1\u20132.5) and haematuria as a unique symptom that was recognized at a median age of 21.75 years (range 8\u201330). Eighteen patients developed ESRD during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 35 are healthy at 45 and 54 years of age. CMT was diagnosed in four cases (12.5%); one of these patients presented an already known mutation on exon 2 of INF2, whereas the other patients presented the same mutation on exon 4, a region that was not previously associated with CMT. 40 Conclusions. We confirmed the high incidence of INF2 mutations in families with AD FSGS. The clinical phenotype was mild at the onset of the disease, but evolution to ESRD was frequent. The incidence of CMT has been for the first time here calculated to be 12.5% of mutation carriers. Our 45 findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model

Additional file 1: of MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner

Figure S1. In vitro characterization of the immortalized CAF154 fibroblasts. The constitutive high levels of hTERT in all the fibroblasts transduced with retroviral particles (examples shown in A) were confirmed. Nevertheless, almost all the fibroblasts stopped growing after a few population doublings (PDs) and underwent senescence (B) with the exception of CAF154-hTERT cells, which expressed high levels of hTERT (A), showed no signs of senescence (B), and proliferated in a continuous fashion in vitro (C). Cumulative PDs were calculated at the end of every passage in relation to the cell number at the first passage. Of note, despite the immortalization process, CAF154-hTERT maintained the capacity to promote the growth of the adjacent cancer cells in co-culture experiments (D). (TIFF 422 kb

Additional file 5: of MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner

Figure S5. FGF-1 and FGF-2 levels are not affected by miR-16. Levels of FGF-1 and FGF-2 in the CM of CAF154-hTERT fibroblasts were transfected with control miR-C and miR-16, collected 72 h after the transfection, and analyzed by multiplex analysis. (TIFF 81 kb

Additional file 3: of MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner

Figure S3. Potential miR-16 target regions in HGF, FGFR-1, and MEK1 mRNA. FGFR-1 3′UTR was mutagenized to delete to potential miR-16-directed region. (TIFF 86 kb

Additional file 2: of MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner

Figure S2. In vivo characterization of the immortalized CAF154 fibroblasts. To exclude that the ectopic expression of hTERT and the prolonged culturing had affected the capacity of the CAFs to promote tumor engraftment rate, we characterized the pro-tumorigenic properties CAF154-hTERT cells in vivo by co-injecting CAF154-hTERT and A549 cell lines in immunocompromized mice. We found that the ectopic expression of hTERT did not affect the pro-tumorigenic capability of CAFs to promote the tumor take (A), the volume of the subcutaneous nodules (B), and the dissemination of human cells to the lungs (C) compared to the non-transfected counterpart CAF154 cell line. Based on this evidence, we concluded that the immortalization process did not alter the pro-tumorigenic features of CAF154 cells both in vitro and in vivo. (TIFF 166 kb