TRADES: A new software to derive orbital parameters from observed transit times and radial velocities. Revisiting Kepler-11 and Kepler-9

Aims. With the purpose of determining the orbital parameters of exoplanetary systems from observational data, we have developed a software, named TRADES (TRAnsits and Dynamics of Exoplanetary Systems), to simultaneously fit observed radial velocities and transit times data. Methods. We implemented a dynamical simulator for N-body systems, which also fits the available data during the orbital integration and determines the best combination of the orbital parameters using grid search, $\chi^2$ minimization, genetic algorithms, particle swarm optimization, and bootstrap analysis. Results. To validate TRADES, we tested the code on a synthetic three-body system and on two real systems discovered by the Kepler mission: Kepler-9 and Kepler-11. These systems are good benchmarks to test multiple exoplanet systems showing transit time variations (TTVs) due to the gravitational interaction among planets. We have found that orbital parameters of Kepler-11 planets agree well with the values proposed in the discovery paper and with a a recent work from the same authors. We analyzed the first three quarters of Kepler-9 system and found parameters in partial agreement with discovery paper. Analyzing transit times (T0s) covering 12 quarters of Kepler data, that we have found a new best-fit solution. This solution outputs masses that are about 55% of the values proposed in the discovery paper; this leads to a reduced semi-amplitude of the radial velocities of about 12.80 m/s.Comment: 14 pages, 13 figures, 6 tables; accepted for publication in Astronomy & Astrophysics, and corrected by the Language Edito

Heparanase and Renal Fibrosis

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A case of tension-type headache in fibromyalgia

Ref.: Ms. No. TJHP-D-10-00029R1 A 57 years-old-woman was admitted to our ward for a daily tension-type headache, non responsive to usual pharmacological treatment. Five years ago she underwent a hysterectomy. Since then, she referred muscular rigor of the neck and the shoulder girdle, intense constrictive pain localized in the occipital spine. She also reported weakness of the upper and lower limbs, tingling, tremors and difficulties in walking and climbing. She referred widespread pain, unusually severe, above all at joints and muscles, without any sign of inflammation at clinical examination. The diagnosis of a connective tissue was excluded, remaining the diagnosis of tension-type headache in Fibromyalgia the most probable one. The patient has been treated with antidepressants, anxiolytics, and antiepileptic drugs with improvement of the symptoms

A PSF-based approach to Kepler/K2data – III. Search for exoplanets and variable stars within the open cluster M 67 (NGC 2682)

In the third paper of this series we continue the exploitation of Kepler/K2 data in dense stellar fields using our PSF-based method. This work is focused on a ~720-arcmin^2 region centred on the Solar-metallicity and Solar-age open cluster M 67. We extracted light curves for all detectable sources in the Kepler channels 13 and 14, adopting our technique based on the usage of a high-angular-resolution input catalogue and target-neighbour subtraction. We detrended light curves for systematic errors, and searched for variables and exoplanets using several tools. We found 451 variables, of which 299 are new detection. Three planetary candidates were detected by our pipeline in this field. Raw and detrended light curves, catalogues, and K2 stacked images used in this work will be released to the community.Comment: 14 pages, 9 figures (1 at low resolution), 3 tables. Accepted for publication in MNRAS on August 24, 2016. Electronic materials are available at http://groups.dfa.unipd.it/ESPG/Kepler-K2.htm

Inhibition of heparanase protects against chronic kidney dysfunction following ischemia/reperfusion injury

Renal ischemia/reperfusion (I/R) injury occurs in patients undergoing renal transplantation and with acute kidney injury and is responsible for the development of chronic allograft dysfunction as characterized by parenchymal alteration and fibrosis. Heparanase (HPSE), an endoglycosidase that regulates EMT and macrophage polarization, is an active player in the biological response triggered by ischemia/reperfusion (I/R) injury. I/R was induced in vivo by clamping left renal artery for 30 min in wt C57BL/6J mice. Animals were daily treated and untreated with Roneparstat (an inhibitor of HPSE) and sacrificed after 8 weeks. HPSE, fibrosis, EMT-markers, inflammation and oxidative stress were evaluated by biomolecular and histological methodologies together with the evaluation of renal histology and measurement of renal function parameters. 8 weeks after I/R HPSE was upregulated both in renal parenchyma and plasma and tissue specimens showed clear evidence of renal injury and fibrosis. The inhibition of HPSE with Roneparstat-restored histology and fibrosis level comparable with that of control. I/R-injured mice showed a significant increase of EMT, inflammation and oxidative stress markers but they were significantly reduced by treatment with Roneparstat. Finally, the inhibition of HPSE in vivo almost restored renal function as measured by BUN, plasma creatinine and albuminuria. The present study points out that HPSE is actively involved in the mechanisms that regulate the development of renal fibrosis arising in the transplanted organ as a consequence of ischemia/reperfusion damage. HPSE inhibition would therefore constitute a new pharmacological strategy to reduce acute kidney injury and to prevent the chronic pro-fibrotic damage induced by I/R

Validation of TESS exoplanet candidates orbiting solar analogues in the all-sky PLATO input catalogue

Funding: G.M. acknowledges the support of the Erasmus+ Programme of the European Union and of the doctoral grant funded by the University of Padova and by the Italian Ministry of Education, University and Research (MIUR). G.M. is also grateful to the Centre for Exoplanet Science, University of St Andrews (StA-CES) for hospitality and computing resources. GPi, LBo, VNa, and FZM acknowledge the funding support from Italian Space Agency (ASI) regulated by ‘Accordo ASI-INAF n. 2013-016-R.0 del 9 luglio 2013 e integrazione del 9 luglio 2015 CHEOPS Fasi A/B/C’. We acknowledge the support of PLATO ASI-INAF agreements n.2015-019-R0-2015 and n. 2015-019-R.1-2018. T.G.W. and A.C.C. acknowledge support from STFC consolidated grant number ST/V000861/1, and UKSA grant ST/R003203/1.The Transiting Exoplanet Survey Satellite (TESS) is focusing on relatively bright stars and has found thousands of planet candidates. However, mainly because of the low spatial resolution of its cameras (≈ 21 arcsec/pixel), TESS is expected to detect several false positives (FPs); hence, vetting needs to be done. Here, we present a follow-up program of TESS candidates orbiting solar-analogue stars that are in the all-sky PLATO input catalogue. Using Gaia photometry and astrometry we built an absolute colour-magnitude diagram and isolated solar-analogue candidates’ hosts. We performed a probabilistic validation of each candidate using the vespa software and produced a prioritized list of objects that have the highest probability of being genuine transiting planets. Following this procedure, we eliminated the majority of FPs and statistically vetted 23 candidates. For this remaining set, we performed a stellar neighbourhood analysis using Gaia Early Data Release 3 and centroid motion tests, greatly enhancing the on-target probability of 12 of them. We then used publicly available high-resolution imaging data to confirm their transit source and found five new, fully validated planets. For the remaining candidates, we propose on-off photometry to further refine the list of genuine candidates and prepare for the subsequent radial velocity follow-up.Publisher PDFPeer reviewe

Eparanasi: un nuovo biomarker di fibrosi e un potenziale target farmacologico per ridurre la progressione del danno renale cronico

Il trattamento poli-farmacologico ha determinato, nel corso degli anni, un significativo rallentamento della progressione della malattia renale cronica verso lo stadio di uremia terminale, ma siamo ancora distanti dallo sviluppo di interventi terapeutici in grado di bloccare questo inesorabile e irreversibile processo. Studi clinico-patologici hanno chiaramente dimostrato che il principale elemento coinvolto nel danno renale è la fibrosi tubulo-interstiziale e che il meccanismo patogenetico alla base di questa condizione ha inizio in larga parte nel compartimento tubulare. In particolare, il processo di transizione epitelio-mesenchimale gioca un ruolo importante nella genesi del danno cronico. Durante questo processo, le cellule epiteliali tubulari subiscono un incremento significativo di markers di superficie di natura mesenchimale e, grazie al rimodellamento del citoscheletro e alla degradazione della membrana basale, sono in grado di migrare nell'interstizio dove svolgono un ruolo chiave nel processo patogenetico. In questo contesto, sembra avere un ruolo chiave l'enzima eparanasi, una endo-β-D-glucuronidasi che taglia le catene dell'eparan-solfato a livello di siti specifici intracatena, e partecipa attivamente alla degradazione e al rimodellamento della matrice extracellulare. La degradazione dei vari costituenti dell'ECM, inclusi i proteoglicani eparan-solfato fa-vorisce il rilascio di fattori trofici quali il FGF-2 che induce l'espressione dei marcatori mesenchimali alfa-SMA, VIM e FN, porta alla degradazione della membrana basale mediante la secrezione di metalloproteinasi della matrice ed aumenta la motilità cellulare. L'epressione dell'eparanasi è regolata da fattori di trascrizione, dalla metilazione del DNA e da varie molecole endogene. L'importanza di questo enzima è stata confermata clinicamente dal riscontro di una sua iperespressione in preparati istologici di biopsie effettuate in soggetti affetti da nefropatie croniche (per esempio, nefropatia diabetica). Pertanto visto l'importante ruolo dell'eparanasi sono in fase di standardizzazione numerose strategie per inibire la sua espressione genica e/o la sua attività enzimatica. Infine, è stato proposto il suo possibile utilizzo come biomarker di progressione del danno tubulo-interstiziale da utilizzare routinariamente in ambito nefrologico

In vitro identification of new transcriptomic and miRNomic profiles associated with pulmonary fibrosis induced by high doses everolimus: Looking for new pathogenetic markers and therapeutic targets

The administration of Everolimus (EVE), a mTOR inhibitor used in transplantation and cancer, is often associated with adverse effects including pulmonary fibrosis. Although the underlying mechanism is not fully clarified, this condition could be in part caused by epithelial to mesenchymal transition (EMT) of airway cells. To improve our knowledge, primary bronchial epithelial cells (BE63/3) were treated with EVE (5 and 100 nM) for 24 h. EMT markers (α-SMA, vimentin, fibronectin) were measured by RT-PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter. mRNA and microRNA profiling were performed by Illumina and Agilent kit, respectively. Only high dose EVE increased EMT markers and reduced the transepithelial resistance of BE63/3. Bioinformatics showed 125 de-regulated genes that, according to enrichment analysis, were implicated in collagen synthesis/metabolism. Connective tissue growth factor (CTGF) was one of the higher up-regulated mRNA. Five nM EVE was ineffective on the pro-fibrotic machinery. Additionally, 3 miRNAs resulted hyper-expressed after 100 nM EVE and able to regulate 31 of the genes selected by the transcriptomic analysis (including CTGF). RT-PCR and western blot for MMP12 and CTGF validated high-throughput results. Our results revealed a complex biological network implicated in EVE-related pulmonary fibrosis and underlined new potential disease biomarkers and therapeutic targets

In vitro effects of interleukin (IL)-1 beta inhibition on the epithelial-to-mesenchymal transition (EMT) of renal tubular and hepatic stellate cells

BACKGROUND: The epithelial to mesenchymal transition (EMT) is a multi-factorial biological mechanism involved in renal and hepatic fibrosis and the IL-1 beta has been assumed as a mediator of this process although data are not exhaustive. Therefore, the aim of our study was to evaluate the role of this cytokine in the EMT of renal proximal tubular epithelial cells (HK-2) and stellate cells (LX-2) and the protective/anti-fibrotic effect of its inhibition by Canakinumab (a specific human monoclonal antibody targeted against IL-1beta). METHODS: Both cell types were treated with IL-1 beta (10 ng/ml) for 6 and 24 h with and without Canakinumab (5 \u3bcg/ml). As control we used TGF-beta (10 ng/ml). Expression of EMT markers (vimentin, alpha-SMA, fibronectin) were evaluated through western blotting and immunofluorescence. Genes expression for matrix metalloproteinases (MMP)-2 was measured by Real-Time PCR and enzymatic activity by zymography. Cellular motility was assessed by scratch assay. RESULTS: IL-1 beta induced a significant up-regulation of EMT markers in both cell types and increased the MMP-2 protein expression and enzymatic activity, similarly to TGF-beta. Moreover, IL-1 beta induced a higher rate of motility in HK-2. Canakinumab prevented all these modifications in both cell types. CONCLUSIONS: Our results clearly demonstrate the role of IL-1 beta in the EMT of renal/stellate cells and it underlines, for the first time, the therapeutic potential of its specific inhibition on the prevention/minimization of organ fibrosis