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TICA: Transcriptional Interaction and Coregulation Analyzer

Genomics, Proteomics & Bioinformatics 2018年第5期16卷 342-353页

作者： Stefano perna Pietro Pinoli Stefano Ceri Limsoon Wong Dipartimento di Elettronica Informazione e Bioingegneria Politecnico di Milano School of Computing National University of Singapore

Transcriptional regulation is critical to cellular processes of all organisms. Regulatory mechanisms often involve more than one transcription factor(TF) from different families, binding together and attaching to the DNA as a single complex. However, only a fraction of the regulatory partners of each TF is currently known. In this paper, we present the Transcriptional Interaction and Coregulation Analyzer(TICA), a novel methodology for predicting heterotypic physical interaction of TFs. TICA employs a data-driven approach to infer interaction phenomena from chromatin immunoprecipitation and sequencing(ChIP-seq) data. Its prediction rules are based on the distribution of minimal distance couples of paired binding sites belonging to different TFs which are located closest to each other in promoter regions. Notably, TICA uses only binding site information from input ChIP-seq experiments, bypassing the need to do motif calling on sequencing data. We present our method and test it on ENCODE ChIP-seq datasets, using three cell lines as reference including HepG2, GM12878, and K562. TICA positive predictions on ENCODE ChIP-seq data are strongly enriched when compared to protein complex(CORUM) and functional interaction(BioGRID) databases. We also compare TICA against both motif/ChIP-seq based methods for physical TF–TF interaction prediction and published literature. Based on our results, TICA offers significant specificity(average 0.902) while maintaining a good recall(average 0.284) with respect to CORUM, providing a novel technique for fast analysis of regulatory effect in cell lines. Furthermore, predictions by TICA are complementary to other methods for TF–TF interaction prediction(in particular, TACO and CENTDIST). Thus, combined application of these prediction tools results in much improved sensitivity in detecting TF–TF interactions compared to TICA alone(sensitivity of 0.526 when combining TICA with TACO and 0.585 when combining with CENTDIST)with little compromise

关键词： Transcription factors Coregulation Protein–protein interactions Machine learning Data-driven analysis

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Search for two-neutrino double-beta decay of^(136)Xe to the 0^(+)_(1)excited state of 136Ba with the complete EXO-200 dataset

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Chinese Physics C 2023年第10期47卷 1-9页

作者： S.Al Kharusi G.Anton I.Badhrees P.S.Barbeau D.Beck V.Belov T.Bhatta M.Breidenbach T.Brunner G.F.Cao W.R.Cen C.Chambers B.Cleveland M.Coon A.Craycraft T.Daniels L.Darroch S.J.Daugherty J.Davis S.Delaquis A.Der Mesrobian-Kabakian R.DeVoe J.Dilling A.Dolgolenko M.J.Dolinski J.Echevers W.Fairbank Jr. D.Fairbank J.Farine S.Feyzbakhsh P.Fierlinger Y.S.Fu D.Fudenberg P.Gautam R.Gornea G.Gratta C.Hall E.V.Hansen J.Hoessl P.Hufschmidt M.Hughes A.Iverson A.Jamil C.Jessiman M.J.Jewell A.Johnson A.Karelin L.J.Kaufman T.Koffas R.Krücken A.Kuchenkov K.S.Kumar Y.Lan A.Larson B.G.Lenardo D.S.Leonard G.S.Li S.Li Z.Li C.Licciardi Y.H.Lin R.MacLellan T.McElroy T.Michel B.Mong D.C.Moore K.Murray O.Njoya O.Nusair A.Odian I.Ostrovskiy a.perna A.Piepke A.Pocar F.Retière A.L.Robinson P.C.Rowson J.Runge S.Schmidt D.Sinclair K.Skarpaas A.K.Soma V.Stekhanov M.Tarka S.Thibado J.Todd T.Tolba T.I.Totev R.Tsang B.Veenstra V.Veeraraghavan P.Vogel J.-L.Vuilleumier M.Wagenpfeil J.Watkins M.Weber L.J.Wen U.Wichoski G.Wrede S.X.Wu Q.Xia D.R.Yahne L.Yang Y.-R.Yen O.Ya.Zeldovich T.Ziegler 无 Physics Department McGill UniversityMontrealQuebec H3A 2T8Canada Erlangen Centre for Astroparticle Physics(ECAP) Friedrich-Alexander-University Erlangen-NürnbergErlangen 91058Germany Physics Department Carleton UniversityOttawaOntario K1S 5B6Canada Department of Physics Duke Universityand Triangle Universities Nuclear Laboratory(TUNL)DurhamNorth Carolina 27708USA Physics Department University of IllinoisUrbana-ChampaignIllinois 61801USA Institute for Theoretical and Experimental Physics named by A.I.Alikhanov of National Research Centre“Kurchatov Institute” Moscow 117218Russia Department of Physics University of South DakotaVermillionSouth Dakota 57069USA SLAC National Accelerator Laboratory Menlo ParkCalifornia 94025USA TRIUMF VancouverBritish Columbia V6T 2A3Canada Institute of High Energy Physics Beijing 100049China Department of Physics Laurentian UniversitySudburyOntario P3E 2C6Canada Physics Department Colorado State UniversityFort CollinsColorado 80523USA Department of Physics and Physical Oceanography University of North Carolina at WilmingtonWilmingtonNC 28403USA Physics Department and CEEM Indiana UniversityBloomingtonIndiana 47405USA Physics Department Stanford UniversityStanfordCalifornia 94305USA Department of Physics Drexel UniversityPhiladelphiaPennsylvania 19104USA Amherst Center for Fundamental Interactions and Physics Department University of MassachusettsAmherstMA 01003USA Technische Universität München Physikdepartment and Excellence Cluster UniverseGarching 80805Germany Physics Department University of MarylandCollege ParkMaryland 20742USA Department of Physics and Astronomy University of AlabamaTuscaloosaAlabama 35487USA Wright Laboratory Department of PhysicsYale UniversityNew HavenConnecticut 06511USA IBS Center for Underground Physics Daejeon 34126Korea Department of Physics and Astronomy Stony Brook UniversitySUNYStony BrookNew York 11794USA Kellogg Lab CaltechPasadenaCalifornia 91125USA LHEP Albert Einstein CenterUniversi

A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminate signal from background *** detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of *** the addition of the Phase II dataset taken with an upgraded detector,the median 90%confidence level half-life sensitivity of 2νββdecay to the 0+1 state of 136Ba is 2.9×10^(24)yr using a total^(136)Xe exposure of 234.1 kg *** statistically significant evidence for 2νββdecay to the 0^(+)_(1)state is observed,leading to a lower limit of T2ν1/2(0^(+)→0^(+)_(1))>1.4×10^(24)yr at 90%confidence level,improved by 70%relative to the current world's best constraint.

关键词： EXO-200 experiment neutrinoless double beta decay excited state

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Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes

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Neural Regeneration Research 2020年第9期15卷 1757-1766页

作者： Massimo Santoro Roberto Piacentini Alessia.perna Eugenia Pisano Anna Severino Anna Modoni Claudio Grassi Gabriella Silvestri IRCCS Fondazione Don Carlo Gnocchi MilanItaly Department of Neuroscience Universita Cattolica del Sacro CuoreRomeItaly Department of Cardiovascular and Thoracic Sciences Universita Cattolica del Sacro CuoreRomeItaly Fondazione Policlinico Universitario A.Gemelli IRCCS RomeItaly

Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014.

关键词： alternative splicing calcium homeostasis CUG-BP1 foci MBNL1 myotonic dystrophy type 1 myotubes resveratrol

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Stepwise approach and surgery for gallbladder adenomyomatosis: a mini-review

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Hepatobiliary & Pancreatic Diseases International 2013年第2期12卷 136-142页

作者： Gianluca Pellino Guido Sciaudone Giuseppe Candilio Giuseppe perna Antonio Santoriello Silvestro Canonico Francesco SelvaggiAuthor Unit of General and Geriatric Surgery School of Medicine Second University of Naples

BACKGROUND: Gallbladder adenomyomatosis (GBA) is a hyperplastic disease affecting the wall of the gallbladder, with some typical features. It has historically been considered a benign condition, nevertheless recent reports highlighted a potential role of GBA in predisposing to malignancies of the gallbladder. DATA SOURCES: We reviewed the literature concerning GBA from its identification until July 2012. Owing to the relative rarity of the disease, studies often are case reports or case series. Thus we herein report a summary of the key-points concerning diagnosis and treatment of GBA, easily applicable in everyday practice, rather than a systematic review. Also, results are integrated with our recent experience. RESULTS: In our experience, we observed a trend toward an increase of GBA during the last years, probably due to enhanced ultrasonographic technical advancements and physician’s expertise. GBA has distinctive imaging features. Several recent reports highlight the potential risk of cancer associated with GBA; however the disease is still classified as a benign condition. Although its correlation with malignancy has not been demonstrated, it is prudent to recommend cholecystectomy in some cases. However, in selected asymptomatic patients, a wait-and-see policy is a viable alternative. We propose an algorithm, based on GBA pathological pattern (diffuse, segmental, localized or fundal), suitable for ***: In symptomatic patients and if the diagnosis is doubtful, cholecystectomy is mandatory. Postponing surgery is an option to be offered to asymptomatic patients with low-risk GBA pattern who adhere to scheduled follow-ups.

关键词： gallbladder adenomyomatosis gallbladder carcinoma cholecystectomy ultrasonography

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Very low calorie ketogenic diet and common rheumatic disorders:A case report

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World Journal of Clinical Cases 2023年第9期11卷 1985-1991页

作者： Mariangela Rondanelli Zaira Patelli Clara Gasparri Francesca Mansueto Cinzia Ferraris Mara Nichetti Tariq A Alalwan Ignacio Sajoux Roberto Maugeri Simone perna Department of Public Health Experimental and Forensic MedicineUnit of Human and Clinical NutritionIRCCS Mondino FoundationPavia 27100Italy Endocrinology and Nutrition Unit Azienda di Servizi alla Persona"Istituto Santa Margherita"University of PaviaPavia 27100Italy Food Education and Sport Nutrition Laboratory Department of Public HealthExperimental and Forensic MedicineUniversity of PaviaPavia 27100Italy Department of Biology College of ScienceUniversity of BahrainSakhir 32038Bahrain Chief Scientific Office Medical Department Pronokal GroupBarcelona 08001Spain Medical Direction PronoKal GroupSavigliano 12038Italy

BACKGROUND The scientific literature provides evidence that nutritional ketosis can be an important support in the treatment of pathologies in which inflammation is present,as recent studies have shown that ketone bodies have anti-inflammatory activity in numerous diseases,including rheumatic *** report the case of a 22-year-old woman with class I obesity and juvenile idiopathic arthritis who started treatment with a very low calorie ketogenic diet(VLCKD).CASE SUMMARY The patient was a 22-year-old woman diagnosed with juvenile idiopathic arthritis at age 4 years and with a body mass index(BMI)of 30.8 kg/m2,waist circumference(WC)80 cm,fat mass(FM)28.1 kg,free FM 45.7 kg,and visceral adipose tissue(VAT)3.5 kg,assessed on bioimpedance *** was treated using a commercial VLCKD weight-loss program(PNK®method);this program provides high-biological-value protein preparations and natural *** protein preparation contains 15 g protein,4 g carbohydrate,3 g fat,and 50 mg omega-3 docosahexaenoic acid,with an energy content of 90–120 *** four months on the program,the BMI was 28.6 kg/m2,WC 73 cm,FM 23.2 kg,free FM 41.9 kg,and VAT 2.9 *** VLCKD enabled the patient to reach her target weight and to reduce her joint pain and *** inflammatory indices also normalized.

关键词： Very low calorie ketogenic diet Inflammation PNK

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