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Tibolone m.dulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 com.lexes in the hippocam.us of aged m.le m.ce

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Neural Regeneration Research 2017年第4期12卷 588-595页

作者： Teresa Neri-Gom.z Judith Espinosa-Raya sofia Diaz Cintra Julia Segura-Uribe Sandra Orozco-Suarez Juan m.nuel Gallardo Christian Guerra-Araiza Unidad de Investigación m.dica en Farm.cología Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Ciudad de México México Laboratorio de Farm.cología Conductual Escuela Superior de Medicina Instituto Politécnico Nacional Plan de San Luis y Díaz Mirón Col. Sto. Tomás Ciudad de México México Departam.nto de Neurobiología del Desarrollo y Neurofisiología Instituto de Neurobiología Universidad Nacional Autónoma de México Campus Juriquilla Querétaro Querétaro México Enferm.dades Neurológicas (Neurological Diseases) Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Ciudad de México México Enferm.dades Nefrológicas (Kidney Diseases) Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Ciudad de Mexico Mexico

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid horm.nes m.y have a negative im.act on the form.tion of neurofibrillary tangles （NFTs）; these horm.nes can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Horm.ne replacem.nt therapy decreases NFTs, but it increases the risk of som. types of cancer. However, other synthetic horm.nes such as tibolone （TIB） have been used for horm.ne replacem.nt therapy. The aim.of this work was to evaluate the long-term.effects of TIB （0.01 m./kg and 1m./kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 com.lexes in the hippocam.us of aged m.le m.ce. We observed that the content of PHF-1 decreased with TIB adm.nistration. In contrast, no changes were observed in the active form.of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form.of Akt while increased that of p110 and p85. The content of CDK5 was differentially m.dified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with adm.nistration of low dose of TIB. Our results suggest a possible m.chanism.of action of TIB in the hippocam.us of aged m.le m.ce. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 com.lexes, TIB m.y m.dulate neuronal plasticity and regulate learning and m.m.ry processes.

关键词： nerve regeneration Tibolone hippocam.us aged m.ce sex steroids Akt GSK3β PI3K neuralplasticity Tau neurofibrillary tangles neural regeneration

Cross Skin Reactivity to Tyrosine Kinase Inhibitors in a Patient with Chronic m.elogenous Leukem.a

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Journal of Cancer Therapy 2013年第7期4卷 1141-1144页

作者： V. Broshtilova m. Balabanova Departm.nt of Derm.tology and Venereology Faculty of Medicine Sofia Medical University Sofia Bulgaria

Tyrosine kinase inhibitors (TKI) targeting the bcr-abl protein, c-kit and the platelet-derived growth factor receptors, are significant part of the pathogenic therapy of chronic m.elogenous leukem.a. A broad spectrum.of cutaneous side effects has been described with the clinical use of im.tinib m.sylate, ranging from.various acute rashes to toxic epiderm.l necrolysis. Herein, a case of cross skin toxicity to TKI in a patient with chronic m.elogenous leukem.a is presented. In the course of im.tinib m.sylate therapy the patient developed a grade 4 diffuse lichenoid drug eruption. Six m.nths after switching to nilotinib, hyperpigm.nted m.cules and patches spread over his trunk and extrem.ties. To date, few cases of cross skin reactivity to im.tinib and nilotinib have been described, none of which showing different clinical phenotypes. Further understanding of the underlying m.chanism. and leading to the developm.nt of skin rashes from.different class of TKI is im.ortant to highlight new drug targets and m.dify the current therapies to a level of m.xim.l efficacy.

关键词： Cross Toxicity Lichenoid Drug Reaction Hyperpigm.ntation

Quantitative m.ltiparam.tric m.gnetic resonance im.ging can aid non-alcoholic steatohepatitis diagnosis in a Japanese cohort

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World Journal of Gastroenterology 2021年第7期27卷 609-623页

作者： Kento Im.jo Louise Tetlow Andrea Dennis Elizabeth Shum.ayawonda sofia m.uchti Tim.thy J Kendall Eve Fryer Shogi Yam.naka Yasushi Honda Takaom. Kessoku Yuji Ogawa m.sato Yoneda Satoru Saito Catherine Kelly m.tt D Kelly Rajarshi Banerjee Atsushi Nakajim. Departm.nt of Gastroenterology and Hepatology Yokohama City University School of MedicineYokohama 236-0004Japan Innovation PerspectumOxford OX42LLUnited Kingdom Centre for Inflam.ation Research University of EdinburghEdinburghUnited KingdomEdinburgh EH164TJUnited Kingdom Departm.nt of Cellular Pathology Oxford University Hospitals NHS Foundation TrustOxford OX39DUUnited Kingdom Anatom.c and Clinical Pathology Departm.nt Yokohoma City University HospitalYokohoma 236-0004Japan Departm.nt of Gastroenterology Yokohama City University Graduate School of MedicineYokohama 236-0004Japan

BACKGROUND Non-invasive assessm.nt of non-alcoholic steatohepatitis(NASH)is increasing in desirability due to the invasive nature and costs associated with the current form.of assessm.nt;liver *** m.ltiparam.tric m.gnetic resonance im.ging(m.m.I)to m.asure liver fat(proton density fat fraction)and fibroinflam.atory disease[iron-corrected T1(cT1)],as well as elastography techniques[vibration-controlled transient elastography(VCTE)liver stiffness m.asure],m.gnetic resonance elastography(m.E)and 2D Shear-Wave elastography(SWE)to m.asure stiffness and fat(controlled attenuated param.ter,CAP)are em.rging alternatives which could be utilised as safe surrogates to liver *** To evaluate the agreem.nt of non-invasive im.ging m.dalities with liver biopsy,and their subsequent diagnostic accuracy for identifying NASH *** From.January 2019 to February 2020,Japanese patients suspected of NASH were recruited onto a prospective,observational study and were screened using noninvasive im.ging techniques;m.m.I with Liverm.ltiScan®,VCTE,m.E and *** were subsequently biopsied,and sam.les were scored by three independent *** diagnostic perform.nces of the non-invasive im.ging m.dalities were assessed using area under receiver operating characteristic curve(AUC)with the m.dian of the histology scores as the gold standard *** between all three independent pathologists was further explored using Krippendorff’s alpha(a)from.weighted kappa *** N=145 patients with m.an age of 60(SD:13 years.),39%fem.les,and 40%with body m.ss index≥30 kg/m. were included in the *** identifying patients with NASH,m. liver fat and cT1 were the strongest perform.ng individual m.asures(AUC:0.80 and 0.75 respectively),and the m.m.I m.trics com.ined(cT1 and m. liver fat)were the overall best non-invasive test(AUC:0.83).For identifying fibrosis≥1,m.E perform.d best(AUC:0.97),com.ared to VCTE-liver stiffness m.asure(AU

关键词： Corrected T1 Fibro-inflam.ation Non-invasive im.ging Non-alcoholic steatohepatitis m.ltiparam.tric m.gnetic resonance im.ging Non-alcoholic fatty liver disease

Population dynam.cs, pathogen detection and insecticide resistance of m.squito and sand fly in refugee cam.s, Greece

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Infectious Diseases of Poverty 2020年第2期9卷 50-62页

作者： Em.anouil Alexandras Fotakis loannis Apostolou Giantsis Javier Castells Sierra Filianna Tanti sofia Balaska Konstantinos m.vridis Sofoklis Kourtidis John Vontas Alexandra Chaskopoulou Departm.nt of Crop Science Pesticide Science LabAgricultural University of AthensAthensGreece Institute of m.lecular Biology and Biotechnology Foundation for Research and Technology HellasHeraklionCreteGreece European Biological Control Laboratory USDA-ARSThessalonikiGreece Departm.nt of Biology National and Kapodistrian University of AthensAthensGreece General Directorate of Public Health and Social Welfare Region of Central MacedoniaThessalonikiGreece

Background:As of 2015 thousands of refugees are being hosted in tem.orary refugee cam.s in *** populations,travelling and living under poor conditions with lim.ted access to healthcare are at a high risk of exposure to vector borne disease(VBD).This study sought to evaluate the risk for VBD transm.ssion within refugee cam.s in Greece by analyzing the m.squito and sand fly populations present,in light of designing effective and efficient context specific vector and disease control ***:A vector/pathogen surveillance network targeting m.squitoes and sand flies was deployed in four tem.orary refugee cam.s in *** collections were conducted bi-weekly during June-Septem.er 2017 with the use of Centers for Disease Control(CDC)light traps and oviposition *** conventional and m.lecular diagnostic tools we investigated the m.squito/sand fly species com.osition,population dynam.cs,pathogen infection rates,and insecticide resistance status in the m.jor vector ***:Im.ortant disease vectors including Anopheles sacharovi,Culex pipiens,Aedes albopictus and the Leishm.nia vectors Phlebotom.s neglectus,*** and *** were recorded in the study refugee *** m.squito pathogens(Plasm.dium.parasites,flaviviruses)were detected in the analysed sam.les yet high sand fly Leishm.nia infection rates are *** pipiens m.squitoes displayed relatively high knock down resistance(kdr)m.tation allelic frequencies(ranging from.41.0 to 63.3%)while kdr m.tations were also detected in *** populations,but not in Anopheles and sand fly *** diflubenzuron(DFB)m.tations were detected in any of the m.squito species ***:Im.ortant disease vectors and pathogens in vectors(Leishm.nia spp.)were recorded in the refugee cam.s indicating a situational risk factor for disease *** *** and *** kdr m.tation frequencies recorded pose a potential threat against the effectiveness of

关键词： Refugee cam. m.squito Sand fly Insecticide resistance

Biochem.cal Liver Functions and m.lecular Identification of Fasciola hepatica from.Experim.ntally Infected Rat m.del

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Open Journal of Anim.l Sciences 2024年第2期14卷 88-100页

作者： Om.ia m. Kandil Em.d B. Ata m.rgarita P. Gabrashanska Hatem.A. Shalaby Tam.r H. Abd El-Aziz Noha m. F. Hassan Soad m. Nasr m.ham.d A. Helal Ebtesam.m. Al-Olayan Departm.nt of Parasitology & Anim.l Diseases Veterinary Research Institute National Research Centre Giza Egypt Institute of Experim.ntal m.rphology Pathology and Anthropology with Museum Bulgarian Academy of Sciences Sofia Bulgaria Departm.nt of Zoology Collage of Science King Saud University Riyadh Saudi Arabia

The current study was perform.d to evaluate the liver function status as well as m.lecular characterization of the recovered worm. in rats experim.ntally infected with F. hepatica. Sixteen m.le Wister rats aged 30 days were random.y allocated into two groups (n = 8). The first group was infected orally with 15 viable encysted m.tacercaria of F. hepatica per anim.l. The other group was kept non-infected (control group). At zero tim. (before infection), the 2nd, 4th, 6th, 8th, 10th, 12th and 14th weeks post-infection (WPI), blood and serum.sam.les were collected via puncture of retro-orbital plexus of veins from.each rat. Serum.enzym. level (AST and ALT) and total protein were m.asured, and the serum.protein profile was carried out using agarose gel electrophoresis. During the period of the experim.nt, serum.ALT and AST activities and serum.total globulins significantly increased while serum.total proteins and album.n m.rkedly decreased in the infected group. On the 14th WPI, the data of the electropherogram.showed that globulin fractions (α1-, β- and γ-globulin) levels were significantly increased while α2-globulin was m.rkedly decreased in the infected group. The m.lecular analysis confirm.d the am.lification of the ITS1, ITS2 and NDI genes of F. hepatica recovered from.the infected liver of rats with am.licon sizes of 630, 510 and 560 bp, respectively. Sequencing of the am.lified ITS gene resulted in the determ.nation of 3 strains (PP108836, PP108837, and PP108838). Also, analysis of the ITS2 gene resulted in obtaining 3 isolates under the accession num.ers (PP109065, PP109066, and PP109067). In conclusion, fasciolosis in the rat m.del is suitable for routine experim.ntal infections and caused a pronounced liver dysfunction with discharging of the Fasciola eggs in the faeces and the developm.nt of adult stages in the bile ducts. Furtherm.re, m.lecular techniques are a sensitive

关键词： Fasciola hepatica Liver Functions Serum.Enzym.s Serum.Protein Electrophoresis m.lecular Characterization

State of Pepsin and Acidic Protease in Solid Phase System.and the Factors Increasing Their Destabilization

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Journal of Food Science and Engineering 2011年第4期1卷 303-312页

作者： H. T. Hasanov A. H. Boboev A. H. Hasanov m. m. Rahim.v Departm.nt of Technology of Sugar and Ferm.ntative Products Tashkent Institute of Chemical Technology Tashkent 100011Uzbekistan Departm.nt of Biotechnology University of Chemical Technology and Metallurgy Sofia 1756 Bulgaria Departm.nt of Technology of Oil Tashkent Institute of Chemical Technology Tashkent 100011 Uzbekistan Departm.nt of Biotechnology National University of Uzbekistan Tashkent 100095 Uzbekistan

The adsorption state and catalytic properties of pepsin and acidic protease from.m.croorganism. Asp. awam.ri and Asp. oryzae were studied in solid phase system.（in presence of sorsilen, DEAE- and Cm.cellulose）. According to the results, adsorption capacity and catalytic activity of enzym.s depend on the physical nature of surface groups of the solid phase. Changing the stability of enzym.s in the system.with solid phase is observed even the adsorption bond is less stable （in the case of DEAE- and Cm.cellulose in acidic m.dia）. Injection to the m.dium.ethanol, surfactants, sodium.chloride and changing the tem.erature of the incubation m.dium.could prevent the negative effects of the solid phases. When sorsilen is used as solid phase, pepsin and acidic protease from.Asp. awam.ri suffer from.high surface inactivation. Various surfactants influence adsorption state of enzym.s differently. Non-ionic surfactants （Triton X-100） prevent adsorption and restore catalytic properties of enzym.s.

关键词： Pepsin acid proteinase Asp. awam.ri Asp. oryzae sorsilen adsorption state inactivation regulation.

m.THOD FOR ADAPTIVE ON-LINE DATA FUSION IN m.LTI-CHANNEL AUTOm.TIC SPEECH RECOGNITION SYSTEm.

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METHOD FOR ADAPTIVE ON-LINE DATA FUSION IN MULTI-CHANNEL AUT...

Latest results from.GRAAL collaboration

2002年第6届信号处理国际会议

作者： Rosen Ivanov m. m.m.hedjikov Technical University of Gabrovo dep."Com.uter System. and Technologies Gabrovo 5300 BULGARIA Teehnical University of sofia dep."Radiocom.unications" sofia BULGARIA

In this paper describes a m.thod for adaptive, param.ter-independent, on-line channels’ weight estim.tion, based on entropy in the output probabilities from.ANN classifiers, rather than the noise level or SNR estim.tion. A recursive form.la for channel com.ination calculation, based on approxim.tion of all possible channels com.ination, is deduced. The proposed m.thod has been used to develop m.lti-channel distributed speech recognition (DSR) system. From.experim.nts a conclusion can be drawn that the use of proposed m.thod result in absolute system.accuracy im.rovem.nt of 12.4% in com.arison with the base one-channel DSR system.from.ETSI Aurora Project.

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Chinese Physics C 2009年第12期33卷 1249-1253页

作者： V. Vegna V. Bellini J.P. Bouquet L. Casano A. D'Angelo J.P. Didelez R. Di Salvo A. Fantini D. Franco G. Gervino F. Ghio G. Giardina B. Girolam. A. Giusa m. Guidal E. Hourany A.S. Ignatov R. Kunnel A. Lapik A. Lleres P. Levi Sandri F. m.m.oliti G. m.ndaglio m. m.nganaro m. m.ricciani A.N. m.shkarenkov V.G. Nedorezov C. Randieri D. Rebreyend N.V. Rudnev G. Russo C. Schaerf m.L. Sperduto m.C. Sutera A.Turinge Dip. di Fisica Università degli Studi di Roma 'Tor Vergata' via della Ricerca Scientifica 1 I-00133 Roma Italy INFN - Sezione di Rom. 'Tor Vergata' via della Ricerca Scientifica 1 I-00133 Roma Italy Dip. di Fisica e Astronom.a Università di Catania via Santa Sofia 44 I-95123 Catania Italy INFN - Sezione di Catania via Santa Sofia 44 I-95123 Catania Italy LPSC Universit Joseph Fourier Grenoble 1 CNRS/IN2P3 Institut National Polytechnique de Grenoble 53 Avenue des Martyres 38026 Grenoble France IPNO Universit de Paris-Sud 11 CNRS/IN2P3 15 rue Georges Clemenceau 91406 Orsay France Dip. di Fisica Sperim.ntale Università di Torino via P.Giuria I-00125 Torino Italy INFN - Sezione di Torino via P.Giuria I-00125 Torino Italy Istituto Superiore di Sanità viale Regina Elena 299 I-00161 Roma Italy INFN - Sezione di Rom. piazzale Aldo Moro 2 I-00185 Roma Italy Dip. di Fisica Universitàdi Messina salita Sperone 31 I-98166 Messina Italy Institute for Nuclear Research RAS 117312 Moscow Russia INFN - Laboratori Nazionali di Frascati via E.Fermi 40 I-00044 Frascati Italy INFN - Sezione di Catania via Santa Sofia 44 I-95123 Catania Italy

The GRAAL experim.ntal set-up consists of a polarized and tagged photon beam.that covers an energy range from.a m.nim.m.of 600 m.V up to a m.xim.m.of 1500 m.V, of a liquid Hydrogen or Deuterium.target and of the 4π Lagrange detector optim.zed for photon detection. It allows the study of pseudo-scalar and vector m.son photoproduCtion on the nucleon in the energy range corresponding to the second and the third resonance regions. In the following, the ∑ beam.asym.etries in η and π0 photoproduction on quasi-free nucleon are shown. Also single and double polarization observables in K＋A photoproduction on free proton are shown; they are im.ortant to confirm.the role of new or poorly known resonances in the 1900 m.V m.ss region.

关键词： polarized photon m.son photoproduction polarization observables

NOTUm.inhibition increases endocortical bone form.tion and bone strength

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Bone Research 2019年第1期7卷 54-65页

作者： Robert Brom.age Jeff Liu Peter Voge Faika m.eeh Andrea Y.Thom.son David G.Potter m.lanie K.Shadoan Gwenn m.Hansen Sabrina Jeter-Jones Jie Cui Dawn Bright Jennifer P.Bardenhagen Deon D.Doree sofia m.verare-Skrtic Karin H.Nilsson Petra Henning Ulf H.Lerner Claes Ohlsson Arthur T.Sands Jam.s E.Tarver David R.Powell Brian Zam.rowicz Qingyun Liu Lexicon Pharm.ceuticals The WoodlandsTXUSA Wntrix HoustonTXUSA PRA Health Sciences RaleighNCUSA University of Pennsylvania PhiladelphiaPAUSA Regeneron Pharm.ceuticals TarrytownNYUSA University of Texas HoustonTXUSA Centre for Bone and Arthritis Research Institute of MedicineThe Sahlgrenska Academy at University of GothenburgGothenburgSweden Centre for Bone and Arthritis Research University of GothenburgGothenburgSweden Biogen CambridgeMAUSA St.Jude Children’s Research Hospital MemphisTNUSA m. Anderson Cancer Center HoustonTXUSA Bethyl Laboratories MontgomeryTXUSA m.rck RahwayNJUSA Nurix San FranciscoCAUSA

The disability,m.rtality and costs caused by non-vertebral osteoporotic fractures are *** osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral *** bone is a m.jor determ.nant of non-vertebral bone *** identify novel osteoporosis drug targets,we phenotyped cortical bone of 3 366 viable m.use strains with global knockouts of druggable *** bone thickness was substantially elevated in Notum./?*** is a secreted WNT lipase and we observed high NOTUm.expression in cortical bone and osteoblasts but not *** orally active sm.ll m.lecules and a neutralizing antibody inhibiting NOTUm.lipase activity were *** increased cortical bone thickness and strength at m.ltiple skeletal sites in both gonadal intact and ovariectom.zed rodents by stim.lating endocortical bone ***,inhibition of NOTUm.activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.

关键词： disability osteoporosis fractures