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Journal of Genetics and Genomics 2015年第6期42卷 287-299页

作者： Gerson Dierley Keppeke S.John calise Edward K.L.chan luis eduardo c.andrade Rheumatology Division Federal University of Sao Paulo Department of Oral Biology University of Florida Immunology Division Fleury Medicine and Health Laboratories

Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（cTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（cTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of cTPS and IMPDH2 in the generation of RR *** La and cOS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR *** He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were cTPS alone,and 31% were IMPDH2/cTPS mixed,while in cOS-7 cells,42% of RR were IMPDH2 alone,41% were cTPS alone,and 10% were IMPDH2/cTPS *** and MPA treatments induced only IMPDH2-based *** were also transfected with an N-terminal hemagglutinin（NHA）-tagged cTPS1 *** 95% of NHA-cTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented cTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented cTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented cTPS1-based *** results may help in understanding the relationship between cTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.

关键词： Nucleotide synthesis Enzyme aggregation Enzyme inhibition IMPDH2 cTPS

Anti-rods/rings autoantibody generation in hepatitis cpatients during interferon-α/ribavirin therapy

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World Journal of Gastroenterology 2016年第6期22卷 1966-1974页

作者： Gerson Dierley Keppeke S John calise Edward KL chan luis eduardo c andrade Rheumatology Division Escola Paulista de MedicinaUniversidade Federal de São PauloSP 04023-062Brazil Department of Oral Biology University of FloridaGainesvilleFL 32610-0424United States 3 Immunology DivisionFleury Medicine and Health Laboratories São PauloSP 04102-050Brazil

chronic inflammation associated with hepatitis c virus(HcV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon α(IFN-α) together with a daily dose of ribavirin. HcV patients frequently present circulating non-organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies(ANA). Between 20% to 40% of HcV patients treated with IFN-α and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings(RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings(antiRR) autoantibody production by HcV patients after IFN-α/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HcV patients is inosine-5'-monophosphate dehydrogenase 2(IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon.

关键词： Rods and rings autoantibodies Hepatitis c ribavirin Interferon-α

Towards an integrated risk analysis security framework according to a systematic analysis of existing proposals

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Frontiers of computer Science 2024年第3期18卷 199-216页

作者： Antonio SANTOS-OLMO luis Enrique SÁNcHEZ David G.ROSADO Manuel A.SERRANO carlos BLANcO Haralambos MOURATIDIS eduardo FERNÁNDEZ-MEDINA GSyA Research Group University of Castilla-La ManchaCiudad Real 13071Spain Institute for Analytics and Data Science University of EssexColchester CO43SQUK Alarcos Research Group University of Castilla-La ManchaCiudad Real 13071Spain ISTR Research group Department of Computer Science and ElectronicsUniversity of CantabriaSantander 39005Spain

The information society depends increasingly on risk assessment and management systems as means to adequately protect its key information *** availability of these systems is now vital for the protection and evolution of ***,several factors have led to an increasing need for more accurate risk analysis *** are:the speed at which technologies evolve,their global impact and the growing requirement for companies to *** analysis processes must consequently adapt to these new circumstances and new technological *** objective of this paper is,therefore,to present the results of an exhaustive analysis of the techniques and methods offered by the scientific community with the aim of identifying their main weaknesses and providing a new risk assessment and management *** analysis was carried out using the systematic review protocol and found that these proposals do not fully meet these new *** paper also presents a summary of MARISMA,the risk analysis and management framework designed by our research *** basis of our framework is the main existing risk standards and proposals,and it seeks to address the weaknesses found in these *** is in a process of continuous improvement,as is being applied by customers in several European and American *** consists of a risk data management module,a methodology for its systematic application and a tool that automates the process.

关键词： information security management security system security risk assessment and management

A Data Security Framework for cloud computing Services

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computer Systems Science & Engineering 2021年第5期37卷 203-218页

作者： luis-eduardo Bautista-Villalpando Alain Abran Department of Electronic Systems Autonomous University of AguascalientesAguascalientes20131Mexico Department of Software Engineering and Information Technology ETSUniversity of QuebecMontrealH3C 1K3Canada

cyberattacks are difficult to prevent because the targeted companies and organizations are often relying on new and fundamentally insecure cloudbased technologies,such as the Internet of *** increasing industry adoption and migration of traditional computing services to the cloud,one of the main challenges in cybersecurity is to provide mechanisms to secure these *** work proposes a Data Security Framework for cloud computing services(ccS)that evaluates and improves ccS data security from a software engineering perspective by evaluating the levels of security within the cloud computing paradigm using engineering methods and techniques applied to *** framework is developed by means of a methodology based on a heuristic theory that incorporates knowledge generated by existing works as well as the experience of their *** paper presents the design details of the framework,which consists of three stages:identification of data security requirements,management of data security risks and evaluation of data security performance in ccS.

关键词： cloud computing services computer security data security data security requirements data risk data security measurement

Is autoimmune hepatitis a frequent finding among HcV patients with intense interface hepatitis?

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World Journal of Gastroenterology 2010年第29期16卷 3704-3708页

作者： Rosilene G Badiani Vitória Becker Renata M Perez carla AL Matos Lara B Lemos Valéria P Lanzoni luis eduardo c andrade Alessandra Dellavance Antonio eduardo B Silva Maria Lucia G Ferraz Division of Gastroenterology Federal University of Sao Paulo04023-900Sao PauloBrazil Department of Internal Medicine Federal University of Rio de Janeiro21941-913Rio de JaneiroBrazil Department of Pathology Immunology Group Fleury Medicine and Health 不详

AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis c virus(HcV)-infected patients with intense interface ***:Among 1759 patients with hepatitis c submitted to liver biopsy,92(5.2%) presented intense interface *** patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis c and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal *** histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of autoimmune hepatitis,only one patient was classified with a definitive diagnosis of autoimmune *** overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis c we sought to identify the variables associated with this *** presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol ***:Although possible,overlap with autoimmune hepatitis is a very rare association in HcV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables.

关键词： Hepatitis c Liver biopsy Antinuclear antibody Autoimmune hepatitis Interface hepatitis

the 20GD Superfamily： Emerging Functions in Plant Epigenetics and Hormone Metabolism

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Molecular Plant 2018年第10期11卷 1222-1224页

作者： Riad Nadi eduardo Mateo-Bonmati Lucia Juan-Vicente Jose luis Micol Instituto de Bioingenieria Universidad Miguel Hern&ndez Campus de Elche 03202 Elche Spain

The 2-oxoglutarate and Fe （ll）-dependent dioxygenase （2OGD） superfamily includes oxidative enzymes with an active site con- taining two histidines and （in most cases） one aspartic or glutamic acid residue. This conserved motif is termed the 2-His-1-carboxylate facial triad, chelates iron, and is housed within a double-stranded β-helix fold, also known as the DSBH, jelly-roll, cupin, or Jumonji c fold （Martinez and Hausinger, 2015）. The reactions catalyzed by 2OGDs （also called 2ODDs, 2ODQs, and 2OGXs） include but are not limited to demethylation, demethylenation, hydroxytation, halogenation, desaturation, ring cleavage, ring closure, and epimerization （Farrow and Facchini, 2014）.

关键词： DEMETHYLASE DIVERSITY

Effect of treatment failure on the cag A EPIYA motif in Helicobacter pylori strains from colombian subjects

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World Journal of Gastroenterology 2017年第11期23卷 1980-1989页

作者： Javier Andres Bustamante-Rengifo Andres Jenuer Matta Alvaro Jairo Pazos luis eduardo Bravo Department of Microbiology School of Basic ScienceUniversidad del Valle Registro Poblacional de cáncer de cali Department of PathologySchool of MedicineUniversidad del Valle Department of Biology Universidad de Narino

AIM To evaluate effect of treatment failure on cag A and vac A genotypes in Helicobacter pylori(H. pylori) isolates from *** One hundred and seventy-six participants infected with H. pylori from colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13c-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cag A and vac A genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA(RAPD) *** Treatment effectiveness was at 74.6%. Of the par-ticipants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of posttreatment infection was 64%(16/25) and 40%(10/25) by histology and culture, respectively. Upon comparing the cag A and vac A genotypes found before and after therapy, multiple cag A genotypes(cag A-positive and cag A-negative) were found before treatment; in contrast, cag A-negative genotypes decreased after treatment. vac A s1m1 genotype was highly prevalent in patients before and after therapy. The 3'cag A region was successfully amplified in 95.5%(21/22) of the isolates obtained before and in 81.8%(18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7%(16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before *** Unsuccessful treatment limits colonization by lowvirulence strains resulting in partial and selective eradication in mixed infections, and acts on the cag A-positive strains inducing genetic rearrangements in cag A variable region that produces a loss or gain of EPIYA repetitions.

关键词： Helicobacter pylori RAPD-PcR Treatment failure EPIYA motifs 3’ cag A variable region

Genomic variability of Helicobacter pylori isolates of gastric regions from two colombian populations

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World Journal of Gastroenterology 2017年第5期23卷 800-809页

作者： Andrés Jenuer Matta Alvaro Jairo Pazos Javier Andrés Bustamante-Rengifo luis eduardo Bravo Registro Poblacional de cáncer de cali Department of PathologySchool of MedicineUniversidad del Valle Department of Biology Universidad de Narino

AIMTo compare the genomic variability and the multiple colonization of Helicobacter pylori (H. pylori) in patients with chronic gastritis from two colombian populations with contrast in the risk of developing gastric cancer (Gc): Túquerres-Nariño (High risk) and Tumaco-Nariño (Low risk).METHODSFour hundred and nine patients from both genders with dyspeptic symptoms were studied. Seventy-two patients were included in whom H. pylori was isolated from three anatomic regions of the gastric mucosa, (31/206) of the high risk population of Gc (Túquerres) and (41/203) of the low risk population of Gc (Tumaco). The isolates were genotyped by PcR-RAPD. Genetic diversity between the isolates was evaluated by conglomerates analysis and multiple correspondence *** proportion of virulent genotypes of H. pylori was 99% in Túquerres and 94% in Tumaco. The coefficient of similarity of Nei-Li showed greater genetic diversity among isolates of Túquerres (0.13) than those of Tumaco (0.07). After adjusting by age, gender and type of gastritis, the multiple colonization was 1.7 times more frequent in Túquerres than in Tumaco (P = 0.05).cONcLUSIONIn Túquerres, high risk of Gc there was a greater probability of multiple colonization by H. pylori. From the analysis of the results of the PcR-RAPD, it was found higher genetic variability in the isolates of H. pylori in the population of high risk for the development of Gc.

关键词： Helicobacter pylori Pathogenicity islet cag cagA vacA Multiple colonization PcR-RAPD

Y-chromosome microdeletions in nonobstructive azoospermia and severe oligozoospermia

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Asian Journal of Andrology 2017年第3期19卷 338-345页

作者： carolina Goncalves Mariana cunha eduardo Rocha Susana Fernandess, Joaquina Silva luis Ferraz cristiano Oliveira Alberto Barros Mairio Sousa Department of Biology ClCECO University of Aveiro Campus Universitario de Santiago 3810-193 Aveiro Portugal Department of Microscopy Laboratory of Cell Biology Institute of Biomedical Sciences Abel Salazar University of Porto (ICBAS-UP) Rua Jorge Viterbo Ferreira 228 4050-313 Porto Portugal and Multidisciplinary Unit for Biomedical Research ICBAS-UP Portugal centre for Reproductive Genetics Prof. Alberto Barros Av. do Bessa 240 1° Dto. Frente 4100-009 Porto Portugal Department of Microscopy Laboratory of Histology and Embryology ICBAS-UP Rua Jorge Viterbo Ferreira 228 4050-313 Porto Portugal Department of Genetics Faculty of Medicine University of Porto Alameda Prof. Hernani Monteiro 4200-319 Porto Portugal and Institute for Innovation and Health Research (13S) University of Porto Portugal Department of Urology Hospital Center of Vila Nova de Gala Rua Conceicao Fernandes 4430-502 Vila Nova de Gala Portugal.

The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （IcSI）, either using fresh （TESE） or frozen-thawed （TESE-c） testicular sperm and ejaculated sperm （EJAc）. The originality of this work resides in the comparisons between the different types of Y-microdeletions （AZFa, AZFb, and AZFc） and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn （NB） outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia （18 performed IcSI with ejaculated sperm） and 92 secretory azoospermia （65 went for TESE with 40 having successful sperm retrieval and performed IcSI）. There were 51 TESE treatment cycles and 43 TESE-c treatment cycles, with a birth of 19 NB （2 in AZFa/TESE-c, 12 in AZFc/TESE, and 5 in AZFc/TESE-c）. Of the 29 EJAc cycles, there was a birth of 8 NB （in AZFc）. In TESE and EJAc cycles, there were no significant differences in embryological and clinical parameters. In TESE-c cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.

关键词： intracytoplasmic sperm injection newborn outcomes nonobstructive azoospermia severe oligozoospermia testicularsperm extraction Y-chromosome microdeletions

Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

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World Journal of Gastroenterology 2007年第7期13卷 1067-1073页

作者： Andre castro lyra Milena Botelho Pereira Soares luiz Flavio Maia da Silva Marcos Fraga Fortes André Goyanna Pinheiro Silva Augusto césar de andrade Mota Sheilla A Oliveira eduardo lorens Braga Wilson andrade de carvalho Bernd Genser Ricardo Ribeiro dos Santos luiz Guilherme costa lyra Hos-pital Sao Rafael Salvador Bahia Brazil centro de Pesquisas Goncalo Moniz Fundacao Oswaldo Cruz Salvador Bahia Brazil BGStats consulting Graz Austria

AIM： To evaluate the safety and feasibility of bone marrow cell （BMc） transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS： Ten patients （eight males） with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as child-Pugh B and three as child-Pugh c. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMcs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS： The median age of the patients was 52 years （range 24-70 years）. All patients were discharged 48 h after BMc infusion. Two patients complained ofmild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 （2.19 ± 0.9） and 4 mo （2.10 ± 1.0） after cell transplantation that baseline levels （238 ± 1.2）. Albumin levels 4 mo after BMc infusion （3.73 ± 0.5） were higher than baseline levels （3.47 ± 0.5）. International normalized ratio （INR） decreased from 1.48 （SD = 0.23） to 1.43 （SD = 0.23） one month after cell transplantation. cONcLUSION： BMc infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMc transplantation in patients with advanced chronic liver disease.

关键词： Bone marrow cell transplantation Liverfailure Stem cell cirrhosis