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Advances in Bioscience and Biotechnology 2012年第4期3卷 336-343页

作者： carol milena barreto-rodriguez Jessica Paola Ramirez-Angulo Jorge Mario Gomez-Ramirez Luke Achenie Andres Fernando Gonzalez-Barrios Grupo de Diseno de Productos y Procesos(GDPP) Department of Chemical EngineeringUniversidad de los AndesBogotaColombia Multiscale and Multiphysics Modeling Lab Department of Chemical EngineeringVirginia Polytechnic Institute and State UniversityBlacksburgVirginia

In silico approaches for metabolites optimization have been derived from the flood of sequenced and annotated genomes. However, there exist still numerous degrees of freedom in terms of optimization algorithm approaches that can be exploited in order to enhance yield of processes which are based on biological reactions. Here, we propose an evolutionary approach aiming to suggest different mutant for augmenting ethanol yield using glycerol as substrate in Escherichia coli. We found that this algorithm, even though is far from providing the global optimum, is able to uncover genes that a global optimizer would be incapable of. By over-expressing accB, eno, dapE, and accA mutants in ethanol production was augmented up to 2 fold compared to its counterpart E. coli BW25113.

关键词： Bi-level Optimization Escherichia coli Metabolic Flux Analysis Genetic Algorithm

Astrocytes and retrograde degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease:removing axonal debris

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Translational Neurodegeneration 2021年第4期10卷 554-572页

作者： Ingrid Morales Ricardo Puertas-Avendaño Alberto Sanchez Adrian Perez-barreto Clara rodriguez-Sabate Manuel rodriguez Laboratory of Neurobiology and Experimental Neurology Department of Basic Medical SciencesFaculty of MedicineLa Laguna UniversityLa LagunaTenerifeCanary IslandsSpain Center for Networked Biomedical Research on Neurodegenerative Diseases(CIBERNED) MadridSpain

Objective:The dopaminergic nigrostriatal neurons(DA cells)in healthy people present a slow degeneration with aging,which produces cellular debris throughout *** 2%-5%of people present rapid cell degeneration of more than 50%of DA cells,which produces Parkinson's disease(PD).Neuroinflammation accelerates the cell degeneration and may be critical for the transition between the slow physiological and the rapid pathological degeneration of DA cells,particularly when it activates microglial cells of the medial forebrain bundle near dopaminergic *** synaptic debris produced by DA cell degeneration may trigger the parkinsonian neuroinflammation,this study investigated the removal of axonal debris produced by retrograde degeneration of DA cells,paying particular attention to the relative roles of astrocytes and ***:Rats and mice were injected in the lateral ventricles with 6-hydroxydopamine,inducing a degeneration of dopaminergic synapses in the striatum which was not accompanied by non-selective tissue damage,microgliosis or *** possible retrograde degeneration of dopaminergic axons,and the production and metabolization of DA-cell debris were studied with immunohistochemical methods and analyzed in confocal and electron microscopy ***:The selective degeneration of dopaminergic synapses in the striatum was followed by a retrograde degeneration of dopaminergic axons whose debris was found within spheroids of the medial forebrain *** spheroids retained mitochondria and most(e.g.,tyrosine hydroxylase,the dopamine transporter protein,and amyloid precursor protein)but not all(e.g.,α-synuclein)proteins of the degenerating dopaminergic *** showed initial(autophagosomes)but not late(lysosomes)components of autophagy(incomplete autophagy).These spheroids were penetrated by astrocytic processes of the medial forebrain bundle,which provided the lysosomes needed to continue the degradation of dopaminergic debri

关键词： Astrocyte Phagocytosis Parkinson's disease Dying-back degeneration Medial forebrain bundle Spheroid

Bioactive Amines: Aspects of Quality and Safety in Food

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Food and Nutrition Sciences 2014年第2期5卷 138-146页

作者： Mariana Bacellar Ribas rodriguez Carla da Silva Carneiro Marcia barreto da Silva Feijó Carlos Adam Conte Júnior Sérgio Borges Mano Department of Food Science Federal Fluminense University Niterói Brazil. Department of Food Technology Federal Fluminense University Niterói Brazil Department of Natural Products and Food Federal University of Rio de Janeiro Rio de Janeiro Brazil

Presented in several types of food, bioactive amines are described as organic bases of low molecular weight. They have vasoactive, psychoactive and toxicological characteristics and constitute a potential health risk. The concentration of amines formed in foods depends on the type of microorganisms present, the action of decarboxylase enzymes produced by microorganisms on specific amino acids and favorable conditions for enzymatic activity. The presence of these chemical metabolites has been suggested as a quality indicator in routine analyzes for food production and marketing monitoring. The detection of bioactive amines can be performed by chromatographic methods, fluorometric and enzymatic kits. Bioactive amine formation can be prevented mainly through the adoption of good manufacturing practices, but the industry can also use other methods such as temperature control in the production chain, modified atmosphere packaging and food irradiation. This review aims to address the formation of bioactive amines in foods, emphasizing the formation and classification of these metabolites, aspects related to health, acceptable limits, detection methods and control methods used in the industry to ensure food safety and quality. The success of this approach is linked to the importance of bioactive amines as quality indicators, as well as the discussion on the development of methodologies for determining these substances and discussion of acceptable parameters in food.

关键词： Bioactive Amines Detection Methods Toxicity Acceptable Limits Food Quality

Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas

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World Journal of Gastroenterology 2018年第43期24卷 4928-4938页

作者： carolina Rosal Teixeira de Souza Marcelli carolini Alves Almeida Andre Salim Khayat Emerson Lucena da Silva Paulo Cardoso Soares Luiz Claudio Chaves Rommel Mario rodriguez Burbano Laboratory of Human Cytogenetics Institute of Biological Sciences Federal University of Para Belem Para 66075-110 Brazil Oncology Research Center Federal University of Para Joao deBarros Barreto University Hospital Belem Para 66073-000Brazil Ophir Loyola Hospital Belem Para 66060-281 Brazil

AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, *** Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the *** The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋（H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the *** HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

关键词： Gastric cancer Gastric adenocarcinomas Microorganisms Helicobacter pylori cagA Epstein-Barr virus Human papillomavirus

Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

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World Journal of Gastroenterology 2016年第43期22卷 9506-9514页

作者： Danielle Queiroz Calcagno Sylvia Santomi Takeno carolina Oliveira Gigek Mariana Ferreira Leal Fernanda Wisnieski Elizabeth Suchi Chen Taíssa Maíra Thomaz Araújo Eleonidas Moura Lima Maria Isabel Melaragno Samia Demachki Paulo Pimentel Assumpcao Rommel rodriguez Burbano Marília Cardoso Smith Disciplina de Genética Departamento de Morfologia e GenéticaUniversidade Federal de Sao Paulo Núcleo de Pesquisas em Oncologia Hospital Universitário Joao de Barros Barreto Departamento de Biologia Molecular Universidade Federal da Paraíba Disciplina de Gastroenterologia Cirúrgica Universidade Federal de Sao Paulo Departamento de Ortopedia e Traumatologia Universidade Federal de Sao Paulo

AIM To identify common copy number alterations on gastric cancer cell *** Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR *** The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11RA) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 RA and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.

关键词： IL11RA Gastric cancer Genomic profiling MELK 9p13.3

Presence of c.3956del C mutation in familial adenomatous polyposis patients from Brazil

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World Journal of Gastroenterology 2015年第31期21卷 9413-9419页

作者： caroline Aquino Moreira-Nunes Diego di Felipe ávila Alcantara Sérgio Figueiredo Lima-Júnior Sandro Roberto de Araújo Cavalléro Juan Antonio Rey Giovanny Reboucas Pinto Paulo Pimentel de Assumpcao Rommel rodriguez Burbano Biological Science Institute Federal University of Pará Nucleus of Research in Oncology Federal University of Pará Molecular Neuro-oncogenetics Laboratory Research Unit-Unidad de InvestigaciónHospital Universitario La Paz Genetics and Molecular Biology Laboratory Federal University of Piaui

AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis(FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP,family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the Jo?o de Barros barreto University Hospital(Belem,Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations,Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. RESULTS: Through interviews with relatives and a search of medical records,it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene,and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP,family members without disease symptoms showed the mutation in the APC gene. In the present study,we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956 del C mutation was found in all families from this study,and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration(i.e.,a de novo mutation that arose

关键词： Familial adenomatous polyposis APC Torrent sequencing Colorectal cancer

Traps and trumps from adjacent-to-tumor samples in gastric cancer research

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Chinese Journal of Cancer Research 2018年第5期30卷 564-567页

作者： Paulo Pimentel de Assumpcao Andre Salim Khayat Taissa Maira Thomaz Araujo Williams Fernandes Barra Geraldo Ishak Mine Maria Pereira Cruz Ramos Sidney Emanuel Batista dos Santos Andrea Kely Campos Ribeiro dos Santos Samia Demachki Paula Barauna de Assumpcao Danielle Queiroz Calcagno Ney Pereira Carneiro dos Santos Monica Barauna de Assumpcao Fabiano Cordeiro Moreira Andre Mauricio Ribeiro dos Santos carolina Barauna de Assumpcao Gregory Joseph Riggins Rommel Mario rodriguez Burbano Oncology Research Center Federal University of Para Belem 66075-110 Brazil PhD Program in Genetics and Molecular Biology Federal University of Para Belem 66075-110 Brazil Gastrointestinal Endoscopy Service Joao de Barros Barreto University Hospital Belem 66073-000 Brazil Department of Surgical Oncology Oswaldo Cruz Germany Hospital Sao Paulo 01327-001 Brazil Department of Neurosurgery Johns Hopkins University Baltimore 21287 USA Laboratory of Molecular Biology Ophir Loyola Hospital Belem 66060-281 Brazil

The search for cancer biomarkers is frequently based on comparisons between tumors and adjacent-to-tumor samples. However, even after histological confirmation of been free of cancer cells, these adjacent-to-tumor samples might harbor molecular alterations which are not sufficient to cause them to look like cancer, but can differentiate these cells from normal cells. When comparing them, potential biomarkers are missed, and mainly the opportunity of finding initial aberrations presents in both tumors and adjacent samples, but not in true normal samples from non-cancer patients, resulting in misinterpretations about the carcinogenic process. Nevertheless, collecting adjacent-to-tumor samples brings trumps to be explored. The addition of samples from non-cancer patients opens an opportunity to increase the finds of the molecular cascade of events in the carcinogenic process. Differences between normal samples and adjacent samples might represent the first steps of the carcinogenic process. Adding samples of non-cancer patients to the analysis of molecular alterations relevant to the carcinogenic process opens a new window of opporttmides to the discovery of cancer biomarkers and molecular targets.

关键词： Adjacent-to-tumor trumps traps

Role of mi RNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

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World Journal of Gastroenterology 2016年第35期22卷 7951-7962页

作者： Kelly Cristina da Silva Oliveira Taíssa Maíra Thomaz Araújo Camila Inagaki Albuquerque Gabriela Alcantara Barata carolina Oliveira Gigek Mariana Ferreira Leal Fernanda Wisnieski Fernando Augusto Rodrigues Mello Junior André Salim Khayat Paulo Pimentel de Assumpcao Rommel Mário rodriguez Burbano Marília Cardoso Smith Danielle Queiroz Calcagno Núcleo de Pesquisas em Oncologia Universidade Federal do Pará Hospital Universitário Joao de Barros Barreto Disciplina de Genética Departamento de Morfologia e Genética Universidade Federal de Sao Paulo Laboratório de Citogenética Humana Instituto de Ciências Biológicas Universidade Federal do Pará

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.

关键词： Gastric cancer Epigenetic Diagnostic biomarkers miRNAs Prognostic biomarkers