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Co-occurrence of germline pathogenic variants for different hereditary cancer syndromes in patients with Lynch syndrome

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Cancer Communications 2021年第3期41卷 218-228页

作者： Rosario Ferrer-Avargues Maria Isabel Castillejo Estela Damaso Virginia Diez-Obrero Noemi Garrigos Tatiana Molina Alan Codoner-Alejos Angel Segura ana beatriz sanchez-heras Adela Castillejo Jose Luis Soto Foundation for the Promotion of Health and Biomedical Research of Valencia Region(FISABIO) FISABIO-Elche Health DepartmentElche 032303Spain Molecular Genetics Unit.Elche University Hospital Elche 032303Spain Department of Molecular Biopathology Immunological Center of AlicanteSan Juan-Alicante 03550Spain Medical Oncology Department Cancer Genetic Counseling Unit.La Fe University HospitalValencia 46026Spain Medical Oncology Department Cancer Genetic Counseling Unit.Elche University HospitalElche 03203Spain

Background:Lynch syndrome(LS)is a hereditary condition characterized by a high risk of colorectal cancer,endometrial cancer,and other neoplasia associated with germline alterations in DNA mismatch repair *** classical genetic diagnostic strategy for LS consists of the Sanger sequencing of genes associated with the suspected ***-generation sequencing(NGS)enables the simultaneous sequencing of a large number of hereditary cancer ***,we aimed to study whether other germline pathogenic variants of hereditary cancer genes are present in patients with ***:A cohort of 84 probands with a previous genetic diagnosis of LS by Sanger sequencing was reanalyzed using NGS via a commercial panel of 94 hereditary cancer genes by hybrid *** American College of Medical Genetics and Genomics criteria were used to classify the clinical significance of the *** findings of NGS were confirmed by Sanger *** possible,genetic analyses of the new findings in the proband’s relativeswere also performed by Sanger ***:We identified five families(6%),out of 84,with at least two germline pathogenic variants conferring to high or moderate risk in different dominant cancer-predisposing genes:[MLH1-BRCA2-NBN],[MLH1-BRCA1],[MSH2-ATM],[MSH6-NF1],and[MLH1-FANCA].Interestingly,only one out of these five families exhibited a clinical phenotype associated with the new pathogenic *** family with three pathogenic variants of the[MLH1-BRCA2-NBN]genes showed a high aggregation of tumors associated with LS and breast and ovarian cancer ***:Our results showed that the co-occurrence of more than one pathogenic variant in cancer-predisposing genes was remarkable among cases of *** cases,no clinicial manifestations were associated with the secondary pathogenic *** studies are needed to confirm these findings and elucidate their clinical *** of LS families should be considered only in fa

关键词： cancer panel hereditary cancer lynch syndrome moderate penetrance genes multilocus inherited neoplasia alleles syndrome next-generation sequencing secondary findings

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Intraexaminer repeatability and agreement in stereoacuity measurements made in young adults

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International Journal of Ophthalmology(English edition) 2015年第2期8卷 374-381页

作者： beatriz Antona ana Barrio Isabel sanchez Enrique Gonzalez Guadalupe Gonzalez Department of Optics II (Optometry and Vision) Faculty of Optics and Optometry Complutense University of Madrid

AIM: To determine the repeatability and agreement of stereoacuity measurements made using some of the most widely used clinical tests: Frisby, TNO, Randot and ***: Stereoacuity was measured in two different sessions separated by a time interval of at least 24 h but no longer than 1wk in 74 subjects of mean age 20.6y using the four methods. The study participants were divided into two groups: subjects with normal binocular vision and subjects with abnormal binocular ***: Best repeatability was shown by the Frisby and Titmus [coefficient of repeatability(COR): ±13 and±12s arc respectively] in the subjects with normal binocular vision though a clear ceiling effect was *** the subjects with abnormal binocular vision, best repeatability was shown by the Frisby(COR: ±69s arc)and Randot(COR: ±72s arc). In both groups, the TNO test showed poorest agreement with the other ***:Therepeatabilityofstereoacuitymeasures was low in subjects with poor binocular vision yet fairly good in subjects with normal binocular vision with the exception of the TNO test. The reduced agreement detected between the tests indicates they cannot be used interchangeably.

关键词： stereoacuity repeatability agreement tereopsis

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Conserved Curvature of RNA Polymerase Ⅰ Core Promoter Beyond rRNA Genes: The Case of the Tritryps

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Genomics, Proteomics & Bioinformatics 2015年第6期13卷 355-363页

作者： Pablo Smircich María ana Duhagon beatriz Garat Molecular Interactions Laboratory School of Sciences University of the Republic Genetics Departament School of Medicine University of the Republic

In trypanosomatids, the RNA polymerase I （RNAPI）-dependent promoters controlling the ribosomal RNA （rRNA） genes have been well identified. Although the RNAPI transcription machinery recognizes the DNA conformation instead of the DNA sequence of promoters, no con- formational study has been reported for these promoters. Here we present the in silico analysis of the intrinsic DNA curvature of the rRNA gene core promoters in Trypanosoma brucei, Trypanosoma cruzi, and Leiskmania major. We found that, in spite of the absence of sequence conservation, these promoters hold conformational properties similar to other eukaryotic rRNA promoters. Our results also indicated that the intrinsic DNA curvature pattern is conserved within the Leishmania genus and also among strains of T. cruzi and T. brucei. Furthermore, we analyzed the impact of point mutations on the intrinsic curvature and their impact on the promoter activity. Furthermore, we found that the core promoters of protein-coding genes transcribed by RNAPI in T. brucei show the same conserved conformational characteristics. Overall, our results indicate that DNA intrinsic curvature of the rRNA gene core promoters is conserved in these ancient eukaryotes and such con- served curvature might be a requirement of RNAPI machinery for transcription of not only rRNA genes but also protein-coding genes.

关键词： Intrinsic curvature RNA polymerase I Core promoter Trypanosoma Leishmania

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Monoclonal Antibody Production and Immunolocalization of a Salinity Stress-Related Protein in Rice (Oryza sativa)

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Rice science 2011年第2期18卷 95-101页

作者： Jackson MARCONDES ana beatriz GARCIA Faculdade de Ciências Agrárias e Veterinárias Universidade Estadual Paulista Centro de Biociências e Biotecnologia Universidade Estadual do Norte Fluminense

Among various physiological responses to salt stress, the synthesis of a lectin-related protein of 14.5 kDa was observed in rice plants （Oryza sativa L.） under the treatment of 170 mmol/L NaCl. In order to better understand the role of the SALT protein in the physiological processes involving salinity, it was irnmunolocalized in mesophilic cells of leaf sheath and blade of a rice variety IAC-4440 following monoclonal antibodies produced by hybridome culture technique. This variety turned out to be an excellent model for that purpose, since it accumulates SALT protein even in absence of salt treatment and it has been classified as moderately sensitive to salinity and a superior grain producer. This feature was relevant for this work since it allowed the use of plants without the deleterious effects caused by salinity. Immunocytochemistry assays revealed that the SALT protein is located in the stroma of chloroplasts under non-stressing condition. Since the chloroplast is the main target affected by salinity and considering that the SALT protein does not present any apparent signal peptide for organelle localization, its lectin-like activity seems to play an important role in the establishment of stable complexes, either to other proteins or to oligosaccharides that are translocated to the chloroplast.

关键词： salt stress SALT protein immunocytochemistry chloroplast rice

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Effects of melatonin on the oxidative damage and pancreatic antioxidant defenses in ceruleininduced acute pancreatitis in rats

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Hepatobiliary & Pancreatic Diseases International 2014年第4期13卷 442-446页

作者： Cristina Carrasco ana beatriz Rodríguez José A Pariente Department of Physiology Neuroimmunophysiology and Chrononutrition Research Group University of Extremadura

BACKGROUND： Oxidative stress is recognized as a pivotal effector of several pathogenic processes, including acute pancreatitis. Reactive oxygen species not just cause damage on the main cellular components, but also influence the expression of antioxidant system genes. Antioxidant molecules, such as melatonin, could be good candidates for the treatment of this multidimensional disease. The present study was to evaluate the chemopreventive effect of melatonin in a rat model of ceruleininduced acute ***： Four subcutaneous injections of cerulein（20 μg/kg body weight） were given to Wistar rats at two hours intervals;melatonin was injected intraperitoneally（25 mg/kg body weight）30 minutes before each injection of cerulein. Lipid peroxidation,protein oxidation（carbonyl groups）, total antioxidant status,and glutathione peroxidase activity were determined in pancreatic tissue using commercial ***： The chemopreventive administration of melatonin caused a reduction in lipid peroxidation and protein oxidation due to injections of cerulein. Additionally, melatonin treatment was also able to revert glutathione peroxidase activity and total antioxidant status near to control levels, suggesting that melatonin could prevent from oxidative phenomena in the pancreas, such as lipid peroxidation and protein oxidation,and could stimulate, directly or indirectly, the expression of antioxidant ***： Melatonin, a polyvalent antioxidant, protected the pancreatic damage via the decrease of oxidative stress andincrease of the activities of antioxidant enzymes in ceruleininduced acute pancreatitis.

关键词： acute pancreatitis antioxidants cerulein melatonin oxidative stress

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In vitro antioxidant,antilipoxygenase and antimicrobial activities of extracts from seven climbing plants belonging to the Bignoniaceae

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Journal of Integrative Medicine 2018年第4期16卷 255-262页

作者： Carola analla Torres Cristina Marisel Perez Zamora Maria beatriz Nunez ana Maria Gonzalez Laboratory of Microbiology and Pharmaceutical Technology Department of Basic and Applied SciencesNational University of Chaco AustralPresidencia Roque Saenz Pena 3700ChacoArgentina National Council for Scientific and Technical Research(CONICET) Godoy Cruz 2290Buenos Aires C1425FQBArgentina Institute of Botany of the Northeast(IBONE-CONICET) Sargento Juan Bautista Cabral 2131CorrientesArgentina

Objectives： This study aimed to evaluate the in vitro antioxidant capacity, to determine the anti-inflammatory effect due to lipoxygenase inhibition and to test the antimicrobial activity of ethanolic extracts from leaves of seven climbing species belonging to the Bignoniaceae family. These species are Adenocalyrnrna rnarginatum （Cham.） DC., Amphilophium vauthieri DC., Cuspidaria convoluta （VEIL） A. H. Gentry, Dolichandra dentata （K. Schum.） L. G. Lohmann, Fridericia caudigera （S. Moore） L. G. Lohmann, Fridericia chica （Bonpl.） L. G. Lohmann and Tanaecium selloi （Spreng.） L. G. Lohmann. Methods： The antioxidant activity was evaluated using three methods, 2,2＇-azino-bis（3-ethylbenzothiazo line-6-sulfonic acid）（ABTS）, 2,2-diphenyl-l-picrylhydrazyl （DPPH）, and ferric reducing antioxidant power. Lipoxygenase-inhibiting activity was assayed spectrophotometrically; the result was expressed as percent inhibition. The antimicrobial activity was assessed using the agar disk diffusion method. Minimal inhibitory concentration （MIC） and minimal bactericidal]fungicidal concentration were also determined for each extract against 12 pathogenic bacterial strains of Staphylococcus aureus and seven fungal strains of the Candida genus. The identification of the major compounds present in the most promising extract was established by high-performance liquid chromatography-tandem mass spectrometry. Results： C convoluta, F. caudigera, and F. chica exhibited the best antioxidant activity by scavenging DPPH and ABTS~ radicals and reducing Fe3＋ ion. These extracts showed a notable inhibition of lipnxygenase. F. caudigera was found to have the lower MIC value against S. aureus strains and six Candida species. The extracts of F. caudigera and C. convoluta were active even against methicillin-resistant S. aureus. C convoluta had higher total phenol content, better antioxidant activity and superior anti- inflammatory and antimicrobial activity. The main phenolic compounds found in this extract

关键词： Cuspidaria Fridericia Antioxidants Lipoxygenase Antimicrobials Herbal drugs Free radical scavengers

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Immunomodulatory biomaterial-based wound dressings advance the healing of chronic wounds via regulating macrophage behavior

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Regenerative Biomaterials 2022年第1期9卷 1131-1142页

作者： ana beatriz Sousa Artur P.Águas Mário A.Barbosa Judite N.Barbosa i3S—Instituto de Inovaçäo e Investigaçäo em Saúde Universidade do PortoRua Alfredo Allen2084200-125 PortoPortugal INEB—Instituto de Engenharia Biomédica Rua Alfredo Allen2084200-125 PortoPortugal ICBAS—Instituto de Ciências Biomédicas Abel Salazar Universidade do PortoRua de Jorge Viterbo Ferreira2284050-313 PortoPortugal UMIB—Unit for Multidisciplinary Biomedical Research of ICBAS—Instituto de Ciências Biomédicas de Abel Salazar Universidade do PortoRua de Jorge Viterbo Ferreira2284050-313 PortoPortugal

Successful wound healing is a process that has three overlying phases:inflammatory,proliferative and *** wounds are characterized by a perpetuated inflammation that inhibits the proliferative and remodeling phases and impairs the wound *** are key modulators of the wound healing ***,they are responsible for the wound cleaning and for the phagocytosis of pathogens and afterwards they lead to the resolution of the inflammatory response and they express growth factors important for angiogenesis and cytokines and growth factors needed for cell proliferation and deposition of extracellular *** phenotype of the macrophage changes gradually throughout the healing process from the initial M1 pro-inflammatory phenotype characteristic of the acute response to the M2 pro-regenerative phenotype that allows an accurate tissue *** chronic wounds,M1 pro-inflammatory macrophages persist and impair tissue *** such,immunomodulatory biomaterials arise as promising solutions to accelerate the wound healing *** this review,we discuss the importance of macrophages and their polarization throughout the different phases of wound healing;macrophage dysfunction in chronic wounds and the use of immunomodulatory biomaterials to overcome the critical problem of chronic wounds-the continued inflammatory phase that impairs healing.

关键词： wound healing chronic wounds macrophage immunomodulatory biomaterials

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Network of GRAS transcription factors in plant development,fruit ripening and stress responses

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Horticulture Research 2023年第12期10卷 286-303页

作者： Catarina Neves beatriz Ribeiro Rute Amaro Jesús Expósito Jérôme Grimplet ana Margarida Fortes BioISI-Biosystems and Integrative Sciences Institute Faculty of SciencesUniversity of LisbonCampo Grande1749-016 LisboaPortugal Centro de Investigación y Tecnología Agroalimentaria de Aragón(CITA) Departamento de Ciencia VegetalGobierno de AragónAvda.Montañana 93050059 ZaragozaSpain Instituto Agroalimentario de Aragón-IA2(CITA-Universidad de Zaragoza) Calle Miguel Servet 17750013 ZaragozaSpain

The plant-specific family of GRAS transcription factors has been wide implicated in the regulation of transcriptional reprogramming associated with a diversity of biological functions ranging from plant development processes to stress *** analyses of GRAS transcription factors supported by in silico structural and comparative analyses are emerging and clarifying the regulatory networks associated with their biological *** this review,a detailed analysis of GRAS proteins’structure and biochemical features as revealed by recent discoveries indicated how these characteristics may impact subcellular location,molecular mechanisms,and *** issues associated with GRAS classification into different subfamilies in diverse plant species even in the presence of robust genomic resources are discussed,in particular how it affects assumptions of biological *** into the mechanisms driving evolution of this gene family and how genetic and epigenetic regulation of GRAS contributes to subfunctionalization are ***,this review debates challenges and future perspectives on the application of this complex but promising gene family for crop improvement to cope with challenges of environmental transition.

关键词： function GRAS plant

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Allicin neuroprotective effect during oxidative/inflammatory injury involves AT1-Hsp70-iNOS counterbalance axis

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BIOCELL 2020年第4期44卷 671-681页

作者： LUCIana MAZZEI MARÍA BELÉN RUIZ-ROSO NATALIA DE LAS heras SANDRA BALLESTEROS CAROLINA TORRESPALAZZOLO LEÓN FERDER ALEJANDRA beatriz CAMARGO WALTER MANUCHA Instituto de Medicina y Biología Experimental de Cuyo(IMBECU) Consejo Nacional de Investigaciones Científicas y Tecnológicas(CONICET)Mendoza5500Argentina Área de Farmacología Departamento de PatologíaFacultad de Ciencias MédicasUniversidad Nacional de Cuyo Centro UniversitarioMendoza5500Argentina Departamento de Fisiología Facultad de MedicinaUniversidad ComplutenseMadrid34523España IBAM Universidad Nacional de CuyoCONICETFacultad de Ciencias AgrariasMendozaM5528AHBArgentina Department of Pediatrics Nephrology DivisionMiller School of MedicineUniversity of MiamiMiami33012USA

The ancestral cultures have described many therapeutic properties of garlic,therefore,it is of central interest to elucidate the molecular basis explaining this millenary empirical ***,it has been demonstrated a neuroprotective effect of allicin–a phytochemical present in garlic-linked to oxidative-inflammatory *** improved neuronal injury by heat shock protein 70(Hsp70)and inducible nitric oxide synthase(iNOS)***,allicin exerts renal protection involving a possible angiotensin type 1 receptor(AT1)*** connection,AT1 overexpression has been recognized as a central deleterious factor in many brain ***,there are no studies that evaluate AT1-Hsp70-iNOS interaction as a mechanism linked to ***,our central aim is to evaluate if the allicin protective effect is associated with an AT1-Hsp70-iNOS counterbalance *** this study,a murine microglial cell line(BV-2)was injured with lipopolysaccharides and treated or not with ***,it was evaluated cell viability,proinflammatory cytokine levels,cellular oxidative stress,iNOS,Hsp70,and AT1 protein expression(cellular and mitochondrial fractions),nitrite levels,and protein-protein *** results demonstrated that allicin could prevent neuronal injury due to a reduction in oxidative stress and inflammatory status mediated by an AT1-Hsp70-iNOS counterbalance axis linked to direct protein-protein interaction.

关键词： Allicin neuroinflammation BV-2 cells AT1 receptors iNOS Hsp70

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3-D Characterization of CdSe Nanoparticles Attached to Carbon Nanotubes

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Nano Research 2008年第1期1卷 89-97页

作者： ana B.Hungría beatriz H.Juárez Christian Klinke Horst Weller Paul A.Midgley Department of Materials Science and Metallurgy University of CambridgePembroke StreetCambridgeCB23QZUK 2 Institute of Physical ChemistryUniversity of Hamburg20146 HamburgGermany

The crystallographic structure of CdSe nanoparticles attached to carbon nanotubes has been elucidated by means of high resolution transmission electron microscopy and high angle annular dark field scanning transmission electron microscopy *** rod-like nanoparticles,grown in solution together with carbon nanotubes,undergo a morphological transformation and become attached to the carbon *** tomography reveals that the nanoparticles are hexagonal-based with the(001)planes epitaxially matched to the outer graphene layer.

关键词： Electron tomography CdSe nanoparticles STEM HRTEM carbon nanotubes

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