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1.
Sci Rep ; 9(1): 7187, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31076588

RESUMO

We have used cryo Electron Tomography, proteomics and immunolabeling to study centrosomes isolated from the young lamb thymus, an efficient source of quiescent differentiated cells. We compared the proteome of thymocyte centrosomes to data published for KE37 cells, focusing on proteins associated with centriole disengagement and centrosome separation. The data obtained enhances our understanding of the protein system joining the centrioles, a system comprised of a branched network of fibers linked to an apparently amorphous density that was partially characterized here. A number of proteins were localized to the amorphous density by immunolabeling (C-NAP1, cohesin SMC1, condensin SMC4 and NCAPD2), yet not DNA. In conjuction, these data not only extend our understanding of centrosomes but they will help refine the model that focus on the protein system associated with the centriolar junction.

3.
Mol Nutr Food Res ; 62(9): e1700992, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29573169

RESUMO

SCOPE: This study was undertaken to expand our insights into the mechanisms involved in the tolerance to resveratrol (RSV) that operate at system-level in gut microorganisms and advance knowledge on new RSV-responsive gene circuits. METHODS AND RESULTS: Whole genome transcriptional profiling was used to characterize the molecular response of Lactobacillus plantarum WCFS1 to RSV. DNA repair mechanisms were induced by RSV and responses were triggered to decrease the load of copper, a metal required for RSV-mediated DNA cleavage, and H2 S, a genotoxic gas. To counter the effects of RSV, L. plantarum strongly up- or downregulated efflux systems and ABC transporters pointing to transport control of RSV across the membrane as a key mechanism for RSV tolerance. L. plantarum also downregulated tRNAs, induced chaperones, and reprogrammed its transcriptome to tightly control ammonia levels. RSV induced a probiotic effector gene and a likely deoxycholate transporter, two functions that improve the host health status. CONCLUSION: Our data identify novel protective mechanisms involved in RSV tolerance operating at system level in a gut microbe. These insights could influence the way RSV is used for a better management of gut microbial ecosystems to obtain associated health benefits.


Assuntos
Antioxidantes/metabolismo , Proteínas de Bactérias/metabolismo , Reparo do DNA , Regulação Bacteriana da Expressão Gênica , Lactobacillus plantarum/metabolismo , Modelos Biológicos , Resveratrol/metabolismo , Animais , Proteínas de Bactérias/agonistas , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Transporte Biológico , Cobre/química , Cobre/metabolismo , Suplementos Nutricionais , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Sulfeto de Hidrogênio/antagonistas & inibidores , Sulfeto de Hidrogênio/metabolismo , Lactobacillus plantarum/crescimento & desenvolvimento , Lactobacillus plantarum/isolamento & purificação , Probióticos , Propionatos/metabolismo , RNA Bacteriano/antagonistas & inibidores , RNA Bacteriano/metabolismo , RNA de Transferência/antagonistas & inibidores , RNA de Transferência/metabolismo , Saliva/microbiologia
4.
Stem Cells Dev ; 26(8): 573-584, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-27958775

RESUMO

During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed these data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1,400 differentially expressed genes. More than 200 genes were shortlisted based on the gene ontology (GO) annotation term "transcription." By morpholino-based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function.


Assuntos
Células-Tronco Adultas/metabolismo , Células-Tronco Embrionárias/metabolismo , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , Fígado/citologia , Transcriptoma , Células-Tronco Adultas/citologia , Animais , Células Cultivadas , Células-Tronco Embrionárias/citologia , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Hematopoéticas/citologia , Fígado/embriologia , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
5.
Nucleic Acids Res ; 44(W1): W267-71, 2016 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-27166368

RESUMO

The CRISPR/Cas technology is enabling targeted genome editing in multiple organisms with unprecedented accuracy and specificity by using RNA-guided nucleases. A critical point when planning a CRISPR/Cas experiment is the design of the guide RNA (gRNA), which directs the nuclease and associated machinery to the desired genomic location. This gRNA has to fulfil the requirements of the nuclease and lack homology with other genome sites that could lead to off-target effects. Here we introduce the Breaking-Cas system for the design of gRNAs for CRISPR/Cas experiments, including those based in the Cas9 nuclease as well as others recently introduced. The server has unique features not available in other tools, including the possibility of using all eukaryotic genomes available in ENSEMBL (currently around 700), placing variable PAM sequences at 5' or 3' and setting the guide RNA length and the scores per nucleotides. It can be freely accessed at: http://bioinfogp.cnb.csic.es/tools/breakingcas, and the code is available upon request.


Assuntos
Proteínas de Bactérias/genética , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endonucleases/genética , Genoma , RNA Guia/síntese química , Software , Proteínas de Bactérias/metabolismo , Proteína 9 Associada à CRISPR , Endonucleases/metabolismo , Eucariotos/genética , Edição de Genes , Armazenamento e Recuperação da Informação , Internet , Motivos de Nucleotídeos , RNA Guia/genética
6.
Nucleic Acids Res ; 43(W1): W193-9, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25940629

RESUMO

Drug repositioning, using known drugs for treating conditions different from those the drug was originally designed to treat, is an important drug discovery tool that allows for a faster and cheaper development process by using drugs that are already approved or in an advanced trial stage for another purpose. This is especially relevant for orphan diseases because they affect too few people to make drug research de novo economically viable. In this paper we present NFFinder, a bioinformatics tool for identifying potential useful drugs in the context of orphan diseases. NFFinder uses transcriptomic data to find relationships between drugs, diseases and a phenotype of interest, as well as identifying experts having published on that domain. The application shows in a dashboard a series of graphics and tables designed to help researchers formulate repositioning hypotheses and identify potential biological relationships between drugs and diseases. NFFinder is freely available at http://nffinder.cnb.csic.es.


Assuntos
Reposicionamento de Medicamentos , Perfilação da Expressão Gênica , Software , Transcriptoma/efeitos dos fármacos , Antineoplásicos/farmacologia , Genômica/métodos , Humanos , Internet , Neoplasias da Bainha Neural/genética , Neoplasias da Bainha Neural/metabolismo
7.
Clin Implant Dent Relat Res ; 12 Suppl 1: e77-82, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19076177

RESUMO

BACKGROUND: Conventional prosthetic treatment of the edentulous and resorbed maxilla with zygomatic implants is a lengthy procedure. Today, immediate/early loading is a clinical reality and it is possible that such protocols could be used also for zygomatic implants. PURPOSE: The aim of the present study is to report on the clinical outcomes of immediate/early loading of zygomatic implants for prosthetic rehabilitation of edentulous and severely resorbed maxillary cases. MATERIALS AND METHODS: A total of 47 zygomatic and 129 regular implants were placed in 25 consecutive patients with total (N = 23) or partial (N = 2) edentulism in the maxilla. The patients had less than 4 mm of available bone height and width distal to the canine pillars. Straight and angulated abutments and impression copings were attached to the implants during surgery. Impressions and bite registrations were made and 19 patients received a bridge within 24 hours and six patients were rehabilitated within 5 days. Screw-retained full arch restorations were used in 23 patients and cemented in 2 patients. The patients were instructed for a soft diet during 4 months. Follow-up controls were performed at 1, 4, and 12 months and thereafter annually. All patients were followed for at least 2 years and up to 5 years in function. RESULTS: All zygomatic implants were stable during the follow-up (cumulative survival rate 100%). One regular implant placed in the pterygoid plate failed after 52 months of loading (cumulative survival rate 99.2%). Apart from fracture of one abutment screw and of anterior teeth in five patients, no other complications were noted. CONCLUSIONS: Within the limitations of the present study, it is concluded that immediate/early loading is a viable treatment modality for prosthetic rehabilitation of the severely resorbed maxilla using zygomatic and conventional implants.


Assuntos
Implantação Dentária Endo-Óssea/métodos , Implantes Dentários , Prótese Dentária Fixada por Implante , Prótese Total Imediata , Prótese Parcial Imediata , Zigoma/cirurgia , Adulto , Idoso , Perda do Osso Alveolar/reabilitação , Cimentação , Análise do Estresse Dentário , Prótese Total Superior , Feminino , Seguimentos , Humanos , Arcada Edêntula/reabilitação , Tábuas de Vida , Masculino , Maxila/cirurgia , Pessoa de Meia-Idade , Fatores de Tempo
8.
Clin Implant Dent Relat Res ; 12(1): 55-61, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19076181

RESUMO

BACKGROUND: The surgical protocol for zygomatic fixtures prescribes an intrasinus approach ideally maintaining the sinus membrane intact and the implant body inside the sinus while gaining access to the zygomatic bone. In the presence of a pronounced buccal concavity, the implant head has to be placed far from the alveolar crest in a palatal direction, which results in a bulky bridge construction. PURPOSE: The aim of this study was to report on the preliminary experiences with zygomatic implants placed with an extrasinus approach in order to have the implant head emerging at or near the top of the alveolar crest. MATERIALS AND METHODS: Twenty consecutive patients with pronounced buccal concavities in the edentulous posterior maxilla were treated with 104 regular and 36 zygomatic implants as support of fixed dental bridges. Sixteen patients were treated bilaterally and four patients were treated unilaterally. The zygomatic implants were inserted by using an extrasinus surgical approach with the implant body passing from the alveolar crest through the buccal concavity into the zygomatic bone. This enabled placement of the implant head at or close to the alveolar crest. The patients were followed from 36 to 48 months after occlusal loading with a mean follow-up of 41 months. The relation of the zygomatic implants to the crest was measured and compared with a control group of 20 patients treated with conventional placement of zygomatic implants. RESULTS: No implants were lost during the study period. No pain, discomfort, or complications related to the extrasinus path of the zygomatic implants were recorded after the initial healing period and up to the 36th-month checkup. The zygomatic implants emerged, on average, 3.8 mm (SD 2.6) palatal to the top of the crest compared with 11.2 mm (SD 5.3) to the conventional technique. CONCLUSION: The present 3-year clinical study shows that an extrasinus approach can be utilized when placing zygomatic implants in patients with pronounced buccal concavities in the posterior maxilla. Moreover, the technique results in an emergence of the zygomatic fixture close to the top of the crest, which is beneficial from a cleaning and patient-comfort point of view.


Assuntos
Implantação Dentária Endo-Óssea/métodos , Implantes Dentários , Arcada Edêntula/cirurgia , Maxila/cirurgia , Zigoma/cirurgia , Adulto , Processo Alveolar/patologia , Processo Alveolar/cirurgia , Dente Suporte , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Prótese Total Imediata , Feminino , Seguimentos , Humanos , Arcada Edêntula/patologia , Masculino , Maxila/patologia , Seio Maxilar/patologia , Seio Maxilar/cirurgia , Pessoa de Meia-Idade , Osseointegração/fisiologia , Resultado do Tratamento
9.
Dentum (Barc.) ; 8(2): 57-62, abr.-jun. 2008. ilus
Artigo em Espanhol | IBECS | ID: ibc-78631

RESUMO

Las carillas de porcelana son un tratamiento predecible, conservador con el diente y muy estético, que se ha ido practicando cada vez más debido al aumento de la demanda estética de nuestros pacientes y a la mejora de las porcelanas. Presentamos un caso clínico de rehabilitación del sector anterior utilizando carillas de porcelana feldespática, en donde el éxito clínico del tratamiento depende de un correcto diagnóstico, el plan de tratamiento, la preparación dental, la fabricación en el laboratorio de la cerámica y la técnica adhesiva utilizada (AU)


Porcelain veneers are a predictable treatment, conservative with the teeth and very aesthetic, that are being used more and more due to the aesthetic demand of our patients and the improvement of the porcelains. We present a clinical case of rehabilitation of the anterior sector using felspathic porcelain veneers, where the clinical success of the treatment depends on a correct diagnosis, the plan of treatment, the dental preparation, the making of the ceramic in the laboratory and the adhesive technique used (AU)


Assuntos
Humanos , Porcelana Dentária/uso terapêutico , Facetas Dentárias , Estética Dentária
10.
Recife; Rede Brasileira de Redução de Danos; 2003. 85 p. ilus.
Monografia em Português | Sec. Munic. Saúde SP, DST_AIDS-Acervo | ID: sms-3788

RESUMO

Discute questões sobre o consumo de álcool no mundo. Apresenta propostas relativas ao consumo de álcool/redução de danos no âmbito da saúde, sua relação com a violência doméstica e urbana, o ambiente de trabalho da população trabalhadora urbana e rural, o trânsito, as populações especiais e de alto risco, as políticas públicas, a saúde indígena.


Assuntos
Redução do Dano , Drogas Ilícitas , Alcoolismo
11.
Recife; Rede Brasileira de Deução de Danos; 2003. 85 p. ilus.
Monografia em Português | LILACS | ID: lil-361876

RESUMO

Discute questões sobre o consumo de álcool no mundo. Apresenta propostas relativas ao consumo de álcool/redução de danos no âmbito da saúde, sua relação com a violência doméstica e urbana, o ambiente de trabalho da população trabalhadora urbana e rural, o trânsito, as populações especiais e de alto risco, as políticas públicas, a saúde indígena


Assuntos
Alcoolismo , Redução do Dano , Drogas Ilícitas
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