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[PMID]:28381295
[Au] Autor:Mucksová J; Plachý J; Stanek O; Hejnar J; Kalina J; Benesová B; Trefil P
[Ad] Endereço:BIOPHARM, Research Institute of Biopharmacy and Veterinary Drugs, Jílové U Prahy, Czech Republic.
[Ti] Título:Cytokine response to the RSV antigen delivered by dendritic cell-directed vaccination in congenic chicken lines.
[So] Source:Vet Res;48(1):18, 2017 Apr 05.
[Is] ISSN:1297-9716
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Systems of antigen delivery into antigen-presenting cells represent an important novel strategy in chicken vaccine development. In this study, we verified the ability of Rous sarcoma virus (RSV) antigens fused with streptavidin to be targeted by specific biotinylated monoclonal antibody (anti-CD205) into dendritic cells and induce virus-specific protective immunity. The method was tested in four congenic lines of chickens that are either resistant or susceptible to the progressive growth of RSV-induced tumors. Our analyses confirmed that the biot-anti-CD205-SA-FITC complex was internalized by chicken splenocytes. In the cytokine expression profile, several significant differences were evident between RSV-challenged progressor and regressor chicken lines. A significant up-regulation of IL-2, IL-12, IL-15, and IL-18 expression was detected in immunized chickens of both regressor and progressor groups. Of these cytokines, IL-2 and IL-12 were most up-regulated 14 days post-challenge (dpc), while IL-15 and IL-18 were most up-regulated at 28 dpc. On the contrary, IL-10 expression was significantly down-regulated in all immunized groups of progressor chickens at 14 dpc. We detected significant up-regulation of IL-17 in the group of immunized progressors. LITAF down-regulation with iNOS up-regulation was especially observed in the progressor group of immunized chickens that developed large tumors. Based on the increased expression of cytokines specific for activated dendritic cells, we conclude that our system is able to induce partial stimulation of specific cell types involved in cell-mediated immunity.
[Mh] Termos MeSH primário: Antígenos Virais/imunologia
Galinhas/virologia
Citocinas/fisiologia
Células Dendríticas/imunologia
Vírus do Sarcoma de Rous/imunologia
Sarcoma Aviário/prevenção & controle
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Animais
Animais Congênicos/imunologia
Animais Congênicos/virologia
Anticorpos Biespecíficos/imunologia
Antígenos CD/imunologia
Galinhas/imunologia
Células Dendríticas/virologia
Imunidade Celular/imunologia
Lectinas Tipo C/imunologia
Antígenos de Histocompatibilidade Menor/imunologia
Receptores de Superfície Celular/imunologia
Sarcoma Aviário/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bispecific); 0 (Antigens, CD); 0 (Antigens, Viral); 0 (Cytokines); 0 (DEC-205 receptor); 0 (Lectins, C-Type); 0 (Minor Histocompatibility Antigens); 0 (Receptors, Cell Surface); 0 (Viral Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1186/s13567-017-0423-8


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[PMID]:27862163
[Au] Autor:Takagi Y; Kadowaki H; Kobayashi I; Ito K; Ito K; Shirai M; Asai F
[Ad] Endereço:Laboratory of Veterinary Pharmacology, Azabu University, Sagamihara, Kanagawa, Japan.
[Ti] Título:Effects of high-sodium intake on systemic blood pressure and vascular responses in spontaneously diabetic WBN/Kob-Lepr rats.
[So] Source:Clin Exp Pharmacol Physiol;44(2):305-312, 2017 Feb.
[Is] ISSN:1440-1681
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:The prevalence of type 2 diabetes mellitus (T2DM) and hypertension has markedly increased worldwide. The purpose of the present study was to examine the effects of a high-salt intake on the systolic blood pressure (SBP) and vascular responses in WBN/Kob-Lepr (WBKDF) rats, a new spontaneous animal model of T2DM. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (NS, 0.26%) diet or high-sodium (HS, 8%) diet for 14 weeks: (i) Wistar rats on NS diet (Wistar-NS); (ii) Wistar rats on HS diet (Wistar-HS); (iii) WBKDF rats on NS diet (WBKDF-NS); (iv) WBKDF rats on HS diets (WBKDF-HS). Neither WBKDF-NS nor Wistar-NS rats showed significant changes in SBP throughout the experiment, but both WBKDF-HS and Wistar-HS exhibited significant elevation of SBP, which was more prominent (P<.01) in WBKDF-HS than in Wistar-HS. Phenylephrine-induced contractions of isolated thoracic aortic rings were significantly (P<.01) enhanced in WBKDF-HS and Wistar-HS compared with the respective strain of rats on the NS diet. In contrast, acetylcholine- and nitroprusside-induced relaxation were significantly (P<.01) diminished in both WBKDF-HS and Wistar-HS, and these HS diet-induced changes were more profound (P<.01) in WBKDF rats than in Wistar rats. Significantly (P<.05) higher plasma concentrations of 8-iso-prostaglandin F and sodium ions were observed in WBKDF-HS than in Wistar-HS. The current study demonstrated that WBKDF-HS rats developed salt-sensitive hypertension associated with vascular dysfunction. The WBKDF rat may be a useful model for investigating the etiology of hypertension with T2DM.
[Mh] Termos MeSH primário: Pressão Sanguínea/efeitos dos fármacos
Diabetes Mellitus Experimental/fisiopatologia
Diabetes Mellitus Tipo 2/fisiopatologia
Obesidade/fisiopatologia
Cloreto de Sódio na Dieta/efeitos adversos
Vasoconstrição/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Animais Congênicos
Aorta Torácica/efeitos dos fármacos
Aorta Torácica/fisiopatologia
Glicemia/análise
Diabetes Mellitus Experimental/sangue
Diabetes Mellitus Experimental/complicações
Diabetes Mellitus Tipo 2/sangue
Diabetes Mellitus Tipo 2/complicações
Hipertensão/etiologia
Insulina/sangue
Rim/patologia
Rim/fisiopatologia
Masculino
Obesidade/sangue
Obesidade/complicações
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Insulin); 0 (Sodium Chloride, Dietary)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1111/1440-1681.12700


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[PMID]:27755386
[Au] Autor:Koh-Tan HH; Dashti M; Wang T; Beattie W; Mcclure J; Young B; Dominiczak AF; McBride MW; Graham D
[Ad] Endereço:aInstitute of Cardiovascular & Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK bDepartment of Anatomical Pathology, Pathology North (Hunter), John Hunter Hospital, New Lambton, New South Wales, Australia.
[Ti] Título:Dissecting the genetic components of a quantitative trait locus for blood pressure and renal pathology on rat chromosome 3.
[So] Source:J Hypertens;35(2):319-329, 2017 Feb.
[Is] ISSN:1473-5598
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We have previously confirmed the importance of rat chromosome 3 (RNO3) genetic loci on blood pressure elevation, pulse pressure (PP) variability and renal pathology during salt challenge in the stroke-prone spontaneously hypertensive (SHRSP) rat. The aims of this study were to generate a panel of RNO3 congenic sub-strains to genetically dissect the implicated loci and identify positional candidate genes by microarray expression profiling and analysis of next-generation sequencing data. METHOD AND RESULTS: A panel of congenic sub-strains were generated containing Wistar-Kyoto (WKY)-introgressed segments of varying size on the SHRSP genetic background, focused within the first 50 Mbp of RNO3. Haemodynamic profiling during salt challenge demonstrated significantly reduced systolic blood pressure, diastolic blood pressure and PP variability in SP.WKYGla3a, SP.WKYGla3c, SP.WKYGla3d and SP.WKYGla3e sub-strains. Only SBP and DBP were significantly reduced during salt challenge in SP.WKYGla3b and SP.WKYGla3f sub-strains, whereas SP.WKYGla3g rats did not differ in haemodynamic response to SHRSP. Those sub-strains demonstrating significantly reduced PP variability during salt challenge also demonstrated significantly reduced renal pathology and proteinuria. Microarray expression profiling prioritized two candidate genes for blood pressure regulation (Dnm1, Tor1b), localized within the common congenic interval shared by SP.WKYGla3d and SP.WKYGla3f strains, and one candidate gene for salt-induced PP variability and renal pathology (Rabgap1), located within the region unique to the SP.WKYGla3d strain. Comparison of next-generation sequencing data identified variants within additional positional genes that are likely to affect protein function. CONCLUSION: This study has identified distinct intervals on RNO3-containing genes that may be important for blood pressure regulation and renal pathology during salt challenge.
[Mh] Termos MeSH primário: Pressão Sanguínea/genética
Dinamina I/genética
Hipertensão/genética
Chaperonas Moleculares/genética
Locos de Características Quantitativas
[Mh] Termos MeSH secundário: Animais
Animais Congênicos
Mapeamento Cromossômico
Cromossomos de Mamíferos
Perfilação da Expressão Gênica
Sequenciamento de Nucleotídeos em Larga Escala
Hipertensão/patologia
Rim/metabolismo
Masculino
Análise de Sequência com Séries de Oligonucleotídeos
Ratos
Ratos Endogâmicos SHR
Ratos Endogâmicos WKY
Análise de Sequência de DNA
Cloreto de Sódio na Dieta/administração & dosagem
Acidente Vascular Cerebral/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Molecular Chaperones); 0 (Sodium Chloride, Dietary); 0 (Tor1b protein, rat); EC 3.5.1.50 (Dynamin I)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161019
[St] Status:MEDLINE
[do] DOI:10.1097/HJH.0000000000001155


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[PMID]:28105932
[Au] Autor:Korbolina EE; Zhdankina AA; Fursova AZ; Kozhevnikova OS; Kolosova NG
[Ad] Endereço:Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia. lungry@bionet.nsc.ru.
[Ti] Título:Genes of susceptibility to early neurodegenerative changes in the rat retina and brain: analysis by means of congenic strains.
[So] Source:BMC Genet;17(Suppl 3):153, 2016 Dec 22.
[Is] ISSN:1471-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There has been considerable interest in discovery of the genetic architecture of complex traits, particularly age-related neurodegenerative disorders. To predict disease risk and to understand its genetic basis in humans, it is necessary to study animal models. Our previous research on the accelerated-senescence OXYS strain has revealed two quantitative trait loci (QTLs) on rat chromosome 1 that are associated with early cataract and/or retinopathy as well as with behavioral abnormalities. Each locus was partially mapped within the introgressed segments in a certain congenic strain: WAG/OXYS-1.1 or WAG/OXYS-1.2. Retinal transcriptome profiling of 20-day-old congenic and OXYS rats by high-throughput RNA sequencing uncovered relevant candidate genes and pathways. Nonetheless, the question remained open whether the same genetic components simultaneously have effects on various manifestations of the accelerated-senescence phenotype in OXYS rats. The present study was designed to analyze the genes of susceptibility to early neurodegenerative processes taking place in the OXYS rat retina and brain and to assess their potential functional clustering. The study was based on the findings from recent publications (including mapping of quantitative trait loci) and on comparative phenotyping of congenic rat strains. RESULTS: The backcrossing of Wistar Albino Glaxo (WAG) and OXYS strains to generate the congenics resulted in two congenic strains with high susceptibility to cataract and retinopathy but with no obvious signs of Alzheimer's disease-like brain pathology that are specific for OXYS rats. Thus, the genes of susceptibility to brain neurodegeneration were not introgressed into the congenic strains or there is a strong effect of the genetic background on the disease phenotype. Moreover, the progression of retinopathy with age was relatively less severe in the WAG background compared to the OXYS background. A comparative analysis of previously defined QTLs and congenic segments led to identification of candidate genes with a suspected effect on brain neurodegeneration including the genes showing differential expression in the congenic strains. CONCLUSION: Overall, our findings suggest that the cause of the cataract and the cause of retinopathy phenotypes in OXYS rats may be genetically linked to each other within the introgressed segments in the WAG/OXYS-1.1 and/or WAG/OXYS-1.2 congenic strains.
[Mh] Termos MeSH primário: Doença de Alzheimer/patologia
Encéfalo/metabolismo
Degeneração Macular/patologia
Retina/metabolismo
[Mh] Termos MeSH secundário: Envelhecimento
Doença de Alzheimer/diagnóstico por imagem
Doença de Alzheimer/genética
Animais
Animais Congênicos
Comportamento Animal
Encéfalo/diagnóstico por imagem
Encéfalo/patologia
Catarata/genética
Catarata/patologia
Modelos Animais de Doenças
Suscetibilidade a Doenças
Degeneração Macular/genética
Imagem por Ressonância Magnética
Masculino
Fenótipo
Análise de Componente Principal
Locos de Características Quantitativas
Ratos
Ratos Wistar
Retina/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1186/s12863-016-0461-7


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[PMID]:27926922
[Au] Autor:Grove E; Eckardt S; McLaughlin KJ
[Ad] Endereço:Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
[Ti] Título:High-Speed Mouse Backcrossing Through the Female Germ Line.
[So] Source:PLoS One;11(12):e0166822, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transferring mouse mutations into specific mouse strain backgrounds can be critical for appropriate analysis of phenotypic effects of targeted genomic alterations and quantitative trait loci. Speed congenic breeding strategies incorporating marker-assisted selection of progeny with the highest percentage target background as breeders for the next generation can produce congenic strains within approximately 5 generations. When mating selected donor males to target strain females, this may require more than 1 year, with each generation lasting 10 to 11 weeks including 3 weeks of gestation and 7 to 8 weeks until the males reach sexual maturity. Because ovulation can be induced in female mice as early as 3 weeks of age, superovulation-aided backcrossing of marker-selected females could accelerate the production of congenic animals by approximately 4 weeks per generation, reducing time and cost. Using this approach, we transferred a transgenic strain of undefined genetic background to >99% C57BL/6J within 10 months, with most generations lasting 7 weeks. This involved less than 60 mice in total, with 9 to 18 animals per generation. Our data demonstrate that high-speed backcrossing through the female germline is feasible and practical with small mouse numbers.
[Mh] Termos MeSH primário: Células Germinativas/fisiologia
Reprodução/fisiologia
[Mh] Termos MeSH secundário: Animais
Animais Congênicos/fisiologia
Feminino
Endogamia/métodos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Fenótipo
Locos de Características Quantitativas/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170703
[Lr] Data última revisão:
170703
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161208
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0166822


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[PMID]:27716393
[Au] Autor:Dumas ME; Domange C; Calderari S; Martínez AR; Ayala R; Wilder SP; Suárez-Zamorano N; Collins SC; Wallis RH; Gu Q; Wang Y; Hue C; Otto GW; Argoud K; Navratil V; Mitchell SC; Lindon JC; Holmes E; Cazier JB; Nicholson JK; Gauguier D
[Ad] Endereço:Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College, London, SW7 2AZ, UK. m.dumas@imperial.ac.uk.
[Ti] Título:Topological analysis of metabolic networks integrating co-segregating transcriptomes and metabolomes in type 2 diabetic rat congenic series.
[So] Source:Genome Med;8(1):101, 2016 09 30.
[Is] ISSN:1756-994X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge. Here, we introduce a systems genetics approach based on the topological analysis of a combined molecular network made of genes and metabolites identified through expression and metabotype quantitative trait locus mapping (i.e., eQTL and mQTL) to prioritise biological characterisation of candidate genes and traits. METHODS: We used systematic metabotyping by H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualize the shortest paths between metabolites and genes significantly associated with each genomic block. RESULTS: Despite strong genomic similarities (95-99 %) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting the metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific mQTLs and genome-wide eQTLs. Variation in key metabolites like glucose, succinate, lactate, or 3-hydroxybutyrate and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing the shortest path length drove prioritization of biological validations by gene silencing. CONCLUSIONS: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulation and to characterize novel functional roles for genes determining tissue-specific metabolism.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/genética
Diabetes Mellitus Tipo 2/metabolismo
Metaboloma
Locos de Características Quantitativas
Característica Quantitativa Herdável
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Animais Congênicos
Mapeamento Cromossômico
Diabetes Mellitus Tipo 2/patologia
Modelos Animais de Doenças
Feminino
Perfilação da Expressão Gênica
Regulação da Expressão Gênica
Ontologia Genética
Redes Reguladoras de Genes
Estudos de Associação Genética
Predisposição Genética para Doença
Seres Humanos
Masculino
Redes e Vias Metabólicas
Anotação de Sequência Molecular
Ratos Endogâmicos BN
Biologia de Sistemas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161008
[St] Status:MEDLINE


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[PMID]:27154353
[Au] Autor:Clark AA; Nurmukhambetova S; Li X; Munger SD; Lees JR
[Ad] Endereço:Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
[Ti] Título:Odorants specifically modulate chemotaxis and tissue retention of CD4+ T cells via cyclic adenosine monophosphate induction.
[So] Source:J Leukoc Biol;100(4):699-709, 2016 Oct.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Retention of T cells within affected tissue is a critical component of adaptive immune inflammation. However, the mechanisms involved in T cell retention remain largely undefined. Previous studies revealed the capacity of cAMP signaling to regulate immune cell migration, as well as dynamic regulation of receptors that could induce cAMP production in immune cells. The potential for cAMP to act as a retention signal has been mostly unexplored, partially as a result of this second messenger's well-characterized inhibition of effector function in immune cells. Here, we report that cAMP regulates the tissue retention of mouse T cells at concentrations well below those that inhibited proliferation or decreased acquisition of an effector phenotype. Stimulation of CD4 T cells with odorants known to be cognate ligands for T cell-expressed olfactory receptors induced cAMP and inhibited chemokine-driven chemotaxis without decreasing T cell proliferation or effector functions. Similar effects were observed following treatment with relatively low concentrations of the cAMP analog Sp-5,6-dichloro-1-ß-d-ribofuranosylbenzimidazole-3',5'-monophosphorothioate. Furthermore, pretreatment with odorants or cAMP at concentrations that did not inhibit effector function induced T cell tissue retention in mice by inhibiting chemokine-dependent T cell egress from the footpad to the draining lymph node. Together, these results suggest that odorant receptor-mediated increases in intracellular cAMP can modulate T cell tissue trafficking and may offer new therapeutic targets for controlling T cell tissue accumulation.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/efeitos dos fármacos
Quimiotaxia de Leucócito/efeitos dos fármacos
AMP Cíclico/biossíntese
Ácidos Dicarboxílicos/farmacologia
Odorantes
[Mh] Termos MeSH secundário: Imunidade Adaptativa
Animais
Animais Congênicos
Antígenos CD/biossíntese
Antígenos de Diferenciação de Linfócitos T/biossíntese
Linfócitos T CD4-Positivos/citologia
Linfócitos T CD4-Positivos/transplante
Linhagem Celular Tumoral
Células Cultivadas
Quimiocina CCL21/farmacologia
Quimiocina CXCL12/farmacologia
Colforsina/farmacologia
AMP Cíclico/farmacologia
Diclororribofuranosilbenzimidazol/análogos & derivados
Diclororribofuranosilbenzimidazol/farmacologia
Ácidos Graxos/farmacologia
Hidrazonas/farmacologia
Isoxazóis/farmacologia
Lectinas Tipo C/biossíntese
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos C57BL
Receptores Odorantes/sangue
Receptores Odorantes/efeitos dos fármacos
Tionucleotídeos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-(5-tert-butylisoxazol-3-yl)-2-((3-chlorophenyl)hydrazono)-3-oxopropionitrile); 0 (Antigens, CD); 0 (Antigens, Differentiation, T-Lymphocyte); 0 (CD69 antigen); 0 (Chemokine CCL21); 0 (Chemokine CXCL12); 0 (Dicarboxylic Acids); 0 (Fatty Acids); 0 (Hydrazones); 0 (Isoxazoles); 0 (Lectins, C-Type); 0 (Receptors, Odorant); 0 (Thionucleotides); 120912-54-1 (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole-3',5'-monophosphorothioate); 1F7A44V6OU (Colforsin); 53-85-0 (Dichlororibofuranosylbenzimidazole); 97SEH7577T (pelargonic acid); E0399OZS9N (Cyclic AMP); F2VW3D43YT (azelaic acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171001
[Lr] Data última revisão:
171001
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160508
[St] Status:MEDLINE


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[PMID]:27113531
[Au] Autor:Nie Y; Kumarasamy S; Waghulde H; Cheng X; Mell B; Czernik PJ; Lecka-Czernik B; Joe B
[Ad] Endereço:Program in Physiological Genomics, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio;
[Ti] Título:High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass.
[So] Source:Physiol Genomics;48(6):409-19, 2016 06.
[Is] ISSN:1531-2267
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Through linkage analysis of the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), a blood pressure (BP) quantitative trait locus (QTL) was previously located on rat chromosome 9. Subsequent substitution mapping studies of this QTL revealed multiple BP QTLs within the originally identified logarithm of odds plot by linkage analysis. The focus of this study was on a 14.39 Mb region, the distal portion of which remained unmapped in our previous studies. High-resolution substitution mapping for a BP QTL in the setting of a high-salt diet indicated that an SHR-derived congenic segment of 787.9 kb containing the gene secreted phosphoprotein-2 (Spp2) lowered BP and urinary protein excretion. A nonsynonymous G/T polymorphism in the Spp2 gene was detected between the S and S.SHR congenic rats. A survey of 45 strains showed that the T allele was rare, being detected only in some substrains of SHR and WKY. Protein modeling prediction through SWISSPROT indicated that the predicted protein product of this variant was significantly altered. Importantly, in addition to improved cardiovascular and renal function, high salt-fed congenic animals carrying the SHR T variant of Spp2 had significantly lower bone mass and altered bone microarchitecture. Total bone volume and volume of trabecular bone, cortical thickness, and degree of mineralization of cortical bone were all significantly reduced in congenic rats. Our study points to opposing effects of a congenic segment containing the prioritized candidate gene Spp2 on BP and bone mass.
[Mh] Termos MeSH primário: Pressão Sanguínea/genética
Osso e Ossos/metabolismo
Cromossomos Humanos Par 9/genética
Fosfoproteínas/genética
Locos de Características Quantitativas/genética
[Mh] Termos MeSH secundário: Alelos
Animais
Animais Congênicos/genética
Mapeamento Cromossômico/métodos
Ligação Genética/genética
Seres Humanos
Hipertensão/genética
Masculino
Ratos
Ratos Endogâmicos Dahl
Ratos Endogâmicos SHR/genética
Ratos Endogâmicos WKY
Cloreto de Sódio na Dieta/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Phosphoproteins); 0 (Sodium Chloride, Dietary)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160427
[St] Status:MEDLINE
[do] DOI:10.1152/physiolgenomics.00004.2016


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[PMID]:27073989
[Au] Autor:Cheng X; Waghulde H; Mell B; Smedlund K; Vazquez G; Joe B
[Ad] Endereço:Program in Physiological Genomics, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, United States of America.
[Ti] Título:Pleiotropic Effect of a High Resolution Mapped Blood Pressure QTL on Tumorigenesis.
[So] Source:PLoS One;11(4):e0153519, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study is focused on a translationally significant, genome-wide-association-study (GWAS) locus for cardiovascular disease (QT-interval) on human chromosome 17. We have previously validated and high resolution mapped the homologous genomic segment of this human locus to <42.5 kb on rat chromosome 10. This <42.5 kb segment in rats regulates both QT-interval and blood pressure and contains a single protein-coding gene, rififylin (Rffl). The expression of Rffl in the hearts and kidneys is differential between Dahl S and S.LEW congenic rats, which are the strains used for mapping this locus. Our previous study points to altered rate of endocytic recycling as the underlying mechanism, through which Rffl operates to control both QT-interval and blood pressure. Interestingly, Rffl also contributes to tumorigenesis by repressing caspases and tumor suppressor genes. Moreover, the expression of Methyl-CpG Binding Domain Protein 2 (Mbd2) in the hearts and kidneys is also higher in the S.LEW congenic strain than the background (control) Dahl S strain. Mbd2 can repress methylated tumor suppressor genes. These data suggest that the S.LEW congenic strain could be more susceptible to tumorigenesis. To test this hypothesis, the S and S.LEW strains were compared for susceptibility to azoxymethane-induced colon tumors. The number of colon tumors was significantly higher in the S.LEW congenic strain compared with the S rat. Transcriptomic analysis confirmed that the chemical carcinogenesis pathway was significantly up-regulated in the congenic strain. These studies provide evidence for a GWAS-validated genomic segment on rat chromosome 10 as being important for the regulation of cardiovascular function and tumorigenesis.
[Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/genética
Pressão Sanguínea/genética
Carcinogênese/genética
Hipertensão/genética
Locos de Características Quantitativas
Ubiquitina-Proteína Ligases/genética
[Mh] Termos MeSH secundário: Animais
Animais Congênicos
Apoptose/genética
Determinação da Pressão Arterial
Seres Humanos
Característica Quantitativa Herdável
Ratos
Ratos Endogâmicos Dahl
Ratos Endogâmicos Lew
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); EC 2.3.2.27 (Rffl protein, mouse); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160414
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0153519


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[PMID]:27031336
[Au] Autor:Sedová L; Pravenec M; Krenová D; Kazdová L; Zídek V; Krupková M; Liska F; Kren V; Seda O
[Ad] Endereço:Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and the General Teaching Hospital, Prague, Czech Republic.
[Ti] Título:Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.
[So] Source:PLoS One;11(3):e0152708, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16) and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx) into the genomic background of the spontaneously hypertensive rat (SHR) strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference) and diastolic (10-15 mmHg difference) blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001). The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes) are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1). Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic syndrome.
[Mh] Termos MeSH primário: Animais Congênicos/genética
Cromossomos Humanos Par 16/genética
Síndrome Metabólica/genética
Ratos Endogâmicos BN/genética
Ratos Endogâmicos SHR/genética
[Mh] Termos MeSH secundário: Animais
Animais Congênicos/metabolismo
Animais Congênicos/fisiologia
Genoma
Teste de Tolerância a Glucose
Hemodinâmica
Seres Humanos
Masculino
Síndrome Metabólica/metabolismo
Síndrome Metabólica/fisiopatologia
Metaboloma
Ratos Endogâmicos BN/metabolismo
Ratos Endogâmicos BN/fisiologia
Ratos Endogâmicos SHR/metabolismo
Ratos Endogâmicos SHR/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1608
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160401
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0152708



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