RESUMO
PURPOSE: Immunoscore can effectively predict prognosis in patients with colon cancer; however, its clinical application is limited. We modified the Immunoscore and created a tumor immune microenvironment (TIM) classification system for gastric carcinoma. Unlike previous studies that used small sample sizes or focused on particular immune-cell subtypes, our simplified system enables pathologists to classify gastric carcinomas intuitively using H&E-stained sections. METHODS: Samples from 326 patients with advanced gastric carcinoma were reviewed and analyzed by pathologists using simple determination and digital image analysis. Comprehensive results of cancer-panel sequencing, Epstein-Barrâvirus (EBV) status, and PD-L1, HER2, ATM, PTEN, MET, FGFR2, and EGFR immunohistochemistry were evaluated with respect to the TIM class. RESULTS: The TIM was classified as "hot" (n = 22), "immunosuppressed" (n = 178), "excluded" (n = 83), or "cold" (n = 43). TIM category was significantly associated with numbers of frameshift mutations (P < 0.001) and high tumor mutational burden (P < 0.004), and predicted overall survival. It was also significantly associated with age, histological type, degree of fibrosis, PD-L1 expression, loss of ATM and PTEN expression (P < 0.001), sex, EBV positivity, and HER2 overexpression (P < 0.04). "Hot" tumors were frequent in PD-L1 expressing and EBV-positive samples, and in those with ATM and PTEN loss. "Excluded" tumors were frequent in HER2-positive cases, whereas "cold" tumors were more frequent in younger patients with poorly cohesive histology and high fibrosis levels. CONCLUSIONS: TIM classification system for gastric carcinoma has prognostic significance and results in classes that are associated with molecular characteristics.
Assuntos
Mutação da Fase de Leitura , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
Salinity is a major environmental stress to plants. In this study, the ability of plants to tolerate salt was investigated by studying growth, physiological characteristics, and expression levels of genes related to the salt-stress response in the salt-tolerant rice mutant (Till-II-877), which was derived from γ-ray irradiation. Compared to plants grown under normal conditions, the height and root length of wild type (WT) were reduced by approximately 40 and 29% following exposure to salt stress for 3 weeks, whereas Till-II-877 line showed 29 and 23% reductions in plant height and root length, respectively. No significant changes were observed in total chlorophyll content, and the malondialdehyde content of the mutant increased less than that of the WT under salt treatment. Gene expression was compared between the WT and mutant lines using microarray analysis. An unbiased analysis of the gene expression datasets allowed us to identify the pathways involved in salt-stress responses. Among the most significantly affected pathways, changes in gene expression were observed in α-linolenic acid and linoleic acid metabolism (in lipid metabolism), fructose and mannose metabolism and glycolysis-gluconeogenesis (in carbohydrate metabolism), cysteine and methionine metabolism (in amino acid metabolism), and carbon fixation (in the energy metabolism of photosynthetic organisms) under salt stress. These results show that the differential response of plants subjected to salt stress was due to changes in multiple metabolic pathways. These findings increase our understanding of the effects of salt stress in rice and may aid in the development of salt-tolerant rice cultivars.
Assuntos
Regulação da Expressão Gênica de Plantas , Genoma de Planta , Mutação/genética , Oryza/genética , Oryza/fisiologia , Estresse Fisiológico/genética , Carotenoides/metabolismo , Clorofila/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ontologia Genética , Genes de Plantas , Malondialdeído/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Cloreto de Sódio/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacosRESUMO
This study evaluated the chemical and genetic diversity of high-seed-yield sorghum germplasms from Korea, the United States, and South Africa. We identified significant differences in the chemical contents of whole plants at the heading stage in all cultivars, including differences in crude protein, fat, fiber, ash, neutral detergent fiber, acid detergent fiber, mineral, and fatty acid contents. Our results suggest that Banwoldang is the most appropriate cultivar for roughage because of its high protein yield. We identified significant differences in the tannin, flavonoid, amylose, mineral, crude fat, fatty acid, and 3-deoxyanthocyanin contents in the whole grain from all cultivars, but not in the mineral or crude fat contents. Tannin levels were generally low. IS645 contained the highest levels of flavonoids and linolenic acid compounds, and Moktak had the highest amylose and deoxyanthocyanidin content in the grain. To assess genetic diversity, we used 10 simple sequence repeat (SSR) primer sets to identify 38 alleles with 3-8 alleles per locus. Based on phylogenetic analysis of the SSR markers, the sorghum cultivars were divided into three major groups. Comparison of clusters based on chemical compositions with those based on SSRs showed that the groups formed by the three native Korean cultivars clustered similarly in molecular dendrograms. Association analysis was conducted for the 10 SSR marker; 48 chemical and growth traits were present for two marker traits (seed color and whole plant fatty acid content) with significant marker-trait associations. These markers could be used to select sorghum cultivars for breeding programs.
Assuntos
Loci Gênicos , Variação Genética , Filogenia , Sementes/genética , Sorghum/genética , Alelos , Antocianinas/metabolismo , Cruzamentos Genéticos , Ácidos Graxos/metabolismo , Flavonoides/metabolismo , Repetições de Microssatélites , Melhoramento Vegetal , Proteínas de Plantas/metabolismo , República da Coreia , Sementes/metabolismo , Sorghum/classificação , Sorghum/metabolismo , África do Sul , Taninos/metabolismo , Estados UnidosRESUMO
Under certain circumstances, transposable elements (TE) can create or reverse mutations and alter the genome size of a cell. Sorghum (Sorghum bicolor L.) is promising for plant transposon tagging due to its small genome size and its low content of repetitive DNA. We developed a marker system based on targeted region amplification polymorphisms (TE-TRAP) that uses the terminal inverted repeats (TIRs) of transposons. A total of 3816 class 2 transposons belonging to the PIF/Harbinger family were identified from the whole sorghum genome that produced five primers, including eight types of TIRs. To define the applicability and utilization of TE-TRAP, we used 21 individuals that had been bred after ɤ-ray irradiation. In total, 31 TE-TRAP, 16 TD, and 21 AFLP primer combinations generated 1133, 223, and 555 amplicons, respectively. The percent polymorphic marker was 62.8, 51.1, and 59.3% for the TE-TRAP, TD, and AFLP markers, respectively. Phylogenetic and principal component analyses revealed that TE-TRAP divided the 21 individuals into three groups. Analysis of molecular variance suggested that TE-TRAP had a higher level of genetic diversity than the other two marker systems. After verifying the efficiency of TE-TRAP, 189 sorghum individuals were used to investigate the associations between the markers and the ɤ-ray doses. Two significant associations were found among the polymorphic markers. This TE-based method provides a useful marker resource for mutation breeding research.
Assuntos
Elementos de DNA Transponíveis/genética , Filogenia , Melhoramento Vegetal , Sorghum/genética , Relação Dose-Resposta à Radiação , Raios gama , Marcadores Genéticos , Genoma de Planta/efeitos da radiação , Mutação , Sorghum/crescimento & desenvolvimento , Sorghum/efeitos da radiaçãoRESUMO
Comparative genomic hybridization (CGH) is a powerful tool used to analyze changes in copy number, polymorphisms, and structural variations in the genome. Gene copy number variation (CNV) is a common form of natural diversity in the genome, which can create new genes and alter gene structure. Thus, CNVs may influence phenotypic variation and gene expression. In this study, to detect CNVs, we irradiated rice seeds with gamma rays (300 Gy) and selected two dwarf mutagenized plants, GA-III-189 and -1052, in the M3 generation. These plants were subjected to CGH analysis using Agilent's RICE CGH array. Most of the CNVs identified were less than 10 kb in length. We detected 90 amplified and 18 deleted regions in GA-III-189, and 99 amplified and 11 deleted regions in GA-III-1052. Of note, CNVs were located on chromosome 12 in both GA-III-189 and -1052, which contained 39 commonly amplified regions in 29 genes. The commonly amplified genes included six genes encoding F-box domain-containing proteins. Alterations in these F-box domain-containing genes were confirmed by quantitative RT-PCR. Integration of CGH and gene expression data identified copy number aberrations and novel genes potentially involved in the dwarf phenotype. These CGH and gene expression data may be useful for uncovering the mechanisms underlying the dwarf phenotype.
Assuntos
Hibridização Genômica Comparativa , Raios gama , Mutação/efeitos da radiação , Oryza/genética , Oryza/efeitos da radiação , Variações do Número de Cópias de DNA , Raios gama/efeitos adversos , Expressão Gênica , Estudos de Associação Genética , FenótipoRESUMO
OBJECTIVE: Urban Jamaican adolescent girls face significant risk for sexually transmitted infections including HIV. Studies from the United States of America have found that parents influence adolescents' sexual risk attitudes and behaviours through parent-child sexual communication and monitoring/ supervision. Data from an ongoing mother-daughter HIV risk reduction intervention study in Kingston, Jamaica identified an additional influence of adolescent girls' sexual risk - maternal sexual role modelling (MSRM). As no reliable and valid questionnaires existed to measure MSRM, one was developed. The objective of the current study was to evaluate the psychometric properties of the Jamaican Maternal Sexual Role Modelling questionnaire. METHOD: Data were collected from 209 Jamaican female adolescents recruited from Kingston, St Andrew and St Catherine parishes. RESULTS: The final 19-item Jamaican MSRM questionnaire was found to have excellent internal reliability (Cronbach's alpha = 0.89). Content validity expert ratings and modified kappa statistics were all 1.0. Principal component analysis identified a three-factor structure that accounted for 53.7% of the variance. Greater MSRM scale scores, indicating more positive and protective maternal sexual role modelling, were associated with less sexual experience, lower intentions to have sex, greater intentions to use condoms if having sex and greater condom use self-efficacy among adolescent girls. CONCLUSION: The MSRM scale was found to be a reliable and valid measure of Jamaican adolescent females' perceptions of their mothers' sexual role modelling. Further research is needed to assess the reliability and validity of the instrument with other populations.
OBJETIVO: Las jóvenes adolescentes urbanas de Jamaica, enfrentan un riesgo significativo de infecciones de trasmisión sexual, incluyendo el VIH. Estudios de los Estados Unidos de América han encontrado que los padres influyen en las conductas y actitudes de riesgo sexual de los adolescentes a través de la comunicación entre padres e hijos sobre asuntos de sexo, acompañada de supervisión y monitoreo. Datos obtenidos a partir de un estudio de intervención que se desarrolla actualmente en Kingston, Jamaica, para reducir el riesgo de VIH madre-hija, identificaron una influencia adicional de riesgo sexual entre las adolescentes: la modelación del rol sexual materno (MRSM). Como que no existían cuestionarios válidos y fiables para medir la MRSM, se desarrolló uno a propósito de este trabajo. El objetivo del presente estudio fue evaluar las propiedades psicométricas del cuestionario de la modelación del rol sexual materno jamaicano. MÉTODO: Se recopilaron datos de 209 adolescentes jamaicanas reclutadas en los distritos de Kingston, St Andrew y St Catherine. RESULTADOS: Se halló que el cuestionario final MRSM jamaicano de 19 ítems poseía excelente fiabilidad interna (alfa de Cronbach = 0.89). Las valoraciones (ratings) de los expertos con respecto a la validez del contenido, así como las estadísticas Kappa modificadas, fueron todas 1.0. El análisis del componente principal identificó una estructura de tres factores que daba cuenta del 53.7% de la varianza. Mayores puntuaciones de la escala MRSM, que indicaban una modelación del rol sexual materno más positiva y protectora, estuvieron asociadas con menor experiencia sexual, menos intenciones de tener sexo, más intenciones de usar condón a la hora de mantener relaciones sexuales, y mayor auto-eficacia en el uso de condón entre las adolescentes. CONCLUSIÓN: Se halló que la escala MRSM es fiable y constituye una medida válida de las percepciones que las adolescentes jamaicanas tienen en relación con la modelación del rol sexual de sus madres. Se necesita continuar las investigaciones a fin de evaluar la fiabilidad y validez del instrumento con otras poblaciones.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Comparação Transcultural , Identidade de Gênero , Comportamento Imitativo , Relações Mãe-Filho , Inquéritos e Questionários , Comportamento Sexual , População Urbana , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Jamaica , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Educação Sexual , Estados Unidos , Sexo sem Proteção/prevenção & controle , Sexo sem Proteção/psicologiaRESUMO
OBJECTIVE: Urban Jamaican adolescent girls face significant risk for sexually transmitted infections including HIV Studies from the United States ofAmerica have found that parents influence adolescents' sexual risk attitudes and behaviours through parent-child sexual communication and monitoring/supervision. Data from an ongoing mother-daughter HIVrisk reduction intervention study in Kingston, Jamaica identified an additional influence of adolescent girls' sexual risk - maternal sexual role modelling (MSRM). As no reliable and valid questionnaires existed to measure MSRM, one was developed. The objective of the current study was to evaluate the psychometric properties of the Jamaican Maternal Sexual Role Modelling questionnaire. METHOD: Data were collected from 209 Jamaican female adolescents recruited from Kingston, St Andrew and St Catherine parishes. RESULTS: The final 19-item Jamaican MSRM questionnaire was found to have excellent internal reliability (Cronbach's alpha = 0.89). Content validity expert ratings and modified kappa statistics were all 1.0. Principal component analysis identified a three-factor structure that accounted for 53.7% of the variance. Greater MSRM scale scores, indicating more positive and protective maternal sexual role modelling, were associated with less sexual experience, lower intentions to have sex, greater intentions to use condoms if having sex and greater condom use self-efficacy among adolescent girls. CONCLUSION: The MSRM scale was found to be a reliable and valid measure of Jamaican adolescent females'perceptions of their mothers'sexual role modelling. Further research is needed to assess the reliability and validity of the instrument with other populations.
Assuntos
Comparação Transcultural , Identidade de Gênero , Comportamento Imitativo , Relações Mãe-Filho , Comportamento Sexual , Inquéritos e Questionários , População Urbana , Adolescente , Adulto , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Humanos , Jamaica , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Educação Sexual , Estados Unidos , Sexo sem Proteção/prevenção & controle , Sexo sem Proteção/psicologiaRESUMO
A dual site project was conducted to assess determinants of injection and sex-related risk behaviors among Puerto Rican drug users. The project focused on injection drug users and crack smokers, and was conducted in East Harlem, NY and Bayamón, PR in 1996-2000. Qualitative methods included ethnographic mapping, focus groups, in-depth interviews, and observations. A survey component (East Harlem, n = 800; Bayamón, n = 400) was also conducted. Procedures to ensure integration of methodologies and comparability of data were developed. This paper describes the qualitative and survey methods used, and presents the comparative HIV risk behaviors. The integration of the two methodologies served multiple functions: each component identified issues to be addressed in the other, enhanced cross-site comparability of data, and assisted in interpretation of findings. The survey data showed high levels of risk behaviors in both communities, with significantly higher levels of risk reported in Bayamón. Conducting studies of similar ethnic groups in different communities provides opportunities to examine diverse sources of influence on risk behaviors. The integration of qualitative and quantitative methods can enhance comparability and understanding of findings, particularly when there are differences in behaviors between communities.
Assuntos
Soroprevalência de HIV , Hispânico ou Latino/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Feminino , Grupos Focais , Humanos , Masculino , Uso Comum de Agulhas e Seringas , Cidade de Nova Iorque/epidemiologia , Porto Rico/epidemiologia , Porto Rico/etnologia , Assunção de Riscos , Comportamento SexualRESUMO
This article investigates the association between residential status and human immunodeficiency virus (HIV) risk behaviors among island and New York Puerto Rican injection drug users (IDUs). We assigned 561 subjects from New York City and 312 from Puerto Rico to five residential status categories: living in parent's home, living in own home, living in other's home, living in temporary housing (hotel, single-room occupancy [SRO] hotels), and homeless (living in streets/shelters). Dependent variables included injection- and sex-related risk behaviors (sharing syringes, sharing other injection paraphernalia, shooting gallery use, and having paid sex). Chi square, t tests, and multivariate logistic analysis tests were performed separately by site. About one-quarter of the sample in each site was homeless. Island Puerto Ricans were more likely to live with their parents (44% vs. 12%, p < .001), and more New York IDUs lived in their own home (30% vs. 14%, p < .001). In New York, gallery use and paid sex were associated with living in other's home, living in parent's home, and being homeless. Sharing paraphernalia was related to living in other's home, living in temporary housing, and being homeless. In Puerto Rico, having paid sex was associated with homelessness. High-risk behaviors were more likely among homeless IDUs in both sites. Programs to provide housing and target outreach and other prevention programs for homeless IDUs would be helpful in reducing HIV risk.
Assuntos
Soropositividade para HIV/etnologia , Características de Residência , Assunção de Riscos , Abuso de Substâncias por Via Intravenosa/etnologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Porto Rico/etnologia , Comportamento Sexual , Estados Unidos/epidemiologiaRESUMO
Frequency of injection has been consistently found to be higher among Puerto Rican Injection drug users (IDUs) than among other groups of IDUs. Several explanations have been suggested, but an empirical explanation has yet to be presented. This study compares the frequency of injection of Puerto Rican IDUs in East Harlem, New York, with that of IDUs in Bayamon, Puerto Rico. Study subjects comprised 521 Puerto Rican IDUs from East Harlem and 303 IDUs from Bayamon. The mean frequency of injection among IDUs in East Harlem was 2.8, the corresponding mean in Bayamon was 5.4. Younger IDUs reported a higher number of daily injection episodes than older IDUs, and the IDU group in Bayamon was 5 years younger than the group in East Harlem. The drug use variables accounted for a greater portion of the between-city difference than the demographic and psychosocial variables. Use of noninjected drugs, as well as the use of prescribed methadone, were found to be associated with a lower number of daily injections. Conversely, injection of cocaine, injection of cocaine mixed with heroin ("speedball"), and injection of larger amounts of drug solution were found to be associated with a higher number of daily injections.
Assuntos
Abuso de Substâncias por Via Intravenosa/psicologia , Adulto , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Hispânico ou Latino/psicologia , Humanos , Masculino , Cidade de Nova Iorque/epidemiologia , Porto Rico/epidemiologia , Porto Rico/etnologia , Assunção de Riscos , Abuso de Substâncias por Via Intravenosa/complicaçõesRESUMO
This study assessed trends in HIV seroprevalence and needle-sharing behaviors among Puerto Rican injection drug users (IDUs) in Puerto Rico and New York. Data from two studies of IDUs conducted from 1992 through 1995 and 1998 through 1999 in Bayamón, Puerto Rico, and East Harlem, New York, were examined to assess trends over this period. Separate analyses were conducted for IDUs who were current crack smokers. Significant decreasing trends in seroprevalence were found among IDUs in the New York and Puerto Rico samples (p <.001). Significant decreasing trends in receptive and distributive needle sharing were found in the New York sample, and a significant decline in receptive sharing was found in the Puerto Rico sample. Overall, higher levels of needle-sharing behaviors were reported in Puerto Rico compared with New York. Decreasing trends in needle sharing and seroprevalence in both communities are an encouraging finding. Ongoing epidemiologic studies to monitor the epidemic and continued prevention efforts to help maintain or further these declines are needed, particularly to address the higher rates of needle sharing in Puerto Rico.