Sample records for gene promotors
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International Nuclear Information System (INIS)
Naqvi, S.M.S.; Mahmood, T.
2005-01-01
Plants respond to a number of environmental stimuli by modulating expression of genes. One such family of genes is now known as germin/germin-like protein genes (Glps). In order to detect any Glp gene response in rice, a pair of degenerate primers was designed based on consensus region from Glp sequences in Genbank. Using these primers a DNA fragment of about 550 bp was obtained by PCR amplification from genomic template. This 550 bp DNA was used as probe in Northern analysis. These studies provided evidence pointing to differential response of Glp expression to salt stress. RNA obtained from the roots was used for synthesis of cDNA. This cDNA was amplifiable with sense primer (RGLP1) from above mentioned pair and oligo-(dt) yielding a fragment of approx. 800 bp. Restriction analysis revealed that the PCR product was heterogeneous. After establishing that 800 bp fragment was the desired product, it was cloned in pCRII-TOPO. Five clones were picked up and analyzed by restriction analysis and sequencing. Two different Glp cDNAs were represented by these partial clones. Remaining sequence of the 5' end for clone 4 and 16 was obtained by Rapid Amplification of cDNA ends (RACE). The resultant sequences have been submitted to Genbank as Oryza sativa Rice Germin-like Protein 1 and 2 (osRGLP1 and 2). When full length genes corresponding to these sequences were amplified from genomic templates, resulting fragments were nearly 150 by larger than cDNAs. Cloning of structural genes for osRGLP1 revealed presence of a 162 bp intron in the coding region near 3' end. Preliminary evidence shows that expression of both osRGLP1 and 2 is severely reduced during salt stress. Another approach to establish both osRGLP1 and 2 genes involvement in stress tolerance is to study the ability of their promotor regions to drive expression of some reporter gene during stress. Promotor regions of about 1100 bp has been amplified and cloned and has been confirmed by restriction analysis and nested
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Promotores as researchers: expanding the promotor role in community-based research.
Nelson, Atiba; Lewy, Robin; Dovydaitis, Tiffany; Ricardo, Francine; Kugel, Candace
2011-09-01
The community health worker, known as promotor in the Hispanic community, is an accepted member of the public health team whose core role is that of bridging target communities with health services. However, the promotor's role in research has not been considered a core function of their work. This article will present the promotor in the additional role of researcher, as conceived by the Migrant Clinicians Network for the Hombres Unidos Contra La Violencia Familiar (Men United Against Family Violence) sexual violence/intimate partner violence project. The Hombres Unidos project used promotores as survey facilitators, gathering male Hispanic farmworkers' perspectives on the sensitive topic of sexual violence and intimate partner violence. This article demonstrates that when trained, the promotores' linguistic and cultural competence make them a valuable addition to the research team, especially when collecting sensitive information.
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Promotores' perspectives on a male-to-male peer network.
Macia, Laura; Ruiz, Hector Camilo; Boyzo, Roberto; Documet, Patricia Isabel
2016-06-01
Little documentation exists about male community health workers (promotores) networks. The experiences of promotores can provide input on how to attract, train, supervise and maintain male promotores in CHW programs. We present the experience and perspectives of promotores who participated in a male promotores network assisting Latino immigrant men in an emerging Latino community. All promotores in this community-based participatory study received payment for work 10 hours a week. We conducted qualitative interviews with all promotores starting the program, after 5 and 13 months. Three main themes emerged: 1) Men decided to become promotores to help others, yet appreciated being paid. 2) Promotores' learning experience was ongoing and was facilitated by a cooperative dynamic among them. Learning how to listen was crucial for promotores 3) Promotores experienced difficulty separating their personal lives form their role as a promotor We conclude that paying promotores facilitates the fulfillment of their drive to serve the community. Enhancing listening abilities needs to be part of promotores' training curricula. Finally, it is advisable to build a project with many opportunities for promotores and project staff to share professional and non-professional time and discuss their challenges. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Promotores as Researchers: Expanding the Promotor Role in Community-Based Research
Nelson, Atiba; Lewy, Robin; Dovydaitis, Tiffany; Ricardo, Francine; Kugel, Candace
2011-01-01
The community health worker, known as promotor in the Hispanic community, is an accepted member of the public health team whose core role is that of bridging target communities with health services. However, the promotor’s role in research has not been considered a core function of their work. This article will present the promotor in the additional role of researcher, as conceived by the Migrant Clinicians Network for the Hombres Unidos Contra La Violencia Familiar (Men United Against Family Violence) sexual violence/intimate partner violence project. The Hombres Unidos project used promotores as survey facilitators, gathering male Hispanic farmworkers’ perspectives on the sensitive topic of sexual violence and intimate partner violence. This article demonstrates that when trained, the promotores’ linguistic and cultural competence make them a valuable addition to the research team, especially when collecting sensitive information. PMID:21427265
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Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma.
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Lisa J Martin
Full Text Available Autophagy is a cellular process directed at eliminating or recycling cellular proteins. Recently, the autophagy pathway has been implicated in immune dysfunction, the pathogenesis of inflammatory disorders, and response to viral infection. Associations between two genes in the autophagy pathway, ATG5 and ATG7, with childhood asthma were investigated.Using genetic and experimental approaches, we examined the association of 13 HapMap-derived tagging SNPs in ATG5 and ATG7 with childhood asthma in 312 asthmatic and 246 non-allergic control children. We confirmed our findings by using independent cohorts and imputation analysis. Finally, we evaluated the functional relevance of a disease associated SNP.We demonstrated that ATG5 single nucleotide polymorphisms rs12201458 and rs510432 were associated with asthma (p = 0.00085 and 0.0025, respectively. In three independent cohorts, additional variants in ATG5 in the same LD block were associated with asthma (p<0.05. We found that rs510432 was functionally relevant and conferred significantly increased promotor activity. Furthermore, Atg5 expression was increased in nasal epithelium of acute asthmatics compared to stable asthmatics and non-asthmatic controls.Genetic variants in ATG5, including a functional promotor variant, are associated with childhood asthma. These results provide novel evidence for a role for ATG5 in childhood asthma.
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May, Marlynn L; Contreras, Ricardo B
2007-07-01
To analyze how organizational structures and scope (geographic and programmatic) generate dissonance between the organization and its workers, creating a paradox with policy implications for access to health care in hard-to-reach populations. The workers are lay community health workers called promotor(a)s. The organizations are community based organizations in which the promotor(a)s work, either as volunteers, part-time or as full-time wage staff. Ethnographic study of 12 organizations and their promotor(a)s. Data gathering included interviews with organization directors, promotor(a)s, service providers working with the organizations, and community residents served by the organizations and workers. In addition, promotor(a)s were observed in the course of their work. Sampling was a non-probability, snowball procedure for identifying the organizations and the workers within them. A paradox is emerging between (a) promotor(a)s who perceive their work to be locally focused and tightly integrated with the communities they serve and live in, and (b) the employing organizations that are expanding in geographical and programmatic scope because the work promotor(a)s do is in increasing demand by agencies and funding sources external to the communities served. The paradox potentially threatens to undermine and transform the work and working environment of the promotor(a)s. The challenge is to find a balance that will sustain a workable and working relationship among the organization, the workers, and the communities served. Care is needed in setting out policies that translate the paradox into greater congruence among organization, workers and communities. Policy needs discussed focus on (a) worker training, (b) worker employment and deployment, and (c) funding source recognition of the paradox.
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Seleccion y Capacitacion de Promotores.
Gomez, Dra. Gaby Fujimoto
1990-01-01
The program philosophies of a Latin American nonacademic school program for children aged 0-6 years are discussed. The role of the natural educator is analyzed. Promotors of these programs are described, and strategies for finding them are suggested. (DG)
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Cupertino, Ana Paula; Saint-Elin, Mercedes; de Los Rios, Johana Bravo; Engelman, Kimberly K; Greiner, K Allen; Ellerbeck, Edward F; Nápoles, Anna M
2015-01-01
To describe community-based participatory processes used to develop promotore training on cancer research, and to assess the feasibility of training promotores from rural communities to disseminate cancer research information. Prospective, cohort design. Rural communities in the state of Kansas. 34 Spanish-speaking promotores attended an information session; 27 enrolled and 22 completed training. With input from a community advisory board, the authors developed a leadership and cancer curriculum and trained Spanish-speaking promotores to disseminate information on cancer research. Promotores completed pretraining and post-training surveys in Spanish to assess demographic characteristics and changes in knowledge of cancer, cancer treatment and cancer research studies, and intent to participate in cancer research. Cancer knowledge, awareness of cancer clinical trials, interest in participating in cancer clinical research studies. Compared to pretraining, after training, promotores were more likely to correctly define cancer, identify biopsies, describe cancer stages, and report ever having heard of cancer research studies. Completion rates of the training and willingness to participate in cancer research were high, supporting the feasibility of training promotores to deliver community-based education to promote cancer research participation. Nursing professionals and researchers can collaborate with promotores to disseminate cancer education and research among underserved rural Latino communities in Kansas and elsewhere. Members of these communities appear willing and interested in improving their knowledge of cancer and cancer clinical trials.
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Fernando Alves de Azevedo
2006-11-01
Full Text Available The objective of this work was the transformation of tobacco and 'Valencia' sweet orange with the GUS gene driven by the citrus phenylalanine ammonia-lyase (PAL gene promoter (CsPP. Transformation was accomplished by co-cultivation of tobacco and 'Valência' sweet orange explants with Agrobacterium tumefaciens containing the binary vector CsPP-GUS/2201. After plant transformation and regeneration, histochemical analyses using GUS staining revealed that CsPP promoter preferentially, but not exclusively, conferred gene expression in xylem tissues of tobacco. Weaker GUS staining was also detected throughout the petiole region in tobacco and citrus CsPP transgenic plants.O objetivo deste trabalho foi realizar a transformação de plantas de tabaco e laranja 'Valência' com o gene GUS controlado pelo promotor do gene da fenilalanina amônia-liase (PAL de citros (CsPP. Foi realizada transformação genética por meio do co-cultivo de explantes de tabaco e laranja 'Valência' com Agrobacterium tumefaciens que continha o vetor binário CsPP-GUS/2201. Após a transformação e a regeneração, a detecção da atividade de GUS por ensaios histoquímicos revelou que o promotor CsPP, preferencialmente, mas não exclusivamente, confere expressão gênica em tecidos do xilema de tabaco. Expressão mais baixa de GUS também foi detectada na região de tecido de pecíolo, em plantas transgênicas (CsPP de tabaco e laranja 'Valência'.
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Antonio Carlos Torres
2003-06-01
Full Text Available Promotores tecido-específico controlam a transcrição de genes em diferentes tecidos vegetais bem como em diferentes estádios de desenvolvimento da planta, levando à indução de distintos níveis de atividade transiente e/ou estável do gene. Tais promotores podem ser empregados para a expressão seletiva de genes de interesse. O promotor rol A de Agrobacterium rhizogenes, por exemplo, é floema-específico, sugerindo que possa ser empregado em estratégias de defesa de plantas que são infectadas por vírus com replicação restrita ao floema. A expressão do gene marcador da ß-glucuronidase (gus dirigido pelo promotor rol A (pBRA3 foi observada em plantas transgênicas de batata (cvs. Macaca e Baronesa. Entrenós e secções de folhas foram submetidos ao cocultivo com A. tumefaciens. A atividade do gene gus avaliada em brotações resistentes à canamicina não se restringiu ao floema (alto nível de expressão do gene, mas também se manifestou no xilema dos caules. As expressões transiente e estável são, no entanto, tecido-específicas, localizadas sobretudo no sistema vascular de entrenós e ausente em raízes e folhas. As plantas gus positivas foram micropropagadas, plantadas em casa de vegetação e avaliadas por PCR, utilizando-se 'primers' específicos para o gene npt II. Nenhuma alteração fenotípica foi observada em plantas transgênicas, em relação às não transformadas.Tissue-especific promoters allow the modulation of gene transcription in different tissue types as well as in different stages of plant development, leading different levels of transient and stable activity of the gene product. These promoters have been employed for selective gene expression. The Agrobacterium rhizogenes rol A gene promoter (BRA3 controls phloem-specific expression indicating that this promoter might have an important role in plant defense strategies against virus which replicated only in the phloem. The expression of
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Promotores de salud and community health workers: an annotated bibliography.
WestRasmus, Emma K; Pineda-Reyes, Fernando; Tamez, Montelle; Westfall, John M
2012-01-01
For underserved and disenfranchised communities in the United States, affordable, effective health care can be nearly inaccessible, which often leads to the exclusion of these communities from relevant medical information and care. Barriers to care are especially salient in minority communities, where language, traditions and customs, socioeconomics, and access to education can serve as additional roadblocks to accessing health care information and services. These factors have contributed to a national health disparity crisis that unnecessarily places some communities in a vulnerable position without adequate prevention and treatment opportunities. One solution to the exclusion some communities face in the health care system may be the promotores de salud (PdS)/community health worker (CHW), an approach to culturally competent health care delivery whose popularity in the mainstream health care system has been steadily growing in recent decades. Known by a wide variety of names and broad in the spectrum of health issues they address, the PdS/CHW serves as cultural brokers between their own community and the formal health care system and can play a crucial role in promoting health and wellness within their community. This annotated bibliography was created to educate the reader about the history, definition, key features, utility, outcomes, and broad potential of the CHW approach in a variety of populations. Intended to serve as a reference point to a vast body of information on the CHW/PdS approach, this document is a resource for those wishing to effect change in the disparities within the health care system, and to improve the access to, quality, and cost of health care for underserved patients and their communities. Promotores de Salud is a Spanish term that translates to Health Promoter. A female health worker may be referred to as a Promotora, a male as a Promotor, and the plural of both is Promotores. For the purposes of this bibliography, the terms community
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Using Job Analysis Techniques to Understand Training Needs for Promotores de Salud.
Ospina, Javier H; Langford, Toshiko A; Henry, Kimberly L; Nelson, Tristan Q
2018-04-01
Despite the value of community health worker programs, such as Promotores de Salud, for addressing health disparities in the Latino community, little consensus has been reached to formally define the unique roles and duties associated with the job, thereby creating unique job training challenges. Understanding the job tasks and worker attributes central to this work is a critical first step for developing the training and evaluation systems of promotores programs. Here, we present the process and findings of a job analysis conducted for promotores working for Planned Parenthood. We employed a systematic approach, the combination job analysis method, to define the job in terms of its work and worker requirements, identifying key job tasks, as well as the worker attributes necessary to effectively perform them. Our results suggest that the promotores' job encompasses a broad range of activities and requires an equally broad range of personal characteristics to perform. These results played an important role in the development of our training and evaluation protocols. In this article, we introduce the technique of job analysis, provide an overview of the results from our own application of this technique, and discuss how these findings can be used to inform a training and performance evaluation system. This article provides a template for other organizations implementing similar community health worker programs and illustrates the value of conducting a job analysis for clarifying job roles, developing and evaluating job training materials, and selecting qualified job candidates.
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Evidence for plasticity genotypes in a gene-gene-environment interaction : the TRAILS study
Nederhof, E; Bouma, Esther; Riese, Harriette; Laceulle, Odilia; Ormel, J.; Oldehinkel, A.J.
2010-01-01
The purpose was to study how functional polymorphisms in the brain derived neurotrophic factor gene (BDNF val66met) and the serotonin transporter gene linked promotor region (5-HTTLPR) interact with childhood adversities in predicting Effortful Control. Effortful Control refers to the ability to
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Adelar Almeida Pinto
2002-12-01
Full Text Available O mamoeiro (Carica papaya L. e a videira (Vitis vinifera L. destacam-se entre as fruteiras produzidas no Brasil por serem plantadas em quase todo o território nacional e apresentarem importância econômica e social. A tecnologia de produção de organismos geneticamente modificados, também conhecidos como "transgênicos", tem grande potencial de uso no desenvolvimento de fruteiras melhoradas. Porém, questões de propriedade intelectual limitam o uso da engenharia genética por países em desenvolvimento, que normalmente não detêm direitos sobre processos ou produtos necessários ao uso desta. Neste contexto, o presente estudo buscou avaliar promotores de expressão gênica alternativos ao CaMV 35S, que é o mais utilizado no desenvolvimento de transgênicos, mas é patenteado. Para tanto, construções gênicas com o gene gus sob a regulação de diferentes promotores foram testadas para expressão transiente em diversos tecidos de mamoeiro e videira. Expressão transiente foi avaliada em embriões somáticos, folhas, caules, raízes e frutos. O promotor do gene UBQ3, que é constitutivo e se encontra em domínio publico, mostrou ser uma alternativa promissora para futuros trabalhos de transformação genética de mamoeiro, mas não de videira.Papaya (Carica papaya L. and grapes (Vitis vinifera L. are among the most important fruit crops produced in Brazil, and are cultivated in several regions around the country being of economical and social importance. Genetic engineering has great potential on the development of genetically improved fruit crops. However, intellectual property issues constantly limit the commercial use of this technology in developing countries. Thus, the present study aimed to evaluate gene promoters as alternatives to the 35S CaMV, which is the most used so far in the development of transgenic plants, but it is patented. In order to do that, the expression of the gus gene under the regulation of distinct promoters was
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Óscar Bedoya
2011-06-01
Full Text Available A new promoter prediction program called CNN-Promoter is presented. CNN-Promoter allows DNA sequences to be submitted and predicts them as promoter or non-promoter. Several methods have been developed to predict the promoter regions of genomes in eukaryotic organisms including algorithms based on Markov's models, decision trees, and statistical methods. Although there are plenty of programs proposed, there is still a need to improve the sensitivity and specificity values. In this paper, a new program is proposed; it is based on the consensus strategy of using experts to make a better prediction. The consensus strategy is developed by using neural networks. During the training process, the sensitivity and specificity were 100 % and during the test process the model reaches a sensitivity of 74.5 % and a specificity of 82.7 %.En este artículo se presenta un programa nuevo para la predicción de promotores llamado CNN-Promoter, que toma como entrada secuencias de ADN y las clasifica como promotor o no promotor. Se han desarrollado diversos métodos para predecir las regiones promotoras en organismos eucariotas, muchos de los cuales se basan en modelos de Markov, árboles de decisión y métodos estadísticos. A pesar de la variedad de programas existentes para la predicción de promotores, se necesita aún mejorar los valores de sensibilidad y especificidad. Se propone un nuevo programa que se basa en la estrategia de mezcla de expertos usando redes neuronales. Los resultados obtenidos en las pruebas alcanzan valores de sensibilidad y especificidad de 100 % en el entrenamiento y de 74,5 % de sensibilidad y 82,7 % de especificidad en los conjuntos de validación y prueba.Neste artigo a presenta-se um novo programa para a predição de promotores chamado CNN-Promoter, que toma como entrada sequências de DNA e as classifica como promotor ou não promotor. Desenvolveramse diversos métodos para predizer as regiões promotoras em organismos eucariotas
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Effects of a promotor-based intervention to promote physical activity: Familias Sanas y Activas.
Ayala, Guadalupe X
2011-12-01
This within-participants, single time-series study tested a train-the-trainer, promotor-based physical activity (PA) intervention to improve fitness and health indicators. Thirty unpaid promotores were trained to promote PA through free exercise classes. Measurements of 337 female community participants at baseline, 6 months, and 12 months assessed changes in health indicators, including systolic and diastolic blood pressure, waist circumference, body mass index (defined as weight in kilograms divided by the square of height in meters), aerobic fitness, and hamstring flexibility, as well as self-reported health indicators (PA, depression) and psychosocial factors (barriers, self-efficacy, and social support-all specific to PA). Mixed effects models showed intervention participation improved systolic blood pressure (P ≤ .001), waist circumference (P ≤ .001), fitness (P ≤ .001), and hamstring flexibility (P ≤ .001). We also noted improvements in use of community resources (P ≤ .05), depressed mood and anhedonia (P ≤ .01), perceived barriers to be physically active (P ≤ .05), and community support for PA (P ≤ .001). Self-efficacy decreased (P ≤ .05), and participation dose (i.e., exposure), as measured by attendance at exercise classes, was not associated with observed changes. Promotores can promote PA in their community and achieve meaningful changes in the residents' health.
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Ramírez, Denise Moreno; Vea, Lourdes; Field, James A; Baker, Paul B; Gandolfi, A Jay; Maier, Raina M
Community health workers (promotores de salud) have the ability to empower communities to mitigate negative health outcomes. Current training efforts in environmental topics are lacking. This project addressed this gap by developing 4 transferable training modules on environmental health. By applying a series of surveys, interviews, and trainings, we evaluated their relevance. Partners provided favorable feedback for 3 of the 4 modules. It was also learned that the development method could be improved by engaging technically trained promotores de salud in the role of co-creators. This project has implications for environmental justice communities as it can lessen information disparities.
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Una experiencia de campo con una cooperativa de promotores ambientales
Bazán, Claudia I.; Ferrari, Liliana
2014-01-01
La presente ponencia describe el trabajo que se está realizando con una cooperativa de promotores ambientes, El CorreCamino, cuya propuesta no es pensada como una actividad marginal sino que toma el proceso de reciclado como contribución social y enfatiza el papel activo del trabajador en solidaridad con los vecinos y el espacio ambiental. La metodología utilizada es la Investigación Acción Participativa (IAP) cuyo principal objetivo es aunar los ...
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Estudio preliminar: orégano como promotor de crecimiento en lechones destetados
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Santiago Parrado M.
2006-12-01
Full Text Available A pesar de la comprobada capacidad de mejorar el desempeño en los cerdos, el uso de antimicrobianos como promotores de crecimiento viene siendo progresivamente restringido en diversos países. Las nuevas reglamentaciones tienden a buscar nuevas alternativas al uso de antibióticos y quimioterapéuticos como promotores de crecimiento. Una de estas alternativas son los nutraceúticos que constituyen una de las opciones investigadas. El objetivo del trabajo fue evaluar los efectos antimicrobianos del orégano sobre la digestibilidad aparente de los nutrientes, en la ganancia diaria de peso, conversión alimenticia y presentación de diarreas en lechones recién destetados. Fueron estudiados tres grupos de lechones de 21 días de edad de la raza F1 (Landrace x Large White, durante cuatro semanas de los cuales uno de dichos grupos fue tomado como grupo control (alimento comercial, y los otros dos grupos con alimento fabricado en la granja a diferentes concentraciones de orégano (0,03 y 0,06 % respectivamente. Las dietas fabricadas son a base de harina de maíz y soya suplementados con los aminoácidos y minerales esenciales para la dieta del lechón. El proyecto tuvo duración de un mes en el cuales se midió semanalmente el peso ganado por los animales y la conversión alimenticia de los mismos; de igual forma se comparó la eficacia del orégano con respecto a una dieta normal de concentrado. Los resultados del estudio mostraron diferencias significativas entre los grupos estudiados, en cuanto a las variables ganancia diaria de peso, índice de conversión y presentación de diarreas. Se llegó a una conclusión muy significativa donde las alternativas para los antibióticos promotores de crecimiento mejoran los parámetros productivos en lechones además, del efecto antimicrobiano que poseen.
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Raquel Aparecida de Oliveira
2006-01-01
Full Text Available El estudio tuvo como objetivo conocer las percepciones de los alumnos de graduación en enfermería, en cuanto a su calidad de vida. El abordaje adoptado fue cualitativo. Llos datos fueron colectados a través de la entrevista individual, con cinco alumnos, y se orientó por preguntas abiertas: para usted qué significa tener calidad de vida; relata experiencias personales u observadas en tu cotidiano como alumno, sobre que aspectos consideras como promotores y no promotores de su calidad de vida. El análisis temático de los discursos posibilitó aprehendio a las promotoras de la calidad de vida: experiencias extra-curriculares; relación profesor-alumno; relacionamiento entre los alumnos. Los aspectos señalados como no promotores fueron: la falta de acogida por parte de profesores y enfermeros del campo; la falta de integración con el equipo y con los alumnos de otros cursos del campus; la carga horaria excesiva para el alumno que trabaja. Los resultados permitieron proponer estratégias viables para la mejoría de la búsqueda de un cuidado com calidad a la clientela.
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COMPORTAMENTOS PROMOTORES DE SAÚDE: PROPRIEDADES PSICOMÉTRICAS DE UM INSTRUMENTO DE AVALIAÇÃO
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Catarina Cardoso Tomás
2015-01-01
Full Text Available Con el objetivo de evaluar las propiedades psicométricas de un instrumento para evaluar los niveles de comportamientos promotores de la salud, así como para conocerlos en una muestra de 1213 adolescentes portugueses en relación a su edad, sexo y años de escolaridad, se realizó este estudio de tipo cuantitativo, descriptivo, correlacional, retrospetivo y transversal. El instrumento tiene buena consistencia interna (Cronbach’s Alpha de 0,889 y correlación razonable entre los elementos (entre -0,009 e 0,788, confirmado por los seis factores definidos por los autores de la escala. Los niveles de comportamientos promotores de la salud en la muestra son buenos (x=3,70, siendo mayor en las niñas que en los niños, y la juventud en detrimento de los jóvenes mayores. Por lo tanto se demuestra la confiabilidad del instrumento en la evaluación de los comportamientos saludables en los adolescentes portugueses y la necesidad de una intervención de salud en esta población.
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ARCHIPIÉLAGOS PROMOTORES DE CAMBIOS ANÁLISIS ESPACIAL DE DINOSAURIO MALL
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FRATINI NOEMÍ
2010-05-01
Full Text Available Durante las últimas décadas, las ciudades posindustriales latinoamericanas se han constituido como nodos de la red mundial. La apertura de sus economías nacionales, posibilitó que algunas de estas ciudades se conviertan en los lugares preferidos para la localización de funciones y actividades de enlace con las redes globales de carácter comercial, productivo, financiero y cultural. Estos espacios urbanos avanzan progresivamente hacia polos segmentados de desarrollo que se manifiestan en la sociedad a través del acceso diferencial a bienes y servicios, surgiendo una dualidad espacial, aparentemente planteada, entre el espacio público y privado, y promoviendo fenómenos de exclusión o inclusión en una tensión permanente. Así se configuran en archipiélagos promotores de cambio y sujetos a diversas dimensiones de análisis. Para interpretar este fenómeno en relación a la inversión de capital, se ha seleccionado como territorio de análsis, un área del sector noroeste de la ciudad de Córdoba, Argentina. Se trata de un complejo comercial de gran magnitud y significación simbólica para la ciudad: Grupo Dinosaurio. El presente trabajo ensaya una aproximación exploratoria para identificar las tensiones producto de los conflictos por el avance en el espacio urbano de inversiones en espacios segmentados, promotores de cambio y su relación con el espacio público- privado, y la consecuente segregación socio- espacial.
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Robert Partridge
2007-12-01
Full Text Available Los promotores de salud, las parteras y otros proveedores de cuidados médicos básicos trabajan en comunidades locales de todo el mundo para mejorar y facilitar la atención sanitaria. No hay suficiente información que describa los programas educacionales dirigidos a mejorar los conocimientos y las habilidades de los promotores de salud y sobre su impacto sanitario a largo plazo. Muchas iniciativas educacionales dirigidas a los promotores de salud consisten en intervenciones aisladas que permiten evaluar sus conocimientos inmediatamente después de la intervención, pero no miden los progresos a largo plazo en la base de conocimientos o la atención sanitaria. La Alianza Pediátrica Global -una organización sin ánimo de lucro basada en los EE.UU. que trabaja con personal médico y sanitario local- creó un programa educacional para promotores sanitarios y parteras en Ecuador, Guatemala, México y Nicaragua con un enfoque centrado en reducir la mortalidad materna e infantil y en mejorar la atención primaria y de urgencias. En este artículo se describen estas iniciativas educacionales diseñadas para mejorar las habilidades de los promotores de salud y las parteras mediante un entrenamiento médico avanzado y sostenible, ajustadas a las necesidades específicas de cada comunidad.
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Choi, Bernard C K; Pak, Anita W P
2007-01-01
Multidisciplinary, interdisciplinary and transdisciplinary teams are increasingly encouraged in health research, services, education and policy. This paper is the second in a series. The first discussed the definitions, objectives, and evidence of effectiveness of multiple disciplinary teamwork. This paper continues to examine the promotors, barriers, and ways to enhance such teamwork. The paper is a literature review based on Google and MEDLINE (1982-2007) searches. "Multidisciplinarity", "interdisciplinarity", "transdisciplinarity" and "definition" were used as keywords to identify the pertinent literature. The promotors of teamwork success include: good selection of team members, good team leaders, maturity and flexibility of team members, personal commitment, physical proximity of team members, the Internet and email as a supporting platform, incentives, institutional support and changes in the workplace, a common goal and shared vision, clarity and rotation of roles, communication, and constructive comments among team members. The barriers, in general, reflect the situation in which the promotors are lacking. They include: poor selection of the disciplines and team members, poor process of team functioning, lack of proper measures to evaluate success of interdisciplinary work, lack of guidelines for multiple authorship in research publications, language problems, insufficient time or funding for the project, institutional constraints, discipline conflicts, team conflicts, lack of communication between disciplines, and unequal power among disciplines. Not every health project needs to involve multiple disciplines. Several questions can help in deciding whether a multiple disciplinary approach is required. If multiple disciplinarity is called for, eight strategies to enhance multiple disciplinary teamwork are proposed. They can be summarised in the acronym TEAMWORK - Team, Enthusiasm, Accessibility, Motivation, Workplace, Objectives, Role, Kinship.
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Índice de Promotor Neto y su relación con la satisfacción del cliente y la lealtad
Directory of Open Access Journals (Sweden)
Eric González Rodríguez
2014-01-01
Full Text Available El presente estudio se enfoca en el uso del Índice de Promotores Netos desarrollado por Frederik Reichheld y la firma consultora Bain & Company, como herramienta para conocer la percepción de los clientes sobre el servicio que reciben de sus proveedores, esta herramienta es una alternativa al modelo SERVQUAL ampliamente usado desde hace varios años. Este índice consta solo de dos preguntas, lo que lo hace una herramienta más sencilla de utilizar que otros modelos. Actualmente este modelo es utilizado por compañías globales como General Electric, Honeywell, American Express, Lenovo entre otras. La aplicación de esta herramienta se realiza en una empresa de manufactura del ramo aeroespacial en México que cuenta con clientes en diferentes partes del mundo. Este estudio se centra en la relación que guarda el Índice de Promotores Netos con la Satisfacción y la Lealtad de los clientes (método Vestas. También se investiga la influencia que puede existir entre algunos factores que componen el servicio tales como Respuesta, Tiempo de Entrega, Competitividad en Precio, Calidad y Confiabilidad con dicho Índice. Cabe mencionar que en otros estudios publicados en revistas como el Harvard Business Review se ha comprobado la correlación existente entre el crecimiento en la rentabilidad con el incremento en el Índice de Promoción, por tal motivo la relevancia de este estudio. En esta investigación se plantean una serie de hipótesis para comprobar la relación existente entre estos factores con el Índice de Promotores Netos. Para tratar de comprobar las hipótesis se utiliza la modelación de ecuaciones estructurales a través del software SmartPLS. Con base al análisis y a los resultados obtenidos en este estudio, se presentan las conclusiones y recomendaciones. Donde se concluye que existe una fuerte relación de determinados factores con el Índice de Promotores Netos, la Satisfacción y la Lealtad por lo que una estrategia basada en la
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Directory of Open Access Journals (Sweden)
Kolima Peña Calzada
2015-09-01
Full Text Available El objetivo de la investigación fue evaluar el efecto de un promotor del crecimiento activado molecularmente sobre la germinación y producción del cultivo de frijol (Phaseolus vulgaris L.. Se hicieron dos experimentos, uno in vitro con un diseño completamente aleatorizado y otro en campo con dos variantes y 8 réplicas (diseño de bloques al azar. El tratamiento en ambos ensayos fue inmersión de las semillas en una solución del promotor al 0,02% por 3 horas y otro grupo testigo con inmersión por igual tiempo en agua natural. Los resultados mostraron que la germinación y la altura de las plantas fueron mejores con la inmersión en el producto en ambos experimentos. En el ensayo de campo los vainas por planta no hubo diferencia entre los tratamientos. En los granos por vaina y granos por planta el grupo tratado fue superior al control en 16,70 y 15,22% respectivamente. La masa de 100 granos no mostró diferencia entre ambos tratamientos. El rendimiento agrícola fue superior en los tratados(1,22t.ha-1 vs. 1,02. Con ambos experimentos se determinó que el promotor del crecimiento influyó positivamente en la germinación, desarrollo y producción del cultivo del frijol.
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Autism Between the PhD Student and the Promotor. A Case Study
Directory of Open Access Journals (Sweden)
Perkowski Maciej
2017-12-01
Full Text Available Contemporary societies struggle with the problem of education being inadequate to the reality. The crisis (and, consequently, the deficit of authorities is present in all levels of education. It seems that the classical vertical mechanism “student-master” should experience a renaissance. Instead of theoretical argumentation, it is worth learning about the case of a particular relationship – between a doctoral student who is a non-speaking autistic person and the promotor who tries to oppose it constructively. Both lawyers (as the cooperation is currently taking place in doctoral law studies apart from the preparation of the dissertation, are experimenting methodologically, entering the “student-master” relationship with mutual benefit. They are subject to ongoing verification in this area – both domestic and foreign.
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The histone genes in HeLa cells are on individual transcriptional units
International Nuclear Information System (INIS)
Hackett, P.B.; Traub, P.; Gallwitz, D.
1978-01-01
The distances of the five major histone genes from their promotors have been investigated in order to determine whether in human cells these genes could be transcribed as a single polycistronic transcriptional unit. By measuring the decreases of both histone protein and histone mRNA synthesis as functions of the ultraviolet light dosage, it was possible to calculate the distances of the histone genes from their promotors. The inactivation kinetics for histone genes H1 and H3 are first-order, indicating a single type of transcriptional unit for each gene. The dose-response kinetics for genes H2A, H2B and H4 are first-order with two distinct rates; 10 to 15% of the genes for each of these histones appear to be much more sensitive to ultraviolet light inactivation than are the majority. It is concluded that the transcriptional units for 85 to 90% of the genes for H2A, H2B and H4 are similar. As determined by the inhibition of protein synthesis, the inactivation coefficients for the major component of each histone are: H1, 907 mm 2 /erg; H2A, 878 mm 2 /erg; H2B, 871 mm 2 /erg; H3, 965 mm 2 /erg; and H4, 792 mm 2 /erg. The sensitivities of histone mRNA synthesis to irradiation were measured by translation in vitro with similar results. The calculated target sizes for the genes (in base-pairs) are: H1, 1190; H2A, 1240; H2B, 1250; H3, 1130; and H4, 1380. This similarity in target sizes for all five of the histones genes indicates that they are primarily transcribed from individual transcriptional units. (author)
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Development of gene diagnosis for diabetes and cholecystis based on gene analysis of CCK-A receptor
International Nuclear Information System (INIS)
Kono, Akira
1998-01-01
The gene structures of CCK, A type receptor in human, the rat and the mouse were investigated aiming to clarify that the aberration of the gene is involved in the incidences of diabetes and cholecystis. In this fiscal year, 1997, the normal structure of the gene and the accurate base sequence were analyzed using DNA fragments bound to 32 P-labelled cDNA of human CCKAR originated from the gene library of leucocyte. This gene contained about 2.2 x 10 5 base pairs and the base sequence was completely determined and registered to Japan DNA data bank (D85606). In addition, the genome structures and base sequences of mouse and rat CCKAR were analyzed and registered (D 85605 and D 50608, respectively). The differences in the base sequence of CCKAR among the species were found in the promotor region and the intron regions, suggesting that there might be differences in splicing among species. (M.N.)
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Energy Technology Data Exchange (ETDEWEB)
NONE
2004-07-01
The technology program ProMOTOR, related to the technology of internal combustion engines, covered the whole chain from fuels to engine, and from engine combustion to exhaust gas clean-up. One of the main challenges in the engine sector is to decrease emissions significantly. In order to meet this challenge, the whole chain has to be considered. The program was designed in close cooperation with the national industry of this sector. The main objective of the program was to support product development of the engine- related industry in order to develop and maintain international competitiveness. Corporate projects formed a substantial part of the program, amounting to about 70% of the whole budget volume. Good results were achieved in every sector of the program. In the sector of 'Engine Theory' great efforts were directed to the development of calculation and simulation procedures and protocols. The efforts paid off, and significant progress was achieved. Close international cooperation and academic theses give indication of the high level. In addition to computational work optical method to study incylinder phenomena was developed. Research infrastructure was improved in many different areas. A new research engine, EVE (Extreme Value Engine), makes it possible to vary the operational parameters and the engine process in such ways which are not possible in ordinary engines. A very high boost pressure and freely selectable valve timing are important new features providing more freedom in testing. The mechanical structure of this engine, which is designed for extremely high mean effective pressures, is unique. A research device for piston ring tribology and a large bearing test rig were also designed and constructed for tribology research. The research facilities for work on heavy vehicles and engines improved significantly. Today it is possible to run complete heavy-duty vehicles on a chassis dynamometer and test engines, for example, according to
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Directory of Open Access Journals (Sweden)
Paulo César Busato
2010-07-01
Full Text Available O artigo trata de analisar a posição dos sujeitos do processo à luz do novo projeto de Código de Processo Penal, especialmente doPromotor de Justiça. Reconhece-se a adoção de um perfil prevalentemente acusatório no projeto, ainda que não seja uma orientação plena. A partir desta perspectiva, busca-se analisar a iniciativa de produção probatória às partes, mantendo o juiz a distância, bem como a entrega efetiva do comando da investigação ao Ministério Público, como elementos capazes de situar o que deve ser a postura processual do Promotor de Justiça. Conclui-se pelo reconhecimento de uma tendência evolutiva do sistema processualbrasileiro em direção a um modelo acusatório, estabelecendo as bases ideais da postura do Promotor de Justiça em um sistema desta ordem.Abstract:The article attempts to analyze the position of subjects of the process under the new draft Criminal Procedure Code, especiallythe prosecutor. We recognize the adoption of a predominantly adversarial profile in the project, although not a full orientation. From this perspective, we seek to analyze the initiativeto produce evidence to the parts, keeping the distance of the judge, and also the effective delivery of the command of the investigationto prosecutors as evidence to situate what must be the procedural posture of the prosecutor. It is the recognition of an evolutionary trend of the Brazilian legal system towards an adversarial model, establishing the basis of the ideal position of prosecutor in a system of this nature.
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Directory of Open Access Journals (Sweden)
Close Eimear
2010-05-01
Full Text Available Abstract Background Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance. The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. Methods We have evaluated six candidate genes in one of these regions (11q23, namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. Results Promotor SNPs (-607, -137 in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P IL18-137/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C/-137C (P Conclusion Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine's role in maintaining inflammation in active CD.
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Índice de Promotor Neto y su relación con la satisfacción del cliente y la lealtad
Eric González Rodríguez; Juan Baldemar Garza Villegas
2014-01-01
El presente estudio se enfoca en el uso del Índice de Promotores Netos desarrollado por Frederik Reichheld y la firma consultora Bain & Company, como herramienta para conocer la percepción de los clientes sobre el servicio que reciben de sus proveedores, esta herramienta es una alternativa al modelo SERVQUAL ampliamente usado desde hace varios años. Este índice consta solo de dos preguntas, lo que lo hace una herramienta más sencilla de utilizar que otros modelos. Actualmente este modelo es u...
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Directory of Open Access Journals (Sweden)
Bruna Dorabiallo Oliveira
2017-06-01
Full Text Available O turismo de eventos provoca grande atratividade econômica para as localidades receptoras, uma vez que os eventos geram fluxo programado de visitantes e o turista tem um gasto médio superior aos demais tipos de turista. Compreender os atributos que a localidade deve apresentar para ser atrativa aos organizadores e promotores de eventos é uma maneira de planejar e desenvolver o turismo em uma região. Com o objetivo de analisar os conjuntos de atributos considerados na escolha de um destino para evento, o presente estudo apresenta uma pesquisa exploratória e através de pesquisa bibliográfica indica os estudos publicados nessa temática na perspectiva dos organizadores e promotores de eventos. Foram analisados 27 artigos que discutem os atributos inerentes à tomada de decisão de destinos para eventos e descritos os 21 diferentes conjuntos de atributos identificados. Verificou-se que se pode categorizar os atributos entre os relacionados ao evento ou ao destino, sendo que estrutura para eventos, hospedagem e custos são predominantes nos estudos, enquanto existem outros atributos são considerados por autores específicos.
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Directory of Open Access Journals (Sweden)
Corella, Dolores
2009-03-01
Full Text Available Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolim-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 514C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C metabolism; the interaction between polyunsaturated fatty acids (PUFA and the 75G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the 1131TC in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken.Las recomendaciones dietéticas actuales referentes al consumo de grasas en la dieta han sido realizadas sin tener en cuenta las posibles diferencias genéticas de las personas que podrían ser las responsables de las diferentes respuestas interindividuales que frecuentemente se observan ante la misma dieta. La presencia de variabilidad genética ha sido puesta de manifiesto para todos los genes relacionados con el metabolismo lipídico, por lo que existe un ingente número de genes y de variantes genéticas para ser incluidas en los estudios sobre interacciones dieta-genotipo en el ámbito específico del consumo de grasas y aceites. Se revisarán algunos ejemplos sobre interacciones grasa
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APROXIMACIONES COMPUTACIONALES PARA LA IDENTIFICACIÓN DE PROMOTORES EUCARIOTAS TIPO II
Directory of Open Access Journals (Sweden)
M. Mejía-Guerra
2006-06-01
Full Text Available La identificación de segmentos funcionales dentro del DNA es uno de los campos más estudiados en la actualidad, debido a la generación de grandes volúmenes de información a partir de los proyectosgenómicos, las predicciones computacionales han atraído la atención de la comunidad científica en general.En este marco la identificación de secuencias reguladoras se erige como un importante campo del análisis de genomas; sin embargo, dada la enorme complejidad del proceso de regulación de la transcripciónaunque promisorios el problema de la predicción de las zonas reguladoras no se ha solucionado en su totalidad.Este artículo presenta una descripción de algunas aproximaciones desarrolladas para la identificación de promotores y sus elementos cis-reguladores, también se describen las estructuras de señales funcionales y estructurales que son diana de reconocimiento de algunos de estos programas de predicción aplicados al gen que codifica para la subunidad NR1 del receptor de glutamato sensible a N-metil-D-aspartato (iGluR-NMDA el cual ha sido objeto de estudio desde la década de los noventa.
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Directory of Open Access Journals (Sweden)
Patrícia Tomazini Medeiros
2009-06-01
Full Text Available http://dx.doi.org/10.5007/2175-7925.2009v22n3p157 Com o objetivo de avaliar o desempenho e o custo de produção de frangos de corte, foram testados probióticos e prebióticos como promotores de crescimento alternativos aos antimicrobianos (colistina/avilamicina, na ração de 6.450 pintos de corte, machos, da linhagem Cobb, criados de 1 a 42 dias de idade, distribuídos em um delineamento inteiramente casualisado, formado por oito tratamentos de rações experimentais, com 13 – 17 repetições de 50 aves cada por tratamento. Os probióticos foram o Bacillus subtilis em diferentes concentrações e/ou recomendação de uso, uma mistura de Saccharomyces cerevisiae mais Aspergillus oryzae ou um prebiótico composto de mananoligossacarídeos (MOS adicionados em uma ração inicial e outra de crescimento comum a todos os tratamentos. Não se verificou diferenças significativas na conversão alimentar entre tratamentos. Entretanto, o peso médio dos animais que receberam Bacillus subtilis (1,6 x 109CFU/g ou uma mistura de probióticos foi maior ou semelhante ao peso das aves alimentadas com os antimicrobianos. Conclui-se que é possível substituir os antimicrobianos utilizados, pelos probióticos avaliados como promotores de crescimento sem prejuízos no desempenho e no custo de produção de frangos de corte.
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Directory of Open Access Journals (Sweden)
Martha Patricia Reyes González
2014-01-01
Full Text Available Objetivo: Diseñar y evaluar un programa de formación de promotores, con componentes educativos y participativos, que permitan desarrollar procesos locales hacia un mayor control de la tuberculosis en comunidades de alta incidencia de tuberculosis en Chiapas, México.Métodos: Se elaboró un programa basado en un diagnóstico epidemiológico y sociocultural de la tuberculosis en la región; se diseñaron y aplicaron cursos-talleres participativos para una mejor comprensión de la enfermedad y capacitación para la formación de promotores en el diagnóstico y tratamiento de la tuberculosis, con aportes de la biomedicina y de las teorías de participación comunitaria y constructivista.Resultados: Se enfatiza que la participación comunitaria fue esencial en la reflexión y definición del problema de la tuberculosis, así como los posibles caminos a seguir. Se demostró que fue una forma de generar un alto compromiso en la obtención de resultados en el diagnóstico y tratamiento de la enfermedad y en la eficacia de la comunicación con la población.Las localidades incluidas fueron Verapaz, Tres Maravillas y Nuevo México del municipio de Frontera Comalapa, Chiapas. Encontramos que la participación de la población en programas de salud, en especial sobre la tuberculosis, había sido de forma pasiva, pues había tomado el papel de receptora solamente en pláticas informativas, sin confirmar aprendizajes. Estas localidades se ubicaban en los primeros lugares de incidencia por tuberculosis a nivel nacional. El curso fue planificado para capacitar a 15 personas como promotores: 10 de Nuevo México, 4 de Verapaz y uno de Tres Maravillas, quienes trabajaron en beneficio de su comunidad y fueron bien recibidas por los pacientes y familiares.Conclusión: La participación comunitaria para reflexionar y definir el problema de la tuberculosis, así como los posibles caminos a seguir, demostró generar un alto compromiso en la obtención de resultados
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Directory of Open Access Journals (Sweden)
Martha Patricia Reyes González
2014-01-01
Full Text Available Objetivo: Diseñar y evaluar un programa de formación de promotores, con componentes educativos y participativos, que permitan desarrollar procesos locales hacia un mayor control de la tuberculosis en comunidades de alta incidencia de tuberculosis en Chiapas, México. Métodos: Se elaboró un programa basado en un diagnóstico epidemiológico y sociocultural de la tuberculosis en la región; se diseñaron y aplicaron cursos-talleres participativos para una mejor comprensión de la enfermedad y capacitación para la formación de promotores en el diagnóstico y tratamiento de la tuberculosis, con aportes de la biomedicina y de las teorías de participación comunitaria y constructivista. Resultados: Se enfatiza que la participación comunitaria fue esencial en la reflexión y definición del problema de la tuberculosis, así como los posibles caminos a seguir. Se demostró que fue una forma de generar un alto compromiso en la obtención de resultados en el diagnóstico y tratamiento de la enfermedad y en la eficacia de la comunicación con la población. Las localidades incluidas fueron Verapaz, Tres Maravillas y Nuevo México del municipio de Frontera Comalapa, Chiapas. Encontramos que la participación de la población en programas de salud, en especial sobre la tuberculosis, había sido de forma pasiva, pues había tomado el papel de receptora solamente en pláticas informativas, sin confirmar aprendizajes. Estas localidades se ubicaban en los primeros lugares de incidencia por tuberculosis a nivel nacional. El curso fue planificado para capacitar a 15 personas como promotores: 10 de Nuevo México, 4 de Verapaz y uno de Tres Maravillas, quienes trabajaron en beneficio de su comunidad y fueron bien recibidas por los pacientes y familiares. Conclusión: La participación comunitaria para reflexionar y definir el problema de la tuberculosis, así como los posibles caminos a seguir, demostró generar un alto compromiso en la obtención de
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Directory of Open Access Journals (Sweden)
Martha Patricia Reyes González
2014-01-01
Full Text Available Objetivo : Diseñar y evaluar un programa de formación de promotores, con componentes educativos y participativos, que permitan desarrollar procesos locales hacia un mayor control de la tuberculosis en comunidades de alta incidencia de tuberculosis en Chiapas, México. Métodos: Se elaboró un programa basado en un diagnóstico epidemiológico y sociocultural de la tuberculosis en la región ; se diseñaron y aplicaron cursos - talleres participativos para una mejor comprensión de la enfermedad y capacitación para la formación de promotores en el diagnóstico y tratamiento de la tuberculosis, con aportes de la biomedicina y de las teorías de participación comunitaria y constructivista. Resultados: S e enfatiza que la participación comunitaria fue es encial en la reflexión y definición del problema de la tuberculosis, así como los posibles caminos a seguir. Se demostró que fue una forma de generar un alto compromiso en la obtención de resultados en el diagnóstico y tratamiento de la enfermedad y en la eficacia de la comunicación con la población. Las localidades incluidas fueron Verapaz, Tres Maravillas y Nuevo México del municipio de Frontera Comalapa, Chiapas. Encontramos que la participación de la población en programas de salud , en especial sobre l a tuberculosis, había sido de forma pasiva, pues había tomado el papel de receptor a solamente en pláticas informativas, si n confirmar aprendizajes. Estas localidades se ubicaban en los primeros lugares de incidencia por tuberculosis a nivel nacional. El curso fue planificado para capacitar a 15 personas como promotores : 10 de Nuevo México, 4 de Verapaz y uno de Tres Maravillas, quienes trabajaron en beneficio de su comunidad y fueron bien recibid a s por los pacientes y familiares. Conclusión: La participac ión comunitaria para reflexionar y definir el problema de la tuberculosis, así como los posibles caminos a seguir, demostró generar un alto compromiso en la obtenci
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Denise Perone
2005-01-01
Estudamos 32 crianças com HC devido à agenesia ou ectopia tireoideana para mutações no PAX8 e 30 crianças com hipoplasia da tireóide para mutações no rTSH. Todos os exons de ambos os genes foram amplificados a partir do DNA genômico, seguido por seqüenciamento direto. Encontramos, em dois pacientes com ectopia, duas alterações no gene PAX8, uma no promotor, e outra no exon um. Os outros indivíduos estudados apresentaram as seqüências codificáveis dos genes PAX8 e rTSH normais. Em relação ao c...
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International Nuclear Information System (INIS)
Brautigam, A.R.
1975-01-01
A technique is presented for mapping promotor sites that utilizes the introduction of transcription-terminating lesions in DNA through uv irradiation which prevents transcription of genes in proportion to their distance from the promotor. This technique was applied to and evaluated in investigations of the transcriptional linkage of bacteriophage T7. All results substantiate the hypothesis that transcription in vivo does not proceed beyond the first uv lesion encountered in the template DNA and that such premature termination of transcription is the principal effect of the uv irradiation on the transcriptional template function of DNA. UV-induced inhibition of the initiation of transcription is insignificant by comparison. Uv inactivation of expression of individual T7 genes was found to follow pseudo first-order kinetics, allowing a gene-specific uv inactivation cross section to be evaluated for each gene. Promotor locations were inferred from the discontinuity in the numerical values of inactivation cross sections arising at the start of each new unit. By such analysis the bacteriophage T7 genome was found to consist of seven transcription units. In vivo E. coli RNA polymerase transcribes the T7 early region as a single unit from a pomotor region located at the left end of the genome. The T7 late region was found to consist of six transcription units, with promotors located just ahead of genes 1.7, 7, 9, 11, 13 and 17
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Technical development of alcohol for fuel. Inspection and breeding of superior bacteria
Energy Technology Data Exchange (ETDEWEB)
1987-09-01
Heat- and alcohol-resistant bacteria for alcoholic fermentation were separated from the soils in Japan and abroad and the performance was evaluated to develop superior bacteria for ethanol fermentation. The superior bacteria pertinent to alcoholic fermentation were bred by domestication, variation treatment, cell fusion and gene manipulation. The productivity of ethanol was increased by controlling pH of thermophilic, aerobic cellulase and culturing the mixture of added nutrients. CMC ase and Beta-glucosidase genes, the component enzymes of cellulase, were successfully developed by Zymomonas sp. A promotor selecting vector of Zymomonas was produced for developing xylolase gene to acquire an active promotor.
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LENUS (Irish Health Repository)
Brophy, Karen
2010-01-01
BACKGROUND: Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. METHODS: We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. RESULTS: Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137\\/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C\\/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. CONCLUSION: Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine\\'s role in maintaining inflammation in active CD.
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LENUS (Irish Health Repository)
Brophy, Karen
2010-05-17
Abstract Background Recent whole genome analysis and follow-up studies have identified many new risk variants for coeliac disease (CD, gluten intolerance). The majority of newly associated regions encode candidate genes with a clear functional role in T-cell regulation. Furthermore, the newly discovered risk loci, together with the well established HLA locus, account for less than 50% of the heritability of CD, suggesting that numerous additional loci remain undiscovered. Linkage studies have identified some well-replicated risk regions, most notably chromosome 5q31 and 11q23. Methods We have evaluated six candidate genes in one of these regions (11q23), namely CD3E, CD3D, CD3G, IL10RA, THY1 and IL18, as risk factors for CD using a 2-phase candidate gene approach directed at chromosome 11q. 377 CD cases and 349 ethnically matched controls were used in the initial screening, followed by an extended sample of 171 additional coeliac cases and 536 additional controls. Results Promotor SNPs (-607, -137) in the IL18 gene, which has shown association with several autoimmune diseases, initially suggested association with CD (P < 0.05). Follow-up analyses of an extended sample supported the same, moderate effect (P < 0.05) for one of these. Haplotype analysis of IL18-137\\/-607 also supported this effect, primarily due to one relatively rare haplotype IL18-607C\\/-137C (P < 0.0001), which was independently associated in two case-control comparisons. This same haplotype has been noted in rheumatoid arthritis. Conclusion Haplotypes of the IL18 promotor region may contribute to CD risk, consistent with this cytokine\\'s role in maintaining inflammation in active CD.
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Directory of Open Access Journals (Sweden)
Lluis i Ginovart, Josep
2014-06-01
Full Text Available The construction of Gothic cathedrals can be seen as a transfer of knowledge between ecclesiastical figures the bishop and Chapter, and medieval architect. The beauty of the cathedral depended on the practica of medieval mason, versus the teorica of the church promoter. An example of this is the example of mainstreaming, the one of the construction of the Cathedral of Tortosa. Metrology and proportion of the architecture of the cathedral, derived directly from the philosophical sources of the Gothic order. The main authors of reference are identified in the chapter library; Augustine ACTo 20, Calcidius and Capella ACTo nº 80, Macrobius ACTo 236. This has allowed us to establish contact points between knowledge of the promoter and the gothic builder.La construcción de las catedrales góticas puede considerarse como un trasvase de conocimiento entre las figuras eclesiásticas del obispo y Capítulo, y el arquitecto medieval. La belleza de la catedral dependía de la practica del constructor medieval, y de la teorica de sus promotores. Una muestra de esta transversalidad es el ejemplo de la construcción de la catedral de Tortosa. La metrología y la proporción de la arquitectura de la catedral, emanan directamente de las fuentes filosóficas del orden gótico. Los principales autores de referencia están identificados en su biblioteca capitular: San Agustín (ACTo 20, Calcidio y Capella (ACTo nº 80 y Macrobio (ACTo 236. Esta circunstancia ha permitido establecer unos puntos de contacto entre los saberes del promotor y del constructor góticos.
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Directory of Open Access Journals (Sweden)
Eliza Hawrylik
2017-06-01
Full Text Available The aim of the study was the evaluation of usefulness of Escherichia coli K-12 RFM 443 katG::lux for cytotoxicity and genotoxicity monitoring of metoprolol in the environment. Metoprolol is one of the most popular cardiac drug which belongs to the group of β – blockers. The drug was applied at concentrations ranging from 10-1 mg/cm3 to 10-5 mg/cm3. Obtained data indicated the influence of metoprolol on lux gene expression and katG promotor activity in E.coli K-12. The results indicato the possibility of using of Escherichia coli K-12 RFM 443 strain with katG::lux gene construct in the monitoring of cytotoxicity and genotoxicity cardiac drug residues in the environment.
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Directory of Open Access Journals (Sweden)
Graciana Alves Duarte
2010-06-01
Full Text Available OBJETIVO: Analisar opiniões de juízes e promotores de justiça sobre a legislação brasileira e as circunstâncias em que o aborto induzido deveria ser permitido. MÉTODOS: Estudo transversal realizado com 1.493 juízes e 2.614 promotores no Brasil entre 2005 e 2006. Os participantes preencheram um questionário estruturado sobre características sociodemográficas, opiniões acerca da legislação que trata do aborto e circunstâncias para permiti-lo. Realizaram-se análises bivariada e multivariada por regressão de Poisson. RESULTADOS: A maioria (78% dos participantes opinou que as circunstâncias nas quais não se pune o aborto deveriam ser ampliadas, ou mesmo que o aborto não deveria ser considerado crime. As maiores proporções de opiniões favoráveis a que o aborto seja permitido referiram-se a risco para a vida da gestante (84%, anencefalia (83%, malformação congênita grave (82% e gravidez resultante de estupro (82%. As variáveis relativas à religião foram as mais freqüentemente associadas a essas opiniões. CONCLUSÕES: Observou-se uma tendência a considerar a necessidade de mudanças na atual legislação brasileira no sentido de ampliar as circunstâncias nas quais não se pune o aborto e até deixar de considerá-lo como um crime, independentemente da circunstância em que é praticado.OBJETIVO: Analizar opiniones de jueces y promotores de justicia sobre la legislación brasilera y las circunstancias en que el aborto inducido debería ser permitido. MÉTODOS: Estudio transversal realizado con 1.493 jueces y 2.614 promotores en Brasil entre 2005 y 2006. Los participantes llenaron un cuestionario estructurado sobre características sociodemográficas, opiniones acerca de la legislación que trata el aborto y circunstancias para permitirlo. Se realizaron análisis bivariado y multivariado por regresión de Poisson. RESULTADOS: La mayoría (78% de los participantes opinó que las circunstancias en las cuales no se castiga
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Cloning and expression of chaetomium thermophilum xylanase 11-A gene in prokaryote
International Nuclear Information System (INIS)
Wajid, S.; Latif, F.; Afzal, S.; Rajoka, I.
2008-01-01
The xylanase gene was cloned into pET32a(+) and expressed in E. coli BL21 under T7 promotor alongwith fusion protein. The SDS-PAGE and western blot analysis showed a protein of 42 kDa. The best expression of xylanase enzyme was found by using xylose as carbon source and lactose as an inducer. The maximum activity of xylanase expressed in E. coli was 6.02 U/mL in the presence of 2% xylose in DS medium. The activity of recombinant xylanase was observed on 1% xylan LB agar plates, showed halos of xylan clearance when lactose was used as an inducer. (author)
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MSc. Yanira Zaita Ferrer; MSc. Milena Galbán Díaz; Lic. Raquel Bauta Bauta
2016-01-01
La farmacodependencia y automedicación es una dificultad que reviste importancia por parte del farmacéutico y requiere un aumento de la comunicación entre estos y los pacientes, siendo la promoción de salud la práctica más aceptada en el panorama actual y la vía para contrarrestar este hábito. La investigación consistió en identificar las potencialidades e insuficiencias en la formación del Técnico Medio en Servicios Farmacéuticos como promotor de salud. Los métodos utilizados en la investiga...
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Villa-Torres, Laura; Fleming, Paul J; Barrington, Clare
2015-02-01
The promotor de salud, or community health worker (CHW) role, is highly feminized and little is known about how men view their participation in CHW programs. We conducted in-depth interviews with Latino men in North Carolina to explore this gap. We used systematic coding and display procedures informed by Grounded Theory to analyze the data. Men described their communities as lacking cohesion, making integration of Latino immigrants difficult. Most did not consider themselves leaders or feel they had leaders in their communities. Their perceptions of the feminized CHW role as well as the volunteer or low-paid nature of CHW work conflicted with men's provider role. They also did not think they could perform the CHW role because they lacked education, skills, and broad networks. Efforts to increase male participation in CHW programs in new Latino immigrant destinations will need to understand and address these gender and migration-related dynamics in order to engage both women and men in improving the health of their communities.
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Directory of Open Access Journals (Sweden)
Borau i Morell, Cristina
2002-12-01
Full Text Available The issue of this article is the patronage or promotion of de chapels in gothic churches as a mean of consolidation of people's social prestige. All along the XIV century the cathedral and the three parishes of Sta. Maria del Mar, Sta. Maria del Pi and Sant Just in Barcelona had been rebuilt. Church authorities had expected that changuig the romanic churches into the the gothic style known today would be slow and expensive, that is why they decided to confer the new chapels to wealthy people who in turn were supposed to give the eclesiastical institution a generous donation. The promotors of these chapels were mostly merchants and royal civil servants who were at that time in the best social position. Most of them belonged to families who had achieved this position in the past, but we have concentrated in those who were the last ones to obtain better standards of social consideration. The monitoring of their social development has been done thoug legal documentation.
El tema d'aquest article es el mecenatge o promoció de capelles a les esglésies gòtiques corn a instrument de consolidació del prestigi social. Al llarg del segle XIV es van renovar la catedral i les tres grans esglésies parroquials de Barcelona: Sta. Maria del Mar, Sta. Maria del Pi i Sant Just. Les autoritats eclesiàstiques van preveure, des del principi, que la transformació d'aquells temples romànics en els gòtics de l'actualitat seria lenta i molt cara. Per això van decidir concedir les noves capelles que s'anaven construint a persones adinerades, a canvi que paguessin un generós donatiu. Els promotors d'aquelles capelles eren, majoritàriament, mercaders i oficials reials, els sectors socials que mes van prosperar en aquell context. Bona part d'aquells promotors pertanyia a famílies que ja havien iniciat l'escalada estamental anteriorment, però nosaltres ens hem centrat en els que van protagonitzar nous ascensos socials. El seguiment de la seva traject -
International Nuclear Information System (INIS)
Kim, Dong Sub; Kim, Jinbaek; Ha, Bokeun; Kim, Sang Hoon; Kim, Sunhee
2013-05-01
Physiological analysis of monocot model plant (rice) in response to ionizing radiation (cosmic-ray, gamma-ray, Ion beam). - Identification of antioxidant characters through cytochemical analysis. - Comparison of antioxidant activities in response to ionizing irradiation. - Evaluation of anthocyanin quantity in response to ionizing irradiation. Ionization energy response gene family analysis via bioinformatic validation. - Expression analysis of monocot and dicot gene families. - In silico and bioinformatic approach to elucidate gene function. Characterization and functional analysis of genes specifically expressed in response to ionizing irradiation (cosmic-ray, gamma-ray, Ion beam). - High throughput trancriptomic analysis of plants under ionizing radiation using microarray. - Promotor and cis-element analysis of genes specifically expressed in response to ionizing radiation. - Validation and function analysis of candidate genes. - Elucidation of plant mechanism of sensing and response to ionization energy. Development of bioindicator plants detecting ionization energy. - Cloning and identification of 'Radio marker genes (RMG)'. - Development of Over-expression (O/E) or Knock-out (K/O) plant using RMG. Development of Genechip as an ionization energy detector. - Expression profiling analysis of genes specifically expression in response to ionization energy. - Prepare high-conserved gene specific oligomer. - Development of ionization energy monitoring Genechip and application
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Energy Technology Data Exchange (ETDEWEB)
Kim, Dong Sub; Kim, Jinbaek; Ha, Bokeun; Kim, Sang Hoon; Kim, Sunhee
2013-05-15
Physiological analysis of monocot model plant (rice) in response to ionizing radiation (cosmic-ray, gamma-ray, Ion beam). - Identification of antioxidant characters through cytochemical analysis. - Comparison of antioxidant activities in response to ionizing irradiation. - Evaluation of anthocyanin quantity in response to ionizing irradiation. Ionization energy response gene family analysis via bioinformatic validation. - Expression analysis of monocot and dicot gene families. - In silico and bioinformatic approach to elucidate gene function. Characterization and functional analysis of genes specifically expressed in response to ionizing irradiation (cosmic-ray, gamma-ray, Ion beam). - High throughput trancriptomic analysis of plants under ionizing radiation using microarray. - Promotor and cis-element analysis of genes specifically expressed in response to ionizing radiation. - Validation and function analysis of candidate genes. - Elucidation of plant mechanism of sensing and response to ionization energy. Development of bioindicator plants detecting ionization energy. - Cloning and identification of 'Radio marker genes (RMG)'. - Development of Over-expression (O/E) or Knock-out (K/O) plant using RMG. Development of Genechip as an ionization energy detector. - Expression profiling analysis of genes specifically expression in response to ionization energy. - Prepare high-conserved gene specific oligomer. - Development of ionization energy monitoring Genechip and application.
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Leandro Batista Costa; Marcos Livio Panhoza Tse; Valdomiro Shigueru Miyada
2007-01-01
Avaliou-se, por meio do desempenho e da morfometria de órgãos, o uso de extratos vegetais como alternativas aos antimicrobianos promotores de crescimento para leitões recém-desmamados. Um experimento em blocos casualizados, com 35 dias de duração, foi realizado para testar cinco tratamentos: ração basal; antimicrobiano - ração basal com colistina + tiamulina (75 ppm de cada); extratos vegetais - ração basal com 420 ppm de cravo (Ec); orégano (Eo) e cravo + orégano (Ec + Eo), respectivamente. ...
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Teather, R M; Bramhall, J; Riede, I; Wright, J K; Fürst, M; Aichele, G; Wilhelm, U; Overath, P
1980-01-01
The previously described hybrid plasmid pC7 which carries lacI+O+delta(Z)Y+A+ on a 12.3 X 10(6)-Mr DNA fragment [Teather et al. (1978) Mol. Gen. Genet. 159, 239-248] was partially digested with the restriction endonuclease EcoRI under conditions reducing the recognition sequence to d(A-A-T-T) and ligated to the vector pB322. lac Y-carrying inserts of various sized (Mr 1.5-4.7 X 10(6)) were obtained. Hybrid plasmid pTE18 (2300-base-pair insert) carries part of the I (repressor) gene, the promotor-operator region, part of the Z (beta-galactosidase) gene, the Y (lactose carrier) gene and part of the A (transacetylase) gene. Upon induction of pTE18-harbouring strains the Y-gene product is expressed at a nearly constant rate for several generations and accumulates to a level of 12-16% of the total cytoplasmic membrane protein. Integration into the membrane leads to active carrier as judged by binding and transport measurements.
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Cicero Nunes Moreira
2013-09-01
Full Text Available MOREIRA, Cícero. N. De soldado de cristo a Promotor de direitos humanos: história, religião e cultura na Polícia Militar de Minas Gerais (1950–2004. Dissertação (Mestrado 2013. 152f - Pontifícia Universidade Católica de Minas Gerais, Programa de Pós-graduação em Ciências da Religião, Belo Horizonte. Palavras-chaves: Polícia Militar. Identidade. Catolicismo. Devoções. Capelania Militar, Protestantismo. Evangélicos. Direitos Humanos.
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Silvia Veganzones-de-Castro
2012-03-01
Full Text Available Introduction: p16 gene plays an important role in the cell cycle regulation and is considered an important tumor suppressor gene. Several mechanisms of gene inactivation have been described; in this study we have focused on p16 gene promoter methylation. In colorectal cancer p16 gene methylation is a frequent event. Methods: 326 patients with sporadic colorectal cancer were included. DNA was extracted from tumor tissue samples obtained during the surgical procedure. Promoter methylation was analyzed using bisulfite modification and was detected by quantitative methylation-specific PCR. Frequency of p16 methylation was analyzed and compared with other clinicopathological variables. Results: p16 gene methylation was detected in 24,8% of patients. Methylation was associated with differentiation grade and with tumor location: methylation was frequent in poorly differentiated tumors and had low frequency in distal colon. The p16 promoter methylation discriminated a subgroup of patients with better prognosis in poorly differentiated tumors. Conclusions: p16 methylation was a frequent event in our population and was able to induce differences in the overall survival of patients with poorly differentiated tumors.Introducción: el gen p16 está implicado en la regulación del ciclo celular y se considera un importante gen supresor de tumores. Objetivos: se han descrito diferentes mecanismos de inactivación génica, en este estudio nos hemos centrado en la metilación del promotor del gen p16. En el cáncer colorrectal la metilación de p16 es una alteración frecuente. Material y métodos: se incluyeron 326 pacientes con cáncer colorrectal esporádico. El ADN se extrajo de muestras tumorales obtenidas durante la cirugía. La metilación del promotor se analizó mediante un proceso de modificación con bisulfito y posterior PCR cuantitativa especifica para metilación. Se analizó la frecuencia de la metilación de p16 y se comparó con las variables
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Boyacioglu, Seda Orenay; Kasap, Elmas; Yuceyar, Hakan; Korkmaz, Mehmet
2016-01-01
Helicobacter pylori, intestinal metaplasia (IM), and gene methylation play important roles in gastric carcinogenesis. However, the association among H. pylori infection, IM, gastric cancer (GC), and gene methylation is not fully understood. Cell cycle control involving retinoblastoma 1 (RB1) gene is one of the main regulatory pathways reported to be altered in gastric carcinogenesis. The purpose of this research is to assess the methylation status of RB1 gene in GC and IM with or without H. pylori infection, and to discuss the possible role of H. pylori-induced RB1 gene methylation in the mechanism of gastric carcinogenesis. The methylation profile of RB1 gene was analyzed by sodium bisulfite modification and methylation-specific PCR in GC (n = 24), IM patients with H. pylori positive (n = 20) and negative (n = 20), and control subjects (n = 20). According to methylation levels in RB1 gene; the high correlation values were detected between H. pylori positive-IM group and GC group, and between H. pylori positive-IM and H. pylori negative-IM groups (p gene. High methylation levels in RB1 gene in H. pylori positive individuals may suggest an elevated risk of gastric cancer occurrence.
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McDonough, A Manuela; Vargas, Marcela; Nguyen-Rodriguez, Selena; Garcia, Melawhy; Galvez, Gino; Rios-Ellis, Britt
2016-01-01
Although cervical cancer can be prevented through screening and follow-up, Latinas' rate of Pap tests remains low due to knowledge gaps and cultural and attitudinal factors. This study used a single-group pre-/post-test design to evaluate the effectiveness of Mujer Sana, Familia Fuerte (Healthy Woman, Strong Family), an intervention intended to improve Latinas' cervical cancer prevention knowledge, attitudes, self-efficacy to obtain a Pap test, and intention to get tested. The intervention is delivered through a single session by promotores de salud, who use a culturally competent, linguistically appropriate toolkit. A total of 5,211 Latinas participated in the study. The evaluation indicated that participants had increases in knowledge, positive attitudes, self-efficacy, and intention to test. Latinas have a low rate of cervical cancer screening but a high rate of cervical cancer, and Mujer Sana, Familia Fuerte shows promise as a public health practice for use with this population.
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Reginaldo de Freitas; José Brandão Fonseca; Rita da Trindade Ribeiro Nobre Soares; Horacio Santiago Rostagno; Paulo Rubens Soares
2001-01-01
Três experimentos foram conduzidos com o objetivo de avaliar a utilização do alho na alimentação de frangos de corte, como promotor de crescimento. No primeiro experimento, foram utilizados 480 pintos de corte, sexados, distribuídos em seis tratamentos com oito repetições (quatro de machos e quatro de fêmeas), com dez aves cada uma. Os tratamentos foram: ração basal com milho, farelo de soja e fosfato bicálcio (RB1); RB1 + 0,2% de alho; RB1 + 0,4% de alho, RB1 + 0,6% de alho; RB1 + 0,001% de ...
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Directory of Open Access Journals (Sweden)
Hendrik Dirk ede Heer
2015-06-01
Full Text Available AbstractBackgroundCommunity resources (parks, recreational facilities provide opportunities for health promotion, but little is known about how to promote utilization of these resources and their impact on cardiovascular disease risk (CVD. MethodsThis cohort study evaluated the impact of an intervention called Mi Corazon Mi Comunidad (MiCMiC, which consisted of promoting use of community physical activity and nutrition resources by Promotoras de Salud/Community Health Workers. Participants were assessed at baseline and following the 4-month intervention. Attendance records were objectively collected to assess utilization of intervention programming. ResultsA total of 5 consecutive cohorts were recruited between 2009 and 2013. Participants were mostly females (86.0%, on average 46.6 years old, and 81% were low in acculturation. Participants who completed follow-up (n=413 showed significant improvements in reported health behaviors and body composition. Higher attendance significantly predicted greater improvements. The baseline to 4-month change for the highest versus the lowest attendance quartiles were (-5.2 lbs vs. +0.01 lbs, p<.001, waist circumference (-1.20 inches vs. -0.56 inches, p=.047, hip circumference (-1.13 inches vs. -0.41 inches, p<.001; hours of exercise/week (+3.87 hours vs. +0.81 hrs, p<.001, proportion of participants eating 5 servings of fruits and vegetables/day (+54.7% vs. 14.7%, p<.001.ConclusionsFollowing the Promotora-led MiCMiC intervention, substantial improvements in health behaviors and modest improvements in cardiovascular risk factors were found. Greater utilization of community resources was associated with more favorable changes. This study provided preliminary evidence for the effectiveness of Promotora-led interventions for promoting use of existing community resources in CVD risk reduction. Key Words: Community resources, community health workers, U.S.- Mexico border, Hispanic, cardiovascular disease, cohort
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de Heer, Hendrik Dirk; Balcazar, Hector G; Wise, Sherrie; Redelfs, Alisha H; Rosenthal, E Lee; Duarte, Maria O
2015-01-01
Community resources (parks, recreational facilities) provide opportunities for health promotion, but little is known about how to promote utilization of these resources and their impact on cardiovascular disease risk (CVD). This cohort study evaluated the impact of an intervention called Mi Corazon Mi Comunidad (MiCMiC), which consisted of promoting use of community physical activity and nutrition resources by Promotoras de Salud/Community Health Workers. Participants were assessed at baseline and following the 4-month intervention. Attendance records were objectively collected to assess utilization of intervention programing. A total of five consecutive cohorts were recruited between 2009 and 2013. Participants were mostly females (86.0%), on average 46.6 years old, and 81% were low in acculturation. Participants who completed follow-up (n = 413) showed significant improvements in reported health behaviors and body composition. Higher attendance significantly predicted greater improvements. The baseline to 4-month change for the highest vs. the lowest attendance quartiles were for weight (-5.2 vs. +0.01 lbs, p < 0.001), waist circumference (-1.20 vs. -0.56 inches, p = 0.047), hip circumference (-1.13 vs. -0.41 inches, p < 0.001); hours of exercise/week (+3.87 vs. +0.81 hours, p < 0.001), proportion of participants eating five servings of fruits and vegetables/day (+54.7 vs. 14.7%, p < 0.001). Following the Promotora-led MiCMiC intervention, substantial improvements in health behaviors and modest improvements in cardiovascular risk factors were found. Greater utilization of community resources was associated with more favorable changes. This study provided preliminary evidence for the effectiveness of Promotora-led interventions for promoting use of existing community resources in CVD risk reduction.
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Pereira, Christiane Maria Leite; Dornelas, Jairo Simião
2010-01-01
Este estudo buscou identificar fatores promotores e inibidores do alinhamento estratégico entre a tecnologia da informação e a estratégia empresarial em uma situação de fusão de empresas em um ambiente varejista. O caso possibilitou identificar percepções do corpo gerencial acerca das características promotoras e inibidoras do alinhamento. O estudo destacou eventos nos momentos antes do processo de fusão e no seu desenrolar, tal que se pôde associar aos fatores clássicos identificados na lite...
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Directory of Open Access Journals (Sweden)
Jeane Eliete Laguila Visentainer
2008-12-01
Full Text Available A compatibilidade genética HLA entre doador e receptor é um fator importante para o sucesso do transplante de células progenitoras hematopoiéticas (TCPH. No entanto, outros genes não-HLA estão sendo investigados em relação ao seu papel na incidência e gravidade da doença do enxerto contra o hospedeiro e na sobrevida, por modularem a intensidade da inflamação e os danos teciduais. Estes genes, não-HLA, incluem os genes de citocinas com polimorfismos dentro das seqüências 5' ou 3' regulatórias dos genes. Os polimorfismos ou microssatélites podem alterar a ligação dos fatores de transcrição aos sítios dentro dos genes promotores e a quantidade de citocina produzida. Este estudo revisa o papel potencial destes polimorfismos genéticos relativos às citocinas em prever o curso do TCPH.HLA genetic matching of donor and recipient is an important requirement for optimizing outcome following hematopoietic stem cell transplantation (HSCT. However, other non-HLA genes are being investigated for their role in graft-versus-host disease incidence and severity and in survival, by modulating the intensity of inflammation and tissue injury. These non-HLA-encoded genes include cytokine genes with polymorphisms within the 5' or 3' regulatory sequences of the genes. The polymorphisms or microsatellites may alter the transcription factor binding sites within the gene promoters and the amount of cytokine produced. This chapter summarizes the potential role of these genetic polymorphisms regarding the cytokines in predicting outcome of HSCT.
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DEFF Research Database (Denmark)
Østergaard, Trine G.; Hansen, Lars Henrik; Binderup, Mona-Lise
2007-01-01
A new bacterial test system for detection of genotoxic compounds was developed, based on two new Sahnonella typhimurium tester strains, TGO1 and TGO2. Both strains contain a gene fusion between a strong SOS-promotor, P-cda, and the gfp gene, which allows detection of genotoxic compounds that indu...
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O CONFLITO COMO PROMOTOR DA LIBERDADE NA REPÚBLICA MAQUIAVELIANA
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Luis Fernando de Carvalho Sousa
2016-12-01
The Machiavellian thinking is cause of disputes and controversies between several researchers. These conflicts usually revolve around the interpretation of political positions and implications of concepts used by the author. This article seeks to understand the issue of conflict in the Machiavellian republic and its actors, aiming to identify the role of the people in the conflict and the role that Machiavelli attributes to it as one of the key players in maintaining in promoting freedom within the republican regime proposed by the philosopher. This element appears as one of the key players in the maintenance and promotion of democracy. In this sense, become key elements to understand the political disputes in the republic. Through a bibliographical research the article sought to understand this conflicting relationship that takes place within the republican environment and concluded that although there are divergences around the dispositions within the republic the role of resolving them always rests with the institutions. Keywords: Machiavelli; Conflict; Freedom; Republic; People. EL CONFLICTO COMO UN PROMOTOR DE LA LIBERTAD EN LA REPÚBLICA MAQUIAVÉLIANA RESUMEN El pensamiento maquiavélico es causa de conflictos y controversias entre varios investigadores. Estos conflictos por lo general giran en torno a la interpretación de las posiciones políticas e implicaciones de los conceptos utilizados por el autor. En este artículo se busca entender el tema del conflicto en la república maquiavélica y sus actores, con el objetivo de identificar el papel del pueblo en los conflictos y el papel que Maquiavelo atribuye a él como uno de los jugadores clave en el mantenimiento en la promoción de la libertad dentro del régimen republicano propuesto por el filósofo. Este elemento aparece como uno de los jugadores clave en el mantenimiento y promoción de la democracia. En este sentido, se convierten en elementos clave para entender los conflictos políticos en la rep
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The Optimedin gene is a downstream target of Pax6
Czech Academy of Sciences Publication Activity Database
Grinchuk, O.; Kozmik, Zbyněk; Wu, X.; Tomarev, S.
2005-01-01
Roč. 280, č. 42 (2005), s. 35228-35237 ISSN 0021-9258 R&D Projects: GA ČR GA204/04/1358 Institutional research plan: CEZ:AV0Z50520514 Keywords : Pax6 * optimedin * promotor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.854, year: 2005
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T. P. Kazubskaya
2012-01-01
Full Text Available The methylation status of the tumor suppressor genes RASSF1A, RARβ2, and SEMA3B was studied in the samples of cancer and its histologically normal tissue of the breast and ovaries. The high rate of abnormal methylation of the CpG islet in the RASSF1A, RARβ2, and SEMA3B genes was found in the tumors of the breast (78% (32/41, 46% (26/56, and 35% (22/65, respectively and ovaries 73% (33/45, 30% (15/50, and 50% (25/51. Hypermethylation in the CpG islets belonging to the RASSF1A and RARβ2 genes was first ascertained in 90% of the patients with polyneoplasms involving the breast and ovaries. Abnormal methylation of the promotor region of the RASSF1A gene was shown to be detectable in preclinical-stage and anaplasia-degree breast and ovarian cancer. There was a correlation of the rate of methylation in the promoter regions of the RARβ2 and SEMA3B genes with clinical-stage and anaplasia-degree breast and ovarian cancer. Analysis of gene methylation in biological fluids provides considerable opportunity to use methylation of DNA as a marker in clinical practice.
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Directory of Open Access Journals (Sweden)
Castagnino Guido Laércio
2006-01-01
Full Text Available Estudou-se o desenvolvimento na área de cria de 14 núcleos com quatro favos a partir da divisão de nove colméias de abelhas Apis mellifera africanizada, distribuídos em dois tratamentos: TPL - núcleos alimentados com açúcar invertido + 3,5ml do suplemento de aminoácido vitamínico (Promotor L®, composto por seis núcleos e o TAI - núcleos alimentados com açúcar invertido, composto por oito núcleos. Os núcleos foram alimentados semanalmente em alimentadores individuais tipo bandeja, e as avaliações realizadas em quatro períodos, totalizando 74 dias Os tratamentos não apresentaram diferença significativa, sendo que, numericamente, o TPL apresentou área de cria inferior ao TAI (233,63 vs. 273,02cmsuperscript two, respectivamente. Quanto aos períodos o quarto período foi superior (P<0,05 ao primeiro e ao segundo, sendo que o terceiro período não apresentou diferença significativa (P<0,05 em relação aos demais. A utilização do TAI foi economicamente mais favorável em relação ao TPL em R$0,21 em relação ao custo para produção de 1kg de alimento.
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Promotores��� perspectives on a male-to-male peer network
Macia, Laura; Ruiz, Hector Camilo; Boyzo, Roberto; Documet, Patricia Isabel
2016-01-01
Little documentation exists about male community health workers (promotores) networks. The experiences of promotores can provide input on how to attract, train, supervise and maintain male promotores in CHW programs. We present the experience and perspectives of promotores who participated in a male promotores network assisting Latino immigrant men in an emerging Latino community. All promotores in this community-based participatory study received payment for work 10 hours a week. We conducte...
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C. Oleskovicz
2004-08-01
Full Text Available cDNAs dos genes bone morphogenetic protein-2 (BMP-2 e bone morphogenetic protein-4 (BMP-4 foram sintetizados a partir de RNA total extraído de tecidos ósseos de pacientes que apresentavam trauma facial (fraturas do maxilar entre o 7º e o 10º dia pós-trauma e clonados num vetor para expressão em células mamíferas, sob controle do promotor de citomegalovírus (CMV. Os vetores contendo os genes BMP-2 e o BMP-4 foram utilizados para a transfecção de fibroblastos bovinos. mRNAs foram indiretamente detectados por RT-PCR nas células transfectadas. As proteínas BMP-2 e BMP-4 foram detectadas mediante análises de Western blot. Os resultados demonstram a possibilidade de produção desses fatores de crescimento celular em fibroblastos bovinos. Essas células poderão ser utilizadas como fontes doadoras de material genético para a técnica de transferência nuclear na geração de animais transgênicos.
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Integrones: los coleccionistas de genes Integrons: gene collectors
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J. A. Di Conza
2010-02-01
Full Text Available Los integrones son estructuras genéticas que han despertado gran interés, debido a que algunos de ellos vehiculizan genes de resistencia a los antimicrobianos. Están formados por un fragmento que codifica una integrasa (intI y, a continuación, una secuencia attI a la que se unen los genes en casetes que codifican diferentes mecanismos de resistencia. Dentro de intI, en su extremo 3´, hay una secuencia promotora Pc a partir de la cual se transcriben los casetes de resistencia integrados, ya que estos genes carecen de promotor. Sin embargo, estos casetes presentan una secuencia específica denominada attC, la cual es reconocida por la integrasa que se une, por recombinación, a la secuencia attI del integrón en la orientación adecuada para su expresión. Los integrones se han clasificado según la secuencia de su integrasa, pero en la actualidad se prefiere clasificarlos según su localización. Se habla, en general, de "integrones móviles" para referirse a aquellos asociados a secuencias de inserción, transposones y/o plásmidos conjugativos, los que en su mayoría median mecanismos de resistencia, y de "superintegrones", de localización cromosómica y con grandes arreglos de genes en casetes. Los integrones móviles de clase 1 son los más abundantes en aislamientos clínicos y suelen estar asociados a transposones del subgrupo Tn21, seguidos por los de clase 2, derivados principalmente de Tn7. Estos elementos no son móviles por sí mismos, pero su asociación con elementos que sí lo son facilita su transferencia horizontal, lo que explica su amplia difusión entre las bacterias. Esta revisión intenta recopilar la información disponible acerca de los integrones móviles descritos en Argentina hasta la fecha.Integrons gained great interest due to their participation in resistance gene recruitment and expression. Their basic structure includes a fragment that encodes an integrase (intI followed by a recognition sequence (attI into
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Francine Lorena Cuquel
2001-05-01
Full Text Available Deficiência nutricional em plantas pode causar clorose, necrose, desfolha, redução do crescimento e da produtividade e senescência prematura. Aplicações xógenas de citocinina podem aliviar tais sintomas. Este estudo foi efetuado para avaliar os efeitos da produção auto-regulada de citocinina na tolerância de plantas de petúnia (Petunia x hybrida à deficiência nutricional. Um gene quimérico contendo o promotor SAG12 unido ao gene ipt, o qual codifica a produção de isopentenyl transferase, uma enzima da rota metabólica da biossíntese de citocinina, foi introduzido em petúnia através de transformação mediada por Agrobacterium. Duas plantas contendo o gene ipt foram selecionadas e autopolinizadas para obtenção das linhas a serem submetidas à deficiência nutricional. Ambas as linhas PSAG12–ipt avaliadas foram mais tolerantes à deficiência nutricional que as plantas do tipo selvagem. Os resultados indicam que a produção endógena de citocinina pode aumentar a tolerância das plantas à deficiência nutricional.
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Masome Zeinali
2016-09-01
Full Text Available Introduction: Ethanol made by a biomass is one of the useful strategies in terms of economic and environmental and as a clean and safe energy to replace fossil fuels considered and examined. Materials and methods: In this study, key enzyme in the production of ethanol (Pyruvate decarboxylase from Zymomonas mobilis bacteria was isolated and cloned at E. coli bacteria by freeze and thaw method. For gene cloning, we used specific primers of pdc and PCR reaction and then pdc gene isolated and pET 28a plasmid double digested with (Sal I and Xho I enzymes. Digestion Products were ligated by T4 DNA ligase in 16 °C for 16 hours. Results: Results of bacteria culture showed that a few colonies containing pET 28a plasmid could grow. Result of colony pcr of pdc gene with specific primers revealed 1700 bp bands in 1% agarose gel electrophoresis. The results of PCR with T7 promotor forward primer and pdc revers primer have proved the accurate direction of integration of pdc gene into plasmid and revealed 1885 bp band. Double digestion of recombinant plasmid with SalI and XhoI enzymes revealed same bands. Finally, RT showed the expected band of 1700 bp that implies the desired gene expression in the samples. Discussion and conclusion: Due to the increased production of ethanol via pyruvate decarboxylase gene cloning in expression plasmids with a strong promoter upstream of the cloning site can conclude that, pyruvate decarboxylase cloning as a key gene would be useful and according to beneficial properties of E. coli bacteria, transfering the gene to bacteria appears to be reasonable.
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Reginaldo de Freitas
2001-06-01
Full Text Available Três experimentos foram conduzidos com o objetivo de avaliar a utilização do alho na alimentação de frangos de corte, como promotor de crescimento. No primeiro experimento, foram utilizados 480 pintos de corte, sexados, distribuídos em seis tratamentos com oito repetições (quatro de machos e quatro de fêmeas, com dez aves cada uma. Os tratamentos foram: ração basal com milho, farelo de soja e fosfato bicálcio (RB1; RB1 + 0,2% de alho; RB1 + 0,4% de alho, RB1 + 0,6% de alho; RB1 + 0,001% de lincomicina e RB1 + 0,0025% de bacitracina de zinco. No segundo experimento, utilizaram-se 240 pintos de corte, sexados, distribuídos em três tratamentos com oito repetições (quatro de machos e quatro de fêmeas com dez aves cada uma. Os tratamentos foram ração basal com milho, farelo de soja e farinha de carne e ossos (RB2; RB2 + 0,2% de alho e RB2 + 0,4% de alho. No terceiro experimento, foram utilizadas 120 pintos de corte (fêmeas, criadas até aos 42 dias de idade, distribuídos em três tratamentos como descrito para o segundo experimento. Em todos os experimentos, foram avaliados consumo de ração, ganho de peso e conversão alimentar. No primeiro e segundo experimentos, avaliou-se também o peso de intestino delgado. Em nenhum dos três experimentos, foram observados efeitos significativos dos tratamentos sobre as características avaliadas. As aves apresentaram desempenho normal, sugerindo que as condições nas quais foram desenvolvidas os experimentos não foram adequadas para obter respostas, devido à utilização de promotores de crescimento.Three experiments were carried out to evaluate garlic in broilers diets as growth promoter. In the first experiment 480 one day old chicks, sexed, were distributed in six treatments with eight replicates (four with males and four with females, with ten birds each. The treatments were: basal diet with corn , soybean meal and dicalcium phosphaate (RB1, RB1 + 0.2% garlic; RB1 + 0.4%garlic; RB1
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Cloning, sequence and expression of the pel gene from an Amycolata sp.
Brühlmann, F; Keen, N T
1997-11-20
The pel gene from an Amycolata sp. encoding a pectate lyase (EC 4.2.2.2) was isolated by activity screening a genomic DNA library in Streptomyces lividans TK24. Subsequent subcloning and sequencing of a 2.3 kb BamHI BglII fragment revealed an open reading frame of 930 nt corresponding to a protein of 29,660 Da. The overall G + C content for the coding region was 65%, with a strong G + C preference in the third (wobble) codon position (93%). A putative ribosome-binding site 5'-GGGAG-3' preceded the translational start codon by 7 base pairs. The Amycolata pectate lyase contains a signal peptide of 26 amino acids, that is cleaved after the sequence Ala-Thr-Ala. The size of the deduced protein as well as its N-terminal amino-acid sequence match the wild-type pectate lyase from the Amycolata sp. Expression of the pel gene in S. lividans TK24 resulted in high pectate lyase activity in the culture supernatant, concomitant with the appearance of a dominant protein band on a sodium dodecyl polyacrylamide gel at 30 kDa. No pectate lyase activity was detected in E. coli BL21 with the pel gene under the strong T7 promotor. The deduced amino-acid sequence showed 40% identity with PelE from Erwinia chrysanthemi and the pectate lyase from Glomerella cingulata. The Amycolata pectate lyase clearly belongs to the pectate lyase superfamily, sharing all functional amino acids and likely has a similar structural topology as Pels from Erwinia chrysanthemi and Bacillus subtilis.
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Lic. Yisell Morales Álvarez
2016-03-01
Full Text Available El objetivo del presente trabajo radica en poner de manifiesto los presupuestos relativos a la Educación para la Salud y la Hipertensión Arterial Infantil, donde la escuela ha de contribuir a lograr una educación integral en los niños y niñas, de forma tal que sean capaces de tomar decisiones responsables, las que van a tener consecuencias claras sobre su salud y la de quienes los rodean. Es por ello que se les debe ayudar a tener una opinión informada que le permita tomar decisiones conscientes sobre los factores de riesgo de la Hipertensión Arterial, a adquirir los recursos conceptuales, procedimentales y actitudinales necesarios para alcanzar un estilo de vida saludable. Para ello se analizan el Programa Director de Promoción y Educación para la Salud en el Sistema Nacional como fundamentos para abordar la temática. También se presentan las consideraciones generales, como resultado práctico alcanzado, para llevar a cabo un círculo de interés que favorezca el desarrollo de un movimiento de pioneros promotores de salud en el seminternado “Camilo Cienfuegos Gorriarán” de Santa Clara, con el que se transformó la orientación valorativa de los estudiantes ante la necesidad del control de los factores de riesgo, en la manifestación y aparición de la Hipertensión Arterial Infantil.
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Ruhé, Henricus G.; Ooteman, Wendy; Booij, Jan; Michel, Martin C.; Moeton, Martina; Baas, Frank; Schene, Aart H.
2009-01-01
BACKGROUND: In major depressive disorder, selective serotonin reuptake inhibitors target the serotonin transporter (SERT). Their response rates (30-50%) are modified by SERT promotor polymorphisms (5-HTTLPR). OBJECTIVES: To quantify the relationship between SERT occupancy and response, and whether
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De Anne Karen Hilfinger Messias
1983-12-01
Full Text Available Reidratação oral, iniciado do princípio da diarréia, pode combater efetivamente a desidratação, eliminar uma dependência de recursos e tecnologia de tratamento parenteral e prevenir uma resultante desnutrição. O êxito desta terapia é um avanço importante na fea de doenças diarréicas. A sua base científica se encontra na fisiologia da absorção de água e eletrólitos pela mucosa do intestino delgado. Num programa de assistência primária, é necessário criar uma tecnologia apropriada que facilite a transferência dos conhecimentos científicos à realidade das condições locais. A autora atua na zona rural do Baixo Amazonas, uma região onde a diarréia figura entre as causas principais de morbidade e mortalidade infantil. Este trabalho descreve os métodos utilizados para a divulgação e implementação do "Soro Caseiro" através de elementos comunitários treinados para serem Promotores de Saúde.
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Patrícia Santos Lopes
2008-06-01
Full Text Available The purpose of this research was to determine the potential of papain and pequi oil as penetration enhancers for diclofenac sodium (DS across human skin in vitro. The permeation studies were conducted with vertical diffusion cells. The enhancers were associated or not in gels in different concentrations. In vitro studies reveled that papain 0.2% (w/v presented an elevated enhancer property for diclofenac sodium (J = 0.3369 mg/cm²x h. Pequi oil 10% (w/v generated a reduced flux value (J = 0.1848 mg/cm²x h and a combination of both enhancers presented a medium value of J = 0.2187 mg/cm²x h. Papain was found to be better enhancer than pequi oil.O objetivo desta pesquisa foi determinar in vitro o potencial da papaína e do óleo de pequi como promotores de penetração cutânea para o diclofenaco de sódio (DS através de pele humana. Os estudos de penetração foram conduzidos em células de difusão vertical. Os promotores foram associados ou não em géis em concentrações distintas. A avaliação in vitro revelou que a papaína 0,2% p/p apresentou propriedade promotora maior para o diclofenaco de sódio (J = 0,3369 mg/cm²x h. O óleo de pequi 10,0% p/v promoveu redução do fluxo (J = 0,1848 mg/cm²x h e a combinação de ambos os promotores apresentou valor mediano de fluxo de J = 0,2187 mg/cm²x h. A partir dos resultados, verificou-se que a papaína exerceu ação promotora de penetração cutânea melhor que o óleo de pequi.
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Chemical inducible promotor used to obtain transgenic plants with a silent marker
Chua, Nam-Hai; Aoyama, Takashi
2000-01-01
A chemically inducible promoter is described which may be used to transform plants with genes which are easily regulatable by adding plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter described is one which is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.
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Raibaud, O; Débarbouillé, M; Cossart, P
1982-01-01
A 5,800-bp (base pair) HindIII-EcoRI DNA fragment containing malT, the positive regulator gene of the maltose regulon, and most of malP, the structural gene for maltodextrin phosphorylase, was cloned into pBR322. A sequence of 802 bp was established in a DNA segment containing the promotor for malPQ and the promoter for malT. A total of 611 bp separates the initiation codons for these two genes, which are transcribed in opposite directions. The malT product was identified as a 94,000 dalton polypeptide.
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MSc. Yanira Zaita Ferrer
2016-06-01
Full Text Available La farmacodependencia y automedicación es una dificultad que reviste importancia por parte del farmacéutico y requiere un aumento de la comunicación entre estos y los pacientes, siendo la promoción de salud la práctica más aceptada en el panorama actual y la vía para contrarrestar este hábito. La investigación consistió en identificar las potencialidades e insuficiencias en la formación del Técnico Medio en Servicios Farmacéuticos como promotor de salud. Los métodos utilizados en la investigación abarcaron los del nivel teórico y empírico. Como resultados se obtuvo que existen insuficiencias en los programas de las asignaturas del plan de estudio, relacionados con los contenidos sobre promoción de salud y el no aprovechamiento de los espacios y momentos para la misma; así como la determinación de potencialidades. Se concluye, que es necesaria la búsqueda de alternativas educativas sustentadas en la formación de valores, capacidades, hábitos y habilidades, que trascienda los escenarios oficiales donde se puedan realizar actividades encaminadas a la promoción de salud.
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Raible, Kevin M; Sen, Bhaswati; Law, Nancy; Bias, Tiffany E; Emery, Christopher L; Ehrlich, Garth D; Joshi, Suresh G
2017-11-16
Acinetobacter baumannii is a nosocomial pathogen which is establishing as a major cause of morbidity and mortality within the healthcare community. The success of this pathogen is largely due to its ability to rapidly gain resistance to antimicrobial therapies and its capability to persist in an abiotic environment through the production of a biofilm. Our tertiary-care hospital has showed high incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. In this study we explore both genotypic and phenotypic properties of 26 CRAB isolates: 16 isolates were collected from January 2010 to March 2011, and 10 were collected between February and May 2015. We determined that all 26 CRAB isolates possessed multiple β-lactamase genes, including genes from Groups A, C, and D. Specifically, 42% of the isolates possesses the potentially plasmid-borne genes of OXA-23-like or OXA-40-like β-lactamase. The presence of mobile gene element integron cassettes and/or integrases in 88% of the isolates suggests a possible mechanism of dissemination of antibiotic resistance genes. Additionally, the location of insertion sequence (IS) ISAba1 in promotor region of of the OXA-51-like, ADC-7, and ampC genes was confirmed. Multilocus sequence typing (MLST) demonstrated that all 26 CRAB isolates were either sequence type (ST)-229 or ST-2. Interestingly, ST-2 went from being the minority CRAB strain in the 2010-2011 isolates to the predominant strain in the 2015 isolates (from 32 to 90%). We show that the ST-2 strains have an enhanced ability to produce biofilms in comparison to the ST-229 strains, and this fact has potentially led to more successful colonization of the clinical environment over time. This study provides a longitudinal genetic and phenotypic survey of two CRAB sequence types, and suggests how their differing phenotypes may interact with the selective pressures of a hospital setting effecting strain dominance over a 5-year period.
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Liu, Y.
2016-01-01
Y. Liu
Prof. dr. F. Govers (promotor); Prof. dr. J.M. Raaijmakers (promotor); Dr. I. de Bruijn (co-promotor); Wageningen University, 13 June 2016, 170 pp.
The fish egg microbiome: diversity and activity against the oomycete pathogen
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Dra. Ana Maria Girotti Sperandio
2015-12-01
Full Text Available Este artigo visa apresentar o processo de aplicação do Índice de Bem-Estar Urbano (IBEU realizado em 2014, no município de Conchal-São Paulo, Brasil. Destaca a importância de estudos quantitativos para futuras o desenvolvimento de politicas publicas a serem adotadas no local, que vise alcançar um bem-estar diferencial da população urbana. Os dados utilizados para o estudos foram os do Censo Demográfco Brasileiro (IBGE, 2010. A metodologia e a criação do IBEU foram elaboradas pelo Observatório das Metrópoles, diferindo-se nesse estudo pela aplicação do índice ser em um município de pequeno porte com 25.229 habitantes. Os cinco indicadores utilizados são: mobilidade urbana, condições ambientais urbanas, condições habitacionais urbanas, atendimento de serviços coletivos urbanos e infraestrutura urbana. Ao fnal do estudo identifcou-se que o Índice de Bem-Estar de Conchal foi de 0.863, que é considerado de bom para ótimo. Este estudo foi vinculado à disciplina Ambiente Urbano como Promotor da Saúde da FEC/UNICAMP, ao LABINUR e ao GEPUCS.
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W Negara
2009-11-01
Full Text Available This study was designed to evaluate the efficacy of organic acid salt Zn from complete feed silage based on corn by product as an alternative to subtitute antibiotic function as a growth promotor for broiler. Ninety day old commercial Cobb broiler chickens were randomly distributed into six groups having three replicates of five birds in each group. Negative control (R0 birds were offered standard basal diet and no challenged, positive control (R1 birds were offered standard basal diet and challenged with 107 Salmonella typhimurium. Treatment R2, R3, R4 and R5 were challenged by 107 CFU of Salmonella typhimurium which added in feed with 0.1% flouroquinolone, 0.1%, 0.2%, and 0.3% of organic acid salts. The result showed that dietary of organic acid salts affect consumption, weight gain, and final body weight (P<0.05. Meanwhile, feed conversion (FCR was not affected by antibiotics nor organic acids. Our conclusion, Dietary organic acid salt from complete feed silage corn based by product until dose 0.2% can improve the performance of broiler chickens infected Salmonella typhimurium. (Animal Production 11(3: 170-175 (2009 Key Words: broiler, organic acid, Salmonella typhimurium
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JPRS Report, Science & Technology, China
1991-01-04
Leptospira [Bao Lang, Dai Baomin; ZHONGHUA WEISHENGWUXUE HE MIANYIXUE ZAZHI, N o 5, O ct 90...the protein struc- ture of trichosanthin, the chemical structure and artifi- [English abstract of article by Zhang Xiaodong [1728 cial synthesis of...research in 1987 and built an promotor in either direction, the expressed gene product open laboratory in 1989; 26 projects, including metal will be a
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Eliana, Fatimah; Suwondo, Pradana; Asmarinah, Asmarinah; Harahap, Alida; Djauzi, Samsuridjal; Prihartono, Joedo; Pemayun, Tjokorda Gde Dalem
2017-07-01
graves' disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves' disease in Indonesia. this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves' ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in
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Fatimah Eliana
2017-11-01
Full Text Available Background: graves’ disease (GD is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg and thyroid receptor antibody (TRAb; that affecting the relapse of patients with Graves’ disease in Indonesia. Methods: this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. Results: the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008, age at diagnosis (p=0.021, 2nd degree of Graves’ ophthalmopathy (p=0.001, enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040, duration of remission period (p=0.029, GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016, CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003, the number of regulatory T cells (p=0.001 and TRAb levels (p=0.002. Conclusion: genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and
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Comparative study of Chalcone synthase promoters across plant families
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Francisco Buitrago
2009-07-01
Full Text Available En la era post-genómica, el entendimiento de la regulación génica se ha convertido en un reto y una prioridad de investigación. En este trabajo realizamos un estudio comparativo de las secuencias reguladoras del gen de la chalcón sintetasa de varias familias botánicas. Veintidós secuencias de promotores de Chalcone Synthase fueron comparados teniendo en cuenta tres elementos Cis reguladores: Caja-G, Caja-H y Caja-TATA, que podrían estar actuando como una sola unidad cooperativa. Nuestra comparación muestra que estos elementos puede que se conserven en algunas especies e inclusive que se conserven a nivel de familia. Sin embargo, en algunas especies no todos los elementos Cis fueron encontrados, mostrando que no todas las especies se regulan bajo los mismos parámetros. Adicionalmente, una comparación entre promotores de una misma especie con una familia de multigenes Chs, mostró que los genes duplicados son variables en la composición del elemento Cis, sugiriendo que estos genes pueden estarse expresando de maneras diferentes.
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Cubillos-Hinojosa Juan
2009-04-01
Full Text Available
Se realizó un experimento en condiciones de laboratorio e invernadero, con el propósito de evaluar el efecto de la cepa nativa TCN-014 y la cepa comercial TCC-005 de Trichoderma harzianum sobre la germinación y el crecimiento temprano del maracuyá. Se adecuaron inóculos de 104, 106 y 108 conidias/mL para cada cepa y se aplicaron a semillas de maracuyá; se evaluó el número de semillas germinadas durante 15 días; se calculó el porcentaje de germinación, el índice de velocidad de germinación y el tiempo medio de germinación. Posteriormente las semillas germinadas se llevaron a condiciones de invernadero y transcurridos dos meses se midió la altura de las plántulas, el grosor del tallo, el número de hojas, la longitud de la raíz y el peso seco total. Todos los tratamientos estimularon la germinación de las semillas y el desarrollo de las plántulas; sin embargo la cepa nativa en concentraciones 106 y 108 conidias/mL mostró resultados superiores frente a la cepa comercial. Los resultados sugieren una acción efectiva de T. harzianum como promotor de crecimiento vegetal, mostrando que tiene potencial para la elaboración de un bioproducto útil para el manejo ecológico del cultivo de maracuyá.
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Otiniano, Angie Denisse; Carroll-Scott, Amy; Toy, Peggy; Wallace, Steven P
2012-08-01
Promotores have unique access to underserved and hard-to-reach Latino communities facing health disparities. Although promotores are involved in community change, they rarely receive training that gives them the skills to be partners in research. We present a case study of promotoras who participated in a research capacity building course focused on assessing community health needs. Data comes from course application surveys, follow-up notes, and narratives from qualitative phone interviews of eight promotoras. Content analysis drawing from grounded theory was conducted to identify and describe emerging themes. Four themes emerged as promotoras discussed their experience learning basic research skills and teaching others: (1) challenges, (2) support, (3) building capacity, and (4) using research. Promotores play an important role in the health of Latino communities and are increasingly asked to participate in research processes; however they have few opportunities for training and professional development in this area. Capacity building opportunities for promotores need to be tailored to their needs and provide them with support. Fostering collaboration between promotores and partnering with local community-based organizations can help facilitate needed research skill-building among promotores.
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Expression of TIMP1, TIMP2 genes by ionizing radiation
International Nuclear Information System (INIS)
Park, Kun Koo; Jin, Jung Sun; Park, Ki Yong; Lee, Yun Hee; Kim, Sang Yoon; Noh, Young Ju; Ahn, Seung Do; Kim, Jong Hoon; Choi, Eun Kyung; Chang, Hye Sook
2001-01-01
Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angio genesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity (D o ), radiation cytotoxicity and metastatic potential were measured by clonogenic assay, MTT assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promotor region was cloned and TIMP1 luciferase reporter vector was constructed, The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was performed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promotor. D o of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. MTT assay confirmed cell viability, over 94% at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-l and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 spectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell
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Looking on the bright side: biased attention and the human serotonin transporter gene.
Fox, Elaine; Ridgewell, Anna; Ashwin, Chris
2009-05-22
Humans differ in terms of biased attention for emotional stimuli and these biases can confer differential resilience and vulnerability to emotional disorders. Selective processing of positive emotional information, for example, is associated with enhanced sociability and well-being while a bias for negative material is associated with neuroticism and anxiety. A tendency to selectively avoid negative material might also be associated with mental health and well-being. The neurobiological mechanisms underlying these cognitive phenotypes are currently unknown. Here we show for the first time that allelic variation in the promotor region of the serotonin transporter gene (5-HTTLPR) is associated with differential biases for positive and negative affective pictures. Individuals homozygous for the long allele (LL) showed a marked bias to selectively process positive affective material alongside selective avoidance of negative affective material. This potentially protective pattern was absent among individuals carrying the short allele (S or SL). Thus, allelic variation on a common genetic polymorphism was associated with the tendency to selectively process positive or negative information. The current study is important in demonstrating a genotype-related alteration in a well-established processing bias, which is a known risk factor in determining both resilience and vulnerability to emotional disorders.
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Fitch, J M; Gordon, M K; Gibney, E P; Linsenmayer, T F
1995-01-01
The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1
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Schmauss, C.
2015-01-01
Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects. In fluoxetine-treated mice, HDAC inhibitors increased enrichment of acetylated histone H4 protein and RNA polymerase II at promotor 3 of the brain-derived neurotrophic factor (Bdnf) gene and increased Bdnf transcription from this promotor. Reducing Bdnf-stimulated tropomyosin kinase B receptor activation in fluoxetine-treated mice with low HDAC activity abolished the behavioral effects of fluoxetine, suggesting that the HDAC-triggered epigenetic stimulation of Bdnf expression is critical for therapeutic efficacy. PMID:25639887
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Zhu, Honglin; Mi, Wentao; Luo, Hui; Chen, Tao; Liu, Shengxi; Raman, Indu; Zuo, Xiaoxia; Li, Quan-Zhen
2016-07-13
CpG sites in the promotor region of the gene. Our study has demonstrated that significant number of differential genes in SLE were involved in IFN, TLR signaling pathways, and inflammatory cytokines. The enrichment of differential genes has been associated with aberrant DNA methylation, which may be relevant to the pathogenesis of SLE. Our observations have laid the groundwork for further diagnostic and mechanistic studies of SLE and LN.
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The expression of GFP under the control of fibroin promotor in ...
Indian Academy of Sciences (India)
... mediated rapid amplification of cDNA ends (RLM-RACE). The expression vector (pGFP-N2/Fib) was constructed by use of replacing the CMV promoter with the fibroin promoter. The results of visual screening under a fluorescent inverted microscope and Western blot analysis indicated that the GFP gene was expressed in ...
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Avaliação molecular e fenotípica da superexpressão e do silenciamento de MEF2C em miócitos cardíacos
Ana Helena Macedo Pereira
2013-01-01
Resumo: Os fatores MEF2 (Myocyte Enhancer Factor 2) pertencem à família MADS Box (MCM1-Agamous-Deficiens-Serum response factor) e foram descritos pela primeira vez como fatores de transcrição que se ligam a sequencias de DNA ricas em A/T nos promotores de vários genes músculo específicos. Existem 4 genes da família MEF2 que foram identificados em vertebrados: MEF2A, B, C e D que são expressos de forma distinta durante a embriogênese e nos tecidos adultos. Estudos anteriores do nosso laboratór...
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Balcázar, Héctor; Fernández-Gaxiola, Ana Cecilia; Pérez-Lizaur, Ana Bertha; Peyron, Rosa Adriana; Ayala, Carma
2015-03-12
In Mexico, cardiovascular disease and its risk factors are growing problems and major public health concerns. The objective of this study was to implement cardiovascular health promotion and disease prevention activities of the Salud para su Corazón model in a high-risk, impoverished, urban community in Mexico City. We used a pretest-posttest (baseline to 12-week follow-up) design without a control group. Material from Salud para su Corazón was validated and delivered by promotores (community health workers) to community members from 6 geographic areas. Two validated, self-administered questionnaires that assessed participants' knowledge and behaviors relating to heart health were administered. We used t tests and χ(2) tests to evaluate pretest and posttest differences, by age group (≤60 and >60 years), for participants' 3 heart-healthy habits, 3 types of physical activity, performance skills, and anthropometric and clinical measurements. A total of 452 (82%) adult participants completed the program. Heart-healthy habits from pretest to posttest varied by age group. "Taking action" to modify lifestyle behaviors increased among adults aged 60 or younger from 31.5% to 63.0% (P < .001) and among adults older than 60 from 30.0% to 45.0% (P < .001). Positive responses for cholesterol and fat consumption reduction were seen among participants 60 or younger (P = .03). Among those older than 60, salt reduction and weight control increased (P = .008). Mean blood glucose concentration among adults older than 60 decreased postintervention (P = .03). Significant improvements in some heart-healthy habits were seen among adult participants. The model has potential to improve heart-healthy habits and facilitate behavioral change among high-risk adults.
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Gómez Jiménez, María Dolores; Cañas Clemente, Luis Antonio; Madueño Albi, Francisco; Beltrán Porter, José Pío
2000-01-01
Agricultura. La presente invención se relaciona con la obtención de secuencias de ADN reguladoras (promotores) y, usando dichas secuencias, la construcción de nuevos genes quiméricos capaces de expresarse de forma específica en las anteras de plantas transgénicas. La invención también se refiere a la obtención de plantas androestériles y semillas híbridas.
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Directory of Open Access Journals (Sweden)
Antonio Bento Mancio
2005-08-01
Full Text Available Objetivou-se avaliar o desempenho de 40 bezerros F1 Holandês x Gir com peso médio de 36 kg, provenientes de rebanhos leiteiros alimentados com leite integral ou colostro fermentado, associado ou não com óleo de soja, com ou sem promotor de crescimento (Zeranol. Foram avaliados o ganho de peso, a circunferência torácica, altura de cernelha dos animais, o consumo de leite ou de colostro fermentado e o consumo de ração concentrada, entre o 15º e 60º dia de idade. A utilização de Zeranol não promoveu diferença no consumo de ração concentrada quando se utilizou leite integral. Os animais que receberam colostro fermentado mais promotor de crescimento apresentaram consumo de ração concentrada 44,23% maior que aqueles sem promotor de crescimento e 132% superior ao dos animais alimentados com leite integral e Zeranol. Para ganho de peso, não houve efeito entre as associações de óleo de soja e Zeranol. Os bezerros do tratamento com leite e Zeranol apresentaram maior altura de cernelha (-85,70 cm. A utilização de óleo de soja ou de Zeranol não influenciou a circunferência torácica (média de 88,19 cm. Os bezerros submetidos aos dois tipos de dieta líquida apresentaram taxa de crescimento constante e semelhante, demonstrando que o colostro fermentado é capaz de promover ganhos de peso da mesma magnitude que o leite integral.The objective of this trial was to study the effects of replacing milk with whole milk or fermented colostrum, supplemented or not with soy oil and with or without growth promoter (Zeranol on performance of 40 F1 Holstein x Gir calves averaging 36 kg. Weight gain, thoracic circumference, withers height and milk or fermented colostrums intake, and concentrated ration intake were the variables investigated from age 15 to 60 days. No significant difference on feed intake was observed when whole milk and Zeranol were fed. Feed intake of animals fed fermented colostrum with Zeranol increased by 44.23% than those
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Directory of Open Access Journals (Sweden)
Mathias Djalma Appelt
2007-11-01
Full Text Available Avaliou-se o efeito da suplementação de dietas com diferentes promotores de crescimento sobre o desempenho e rendimento de carcaça de frangos de corte de 1 a 42 dias de idade. Foram utilizados 576 pintos da linhagem Cobb 500, machos, alojados em cama reutilizada, distribuídos em um delineamento inteiramente casualizado, em esquema fatorial 2 x 3 (forma física da ração x diferentes promotores de crescimento, totalizando 6 tratamentos, com 6 repetições e 16 aves por unidade experimental. As características de desempenho avaliadas foram ganho de peso, peso final, consumo de ração, conversão alimentar, mortalidade e o índice de eficiência produtiva. Avaliou-se também o rendimento de carcaça, bem como rendimento em cortes, coração, fígado e gordura abdominal. Os resultados obtidos demonstram não haver efeito dos tratamentos estudados sobre as características de desempenho e rendimento de carcaça.This study evaluated the supplementation effect of diets with different growth promoters on the performance and carcass yield in broilers from 1 to 42 days of age. Five hundred seventy six broilers of the Coob 500 lineage were used, all males, lodged in reused litter, allocated according to a completely randomized design in a 2 x 3 factorial scheme (physical forms of the ration x growth promoters, totalizing 6 treatments, 6 repetitions per treatment and 16 broilers per experimental unit. The performance parameters evaluated were weight gain, final weight, feed consumption, feed conversion, mortality and index productive efficiency. The carcass yield was also evaluated, as the cuts yield and percentage of abdominal fat at 42 days. The results demonstrated no effect of the treatments studied on the performance characteristics and carcass yield.
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Leptin promotor mutations affect leptin levels and performance traits in dairy cows
Liefers, S.C.; Pas, te M.F.W.; Veerkamp, R.F.; Platje, M.; Delavaud, C.; Chilliard, Y.; Lende, van der T.
2005-01-01
Leptin concentrations in body fluids and tissues undergo dynamic changes during the periparturient period. Polymorphisms in the leptin gene have been shown to be associated with differences in leptin concentration during late pregnancy but not during lactation. As the promoter of leptin regulates
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Directory of Open Access Journals (Sweden)
Alonso Álvarez, Raquel
2007-12-01
Full Text Available The objective of this paper is the revision of the ways for those the Order of Císter in the Kingdoms of Castile and Leon was spread. With this purpose, a study of its promoters, and how the more important related with the Traba’s group are found, has been made. From this analysis it is deduced that the devotion to the new order was transmitted fundamentally through the aristocratic family nets. In adition, a new perspective to approach the knowledge of the medieval monasteries as conservatives of the family memoirs and the paper carried out by the noble women from Castile and Leon in this complex manorial net is proposed.
El objetivo de este artículo es la revisión de los cauces por los que se difundió la Orden del Císter en los reinos de Castilla y León. Para ello, se ha hecho un estudio de sus promotores y de cómo se encuentran los más importantes relacionados con el grupo de los Traba. De este análisis se deduce que la devoción a la nueva orden fue transmitida fundamentalmente a través de las redes familiares aristocráticas. Además, se propone una nueva perspectiva para abordar el conocimiento de los monasterios medievales como conservadores de las memorias familiares y el papel desempeñado por las mujeres nobles castellano-leonesas en este complejo entramado señorial. -
Directory of Open Access Journals (Sweden)
Michela de Souza Cotian
2014-03-01
Full Text Available Objetivo: Conduzir uma revisão sistemática sobre resiliência psicológica e/ou hardiness em militares, explorando seus aspectos psicossociais, neurobiológicos, preditores e promotores. Métodos: Utilizaram-se as bases de dados PubMed/MedLine, ISI/Web of Science e PsycINFO, incluindo artigos empíricos publicados nas línguas inglesa, portuguesa e espanhola até maio de 2012. Os seguintes termos foram utilizados: “militar*”, “Army”, “war”, “veteran*”, “resilien*” e “hardiness”. Resultados: Foram incluídos 32 estudos selecionados a partir de 1.205 artigos. O foco da maioria das pesquisas recai sobre a correlação resiliência/hardiness e aspectos psicossociais. Confirmou-se o papel protetivo da resiliência/hardiness quanto ao transtorno de estresse pós-traumático (TEPT, assim como a associação direta entre resiliência e saúde. Neuropeptídeo Y (NPY e deidroepiandrosterona (DHEA foram os biomarcadores mais estudados. Os níveis de NPY no plasma podem representar um correlato biológico de resiliência ou recuperação dos efeitos adversos do estresse. Somente dois estudos abordaram fatores preditores de resiliência em amostras militares, sugerindo ser a exposição a situações adversas, o apoio social e o gênero fatores considerados preditores desse construto. Apenas um estudo avaliou a eficiência de intervenção para fortalecer a resiliência. Conclusão: Apesar da crucial relevância da resiliência, há poucos estudos em amostras militares. Estudos neurobiológicos como os do NPY são promissores. A ausência de ensaio randomizado controlado avaliando eficácia de intervenções promotoras da resiliência demonstra como esse construto vem sendo negligenciado nessa profissão de risco, constituindo área prioritária para foco de estudos futuros.
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Directory of Open Access Journals (Sweden)
Mônica Maria de Almeida Brainer
2003-01-01
Full Text Available Feeding cupric citrate as alternative to cupric sulfate to broilers has been suggested in the literature. Day-old male broiler chicks (1,200 were used in an experiment to evaluate the efficacy of cupric citrate supplementation (75 mg Cu kg-1 during the 1-21, 22-42 or 1-42 d periods in comparison to an unsupplemented diet and a diet supplemented with cupric sulfate (200 mg Cu kg-1, 1-42 d. A randomized block design was used, with five treatments, six replicates and 40 birds per pen. The diets, based on corn and soybean meal, and water were offered ad libitum during the 42-day experimental period. Over the entire period, there was no effect of copper supplementation (P > 0.05 on bird live weight, weight gain, feed intake, feed conversion and mortality. Cupric citrate supplementation on the 22-42 d period resulted in worse feed conversion as compared to broilers receiving cupric sulfate (2.014 vs. 1.967, P Citrato cúprico foi apontado como alternativa ao sulfato cúprico como promotor de crescimento na dieta de frangos. Este trabalho avaliou a eficácia do citrato cúprico em diferentes fases da criação de frangos de corte. Foram utilizados 1200 pintos machos, em um experimento em blocos casualizados, com cinco tratamentos, seis repetições e 40 aves por parcela. Os tratamentos consistiram de uma dieta não suplementada ou suplementada com citrato cúprico anidro (75 mg Cu kg-1 de 1 a 21 dias, de 22 a 42 dias ou de 1 a 42 dias, ou com sulfato cúprico pentahidratado (200 mg Cu kg-1 de 1 a 42 dias. Foram avaliados o desempenho das aves e o resíduo de cobre na cama. Dietas, à base de milho e farelo de soja, e água foram fornecidas à vontade durante todo o período experimental. Não houve efeito da suplementação de cobre (P > 0,05 sobre o peso vivo, ganho de peso, consumo de ração, conversão alimentar e mortalidade mais refugagem. Os frangos que receberam citrato cúprico na ração a partir dos 22 dias tiveram, no período 22-42 dias
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Directory of Open Access Journals (Sweden)
Régis Fernando Pastorelo Meurer
2010-12-01
Full Text Available This work was carried out to evaluate the use of Bacillus subtilis probiotic C-3102 (10(10cfu/g in diets with or without growth promoters on the performance of broilers in the period from 1 to 42 days of age. It was used 1,200 Cobb line broilers, distributed in a complete randomized block with five diets: negative controller (without promoters; Bacillus subtilis (30 g/t ration; Bacillus subtilis (50 g/t ration; Bacillus subtilis (30 g/t ration + colistin (10 ppm; avilamycin (10 ppm + colistin (10 ppm. Each diet was evaluated in 10 repetitions with 24 birds. From 21 to 42 days of age, feed intake, weight gain and feed conversion were evaluated, and at 42 days of age, productive efficiency index was evaluated. At the end of the experimental period, it was observed an increase in the consumption of diet with the lowest dose of Bacillus subtilis (30 g in relation to that one with Bacillus subtillis (30 g + colistin (10 ppm. The values of weight gain obtained with the diet with the lowest dose of Bacillus subtillis (30 g and with avilamycin (10 ppm + colistine (10 ppm were higher than those of the birds fed control diet (without promoters. For feed conversion, the best results were obtained by supplying diets containing 50 g of Bacillus subtillis, diet with 30 g of Bacillus subtillis + 10 ppm of colistin; and diet with 10 ppm of avilamycin + 10 ppm colistin. For the analysis of productive efficiency index, the best results were obtained with diets containing additives (probiotics and/or antibiotics in comparison to the control diet. Bacillus subtillis C-3102 probiotic, at concentration 10(10 cfu/g, is an efficient substitute of antibiotics.Este trabalho foi realizado para avaliar o uso do probiótico Bacillus subtilis C-3102 (10(10 ufc/g em dietas contendo ou não promotores de crescimento sobre o desempenho de frangos de corte no período de 1 a 42 dias de idade. Foram utilizados 1.200 frangos de corte da linhagem Cobb, distribuídos em delineamento
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A preliminary study on a specifically expressed arabidopsis promotor in vascular bundle
International Nuclear Information System (INIS)
Gu Yunhong; Xie Chuanxiao; Wu Lifang; Yu Zengliang
2003-01-01
From a population of about 3500 single plants in Arabidopsis promoter trapping bank, one plant whose GUS-gene had been specifically expressed in vascular bundle, was screened by the method of gus tissue staining. The T-DNA flanking sequence was amplified using TAIL-PCR. This band will be purified and connected to TA cloning vector. After sequencing and searching in the genebank, its function will be demonstrated through transformation
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Health council report 'Antimicrobial growth promoters'.
Goettsch, W; Degener, JE
1999-01-01
The Health Council of the Netherlands has issued a report on the risk of development of resistance among bacteria as result of the use of antibiotics as growth promotors in livestock farming. The committee appointed by the Health Council conclude that the use of antimicrobial growth promotors
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Directory of Open Access Journals (Sweden)
Germán Amézquita Becerra
2009-01-01
Full Text Available Este artículo describe el proceso investigativo por el cual se exploró y puso en práctica la tecnología Grid como elemento promotor del proceso de clasificación no supervisada de imágenes satelitales LANDSAT; se ha implementado un servicio Grid que aplica autómatas celulares como técnica de inteligencia artificial. Las anteriores tareas se han logrado estableciendo una infraestructura Grid y un modelo de implementación que da soporte al servicio Grid. El modelo del servicio visualiza el contenedor de servicios y el contenedor de "portlet", los cuales se integran para formar tanto el cliente como el servidor. El autómata celular utilizado, esta definido en vecindarios de dos dimensiones y se establece la proyección de los niveles digitales de tres de las bandas de la imagen y la ubicación de cada una de ellas sobre el vecindario definido. El algoritmo se basa en reglas de transición que generan modificaciones a los vecindarios hasta obtener las categorías deseadas. Como resultado del proceso de clasificación se genera una nueva imagen en la cual se expresan las categorías en valores de 0 a 255 y se establece falso color para visualizar los resultados obtenidos.
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ABC transporters van Botrytis cinerea in biotische en abiotische interacties
Schoonbeek, H.
2005-01-01
Op 29 november 2004 promoveerde Henk-jan Schoonbeek aan Wageningen Universiteit op het proefschrift getiteld 'ABC transporters from Botrytis cinerea in biotic and abiotic interactions'. Promotor was Prof. dr. ir. P.J.G.M. de Wit en co-promotor was dr.ir. M.A. de Waard, leerstoelgroep Fytopathologie,
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Navot Pikkel, Dvora
2017-01-01
The study, which was guided by Prof.dr J.b. Rijsman as promotor and by Dr. Y.T. Tal as co- promotor, was a comparative interventional study that was designed to evaluate the effectiveness of different teaching & educational strategies of risk management and patient's safety in medicine. Eventually,
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Gessler, Florian; Baumgarten, Peter; Bernstock, Joshua D; Harter, Patrick; Lescher, Stephanie; Senft, Christian; Seifert, Volker; Marquardt, Gerhard; Weise, Lutz
2017-06-01
The classification, treatment and prognosis of high-grade gliomas has been shown to correlate with the expression of molecular markers (e.g. MGMT promotor methylation and IDH1 mutations). Acquisition of tumor samples may be obtained via stereotactic biopsy or open craniotomy. Between the years 2009 and 2013, 22 patients initially diagnosed with HGGs via stereotactic biopsy, that ultimately underwent open craniotomy for resection of their tumor were prospectively included in an institutional glioma database. MGMT promotor analysis was performed using methylation-specific (MS)-PCR and IDH1R132H mutation analysis was performed using immunohistochemistry. Three patients (13.7%) exhibited IDH1R132H mutations in samples obtained via stereotactic biopsy. Tissue derived from stereotaxic biopsy was demonstrated to have MGMT promotor methylation in ten patients (45.5%), while a non-methylated MGMT promotor was demonstrated in ten patients (45.5%); inconclusive results were obtained for the remaining two patients (9%) within our cohort. The initial histologic grading, IDH1R132H mutation and MGMT promotor methylation results were confirmed using samples obtained during open craniotomy in all but one patient; here inconclusive MGMT promotor analysis was obtained in contrast to that which was obtained via stereotactic biopsy. Tumor samples acquired via stereotactic biopsy provide accurate information with regard to clinically relevant molecular markers that have been shown to impact patient care decisions. The profile of markers analyzed in our cohort was nearly concordant between those samples obtained via stereotactic biopsy or open craniotomy thereby suggesting that clinical decisions may be based on the molecular profile of the tumor samples obtained via stereotactic biopsy.
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2013-09-27
... respondent burden (hours) hours Pilot study collection: Promotores Promotores training pre-test, post- 12 1 5... Regulatory Affairs, OIRA--submission @omb.eop.gov or by fax to 202-395-6974, Attention: NIH Desk Officer. To... community health workers). A pilot evaluation will assess: (a) Overall quality of the program from the...
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Genome-wide identification of the potato WRKY transcription factor family.
Zhang, Chao; Wang, Dongdong; Yang, Chenghui; Kong, Nana; Shi, Zheng; Zhao, Peng; Nan, Yunyou; Nie, Tengkun; Wang, Ruoqiu; Ma, Haoli; Chen, Qin
2017-01-01
WRKY transcription factors play pivotal roles in regulation of stress responses. This study identified 79 WRKY genes in potato (Solanum tuberosum). Based on multiple sequence alignment and phylogenetic relationships, WRKY genes were classified into three major groups. The majority of WRKY genes belonged to Group II (52 StWRKYs), Group III had 14 and Group I consisted of 13. The phylogenetic tree further classified Group II into five sub-groups. All StWRKY genes except StWRKY79 were mapped on potato chromosomes, with eight tandem duplication gene pairs and seven segmental duplication gene pairs found from StWRKY family genes. The expression analysis of 22 StWRKYs showed their differential expression levels under various stress conditions. Cis-element prediction showed that a large number of elements related to drought, heat and salicylic acid were present in the promotor regions of StWRKY genes. The expression analysis indicated that seven StWRKYs seemed to respond to stress (heat, drought and salinity) and salicylic acid treatment. These genes are candidates for abiotic stress signaling for further research.
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Directory of Open Access Journals (Sweden)
Bruno Pereira Ferreira
2010-06-01
Full Text Available This trial was carried out in order to evaluate the effects of growth promoters on broiler chicken diets, from 1 to 10 days. The experiment was in a completely randomized design, with six treatments, four replications and 30 chicks as experimental unity. The treatments were: a basal diet of corn and soybeans meal without additives and basal diet with inclusion of antibiotics (avilamicin and colistin; or prebiotic (mannanoligosaccharides; or prebiotic plus fumaric and propionic acids; or probiotic (Bacillus subtillis; or a pool of probiotics (Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Streptococcus thermophilus and Enterococcus faecium. The parameters assessed were weight gain; feeding intake; feeding conversion; carcass yield; thigh yield; weight of liver, heart and intestine. The results showed that the diets with inclusion of additives were not significant in all parameters studied. It was concluded that the use of antibiotics, prebiotic plus fumaric and propionic acids and the pool of probiotics improved ration intake and the feeding conversion in relation to diet without additives.Este trabalho foi realizado para avaliar os efeitos da adição de diferentes aditivos promotores de crescimento em dietas de frangos de corte de 1 a 10 dias de idade. O delineamento experimental foi o inteiramente casualizado, com seis tratamentos e quatro repetições, com 30 aves por unidade experimental. Os tratamentos foram: dieta sem aditivos, com antibióticos (avilamicina e colistina, com prebiótico (mananoligossacarídeos, com prebiótico mais ácidos fumárico e propiônico, com probiótico (Bacillus subtillis e com mistura de probióticos (Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Streptococcus thermophilus e Enterococcus faecium. Os parâmetros analisados foram: ganho de peso, consumo
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Balcázar, Héctor; Alvarado, Matilde; Cantu, Frank; Pedregon, Veronica; Fulwood, Robert
2009-01-01
In 2002, the National Heart, Lung, and Blood Institute partnered with the Health Resources and Services Administration's (HRSA's) Bureau of Primary Health Care and Office of Rural Health Policy to address cardiovascular health in the US-Mexico border region. From 2003 through 2005, the 2 agencies agreed to conduct an intervention program using Salud para su Corazón with promotores de salud (community health workers) in high-risk Hispanic communities served by community health centers (CHCs) in the border region to reduce risk factors and improve health behaviors. Promotores de salud from each CHC delivered lessons from the curriculum Your Heart, Your Life. Four centers implemented a 1-group pretest-posttest study design. Educational sessions were delivered for 2 to 3 months. To test Salud para su Corazón-HRSA health objectives, the CHCs conducted the program and assessed behavioral and clinical outcomes at baseline, 3 months, 6 months, and 12 months after the intervention. A 2-sample paired t test and analyses of variance were used to evaluate differences from baseline to postintervention. Changes in heart-healthy behaviors were observed, as they have been in previous Salud para su Corazón studies, lending credibility to the effectiveness of a promotores de salud program in a clinical setting. Positive changes were also observed in low-density lipoprotein cholesterol level, triglyceride level, waist circumference, diastolic blood pressure, weight, and glycated hemoglobin (HbA1c). Results suggest that integrating promotores de salud into clinical practices is a promising strategy for culturally competent and effective service delivery. Promotores de salud build coalitions and partnerships in the community. The Salud para su Corazón-HRSA initiative was successful in helping to develop an infrastructure to support a promotores de salud workforce in the US-Mexico border region.
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SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer
International Nuclear Information System (INIS)
Nagahara, Akira; Nakayama, Masashi; Oka, Daizo; Tsuchiya, Mutsumi; Kawashima, Atsunari; Mukai, Masatoshi; Nakai, Yasutomo; Takayama, Hitoshi; Nishimura, Kazuo; Jo, Yoshimasa; Nagai, Atsushi; Okuyama, Akihiko; Nonomura, Norio
2010-01-01
Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.
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SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer
Energy Technology Data Exchange (ETDEWEB)
Nagahara, Akira; Nakayama, Masashi; Oka, Daizo; Tsuchiya, Mutsumi; Kawashima, Atsunari; Mukai, Masatoshi; Nakai, Yasutomo; Takayama, Hitoshi [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan); Nishimura, Kazuo [Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamachi, Higashinari-ku, Osaka, 537-8511 (Japan); Jo, Yoshimasa; Nagai, Atsushi [Department of Urology, Kawasaki Medical University, 577 Matsushima, Kurashiki-City, Okayama 701-0192 (Japan); Okuyama, Akihiko [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan); Nonomura, Norio, E-mail: nono@uro.med.osaka-u.ac.jp [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan)
2010-01-22
Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.
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Sadek, Khaled H; Ezzat, Sameera; Abdel-Aziz, Samira A; Alaraby, Hanaa; Mosbeh, Asmaa; Abdel-Rahman, Mohamed H
2017-09-01
Two polymorphisms, rs755622 and rs5844572, in the promoter region of the macrophage migration inhibitory factor (MIF) gene influence the basal and/or induced transcriptional activity and have been linked to several inflammatory and autoimmune diseases. The aim of this study was to investigate the association between these two polymorphisms and disease susceptibility in patients with biliary atresia (BA). Allele frequencies of rs755622 and rs5844572 were assessed in 60 Egyptian infants with a confirmed diagnosis of BA. DNA was extracted from archival material. For the rs755622, samples were tested using Taqman real-time PCR, and for the rs5844572, samples were tested using fluorescence-based genotyping. The allele frequency in the general population was assessed in 141 healthy adults from the same geographical location. No statistical differences were observed in the allele frequencies of either rs755622 or rs5844572 between BA patients and controls. The homozygous and heterozygous short repeats (5/5, or 5/X) of rs5844572 were observed more frequently (16/28, 57.1%) in BA patients with mild to moderate fibrosis compared with those with marked fibrosis (10/32, 31.3%). The difference was statistically significant (P = 0.032). In conclusion, we observed no association between MIF rs755622 and rs5844572 polymorphisms and susceptibility to BA; however, the rs5844572 could be linked to the rate of progression of the disease and extent of fibrosis. © 2017 John Wiley & Sons Ltd/University College London.
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CSIR Research Space (South Africa)
Koen, Hildegarde S
2017-02-01
Full Text Available KONTEKS: BESTRYDING VAN RENOSTERSTROPERY IN DIE KRUGER WILDTUIN deur Hildegarde Suzanne Koen Promotor(s): Dr. JP de Villiers & Dr. Henk Roodt Departement: Elektriese, Elektroniese en Rekenaar-Ingenieurswese Universiteit: Universiteit van Pretoria Graad...: Philosophiae Doctor (Elektronies) Sleutelwoorde: Renosterstroping, bedoelingskatting, gedeelde bewustheid, kausale netwerke Ongeveer drie renosters word daagliks in Suid-Afrika gestroop. Renosterstroping is ’n ernstige probleem wat nie net die renosterbevolking...
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Variação inter-individual nos níveis de bilirrubina: o papel dos factores genéticos e adquiridos
Rodrigues, Carina; Vieira, Emília; Santos, Rosário; Carvalho, João; Santos-Silva, Alice; Elísio, Costa; Bronze-da-Rocha, Elsa
2011-01-01
A bilirrubina é um pigmento biliar que deriva principalmente do catabolismo da hemoglobina. É um marcador bioquímico de doenças hepáticas e hematológicas e tem vindo a ser alvo de interesse devido à sua capacidade antioxidante. O objectivo deste trabalho foi avaliar a contribuição de vários factores para a variação da concentração da bilirrubina sérica na população portuguesa. Foi analisado o contributo dos polimorfismo genéticos no promotor do gene UGT1A1 (c.-41_40...
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Directory of Open Access Journals (Sweden)
María del Mar Gamboa-Coronado
2011-12-01
Full Text Available Clostridium perfringens es un bacilo Gram positivo, esporulado, anaerobio, ampliamente distribuido en la naturaleza, que produce cuatro toxinas principales α, β, ε y ι, las cuales permiten su clasificación en cinco toxinotipos (A-E. Algunas cepas producen una enterotoxina (CPE, codificada por el gen cpe, que causa diarrea en seres humanos y en algunos animales. La presencia de los genes de estas toxinas y la sensibilidad a los antibióticos se determinó en 81 cepas de C. perfringens previamente aisladas y que habían sido mantenidas a -80°C; 20 de suelos, 20 de origen animal, 20 de origen humano y 21 de alimentos cocidos no relacionados con brotes alimentarios. De acuerdo con los resultados de PCR, todas las cepas fueron clasificadas como C. perfringens tipo A, debido a que solo se les detectó el gen de la toxina α, mientras que el gen de la enterotoxina (cpe se detectó en dos cepas (2.5% aisladas de alimentos, tal como ha sido descrito en otras regiones del mundo. El 44% de las cepas fue resistente a algún antibiótico; clindamicina (41%, cloranfenicol (25%, penicilina (22% y metronidazol (20%. En general, las cepas provenientes de suelos presentaron los mayores porcentajes de resistencia a casi todos los antibióticos. El 40% de las cepas de suelo presentó multiresistencia (a tres o más grupos de antibióticos, el 30% de las de origen humano, el 14% de las de alimentos y el 5% de las de origen animal. Las altas tasas de resistencia encontradas podrían deberse al amplio uso de antibióticos como promotores de crecimiento de plantas y animales y esas cepas resistentes podrían actuar como reservorio de genes de resistencia que pueden transferirse entre bacterias de diversos ambientes.
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Directory of Open Access Journals (Sweden)
R.B. Bernd-Souza
2000-06-01
Full Text Available The effects of an animal RNase fused to the late cotton pollen-specific promoter G9 in a plant system were investigated. Expression of the chimeric genes G9-uidA and G9-RNase in tobacco plants showed that the 1.2-kb promoter fragment of the G9 gene was sufficient to maintain tissue and temporal specificity in a heterologous system. GUS (beta-glucuronidase expression was detected only in pollen from anther stage 6 through anthesis, with maximal GUS activity in pollen from stage 10 anthers. Investigating the effects of the rat RNase on pollen viability at stage 10, we found that pollen viability was reduced from 79 to 8% and from 89 to 40%, in pollen germination and fluoresceine diacetate assays, respectively, in one G9-RNase transgenic line, suggesting a lethal effect of the RNase gene. This indicates that the rat RNase produces deleterious effects in this plant system and may be useful for engineering male sterility.Foram investigados os efeitos da expressão de uma ribonuclease de origem animal em um sistema vegetal, ligando-se esta ao promotor do gene pólen-específico G9 de algodão. Examinou-se a expressão dos genes quiméricos G9-uidA e G9-RNase em plantas de tabaco e determinou-se que o fragmento de 1.2 kb do promotor do gene G9 foi suficiente para manter a especificidade temporal e espacial da expressão, em sistema heterólogo. A expressão do gene GUS foi detectada somente em pólen, do estágio 6 do desenvolvimento da antera até a antese, com atividade máxima em pólen de anteras no estágio 10. Estudos neste estágio com linhagens transgênicas contendo G9-RNase mostraram que um clone transgênico apresentava reduções na viabilidade do pólen de 79 para 8% e de 89 para 40% nos testes de germinação e coloração com diacetato de fluoresceína, respectivamente, sugerindo letalidade na expressão do gene de RNase. Estes resultados indicam que a RNase animal apresenta um efeito deletério em planta e oferece possibilidade de uso
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Directory of Open Access Journals (Sweden)
Carl-Magnus Hogerkorp
Full Text Available A massive and selective loss of CD4+ memory T cells occurs during the acute phase of immunodeficiency virus infections. The mechanism of this depletion is poorly understood but constitutes a key event with implications for progression. We assessed gene expression of purified T cells in Rhesus Macaques during acute SIVmac239 infection in order to define mechanisms of pathogenesis. We observe a general transcriptional program of over 1,600 interferon-stimulated genes induced in all T cells by the infection. Furthermore, we identify 113 transcriptional changes that are specific to virally infected cells. A striking downregulation of several key cell cycle regulator genes was observed and shared promotor-region E2F binding sites in downregulated genes suggested a targeted transcriptional control of an E2F regulated cell cycle program. In addition, the upregulation of the gene for the fundamental regulator of RNA polymerase II, TAF7, demonstrates that viral interference with the cell cycle and transcriptional regulation programs may be critical components during the establishment of a pathogenic infection in vivo.
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Directory of Open Access Journals (Sweden)
Leandro Batista Costa
2007-06-01
Full Text Available Avaliou-se, por meio do desempenho e da morfometria de órgãos, o uso de extratos vegetais como alternativas aos antimicrobianos promotores de crescimento para leitões recém-desmamados. Um experimento em blocos casualizados, com 35 dias de duração, foi realizado para testar cinco tratamentos: ração basal; antimicrobiano - ração basal com colistina + tiamulina (75 ppm de cada; extratos vegetais - ração basal com 420 ppm de cravo (Ec; orégano (Eo e cravo + orégano (Ec + Eo, respectivamente. Os extratos continham óleo essencial de cravo + eugenol e orégano + carvacrol. Para análise do desempenho, foram utilizados 80 leitões, oito repetições por tratamento e dois animais por unidade experimental. Ao final do período experimental, um animal de cada baia, dos quatro primeiros blocos, foi abatido para avaliação da morfometria de órgãos. Foram testados contrastes específicos de importância prática. No período de 24 a 38 dias de idade, os animais do tratamento antimicrobiano apresentaram melhor conversão alimentar (CA em comparação àqueles dos tratamentos com extratos. Os animais do tratamento com cravo (Ec tiveram melhor CA em comparação àqueles do tratamento com orégano (Eo. No período total, os animais do tratamento antimicrobiano apresentaram maior peso aos 59 dias de idade (P59 e ganho diário de peso (GDP em relação à média dos animais dos tratamentos com extratos. Os animais do tratamento Ec + Eo apresentaram maior P59 e GDP em relação à média dos outros tratamentos com extratos. Para a morfometria de órgãos, os antimicrobianos proporcionaram maior peso relativo dos rins em relação à média dos outros tratamentos com extratos vegetais. De modo geral, os antimicrobianos proporcionaram os melhores desempenhos dos leitões em fase de creche. Quanto aos extratos vegetais, a combinação de Ec+Eo acarretou desempenho muito próximo ao obtido com os antimicrobianos, demonstrando ser uma alternativa
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Directory of Open Access Journals (Sweden)
Luiz Humberto Gomes
2000-12-01
mostrou-se eficiente para marcação de células, oferecendo ainda uma fácil visualização das populações e tecidos marcados. Para testar este marcador no estudo de leveduras contaminantes, o gene GFP foi usado para construir um vetor, sob o controle do promotor de ADH2, que é reprimido por glicose, não interferindo assim em nenhuma etapa do processo. A inserção do vetor com a GFP (pYGFP3 em leveduras foi um sucesso, demonstrando alta estabilidade e oferecendo com certeza, um novo método com alta eficiência para o controle de contaminantes em processos fermentativos além de servir como marcador destinado a proteção industrial do material genético.
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Torres, A K; Escartín, N; Monzó, C; Guzmán, C; Ferrer, I; González-Muñoz, C; Peña, P; Monzó, V; Marcaida, G; Rodríguez-López, R
To describe the populational distribution of the UGT1A1*28 variant (genetic variant code rs8175347) located in the promotor of the UGT gene and correlate its genotypes with the results of the fasting test, as well as its relationship with the biochemical disorder of Gilbert's syndrome (GS) in a Valencian population. We studied the prevalence of the genotypes (TA) 6/6 (TA) 6/7 and (TA) 7/7 of the deleterious variant rs8175347 in 144 patients with hyperbilirubinemia, 38 of whom had previously undergone the fasting test to diagnose GS, and in 150 control patients. By analysing the genomic region of the TATA box of the UGT1A1 gene promotor using Sanger sequencing, we established the correlation between the rs8175347 genotypes and the fasting test results and with the patients' biochemical disorders. The rate of heterozygosity of allele (TA) 7 in the control population was 32% and increased to 87.59% among the patients with suspected GS. The rate of genotype TA 7/7 was 81.94% among the patients with hyperbilirubinemia, compared with 11.33% in the control patients. The fasting test showed a 15.79% rate of false negatives and a 5.26% rate of false positives. The high frequency of allele (TA) 7 among the Valencian control population, almost double the 5% reported for European control patients, confirms the high rate of GS reported in the Spanish population, without observing significant differences between the geographical ends of the country. The efficacy and reliability of the fasting test for the diagnosis of GS is questionable. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
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Directory of Open Access Journals (Sweden)
Julio Julio Di Bella Roldán
2004-01-01
Full Text Available La televisión pública, por su mismo origen, es una televisión que se debe preocupar por cómo obtener una mejor calidad con un menor presupuesto en relación con las televisoras privadas. El gran reto cultural que las televisoras públicas afrontan es el de solventar sus recursos económicos para darle una viabilidad a su producción, hacerla rentable, atractiva y que cumpla con los estatutos gubernamentales de promoción a la educación y difusión de la cultura. La televisión pública debe, por los principios que la rigen, permanecer con una visión social responsable y dedicarse a las diversas áreas de la cultura de nuestro país desde una perspectiva interdisciplinaria y humanista, promoviendo contenidos de calidad. El compromiso que debe hacer la televisión pública con la audiencia es un compromiso en el ámbito nacional, llevando una cruzada junto con la Universidad Pública, por la libertad de pensamiento que conlleva una responsabilidad. La Universidad Pública y la televisión pública son, entonces, medios idóneos para la promoción de las expresiones del pensamiento y la cultura de nuestro país.
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Constantin Mavrocordat - Romanian Culture Promotor
Directory of Open Access Journals (Sweden)
Niculina Vârgolici
2015-01-01
Full Text Available For a long time the Phanariot age was considered a dark era and the reforming Prince Constantin Mavrocordat's modernizing activity almost ignored. The signification of the Phanariot Prince's reform policy has to be revalued in the European and Romanian context of the 18th century. The enlighted Prince would reform the administration, justice, fiscal system and education setting up unexistent institutions at that time in Romanian Countries. Both in history and especially in culture, his role as a reformer is undisputable. His efforts in modernizing the Romanian society carried out in a document published in "Mercure de France", 1742 with a suggestive title as Constitution. His reigns signified a renovating period of the political, social, administration and enlightment ideas.
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Hoeft, Kristin S; Rios, Sarah M; Pantoja Guzman, Estela; Barker, Judith C
2015-09-03
Latino children experience more prevalent and severe tooth decay than non-Hispanic white and non-Hispanic black children. Few theory-based, evaluated and culturally appropriate interventions target parents of this vulnerable population. To fill this gap, the Contra Caries Oral Health Education Program, a theory-based, promotora-led education program for low-income, Spanish-speaking parents of children aged 1-5 years, was developed. This article describes qualitative findings of the acceptability of curriculum content and activities, presents the process of refinement of the curriculum through engaging the target population and promotoras, and presents results from the evaluation assessing the acceptability of the curriculum once implemented. Focus groups were conducted with low-income Spanish-speaking parents of children 1-5 years living in a city in an agricultural area of California. Interviews were digitally recorded, translated and transcribed, checked for accuracy and the resulting data was thematically coded and analyzed using a social constructionist approach. The Contra Caries Oral Health Education Program was then implemented with a separate but similar sample, and after completing the program, participants were administered surveys asking about acceptability and favorite activities of the education program. Data were entered into a database, checked for accuracy, open-ended questions were categorized, and responses to close-ended questions counted. Twelve focus groups were conducted (N = 51), 105 parents attended the Contra Caries Oral Health Education Program, and 83 parents filled out surveys. Complete attendance and retention was high (89% and 90%, respectively). This study found that their children's oral health is a high priority. Parents were not only interested in, but actually attended classes focused on increasing their knowledge and skills with respect to early childhood oral health. The Contra Caries content and format was perceived as
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Differentially Methylated DNA Regions in Monozygotic Twin Pairs Discordant for Rheumatoid Arthritis
DEFF Research Database (Denmark)
Svendsen, Anders J; Gervin, Kristina; Lyle, Robert
2016-01-01
: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6......OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated......: We identified several differentially methylated regions associated with RA, which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of RA....
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Carolina Angélica da Silva Parada
2012-01-01
Este trabalho descreve a construção de plasmídeos para expressão e ancoragem de proteínas de alta afinidade a íons Hg2+ e As5+. Os genes merR e arsR de C. metallidurans foram inseridos no vetor que contém o sistema para expressão e ancoragem de proteínas heterólogas em bactérias Gram-negativas originando os plasmídeos pCM-Hg e pCM-As. MerR e ArsR foram produzidas sob comando do promotor pan. E. coli recombinantes apresentaram resistência 100% superior a Hg2+ e As5+. C. metallidurans/pCM-As ap...
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Wang, Y; Smallwood, P M; Cowan, M; Blesh, D; Lawler, A; Nathans, J
1999-04-27
This study examines the mechanism of mutually exclusive expression of the human X-linked red and green visual pigment genes in their respective cone photoreceptors by asking whether this expression pattern can be produced in a mammal that normally carries only a single X-linked visual pigment gene. To address this question, we generated transgenic mice that carry a single copy of a minimal human X chromosome visual pigment gene array in which the red and green pigment gene transcription units were replaced, respectively, by alkaline phosphatase and beta-galactosidase reporters. As determined by histochemical staining, the reporters are expressed exclusively in cone photoreceptor cells. In 20 transgenic mice carrying any one of three independent transgene insertion events, an average of 63% of expressing cones have alkaline phosphatase activity, 10% have beta-galactosidase activity, and 27% have activity for both reporters. Thus, mutually exclusive expression of red and green pigment transgenes can be achieved in a large fraction of cones in a dichromat mammal, suggesting a facile evolutionary path for the development of trichromacy after visual pigment gene duplication. These observations are consistent with a model of visual pigment expression in which stochastic pairing occurs between a locus control region and either the red or the green pigment gene promotor.
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Directory of Open Access Journals (Sweden)
A.G. Pardo
2005-06-01
Full Text Available The model ectomycorrhizal fungus Pisolithus microcarpus isolate 441 was transformed by using Agrobacterium tumefaciens LBA1100 and AGL-1. The selection marker was the Shble gene of Streptoallotecius hidustanus, conferring resistance to phleomycin, under the control of the gpd gene promoter and terminator of Schizophyllum commune. Transformation resulted in phleomycin resistant clones which were confirmed by PCR to contain the resistance cassette. A. tumefaciens-mediated gene transfer would allow the development of RNA interference technology in P. microcarpus.El hongo ectomicorrícico modelo Pisolithus microcarpus aislamiento 441 fue transformado utilizando Agrobacterium tumefaciens LBA 1100 y AGL-1. El marcador de selección fue el gen Shble de Streptoallotecius hidustanus, el cual confiere resistencia a fleomicina, bajo el control del promotor y terminador del gen gpd de Schizophyllum commune. La transformación resultó en clones resistentes a fleomicina comprobándose por PCR la presencia del transgen. La transferencia génica mediada por Agrobacterium podría permitir el desarrollo de la tecnología de interferencia por ARN en P. microcarpus.
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Yu, Qingyue; Hao, Guodong; Zhou, Jianxin; Wang, Jingying; Evivie, Ejiroghene Ruona; Li, Jing
2018-06-22
Glucosinolates are a class of amino acid-derived specialized metabolites characteristic of the Brassicales order. Trp derived indolic glucosinolates are essential for the effective plant defense responses to a wide range of pathogens and herbivores. In Arabidopsis, MYB51 is the key transcription factor positively regulates indolic glucosinolate production by activating certain biosynthetic genes. In this study, we report the isolation and identification of a MYB51 from broccoli designated as BoMYB51. Overexpression of BoMYB51 in Arabidopsis increased indolic glucosinolate production by upregulating biosynthetic genes and resulted in enhanced flagellin22 (Flg22) induced callose deposition. The spatial expression pattern and responsive expression of BoMYB51 to several hormones and stress treatments were investigated by expressing the β-glucuronidase (GUS) reporter gene driven by BoMYB51 promotor in Arabidopsis and quantitative real-time PCR analysis in broccoli. Our study provides information on molecular characteristics of BoMYB51 and possible physiological process BoMYB51 may involve. Copyright © 2018 Elsevier Inc. All rights reserved.
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... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...
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Functional analysis of a novel KRAB/C2H2 zinc finger protein Mipu1
International Nuclear Information System (INIS)
Jiang, Lei; Tang, Daolin; Wang, Kangkai; Zhang, Huali; Yuan, Can; Duan, Dayue; Xiao, Xianzhong
2007-01-01
A novel rat gene, Mipu1, encodes a 608 amino acid protein with an amino-terminal KRAB domain and 14 carboxyl-terminal C 2 H 2 zinc finger motifs. Mipu1 is localized to the nucleus through its KRAB domain or the linker adjacent to its zinc finger region. Using the GST-Mipu1 bound to glutathione-Sepharose beads, a consensus putative DNA binding site (5'-TGTCTTATCGAA-3') was extracted from a random oligonucleotide library. EMSA and target detection assay showed that the probe containing the putative site can bind to purified GST-Mipu1 fusion protein. The oligonucleotide containing the putative site was inserted into the pGL3-promotor vector to produce a reporter construct. The expression of reporter gene was repressed by overexpression of Mipu1 in a dose-dependent manner. Mutation analysis of the consensus sequence indicated that the repression mediated by Mipu1 is sequence-dependent. These results suggest that Mipu1 is a nuclear protein, which functions as a transcriptional repressor
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Gene expression and gene therapy imaging
International Nuclear Information System (INIS)
Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.
2007-01-01
The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)
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Directory of Open Access Journals (Sweden)
Vera E Heininga
Full Text Available In psychiatric genetics research, the volume of ambivalent findings on gene-environment interactions (G x E is growing at an accelerating pace. In response to the surging suspicions of systematic distortion, we challenge the notion of chance capitalization as a possible contributor. Beyond qualifying multiple testing as a mere methodological issue that, if uncorrected, leads to chance capitalization, we advance towards illustrating the potential benefits of multiple tests in understanding equivocal evidence in genetics literature.We focused on the interaction between the serotonin-transporter-linked promotor region (5-HTTLPR and childhood adversities with regard to depression. After testing 2160 interactions with all relevant measures available within the Dutch population study of adolescents TRAILS, we calculated percentages of significant (p < .05 effects for several subsets of regressions. Using chance capitalization (i.e. overall significance rate of 5% alpha and randomly distributed findings as a competing hypothesis, we expected more significant effects in the subsets of regressions involving: 1 interview-based instead of questionnaire-based measures; 2 abuse instead of milder childhood adversities; and 3 early instead of later adversities. Furthermore, we expected equal significance percentages across 4 male and female subsamples, and 5 various genotypic models of 5-HTTLPR.We found differences in the percentages of significant interactions among the subsets of analyses, including those regarding sex-specific subsamples and genetic modeling, but often in unexpected directions. Overall, the percentage of significant interactions was 7.9% which is only slightly above the 5% that might be expected based on chance.Taken together, multiple testing provides a novel approach to better understand equivocal evidence on G x E, showing that methodological differences across studies are a likely reason for heterogeneity in findings - but chance
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Importance of non-synonymous OCA2 variants in human eye colour prediction
DEFF Research Database (Denmark)
Andersen, Jeppe Dyrberg; Pietroni, Carlotta; Johansen, Peter
2016-01-01
in the promotor region of OCA2 (OMIM #611409). Nevertheless, many eye colors cannot be explained by only considering rs12913832:A>G. Methods: In this study, we searched for additional variants in OCA2 to explain human eye color by sequencing a 500 kbp region, encompassing OCA2 and its promotor region. Results: We...... identified three nonsynonymous OCA2 variants as important for eye color, including rs1800407:G>A (p.Arg419Gln) and two variants, rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile), not previously described as important for eye color variation. It was shown that estimated haplotypes consisting...
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Directory of Open Access Journals (Sweden)
María Teresa Marrero Rodríguez
2007-12-01
Full Text Available Se analizó el estado de metilación del promotor del gen para el receptor de la hormona estimulante del tiroides (TSH en el diagnóstico de tumores tiroideos de origen epitelial. El estudio se realizó en tejido tiroideo obtenido de bloques de parafina de diferentes patologías tiroideas (carcinoma papilar, folicular e indiferenciado, y adenomas foliculares. El trabajo se realizó empleando la técnica de modificación del ADN con bisulfito de sodio y el análisis del estado de la metilación del gen RTSH se realizó por el método de reacción en cadena de la polimerasa específica para metilación. Encontramos metilación del promotor para el gen del receptor de TSH en los carcinomas papilares (33 de 40; 82,5 %, en los 10 carcinomas indiferenciados (100 % y en 10 de los 15 carcinomas foliculares analizados (66,6 %. En cambio, no se observó metilación en los 8 adenomas foliculares analizados. Se propone la metilación del gen para el receptor de TSH como un nuevo marcador diagnóstico de malignidad, y una base para emplear agentes desmetilantes conjuntamente con la terapia con radioyodo, en los pacientes con cáncer de tiroides de origen epitelial que no respondan a la terapia.The methylation state of the gene promoter for the receptor of the thyroid stimulating hormone (TSH in the diagnosis of thyroid tumors of epithelial origin was analyzed. The study was conducted in thyroid tissue obtained from paraffin blocks of different thyroid pathologies (papillary, follicular and undifferentiated carcinoma and follicular adenomas. The work was done by using the DNA modification technique with sodium bisulfite, and polymerase chain reaction was applied to analyze the gene methylation state. Methylation of the promoter for the gene of the TSH receptor was found in the papillary carcinomas (33 of 40; 82.5 %, in 10 undifferentiated carcinomas (100 %, and in 10 of the 15 follicular carcinomas analyzed (66.6 %. No methylation was observed in the 8
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Imaging gene expression in gene therapy
International Nuclear Information System (INIS)
Wiebe, Leonard I.
1997-01-01
Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented
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Sghaier, Ikram; Mouelhi, Leila; Rabia, Noor A; Ghazoueni, Ezzedine; Almawi, Wassim Y; Loueslati, Besma Yacoubi
2017-04-05
Interleukin-10 (IL-10) plays an important role in the immunity to hepatitis C virus (HCV). Insofar as IL-10 variants are associated with altered levels of IL-10, previous studies that examined the association of IL-10 polymorphisms with the susceptibility to and progression of chronic HCV, and response to anti-viral treatment were inconsistent. We investigated the association between common IL-10 variants in the intron and the promotor region with HCV and associated features. Study subjects comprised 120 patients infected with HCV-1b, and treated with Peg-IFN/RBV. Genotyping of six IL-10 promoter variants in the intron region (rs1878672, rs1554286, rs1518111) and promotor region (rs1800872, rs1800871, rs1800896) were done by real-time PCR. Compared to G/G, carriage of IL-10 rs1800896 (-1082A/G) A/A genotype was more frequent in patients with sustained virological response (SVR). The decline in viral load over the first 12weeks of treatment was more pronounced in rs1800896 A/A genotype carriers, compared to G/G genotype carriers, and was irrespective of the treatment dosage. Carriage of rs1800896 A/A genotype was positively associated with improvement in viral load decline, which was simultaneous, with and without carriage of the common favourable IL-28B variant. Carriage of both IL-10 rs1800896 G/G and IL-28B non-favourable genotype was associated with twice the risk of getting slow decline of viral load during treatment. Haploview analysis identified ACGCTA and CCGCTG haplotypes to be linked with excellent PegIFN/RBV cure rate, and complete HCV eradication. On the other hand, ACGCTG and CCGCTA haplotypes were associated with resistance to PegIFN/RBV treatment. IL-10 rs1800896 variant markedly influences the clinical outcome of HCV infection, and is a determinant of the response to HCV treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Imaging gene expression in gene therapy
Energy Technology Data Exchange (ETDEWEB)
Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research
1997-12-31
Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented
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Directory of Open Access Journals (Sweden)
Klarissa Almeida Silva
2010-04-01
Full Text Available A discussão que apresento converge para como se opera a construção social da incriminação do sujeito-autor e a construção de verdades judiciárias por parte dos promotores de justiça dos I e II Tribunais do Júri de Minas Gerais. Para tanto, utilizo uma tipologia de homicídios criada anteriormente a partir da leitura de 265 denúncias de homicídios dolosos oferecidas por tais operadores do Sistema de Justiça Criminal entre 2003 e 2005. E acompanho as fases judiciárias em que os processos oriundos dessas denúncias se localizavam entre 2007 e 2009. Isso, no contexto de um sistema caracterizado como “misto” (KANT DE LIMA, 2008 e “frouxamente integrado” (COELHO, 1986. The discussion presented in The Role of the Types of First Degree Murders in the Social Construction of the Incrimination of the Individual by Prosecutors: Belo Horizonte, Cases Between 2007 and 2009 leads to the question of how the social construction of the author’s incrimination and the construction of judiciary truths by Minas Gerais 1st and 2nd Court of Jury prosecutors are operated. We use here a typology of homicides created after 265 charges of fi rst degree murders made by these actors of the Justice System between 2003 and 2005. The steps the prosecutions originated from theses charges had taken between 2007 and 2009 are then described. This is done in the context of a “mixed” (KANT DE LIMA, 2008 and “loosely integrated” (COELHO, 19986 system.
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Directory of Open Access Journals (Sweden)
Maria Rita Fernandes Morais Martins
2002-03-01
Full Text Available No presente trabalho é feita uma breve revisão sobre promotores de permeação cutânea, descrevendo-se os seus mecanismos de ação e alguns exemplos. Abordam-se as vias de permeação de fármacos através da pele e liberação transdérmica. São também focadas as ciclodextrinas e seus derivados, a sua estrutura e propriedades físico-químicas, formação de complexos de inclusão e o seu papel como excipientes em sistemas transdérmicos. As ciclodextrinas constituem um grupo de excipientes que têm um papel de grande importância em formulação farmacêutica. Uma das mais extraordinárias propriedades destas moléculas é a sua capacidade de incrementar a liberação de fármacos através da pele sem, no entanto, afetar a sua função barreira.The present work is a short revision about transdermal permeation enhancers, their mechanism of action including some examples. Routes of permeation across the skin and transdermal delivery are also described. We focus cyclodextrins and their derivatives, structure, chemical properties, formation of inclusion complexes and their action as excipients in transdermal drug delivery systems. Cyclodextrins are a very important group of excipients used in pharmaceutical technology. One of the most extraordinary properties of cyclodextrins is their ability to increase transdermal drug delivery without affecting the barrier function of the skin.
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Polimorfismos en el gen promotor de IL-10 en una muestra de pacientes colombianos con lepra
Directory of Open Access Journals (Sweden)
Nora Cardona-Castro
2012-03-01
Conclusiones. El haplotipo que encontramos asociado con lepra, -1082A-819C-592C/-1082A-819C-592C, se ha relacionado con baja producción de IL-10. Funcionalmente, esta baja producción de IL-10 puede tener consecuencias en la respuesta inmunitaria, además de implicaciones clínicas. Se han reportado diferentes haplotipos de IL-10 como marcadores de vulnerabilidad y resistencia de lepra en otras poblaciones, lo cual sugiere que las diferencias en la distribución de diversos polimorfismos del gen de IL-10 entre grupos étnicos, es un factor importante al determinar la asociación entre enfermedad y genes. DOI: http://dx.doi.org/10.7705/biomedica.v32i1.386
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Directory of Open Access Journals (Sweden)
Maria Leônia Chaves de Resende
2011-06-01
Full Text Available Esse artigo tem por objetivo divulgar as denúncias registradas nos Cadernos do Promotor relativos a Minas Gerais, pertencentes ao fundo da Inquisição de Lisboa, depositados no Arquivo Nacional da Torre de Tombo/Portugal, com ênfase nos estudos de caso relativos a São João del-Rei e TiradentesThe purpose of this article is to make known the accusations registered in the Lisbon Inquisition's Cadernos do Promotor (Prosecutor'S Notebooks and the prosecuted cases pertaining to Minas Gerais, especially the villages of São João del-Rei and Tiradentes. These sources are deposited in Portugal's Arquivo Nacional da Torre de Tombo/Lisboa
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GoGene: gene annotation in the fast lane.
Plake, Conrad; Royer, Loic; Winnenburg, Rainer; Hakenberg, Jörg; Schroeder, Michael
2009-07-01
High-throughput screens such as microarrays and RNAi screens produce huge amounts of data. They typically result in hundreds of genes, which are often further explored and clustered via enriched GeneOntology terms. The strength of such analyses is that they build on high-quality manual annotations provided with the GeneOntology. However, the weakness is that annotations are restricted to process, function and location and that they do not cover all known genes in model organisms. GoGene addresses this weakness by complementing high-quality manual annotation with high-throughput text mining extracting co-occurrences of genes and ontology terms from literature. GoGene contains over 4,000,000 associations between genes and gene-related terms for 10 model organisms extracted from more than 18,000,000 PubMed entries. It does not cover only process, function and location of genes, but also biomedical categories such as diseases, compounds, techniques and mutations. By bringing it all together, GoGene provides the most recent and most complete facts about genes and can rank them according to novelty and importance. GoGene accepts keywords, gene lists, gene sequences and protein sequences as input and supports search for genes in PubMed, EntrezGene and via BLAST. Since all associations of genes to terms are supported by evidence in the literature, the results are transparent and can be verified by the user. GoGene is available at http://gopubmed.org/gogene.
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Promotoras as data collectors in a large study of physical activity in parks.
Marsh, Terry; Derose, Kathryn Pitkin; Rios, Muriel; Cohen, Deborah
2015-05-01
There is a large literature on promotores' involvement in health promotion and a smaller literature on their roles in data collection, most often among predominantly Latino populations. But the extent to which promotores can be successful as the primary data collectors across racially/ethnically and socioeconomically diverse neighborhoods is less well documented. In a study of physical activity in 50 urban neighborhood parks, we found that a team of Spanish/English bilingual promotoras (female promotores) successfully implemented a direct observation protocol in all participant neighborhoods and achieved high interrater reliability (.80-.98). Overall, they were also effective in administering surveys to park users and residents across the racially/ethnically diverse neighborhoods. The promotoras brought to the project important language skills and cultural sensitivity, surveying experience, and familiarity with human subjects and confidentiality issues. Their extensive field experience gained over the course of a long-term collaborative effort helped improve survey and observation protocols. The promotoras reported gaining professional skills, which can strengthen their contributions to other projects. The promotoras were accustomed to being a source of information, and collecting rather than providing information was challenging for some and had to be addressed in order to avoid contamination across study groups. © 2015 Society for Public Health Education.
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Radionuclide reporter gene imaging for cardiac gene therapy
International Nuclear Information System (INIS)
Inubushi, Masayuki; Tamaki, Nagara
2007-01-01
In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, ''reporter genes'' transferred into cell nuclei encode for a protein that retains a complementary ''reporter probe'' of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy. Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy. (orig.)
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Gene cluster statistics with gene families.
Raghupathy, Narayanan; Durand, Dannie
2009-05-01
Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such "gene clusters" is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data
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Gene therapy prospects--intranasal delivery of therapeutic genes.
Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej
2012-01-01
Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.
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Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin
2014-06-01
Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.
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Gene doping: gene delivery for olympic victory
Gould, David
2012-01-01
With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted...
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FunGene: the functional gene pipeline and repository.
Fish, Jordan A; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C Titus; Tiedje, James M; Cole, James R
2013-01-01
Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.
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FunGene: the Functional Gene Pipeline and Repository
Directory of Open Access Journals (Sweden)
Jordan A. Fish
2013-10-01
Full Text Available Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer.While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/ offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.
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Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming
2015-01-01
In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.
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Directory of Open Access Journals (Sweden)
Qifeng Zhou
2017-03-01
Full Text Available Apoptosis (type I programmed cell death of cardiomyocytes is a major process that plays a role in the progression of heart failure. The early response gene IER3 regulates apoptosis in a wide variety of cells and organs. However, its role in heart failure is largely unknown. Here, we investigate the role of IER3 in an inducible heart failure mouse model. Heart failure was induced in a mouse model that imitates a human titin truncation mutation we found in a patient with dilated cardiomyopathy (DCM. Transferase dUTP nick end labeling (TUNEL and ssDNA stainings showed induction of apoptosis in titin-deficient cardiomyocytes during heart failure development, while IER3 response was dysregulated. Chromatin immunoprecipitation and knock-down experiments revealed that IER3 proteins target the promotors of anti-apoptotic genes and act as an anti-apoptotic factor in cardiomyocytes. Its expression is blunted during heart failure development in a titin-deficient mouse model. Targeting the IER3 pathway to reduce cardiac apoptosis might be an effective therapeutic strategy to combat heart failure.
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Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif
2015-05-15
Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.
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Directory of Open Access Journals (Sweden)
Maria Aparecida da Silva
2011-04-01
Full Text Available Objetivou-se avaliar os efeitos da inclusão de óleo essencial de aroeira-vermelha (Schinus terebinthifolius Raddi como promotor de crescimento nas rações de frangos de corte sobre o desempenho e morfometria intestinal desses animais. Foram utilizados 300 pintos de um dia de vida, tipo corte, machos, linhagem Cobb. As aves foram alojadas em 20 boxes de 2m² (15 aves boxe-1, distribuídos em um delineamento inteiramente casualizado, em grupos de quatro (4 tratamentos e cinco (5 repetições, com 15 aves cada. Os grupos foram identificados como T1: dieta sem promotor de crescimento e sem óleo de aroeira-vermelha (controle negativo; T2: dieta com promotor de crescimento e sem óleo de aroeira (antimicrobiano e anticoccidiano - controle positivo; T3: dieta contendo somente antimicrobiano (bacitracina de zinco; T4: dieta com 0,4% de óleo de aroeira-vermelha. Não houve efeito significativo dos tratamentos sobre o desempenho animal (P>0,05. Contudo, quanto aos aspectos morfométricos dos intestinos verificou-se que, aos 21 dias de idade, os animais tratados com promotor de crescimento apresentaram maior relação vilo:cripta, que não diferiu dos tratados com 0,4% de óleo de aroeira-vermelha (P>0,05. As aves arraçoadas com uma dieta sem promotor de crescimento (sem antibiótico e anticoccidiano tiveram a menor relação vilo:cripta (P0,05. Neste estudo, não houve diferença significativa na profundidade das criptas de Lieberkühn e na altura das vilosidades entre os tratamentos (P>0,05. Concluiu-se que a adição de 0,4% de óleo de aroeira promoveu uma melhoria na superfície absortiva intestinal das aves, quando comparado com as aves alimentadas sem promotor de crescimento.The aim was to evaluate the effect of inclusion of Brazilian red pepper oil (Schinus terebinthifolius Raddi, as an additive in feed on performance and intestinal morphometry of broilers. A total of 300 day-old male chicks, Cobb, distributed in a randomized design in groups
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International Nuclear Information System (INIS)
Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong
2005-01-01
Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)
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Neighboring Genes Show Correlated Evolution in Gene Expression
Ghanbarian, Avazeh T.; Hurst, Laurence D.
2015-01-01
When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543
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Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...
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Directory of Open Access Journals (Sweden)
Luis H. León
2015-01-01
Full Text Available Los fertilizantes químicos representan entre 20% y 30% de los costos de producción de un cultivo, utilizados correctamente incrementan la productividad y rentabilidad; sin embargo, cada año aumenta la cantidad de fertilizantes por aplicar, debido a la deficiencia de adsorción en el suelo y absorción por la planta. Siendo el maíz el tercer cultivo de importancia en Perú, con un impacto significativo en la actividad económica y social, en el 2014, solo el 40% del maíz ofertado correspondió a la producción nacional. En busca de alternativas para disminuir el uso de fertilizantes químicos se realizan investigaciones con denominadas rizobacterias promotoras del crecimiento vegetal (PGPR, por sus siglas en ingles. Se identificaron 37 malezas en cultivos de maíz procedentes de campos agrícolas de los distritos de Monsefú y Reque, Región Lambayeque, siendo dicotiledóneas predominantes con 68 % con respecto a monocotiledóneas con 32%. Las bacterias se aislaron de la rizósfera de malezas, obteniendo 305 cultivos puros de bacterias, de los cuales 133 cultivos puros (43,7% se identificaron como Azotobacter spp., investigándose su reacción bioquímica en reducción de nitratos, utilización de sacarosa, glucosa, maltosa, manitol, ramnosa, glicerol y sorbitol, identificándose A. vinelandii (58%, A. paspali (13%, A. armeniacus (8%, A. nigricans (8% y en 13 cultivos no se identificó la especie. Con los cultivos Azotobacter spp. se cuantificó hasta 36,03 ppm de nitrógeno fijado como amonio; 60,75 ppm de ácido indol acético y 6,06 ppm de fósforo solubilizado, se determinó actividad antagónica contra Fusarium verticillioides, proteolítica y quitinolítica y. El 20% de Azotobacter spp. no afectó la emergencia de maíz amarillo duro hibrido simple AGRI- 144, el 33 % la afectó positivamente y el 47% la afectó negativamente. A su vez, ningún Azotobacter spp. afectó la sobrevivencia. Demostrándose el potencial promotor del
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Imaging reporter gene for monitoring gene therapy
International Nuclear Information System (INIS)
Beco, V. de; Baillet, G.; Tamgac, F.; Tofighi, M.; Weinmann, P.; Vergote, J.; Moretti, J.L.; Tamgac, G.
2002-01-01
Scintigraphic images can be obtained to document gene function at cellular level. This approach is presented here and the use of a reporter gene to monitor gene therapy is described. Two main ways are presented: either the use of a reporter gene coding for an enzyme the action of which will be monitored by radiolabeled pro-drug, or a cellular receptor gene, the action of which is documented by a radio labeled cognate receptor ligand. (author)
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Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer
National Research Council Canada - National Science Library
Adegoke, Olufemi
2003-01-01
The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...
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Directory of Open Access Journals (Sweden)
María del Mar Gamboa-Coronado
2011-12-01
Full Text Available Clostridium perfringens es un bacilo Gram positivo, esporulado, anaerobio, ampliamente distribuido en la naturaleza, que produce cuatro toxinas principales α, β, ε y ι, las cuales permiten su clasificación en cinco toxinotipos (A-E. Algunas cepas producen una enterotoxina (CPE, codificada por el gen cpe, que causa diarrea en seres humanos y en algunos animales. La presencia de los genes de estas toxinas y la sensibilidad a los antibióticos se determinó en 81 cepas de C. perfringens previamente aisladas y que habían sido mantenidas a -80°C; 20 de suelos, 20 de origen animal, 20 de origen humano y 21 de alimentos cocidos no relacionados con brotes alimentarios. De acuerdo con los resultados de PCR, todas las cepas fueron clasificadas como C. perfringens tipo A, debido a que solo se les detectó el gen de la toxina α, mientras que el gen de la enterotoxina (cpe se detectó en dos cepas (2.5% aisladas de alimentos, tal como ha sido descrito en otras regiones del mundo. El 44% de las cepas fue resistente a algún antibiótico; clindamicina (41%, cloranfenicol (25%, penicilina (22% y metronidazol (20%. En general, las cepas provenientes de suelos presentaron los mayores porcentajes de resistencia a casi todos los antibióticos. El 40% de las cepas de suelo presentó multiresistencia (a tres o más grupos de antibióticos, el 30% de las de origen humano, el 14% de las de alimentos y el 5% de las de origen animal. Las altas tasas de resistencia encontradas podrían deberse al amplio uso de antibióticos como promotores de crecimiento de plantas y animales y esas cepas resistentes podrían actuar como reservorio de genes de resistencia que pueden transferirse entre bacterias de diversos ambientes.Molecular characterization and antimicrobial resistance of Clostridium perfringens isolates of different origins from Costa Rica. Clostridium perfringens, a Gram positive, spore-forming anaerobe, is widely distributed in nature. Based upon their
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Gene doping: gene delivery for olympic victory.
Gould, David
2013-08-01
With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
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Genes2FANs: connecting genes through functional association networks
2012-01-01
Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs), researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI) network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our finding that disease genes in
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Directory of Open Access Journals (Sweden)
Tsatsoulis Costas
2010-05-01
Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.
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Lin, Pei-Chin; Huang, Hsien-Da; Chang, Chun-Chi; Chang, Ya-Sian; Yen, Ju-Chen; Lee, Chien-Chih; Chang, Wen-Hsin; Liu, Ta-Chih; Chang, Jan-Gowth
2016-08-02
Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, and lncRNA taurine-upregulated gene 1 (TUG1) has been proven to be associated with several human cancers. However, the mechanisms of TUG1-involved regulation remain largely unknown. We examined the expressions of TUG1 in a cohort of 89 patients with non-small cell lung cancer (NSCLC) to determine the association between TUG1 expression and clinical parameters. We used circular chromosome conformation capture (4C) coupled with next-generation sequencing to explore the genome regions that interact with TUG1 and the TUG1-mediated regulation. TUG1 was significantly downregulated, and the TUG1 downregulation correlated with sex (p = 0.006), smoking status (p = 0.016), and tumor differentiation grade (p = 0.001). Knockdown of TUG1 significantly promoted the proliferation of NSCLC cells. According to the bioinformatic analysis result of TUG1 4C sequencing data, 83 candidate genes and their interaction regions were identified. Among these candidate genes, CUGBP and Elav-like family member 1 (CELF1) are potential targets of TUG1 in-trans regulation. To confirm the interaction between TUG1 and CELF1, relative expressions of CELF1 were examined in TUG1 knockdown H520 cells; results showed that CELF1 was significantly upregulated in TUG1 knockdown H520 cells. RNA immunoprecipitation was then performed to examine whether TUG1 RNA was bound to PRC2, a TUG1-involved regulation mechanism reported in previous studies. The results demonstrated that TUG1 RNA was bound to enhancer of zeste protein 2/embryonic ectoderm development (EZH2/EED), which is essential for PRC2. Finally, our designed ChIP assay revealed that the EZH2/EED was bound to the promotor region of CELF1 within 992 bp upstream of the transcript start site. TUG1 is downregulated in NSCLC. Using TUG1 4C sequencing and bioinformatic analysis, we found CELF1 to be a potential target of TUG1 RNA in in-trans regulation. Moreover, subsequent
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MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility
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Daniel Luxen
2017-02-01
Full Text Available Epigenetic silencing by DNA methylation in brain tumors has been reported for many genes, however, their function on pathogenesis needs to be evaluated. We investigated the MTSS1 gene, identified as hypermethylated by differential methylation hybridization (DMH. Fifty-nine glioma tissue samples and seven glioma cell lines were examined for hypermethylation of the MTSS1 promotor, MTSS1 expression levels and gene dosage. GBM cell lines were treated with demethylating agents and interrogated for functional consequences of MTSS1 expression after transient transfection. Hypermethylation was significantly associated with IDH1/2 mutation. Comparative SNP analysis indicates higher incidence of loss of heterozygosity of MTSS1 in anaplastic astrocytomas and secondary glioblastomas as well as hypermethylation of the remaining allele. Reversal of promoter hypermethylation results in an increased MTSS1 expression. Cell motility was significantly inhibited by MTSS1 overexpression without influencing cell growth or apoptosis. Immunofluorescence analysis of MTSS1 in human astrocytes indicates co-localization with actin filaments. MTSS1 is down-regulated by DNA methylation in glioblastoma cell lines and is part of the G-CIMP phenotype in primary glioma tissues. Our data on normal astrocytes suggest a function of MTSS1 at focal contact structures with an impact on migratory capacity but no influence on apoptosis or cellular proliferation.
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Ultraviolet radiation inactivates SV40 by disrupting at least four genetic functions
International Nuclear Information System (INIS)
Brown, T.C.; Cerutti, P.A.
1986-01-01
The most UV sensitive region within the SV40 viral genome contains the transcriptional promotors and enhancers for the early and late viral genes plus part of the origin of DNA replication. Lesions within this regulatory region are 3.2-fold more effective in inactivating viral DNA than is the same amount of damage randomly distributed throughout the viral genome. The region least sensitive to damage lies within the coding portion of the viral coat protein genes, which are expressed only late in infection and would therefore be transcribed from undamaged progeny viral genomes, provided DNA replication occurs. Damage within this region is only 45% as effective in inactivating viral DNA as are randomly distributed lesions. Thus there is a 7-fold difference in the lethal effect of DNA damage within the most and least sensitive regions of the viral genome. Intermediate sensitivities are observed within the transcribed portion of the viral A gene, coding for the T antigen whose expression is required early in infection, and in a region at the terminus of DNA replication. The sum of the individual sensitivities for all regions of the SV40 genome is equal to the total sensitivity of viral DNA subjected to random damage. (author)
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Directory of Open Access Journals (Sweden)
MC Iafigliola
2000-09-01
Full Text Available Foi realizado um experimento objetivando avaliar os efeitos de promotores de crescimento sobre o desempenho e a temperatura corporal de frangos de corte, no período de 1 a 42 dias de idade. Os tratamentos consistiram de uma ração basal não suplementada (Controle, ou suplementada com 200 mg de Cu/kg de sulfato cúprico pentahidratado (Sulfato, 75 mg de Cu/kg de citrato cúprico anidro (Citrato, 20 mg/kg de virginiamicina (VM, ou a associação Citrato + VM, em um experimento em blocos casualizados com seis repetições de 40 aves, criadas sobre cama reutilizada. Não se observou efeito de tratamentos na fase inicial. Na fase final os tratamentos não afetaram o consumo de ração e o ganho de peso, enquanto a conversão alimentar foi melhor para o VM comparado ao Controle. No período total não houve efeito de tratamentos sobre peso vivo, consumo, ganho de peso e conversão alimentar. No período final e total o Sulfato resultou em menor viabilidade das aves comparado ao Citrato, VM e Citrato + VM. Não foi verificado efeito sinérgico quando se usou VM + Citrato. Os tratamentos não influenciaram a temperatura retal das aves consistentemente. O citrato cúprico não revelou ser mais eficiente que o sulfato cúprico.An experiment was carried out to evaluate the effects of growth promoters on the performance and body temperature of broiler chickens 1 to 42 days of age. The treatments were a basal diet unsupplemented (Control, or supplemented of 200 mg Cu/kg as copper sulfate pentahydrate (Sulfate, 75 mg Cu/kg as anhydrous copper citrate (Citrate, 20 mg/kg of virginiamycin (VM, or the combination Citrate + VM. The experiment in floor pens with reutilized litter was in randomized blocks and six replicates of 40 birds. There were no treatment effects in the initial period. Treatments did not affect feed intake and weight gain in the final period; VM resulted improved feed conversion compared to Control. In the overall period, liveweight, weight
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Directory of Open Access Journals (Sweden)
Andrés Felipe Aristizábal-Pachón
2016-12-01
Full Text Available Introducción. La cadherina-E (CDH1 cumple un papel importante en la transición epitelio-mesénquima y está relacionada con la invasión y metástasis en varios tipos de carcinomas. Sin embargo, el efecto de mutaciones y epimutaciones germinales en la susceptibilidad al cáncer de mama no es claro. Objetivo. Evaluar el polimorfismo rs5030625, cambios en el patrón de metilación del promotor y expresión transcripcional de CDH1 en pacientes con cáncer de mama. Materiales y métodos. Fueron colectadas muestras de sangre periférica de 102 pacientes con cáncer de mama y 102 mujeres control. La genotipificación del polimorfismo rs5030625 fue realizado a través de PCR-RFLP; la PCR y el análisis de disociación de alta resolución sensibles a metilación fueron usadas para determinar el estatus y semicuantificar el nivel de metilación del promotor de CDH1; finalmente, la RT-qPCR permitió evaluar el nivel de expresión transcripcional de CDH1. Resultados. Los resultados no mostraron asociación entre el polimorfismo rs5030625 y el cáncer de mama. Se encontraron perfiles aberrantes de metilación del promotor de CDH1, en las pacientes con cáncer de mama, relacionados con las primeras etapas de desarrollo del cáncer. La disminución de la expresión de CDH1 fue asociada con la presencia de metástasis y el estatus metilado del promotor. Conclusión. Alteraciones en CDH1 fueron relacionadas con invasión y metástasis en cáncer de mama, proporcionando evidencia adicional de la relevancia de CDH1 en el desarrollo y progresión del cáncer de mama.
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Sexy gene conversions: locating gene conversions on the X-chromosome.
Lawson, Mark J; Zhang, Liqing
2009-08-01
Gene conversion can have a profound impact on both the short- and long-term evolution of genes and genomes. Here, we examined the gene families that are located on the X-chromosomes of human (Homo sapiens), chimpanzee (Pan troglodytes), mouse (Mus musculus) and rat (Rattus norvegicus) for evidence of gene conversion. We identified seven gene families (WD repeat protein family, Ferritin Heavy Chain family, RAS-related Protein RAB-40 family, Diphosphoinositol polyphosphate phosphohydrolase family, Transcription Elongation Factor A family, LDOC1-related family, Zinc Finger Protein ZIC, and GLI family) that show evidence of gene conversion. Through phylogenetic analyses and synteny evidence, we show that gene conversion has played an important role in the evolution of these gene families and that gene conversion has occurred independently in both primates and rodents. Comparing the results with those of two gene conversion prediction programs (GENECONV and Partimatrix), we found that both GENECONV and Partimatrix have very high false negative rates (i.e. failed to predict gene conversions), which leads to many undetected gene conversions. The combination of phylogenetic analyses with physical synteny evidence exhibits high resolution in the detection of gene conversions.
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Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis
dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana
2015-01-01
Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928
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Patenting human genes: Chinese academic articles' portrayal of gene patents.
Du, Li
2018-04-24
The patenting of human genes has been the subject of debate for decades. While China has gradually come to play an important role in the global genomics-based testing and treatment market, little is known about Chinese scholars' perspectives on patent protection for human genes. A content analysis of academic literature was conducted to identify Chinese scholars' concerns regarding gene patents, including benefits and risks of patenting human genes, attitudes that researchers hold towards gene patenting, and any legal and policy recommendations offered for the gene patent regime in China. 57.2% of articles were written by law professors, but scholars from health sciences, liberal arts, and ethics also participated in discussions on gene patent issues. While discussions of benefits and risks were relatively balanced in the articles, 63.5% of the articles favored gene patenting in general and, of the articles (n = 41) that explored gene patents in the Chinese context, 90.2% supported patent protections for human genes in China. The patentability of human genes was discussed in 33 articles, and 75.8% of these articles reached the conclusion that human genes are patentable. Chinese scholars view the patent regime as an important legal tool to protect the interests of inventors and inventions as well as the genetic resources of China. As such, many scholars support a gene patent system in China. These attitudes towards gene patents remain unchanged following the court ruling in the Myriad case in 2013, but arguments have been raised about the scope of gene patents, in particular that the increasing numbers of gene patents may negatively impact public health in China.
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Identification of RegIV as a novel GLI1 target gene in human pancreatic cancer.
Directory of Open Access Journals (Sweden)
Feng Wang
2011-04-01
Full Text Available GLI1 is the key transcriptional factor in the Hedgehog signaling pathway in pancreatic cancer. RegIV is associated with regeneration, and cell growth, survival, adhesion and resistance to apoptosis. We aimed to study RegIV expression in pancreatic cancer and its relationship to GLI1.GLI1 and RegIV expression were evaluated in tumor tissue and adjacent normal tissues of pancreatic cancer patients and 5 pancreatic cancer cell lines by qRT-PCR, Western blot, and immunohistochemistry (IHC, and the correlation between them. The GLI1-shRNA lentiviral vector was constructed and transfected into PANC-1, and lentiviral vector containing the GLI1 expression sequence was constructed and transfected into BxPC-3. GLI1 and RegIV expression were evaluated by qRT-PCR and Western blot. Finally we demonstrated RegIV to be the target of GLI1 by chromatin immunoprecipitation (CHIP and electrophoretic mobility shift assays (EMSA.The results of IHC and qRT-PCR showed that RegIV and GLI1 expression was higher in pancreatic cancer tissues versus adjacent normal tissues (p<0.001. RegIV expression correlated with GLI1 expression in these tissues (R = 0.795, p<0.0001. These results were verified for protein (R = 0.939, p = 0.018 and mRNA expression (R = 0.959, p = 0.011 in 5 pancreatic cancer cell lines. RegIV mRNA and protein expression was decreased (94.7±0.3%, 84.1±0.5%; respectively when GLI1 was knocked down (82.1±3.2%, 76.7±2.2%; respectively by the RNAi technique. GLI1 overexpression in mRNA and protein level (924.5±5.3%, 362.1±3.5%; respectively induced RegIV overexpression (729.1±4.3%, 339.0±3.7%; respectively. Moreover, CHIP and EMSA assays showed GLI1 protein bound to RegIV promotor regions (GATCATCCA in pancreatic cancer cells.GLI1 promotes RegIV transcription by binding to the RegIV gene promoter in pancreatic cancer.
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Research progress in machine learning methods for gene-gene interaction detection.
Peng, Zhe-Ye; Tang, Zi-Jun; Xie, Min-Zhu
2018-03-20
Complex diseases are results of gene-gene and gene-environment interactions. However, the detection of high-dimensional gene-gene interactions is computationally challenging. In the last two decades, machine-learning approaches have been developed to detect gene-gene interactions with some successes. In this review, we summarize the progress in research on machine learning methods, as applied to gene-gene interaction detection. It systematically examines the principles and limitations of the current machine learning methods used in genome wide association studies (GWAS) to detect gene-gene interactions, such as neural networks (NN), random forest (RF), support vector machines (SVM) and multifactor dimensionality reduction (MDR), and provides some insights on the future research directions in the field.
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Gene Circuit Analysis of the Terminal Gap Gene huckebein
Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes
2009-01-01
The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network. PMID:19876378
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Journal of Biosciences | Indian Academy of Sciences
Indian Academy of Sciences (India)
The expression of GFP under the control of fibroin promotor in primary ovarian cells of Antheraea pernyi ... Effect of pH, temperature and alcohols on the stability of glycosylated and deglycosylated stem bromelain .... pp 783-789 Review.
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Directory of Open Access Journals (Sweden)
Maria Inês Tiraboschi Ferro
2007-06-01
Full Text Available Utilizando a técnica de macroarranjos de cDNA em membranas de náilon, analisou-se o perfil de expressão de 3.575 ESTs ("Expressed Sequence Tags" de cana-de-açúcar, oriundas do projeto SUCEST, em duas variedades, uma tolerante (SP80-0185 e outra suscetível (SP70-3370 ao Raquitismo da Soqueira. Foram analisadas amostras foliares de plantas inoculadas com Leifsonia xyli subsp. xyli., agente etiológico do Raquitismo, contrastadas com plantas não inoculadas (controle, para cada variedade, marcadas com sondas de cDNA e hibridizadas contra os macroarranjos. Após as hibridizações e análises estatísticas dos dados foi possível identificar 49 ESTs com expressão alterada, sendo 44 na variedade tolerante (41 ESTs induzidos e 3 reprimidos e 5 na variedade suscetível (2 ESTs induzidos e 3 reprimidos. Os resultados obtidos sugerem que a tolerância da variedade SP80-0185 de cana-de-açúcar à bactéria fitopatogênica pode estar relacionada com a percepção de sinais extracelulares, visto que ESTs relacionados a vias de transdução de sinais apresentaram expressão gênica induzida na variedade tolerante, os quais codificam para uma EST com similaridade à H+-ATPase da membrana plasmática, fatores de transcrição G-box, OsNAC6, "DNA binding", família MYB e "Zinc Finger" e ainda uma EST com similaridade ao fator de ligação ao G-Box, o qual corresponde a uma seqüência de DNA cis presente em vários promotores de plantas e requerido para o reconhecimento de muitos estímulos ambientais. Na variedade suscetível foi reprimido uma EST com similaridade à lipase. Esta enzima, também de membrana, faz parte da síntese do jasmonato, o qual ativa as defesas vegetais contra patógenos de plantas. Possíveis funções para os genes induzidos ou reprimidos nas cultivares de cana tolerante ou resistente ao Raquitismo são discutidas neste trabalho.The macroarray nylon membrane technology was used to study the differential gene expression of 3
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International Nuclear Information System (INIS)
Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.
1983-01-01
We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully
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Genes from scratch--the evolutionary fate of de novo genes.
Schlötterer, Christian
2015-04-01
Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.
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Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms.
Li, Zhen; Defoort, Jonas; Tasdighian, Setareh; Maere, Steven; Van de Peer, Yves; De Smet, Riet
2016-02-01
Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of "gene duplicability" is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. © 2016 American Society of Plant Biologists. All rights reserved.
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Advances in study of reporter gene imaging for monitoring gene therapy
International Nuclear Information System (INIS)
Mu Chuanjie; Zhou Jiwen
2003-01-01
To evaluate the efficiency of gene therapy, it is requisite to monitor localization and expression of the therapeutic gene in vivo. Monitoring expression of reporter gene using radionuclide reporter gene technique is the best method. Adenoviral vectors expressing reporter gene are constructed using gene fusion, bicistronic, double promoter or bidirectional transcriptional recombination techniques, and transferred into target cells and tissues, then injected radiolabeled reporter probes which couple to the reporter genes. The reporter genes can be imaged invasively, repeatedly, quantitatively with γ-camera, PET and SPECT. Recently, several reporter gene and reporter probe systems have been used in studies of gene therapy. The part of them has been used for clinic trials
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Irradiating rubber laminate containing sensitive agent in layer
International Nuclear Information System (INIS)
Bohm, G.G.A.
1979-01-01
Rubber compounds may be sensitized to cure or partially cure when subjected to irradiation. If certain layers of a rubber laminate are treated with sensitizing materials and other layers wth densensitizing materials a composite is produced having cured and uncured layers after it has been subjected to irradiation. This technique enables the production of composite laminates in which predetermined layers have predetermined physical characteristics which are desirable in the manufacture of the ultimate end product, for example, automotive tires. Several chemicals have been found to accelerate the cure of rubber compounds by irradiation and several have been found which inhibit the cure. Paradichlorobenzene (PDCB) and certain of the thioetherpolythiols are effective cure promotors. Effective retarders include aromatic oils, sulfur, sulfur cure accelerators and some rubber antioxidants and/or antiozonants of the substituted diphenylamine type. The dosage of irradiation is dependent upon several variables: the type of rubber, the promotor or retarder utilized, the level of the promotor or retarder, the thickness of the layer of material, the thickness of adjacent layers of materials, the sequence of the layers of material, the number of the layers of material and whether the irradiation is applied to one or both sides of the composite strip. The dosage may be controlled by the amount of energy employed so that the electrons do not completely penetrate the entire strip. This results in the irradiaton of part of the strip, but not the entire strip. (LL)
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Klocke, Michael; Mundt, Kerstin; Idler, Frank; Jung, Sabrina; Backhausen, Jan E
2005-06-01
The genes for the bacteriocins enterocin A and B were isolated from Enterococcus faecium ATB 197a. Using the pET37b(+) vector, the enterocin genes were fused to an Escherichia coli specific export signal sequence, a cellulose-binding domain (CBD(cenA)) and a S-tag under the control of a T7lac promotor. The constructs were subsequently cloned into E. coli host cells. The expression of the recombinant enterocins had different effects on both the host cells and other Gram-positive bacteria. The expression of entA in Esc. coli led to the synthesis and secretion of functional active enterocin A fusion proteins, which were active against some Gram-positive indicator bacteria, but did not influence the viability of the host cells. In contrast, the expression of enterocin B fusion proteins led to a reduced viability of the host cells, indicating a misfolding of the protein or interference with the cellular metabolism of Esc. coli. Indicator strains of Gram-positive bacteria were not inhibited by purified enterocin B fusion proteins. However, recombinant enterocin B displayed inhibitory activity after the proteolytic cleavage of the fused peptides.
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Down-Regulation of Gene Expression by RNA-Induced Gene Silencing
Travella, Silvia; Keller, Beat
Down-regulation of endogenous genes via post-transcriptional gene silencing (PTGS) is a key to the characterization of gene function in plants. Many RNA-based silencing mechanisms such as post-transcriptional gene silencing, co-suppression, quelling, and RNA interference (RNAi) have been discovered among species of different kingdoms (plants, fungi, and animals). One of the most interesting discoveries was RNAi, a sequence-specific gene-silencing mechanism initiated by the introduction of double-stranded RNA (dsRNA), homologous in sequence to the silenced gene, which triggers degradation of mRNA. Infection of plants with modified viruses can also induce RNA silencing and is referred to as virus-induced gene silencing (VIGS). In contrast to insertional mutagenesis, these emerging new reverse genetic approaches represent a powerful tool for exploring gene function and for manipulating gene expression experimentally in cereal species such as barley and wheat. We examined how RNAi and VIGS have been used to assess gene function in barley and wheat, including molecular mechanisms involved in the process and available methodological elements, such as vectors, inoculation procedures, and analysis of silenced phenotypes.
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Therapeutic genes for anti-HIV/AIDS gene therapy.
Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca
2013-01-01
The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.
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Discovering implicit entity relation with the gene-citation-gene network.
Directory of Open Access Journals (Sweden)
Min Song
Full Text Available In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG network constructed over the same corpus but which uses gene pairs explicitly connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts collected from 18,323 seed articles and their references, we identify 25 gene pairs. A comparison of these pairs with interactions found in BioGRID reveal that 96% of the gene pairs in the GCG network have known interactions. We measure network performance using degree, weighted degree, closeness, betweenness centrality and PageRank. Combining all measures, we find the GCG network has more gene pairs, but a lower matching rate than the GG network. However, combining top ranked genes in both networks produces a matching rate of 35.53%. By visualizing both the GG and GCG networks, we find that cancer is the most dominant disease associated with the genes in both networks. Overall, the study indicates that the GCG network can be useful for detecting gene interaction in an implicit manner.
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Seguridad e higiene en el sector de la construcción: el comienzo del fin de una indignidad
Directory of Open Access Journals (Sweden)
Garnacho Villarrubia, Manuel
1993-02-01
Full Text Available In a presentation of the reality in terms of prevention, safety and labour health in the construction sector and in the process of works execution considering the intervention in event of the "inevitable and excessive risk" of "the Administrations and Promotors", of "the Technical Designers of the Project", of the "Construction Companies" and lastly of "the workers".
Es una presentación de la realidad en aspectos de prevención, seguridad y salud laboral en el sector de la construcción y en el proceso de ejecución de obra planteándose la intervención en el ''riesgo evitable y excesivo" de "las Administraciones y los Promotores'', de "los Técnicos Diseñadores del Proyecto'', de las "Empresas Constructoras" y, por último, de "los Trabajadores". -
Chan, M.F.; van Amerongen, R.; Nijjar, T.; Cuppen, E.; Jones, P.A.; Laird, P.W.
2001-01-01
Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by
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Seok, Junhee; Davis, Ronald W; Xiao, Wenzhong
2015-01-01
Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.
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Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.
Directory of Open Access Journals (Sweden)
Boris P Hejblum
2015-06-01
Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.
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Norrie disease gene is distinct from the monoamine oxidase genes
Sims, Katherine B.; Ozelius, Laurie; Corey, Timothy; Rinehart, William B.; Liberfarb, Ruth; Haines, Jonathan; Chen, Wei Jane; Norio, Reijo; Sankila, Eeva; de la Chapelle, Albert; Murphy, Dennis L.; Gusella, James; Breakefield, Xandra O.
1989-01-01
The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and /or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in “classic” Norrie disease patients. Genomic DNA from these “nondelet...
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Takahashi, T; Guron, C; Shetty, S; Matsui, H; Raghow, R
1997-09-05
To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282 to +106 base pairs (bp)) or its congeners containing site-specific alterations were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and the expression of luciferase was assessed in transient expression assays. The functional consequences of the sequential 5' deletions of the promotor revealed that multiple positive and negative regulatory elements participate in regulating transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the upstream sequence to warrant detailed examination of its structure. Therefore, the functional consequences of site-specific deletions and point mutations of the cis-acting elements of the minimal Msx-1 promoter were systematically examined. Concomitantly, potential transcriptional factor(s) interacting with the cis-acting elements of the minimal promoter were also studied by gel electrophoretic mobility shift assays and DNase I footprinting. Combined analyses of the minimal promoter by DNase I footprinting, electrophoretic mobility shift assays, and super shift assays with specific antibodies revealed that 5'-flanking regions from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic E box (proximal E box), capable of binding a protein immunologically related to the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the promoter activation was seriously hampered if the proximal E box was removed or mutated, and the promoter activity was eliminated completely if the proximal Sp1 site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on Sp1 could be demonstrated by transient expression assays in the Sp1-deficient
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A genetic ensemble approach for gene-gene interaction identification
Directory of Open Access Journals (Sweden)
Ho Joshua WK
2010-10-01
Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of
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Mapping the field : a bibliometric analysis of the literature on university–industry collaborations
Skute, Igors; Zalewska-Kurek, Katarzyna; Hatak, Isabella; de Weerd-Nederhof, Petronella C.
2017-01-01
The substantial acknowledgement of university–industry (U–I) collaborations as promotor of economic progress, innovativeness and competitiveness fostered a continuous research engagement. At the same time, the U–I literature experienced a notable increase in the past decade, transforming into a
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The Mycoplasma hominis vaa gene displays a mosaic gene structure
DEFF Research Database (Denmark)
Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.
1998-01-01
Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...
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Role of hypoxia and hypoxia inducible factor in physiological and pathological conditions
Directory of Open Access Journals (Sweden)
Mozhgan Jahani
2017-11-01
Full Text Available Introduction: Organisms are exposed to oxygen deprivation (Hypoxia in various physiological and pathological conditions. There are different conserve evolutionary responses to counterview with this stress that primary transcriptional response to stress related to hypoxia is interceded by hypoxia-inducible factor (HIF-1 in mammals. This factor can regulate different genes that have essential roles in adaptation to this condition. In this review, the role of this factor in physiological and pathological conditions under hypoxic condition has been evaluated after examining structural features and regulation characteristics of HIF-1. Methods: First, articles related to the keywords of hypoxia and HIF-1 (from 1991-2016 were searched from valid databases such as Springer Link, Google Scholar, PubMed and Science direct. Then, the articles correlated with hypoxia, HIF-1 and their roles in physiological and pathological conditions (120 articles were searched and just 64 articles were selected for this study. Result: According to studies, there are different genes in cells and organs that can be regulated by HIF-1. Activation of genes expression by this protein occurs through its linkage to cis-acting of 50 base pair hypoxia response element (HRE region located in their promotor and enhancer. Depending on circumstances, activation of these genes can be beneficial or harmful. Conclusion: Activation of different genes in hypoxia by HIF-1 has different effects on physiological and pathological conditions. Therefore, HIF-1, as a hypoxia-inducible factor in hypoxic conditions, plays an essential role in the adaptation of cells and organs to changes related to the presence of oxygen.
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Energy Technology Data Exchange (ETDEWEB)
Chen, Lei [Los Alamos National Laboratory
2008-01-01
Open reading frame 11 (ORF11) of Kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family shared by some members of the gamma- herpesvirus subfamily. Little is known about this ORF11 homologous protein family. We have characterized an unknown open reading frame, ORF11, located adjacent and in the opposite orientation to a well-characterized viral IL-6 gene. Northern blot analysis reveals that ORF11 is expressed during the KSHV lytic cycle with delayed-early transcription kinetics. We have determined the 5{prime} and 3{prime} untranslated region of the unspliced ORF11 transcript and identified both the transcription start site and the transcription termination site. Core promoter region, representing ORF11 promoter activity, was mapped to a 159nt fragment 5{prime} most proximal to the transcription start site. A functional TATA box was identified in the core promoter region. Interestingly, we found that ORF11 transcriptional activation is not responsive to Rta, the KSHV lytic switch protein. We also discovered that part of the ORF11 promoter region, the 209nt fragment upstream of the transcription start site, was repressed by phorbol esters. Our data help to understand transcription regulation of ORF11 and to elucidate roles of ORF11 in KSHV pathogenesis and life cycle.
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Identification of Hematopoietic Stem Cell Engraftment Genes in Gene Therapy Studies.
Powers, John M; Trobridge, Grant D
2013-09-01
Hematopoietic stem cell (HSC) therapy using replication-incompetent retroviral vectors is a promising approach to provide life-long correction for genetic defects. HSC gene therapy clinical studies have resulted in functional cures for several diseases, but in some studies clonal expansion or leukemia has occurred. This is due to the dyregulation of endogenous host gene expression from vector provirus insertional mutagenesis. Insertional mutagenesis screens using replicating retroviruses have been used extensively to identify genes that influence oncogenesis. However, retroviral mutagenesis screens can also be used to determine the role of genes in biological processes such as stem cell engraftment. The aim of this review is to describe the potential for vector insertion site data from gene therapy studies to provide novel insights into mechanisms of HSC engraftment. In HSC gene therapy studies dysregulation of host genes by replication-incompetent vector proviruses may lead to enrichment of repopulating clones with vector integrants near genes that influence engraftment. Thus, data from HSC gene therapy studies can be used to identify novel candidate engraftment genes. As HSC gene therapy use continues to expand, the vector insertion site data collected will be of great interest to help identify novel engraftment genes and may ultimately lead to new therapies to improve engraftment.
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Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms[OPEN
Li, Zhen; Van de Peer, Yves; De Smet, Riet
2016-01-01
Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of “gene duplicability” is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. PMID:26744215
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Directory of Open Access Journals (Sweden)
Maria Aparecida da Silva
2009-08-01
Full Text Available In the first trial a total of 250 day-old male chicks were distributed into five treatments and given the following diets: a diet with growth promoter; a diet without added growth promoter; a diet added with avilamycin only; diet supplemented with 0.5g of oregano oil kg diet-1; 1.0g of oregano oil kg diet-1. In other trial a total of 288 day-old chicks was used and distributed into four treatments, which were given the following diets: a diet with anticoccidial agent; a diet without anticoccidial agent; a diet supplemented with 0.5g of oregano oil kg diet-1; a 1.0g of oregano oil kg diet-1. In the first trial the nonmedicated group had the highest crypt depth which differs from chickens fed with growth promoter or with 0.5 and 1.0g of oregano oil kg diet-1. The broilers fed with positive control (antibiotic and anticoccidial had the highest villous: crypt ratio compared with the negative control that had the lowest villous:crypt ratio and the highest oocyst excretion in litter (PInicialmente, foram utilizados, neste estudo, 250 pintos de um dia de idade distribuídos em cinco tratamentos: dieta com promotor de crescimento; dieta sem promotor de crescimento; dieta contendo somente antibiótico; dieta com 0,5g de orégano óleo kg de ração-1 ou com 1,0g de orégano óleo kg de ração-1. No outro ensaio, foram utilizados 288 pintos de um dia de idade distribuídos em quatro grupos: dieta com anticoccidiano; dieta sem anticoccidiano; dieta com 0,5g de orégano óleo kg dieta-1 ou 1,0g de orégano óleo kg de ração-1. No primeiro ensaio, o grupo tratado sem promotor de crescimento apresentou a maior profundidade de cripta quando comparada com os animais tratados com promotor de crescimento ou com 0,5 e 1,0g de orégano óleo kg de ração-1. Os frangos que receberam a dieta com promotor de crescimento (antibiótico+anticoccidiano apresentaram uma maior relação vilo:cripta em comparação com os frangos do controle negativo, os quais tiveram a
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Effect of the absolute statistic on gene-sampling gene-set analysis methods.
Nam, Dougu
2017-06-01
Gene-set enrichment analysis and its modified versions have commonly been used for identifying altered functions or pathways in disease from microarray data. In particular, the simple gene-sampling gene-set analysis methods have been heavily used for datasets with only a few sample replicates. The biggest problem with this approach is the highly inflated false-positive rate. In this paper, the effect of absolute gene statistic on gene-sampling gene-set analysis methods is systematically investigated. Thus far, the absolute gene statistic has merely been regarded as a supplementary method for capturing the bidirectional changes in each gene set. Here, it is shown that incorporating the absolute gene statistic in gene-sampling gene-set analysis substantially reduces the false-positive rate and improves the overall discriminatory ability. Its effect was investigated by power, false-positive rate, and receiver operating curve for a number of simulated and real datasets. The performances of gene-set analysis methods in one-tailed (genome-wide association study) and two-tailed (gene expression data) tests were also compared and discussed.
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Human Gene Therapy: Genes without Frontiers?
Simon, Eric J.
2002-01-01
Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…
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Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing.
Zhao, Yingwen; Fu, Guangyuan; Wang, Jun; Guo, Maozu; Yu, Guoxian
2018-02-23
Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash. Copyright © 2018 Elsevier Inc. All rights reserved.
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A Nonlinear Model for Gene-Based Gene-Environment Interaction
Directory of Open Access Journals (Sweden)
Jian Sa
2016-06-01
Full Text Available A vast amount of literature has confirmed the role of gene-environment (G×E interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction.
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Vertebrate gene predictions and the problem of large genes
DEFF Research Database (Denmark)
Wang, Jun; Li, ShengTing; Zhang, Yong
2003-01-01
To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistent...
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Maulana, Ridwan; Helms-Lorenz, Michelle; Irnidayanti, Yulia; van de Grift, Wim
Self-determination theory (SDT) posits that teacher autonomy, competence, and relatedness support are crucial universal promotors for students' interest in learning, which is in line with the general aims of positive education. This study examines the relationship between the three dimensions of
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International Nuclear Information System (INIS)
Kempen, Pauline M W van; Bockel, Liselotte van; Braunius, Weibel W; Moelans, Cathy B; Olst, Marina van; Jong, Rick de; Stegeman, Inge; Diest, Paul J van; Grolman, Wilko; Willems, Stefan M
2014-01-01
Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV) in a proportion of tumors. HPV-positive OPSCC is considered a distinct molecular entity with a prognostic advantage compared to HPV-negative cases. Silencing of cancer-related genes by DNA promoter hypermethylation may play an important role in the development of OPSCC. Hence, we examined promoter methylation status in 24 common tumor suppressor genes in a group of 200 OPSCCs to determine differentially methylated genes in HPV-positive versus HPV-negative primary OPSCC. Methylation status was correlated with HPV status, clinical features, and patient survival using multivariate methods. Additionally, methylation status of 16 cervical squamous cell carcinomas (SCC) was compared with HPV-positive OPSCC. Using methylation-specific probe amplification, HPV-positive OPSCC showed a significantly higher cumulative methylation index (CMI) compared to HPV-negative OPSCC (P=0.008). For the genes CDH13, DAPK1, and RARB, both HPV-positive and HPV-negative OPSCC showed promoter hypermethylation in at least 20% of the tumors. HPV status was found to be an independent predictor of promoter hypermethylation of CADM1 (P < 0.001), CHFR (P = 0.027), and TIMP3 (P < 0.001). CADM1 and CHFR showed similar methylation patterns in OPSCC and cervical SCC, but TIMP3 showed no methylation in cervical SCC in contrast to OPSCC. Methylation status of neither individual gene nor CMI was associated with survival. These results suggest that HPV-positive tumors are to a greater extent driven by promotor hypermethylation in these tumor suppressor genes. Especially CADM1 and TIMP3 are significantly more frequently hypermethylated in HPV-positive OPSCC and CHFR in HPV-negative tumors
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Reranking candidate gene models with cross-species comparison for improved gene prediction
Directory of Open Access Journals (Sweden)
Pereira Fernando CN
2008-10-01
Full Text Available Abstract Background Most gene finders score candidate gene models with state-based methods, typically HMMs, by combining local properties (coding potential, splice donor and acceptor patterns, etc. Competing models with similar state-based scores may be distinguishable with additional information. In particular, functional and comparative genomics datasets may help to select among competing models of comparable probability by exploiting features likely to be associated with the correct gene models, such as conserved exon/intron structure or protein sequence features. Results We have investigated the utility of a simple post-processing step for selecting among a set of alternative gene models, using global scoring rules to rerank competing models for more accurate prediction. For each gene locus, we first generate the K best candidate gene models using the gene finder Evigan, and then rerank these models using comparisons with putative orthologous genes from closely-related species. Candidate gene models with lower scores in the original gene finder may be selected if they exhibit strong similarity to probable orthologs in coding sequence, splice site location, or signal peptide occurrence. Experiments on Drosophila melanogaster demonstrate that reranking based on cross-species comparison outperforms the best gene models identified by Evigan alone, and also outperforms the comparative gene finders GeneWise and Augustus+. Conclusion Reranking gene models with cross-species comparison improves gene prediction accuracy. This straightforward method can be readily adapted to incorporate additional lines of evidence, as it requires only a ranked source of candidate gene models.
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Holland, Peter W H
2013-01-01
Many homeobox genes encode transcription factors with regulatory roles in animal and plant development. Homeobox genes are found in almost all eukaryotes, and have diversified into 11 gene classes and over 100 gene families in animal evolution, and 10 to 14 gene classes in plants. The largest group in animals is the ANTP class which includes the well-known Hox genes, plus other genes implicated in development including ParaHox (Cdx, Xlox, Gsx), Evx, Dlx, En, NK4, NK3, Msx, and Nanog. Genomic data suggest that the ANTP class diversified by extensive tandem duplication to generate a large array of genes, including an NK gene cluster and a hypothetical ProtoHox gene cluster that duplicated to generate Hox and ParaHox genes. Expression and functional data suggest that NK, Hox, and ParaHox gene clusters acquired distinct roles in patterning the mesoderm, nervous system, and gut. The PRD class is also diverse and includes Pax2/5/8, Pax3/7, Pax4/6, Gsc, Hesx, Otx, Otp, and Pitx genes. PRD genes are not generally arranged in ancient genomic clusters, although the Dux, Obox, and Rhox gene clusters arose in mammalian evolution as did several non-clustered PRD genes. Tandem duplication and genome duplication expanded the number of homeobox genes, possibly contributing to the evolution of developmental complexity, but homeobox gene loss must not be ignored. Evolutionary changes to homeobox gene expression have also been documented, including Hox gene expression patterns shifting in concert with segmental diversification in vertebrates and crustaceans, and deletion of a Pitx1 gene enhancer in pelvic-reduced sticklebacks. WIREs Dev Biol 2013, 2:31-45. doi: 10.1002/wdev.78 For further resources related to this article, please visit the WIREs website. The author declares that he has no conflicts of interest. Copyright © 2012 Wiley Periodicals, Inc.
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2010-01-01
Background Horizontal gene transfer (HGT) is relatively common in plant mitochondrial genomes but the mechanisms, extent and consequences of transfer remain largely unknown. Previous results indicate that parasitic plants are often involved as either transfer donors or recipients, suggesting that direct contact between parasite and host facilitates genetic transfer among plants. Results In order to uncover the mechanistic details of plant-to-plant HGT, the extent and evolutionary fate of transfer was investigated between two groups: the parasitic genus Cuscuta and a small clade of Plantago species. A broad polymerase chain reaction (PCR) survey of mitochondrial genes revealed that at least three genes (atp1, atp6 and matR) were recently transferred from Cuscuta to Plantago. Quantitative PCR assays show that these three genes have a mitochondrial location in the one species line of Plantago examined. Patterns of sequence evolution suggest that these foreign genes degraded into pseudogenes shortly after transfer and reverse transcription (RT)-PCR analyses demonstrate that none are detectably transcribed. Three cases of gene conversion were detected between native and foreign copies of the atp1 gene. The identical phylogenetic distribution of the three foreign genes within Plantago and the retention of cytidines at ancestral positions of RNA editing indicate that these genes were probably acquired via a single, DNA-mediated transfer event. However, samplings of multiple individuals from two of the three species in the recipient Plantago clade revealed complex and perplexing phylogenetic discrepancies and patterns of sequence divergence for all three of the foreign genes. Conclusions This study reports the best evidence to date that multiple mitochondrial genes can be transferred via a single HGT event and that transfer occurred via a strictly DNA-level intermediate. The discovery of gene conversion between co-resident foreign and native mitochondrial copies suggests
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Directory of Open Access Journals (Sweden)
Hao Weilong
2010-12-01
Full Text Available Abstract Background Horizontal gene transfer (HGT is relatively common in plant mitochondrial genomes but the mechanisms, extent and consequences of transfer remain largely unknown. Previous results indicate that parasitic plants are often involved as either transfer donors or recipients, suggesting that direct contact between parasite and host facilitates genetic transfer among plants. Results In order to uncover the mechanistic details of plant-to-plant HGT, the extent and evolutionary fate of transfer was investigated between two groups: the parasitic genus Cuscuta and a small clade of Plantago species. A broad polymerase chain reaction (PCR survey of mitochondrial genes revealed that at least three genes (atp1, atp6 and matR were recently transferred from Cuscuta to Plantago. Quantitative PCR assays show that these three genes have a mitochondrial location in the one species line of Plantago examined. Patterns of sequence evolution suggest that these foreign genes degraded into pseudogenes shortly after transfer and reverse transcription (RT-PCR analyses demonstrate that none are detectably transcribed. Three cases of gene conversion were detected between native and foreign copies of the atp1 gene. The identical phylogenetic distribution of the three foreign genes within Plantago and the retention of cytidines at ancestral positions of RNA editing indicate that these genes were probably acquired via a single, DNA-mediated transfer event. However, samplings of multiple individuals from two of the three species in the recipient Plantago clade revealed complex and perplexing phylogenetic discrepancies and patterns of sequence divergence for all three of the foreign genes. Conclusions This study reports the best evidence to date that multiple mitochondrial genes can be transferred via a single HGT event and that transfer occurred via a strictly DNA-level intermediate. The discovery of gene conversion between co-resident foreign and native
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Direct recovery of infectious Pestivirus from a full-length RT-PCR amplicon
DEFF Research Database (Denmark)
Rasmussen, Thomas Bruun; Reimann, Ilona; Hoffmann, Bernd
2008-01-01
This study describes the use of a novel and rapid long reverse transcription (RT)-PCR for the generation of infectious full-length cDNA of pestiviruses. To produce rescued viruses, full-length RT-PCR amplicons of 12.3 kb, including a T7-promotor, were transcribed directly in vitro, and the result......This study describes the use of a novel and rapid long reverse transcription (RT)-PCR for the generation of infectious full-length cDNA of pestiviruses. To produce rescued viruses, full-length RT-PCR amplicons of 12.3 kb, including a T7-promotor, were transcribed directly in vitro......, and the resulting RNA transcripts were electroporated into ovine cells. Infectious virus was obtained after one cell culture passage. The rescued viruses had a phenotype similar to the parental Border Disease virus strain. Therefore, direct generation of infectious pestiviruses from full-length RT-PCR cDNA products...
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Gene coexpression network analysis as a source of functional annotation for rice genes.
Directory of Open Access Journals (Sweden)
Kevin L Childs
Full Text Available With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional
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The drug target genes show higher evolutionary conservation than non-target genes.
Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie
2016-01-26
Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.
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Identifying potential maternal genes of Bombyx mori using digital gene expression profiling
Xu, Pingzhen
2018-01-01
Maternal genes present in mature oocytes play a crucial role in the early development of silkworm. Although maternal genes have been widely studied in many other species, there has been limited research in Bombyx mori. High-throughput next generation sequencing provides a practical method for gene discovery on a genome-wide level. Herein, a transcriptome study was used to identify maternal-related genes from silkworm eggs. Unfertilized eggs from five different stages of early development were used to detect the changing situation of gene expression. The expressed genes showed different patterns over time. Seventy-six maternal genes were annotated according to homology analysis with Drosophila melanogaster. More than half of the differentially expressed maternal genes fell into four expression patterns, while the expression patterns showed a downward trend over time. The functional annotation of these material genes was mainly related to transcription factor activity, growth factor activity, nucleic acid binding, RNA binding, ATP binding, and ion binding. Additionally, twenty-two gene clusters including maternal genes were identified from 18 scaffolds. Altogether, we plotted a profile for the maternal genes of Bombyx mori using a digital gene expression profiling method. This will provide the basis for maternal-specific signature research and improve the understanding of the early development of silkworm. PMID:29462160
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Novel gene sets improve set-level classification of prokaryotic gene expression data.
Holec, Matěj; Kuželka, Ondřej; Železný, Filip
2015-10-28
Set-level classification of gene expression data has received significant attention recently. In this setting, high-dimensional vectors of features corresponding to genes are converted into lower-dimensional vectors of features corresponding to biologically interpretable gene sets. The dimensionality reduction brings the promise of a decreased risk of overfitting, potentially resulting in improved accuracy of the learned classifiers. However, recent empirical research has not confirmed this expectation. Here we hypothesize that the reported unfavorable classification results in the set-level framework were due to the adoption of unsuitable gene sets defined typically on the basis of the Gene ontology and the KEGG database of metabolic networks. We explore an alternative approach to defining gene sets, based on regulatory interactions, which we expect to collect genes with more correlated expression. We hypothesize that such more correlated gene sets will enable to learn more accurate classifiers. We define two families of gene sets using information on regulatory interactions, and evaluate them on phenotype-classification tasks using public prokaryotic gene expression data sets. From each of the two gene-set families, we first select the best-performing subtype. The two selected subtypes are then evaluated on independent (testing) data sets against state-of-the-art gene sets and against the conventional gene-level approach. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. Novel gene sets defined on the basis of regulatory interactions improve set-level classification of gene expression data. The experimental scripts and other material needed to reproduce the experiments are available at http://ida.felk.cvut.cz/novelgenesets.tar.gz.
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[Gene doping: gene transfer and possible molecular detection].
Argüelles, Carlos Francisco; Hernández-Zamora, Edgar
2007-01-01
The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a "normal" and an "altered" genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.
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International Nuclear Information System (INIS)
Lin, Pei-Chin; Huang, Hsien-Da; Chang, Chun-Chi; Chang, Ya-Sian; Yen, Ju-Chen; Lee, Chien-Chih; Chang, Wen-Hsin; Liu, Ta-Chih; Chang, Jan-Gowth
2016-01-01
Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, and lncRNA taurine-upregulated gene 1 (TUG1) has been proven to be associated with several human cancers. However, the mechanisms of TUG1-involved regulation remain largely unknown. We examined the expressions of TUG1 in a cohort of 89 patients with non-small cell lung cancer (NSCLC) to determine the association between TUG1 expression and clinical parameters. We used circular chromosome conformation capture (4C) coupled with next-generation sequencing to explore the genome regions that interact with TUG1 and the TUG1-mediated regulation. TUG1 was significantly downregulated, and the TUG1 downregulation correlated with sex (p = 0.006), smoking status (p = 0.016), and tumor differentiation grade (p = 0.001). Knockdown of TUG1 significantly promoted the proliferation of NSCLC cells. According to the bioinformatic analysis result of TUG1 4C sequencing data, 83 candidate genes and their interaction regions were identified. Among these candidate genes, CUGBP and Elav-like family member 1 (CELF1) are potential targets of TUG1 in-trans regulation. To confirm the interaction between TUG1 and CELF1, relative expressions of CELF1 were examined in TUG1 knockdown H520 cells; results showed that CELF1 was significantly upregulated in TUG1 knockdown H520 cells. RNA immunoprecipitation was then performed to examine whether TUG1 RNA was bound to PRC2, a TUG1-involved regulation mechanism reported in previous studies. The results demonstrated that TUG1 RNA was bound to enhancer of zeste protein 2/embryonic ectoderm development (EZH2/EED), which is essential for PRC2. Finally, our designed ChIP assay revealed that the EZH2/EED was bound to the promotor region of CELF1 within 992 bp upstream of the transcript start site. TUG1 is downregulated in NSCLC. Using TUG1 4C sequencing and bioinformatic analysis, we found CELF1 to be a potential target of TUG1 RNA in in-trans regulation. Moreover, subsequent experiments showed
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Delimiting Coalescence Genes (C-Genes) in Phylogenomic Data Sets.
Springer, Mark S; Gatesy, John
2018-02-26
coalescence methods have emerged as a popular alternative for inferring species trees with large genomic datasets, because these methods explicitly account for incomplete lineage sorting. However, statistical consistency of summary coalescence methods is not guaranteed unless several model assumptions are true, including the critical assumption that recombination occurs freely among but not within coalescence genes (c-genes), which are the fundamental units of analysis for these methods. Each c-gene has a single branching history, and large sets of these independent gene histories should be the input for genome-scale coalescence estimates of phylogeny. By contrast, numerous studies have reported the results of coalescence analyses in which complete protein-coding sequences are treated as c-genes even though exons for these loci can span more than a megabase of DNA. Empirical estimates of recombination breakpoints suggest that c-genes may be much shorter, especially when large clades with many species are the focus of analysis. Although this idea has been challenged recently in the literature, the inverse relationship between c-gene size and increased taxon sampling in a dataset-the 'recombination ratchet'-is a fundamental property of c-genes. For taxonomic groups characterized by genes with long intron sequences, complete protein-coding sequences are likely not valid c-genes and are inappropriate units of analysis for summary coalescence methods unless they occur in recombination deserts that are devoid of incomplete lineage sorting (ILS). Finally, it has been argued that coalescence methods are robust when the no-recombination within loci assumption is violated, but recombination must matter at some scale because ILS, a by-product of recombination, is the raison d'etre for coalescence methods. That is, extensive recombination is required to yield the large number of independently segregating c-genes used to infer a species tree. If coalescent methods are powerful
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Gene therapy of cancer and development of therapeutic target gene
Energy Technology Data Exchange (ETDEWEB)
Kim, Chang Min; Kwon, Hee Chung
1998-04-01
We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.
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Gene therapy of cancer and development of therapeutic target gene
International Nuclear Information System (INIS)
Kim, Chang Min; Kwon, Hee Chung
1998-04-01
We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene
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Directory of Open Access Journals (Sweden)
Baseler Michael W
2007-11-01
Full Text Available Abstract Background Due to the complex and distributed nature of biological research, our current biological knowledge is spread over many redundant annotation databases maintained by many independent groups. Analysts usually need to visit many of these bioinformatics databases in order to integrate comprehensive annotation information for their genes, which becomes one of the bottlenecks, particularly for the analytic task associated with a large gene list. Thus, a highly centralized and ready-to-use gene-annotation knowledgebase is in demand for high throughput gene functional analysis. Description The DAVID Knowledgebase is built around the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of gene/protein identifiers from a variety of public genomic resources into DAVID gene clusters. The grouping of such identifiers improves the cross-reference capability, particularly across NCBI and UniProt systems, enabling more than 40 publicly available functional annotation sources to be comprehensively integrated and centralized by the DAVID gene clusters. The simple, pair-wise, text format files which make up the DAVID Knowledgebase are freely downloadable for various data analysis uses. In addition, a well organized web interface allows users to query different types of heterogeneous annotations in a high-throughput manner. Conclusion The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at http://david.abcc.ncifcrf.gov/knowledgebase/.
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DEFF Research Database (Denmark)
Egerod, Kristoffer L; Engelstoft, Maja S; Lund, Mari L
2015-01-01
In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion of gastric acid and pepsinogen and endocrine secretion of gastrin, ghrelin, and histamine. Using reporter mice expressing red fluorescent protein (RFP) under control of the SST promotor, we hav...
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Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes
Directory of Open Access Journals (Sweden)
Podder Soumita
2012-01-01
Full Text Available Abstract Background One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Results Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Conclusions Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.
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DEFF Research Database (Denmark)
Rasmussen, Henrik Berg; Madsen, Majbritt Busk
2018-01-01
The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2...
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DEFF Research Database (Denmark)
Eriksen, K W; Kaltoft, K; Mikkelsen, G
2001-01-01
are IL-2Ralpha negative. An aberrant expression of IL-2Ralpha has recently been described in cutaneous T-cell lymphoma (CTCL). Here, we study the regulation of IL-2Ralpha expression and STATs in a tumor cell line obtained from peripheral blood from a patient with Sezary syndrome (SS), a leukemic variant...... of CTCL. We show that (1) STAT3 (a transcription factor known to regulate IL-2Ralpha transcription) is constitutively tyrosine-phosphorylated in SS tumor cells, but not in non-malignant T cells; (2) STAT3 binds constitutively to a STAT-binding sequence in the promotor of the IL-2Ralpha gene; (3) the Janus...... kinase inhibitor, tyrphostine AG490, inhibits STAT3 activation, STAT3 DNA binding, and IL-2Ralpha mRNA and protein expression in parallel; and (4) tyrphostine AG490 inhibits IL-2 driven mitogenesis and triggers apoptosis in SS tumor cells. In conclusion, we provide the first example of a constitutive...
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Prokhorova, Irina V.; Osterman, Ilya A.; Burakovsky, Dmitry E.; Serebryakova, Marina V.; Galyamina, Maria A.; Pobeguts, Olga V.; Altukhov, Ilya; Kovalchuk, Sergey; Alexeev, Dmitry G.; Govorun, Vadim M.; Bogdanov, Alexey A.; Sergiev, Petr V.; Dontsova, Olga A.
2013-11-01
Ribosomes contain a number of modifications in rRNA, the function of which is unclear. Here we show - using proteomic analysis and dual fluorescence reporter in vivo assays - that m2G966 and m5C967 in 16S rRNA of Escherichia coli ribosomes are necessary for correct attenuation of tryptophan (trp) operon. Expression of trp operon is upregulated in the strain where RsmD and RsmB methyltransferases were deleted, which results in the lack of m2G966 and m5C967 modifications. The upregulation requires the trpL attenuator, but is independent of the promotor of trp operon, ribosome binding site of the trpE gene, which follows trp attenuator and even Trp codons in the trpL sequence. Suboptimal translation initiation efficiency in the rsmB/rsmD knockout strain is likely to cause a delay in translation relative to transcription which causes misregulation of attenuation control of trp operon.
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Cáncer de colon, secuencia adenoma carcinoma y pólipo aserrado
Directory of Open Access Journals (Sweden)
MSc. Juan Carlos Calderón Reza
2018-02-01
Full Text Available Los pólipos adenomatosos son muy frecuentes y presentan gran potencial de malignización. De entre ellos el velloso es el de mayor potencial maligno, pero todos los tipos histológicos presentan componente velloso en mayor o menor proporción, por lo que todos se pueden considerar premalignos, este proceso degenerativo conocido como secuencia adenoma carcinoma explicó efectivamente un 85 % de los cánceres colorrectales por décadas. Hoy en día gracias a los avances tecnológicos, se conoce que no todos los cánceres colorrectales presentan la mencionada secuencia, el 10 a 15% restantes, están incluidos dentro del denominado “Serrated neoplasia pathway” cuya característica es la inestabilidad de micro satélites, caracterizada por la inactivación de los genes reparadores del ADN por cambios epigenéticos como la hipermetilación del promotor del gen MLH1 observado en el Síndrome de Lynch
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Bayesian assignment of gene ontology terms to gene expression experiments
Sykacek, P.
2012-01-01
Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488
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Bayesian assignment of gene ontology terms to gene expression experiments.
Sykacek, P
2012-09-15
Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.
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Targeting the human lysozyme gene on bovine αs1- casein gene ...
African Journals Online (AJOL)
Targeting an exogenous gene into a favorable gene locus and for expression under endogenous regulators is an ideal method in mammary gland bioreactor research. For this purpose, a gene targeting vector was constructed to targeting the human lysozyme gene on bovine αs1-casein gene locus. In this case, the ...
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A powerful score-based test statistic for detecting gene-gene co-association.
Xu, Jing; Yuan, Zhongshang; Ji, Jiadong; Zhang, Xiaoshuai; Li, Hongkai; Wu, Xuesen; Xue, Fuzhong; Liu, Yanxun
2016-01-29
The genetic variants identified by Genome-wide association study (GWAS) can only account for a small proportion of the total heritability for complex disease. The existence of gene-gene joint effects which contains the main effects and their co-association is one of the possible explanations for the "missing heritability" problems. Gene-gene co-association refers to the extent to which the joint effects of two genes differ from the main effects, not only due to the traditional interaction under nearly independent condition but the correlation between genes. Generally, genes tend to work collaboratively within specific pathway or network contributing to the disease and the specific disease-associated locus will often be highly correlated (e.g. single nucleotide polymorphisms (SNPs) in linkage disequilibrium). Therefore, we proposed a novel score-based statistic (SBS) as a gene-based method for detecting gene-gene co-association. Various simulations illustrate that, under different sample sizes, marginal effects of causal SNPs and co-association levels, the proposed SBS has the better performance than other existed methods including single SNP-based and principle component analysis (PCA)-based logistic regression model, the statistics based on canonical correlations (CCU), kernel canonical correlation analysis (KCCU), partial least squares path modeling (PLSPM) and delta-square (δ (2)) statistic. The real data analysis of rheumatoid arthritis (RA) further confirmed its advantages in practice. SBS is a powerful and efficient gene-based method for detecting gene-gene co-association.
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Prediction of regulatory gene pairs using dynamic time warping and gene ontology.
Yang, Andy C; Hsu, Hui-Huang; Lu, Ming-Da; Tseng, Vincent S; Shih, Timothy K
2014-01-01
Selecting informative genes is the most important task for data analysis on microarray gene expression data. In this work, we aim at identifying regulatory gene pairs from microarray gene expression data. However, microarray data often contain multiple missing expression values. Missing value imputation is thus needed before further processing for regulatory gene pairs becomes possible. We develop a novel approach to first impute missing values in microarray time series data by combining k-Nearest Neighbour (KNN), Dynamic Time Warping (DTW) and Gene Ontology (GO). After missing values are imputed, we then perform gene regulation prediction based on our proposed DTW-GO distance measurement of gene pairs. Experimental results show that our approach is more accurate when compared with existing missing value imputation methods on real microarray data sets. Furthermore, our approach can also discover more regulatory gene pairs that are known in the literature than other methods.
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The Drosophila melanogaster methuselah gene: a novel gene with ancient functions.
Directory of Open Access Journals (Sweden)
Ana Rita Araújo
Full Text Available The Drosophila melanogaster G protein-coupled receptor gene, methuselah (mth, has been described as a novel gene that is less than 10 million years old. Nevertheless, it shows a highly specific expression pattern in embryos, larvae, and adults, and has been implicated in larval development, stress resistance, and in the setting of adult lifespan, among others. Although mth belongs to a gene subfamily with 16 members in D. melanogaster, there is no evidence for functional redundancy in this subfamily. Therefore, it is surprising that a novel gene influences so many traits. Here, we explore the alternative hypothesis that mth is an old gene. Under this hypothesis, in species distantly related to D. melanogaster, there should be a gene with features similar to those of mth. By performing detailed phylogenetic, synteny, protein structure, and gene expression analyses we show that the D. virilis GJ12490 gene is the orthologous of mth in species distantly related to D. melanogaster. We also show that, in D. americana (a species of the virilis group of Drosophila, a common amino acid polymorphism at the GJ12490 orthologous gene is significantly associated with developmental time, size, and lifespan differences. Our results imply that GJ12490 orthologous genes are candidates for developmental time and lifespan differences in Drosophila in general.
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Constructing an integrated gene similarity network for the identification of disease genes.
Tian, Zhen; Guo, Maozu; Wang, Chunyu; Xing, LinLin; Wang, Lei; Zhang, Yin
2017-09-20
Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .
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Directory of Open Access Journals (Sweden)
Nolan Priedigkeit
2015-02-01
Full Text Available Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC, is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting "disease map" network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks.
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Kannan, Lavanya; Li, Hua; Rubinstein, Boris; Mushegian, Arcady
2013-12-19
The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral ("high ancestrality"). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes.
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Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization
Directory of Open Access Journals (Sweden)
McDonald Karen
2011-08-01
Full Text Available Abstract Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.
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Gene delivery to the lungs: pulmonary gene therapy for cystic fibrosis.
Villate-Beitia, Ilia; Zarate, Jon; Puras, Gustavo; Pedraz, José Luis
2017-07-01
Cystic fibrosis (CF) is a monogenic autosomal recessive disorder where the defective gene, the cystic fibrosis transmembrane conductance regulator (CFTR), is well identified. Moreover, the respiratory tract can be targeted through noninvasive aerosolized formulations for inhalation. Therefore, gene therapy is considered a plausible strategy to address this disease. Conventional gene therapy strategies rely on the addition of a correct copy of the CFTR gene into affected cells in order to restore the channel activity. In recent years, genome correction strategies have emerged, such as zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases. These gene editing tools aim to repair the mutated gene at its original genomic locus with high specificity. Besides, the success of gene therapy critically depends on the nucleic acids carriers. To date, several clinical studies have been carried out to add corrected copies of the CFTR gene into target cells using viral and non-viral vectors, some of them with encouraging results. Regarding genome editing systems, preliminary in vitro studies have been performed in order to repair the CFTR gene. In this review, after briefly introducing the basis of CF, we discuss the up-to-date gene therapy strategies to address the disease. The review focuses on the main factors to take into consideration when developing gene delivery strategies, such as the design of vectors and plasmid DNA, in vitro/in vivo tests, translation to human use, administration methods, manufacturing conditions and regulatory issues.
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Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra
2016-10-03
FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.
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Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.
Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H
2014-01-01
Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.
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Divergence of gene body DNA methylation and evolution of plant duplicate genes.
Directory of Open Access Journals (Sweden)
Jun Wang
Full Text Available It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.
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GeneTopics - interpretation of gene sets via literature-driven topic models
2013-01-01
Background Annotation of a set of genes is often accomplished through comparison to a library of labelled gene sets such as biological processes or canonical pathways. However, this approach might fail if the employed libraries are not up to date with the latest research, don't capture relevant biological themes or are curated at a different level of granularity than is required to appropriately analyze the input gene set. At the same time, the vast biomedical literature offers an unstructured repository of the latest research findings that can be tapped to provide thematic sub-groupings for any input gene set. Methods Our proposed method relies on a gene-specific text corpus and extracts commonalities between documents in an unsupervised manner using a topic model approach. We automatically determine the number of topics summarizing the corpus and calculate a gene relevancy score for each topic allowing us to eliminate non-specific topics. As a result we obtain a set of literature topics in which each topic is associated with a subset of the input genes providing directly interpretable keywords and corresponding documents for literature research. Results We validate our method based on labelled gene sets from the KEGG metabolic pathway collection and the genetic association database (GAD) and show that the approach is able to detect topics consistent with the labelled annotation. Furthermore, we discuss the results on three different types of experimentally derived gene sets, (1) differentially expressed genes from a cardiac hypertrophy experiment in mice, (2) altered transcript abundance in human pancreatic beta cells, and (3) genes implicated by GWA studies to be associated with metabolite levels in a healthy population. In all three cases, we are able to replicate findings from the original papers in a quick and semi-automated manner. Conclusions Our approach provides a novel way of automatically generating meaningful annotations for gene sets that are directly
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2013-01-01
Background The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. Results We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. Conclusion While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral (“high ancestrality”). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes. Reviewers This article was reviewed by Martijn A Huynen, Toni Gabaldón and Fyodor Kondrashov. PMID:24354654
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Directory of Open Access Journals (Sweden)
Sudip Indu
2013-01-01
Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.
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Unal, Mehmet; Ozer Unal, Durisehvar
2004-01-01
Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement. Copyright 2004 Adis Data Information BV
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Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.
Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin
2017-08-01
This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
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Identification of suitable reference genes for gene expression studies of shoulder instability.
Directory of Open Access Journals (Sweden)
Mariana Ferreira Leal
Full Text Available Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results. In the present study, we evaluated the suitability of a set of reference genes using samples from the glenohumeral capsules of individuals with and without shoulder instability. We analyzed the expression of six commonly used reference genes (ACTB, B2M, GAPDH, HPRT1, TBP and TFRC in the antero-inferior, antero-superior and posterior portions of the glenohumeral capsules of cases and controls. The stability of the candidate reference gene expression was determined using four software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1 was the best single reference gene, and HPRT1 and B2M composed the best pair of reference genes from different analysis groups, including simultaneous analysis of all tissue samples. GenEx software was used to identify the optimal number of reference genes to be used for normalization and demonstrated that the accumulated standard deviation resulting from the use of 2 reference genes was similar to that resulting from the use of 3 or more reference genes. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1. Although the use of different reference gene combinations yielded variable normalized quantities, the relative quantities within sample groups were similar and confirmed that no obvious differences were observed when using 2, 3 or 4 reference genes. Consequently, the use of 2 stable reference genes for normalization, especially
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Borrás, Teresa
2017-01-01
Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration. Copyright© 2017 Asia-Pacific Academy of Ophthalmology.
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Hernández-Leo, Davinia
2009-01-01
Hernández-Leo, D., "El proyecto europeo TENCompetence: plataforma para el desarrollo de competencias a lo largo de la vida" IX Jornadas de Promotores de Formación Continua - III Jornadas E-Learning en la Administración Pública, Valladolid, Spain, 24 junio 2009(in Spanish)
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Verslag symposium 23 april: 'The best evidence for dental hygiene practice'
van der Weijden, F.; Slot, D.E.
2015-01-01
De derde week van april 2015 was voor de sectie parodontologie van het Academisch Centrum Tandheelkunde Amsterdam (ACTA) een feestelijke week. Er stonden twee promoties op de agenda: Martijn Rosema en Dagmar Else Slot, beiden onder supervisie van promotor Fridus van der Weijden. Om de feestvreugde
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De gemeente Huissen : proeve eener sociaal-geographische analyse
Oedin, S.
1946-01-01
This research, originally under the auspices of Professor van Vuuren, was accepted by Professor Edelman after the war because of a vacuum in the Social Economic Department of the Agricultural University. Because of the change of promotors the description of the physical environment was extended. The
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Houden promotors en detractors zich aan hun woord?
Haans, H.; Raassens, N.; Keep, van H.
2015-01-01
Mond-tot-mondreclame (word of mouth, WOM) krijgt steeds meer invloed op de ankoopbeslissingen van consumenten (Kozinets et al. 2010). Waar consumenten traditionele marketing steeds meer wantrouwen, zien zij andere consumenten als een objectieve, neutrale bron (Kozinets et al. 2010; Trusov, Bucklin,
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Cultura de integridade em pesquisa: somos agentes promotores
Directory of Open Access Journals (Sweden)
Ana Paula Abdon
2015-03-01
Full Text Available A Revista Brasileira em Promoção da Saúde (Brazilian Journal in Health Promotion, movida pela necessidade de uma cultura que estimule a integridade em pesquisa, quer enfatizar sua preocupação, não apenas com o conteúdo de suas publicações, mas também com os aspectos éticos que envolvem a submissão e a publicação dos manuscritos. Com isso, pretende levantar a discussão sobre boas práticas em pesquisa científica, ressaltando a importância de que este reforço ocorra desde os primeiros estágios da carreira dos pesquisadores. As más condutas éticas ocorrem em virtude das exigências crescente de produção intelectual e consequentemente as pressões sobre os pesquisadores vinculados aos programas de pós-graduação que utilizam os indicadores, principalmente, internacionais(1. A proliferação destas condutas antiéticas também é influenciada pelo “sistema de recompensas” existente, no qual o pesquisador é avaliado pela sua produtividade. O primeiro evento mundial sobre a integridade em pesquisa ocorreu em 2007 na cidade de Lisboa(2 e buscou sensibilizar a comunidade científica e editores para a importância de promover a conduta responsável na pesquisa. Em 2010, houve a segunda conferência mundial em Singapura(3. Desta conferência emergiu a “Declaração de Singapura sobre integridade em pesquisa” trazendo como princípios de integridade: a honestidade, a responsabilidade, o respeito e imparcialidade profissionais e a boa gestão da pesquisa(3. Em 2013, a terceira edição ocorreu em Montreal e teve como grande linha temática as investigações que cruzam as fronteiras e as parcerias internacionais(4. A exemplo destes movimentos internacionais, o Brasil também se mobilizou. Entretanto, esta preocupação é recente e tomou corpo após séries de publicações a respeito desta temática elaborado pela Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP(5 e pela publicação do Relatório da Comissão de Integridade de Pesquisa do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq(6. Paralelo a estas publicações, dois importantes eventos ocorreram nos anos de 2011 e 2012 no Brasil que abordaram ações para promoção da integridade científica norteando pesquisadores e instituições brasileiras, o I e II Brispe (Brazilian Meeting on Research Integrity, Science and Publication Ethics(7. Neste ano de 2015, o Brasil sediará a “4ª Conferência Anual para Integridade da Pesquisa” (4th World Conference on Research Integrity no Rio de Janeiro, que irá explorar a “excelência da investigação científica em seus diferentes sistemas”(8. Somado a estes movimentos nacionais, destacamos a importância de que os periódicos científicos discutam suas políticas editoriais com a comunidade científica para exercermos o papel de educador das boas práticas em pesquisa e prevenir as más condutas, como plágio, autoplágio, fraude, autoria indevida, entre outros. Dentre estes, o plágio vem ganhando destaque no cenário internacional em virtude do crescente número de relatos deste tipo de má conduta. No Brasil, a situação é preocupante, calcula-se a proporção disto quando renomado pesquisador da área afirma “o Brasil encontra-se entre os vinte países com o maior índice de ocorrência de plágio e de redundância (autoplágio o que foi constatado por meio de uma amostra de artigos publicados na PubMed entre 2008 e 2012”(8,p.1. Nas diretrizes do CNPq(6, considera-se plágio: “...apresentação, como se fosse de sua autoria, de resultados ou conclusões anteriormente obtidos por outro autor, bem como de textos integrais ou de parte substancial de textos alheios sem os cuidados detalhados nas Diretrizes.” Em consonância com estes movimentos, a Associação Brasileira de Editores Científicos (ABEC promove eventos e lança textos de pesquisadores renomados no intuito de manter constante debate sobre a qualidade e consolidação das publicações/periódicos editados no país, seguindo os padrões internacionais de editoração e ética. Por fim, as más condutas na pesquisa são assunto de interesse das revistas científicas, que devem implantar mecanismos que permitam identificar e desestimular as práticas fraudulentas na pesquisa e estimular sua integridade. Movida por este desejo, a Revista Brasileira em Promoção da Saúde institui, neste ano de 2015, uma política de submissão/avaliação dos manuscritos que envolverá, além da inclusão de dois documentos obrigatórios, o parecer de aprovação do projeto em comitê de ética em pesquisa com seres humanos ou com animais e a declaração de autoria, a utilização de programa antiplágio em todos os manuscritos submetidos para análise, e com isso, almeja educar autores e proliferar a ideia de que os artigos publicados estão em consonância com a ética e integridade mundiais.
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Cultura de integridade em pesquisa: somos agentes promotores
Ana Paula Abdon
2015-01-01
A Revista Brasileira em Promoção da Saúde (Brazilian Journal in Health Promotion), movida pela necessidade de uma cultura que estimule a integridade em pesquisa, quer enfatizar sua preocupação, não apenas com o conteúdo de suas publicações, mas também com os aspectos éticos que envolvem a submissão e a publicação dos manuscritos. Com isso, pretende levantar a discussão sobre boas práticas em pesquisa científica, ressaltando a importância de que este reforço ocorra desde os primeiros estágios ...
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Energy Technology Data Exchange (ETDEWEB)
Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Tratz, Stephen C.; Gregory, Michelle L.
2006-06-08
With the rising influence of the Gene On-tology, new approaches have emerged where the similarity between genes or gene products is obtained by comparing Gene Ontology code annotations associ-ated with them. So far, these approaches have solely relied on the knowledge en-coded in the Gene Ontology and the gene annotations associated with the Gene On-tology database. The goal of this paper is to demonstrate that improvements to these approaches can be obtained by integrating textual evidence extracted from relevant biomedical literature.
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UniGene Tabulator: a full parser for the UniGene format.
Lenzi, Luca; Frabetti, Flavia; Facchin, Federica; Casadei, Raffaella; Vitale, Lorenza; Canaider, Silvia; Carinci, Paolo; Zannotti, Maria; Strippoli, Pierluigi
2006-10-15
UniGene Tabulator 1.0 provides a solution for full parsing of UniGene flat file format; it implements a structured graphical representation of each data field present in UniGene following import into a common database managing system usable in a personal computer. This database includes related tables for sequence, protein similarity, sequence-tagged site (STS) and transcript map interval (TXMAP) data, plus a summary table where each record represents a UniGene cluster. UniGene Tabulator enables full local management of UniGene data, allowing parsing, querying, indexing, retrieving, exporting and analysis of UniGene data in a relational database form, usable on Macintosh (OS X 10.3.9 or later) and Windows (2000, with service pack 4, XP, with service pack 2 or later) operating systems-based computers. The current release, including both the FileMaker runtime applications, is freely available at http://apollo11.isto.unibo.it/software/
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Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.
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Vipin Narang
Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.
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Directory of Open Access Journals (Sweden)
Yunfeng Shan
2008-01-01
Full Text Available Genomes and genes diversify during evolution; however, it is unclear to what extent genes still retain the relationship among species. Model species for molecular phylogenetic studies include yeasts and viruses whose genomes were sequenced as well as plants that have the fossil-supported true phylogenetic trees available. In this study, we generated single gene trees of seven yeast species as well as single gene trees of nine baculovirus species using all the orthologous genes among the species compared. Homologous genes among seven known plants were used for validation of the finding. Four algorithms—maximum parsimony (MP, minimum evolution (ME, maximum likelihood (ML, and neighbor-joining (NJ—were used. Trees were reconstructed before and after weighting the DNA and protein sequence lengths among genes. Rarely a gene can always generate the “true tree” by all the four algorithms. However, the most frequent gene tree, termed “maximum gene-support tree” (MGS tree, or WMGS tree for the weighted one, in yeasts, baculoviruses, or plants was consistently found to be the “true tree” among the species. The results provide insights into the overall degree of divergence of orthologous genes of the genomes analyzed and suggest the following: 1 The true tree relationship among the species studied is still maintained by the largest group of orthologous genes; 2 There are usually more orthologous genes with higher similarities between genetically closer species than between genetically more distant ones; and 3 The maximum gene-support tree reflects the phylogenetic relationship among species in comparison.
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Simulation and modeling CO2 absorption in biogas with DEA promoted K2CO3 solution in packed column
Nurkhamidah, Siti; Altway, Ali; Airlangga, Bramantyo; Emilia, Dwi Putri
2017-05-01
Absorption of carbon dioxide (CO2) using potassium carbonate (K2CO3) is one of biogas purification method. However, K2CO3 have slow mass transfer in liquid phase. So it is necessary to eliminate the disadvantage of CO2 absorption using K2CO3 by adding promotor (activator). Diethanol amine (DEA) is one of promotor which can increase its reaction rate. Simulation and modeling research of the CO2 absorption from biogas with DEA promoted K2CO3 solution has not been conducted. Thus, the main goal of this research is create model and simulation for the CO2 absorption from biogas with DEA promoted K2CO3 solution, then observe the influence of promoter concentration. DEA concentration varies between 1-5 %wt. From the simulation, we concluded that the CO2 removal rise with the increasing of promoter concentration. The highest CO2 removal is 54.5318 % at 5 % wt DEA concentration.
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Directory of Open Access Journals (Sweden)
Antonio Bento Mancio
2005-08-01
Full Text Available O experimento foi conduzido para se avaliar o desempenho de cabritos tratados com leite de cabra integral ou colostro de vaca fermentado com ou sem óleo de soja, e com aplicação ou não do promotor de crescimento Zeranol. Vinte e quatro cabritos da raça Alpina foram dispostos em delineamento inteiramente casualizado em esquema fatorial 3 x 2. Cada animal recebeu, pela manhã, 1 L da dieta líquida e 250 g/animal/dia de concentrado. Foram avaliados o ganho de peso dos animais, os consumos de concentrado e de matéria seca, a conversão alimentar e o tamanho dos órgãos. Houve diferenças entre as dietas líquidas, com ou sem a aplicação de Zeranol, para ganho de peso aos 29, 36, e 50 dias de idade, mas não para o ganho médio diário. A não aplicação de Zeranol nos tratamentos com leite de cabra e colostro fermentado com óleo de soja proporcionou diferença média de 8% no ganho de peso dos animais alimentados com leite de cabra. Não se observou diferença nos consumos de concentrado e de matéria seca e na conversão alimentar dos animais entre as diferentes dietas líquidas avaliadas. Não houve influência do Zeranol ou do óleo de soja nas dietas líquidas sobre nenhum dos órgãos estudadosThe objective of this experiment was to study the effects of feeding whole goat milk or fermented cow colostrum supplemented or not with soy oil and with or without the growth promoter Zeranol on performance of kid goats. Twenty-four Alpine kid goats assigned to a completely randomized design in a 3 x 2 factorial arrangement were used in this trial. The following variables were investigated: weight gain, intakes of dry matter and concentrate, feed conversion, and organ sizes. Significant differences were observed among liquid diets with or without Zeranol for weight gain at 29, 36, and 50 days old, but not for the average daily gain. No significant differences for intake of both dry matter and concentrate as well as for feed conversion were
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Westenberg, M.A.; Hijum, van S.A.F.T.; Lulko, A.T.; Kuipers, O.P.; Roerdink, J.B.T.M.; Linsen, L.; Hagen, H.; Hamann, B.
2008-01-01
We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,
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Directory of Open Access Journals (Sweden)
A. Gomes
2014-01-01
úrgica aumenta até 50%, mas este grupo é apenas constituÃdo por 14-16% dos casos. A metilação do ADN surgiu como um potencial marcador biológico especÃfico do cancro. A hipermetilação das ilhas CpG localizadas nas regiões promotoras de genes supressores do tumor está agora firmemente estabelecida como um mecanismo importante para a inativação do gene.Este estudo retrospetivo incluiu 40 carcinomas das células escamosas e 40 adenocarcinomas em vários estádios cirúrgicos TNM para definir o perfil da metilação e o possÃvel silenciamento de genes de reparação do ADN - MLH1 e MSH2 - usando metilação PCR especÃfica e expressão da proteÃna por imuno-histoquÃmica no tecido tumoral, lesões pré-neoplásicas e epitélio respiratório com caracterÃsticas histológicas normais.A expressão da proteÃna dos genes MLH1 e MSH2, nas lesões pré-neoplásticas disponÃveis e no epitélio respiratório cilÃndrico normal, pareceu reduzida. A frequência da hipermetilação promotora encontrada nestes genes reparadores de ADN foi elevada, com uma maior prevalência da metilação do gene MLH1 em 72% de carcinoma de células escamosas. As diferenças não são tão óbvias para a hipermetilação do promotor MSH2. Não foi encontrada correlação entre o estado de metilação, a expressão da proteÃna e as caracterÃsticas clÃnico-patológicas.Com um estudo mais amplo, seria alcançada uma melhor caracterização do estado da hipermetilação das lesões neoplásicas e pré-neoplásicas em pequenas biopsias, inerente à histologia, heterogeneidade e preservação do tumor, e, finalmente, à s diferenças na população estudada para elucidar outros mecanismos possÃveis da expressão alterada do hMLH1 e hMSH. Keywords: Adenocarcinoma, Squamous cell carcinoma, Lung, Hypermethylation, MLH1, MSH2
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Using gene expression noise to understand gene regulation
Munsky, B.; Neuert, G.; van Oudenaarden, A.
2012-01-01
Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a
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Gene Conversion in Angiosperm Genomes with an Emphasis on Genes Duplicated by Polyploidization
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Xi-Yin Wang
2011-01-01
Full Text Available Angiosperm genomes differ from those of mammals by extensive and recursive polyploidizations. The resulting gene duplication provides opportunities both for genetic innovation, and for concerted evolution. Though most genes may escape conversion by their homologs, concerted evolution of duplicated genes can last for millions of years or longer after their origin. Indeed, paralogous genes on two rice chromosomes duplicated an estimated 60–70 million years ago have experienced gene conversion in the past 400,000 years. Gene conversion preserves similarity of paralogous genes, but appears to accelerate their divergence from orthologous genes in other species. The mutagenic nature of recombination coupled with the buffering effect provided by gene redundancy, may facilitate the evolution of novel alleles that confer functional innovations while insulating biological fitness of affected plants. A mixed evolutionary model, characterized by a primary birth-and-death process and occasional homoeologous recombination and gene conversion, may best explain the evolution of multigene families.
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G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes
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Lemay Danielle G
2012-09-01
Full Text Available Abstract Background In previous studies, gene neighborhoods—spatial clusters of co-expressed genes in the genome—have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously. Results Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods. Conclusions Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The
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Directory of Open Access Journals (Sweden)
Ming Liu
2016-01-01
Full Text Available Prostate cancer (PCa is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI, smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs = 1.79–4.41. GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032 and 5.33 (p = 0.046, respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007 and 3.11 (p = 0.024, respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041. These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.
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Keifer, Joyce
2017-02-11
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene ( BDNF ), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.
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Characterization of Genes for Beef Marbling Based on Applying Gene Coexpression Network
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Dajeong Lim
2014-01-01
Full Text Available Marbling is an important trait in characterization beef quality and a major factor for determining the price of beef in the Korean beef market. In particular, marbling is a complex trait and needs a system-level approach for identifying candidate genes related to the trait. To find the candidate gene associated with marbling, we used a weighted gene coexpression network analysis from the expression value of bovine genes. Hub genes were identified; they were topologically centered with large degree and BC values in the global network. We performed gene expression analysis to detect candidate genes in M. longissimus with divergent marbling phenotype (marbling scores 2 to 7 using qRT-PCR. The results demonstrate that transmembrane protein 60 (TMEM60 and dihydropyrimidine dehydrogenase (DPYD are associated with increasing marbling fat. We suggest that the network-based approach in livestock may be an important method for analyzing the complex effects of candidate genes associated with complex traits like marbling or tenderness.
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Simple Comparative Analyses of Differentially Expressed Gene Lists May Overestimate Gene Overlap.
Lawhorn, Chelsea M; Schomaker, Rachel; Rowell, Jonathan T; Rueppell, Olav
2018-04-16
Comparing the overlap between sets of differentially expressed genes (DEGs) within or between transcriptome studies is regularly used to infer similarities between biological processes. Significant overlap between two sets of DEGs is usually determined by a simple test. The number of potentially overlapping genes is compared to the number of genes that actually occur in both lists, treating every gene as equal. However, gene expression is controlled by transcription factors that bind to a variable number of transcription factor binding sites, leading to variation among genes in general variability of their expression. Neglecting this variability could therefore lead to inflated estimates of significant overlap between DEG lists. With computer simulations, we demonstrate that such biases arise from variation in the control of gene expression. Significant overlap commonly arises between two lists of DEGs that are randomly generated, assuming that the control of gene expression is variable among genes but consistent between corresponding experiments. More overlap is observed when transcription factors are specific to their binding sites and when the number of genes is considerably higher than the number of different transcription factors. In contrast, overlap between two DEG lists is always lower than expected when the genetic architecture of expression is independent between the two experiments. Thus, the current methods for determining significant overlap between DEGs are potentially confounding biologically meaningful overlap with overlap that arises due to variability in control of expression among genes, and more sophisticated approaches are needed.
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Di, Chao; Xu, Wenying; Su, Zhen; Yuan, Joshua S
2010-10-07
PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms. The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With Arabidopsis as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function. PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out
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... ENTCareers Marketplace Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...
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Establishing gene models from the Pinus pinaster genome using gene capture and BAC sequencing.
Seoane-Zonjic, Pedro; Cañas, Rafael A; Bautista, Rocío; Gómez-Maldonado, Josefa; Arrillaga, Isabel; Fernández-Pozo, Noé; Claros, M Gonzalo; Cánovas, Francisco M; Ávila, Concepción
2016-02-27
In the era of DNA throughput sequencing, assembling and understanding gymnosperm mega-genomes remains a challenge. Although drafts of three conifer genomes have recently been published, this number is too low to understand the full complexity of conifer genomes. Using techniques focused on specific genes, gene models can be established that can aid in the assembly of gene-rich regions, and this information can be used to compare genomes and understand functional evolution. In this study, gene capture technology combined with BAC isolation and sequencing was used as an experimental approach to establish de novo gene structures without a reference genome. Probes were designed for 866 maritime pine transcripts to sequence genes captured from genomic DNA. The gene models were constructed using GeneAssembler, a new bioinformatic pipeline, which reconstructed over 82% of the gene structures, and a high proportion (85%) of the captured gene models contained sequences from the promoter regulatory region. In a parallel experiment, the P. pinaster BAC library was screened to isolate clones containing genes whose cDNA sequence were already available. BAC clones containing the asparagine synthetase, sucrose synthase and xyloglucan endotransglycosylase gene sequences were isolated and used in this study. The gene models derived from the gene capture approach were compared with the genomic sequences derived from the BAC clones. This combined approach is a particularly efficient way to capture the genomic structures of gene families with a small number of members. The experimental approach used in this study is a valuable combined technique to study genomic gene structures in species for which a reference genome is unavailable. It can be used to establish exon/intron boundaries in unknown gene structures, to reconstruct incomplete genes and to obtain promoter sequences that can be used for transcriptional studies. A bioinformatics algorithm (GeneAssembler) is also provided as a
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Directory of Open Access Journals (Sweden)
Reverter Antonio
2008-09-01
Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing
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Directory of Open Access Journals (Sweden)
Xia Yuannan
2006-12-01
Full Text Available Abstract Background DNA microarrays are a powerful tool for monitoring the expression of tens of thousands of genes simultaneously. With the advance of microarray technology, the challenge issue becomes how to analyze a large amount of microarray data and make biological sense of them. Affymetrix GeneChips are widely used microarrays, where a variety of statistical algorithms have been explored and used for detecting significant genes in the experiment. These methods rely solely on the quantitative data, i.e., signal intensity; however, qualitative data are also important parameters in detecting differentially expressed genes. Results AffyMiner is a tool developed for detecting differentially expressed genes in Affymetrix GeneChip microarray data and for associating gene annotation and gene ontology information with the genes detected. AffyMiner consists of the functional modules, GeneFinder for detecting significant genes in a treatment versus control experiment and GOTree for mapping genes of interest onto the Gene Ontology (GO space; and interfaces to run Cluster, a program for clustering analysis, and GenMAPP, a program for pathway analysis. AffyMiner has been used for analyzing the GeneChip data and the results were presented in several publications. Conclusion AffyMiner fills an important gap in finding differentially expressed genes in Affymetrix GeneChip microarray data. AffyMiner effectively deals with multiple replicates in the experiment and takes into account both quantitative and qualitative data in identifying significant genes. AffyMiner reduces the time and effort needed to compare data from multiple arrays and to interpret the possible biological implications associated with significant changes in a gene's expression.
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Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini
2013-03-01
GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is 'the use of genes as medicine'. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.
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Norrie disease gene is distinct from the monoamine oxidase genes.
Sims, K B; Ozelius, L; Corey, T; Rinehart, W B; Liberfarb, R; Haines, J; Chen, W J; Norio, R; Sankila, E; de la Chapelle, A
1989-09-01
The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and/or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in "classic" Norrie disease patients. Genomic DNA from these "nondeletion" Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease.
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Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors
Directory of Open Access Journals (Sweden)
Lamblin Anne-Francoise
2007-10-01
Full Text Available Abstract Background Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs, which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin. Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation. Results To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1, sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4 were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1 were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway. Conclusion This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that
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Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.
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Marta Miró-Murillo
Full Text Available Von Hippel Lindau (Vhl gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs, have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2. Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed-UBC-Cre-ER(T2 adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2 tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2 mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.
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Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data
Ezer, Daphne; Moignard, Victoria; G?ttgens, Berthold; Adryan, Boris
2016-01-01
Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete ...
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Mutational specificity of SOS mutagenesis
International Nuclear Information System (INIS)
Kato, Takeshi
1986-01-01
In an approach to the isolation of mutants of E. coli unable to produce mutations by ultraviolet light, the author has found new umuC-mutants. Their properties could be explained by ''SOS hypothesis of Radman and Witkin'', which has now been justified by many investigators. Analysis of the umuC region of E. coli chromosome cloned in pSK 100 has led to the conclusion that two genes, umuD and umuC, having the capacity of mutation induction express in the same mechanism as that of SOS genes, which is known to be inhibited by LexA protein bonding to ''SOS box'' found at promotor region. Suppressor analysis for mutational specificity has revealed: (i) umuDC-independent mutagens, such as EMS and (oh) 4 Cy, induce selected base substitution alone; and (ii) umuDC-dependent mutagens, such as X-rays and gamma-rays, induce various types of base substitution simultaneously, although they have mutational specificity. In the umuDC-dependent processes of basechange mutagenesis, the spectra of base substitution were a mixture of base substitution reflecting the specific base damages induced by individual mutagens and nonspecific base substitution. In conclusion, base substitution plays the most important role in umuDC-dependent mutagenesis, although mutagenesis of umuDC proteins remains uncertain. (Namekawa, K.)
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Directory of Open Access Journals (Sweden)
Lynne Shanley
2010-12-01
Full Text Available Changes in the expression of the neuropeptide substance P (SP in different populations of sensory neurones are associated with the progression of chronic inflammatory disease. Thus, understanding the genomic and cellular mechanisms driving the expression of the TAC1 gene, which encodes SP, in sensory neurones is essential to understanding its role in inflammatory disease. We used a novel combination of computational genomics, primary-cell culture and mouse transgenics to determine the genomic and cellular mechanisms that control the expression of TAC1 in sensory neurones. Intriguingly, we demonstrated that the promoter of the TAC1 gene must act in synergy with a remote enhancer, identified using comparative genomics, to respond to MAPK signalling that modulates the expression of TAC1 in sensory neurones. We also reveal that noxious stimulation of sensory neurones triggers this synergy in larger diameter sensory neurones – an expression of SP associated with hyperalgesia. This noxious stimulation of TAC1 enhancer-promotor synergy could be strongly blocked by antagonism of the MEK pathway. This study provides a unique insight into the role of long-range enhancer-promoter synergy and selectivity in the tissue-specific response of promoters to specific signal transduction pathways and suggests a possible new avenue for the development of novel anti-inflammatory therapies.
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Discovering genes underlying QTL
Energy Technology Data Exchange (ETDEWEB)
Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)
2002-02-01
A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)
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Kim, Hyunjin; Choi, Sang-Min; Park, Sanghyun
2018-01-01
When a gene shows varying levels of expression among normal people but similar levels in disease patients or shows similar levels of expression among normal people but different levels in disease patients, we can assume that the gene is associated with the disease. By utilizing this gene expression heterogeneity, we can obtain additional information that abets discovery of disease-associated genes. In this study, we used collaborative filtering to calculate the degree of gene expression heterogeneity between classes and then scored the genes on the basis of the degree of gene expression heterogeneity to find "differentially predicted" genes. Through the proposed method, we discovered more prostate cancer-associated genes than 10 comparable methods. The genes prioritized by the proposed method are potentially significant to biological processes of a disease and can provide insight into them.
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Validation of reference genes for quantifying changes in gene expression in virus-infected tobacco.
Baek, Eseul; Yoon, Ju-Yeon; Palukaitis, Peter
2017-10-01
To facilitate quantification of gene expression changes in virus-infected tobacco plants, eight housekeeping genes were evaluated for their stability of expression during infection by one of three systemically-infecting viruses (cucumber mosaic virus, potato virus X, potato virus Y) or a hypersensitive-response-inducing virus (tobacco mosaic virus; TMV) limited to the inoculated leaf. Five reference-gene validation programs were used to establish the order of the most stable genes for the systemically-infecting viruses as ribosomal protein L25 > β-Tubulin > Actin, and the least stable genes Ubiquitin-conjugating enzyme (UCE) genes were EF1α > Cysteine protease > Actin, and the least stable genes were GAPDH genes, three defense responsive genes were examined to compare their relative changes in gene expression caused by each virus. Copyright © 2017 Elsevier Inc. All rights reserved.
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Human gene therapy: novel approaches to improve the current gene delivery systems.
Cucchiarini, Magali
2016-06-01
Even though gene therapy made its way through the clinics to treat a number of human pathologies since the early years of experimental research and despite the recent approval of the first gene-based product (Glybera) in Europe, the safe and effective use of gene transfer vectors remains a challenge in human gene therapy due to the existence of barriers in the host organism. While work is under active investigation to improve the gene transfer systems themselves, the use of controlled release approaches may offer alternative, convenient tools of vector delivery to achieve a performant gene transfer in vivo while overcoming the various physiological barriers that preclude its wide use in patients. This article provides an overview of the most significant contributions showing how the principles of controlled release strategies may be adapted for human gene therapy.
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Thermal oxidation of InP in the presence of nitrates and sulfates of the 4-th group
International Nuclear Information System (INIS)
Mittova, I.Ya.; Shchukarev, A.V.; Soshnikov, V.V.; Kashkarov, V.M.
1999-01-01
Kinetics and thermal oxidation of indium phosphide were investigated in gas phase of 4 group metal (lead and zirconium) salts. These compound promotors were determined to accelerate oxidation. The mechanism of the effect of promoter cation and anion constituents on formation of the resultant heterostructure were discussed [ru
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Fischetto, Giuseppe; Bermon, Stéphane
2013-10-01
During the last 2 decades, progress in deciphering the human gene map as well as the discovery of specific defective genes encoding particular proteins in some serious human diseases have resulted in attempts to treat sick patients with gene therapy. There has been considerable focus on human recombinant proteins which were gene-engineered and produced in vitro (insulin, growth hormone, insulin-like growth factor-1, erythropoietin). Unfortunately, these substances and methods also became improper tools for unscrupulous athletes. Biomedical research has focused on the possible direct insertion of gene material into the body, in order to replace some defective genes in vivo and/or to promote long-lasting endogenous synthesis of deficient proteins. Theoretically, diabetes, anaemia, muscular dystrophies, immune deficiency, cardiovascular diseases and numerous other illnesses could benefit from such innovative biomedical research, though much work remains to be done. Considering recent findings linking specific genotypes and physical performance, it is tempting to submit the young athletic population to genetic screening or, alternatively, to artificial gene expression modulation. Much research is already being conducted in order to achieve a safe transfer of genetic material to humans. This is of critical importance since uncontrolled production of the specifically coded protein, with serious secondary adverse effects (polycythaemia, acute cardiovascular problems, cancer, etc.), could occur. Other unpredictable reactions (immunogenicity of vectors or DNA-vector complex, autoimmune anaemia, production of wild genetic material) also remain possible at the individual level. Some new substances (myostatin blockers or anti-myostatin antibodies), although not gene material, might represent a useful and well-tolerated treatment to prevent progression of muscular dystrophies. Similarly, other molecules, in the roles of gene or metabolic activators [5-aminoimidazole-4
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Directory of Open Access Journals (Sweden)
Claudia Corbi Botto
2016-12-01
Full Text Available La caracterización de una población es el primer paso en el camino hacia su conservación y utilización. La raza Criollo Argentino es una de las referentes de la especie equina en Argentina y, por lo tanto, un patrimonio ganadero local que representa un recurso único en cuanto a la identidad y al sistema productivo del país. El objetivo de este trabajo fue analizar una población de caballos Criollo Argentino del norte de Argentina por medio de la caracterización de la variabilidad genética de cuatro marcadores moleculares del tipo single nucleotide polymorphism (SNP localizados en los genes que codifican para las citoquinas IL-12B y TNF-α. Se recolectaron muestras de 50 caballos Criollo Argentino y se extrajo ADN genómico que se utilizó para tipificar mediante PCR-Pirosecuenciación®, tres SNPs en el promotor del gen TNF-α y uno localizado en el exón 5 del gen IL-12B. Se estimaron frecuencias génicas y genotípicas, equilibrio de Hardy-Weinberg y diversidad genética. En IL-12B se detectaron dos alelos, mientras que en TNF-α se observaron 4 haplotipos, entre ellos uno no descripto hasta el momento en equinos. Los resultados muestran que la heterocigosis esperada fue superior en TNF-α (He=0,764 y la población se encuentra en equilibrio para el locus IL-12B (p-valor ≥0,05. Se destaca la importancia del caballo Criollo Argentino como acervo génico para el estudio de características genéticas y enfermedades de la especie equina.
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Directory of Open Access Journals (Sweden)
Wallace Helen M
2006-10-01
Full Text Available Abstract Background The potential public health benefits of targeting environmental interventions by genotype depend on the environmental and genetic contributions to the variance of common diseases, and the magnitude of any gene-environment interaction. In the absence of prior knowledge of all risk factors, twin, family and environmental data may help to define the potential limits of these benefits in a given population. However, a general methodology to analyze twin data is required because of the potential importance of gene-gene interactions (epistasis, gene-environment interactions, and conditions that break the 'equal environments' assumption for monozygotic and dizygotic twins. Method A new model for gene-gene and gene-environment interactions is developed that abandons the assumptions of the classical twin study, including Fisher's (1918 assumption that genes act as risk factors for common traits in a manner necessarily dominated by an additive polygenic term. Provided there are no confounders, the model can be used to implement a top-down approach to quantifying the potential utility of genetic prediction and prevention, using twin, family and environmental data. The results describe a solution space for each disease or trait, which may or may not include the classical twin study result. Each point in the solution space corresponds to a different model of genotypic risk and gene-environment interaction. Conclusion The results show that the potential for reducing the incidence of common diseases using environmental interventions targeted by genotype may be limited, except in special cases. The model also confirms that the importance of an individual's genotype in determining their risk of complex diseases tends to be exaggerated by the classical twin studies method, owing to the 'equal environments' assumption and the assumption of no gene-environment interaction. In addition, if phenotypes are genetically robust, because of epistasis
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Osato, Naoki
2018-01-19
Transcriptional target genes show functional enrichment of genes. However, how many and how significantly transcriptional target genes include functional enrichments are still unclear. To address these issues, I predicted human transcriptional target genes using open chromatin regions, ChIP-seq data and DNA binding sequences of transcription factors in databases, and examined functional enrichment and gene expression level of putative transcriptional target genes. Gene Ontology annotations showed four times larger numbers of functional enrichments in putative transcriptional target genes than gene expression information alone, independent of transcriptional target genes. To compare the number of functional enrichments of putative transcriptional target genes between cells or search conditions, I normalized the number of functional enrichment by calculating its ratios in the total number of transcriptional target genes. With this analysis, native putative transcriptional target genes showed the largest normalized number of functional enrichments, compared with target genes including 5-60% of randomly selected genes. The normalized number of functional enrichments was changed according to the criteria of enhancer-promoter interactions such as distance from transcriptional start sites and orientation of CTCF-binding sites. Forward-reverse orientation of CTCF-binding sites showed significantly higher normalized number of functional enrichments than the other orientations. Journal papers showed that the top five frequent functional enrichments were related to the cellular functions in the three cell types. The median expression level of transcriptional target genes changed according to the criteria of enhancer-promoter assignments (i.e. interactions) and was correlated with the changes of the normalized number of functional enrichments of transcriptional target genes. Human putative transcriptional target genes showed significant functional enrichments. Functional
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Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon
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Hackett Perry B
2006-06-01
Full Text Available Abstract Background Insertional mutagenesis techniques with transposable elements have been popular among geneticists studying model organisms from E. coli to Drosophila and, more recently, the mouse. One such element is the Sleeping Beauty (SB transposon that has been shown in several studies to be an effective insertional mutagen in the mouse germline. SB transposon vector studies have employed different functional elements and reporter molecules to disrupt and report the expression of endogenous mouse genes. We sought to generate a transposon system that would be capable of reporting the expression pattern of a mouse gene while allowing for conditional expression of a gene of interest in a tissue- or temporal-specific pattern. Results Here we report the systematic development and testing of a transposon-based gene-trap system incorporating the doxycycline-repressible Tet-Off (tTA system that is capable of activating the expression of genes under control of a Tet response element (TRE promoter. We demonstrate that the gene trap system is fully functional in vitro by introducing the "gene-trap tTA" vector into human cells by transposition and identifying clones that activate expression of a TRE-luciferase transgene in a doxycycline-dependent manner. In transgenic mice, we mobilize gene-trap tTA vectors, discover parameters that can affect germline mobilization rates, and identify candidate gene insertions to demonstrate the in vivo functionality of the vector system. We further demonstrate that the gene-trap can act as a reporter of endogenous gene expression and it can be coupled with bioluminescent imaging to identify genes with tissue-specific expression patterns. Conclusion Akin to the GAL4/UAS system used in the fly, we have made progress developing a tool for mutating and revealing the expression of mouse genes by generating the tTA transactivator in the presence of a secondary TRE-regulated reporter molecule. A vector like the gene
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Factores asociados al uso de mosquiteros en el departamento de Piura, Perú.
Directory of Open Access Journals (Sweden)
Fernando Llanos-Zavalaga
2005-06-01
Full Text Available Objetivos: El presente estudio da a conocer los factores asociados al uso de mosquiteros en el departamento de Piura. Materiales y Métodos: Estudio cualitativo realizado en Febrero y Marzo del 2000 en el departamento de Piura, Perú. Los informantes clave fueron los prestadores de salud, promotores y pobladores seleccionados aleatoriamente de dos áreas (alta y mediana endemicidad, aplicándose 12 entrevistas en profundidad (EEP, una por establecimiento, bajo el principio de saturación. Según las EEP y grupos focales (GF realizados se elaboró un mapa de conocimientos. Resultados: Se identificaron como factores asociados al uso de mosquiteros: la percepción de efectividad tanto de mosquiteros convencionales como impregnados con insecticida y la educación y supervisión continua por prestadores y promotores de salud. Los factores asociados al no uso de mosquiteros fueron: la falta de conocimiento integral sobre la enfermedad, sensación de calor y asfixia para mosquiteros convencionales, efectos adversos (reacciones dérmicas y olor del insecticida, el costo de los mosquiteros y la falta de implantación de estrategias conjuntas con aspectos educativos, de soporte, participativas y de colaboración entre los servicios de salud y la comunidad. Conclusiones: No existe buen conocimiento de la enfermedad por parte de la población pero reconocen el mosquitero como una buena medida preventiva. El conocimiento en prestadores de salud, promotores y pobladores sobre los beneficios, uso adecuado y mantenimiento de los mosquiteros impregnados con insecticida fue insuficiente, siendo necesaria la capacitación continua de esta medida preventiva contra la malaria. (Rev Med Hered 2005;16:97-106.
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Aditivos alternativos ao uso de antimicrobianos na alimentação de frangos de corte
Directory of Open Access Journals (Sweden)
Felipe Santos Dalólio
2015-07-01
Full Text Available Objetivou-se com este trabalho avaliar o efeito de diferentes aditivos alternativos aos antimicrobianos promotores de crescimento sobre o desempenho, o rendimento de carcaça e cortes e a qualidade da carne de frangos de corte no período de 1 a 42 dias de idade. Foram utilizadas 480 pintainhas de corte da linhagem Cobb 500, distribuídas em delineamento inteiramente casualizado, com seis tratamentos e quatro repetições de 20 aves cada. Foi avaliado na fase total de criação, 1 a 42 dias, o ganho de peso (GP, a conversão alimentar (CA, o consumo de ração (CR, a viabilidade criatória (VB e o índice de eficiência produtivo (IEP. O rendimento de carcaça e a qualidade da carne foi avaliado aos 42 dias de idade. Avaliou-se as características de perda de peso por cocção (PPC, a maciez objetiva (MO, a capacidade de retenção de água (CRA e o pH. Os parâmetros de desempenho, de rendimento de carcaça e cortes e de qualidade da carne não foram afetados pela suplementação dos diferentes tipos de aditivos alternativos aos antimicrobianos promotores de crescimento (P>0,05. Conclui-se que, os aditivos promotores de crescimento podem ser utilizados na alimentação de frangos de corte, em substituição ao antibiótico, sem comprometer o desempenho e características de carcaça, no período de 1 a 42 dias de idade.
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Ysunza, Alberto M; Diez-Urdanivia, Silvia; Pérez-Gil, Sara E
2017-12-01
Resumen: En este artículo presentamos el proyecto de capacitación llevado a cabo en comunidades de la sierra y costa de Oaxaca, México, desde 1991, por el Centro de Capacitación Integral para Promotores Comunitarios (CECIPROC). La decisión de hacer este trabajo en Oaxaca responde a que ese estado ocupa uno de los primeros lugares de marginación y de desnutrición en menores de 5 años. El objetivo es describir un modelo de capacitación y compartir parte de las experiencias derivadas, tanto del modelo como del trabajo realizado en las distintas áreas (nutrición y alimentación, salud comunitaria, ecología y etnobotánica, y educación y organización), por promotores mujeres y hombres en sus comunidades. La experiencia obtenida en 24 años muestra la factibilidad técnica y social del proyecto en el ámbito de la salud, el reconocimiento social del proyecto del CECIPROC como un organismo civil que ha aportado alternativas como solución a la problemática de salud, el hacer suyo el proyecto por algunos promotores y los diferentes obstáculos a los que se ha enfrentado. Enfatizamos el hecho de que la situación socioeconómica y política prevaleciente en el estado de Oaxaca es una limitante para el buen desarrollo de los programas colectivos de salud, e insistimos en la necesidad de compartir nuestras experiencias para que puedan ser utilizadas en la planificación y ejecución de otros proyectos.
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Essential Bacillus subtilis genes
DEFF Research Database (Denmark)
Kobayashi, K.; Ehrlich, S.D.; Albertini, A.
2003-01-01
To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...
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Integrative characterization of germ cell-specific genes from mouse spermatocyte UniGene library
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Eddy Edward M
2007-07-01
Full Text Available Abstract Background The primary regulator of spermatogenesis, a highly ordered and tightly regulated developmental process, is an intrinsic genetic program involving male germ cell-specific genes. Results We analyzed the mouse spermatocyte UniGene library containing 2155 gene-oriented transcript clusters. We predict that 11% of these genes are testis-specific and systematically identified 24 authentic genes specifically and abundantly expressed in the testis via in silico and in vitro approaches. Northern blot analysis disclosed various transcript characteristics, such as expression level, size and the presence of isoform. Expression analysis revealed developmentally regulated and stage-specific expression patterns in all of the genes. We further analyzed the genes at the protein and cellular levels. Transfection assays performed using GC-2 cells provided information on the cellular characteristics of the gene products. In addition, antibodies were generated against proteins encoded by some of the genes to facilitate their identification and characterization in spermatogenic cells and sperm. Our data suggest that a number of the gene products are implicated in transcriptional regulation, nuclear integrity, sperm structure and motility, and fertilization. In particular, we found for the first time that Mm.333010, predicted to contain a trypsin-like serine protease domain, is a sperm acrosomal protein. Conclusion We identify 24 authentic genes with spermatogenic cell-specific expression, and provide comprehensive information about the genes. Our findings establish a new basis for future investigation into molecular mechanisms underlying male reproduction.
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Genome-wide identification of key modulators of gene-gene interaction networks in breast cancer.
Chiu, Yu-Chiao; Wang, Li-Ju; Hsiao, Tzu-Hung; Chuang, Eric Y; Chen, Yidong
2017-10-03
With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer. However, a genome-wide identification of key modulator genes that may further unveil the landscape of modulated gene interaction is still lacking. We proposed a systematic workflow to screen for key modulators based on genome-wide gene expression profiles. We designed four modularity parameters to measure the ability of a putative modulator to perturb gene interaction networks. Applying the method to a dataset of 286 breast tumors, we comprehensively characterized the modularity parameters and identified a total of 973 key modulator genes. The modularity of these modulators was verified in three independent breast cancer datasets. ESR1, the encoding gene of ER, appeared in the list, and abundant novel modulators were illuminated. For instance, a prognostic predictor of breast cancer, SFRP1, was found the second modulator. Functional annotation analysis of the 973 modulators revealed involvements in ER-related cellular processes as well as immune- and tumor-associated functions. Here we present, as far as we know, the first comprehensive analysis of key modulator genes on a genome-wide scale. The validity of filtering parameters as well as the conservativity of modulators among cohorts were corroborated. Our data bring new insights into the modulated layer of gene-gene interaction and provide candidates for further biological investigations.
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A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.
Shibui, Tatsuro; Hara, Hiroyoshi
2017-09-01
Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017. © 2017 American Institute of Chemical Engineers.
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2014-01-01
Background Lateral Gene Transfer (LGT) has recently gained recognition as an important contributor to some eukaryote proteomes, but the mechanisms of acquisition and fixation in eukaryotic genomes are still uncertain. A previously defined norm for LGTs in microbial eukaryotes states that the majority are genes involved in metabolism, the LGTs are typically localized one by one, surrounded by vertically inherited genes on the chromosome, and phylogenetics shows that a broad collection of bacterial lineages have contributed to the transferome. Results A unique 34 kbp long fragment with 27 clustered genes (TvLF) of prokaryote origin was identified in the sequenced genome of the protozoan parasite Trichomonas vaginalis. Using a PCR based approach we confirmed the presence of the orthologous fragment in four additional T. vaginalis strains. Detailed sequence analyses unambiguously suggest that TvLF is the result of one single, recent LGT event. The proposed donor is a close relative to the firmicute bacterium Peptoniphilus harei. High nucleotide sequence similarity between T. vaginalis strains, as well as to P. harei, and the absence of homologs in other Trichomonas species, suggests that the transfer event took place after the radiation of the genus Trichomonas. Some genes have undergone pseudogenization and degradation, indicating that they may not be retained in the future. Functional annotations reveal that genes involved in informational processes are particularly prone to degradation. Conclusions We conclude that, although the majority of eukaryote LGTs are single gene occurrences, they may be acquired in clusters of several genes that are subsequently cleansed of evolutionarily less advantageous genes. PMID:24898731
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Gene-based Association Approach Identify Genes Across Stress Traits in Fruit Flies
DEFF Research Database (Denmark)
Rohde, Palle Duun; Edwards, Stefan McKinnon; Sarup, Pernille Merete
Identification of genes explaining variation in quantitative traits or genetic risk factors of human diseases requires both good phenotypic- and genotypic data, but also efficient statistical methods. Genome-wide association studies may reveal association between phenotypic variation and variation...... approach grouping variants accordingly to gene position, thus lowering the number of statistical tests performed and increasing the probability of identifying genes with small to moderate effects. Using this approach we identify numerous genes associated with different types of stresses in Drosophila...... melanogaster, but also identify common genes that affects the stress traits....
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Haisma, H J; de Hon, O
2006-04-01
Together with the rapidly increasing knowledge on genetic therapies as a promising new branch of regular medicine, the issue has arisen whether these techniques might be abused in the field of sports. Previous experiences have shown that drugs that are still in the experimental phases of research may find their way into the athletic world. Both the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) have expressed concerns about this possibility. As a result, the method of gene doping has been included in the list of prohibited classes of substances and prohibited methods. This review addresses the possible ways in which knowledge gained in the field of genetic therapies may be misused in elite sports. Many genes are readily available which may potentially have an effect on athletic performance. The sporting world will eventually be faced with the phenomena of gene doping to improve athletic performance. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping.
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Zhao, Xu; Qin, Shengying; Shi, Yongyong; Zhang, Aiping; Zhang, Jing; Bian, Li; Wan, Chunling; Feng, Guoyin; Gu, Niufan; Zhang, Guangqi; He, Guang; He, Lin
2007-07-01
Several studies have suggested the dysfunction of the GABAergic system as a risk factor in the pathogenesis of schizophrenia. In the present study, case-control association analysis was conducted in four GABAergic genes: two glutamic acid decarboxylase genes (GAD1 and GAD2), a GABA(A) receptor subunit beta2 gene (GABRB2) and a GABA(B) receptor 1 gene (GABBR1). Using a universal DNA microarray procedure we genotyped a total of 20 SNPs on the above four genes in a study involving 292 patients and 286 controls of Chinese descent. Statistically significant differences were observed in the allelic frequencies of the rs187269C/T polymorphism in the GABRB2 gene (P=0.0450, chi(2)=12.40, OR=1.65) and the -292A/C polymorphism in the GAD1 gene (P=0.0450, chi(2)=14.64 OR=1.77). In addition, using an electrophoretic mobility shift assay (EMSA), we discovered differences in the U251 nuclear protein binding to oligonucleotides representing the -292 SNP on the GAD1 gene, which suggests that the -292C allele has reduced transcription factor binding efficiency compared with the 292A allele. Using the multifactor-dimensionality reduction method (MDR), we found that the interactions among the rs187269C/T polymorphism in the GABRB2 gene, the -243A/G polymorphism in the GAD2 gene and the 27379C/T and 661C/T polymorphisms in the GAD1 gene revealed a significant association with schizophrenia (Pschizophrenia in the Chinese population.
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Exploring the key genes and pathways in enchondromas using a gene expression microarray.
Shi, Zhongju; Zhou, Hengxing; Pan, Bin; Lu, Lu; Kang, Yi; Liu, Lu; Wei, Zhijian; Feng, Shiqing
2017-07-04
Enchondromas are the most common primary benign osseous neoplasms that occur in the medullary bone; they can undergo malignant transformation into chondrosarcoma. However, enchondromas are always undetected in patients, and the molecular mechanism is unclear. To identify key genes and pathways associated with the occurrence and development of enchondromas, we downloaded the gene expression dataset GSE22855 and obtained the differentially expressed genes (DEGs) by analyzing high-throughput gene expression in enchondromas. In total, 635 genes were identified as DEGs. Of these, 225 genes (35.43%) were up-regulated, and the remaining 410 genes (64.57%) were down-regulated. We identified the predominant gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were significantly over-represented in the enchondromas samples compared with the control samples. Subsequently the top 10 core genes were identified from the protein-protein interaction (PPI) network. The enrichment analyses of the genes mainly involved in two significant modules showed that the DEGs were principally related to ribosomes, protein digestion and absorption, ECM-receptor interaction, focal adhesion, amoebiasis and the PI3K-Akt signaling pathway.Together, these data elucidate the molecular mechanisms underlying the occurrence and development of enchondromas and provide promising candidates for therapeutic intervention and prognostic evaluation. However, further experimental studies are needed to confirm these results.
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Kannan, Lavanya; Li, Hua; Rubinstein, Boris; Mushegian, Arcady
2013-01-01
Background The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. Results We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes...
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Saik, Olga V; Demenkov, Pavel S; Ivanisenko, Timofey V; Bragina, Elena Yu; Freidin, Maxim B; Goncharova, Irina A; Dosenko, Victor E; Zolotareva, Olga I; Hofestaedt, Ralf; Lavrik, Inna N; Rogaev, Evgeny I; Ivanisenko, Vladimir A
2018-02-13
Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or ~ 22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension - 713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in
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International Nuclear Information System (INIS)
Kang, Joo Hyun
2006-01-01
Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner
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PCR-based detection of gene transfer vectors: application to gene doping surveillance.
Perez, Irene C; Le Guiner, Caroline; Ni, Weiyi; Lyles, Jennifer; Moullier, Philippe; Snyder, Richard O
2013-12-01
Athletes who illicitly use drugs to enhance their athletic performance are at risk of being banned from sports competitions. Consequently, some athletes may seek new doping methods that they expect to be capable of circumventing detection. With advances in gene transfer vector design and therapeutic gene transfer, and demonstrations of safety and therapeutic benefit in humans, there is an increased probability of the pursuit of gene doping by athletes. In anticipation of the potential for gene doping, assays have been established to directly detect complementary DNA of genes that are top candidates for use in doping, as well as vector control elements. The development of molecular assays that are capable of exposing gene doping in sports can serve as a deterrent and may also identify athletes who have illicitly used gene transfer for performance enhancement. PCR-based methods to detect foreign DNA with high reliability, sensitivity, and specificity include TaqMan real-time PCR, nested PCR, and internal threshold control PCR.
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Directory of Open Access Journals (Sweden)
Craxton Molly
2007-07-01
Full Text Available Abstract Background Synaptotagmin genes are found in animal genomes and are known to function in the nervous system. Genes with a similar domain architecture as well as sequence similarity to synaptotagmin C2 domains have also been found in plant genomes. The plant genes share an additional region of sequence similarity with a group of animal genes named FAM62. FAM62 genes also have a similar domain architecture. Little is known about the functions of the plant genes and animal FAM62 genes. Indeed, many members of the large and diverse Syt gene family await functional characterization. Understanding the evolutionary relationships among these genes will help to realize the full implications of functional studies and lead to improved genome annotation. Results I collected and compared plant Syt-like sequences from the primary nucleotide sequence databases at NCBI. The collection comprises six groups of plant genes conserved in embryophytes: NTMC2Type1 to NTMC2Type6. I collected and compared metazoan FAM62 sequences and identified some similar sequences from other eukaryotic lineages. I found evidence of RNA editing and alternative splicing. I compared the intron patterns of Syt genes. I also compared Rabphilin and Doc2 genes. Conclusion Genes encoding proteins with N-terminal-transmembrane-C2 domain architectures resembling synaptotagmins, are widespread in eukaryotes. A collection of these genes is presented here. The collection provides a resource for studies of intron evolution. I have classified the collection into homologous gene families according to distinctive patterns of sequence conservation and intron position. The evolutionary histories of these gene families are traceable through the appearance of family members in different eukaryotic lineages. Assuming an intron-rich eukaryotic ancestor, the conserved intron patterns distinctive of individual gene families, indicate independent origins of Syt, FAM62 and NTMC2 genes. Resemblances
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Inferring Gene Regulatory Networks Using Conditional Regulation Pattern to Guide Candidate Genes.
Directory of Open Access Journals (Sweden)
Fei Xiao
Full Text Available Combining path consistency (PC algorithms with conditional mutual information (CMI are widely used in reconstruction of gene regulatory networks. CMI has many advantages over Pearson correlation coefficient in measuring non-linear dependence to infer gene regulatory networks. It can also discriminate the direct regulations from indirect ones. However, it is still a challenge to select the conditional genes in an optimal way, which affects the performance and computation complexity of the PC algorithm. In this study, we develop a novel conditional mutual information-based algorithm, namely RPNI (Regulation Pattern based Network Inference, to infer gene regulatory networks. For conditional gene selection, we define the co-regulation pattern, indirect-regulation pattern and mixture-regulation pattern as three candidate patterns to guide the selection of candidate genes. To demonstrate the potential of our algorithm, we apply it to gene expression data from DREAM challenge. Experimental results show that RPNI outperforms existing conditional mutual information-based methods in both accuracy and time complexity for different sizes of gene samples. Furthermore, the robustness of our algorithm is demonstrated by noisy interference analysis using different types of noise.
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Koo, Ching Lee; Liew, Mei Jing; Mohamad, Mohd Saberi; Salleh, Abdul Hakim Mohamed
2013-01-01
Recently, the greatest statistical computational challenge in genetic epidemiology is to identify and characterize the genes that interact with other genes and environment factors that bring the effect on complex multifactorial disease. These gene-gene interactions are also denoted as epitasis in which this phenomenon cannot be solved by traditional statistical method due to the high dimensionality of the data and the occurrence of multiple polymorphism. Hence, there are several machine learning methods to solve such problems by identifying such susceptibility gene which are neural networks (NNs), support vector machine (SVM), and random forests (RFs) in such common and multifactorial disease. This paper gives an overview on machine learning methods, describing the methodology of each machine learning methods and its application in detecting gene-gene and gene-environment interactions. Lastly, this paper discussed each machine learning method and presents the strengths and weaknesses of each machine learning method in detecting gene-gene interactions in complex human disease.
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A Review for Detecting Gene-Gene Interactions Using Machine Learning Methods in Genetic Epidemiology
Directory of Open Access Journals (Sweden)
Ching Lee Koo
2013-01-01
Full Text Available Recently, the greatest statistical computational challenge in genetic epidemiology is to identify and characterize the genes that interact with other genes and environment factors that bring the effect on complex multifactorial disease. These gene-gene interactions are also denoted as epitasis in which this phenomenon cannot be solved by traditional statistical method due to the high dimensionality of the data and the occurrence of multiple polymorphism. Hence, there are several machine learning methods to solve such problems by identifying such susceptibility gene which are neural networks (NNs, support vector machine (SVM, and random forests (RFs in such common and multifactorial disease. This paper gives an overview on machine learning methods, describing the methodology of each machine learning methods and its application in detecting gene-gene and gene-environment interactions. Lastly, this paper discussed each machine learning method and presents the strengths and weaknesses of each machine learning method in detecting gene-gene interactions in complex human disease.
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Pooyan, Honari; Ahmad, Ebrahimi; Azadeh, Rakhshan
2015-01-01
Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1. 4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients.
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International Nuclear Information System (INIS)
Kim, Jae Sung; Lee, Young Keun; Chung, Byung Yeoup; Lee, Young Bok; Hwang Hye Yeon
2004-10-01
The cell lines 679, 679-29 and 622-46 of L. erythrorhizon could be selected on LS agar medium for the production shikonin in cell suspension culture. The shikonin was increased moderately in suspension culture of cell line 622-46 in LS liquid medium containing BA 2 mg·L -1 and IAA 0.2 mg·L -1 in the dark, and was increased by adding 1 μM Cu 2+ and 100 μM methyl jasmonate The accumulation of shikonin in the liquid medium was increased significantly by 2 Gy irradiation to callus of cell line 622-46 and culture in LS liquid medium containing BA 2 mg·L -1 and IAA 0.2 mg·L -1 in the dark and shikonin in cell debris was higher by 16 Gy irradiation. The activity of p-hydroxybenzoate geranyltransferase was increased by irradiation of 2 Gy and 16 Gy of γ radiation. Seedling hypocotyles of L. erythrorhizon were infected with Agrogacterium rhizogenes strain 15834 harboring a binary vector with an intron bearing the GUS (β-glucuronidase) gene driven by cauliflower mosaic virus (CaMV) 35S promotor as well as the HPT (hygromycin phosphotransferase) gene as the selection marker. Hairy roots isolated were hygromycin resistant and had integrated GUS gene in DNA. The root tip grown on M-9 medium showed normal pigment production pattern in border cells and root hairs
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Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue
Directory of Open Access Journals (Sweden)
Yu Zhang
2013-12-01
Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.
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Refining discordant gene trees.
Górecki, Pawel; Eulenstein, Oliver
2014-01-01
Evolutionary studies are complicated by discordance between gene trees and the species tree in which they evolved. Dealing with discordant trees often relies on comparison costs between gene and species trees, including the well-established Robinson-Foulds, gene duplication, and deep coalescence costs. While these costs have provided credible results for binary rooted gene trees, corresponding cost definitions for non-binary unrooted gene trees, which are frequently occurring in practice, are challenged by biological realism. We propose a natural extension of the well-established costs for comparing unrooted and non-binary gene trees with rooted binary species trees using a binary refinement model. For the duplication cost we describe an efficient algorithm that is based on a linear time reduction and also computes an optimal rooted binary refinement of the given gene tree. Finally, we show that similar reductions lead to solutions for computing the deep coalescence and the Robinson-Foulds costs. Our binary refinement of Robinson-Foulds, gene duplication, and deep coalescence costs for unrooted and non-binary gene trees together with the linear time reductions provided here for computing these costs significantly extends the range of trees that can be incorporated into approaches dealing with discordance.
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Directory of Open Access Journals (Sweden)
Marion Ouedraogo
Full Text Available BACKGROUND: There has been a surge in studies linking genome structure and gene expression, with special focus on duplicated genes. Although initially duplicated from the same sequence, duplicated genes can diverge strongly over evolution and take on different functions or regulated expression. However, information on the function and expression of duplicated genes remains sparse. Identifying groups of duplicated genes in different genomes and characterizing their expression and function would therefore be of great interest to the research community. The 'Duplicated Genes Database' (DGD was developed for this purpose. METHODOLOGY: Nine species were included in the DGD. For each species, BLAST analyses were conducted on peptide sequences corresponding to the genes mapped on a same chromosome. Groups of duplicated genes were defined based on these pairwise BLAST comparisons and the genomic location of the genes. For each group, Pearson correlations between gene expression data and semantic similarities between functional GO annotations were also computed when the relevant information was available. CONCLUSIONS: The Duplicated Gene Database provides a list of co-localised and duplicated genes for several species with the available gene co-expression level and semantic similarity value of functional annotation. Adding these data to the groups of duplicated genes provides biological information that can prove useful to gene expression analyses. The Duplicated Gene Database can be freely accessed through the DGD website at http://dgd.genouest.org.
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Pan, Qian; Peng, Jin; Zhou, Xue; Yang, Hao; Zhang, Wei
2012-07-01
In order to screen out important genes from large gene data of gene microarray after nerve injury, we combine gene ontology (GO) method and computer pattern recognition technology to find key genes responding to nerve injury, and then verify one of these screened-out genes. Data mining and gene ontology analysis of gene chip data GSE26350 was carried out through MATLAB software. Cd44 was selected from screened-out key gene molecular spectrum by comparing genes' different GO terms and positions on score map of principal component. Function interferences were employed to influence the normal binding of Cd44 and one of its ligands, chondroitin sulfate C (CSC), to observe neurite extension. Gene ontology analysis showed that the first genes on score map (marked by red *) mainly distributed in molecular transducer activity, receptor activity, protein binding et al molecular function GO terms. Cd44 is one of six effector protein genes, and attracted us with its function diversity. After adding different reagents into the medium to interfere the normal binding of CSC and Cd44, varying-degree remissions of CSC's inhibition on neurite extension were observed. CSC can inhibit neurite extension through binding Cd44 on the neuron membrane. This verifies that important genes in given physiological processes can be identified by gene ontology analysis of gene chip data.
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Radiopharmaceuticals to monitor the expression of transferred genes in gene transfer therapy
International Nuclear Information System (INIS)
Wiebe, L. I.
1997-01-01
The development and application of radiopharmaceuticals has, in many instances, been based on the pharmacological properties of therapeutic agents. The molecular biology-biotechnology revolution has had an important impact on treatment of diseases, in part through the reduced toxicity of 'biologicals', in part because of their specificity for interaction at unique molecular sites and in part because of their selective delivery to the target site. Immunotherapeutic approaches include the use of monoclonal antibodies (MABs), MAB-fragments and chemotactic peptides. Such agents currently form the basis of both diagnostic and immunotherapeutic radiopharmaceuticals. More recently, gene transfer techniques have been advanced to the point that a new molecular approach, gene therapy, has become a reality. Gene therapy offers an opportunity to attack disease at its most fundamental level. The therapeutic mechanism is based on the expression of a specific gene or genes, the product of which will invoke immunological, receptor-based or enzyme-based therapeutic modalities. Several approaches to gene therapy of cancer have been envisioned, the most clinically-advanced concepts involving the introduction of genes that will encode for molecular targets nor normally found in healthy mammalian cells. A number of gene therapy clinical trials are based on the introduction of the Herpes simplex virus type-1 (HSV-1) gene that encodes for viral thymidine kinase (tk+). Once HSV-1 tk+ is expressed in the target (cancer) cell, therapy can be effected by the administration of a highly molecularly-targeted and systemically non-toxic antiviral drug such as ganciclovir. The development of radiodiagnostic imaging in gene therapy will be reviewed, using HSV-1 tk+ and radioiodinated IVFRU as a basis for development of the theme. Molecular targets that could be exploited in gene therapy, other than tk+, will be identified
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Radiopharmaceuticals to monitor the expression of transferred genes in gene transfer therapy
Energy Technology Data Exchange (ETDEWEB)
Wiebe, L I [University of Alberta, Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research
1997-10-01
The development and application of radiopharmaceuticals has, in many instances, been based on the pharmacological properties of therapeutic agents. The molecular biology-biotechnology revolution has had an important impact on treatment of diseases, in part through the reduced toxicity of `biologicals`, in part because of their specificity for interaction at unique molecular sites and in part because of their selective delivery to the target site. Immunotherapeutic approaches include the use of monoclonal antibodies (MABs), MAB-fragments and chemotactic peptides. Such agents currently form the basis of both diagnostic and immunotherapeutic radiopharmaceuticals. More recently, gene transfer techniques have been advanced to the point that a new molecular approach, gene therapy, has become a reality. Gene therapy offers an opportunity to attack disease at its most fundamental level. The therapeutic mechanism is based on the expression of a specific gene or genes, the product of which will invoke immunological, receptor-based or enzyme-based therapeutic modalities. Several approaches to gene therapy of cancer have been envisioned, the most clinically-advanced concepts involving the introduction of genes that will encode for molecular targets nor normally found in healthy mammalian cells. A number of gene therapy clinical trials are based on the introduction of the Herpes simplex virus type-1 (HSV-1) gene that encodes for viral thymidine kinase (tk+). Once HSV-1 tk+ is expressed in the target (cancer) cell, therapy can be effected by the administration of a highly molecularly-targeted and systemically non-toxic antiviral drug such as ganciclovir. The development of radiodiagnostic imaging in gene therapy will be reviewed, using HSV-1 tk+ and radioiodinated IVFRU as a basis for development of the theme. Molecular targets that could be exploited in gene therapy, other than tk+, will be identified
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Huang, Tian; Wang, Xifeng; Si, Run; Chi, Hao; Han, Binyue; Han, Haitang; Cao, Gengsheng; Zhao, Yaofeng
2018-06-01
Compared with mammals, the bird Ig genetic system relies on gene conversion to create an Ab repertoire, with inversion of the IgA-encoding gene and very few cases of Ig subclass diversification. Although gene conversion has been studied intensively, class-switch recombination, a mechanism by which the IgH C region is exchanged, has rarely been investigated in birds. In this study, based on the published genome of pigeon ( Columba livia ) and high-throughput transcriptome sequencing of immune-related tissues, we identified a transcriptionally forward α gene and found that the pigeon IgH gene locus is arranged as μ-α-υ1-υ2. In this article, we show that both DNA deletion and inversion may result from IgA and IgY class switching, and similar junction patterns were observed for both types of class-switch recombination. We also identified two subclasses of υ genes in pigeon, which share low sequence identity. Phylogenetic analysis suggests that divergence of the two pigeon υ genes occurred during the early stage of bird evolution. The data obtained in this study provide new insight into class-switch recombination and Ig gene evolution in birds. Copyright © 2018 by The American Association of Immunologists, Inc.
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Gene prediction using the Self-Organizing Map: automatic generation of multiple gene models.
Mahony, Shaun; McInerney, James O; Smith, Terry J; Golden, Aaron
2004-03-05
Many current gene prediction methods use only one model to represent protein-coding regions in a genome, and so are less likely to predict the location of genes that have an atypical sequence composition. It is likely that future improvements in gene finding will involve the development of methods that can adequately deal with intra-genomic compositional variation. This work explores a new approach to gene-prediction, based on the Self-Organizing Map, which has the ability to automatically identify multiple gene models within a genome. The current implementation, named RescueNet, uses relative synonymous codon usage as the indicator of protein-coding potential. While its raw accuracy rate can be less than other methods, RescueNet consistently identifies some genes that other methods do not, and should therefore be of interest to gene-prediction software developers and genome annotation teams alike. RescueNet is recommended for use in conjunction with, or as a complement to, other gene prediction methods.
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Directory of Open Access Journals (Sweden)
Qiusheng Kong
Full Text Available Gene expression analysis in watermelon (Citrullus lanatus fruit has drawn considerable attention with the availability of genome sequences to understand the regulatory mechanism of fruit development and to improve its quality. Real-time quantitative reverse-transcription PCR (qRT-PCR is a routine technique for gene expression analysis. However, appropriate reference genes for transcript normalization in watermelon fruits have not been well characterized. The aim of this study was to evaluate the appropriateness of 12 genes for their potential use as reference genes in watermelon fruits. Expression variations of these genes were measured in 48 samples obtained from 12 successive developmental stages of parthenocarpic and fertilized fruits of two watermelon genotypes by using qRT-PCR analysis. Considering the effects of genotype, fruit setting method, and developmental stage, geNorm determined clathrin adaptor complex subunit (ClCAC, β-actin (ClACT, and alpha tubulin 5 (ClTUA5 as the multiple reference genes in watermelon fruit. Furthermore, ClCAC alone or together with SAND family protein (ClSAND was ranked as the single or two best reference genes by NormFinder. By using the top-ranked reference genes to normalize the transcript abundance of phytoene synthase (ClPSY1, a good correlation between lycopene accumulation and ClPSY1 expression pattern was observed in ripening watermelon fruit. These validated reference genes will facilitate the accurate measurement of gene expression in the studies on watermelon fruit biology.
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Kong, Qiusheng; Yuan, Jingxian; Gao, Lingyun; Zhao, Liqiang; Cheng, Fei; Huang, Yuan; Bie, Zhilong
2015-01-01
Gene expression analysis in watermelon (Citrullus lanatus) fruit has drawn considerable attention with the availability of genome sequences to understand the regulatory mechanism of fruit development and to improve its quality. Real-time quantitative reverse-transcription PCR (qRT-PCR) is a routine technique for gene expression analysis. However, appropriate reference genes for transcript normalization in watermelon fruits have not been well characterized. The aim of this study was to evaluate the appropriateness of 12 genes for their potential use as reference genes in watermelon fruits. Expression variations of these genes were measured in 48 samples obtained from 12 successive developmental stages of parthenocarpic and fertilized fruits of two watermelon genotypes by using qRT-PCR analysis. Considering the effects of genotype, fruit setting method, and developmental stage, geNorm determined clathrin adaptor complex subunit (ClCAC), β-actin (ClACT), and alpha tubulin 5 (ClTUA5) as the multiple reference genes in watermelon fruit. Furthermore, ClCAC alone or together with SAND family protein (ClSAND) was ranked as the single or two best reference genes by NormFinder. By using the top-ranked reference genes to normalize the transcript abundance of phytoene synthase (ClPSY1), a good correlation between lycopene accumulation and ClPSY1 expression pattern was observed in ripening watermelon fruit. These validated reference genes will facilitate the accurate measurement of gene expression in the studies on watermelon fruit biology.
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Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance
2009-04-21
To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease
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Gene Composer: database software for protein construct design, codon engineering, and gene synthesis
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Mixon Mark
2009-04-01
Full Text Available Abstract Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene
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Evaluation of suitable reference genes for gene expression studies in bovine muscular tissue
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Dunner Susana
2008-09-01
Full Text Available Abstract Background Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RTqPCR is a technique used to measure mRNA species copy number as a way to determine key genes involved in different biological processes. However, the expression level of these key genes may vary among tissues or cells not only as a consequence of differential expression but also due to different factors, including choice of reference genes to normalize the expression levels of the target genes; thus the selection of reference genes is critical for expression studies. For this purpose, ten candidate reference genes were investigated in bovine muscular tissue. Results The value of stability of ten candidate reference genes included in three groups was estimated: the so called 'classical housekeeping' genes (18S, GAPDH and ACTB, a second set of genes used in expression studies conducted on other tissues (B2M, RPII, UBC and HMBS and a third set of novel genes (SF3A1, EEF1A2 and CASC3. Three different statistical algorithms were used to rank the genes by their stability measures as produced by geNorm, NormFinder and Bestkeeper. The three methods tend to agree on the most stably expressed genes and the least in muscular tissue. EEF1A2 and HMBS followed by SF3A1, ACTB, and CASC3 can be considered as stable reference genes, and B2M, RPII, UBC and GAPDH would not be appropriate. Although the rRNA-18S stability measure seems to be within the range of acceptance, its use is not recommended because its synthesis regulation is not representative of mRNA levels. Conclusion Based on geNorm algorithm, we propose the use of three genes SF3A1, EEF1A2 and HMBS as references for normalization of real-time RTqPCR in muscle expression studies.
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DEFF Research Database (Denmark)
Rattan, Suresh
2018-01-01
The idea of gerontogenes is in line with the evolutionary explanation of ageing as being an emergent phenomenon as a result of the imperfect maintenance and repair systems. Although evolutionary processes did not select for any specific ageing genes that restrict and determine the lifespan...... of an individual, the term ‘gerontogenes’ primarily refers to any genes that may seem to influence ageing and longevity, without being specifically selected for that role. Such genes can also be called ‘virtual gerontogenes’ by virtue of their indirect influence on the rate and process of ageing. More than 1000...... virtual gerontogenes have been associated with ageing and longevity in model organisms and humans. The ‘real’ genes, which do influence the essential lifespan of a species, and have been selected for in accordance with the evolutionary life history of the species, are known as the longevity assurance...
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Directory of Open Access Journals (Sweden)
Mingxin Gan
2014-01-01
Full Text Available Successful applications of the gene ontology to the inference of functional relationships between gene products in recent years have raised the need for computational methods to automatically calculate semantic similarity between gene products based on semantic similarity of gene ontology terms. Nevertheless, existing methods, though having been widely used in a variety of applications, may significantly overestimate semantic similarity between genes that are actually not functionally related, thereby yielding misleading results in applications. To overcome this limitation, we propose to represent a gene product as a vector that is composed of information contents of gene ontology terms annotated for the gene product, and we suggest calculating similarity between two gene products as the relatedness of their corresponding vectors using three measures: Pearson’s correlation coefficient, cosine similarity, and the Jaccard index. We focus on the biological process domain of the gene ontology and annotations of yeast proteins to study the effectiveness of the proposed measures. Results show that semantic similarity scores calculated using the proposed measures are more consistent with known biological knowledge than those derived using a list of existing methods, suggesting the effectiveness of our method in characterizing functional relationships between gene products.
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Learning gene regulatory networks from gene expression data using weighted consensus
Fujii, Chisato; Kuwahara, Hiroyuki; Yu, Ge; Guo, Lili; Gao, Xin
2016-01-01
An accurate determination of the network structure of gene regulatory systems from high-throughput gene expression data is an essential yet challenging step in studying how the expression of endogenous genes is controlled through a complex interaction of gene products and DNA. While numerous methods have been proposed to infer the structure of gene regulatory networks, none of them seem to work consistently over different data sets with high accuracy. A recent study to compare gene network inference methods showed that an average-ranking-based consensus method consistently performs well under various settings. Here, we propose a linear programming-based consensus method for the inference of gene regulatory networks. Unlike the average-ranking-based one, which treats the contribution of each individual method equally, our new consensus method assigns a weight to each method based on its credibility. As a case study, we applied the proposed consensus method on synthetic and real microarray data sets, and compared its performance to that of the average-ranking-based consensus and individual inference methods. Our results show that our weighted consensus method achieves superior performance over the unweighted one, suggesting that assigning weights to different individual methods rather than giving them equal weights improves the accuracy. © 2016 Elsevier B.V.
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Learning gene regulatory networks from gene expression data using weighted consensus
Fujii, Chisato
2016-08-25
An accurate determination of the network structure of gene regulatory systems from high-throughput gene expression data is an essential yet challenging step in studying how the expression of endogenous genes is controlled through a complex interaction of gene products and DNA. While numerous methods have been proposed to infer the structure of gene regulatory networks, none of them seem to work consistently over different data sets with high accuracy. A recent study to compare gene network inference methods showed that an average-ranking-based consensus method consistently performs well under various settings. Here, we propose a linear programming-based consensus method for the inference of gene regulatory networks. Unlike the average-ranking-based one, which treats the contribution of each individual method equally, our new consensus method assigns a weight to each method based on its credibility. As a case study, we applied the proposed consensus method on synthetic and real microarray data sets, and compared its performance to that of the average-ranking-based consensus and individual inference methods. Our results show that our weighted consensus method achieves superior performance over the unweighted one, suggesting that assigning weights to different individual methods rather than giving them equal weights improves the accuracy. © 2016 Elsevier B.V.
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LINE FUSION GENES: a database of LINE expression in human genes
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Park Hong-Seog
2006-06-01
Full Text Available Abstract Background Long Interspersed Nuclear Elements (LINEs are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. Description We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. Conclusion We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. Availability http://www.primate.or.kr/line
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Wang, Tao; Ho, Gloria; Ye, Kenny; Strickler, Howard; Elston, Robert C.
2008-01-01
Genetic association studies achieve an unprecedented level of resolution in mapping disease genes by genotyping dense SNPs in a gene region. Meanwhile, these studies require new powerful statistical tools that can optimally handle a large amount of information provided by genotype data. A question that arises is how to model interactions between two genes. Simply modeling all possible interactions between the SNPs in two gene regions is not desirable because a greatly increased number of degrees of freedom can be involved in the test statistic. We introduce an approach to reduce the genotype dimension in modeling interactions. The genotype compression of this approach is built upon the information on both the trait and the cross-locus gametic disequilibrium between SNPs in two interacting genes, in such a way as to parsimoniously model the interactions without loss of useful information in the process of dimension reduction. As a result, it improves power to detect association in the presence of gene-gene interactions. This approach can be similarly applied for modeling gene-environment interactions. We compare this method with other approaches: the corresponding test without modeling any interaction, that based on a saturated interaction model, that based on principal component analysis, and that based on Tukey’s 1-df model. Our simulations suggest that this new approach has superior power to that of the other methods. In an application to endometrial cancer case-control data from the Women’s Health Initiative (WHI), this approach detected AKT1 and AKT2 as being significantly associated with endometrial cancer susceptibility by taking into account their interactions with BMI. PMID:18615621
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Wang, Tao; Ho, Gloria; Ye, Kenny; Strickler, Howard; Elston, Robert C
2009-01-01
Genetic association studies achieve an unprecedented level of resolution in mapping disease genes by genotyping dense single nucleotype polymorphisms (SNPs) in a gene region. Meanwhile, these studies require new powerful statistical tools that can optimally handle a large amount of information provided by genotype data. A question that arises is how to model interactions between two genes. Simply modeling all possible interactions between the SNPs in two gene regions is not desirable because a greatly increased number of degrees of freedom can be involved in the test statistic. We introduce an approach to reduce the genotype dimension in modeling interactions. The genotype compression of this approach is built upon the information on both the trait and the cross-locus gametic disequilibrium between SNPs in two interacting genes, in such a way as to parsimoniously model the interactions without loss of useful information in the process of dimension reduction. As a result, it improves power to detect association in the presence of gene-gene interactions. This approach can be similarly applied for modeling gene-environment interactions. We compare this method with other approaches, the corresponding test without modeling any interaction, that based on a saturated interaction model, that based on principal component analysis, and that based on Tukey's one-degree-of-freedom model. Our simulations suggest that this new approach has superior power to that of the other methods. In an application to endometrial cancer case-control data from the Women's Health Initiative, this approach detected AKT1 and AKT2 as being significantly associated with endometrial cancer susceptibility by taking into account their interactions with body mass index.
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An intronic microRNA silences genes that are functionally antagonistic to its host gene.
Barik, Sailen
2008-09-01
MicroRNAs (miRNAs) are short noncoding RNAs that down-regulate gene expression by silencing specific target mRNAs. While many miRNAs are transcribed from their own genes, nearly half map within introns of 'host' genes, the significance of which remains unclear. We report that transcriptional activation of apoptosis-associated tyrosine kinase (AATK), essential for neuronal differentiation, also generates miR-338 from an AATK gene intron that silences a family of mRNAs whose protein products are negative regulators of neuronal differentiation. We conclude that an intronic miRNA, transcribed together with the host gene mRNA, may serve the interest of its host gene by silencing a cohort of genes that are functionally antagonistic to the host gene itself.
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Schaid, Daniel J; Sinnwell, Jason P; Jenkins, Gregory D; McDonnell, Shannon K; Ingle, James N; Kubo, Michiaki; Goss, Paul E; Costantino, Joseph P; Wickerham, D Lawrence; Weinshilboum, Richard M
2012-01-01
Gene-set analyses have been widely used in gene expression studies, and some of the developed methods have been extended to genome wide association studies (GWAS). Yet, complications due to linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes per gene-set, have plagued current approaches, often leading to ad hoc "fixes." To overcome some of the current limitations, we developed a general approach to scan GWAS SNP data for both gene-level and gene-set analyses, building on score statistics for generalized linear models, and taking advantage of the directed acyclic graph structure of the gene ontology when creating gene-sets. However, other types of gene-set structures can be used, such as the popular Kyoto Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes, and genes into gene-sets, but assures that positive and negative effects of genes on a trait do not cancel. To control for multiple testing of many gene-sets, we use an efficient computational strategy that accounts for LD and provides accurate step-down adjusted P-values for each gene-set. Application of our methods to two different GWAS provide guidance on the potential strengths and weaknesses of our proposed gene-set analyses. © 2011 Wiley Periodicals, Inc.
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Chapman, Joanne R; Waldenström, Jonas
2015-01-01
The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with β-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.
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Good genes, complementary genes and human mate preferences.
Roberts, S Craig; Little, Anthony C
2008-09-01
The past decade has witnessed a rapidly growing interest in the biological basis of human mate choice. Here we review recent studies that demonstrate preferences for traits which might reveal genetic quality to prospective mates, with potential but still largely unknown influence on offspring fitness. These include studies assessing visual, olfactory and auditory preferences for potential good-gene indicator traits, such as dominance or bilateral symmetry. Individual differences in these robust preferences mainly arise through within and between individual variation in condition and reproductive status. Another set of studies have revealed preferences for traits indicating complementary genes, focussing on discrimination of dissimilarity at genes in the major histocompatibility complex (MHC). As in animal studies, we are only just beginning to understand how preferences for specific traits vary and inter-relate, how consideration of good and compatible genes can lead to substantial variability in individual mate choice decisions and how preferences expressed in one sensory modality may reflect those in another. Humans may be an ideal model species in which to explore these interesting complexities.
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Gene expression studies of reference genes for quantitative real-time PCR: an overview in insects.
Shakeel, Muhammad; Rodriguez, Alicia; Tahir, Urfa Bin; Jin, Fengliang
2018-02-01
Whenever gene expression is being examined, it is essential that a normalization process is carried out to eliminate non-biological variations. The use of reference genes, such as glyceraldehyde-3-phosphate dehydrogenase, actin, and ribosomal protein genes, is the usual method of choice for normalizing gene expression. Although reference genes are used to normalize target gene expression, a major problem is that the stability of these genes differs among tissues, developmental stages, species, and responses to abiotic factors. Therefore, the use and validation of multiple reference genes are required. This review discusses the reasons that why RT-qPCR has become the preferred method for validating results of gene expression profiles, the use of specific and non-specific dyes and the importance of use of primers and probes for qPCR as well as to discuss several statistical algorithms developed to help the validation of potential reference genes. The conflicts arising in the use of classical reference genes in gene normalization and their replacement with novel references are also discussed by citing the high stability and low stability of classical and novel reference genes under various biotic and abiotic experimental conditions by employing various methods applied for the reference genes amplification.
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Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data
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Tintle Nathan L
2012-08-01
Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.
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Comprehensive analysis of gene expression patterns of hedgehog-related genes
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Baillie David
2006-10-01
Full Text Available Abstract Background The Caenorhabditis elegans genome encodes ten proteins that share sequence similarity with the Hedgehog signaling molecule through their C-terminal autoprocessing Hint/Hog domain. These proteins contain novel N-terminal domains, and C. elegans encodes dozens of additional proteins containing only these N-terminal domains. These gene families are called warthog, groundhog, ground-like and quahog, collectively called hedgehog (hh-related genes. Previously, the expression pattern of seventeen genes was examined, which showed that they are primarily expressed in the ectoderm. Results With the completion of the C. elegans genome sequence in November 2002, we reexamined and identified 61 hh-related ORFs. Further, we identified 49 hh-related ORFs in C. briggsae. ORF analysis revealed that 30% of the genes still had errors in their predictions and we improved these predictions here. We performed a comprehensive expression analysis using GFP fusions of the putative intergenic regulatory sequence with one or two transgenic lines for most genes. The hh-related genes are expressed in one or a few of the following tissues: hypodermis, seam cells, excretory duct and pore cells, vulval epithelial cells, rectal epithelial cells, pharyngeal muscle or marginal cells, arcade cells, support cells of sensory organs, and neuronal cells. Using time-lapse recordings, we discovered that some hh-related genes are expressed in a cyclical fashion in phase with molting during larval development. We also generated several translational GFP fusions, but they did not show any subcellular localization. In addition, we also studied the expression patterns of two genes with similarity to Drosophila frizzled, T23D8.1 and F27E11.3A, and the ortholog of the Drosophila gene dally-like, gpn-1, which is a heparan sulfate proteoglycan. The two frizzled homologs are expressed in a few neurons in the head, and gpn-1 is expressed in the pharynx. Finally, we compare the
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A kernel regression approach to gene-gene interaction detection for case-control studies.
Larson, Nicholas B; Schaid, Daniel J
2013-11-01
Gene-gene interactions are increasingly being addressed as a potentially important contributor to the variability of complex traits. Consequently, attentions have moved beyond single locus analysis of association to more complex genetic models. Although several single-marker approaches toward interaction analysis have been developed, such methods suffer from very high testing dimensionality and do not take advantage of existing information, notably the definition of genes as functional units. Here, we propose a comprehensive family of gene-level score tests for identifying genetic elements of disease risk, in particular pairwise gene-gene interactions. Using kernel machine methods, we devise score-based variance component tests under a generalized linear mixed model framework. We conducted simulations based upon coalescent genetic models to evaluate the performance of our approach under a variety of disease models. These simulations indicate that our methods are generally higher powered than alternative gene-level approaches and at worst competitive with exhaustive SNP-level (where SNP is single-nucleotide polymorphism) analyses. Furthermore, we observe that simulated epistatic effects resulted in significant marginal testing results for the involved genes regardless of whether or not true main effects were present. We detail the benefits of our methods and discuss potential genome-wide analysis strategies for gene-gene interaction analysis in a case-control study design. © 2013 WILEY PERIODICALS, INC.
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Directory of Open Access Journals (Sweden)
Gutiérrez Rodrigo A
2008-09-01
Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant
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Gene Expression Commons: an open platform for absolute gene expression profiling.
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Jun Seita
Full Text Available Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000 of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/ which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.
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Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo
2013-08-10
Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. Copyright © 2013 Elsevier B.V. All rights reserved.
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Calcisponges have a ParaHox gene and dynamic expression of dispersed NK homeobox genes.
Fortunato, Sofia A V; Adamski, Marcin; Ramos, Olivia Mendivil; Leininger, Sven; Liu, Jing; Ferrier, David E K; Adamska, Maja
2014-10-30
Sponges are simple animals with few cell types, but their genomes paradoxically contain a wide variety of developmental transcription factors, including homeobox genes belonging to the Antennapedia (ANTP) class, which in bilaterians encompass Hox, ParaHox and NK genes. In the genome of the demosponge Amphimedon queenslandica, no Hox or ParaHox genes are present, but NK genes are linked in a tight cluster similar to the NK clusters of bilaterians. It has been proposed that Hox and ParaHox genes originated from NK cluster genes after divergence of sponges from the lineage leading to cnidarians and bilaterians. On the other hand, synteny analysis lends support to the notion that the absence of Hox and ParaHox genes in Amphimedon is a result of secondary loss (the ghost locus hypothesis). Here we analysed complete suites of ANTP-class homeoboxes in two calcareous sponges, Sycon ciliatum and Leucosolenia complicata. Our phylogenetic analyses demonstrate that these calcisponges possess orthologues of bilaterian NK genes (Hex, Hmx and Msx), a varying number of additional NK genes and one ParaHox gene, Cdx. Despite the generation of scaffolds spanning multiple genes, we find no evidence of clustering of Sycon NK genes. All Sycon ANTP-class genes are developmentally expressed, with patterns suggesting their involvement in cell type specification in embryos and adults, metamorphosis and body plan patterning. These results demonstrate that ParaHox genes predate the origin of sponges, thus confirming the ghost locus hypothesis, and highlight the need to analyse the genomes of multiple sponge lineages to obtain a complete picture of the ancestral composition of the first animal genome.
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Preparation and characterization of magnetic gene vectors for targeting gene delivery
Energy Technology Data Exchange (ETDEWEB)
Zheng, S.W.; Liu, G. [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); Hong, R.Y., E-mail: rhong@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); State Key Laboratory of Multi-phase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080 (China); Li, H.Z. [State Key Laboratory of Multi-phase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080 (China); Li, Y.G., E-mail: ilguoliang@sohu.com [Department of radiology, the First Affiliated Hospital of Soochow University, Suzhou 215007 (China); Wei, D.G., E-mail: dougwei@deas.harvard.edu [Center for Nanoscale Systems, School of Engineering and Applied Science, Harvard University, 11 Oxford Street, Cambridge, MA 02139 (United States)
2012-10-15
Highlights: Black-Right-Pointing-Pointer PEI is ideal candidate polymer for the design of gene delivery systems. Black-Right-Pointing-Pointer PEI-CMD-MNPs exhibited a typical superparamagnetic behavior. Black-Right-Pointing-Pointer PEI-CMD-MNPs were well stable over the entire range of pH and NaCl concentration. Black-Right-Pointing-Pointer DNA-PEI-CMD-MNPs transfected cells by a magnet have higher transfection efficiency and gene expression efficiency. - Abstract: The PEI-CMD-MNPs were successfully prepared by the surface modification of magnetic Fe{sub 3}O{sub 4} nanoparticles with carboxymethyl dextran (CMD) and polyethyleneimine (PEI). The PEI-CMD-MNPs polyplexes exhibited a typical superparamagnetic behavior and were well stable over the entire range of pH and NaCl concentration. These PEI-CMD-MNPs were used as magnetic gene vectors for targeting gene delivery. The prepared MNPs at different surface modification stages were characterized using Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), field emissions canning electron microscopy (FE-SEM), powder X-ray diffraction (XRD) and dynamic laser light scattering (DLS) analysis. The magnetic properties were studied by vibrating sample magnetometer (VSM). To evaluate the performance of the magnetic nanoparticles as gene transfer vector, the PEI-CMD-MNPs were used to delivery green fluorescent protein (GFP) gene into BHK21 cells. The expression of GFP gene was detected by fluorescence microscope. DNA-PEI-CMD-MNPs polyplexes absorbed by the cells were also monitored by Magnetic resonance imaging (MRI). The transfection efficiency and gene expression efficiency of that transfected with a magnet were much higher than that of standard transfection.
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Investigating Gene Function in Cereal Rust Fungi by Plant-Mediated Virus-Induced Gene Silencing.
Panwar, Vinay; Bakkeren, Guus
2017-01-01
Cereal rust fungi are destructive pathogens, threatening grain production worldwide. Targeted breeding for resistance utilizing host resistance genes has been effective. However, breakdown of resistance occurs frequently and continued efforts are needed to understand how these fungi overcome resistance and to expand the range of available resistance genes. Whole genome sequencing, transcriptomic and proteomic studies followed by genome-wide computational and comparative analyses have identified large repertoire of genes in rust fungi among which are candidates predicted to code for pathogenicity and virulence factors. Some of these genes represent defence triggering avirulence effectors. However, functions of most genes still needs to be assessed to understand the biology of these obligate biotrophic pathogens. Since genetic manipulations such as gene deletion and genetic transformation are not yet feasible in rust fungi, performing functional gene studies is challenging. Recently, Host-induced gene silencing (HIGS) has emerged as a useful tool to characterize gene function in rust fungi while infecting and growing in host plants. We utilized Barley stripe mosaic virus-mediated virus induced gene silencing (BSMV-VIGS) to induce HIGS of candidate rust fungal genes in the wheat host to determine their role in plant-fungal interactions. Here, we describe the methods for using BSMV-VIGS in wheat for functional genomics study in cereal rust fungi.
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Newer Gene Editing Technologies toward HIV Gene Therapy
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Premlata Shankar
2013-11-01
Full Text Available Despite the great success of highly active antiretroviral therapy (HAART in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.
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Validation of suitable reference genes for quantitative gene expression analysis in Panax ginseng
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Meizhen eWang
2016-01-01
Full Text Available Reverse transcription-qPCR (RT-qPCR has become a popular method for gene expression studies. Its results require data normalization by housekeeping genes. No single gene is proved to be stably expressed under all experimental conditions. Therefore, systematic evaluation of reference genes is necessary. With the aim to identify optimum reference genes for RT-qPCR analysis of gene expression in different tissues of Panax ginseng and the seedlings grown under heat stress, we investigated the expression stability of eight candidate reference genes, including elongation factor 1-beta (EF1-β, elongation factor 1-gamma (EF1-γ, eukaryotic translation initiation factor 3G (IF3G, eukaryotic translation initiation factor 3B (IF3B, actin (ACT, actin11 (ACT11, glyceraldehyde-3-phosphate dehydrogenase (GAPDH and cyclophilin ABH-like protein (CYC, using four widely used computational programs: geNorm, Normfinder, BestKeeper, and the comparative ΔCt method. The results were then integrated using the web-based tool RefFinder. As a result, EF1-γ, IF3G and EF1-β were the three most stable genes in different tissues of P. ginseng, while IF3G, ACT11 and GAPDH were the top three-ranked genes in seedlings treated with heat. Using three better reference genes alone or in combination as internal control, we examined the expression profiles of MAR, a multiple function-associated mRNA-like non-coding RNA (mlncRNA in P. ginseng. Taken together, we recommended EF1-γ/IF3G and IF3G/ACT11 as the suitable pair of reference genes for RT-qPCR analysis of gene expression in different tissues of P. ginseng and the seedlings grown under heat stress, respectively. The results serve as a foundation for future studies on P. ginseng functional genomics.
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Gene analogue finder: a GRID solution for finding functionally analogous gene products
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Licciulli Flavio
2007-09-01
Full Text Available Abstract Background To date more than 2,1 million gene products from more than 100000 different species have been described specifying their function, the processes they are involved in and their cellular localization using a very well defined and structured vocabulary, the gene ontology (GO. Such vast, well defined knowledge opens the possibility of compare gene products at the level of functionality, finding gene products which have a similar function or are involved in similar biological processes without relying on the conventional sequence similarity approach. Comparisons within such a large space of knowledge are highly data and computing intensive. For this reason this project was based upon the use of the computational GRID, a technology offering large computing and storage resources. Results We have developed a tool, GENe AnaloGue FINdEr (ENGINE that parallelizes the search process and distributes the calculation and data over the computational GRID, splitting the process into many sub-processes and joining the calculation and the data on the same machine and therefore completing the whole search in about 3 days instead of occupying one single machine for more than 5 CPU years. The results of the functional comparison contain potential functional analogues for more than 79000 gene products from the most important species. 46% of the analyzed gene products are well enough described for such an analysis to individuate functional analogues, such as well-known members of the same gene family, or gene products with similar functions which would never have been associated by standard methods. Conclusion ENGINE has produced a list of potential functionally analogous relations between gene products within and between species using, in place of the sequence, the gene description of the GO, thus demonstrating the potential of the GO. However, the current limiting factor is the quality of the associations of many gene products from non
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Energy Technology Data Exchange (ETDEWEB)
Qiyue, Hu; Mingyue, Lun [Suzhou Medical Coll., JS (China)
1995-07-01
Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G{sub 1} phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM{sub 9} cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation.
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International Nuclear Information System (INIS)
Hu Qiyue; Lun Mingyue
1995-07-01
Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G 1 phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM 9 cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation
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Directory of Open Access Journals (Sweden)
Benjamin Mayne
2016-10-01
Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.
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Appendix 1：Upregulated genes in gene expression profile （P<0.05 ...
Indian Academy of Sciences (India)
lazi
Appendix 1: Upregulated genes in gene expression profile«P2）. Probe_s. Gene_Symbol pvalues foldchange. Probe_S. et_ID. Gene_Symbol pvalues foldchange. et_ID. 1370355. 1393751. Scd1. 1.35E-04. 25.77. Loc1009122508.06E-03. 2.55. -at at. 1398250. 1370870. Acot1. 2.43E-02. 12.18. Me1.
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Evolution of stress-regulated gene expression in duplicate genes of Arabidopsis thaliana.
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Cheng Zou
2009-07-01
Full Text Available Due to the selection pressure imposed by highly variable environmental conditions, stress sensing and regulatory response mechanisms in plants are expected to evolve rapidly. One potential source of innovation in plant stress response mechanisms is gene duplication. In this study, we examined the evolution of stress-regulated gene expression among duplicated genes in the model plant Arabidopsis thaliana. Key to this analysis was reconstructing the putative ancestral stress regulation pattern. By comparing the expression patterns of duplicated genes with the patterns of their ancestors, duplicated genes likely lost and gained stress responses at a rapid rate initially, but the rate is close to zero when the synonymous substitution rate (a proxy for time is > approximately 0.8. When considering duplicated gene pairs, we found that partitioning of putative ancestral stress responses occurred more frequently compared to cases of parallel retention and loss. Furthermore, the pattern of stress response partitioning was extremely asymmetric. An analysis of putative cis-acting DNA regulatory elements in the promoters of the duplicated stress-regulated genes indicated that the asymmetric partitioning of ancestral stress responses are likely due, at least in part, to differential loss of DNA regulatory elements; the duplicated genes losing most of their stress responses were those that had lost more of the putative cis-acting elements. Finally, duplicate genes that lost most or all of the ancestral responses are more likely to have gained responses to other stresses. Therefore, the retention of duplicates that inherit few or no functions seems to be coupled to neofunctionalization. Taken together, our findings provide new insight into the patterns of evolutionary changes in gene stress responses after duplication and lay the foundation for testing the adaptive significance of stress regulatory changes under highly variable biotic and abiotic environments.
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International Nuclear Information System (INIS)
Yanai, Itai; Camacho, Carlos J.; DeLisi, Charles
2000-01-01
A universal property of microbial genomes is the considerable fraction of genes that are homologous to other genes within the same genome. The process by which these homologues are generated is not well understood, but sequence analysis of 20 microbial genomes unveils a recurrent distribution of gene family sizes. We show that a simple evolutionary model based on random gene duplication and point mutations fully accounts for these distributions and permits predictions for the number of gene families in genomes not yet complete. Our findings are consistent with the notion that a genome evolves from a set of precursor genes to a mature size by gene duplications and increasing modifications. (c) 2000 The American Physical Society
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Energy Technology Data Exchange (ETDEWEB)
Yanai, Itai; Camacho, Carlos J.; DeLisi, Charles
2000-09-18
A universal property of microbial genomes is the considerable fraction of genes that are homologous to other genes within the same genome. The process by which these homologues are generated is not well understood, but sequence analysis of 20 microbial genomes unveils a recurrent distribution of gene family sizes. We show that a simple evolutionary model based on random gene duplication and point mutations fully accounts for these distributions and permits predictions for the number of gene families in genomes not yet complete. Our findings are consistent with the notion that a genome evolves from a set of precursor genes to a mature size by gene duplications and increasing modifications. (c) 2000 The American Physical Society.
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CAR gene cluster and transcript levels of carotenogenic genes in Rhodotorula mucilaginosa.
Landolfo, Sara; Ianiri, Giuseppe; Camiolo, Salvatore; Porceddu, Andrea; Mulas, Giuliana; Chessa, Rossella; Zara, Giacomo; Mannazzu, Ilaria
2018-01-01
A molecular approach was applied to the study of the carotenoid biosynthetic pathway of Rhodotorula mucilaginosa. At first, functional annotation of the genome of R. mucilaginosa C2.5t1 was carried out and gene ontology categories were assigned to 4033 predicted proteins. Then, a set of genes involved in different steps of carotenogenesis was identified and those coding for phytoene desaturase, phytoene synthase/lycopene cyclase and carotenoid dioxygenase (CAR genes) proved to be clustered within a region of ~10 kb. Quantitative PCR of the genes involved in carotenoid biosynthesis showed that genes coding for 3-hydroxy-3-methylglutharyl-CoA reductase and mevalonate kinase are induced during exponential phase while no clear trend of induction was observed for phytoene synthase/lycopene cyclase and phytoene dehydrogenase encoding genes. Thus, in R. mucilaginosa the induction of genes involved in the early steps of carotenoid biosynthesis is transient and accompanies the onset of carotenoid production, while that of CAR genes does not correlate with the amount of carotenoids produced. The transcript levels of genes coding for carotenoid dioxygenase, superoxide dismutase and catalase A increased during the accumulation of carotenoids, thus suggesting the activation of a mechanism aimed at the protection of cell structures from oxidative stress during carotenoid biosynthesis. The data presented herein, besides being suitable for the elucidation of the mechanisms that underlie carotenoid biosynthesis, will contribute to boosting the biotechnological potential of this yeast by improving the outcome of further research efforts aimed at also exploring other features of interest.
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Validation of commonly used reference genes for sleep-related gene expression studies
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Castro Rosa MRPS
2009-05-01
Full Text Available Abstract Background Sleep is a restorative process and is essential for maintenance of mental and physical health. In an attempt to understand the complexity of sleep, multidisciplinary strategies, including genetic approaches, have been applied to sleep research. Although quantitative real time PCR has been used in previous sleep-related gene expression studies, proper validation of reference genes is currently lacking. Thus, we examined the effect of total or paradoxical sleep deprivation (TSD or PSD on the expression stability of the following frequently used reference genes in brain and blood: beta-actin (b-actin, beta-2-microglobulin (B2M, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, and hypoxanthine guanine phosphoribosyl transferase (HPRT. Results Neither TSD nor PSD affected the expression stability of all tested genes in both tissues indicating that b-actin, B2M, GAPDH and HPRT are appropriate reference genes for the sleep-related gene expression studies. In order to further verify these results, the relative expression of brain derived neurotrophic factor (BDNF and glycerol-3-phosphate dehydrogenase1 (GPD1 was evaluated in brain and blood, respectively. The normalization with each of four reference genes produced similar pattern of expression in control and sleep deprived rats, but subtle differences in the magnitude of expression fold change were observed which might affect the statistical significance. Conclusion This study demonstrated that sleep deprivation does not alter the expression stability of commonly used reference genes in brain and blood. Nonetheless, the use of multiple reference genes in quantitative RT-PCR is required for the accurate results.
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Genes2Networks: connecting lists of gene symbols using mammalian protein interactions databases
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Ma'ayan Avi
2007-10-01
Full Text Available Abstract Background In recent years, mammalian protein-protein interaction network databases have been developed. The interactions in these databases are either extracted manually from low-throughput experimental biomedical research literature, extracted automatically from literature using techniques such as natural language processing (NLP, generated experimentally using high-throughput methods such as yeast-2-hybrid screens, or interactions are predicted using an assortment of computational approaches. Genes or proteins identified as significantly changing in proteomic experiments, or identified as susceptibility disease genes in genomic studies, can be placed in the context of protein interaction networks in order to assign these genes and proteins to pathways and protein complexes. Results Genes2Networks is a software system that integrates the content of ten mammalian interaction network datasets. Filtering techniques to prune low-confidence interactions were implemented. Genes2Networks is delivered as a web-based service using AJAX. The system can be used to extract relevant subnetworks created from "seed" lists of human Entrez gene symbols. The output includes a dynamic linkable three color web-based network map, with a statistical analysis report that identifies significant intermediate nodes used to connect the seed list. Conclusion Genes2Networks is powerful web-based software that can help experimental biologists to interpret lists of genes and proteins such as those commonly produced through genomic and proteomic experiments, as well as lists of genes and proteins associated with disease processes. This system can be used to find relationships between genes and proteins from seed lists, and predict additional genes or proteins that may play key roles in common pathways or protein complexes.
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EXSPRESSION OF MDR-GENES AND MONORESISTANCE GENES IN NON-SMALL-CELL LUNG CANCER
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E. L. Yumov
2014-01-01
Full Text Available We studied the expression of multidrug resistance genes (MDR and monoresistance genes in normal bronchial tissue and tumor tissue of the non-small cell lung cancer (NSCLC after neoadjuvant chemotherapy (NACT (vinorelbine-carboplatine. The study included 30 patients with NSCLC (Т2–4N0–3M0. Normal bronchial tissue, normal lung tissue and tumor tissue collected during surgery following neoadjuvant chemotherapy (NACT served as a material of the study. The expression levels of MDR genes (ABCB1, ABCB2, ABCC1, ABCC2, ABCС5, ABCG1, ABCG2, GSTP and MVP, and monoresistance genes (BRCA1, ERCC1, RRM1, TOP1, TOP2A, TUBB3 and TYMS were estimated by quantitative reverse transcriptase PCR (RT-qPCR. The expression levels of some MDR genes and monoresistance genes (АВСВ1, АВСВ2, ABCG1, ERCC1, GSTP1 and MVP were significantly higher in the bronchi than in tumor tissue. The expression of ABCG1, ABCG2 and ERCC1 genes was higher in patients with T1-2 cancer than in patients with T3-4 cancer. Patients with adenocarcinoma had higher expression of BRCA1, MVP and ABCB1 genes than patients with squamous cell lung cancer. A tendency towards reduction in the expression level of MDR-genes and monoresistance genes was observed in patients with partial tumor regression compared to that observed in patients with stable disease. These findings were consistent with the previous data on reduction in the MDR-gene expression after chemotherapy with a good response in breast cancer patients.
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Jiang, Jinjin; Wang, Yue; Zhu, Bao; Fang, Tingting; Fang, Yujie; Wang, Youping
2015-01-27
Brassica includes many successfully cultivated crop species of polyploid origin, either by ancestral genome triplication or by hybridization between two diploid progenitors, displaying complex repetitive sequences and transposons. The U's triangle, which consists of three diploids and three amphidiploids, is optimal for the analysis of complicated genomes after polyploidization. Next-generation sequencing enables the transcriptome profiling of polyploids on a global scale. We examined the gene expression patterns of three diploids (Brassica rapa, B. nigra, and B. oleracea) and three amphidiploids (B. napus, B. juncea, and B. carinata) via digital gene expression analysis. In total, the libraries generated between 5.7 and 6.1 million raw reads, and the clean tags of each library were mapped to 18547-21995 genes of B. rapa genome. The unambiguous tag-mapped genes in the libraries were compared. Moreover, the majority of differentially expressed genes (DEGs) were explored among diploids as well as between diploids and amphidiploids. Gene ontological analysis was performed to functionally categorize these DEGs into different classes. The Kyoto Encyclopedia of Genes and Genomes analysis was performed to assign these DEGs into approximately 120 pathways, among which the metabolic pathway, biosynthesis of secondary metabolites, and peroxisomal pathway were enriched. The non-additive genes in Brassica amphidiploids were analyzed, and the results indicated that orthologous genes in polyploids are frequently expressed in a non-additive pattern. Methyltransferase genes showed differential expression pattern in Brassica species. Our results provided an understanding of the transcriptome complexity of natural Brassica species. The gene expression changes in diploids and allopolyploids may help elucidate the morphological and physiological differences among Brassica species.
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International Nuclear Information System (INIS)
Vaiphei, S. Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Sharan, R.N.; Chaubey, R.C.; Kma, L.
2015-01-01
In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving 60 Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of 60 Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min -1 at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. (author)
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Smith, Gilbert; Macias-Muñoz, Aide; Briscoe, Adriana D
2016-09-02
Heliconius possess a unique ability among butterflies to feed on pollen. Pollen feeding significantly extends their lifespan, and is thought to have been important to the diversification of the genus. We used RNA sequencing to examine feeding-related gene expression in the mouthparts of four species of Heliconius and one nonpollen feeding species, Eueides isabella We hypothesized that genes involved in morphology and protein metabolism might be upregulated in Heliconius because they have longer proboscides than Eueides, and because pollen contains more protein than nectar. Using de novo transcriptome assemblies, we tested these hypotheses by comparing gene expression in mouthparts against antennae and legs. We first looked for genes upregulated in mouthparts across all five species and discovered several hundred genes, many of which had functional annotations involving metabolism of proteins (cocoonase), lipids, and carbohydrates. We then looked specifically within Heliconius where we found eleven common upregulated genes with roles in morphology (CPR cuticle proteins), behavior (takeout-like), and metabolism (luciferase-like). Closer examination of these candidates revealed that cocoonase underwent several duplications along the lineage leading to heliconiine butterflies, including two Heliconius-specific duplications. Luciferase-like genes also underwent duplication within lepidopterans, and upregulation in Heliconius mouthparts. Reverse-transcription PCR confirmed that three cocoonases, a peptidase, and one luciferase-like gene are expressed in the proboscis with little to no expression in labial palps and salivary glands. Our results suggest pollen feeding, like other dietary specializations, was likely facilitated by adaptive expansions of preexisting genes-and that the butterfly proboscis is involved in digestive enzyme production. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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Directory of Open Access Journals (Sweden)
Zhimin Dai
Full Text Available Biological nitrogen fixation is an essential function of acid mine drainage (AMD microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community.
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Dai, Zhimin; Guo, Xue; Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan
2014-01-01
Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community.
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Yin, Huaqun; Liang, Yili; Cong, Jing; Liu, Xueduan
2014-01-01
Biological nitrogen fixation is an essential function of acid mine drainage (AMD) microbial communities. However, most acidophiles in AMD environments are uncultured microorganisms and little is known about the diversity of nitrogen-fixing genes and structure of nif gene cluster in AMD microbial communities. In this study, we used metagenomic sequencing to isolate nif genes in the AMD microbial community from Dexing Copper Mine, China. Meanwhile, a metagenome microarray containing 7,776 large-insertion fosmids was constructed to screen novel nif gene clusters. Metagenomic analyses revealed that 742 sequences were identified as nif genes including structural subunit genes nifH, nifD, nifK and various additional genes. The AMD community is massively dominated by the genus Acidithiobacillus. However, the phylogenetic diversity of nitrogen-fixing microorganisms is much higher than previously thought in the AMD community. Furthermore, a 32.5-kb genomic sequence harboring nif, fix and associated genes was screened by metagenome microarray. Comparative genome analysis indicated that most nif genes in this cluster are most similar to those of Herbaspirillum seropedicae, but the organization of the nif gene cluster had significant differences from H. seropedicae. Sequence analysis and reverse transcription PCR also suggested that distinct transcription units of nif genes exist in this gene cluster. nifQ gene falls into the same transcription unit with fixABCX genes, which have not been reported in other diazotrophs before. All of these results indicated that more novel diazotrophs survive in the AMD community. PMID:24498417
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Evolutionary history of chordate PAX genes: dynamics of change in a complex gene family.
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Vanessa Rodrigues Paixão-Côrtes
Full Text Available Paired box (PAX genes are transcription factors that play important roles in embryonic development. Although the PAX gene family occurs in animals only, it is widely distributed. Among the vertebrates, its 9 genes appear to be the product of complete duplication of an original set of 4 genes, followed by an additional partial duplication. Although some studies of PAX genes have been conducted, no comprehensive survey of these genes across the entire taxonomic unit has yet been attempted. In this study, we conducted a detailed comparison of PAX sequences from 188 chordates, which revealed restricted variation. The absence of PAX4 and PAX8 among some species of reptiles and birds was notable; however, all 9 genes were present in all 74 mammalian genomes investigated. A search for signatures of selection indicated that all genes are subject to purifying selection, with a possible constraint relaxation in PAX4, PAX7, and PAX8. This result indicates asymmetric evolution of PAX family genes, which can be associated with the emergence of adaptive novelties in the chordate evolutionary trajectory.
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Directory of Open Access Journals (Sweden)
Jean-François Gout
2010-05-01
Full Text Available The understanding of selective constraints affecting genes is a major issue in biology. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated. Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: the rate of gene losses after whole genome duplications in the Paramecium lineage is negatively correlated to the level of gene expression, and this relationship is not a byproduct of other factors known to affect the fate of gene duplicates. This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: in yeast, we find a clear relationship between gene expression level and the fitness impact of reduction in gene dosage. To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression. This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.
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Directory of Open Access Journals (Sweden)
Jing Zhao
Full Text Available Many diseases have complex genetic causes, where a set of alleles can affect the propensity of getting the disease. The identification of such disease genes is important to understand the mechanistic and evolutionary aspects of pathogenesis, improve diagnosis and treatment of the disease, and aid in drug discovery. Current genetic studies typically identify chromosomal regions associated specific diseases. But picking out an unknown disease gene from hundreds of candidates located on the same genomic interval is still challenging. In this study, we propose an approach to prioritize candidate genes by integrating data of gene expression level, protein-protein interaction strength and known disease genes. Our method is based only on two, simple, biologically motivated assumptions--that a gene is a good disease-gene candidate if it is differentially expressed in cases and controls, or that it is close to other disease-gene candidates in its protein interaction network. We tested our method on 40 diseases in 58 gene expression datasets of the NCBI Gene Expression Omnibus database. On these datasets our method is able to predict unknown disease genes as well as identifying pleiotropic genes involved in the physiological cellular processes of many diseases. Our study not only provides an effective algorithm for prioritizing candidate disease genes but is also a way to discover phenotypic interdependency, cooccurrence and shared pathophysiology between different disorders.
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Directory of Open Access Journals (Sweden)
Ettore Mosca
2017-09-01
Full Text Available Autism spectrum disorder (ASD is marked by a strong genetic heterogeneity, which is underlined by the low overlap between ASD risk gene lists proposed in different studies. In this context, molecular networks can be used to analyze the results of several genome-wide studies in order to underline those network regions harboring genetic variations associated with ASD, the so-called “disease modules.” In this work, we used a recent network diffusion-based approach to jointly analyze multiple ASD risk gene lists. We defined genome-scale prioritizations of human genes in relation to ASD genes from multiple studies, found significantly connected gene modules associated with ASD and predicted genes functionally related to ASD risk genes. Most of them play a role in synapsis and neuronal development and function; many are related to syndromes that can be in comorbidity with ASD and the remaining are involved in epigenetics, cell cycle, cell adhesion and cancer.
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Johnson, Emma C; Border, Richard; Melroy-Greif, Whitney E; de Leeuw, Christiaan A; Ehringer, Marissa A; Keller, Matthew C
2017-11-15
A recent analysis of 25 historical candidate gene polymorphisms for schizophrenia in the largest genome-wide association study conducted to date suggested that these commonly studied variants were no more associated with the disorder than would be expected by chance. However, the same study identified other variants within those candidate genes that demonstrated genome-wide significant associations with schizophrenia. As such, it is possible that variants within historic schizophrenia candidate genes are associated with schizophrenia at levels above those expected by chance, even if the most-studied specific polymorphisms are not. The present study used association statistics from the largest schizophrenia genome-wide association study conducted to date as input to a gene set analysis to investigate whether variants within schizophrenia candidate genes are enriched for association with schizophrenia. As a group, variants in the most-studied candidate genes were no more associated with schizophrenia than were variants in control sets of noncandidate genes. While a small subset of candidate genes did appear to be significantly associated with schizophrenia, these genes were not particularly noteworthy given the large number of more strongly associated noncandidate genes. The history of schizophrenia research should serve as a cautionary tale to candidate gene investigators examining other phenotypes: our findings indicate that the most investigated candidate gene hypotheses of schizophrenia are not well supported by genome-wide association studies, and it is likely that this will be the case for other complex traits as well. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Are TMEM genes potential candidate genes for panic disorder?
DEFF Research Database (Denmark)
NO, Gregersen; Buttenschøn, Henriette Nørmølle; Hedemand, Anne
2014-01-01
We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...
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Kwon, Minseok; Leem, Sangseob; Yoon, Joon; Park, Taesung
2018-03-19
With the rapid advancement of array-based genotyping techniques, genome-wide association studies (GWAS) have successfully identified common genetic variants associated with common complex diseases. However, it has been shown that only a small proportion of the genetic etiology of complex diseases could be explained by the genetic factors identified from GWAS. This missing heritability could possibly be explained by gene-gene interaction (epistasis) and rare variants. There has been an exponential growth of gene-gene interaction analysis for common variants in terms of methodological developments and practical applications. Also, the recent advancement of high-throughput sequencing technologies makes it possible to conduct rare variant analysis. However, little progress has been made in gene-gene interaction analysis for rare variants. Here, we propose GxGrare which is a new gene-gene interaction method for the rare variants in the framework of the multifactor dimensionality reduction (MDR) analysis. The proposed method consists of three steps; 1) collapsing the rare variants, 2) MDR analysis for the collapsed rare variants, and 3) detect top candidate interaction pairs. GxGrare can be used for the detection of not only gene-gene interactions, but also interactions within a single gene. The proposed method is illustrated with 1080 whole exome sequencing data of the Korean population in order to identify causal gene-gene interaction for rare variants for type 2 diabetes. The proposed GxGrare performs well for gene-gene interaction detection with collapsing of rare variants. GxGrare is available at http://bibs.snu.ac.kr/software/gxgrare which contains simulation data and documentation. Supported operating systems include Linux and OS X.
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A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer
Directory of Open Access Journals (Sweden)
Mary Qu Yang
Full Text Available Clear cell renal cell carcinoma (ccRCC is the most common and most aggressive form of renal cell cancer (RCC. The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1, as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways. Keywords: ccRCC, Causative mutation, Pathways, Protein-protein interaction, Gene module, eQTL
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Clock gene modulates roles of OXTR and AVPR1b genes in prosociality.
Directory of Open Access Journals (Sweden)
Haipeng Ci
Full Text Available BACKGROUND: The arginine vasopressin receptor (AVPR and oxytocin receptor (OXTR genes have been demonstrated to contribute to prosocial behavior. Recent research has focused on the manner by which these simple receptor genes influence prosociality, particularly with regard to the AVP system, which is modulated by the clock gene. The clock gene is responsible for regulating the human biological clock, affecting sleep, emotion and behavior. The current study examined in detail whether the influences of the OXTR and AVPR1b genes on prosociality are dependent on the clock gene. METHODOLOGY/PRINCIPAL FINDINGS: This study assessed interactions between the clock gene (rs1801260, rs6832769 and the OXTR (rs1042778, rs237887 and AVPR1b (rs28373064 genes in association with individual differences in prosociality in healthy male Chinese subjects (n = 436. The Prosocial Tendencies Measure (PTM-R was used to assess prosociality. Participants carrying both the GG/GA variant of AVPR1b rs28373064 and the AA variant of clock rs6832769 showed the highest scores on the Emotional PTM. Carriers of both the T allele of OXTR rs1042778 and the C allele of clock rs1801260 showed the lowest total PTM scores compared with the other groups. CONCLUSIONS: The observed interaction effects provide converging evidence that the clock gene and OXT/AVP systems are intertwined and contribute to human prosociality.
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Clock gene modulates roles of OXTR and AVPR1b genes in prosociality.
Ci, Haipeng; Wu, Nan; Su, Yanjie
2014-01-01
The arginine vasopressin receptor (AVPR) and oxytocin receptor (OXTR) genes have been demonstrated to contribute to prosocial behavior. Recent research has focused on the manner by which these simple receptor genes influence prosociality, particularly with regard to the AVP system, which is modulated by the clock gene. The clock gene is responsible for regulating the human biological clock, affecting sleep, emotion and behavior. The current study examined in detail whether the influences of the OXTR and AVPR1b genes on prosociality are dependent on the clock gene. This study assessed interactions between the clock gene (rs1801260, rs6832769) and the OXTR (rs1042778, rs237887) and AVPR1b (rs28373064) genes in association with individual differences in prosociality in healthy male Chinese subjects (n = 436). The Prosocial Tendencies Measure (PTM-R) was used to assess prosociality. Participants carrying both the GG/GA variant of AVPR1b rs28373064 and the AA variant of clock rs6832769 showed the highest scores on the Emotional PTM. Carriers of both the T allele of OXTR rs1042778 and the C allele of clock rs1801260 showed the lowest total PTM scores compared with the other groups. The observed interaction effects provide converging evidence that the clock gene and OXT/AVP systems are intertwined and contribute to human prosociality.
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A new gene in A. rubens: A sea star Ig kappa gene.
Vincent, Nadine; Osteras, Magne; Otten, Patricia; Leclerc, Michel
2014-12-01
The sea star Asterias rubens reacts specifically to the antigen:HRP (horse-radish peroxydase) and produces an antibody anti-HRP. We previously identified a candidate Ig kappa gene corresponding to this manuscript. We show now the gene referred to as: "sea star Ig kappa gene in its specificity".
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Evolution by Pervasive Gene Fusion in Antibiotic Resistance and Antibiotic Synthesizing Genes
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Orla Coleman
2015-03-01
Full Text Available Phylogenetic (tree-based approaches to understanding evolutionary history are unable to incorporate convergent evolutionary events where two genes merge into one. In this study, as exemplars of what can be achieved when a tree is not assumed a priori, we have analysed the evolutionary histories of polyketide synthase genes and antibiotic resistance genes and have shown that their history is replete with convergent events as well as divergent events. We demonstrate that the overall histories of these genes more closely resembles the remodelling that might be seen with the children’s toy Lego, than the standard model of the phylogenetic tree. This work demonstrates further that genes can act as public goods, available for re-use and incorporation into other genetic goods.
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Variations in CCL3L gene cluster sequence and non-specific gene copy numbers
Directory of Open Access Journals (Sweden)
Edberg Jeffrey C
2010-03-01
Full Text Available Abstract Background Copy number variations (CNVs of the gene CC chemokine ligand 3-like1 (CCL3L1 have been implicated in HIV-1 susceptibility, but the association has been inconsistent. CCL3L1 shares homology with a cluster of genes localized to chromosome 17q12, namely CCL3, CCL3L2, and, CCL3L3. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the CCL3L1 gene. Findings Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with CCL3L1 and CCL3L3 being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only CCL3L1. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence. Conclusions This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.
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Why is the correlation between gene importance and gene evolutionary rate so weak?
Wang, Zhi; Zhang, Jianzhi
2009-01-01
One of the few commonly believed principles of molecular evolution is that functionally more important genes (or DNA sequences) evolve more slowly than less important ones. This principle is widely used by molecular biologists in daily practice. However, recent genomic analysis of a diverse array of organisms found only weak, negative correlations between the evolutionary rate of a gene and its functional importance, typically measured under a single benign lab condition. A frequently suggested cause of the above finding is that gene importance determined in the lab differs from that in an organism's natural environment. Here, we test this hypothesis in yeast using gene importance values experimentally determined in 418 lab conditions or computationally predicted for 10,000 nutritional conditions. In no single condition or combination of conditions did we find a much stronger negative correlation, which is explainable by our subsequent finding that always-essential (enzyme) genes do not evolve significantly more slowly than sometimes-essential or always-nonessential ones. Furthermore, we verified that functional density, approximated by the fraction of amino acid sites within protein domains, is uncorrelated with gene importance. Thus, neither the lab-nature mismatch nor a potentially biased among-gene distribution of functional density explains the observed weakness of the correlation between gene importance and evolutionary rate. We conclude that the weakness is factual, rather than artifactual. In addition to being weakened by population genetic reasons, the correlation is likely to have been further weakened by the presence of multiple nontrivial rate determinants that are independent from gene importance. These findings notwithstanding, we show that the principle of slower evolution of more important genes does have some predictive power when genes with vastly different evolutionary rates are compared, explaining why the principle can be practically useful
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Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun
2013-01-01
The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867
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Directory of Open Access Journals (Sweden)
Nishida Mutsumi
2007-11-01
Full Text Available Abstract Background The threespine stickleback (Gasterosteus aculeatus has a characteristic reproductive mode; mature males build nests using a secreted glue-like protein called spiggin. Although recent studies reported multiple occurrences of genes that encode this glue-like protein spiggin in threespine and ninespine sticklebacks, it is still unclear how many genes compose the spiggin multi-gene family. Results Genome sequence analysis of threespine stickleback showed that there are at least five spiggin genes and two pseudogenes, whereas a single spiggin homolog occurs in the genomes of other fishes. Comparative genome sequence analysis demonstrated that Muc19, a single-copy mucous gene in human and mouse, is an ortholog of spiggin. Phylogenetic and molecular evolutionary analyses of these sequences suggested that an ancestral spiggin gene originated from a member of the mucin gene family as a single gene in the common ancestor of teleosts, and gene duplications of spiggin have occurred in the stickleback lineage. There was inter-population variation in the copy number of spiggin genes and positive selection on some codons, indicating that additional gene duplication/deletion events and adaptive evolution at some amino acid sites may have occurred in each stickleback population. Conclusion A number of spiggin genes exist in the threespine stickleback genome. Our results provide insight into the origin and dynamic evolutionary process of the spiggin multi-gene family in the threespine stickleback lineage. The dramatic evolution of genes for mucous substrates may have contributed to the generation of distinct characteristics such as "bio-glue" in vertebrates.
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The Caenorhabditis chemoreceptor gene families
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Robertson Hugh M
2008-10-01
Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.
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The Caenorhabditis chemoreceptor gene families.
Thomas, James H; Robertson, Hugh M
2008-10-06
Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.
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Gene Ontology and KEGG Enrichment Analyses of Genes Related to Age-Related Macular Degeneration
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Jian Zhang
2014-01-01
Full Text Available Identifying disease genes is one of the most important topics in biomedicine and may facilitate studies on the mechanisms underlying disease. Age-related macular degeneration (AMD is a serious eye disease; it typically affects older adults and results in a loss of vision due to retina damage. In this study, we attempt to develop an effective method for distinguishing AMD-related genes. Gene ontology and KEGG enrichment analyses of known AMD-related genes were performed, and a classification system was established. In detail, each gene was encoded into a vector by extracting enrichment scores of the gene set, including it and its direct neighbors in STRING, and gene ontology terms or KEGG pathways. Then certain feature-selection methods, including minimum redundancy maximum relevance and incremental feature selection, were adopted to extract key features for the classification system. As a result, 720 GO terms and 11 KEGG pathways were deemed the most important factors for predicting AMD-related genes.
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Bull, L; Holland, O; Blackmore, S
2000-01-01
In this article we examine the effects of the emergence of a new replicator, memes, on the evolution of a pre-existing replicator, genes. Using a version of the NKCS model we examine the effects of increasing the rate of meme evolution in relation to the rate of gene evolution, for various degrees of interdependence between the two replicators. That is, the effects of memes' (suggested) more rapid rate of evolution in comparison to that of genes is investigated using a tunable model of coevolution. It is found that, for almost any degree of interdependence between the two replicators, as the rate of meme evolution increases, a phase transition-like dynamic occurs under which memes have a significantly detrimental effect on the evolution of genes, quickly resulting in the cessation of effective gene evolution. Conversely, the memes experience a sharp increase in benefit from increasing their rate of evolution. We then examine the effects of enabling genes to reduce the percentage of gene-detrimental evolutionary steps taken by memes. Here a critical region emerges as the comparative rate of meme evolution increases, such that if genes cannot effectively select memes a high percentage of the time, they suffer from meme evolution as if they had almost no selective capability.
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International Nuclear Information System (INIS)
Swiecicki, W.K.
1990-01-01
Full text: Mutations of genes Dpo (dehiscing pods) and A (anthocyanin synthesis) played a role in pea domestication. A number of other genes were important in cultivar development for 3 types of usage (dry seeds, green vegetable types, fodder), e.g. fn, fna, le, p, v, fas and af. New genes (induced and spontaneous), are important for present ideotypes and are registered by the Pisum Genetics Association (PGA). Comparison of a pea variety ideotype with the variation available in gene banks shows that breeders need 'new' features. In mutation induction experiments, genotype, mutagen and method of treatment (e.g. combined or fractionated doses) are varied for broadening the mutation spectrum and selecting more genes of agronomic value. New genes are genetically analysed. In Poland, some mutant varieties with the gene afila were registered, controlling lodging by a shorter stem and a higher number of internodes. Really non-lodging pea varieties could strongly increase seed yield. But the probability of detecting a major gene for lodging resistance is low. Therefore, mutant genes with smaller influence on plant architecture are sought, to combine their effect by crossing. Promising seem to be the genes rogue, reductus and arthritic as well as a number of mutant genes not yet genetically identified. The gene det for terminal inflorescence - similarly to Vicia faba - changes plant development. Utilisation of assimilates and ripening should be better. Improvement of harvest index should give higher seed yield. A number of genes controlling disease resistance are well known (eg. Fw, Fnw, En, mo and sbm). Important in mass screening of resistance are closely linked gene markers. Pea gene banks collect respective lines, but mutants induced in highly productive cultivars would be better. Inducing gene markers sometimes seems to be easier than transfer by crossing. Mutation induction in pea breeding is probably more important because a high number of monogenic features are
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Evaluation of suitable reference genes for gene expression studies ...
Indian Academy of Sciences (India)
2011-12-14
Dec 14, 2011 ... MADS family of TFs control floral organ identity within each whorl of the flower by activating downstream genes. Measuring gene expression in different tissue types and developmental stages is of fundamental importance in TFs functional research. In last few years, quantitative real-time. PCR (qRT-PCR) ...
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Vaiphei, S Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Chaubey, R C; Kma, L; Sharan, R N
2015-01-01
In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving (60)Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of (60)Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min(-1) at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
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G-NEST: A gene neighborhood scoring tool to identify co-conserved, co-expressed genes
In previous studies, gene neighborhoods--spatial clusters of co-expressed genes in the genome--have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Sc...
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Radiopharmaceuticals to monitor gene transfer
International Nuclear Information System (INIS)
Wiebe, L. I.; Morin, K. W.; Knaus, E. E.
1997-01-01
Advances in genetic engineering and molecular biology have opened the door to disease treatment by transferring genes to cells that are responsible for the pathological condition being addressed. These genes can serve to supplement or introduce the function of indigenous genes that are either inadequately expressed or that are congenitally absent in the patient. They can introduce new functions such as drug sensitization to provide a unique therapeutic target. Gene transfer is readily monitored in vitro using a range of histochemical and biochemical tests that are ''built in'' to the therapeutic gene cassette. In vivo, in situ monitoring of the gene transfer and gene expression processes can be achieved with these tests only if biopsy is possible. Scintigraphic imaging can offer unique information on both the extent and location of gene expression, provided that an appropriate reporter gene is included in the therapeutic cassette. This overview includes a brief orientation to gene transfer therapy and is followed by a review of current approaches to gene therapy imaging. The concluding section deals with imaging based on radiolabelled nucleoside substrates for herpes simplex type-1 thymidine kinase, with emphasis on IVFRU, a stable potent and selective HSV-1 TK substrate developed in their laboratories
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A BAYESIAN NONPARAMETRIC MIXTURE MODEL FOR SELECTING GENES AND GENE SUBNETWORKS.
Zhao, Yize; Kang, Jian; Yu, Tianwei
2014-06-01
It is very challenging to select informative features from tens of thousands of measured features in high-throughput data analysis. Recently, several parametric/regression models have been developed utilizing the gene network information to select genes or pathways strongly associated with a clinical/biological outcome. Alternatively, in this paper, we propose a nonparametric Bayesian model for gene selection incorporating network information. In addition to identifying genes that have a strong association with a clinical outcome, our model can select genes with particular expressional behavior, in which case the regression models are not directly applicable. We show that our proposed model is equivalent to an infinity mixture model for which we develop a posterior computation algorithm based on Markov chain Monte Carlo (MCMC) methods. We also propose two fast computing algorithms that approximate the posterior simulation with good accuracy but relatively low computational cost. We illustrate our methods on simulation studies and the analysis of Spellman yeast cell cycle microarray data.
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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Jun, Gyungah; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Denning, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Vronskaya, Maria; Johnson, Andrew D; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Hernández, Isabel; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick C; Hardy, John; Naranjo, Maria Candida Deniz; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Scarpini, Elio; Bonuccelli, Ubaldo; Mancuso, Michelangelo; Siciliano, Gabriele; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Frank-García, Ana; Panza, Francesco; Solfrizzi, Vincenzo; Caffarra, Paolo; Nacmias, Benedetta; Perry, William; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Van Broeckhoven, Christine; Farrer, Lindsay A; van Duijn, Cornelia M; Ramirez, Alfredo; Seshadri, Sudha; Schellenberg, Gerard D; Amouyel, Philippe; Williams, Julie
2014-01-01
Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Directory of Open Access Journals (Sweden)
Valentina Escott-Price
Full Text Available Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6 and 14 (IGHV1-67 p = 7.9×10-8 which indexed novel susceptibility loci.The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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Directory of Open Access Journals (Sweden)
Øvstebø Reidun
2010-05-01
Full Text Available Abstract Background Gene expression in lipopolysaccharide (LPS-stimulated monocytes is mainly studied by quantitative real-time reverse transcription PCR (RT-qPCR using GAPDH (glyceraldehyde 3-phosphate dehydrogenase or ACTB (beta-actin as reference gene for normalization. Expression of traditional reference genes has been shown to vary substantially under certain conditions leading to invalid results. To investigate whether traditional reference genes are stably expressed in LPS-stimulated monocytes or if RT-qPCR results are dependent on the choice of reference genes, we have assessed and evaluated gene expression stability of twelve candidate reference genes in this model system. Results Twelve candidate reference genes were quantified by RT-qPCR in LPS-stimulated, human monocytes and evaluated using the programs geNorm, Normfinder and BestKeeper. geNorm ranked PPIB (cyclophilin B, B2M (beta-2-microglobulin and PPIA (cyclophilin A as the best combination for gene expression normalization in LPS-stimulated monocytes. Normfinder suggested TBP (TATA-box binding protein and B2M as the best combination. Compared to these combinations, normalization using GAPDH alone resulted in significantly higher changes of TNF-α (tumor necrosis factor-alpha and IL10 (interleukin 10 expression. Moreover, a significant difference in TNF-α expression between monocytes stimulated with equimolar concentrations of LPS from N. meningitides and E. coli, respectively, was identified when using the suggested combinations of reference genes for normalization, but stayed unrecognized when employing a single reference gene, ACTB or GAPDH. Conclusions Gene expression levels in LPS-stimulated monocytes based on RT-qPCR results differ significantly when normalized to a single gene or a combination of stably expressed reference genes. Proper evaluation of reference gene stabiliy is therefore mandatory before reporting RT-qPCR results in LPS-stimulated monocytes.
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Gene-wide analysis detects two new susceptibility genes for Alzheimer's Disease
Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Jones, Lesley; Holmans, Peter Alan; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L.; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A.; Naj, Adam C.; Sims, Rebecca
2014-01-01
PUBLISHED BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over...
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Efficient strategy for detecting gene × gene joint action and its application in schizophrenia.
Won, Sungho; Kwon, Min-Seok; Mattheisen, Manuel; Park, Suyeon; Park, Changsoon; Kihara, Daisuke; Cichon, Sven; Ophoff, Roel; Nöthen, Markus M; Rietschel, Marcella; Baur, Max; Uitterlinden, Andre G; Hofmann, A; Lange, Christoph
2014-01-01
We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the genome-wide level and has reasonable statistical power under most genetic models. We found that the presence of any gene × gene joint action may imply differences in three types of genetic components: the minor allele frequencies and the amounts of Hardy-Weinberg disequilibrium may differ between cases and controls, and between the two genetic loci the degree of linkage disequilibrium may differ between cases and controls. Using Fisher's method, it is possible to combine the different sources of genetic information in an overall test for detecting gene × gene joint action. The proposed statistical analysis is efficient and its simplicity makes it applicable to GWASs. In the current study, we applied the proposed approach to a GWAS on schizophrenia and found several potential gene × gene interactions. Our application illustrates the practical advantage of the proposed method. © 2013 WILEY PERIODICALS, INC.
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Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver
2015-01-01
Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.
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Targeting the human lysozyme gene on bovine αs1- casein gene ...
African Journals Online (AJOL)
ajl yemi
2011-11-28
Nov 28, 2011 ... Targeting an exogenous gene into a favorable gene locus and for expression under endogenous regulators is ... case, the expression of human lysozyme could be regulated by the endogenous cis-element of αs1- casein gene in .... Mouse mammary epithelial C127 cells (Cell Bank, Chinese. Academy of ...
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Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA
2012-06-19
Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.
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Paralogous Genes as a Tool to Study the Regulation of Gene Expression
DEFF Research Database (Denmark)
Hoffmann, Robert D
The genomes of plants are marked by reoccurring events of whole-genome duplication. These events are major contributors to speciation and provide the genetic material for organisms to evolve ever greater complexity. Duplicated genes, referred to as paralogs, may be retained because they acquired...... regions. These results suggest that a concurrent purifying selection acts on coding and non-coding sequences of paralogous genes in A. thaliana. Mutational analyses of the promoters from a paralogous gene pair were performed in transgenic A. thaliana plants. The results revealed a 170-bp long DNA sequence...... that forms a bifunctional cis-regulatory module; it represses gene expression in the sporophyte while activating it in pollen. This finding is important for many aspects of gene regulation and the transcriptional changes underlying gametophyte development. In conclusion, the presented thesis suggests that...
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Screening key genes for abdominal aortic aneurysm based on gene expression omnibus dataset.
Wan, Li; Huang, Jingyong; Ni, Haizhen; Yu, Guanfeng
2018-02-13
Abdominal aortic aneurysm (AAA) is a common cardiovascular system disease with high mortality. The aim of this study was to identify potential genes for diagnosis and therapy in AAA. We searched and downloaded mRNA expression data from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) from AAA and normal individuals. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, transcriptional factors (TFs) network and protein-protein interaction (PPI) network were used to explore the function of genes. Additionally, immunohistochemical (IHC) staining was used to validate the expression of identified genes. Finally, the diagnostic value of identified genes was accessed by receiver operating characteristic (ROC) analysis in GEO database. A total of 1199 DEGs (188 up-regulated and 1011 down-regulated) were identified between AAA and normal individual. KEGG pathway analysis displayed that vascular smooth muscle contraction and pathways in cancer were significantly enriched signal pathway. The top 10 up-regulated and top 10 down-regulated DEGs were used to construct TFs and PPI networks. Some genes with high degrees such as NELL2, CCR7, MGAM, HBB, CSNK2A2, ZBTB16 and FOXO1 were identified to be related to AAA. The consequences of IHC staining showed that CCR7 and PDGFA were up-regulated in tissue samples of AAA. ROC analysis showed that NELL2, CCR7, MGAM, HBB, CSNK2A2, ZBTB16, FOXO1 and PDGFA had the potential diagnostic value for AAA. The identified genes including NELL2, CCR7, MGAM, HBB, CSNK2A2, ZBTB16, FOXO1 and PDGFA might be involved in the pathology of AAA.
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A role for gene duplication and natural variation of gene expression in the evolution of metabolism.
Directory of Open Access Journals (Sweden)
Daniel J Kliebenstein
Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.
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The use of molecular imaging of gene expression by radiotracers in gene therapy
International Nuclear Information System (INIS)
Richard-Fiardo, P.; Franken, P.R.; Harrington, K.J.; Vassaux, G.; Cambien, B.
2011-01-01
Introduction: Progress with gene-based therapies has been hampered by difficulties in monitoring the biodistribution and kinetics of vector-mediated gene expression. Recent developments in non-invasive imaging have allowed researchers and clinicians to assess the location, magnitude and persistence of gene expression in animals and humans. Such advances should eventually lead to improvement in the efficacy and safety of current clinical protocols for future treatments. Areas Covered: The molecular imaging techniques for monitoring gene therapy in the living subject, with a specific highlight on the key reporter gene approaches that have been developed and validated in preclinical models using the latest imaging modalities. The applications of molecular imaging to biotherapy, with a particular emphasis on monitoring of gene and vector biodistribution and on image-guided radiotherapy. Expert Opinion: Among the reporter gene/probe combinations that have been described so far, one stands out, in our view, as the most versatile and easy to implement: the Na/I symporter. This strategy, exploiting more than 50 years of experience in the treatment of differentiated thyroid carcinomas, has been validated in different types of experimental cancers and with different types of oncolytic viruses and is likely to become a key tool in the implementation of human gene therapy. (authors)
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Strategy of gene silencing in cassava for validation of resistance genes
International Nuclear Information System (INIS)
Cortes, Simon; Lopez, Camilo
2010-01-01
Cassava (Manihot esculenta) is a major source of food for more than 1000 million people in the world and constitutes an important staple crop. Cassava bacterial blight, caused by the gram negative bacterium Xanthomonas axonopodis pv. manihotis, is one of the most important constraints for this crop. A candidate resistance gene against cassava bacterial blight, named RXam1, has been identified previously. In this work, we employed the gene silencing approach using the African cassava mosaic virus (ACMV) to validate the function of the RXam1 gene. We used as positive control the su gen, which produce photo blanching in leaves when is silenced. Plants from the SG10735 variety were bombardment with the ACMV-A-SU+ACMV-B y ACMV-A-RXam1+ACMV-B constructions. The silencing efficiency employing the su gene was low, only one of seven plants showed photo blanching. In the putative silenced plants for the RXam1 gene, no presence of siRNAs corresponding to RXam1 was observed; although a low diminution of the RXam1 gene expression was obtained. The growth curves for the Xam strain CIO136 in cassava plants inoculated showing a little but no significance difference in the susceptibility in the silenced plants compared to not silenced
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Genes contributing to prion pathogenesis
DEFF Research Database (Denmark)
Tamgüney, Gültekin; Giles, Kurt; Glidden, David V
2008-01-01
incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...
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Twenty Years of European Union Support to Gene Therapy and Gene Transfer.
Gancberg, David
2017-11-01
For 20 years and throughout its research programmes, the European Union has supported the entire innovation chain for gene transfer and gene therapy. The fruits of this investment are ripening as gene therapy products are reaching the European market and as clinical trials are demonstrating the safety of this approach to treat previously untreatable diseases.
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IGFBP3 colocalizes with and regulates hypocretin (orexin.
Directory of Open Access Journals (Sweden)
Makoto Honda
Full Text Available The sleep disorder narcolepsy is caused by a vast reduction in neurons producing the hypocretin (orexin neuropeptides. Based on the tight association with HLA, narcolepsy is believed to result from an autoimmune attack, but the cause of hypocretin cell loss is still unknown. We performed gene expression profiling in the hypothalamus to identify novel genes dysregulated in narcolepsy, as these may be the target of autoimmune attack or modulate hypocretin gene expression.We used microarrays to compare the transcriptome in the posterior hypothalamus of (1 narcoleptic versus control postmortem human brains and (2 transgenic mice lacking hypocretin neurons versus wild type mice. Hypocretin was the most downregulated gene in human narcolepsy brains. Among many additional candidates, only one, insulin-like growth factor binding protein 3 (IGFBP3, was downregulated in both human and mouse models and co-expressed in hypocretin neurons. Functional analysis indicated decreased hypocretin messenger RNA and peptide content, and increased sleep in transgenic mice overexpressing human IGFBP3, an effect possibly mediated through decreased hypocretin promotor activity in the presence of excessive IGFBP3. Although we found no IGFBP3 autoantibodies nor a genetic association with IGFBP3 polymorphisms in human narcolepsy, we found that an IGFBP3 polymorphism known to increase serum IGFBP3 levels was associated with lower CSF hypocretin-1 in normal individuals.Comparison of the transcriptome in narcolepsy and narcolepsy model mouse brains revealed a novel dysregulated gene which colocalized in hypocretin cells. Functional analysis indicated that the identified IGFBP3 is a new regulator of hypocretin cell physiology that may be involved not only in the pathophysiology of narcolepsy, but also in the regulation of sleep in normal individuals, most notably during adolescence. Further studies are required to address the hypothesis that excessive IGFBP3 expression may
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Repressive histone methylation regulates cardiac myocyte cell cycle exit.
El-Nachef, Danny; Oyama, Kyohei; Wu, Yun-Yu; Freeman, Miles; Zhang, Yiqiang; Robb MacLellan, W
2018-05-22
Mammalian cardiac myocytes (CMs) stop proliferating soon after birth and subsequent heart growth comes from hypertrophy, limiting the adult heart's regenerative potential after injury. The molecular events that mediate CM cell cycle exit are poorly understood. To determine the epigenetic mechanisms limiting CM cycling in adult CMs (ACMs) and whether trimethylation of lysine 9 of histone H3 (H3K9me3), a histone modification associated with repressed chromatin, is required for the silencing of cell cycle genes, we developed a transgenic mouse model where H3K9me3 is specifically removed in CMs by overexpression of histone demethylase, KDM4D. Although H3K9me3 is found across the genome, its loss in CMs preferentially disrupts cell cycle gene silencing. KDM4D binds directly to cell cycle genes and reduces H3K9me3 levels at these promotors. Loss of H3K9me3 preferentially leads to increased cell cycle gene expression resulting in enhanced CM cycling. Heart mass was increased in KDM4D overexpressing mice by postnatal day 14 (P14) and continued to increase until 9-weeks of age. ACM number, but not size, was significantly increased in KDM4D expressing hearts, suggesting CM hyperplasia accounts for the increased heart mass. Inducing KDM4D after normal development specifically in ACMs resulted in increased cell cycle gene expression and cycling. We demonstrated that H3K9me3 is required for CM cell cycle exit and terminal differentiation in ACMs. Depletion of H3K9me3 in adult hearts prevents and reverses permanent cell cycle exit and allows hyperplastic growth in adult hearts in vivo. Copyright © 2017. Published by Elsevier Ltd.
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Directory of Open Access Journals (Sweden)
Agustin Krisna Wardani
2018-01-01
Kebutuhan kedelai yang mencapai 2,2 juta ton/tahun memaksa Indonesia mengimpor sebanyak 1,62 juta ton. Sebagian besar kedelai impor berupa kedelai transgenik. Dengan munculnya kedelai transgenik di Indonesia, perlu adanya pelabelan Produk Rekayasa Genetika (PRG untuk memenuhi hak-hak konsumen. Teknik yang dilakukan untuk mendeteksi PRG salah satunya menggunakan metode PCR. Penelitian ini bertujuan untuk mengetahui ada tidaknya gen transgenik pada produk susu bubuk kedelai dan formula soya, sehingga produk dapat digolongkan sebagai PRG atau tidak. Selain itu juga bertujuan untuk mengetahui suhu annealing optimum pada primer yang digunakan. Hasil penelitian didapatkan suhu annealing optimum primer CaMV 35S promotor adalah 60oC. Sedangkan untuk primer gen EPSPS-CP4 suhu annealing optimumnya 59oC. Untuk primer NOS terminator suhu annealing optimum tidak ditemukan. Dari amplifikasi DNA sampel, 6 sampel susu bubuk kedelai dan 5 sampel formula soya terdapat sisipan gen EPSPS-CP4 dan gen Promotor CaMV 35S. Dengan demikian 11 sampel tersebut dapat dikatakan sebagai PRG. Kata kunci: Produk rekayasa genetika; PCR; formula soya; susu kedelai bubuk; kedelai transgenik
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Motorized Recreation Sounds Influence Nature Scene Evaluations: The Role of Attitude Moderators
Benfield, Jacob; Taff, B. D.; Weinzimmer, David; Newman, Peter
2018-01-01
Soundscape assessment takes many forms, including letting the consequences of the soundscape be an indicator of soundscape quality or value. As a result, much social science research has been conducted to better quantify problem soundscapes and the subsequent effects on humans exposed to them. Visual evaluations of natural environments are one area where research has consistently shown detrimental effects of noisy or anthropogenic soundscapes (e.g., those containing noise from motorized recreation), but the potential moderating role of individual attitudes toward elements within the soundscape has not been sufficiently explored. This study demonstrates that both pro-motorized recreation and pro-motorized recreation management attitudes can alter the effect of motorized recreation noise on scenic evaluations in opposing directions. Pro-recreation attitudes lessen the effect of the soundscape, while pro-management attitudes heighten the negative effect of anthropogenic sounds on scenic evaluation. The implications for other areas of soundscape research, especially with regard to soundscape quality assessment through experienced outcomes, are discussed, including possible strategies for prioritizing known or relevant moderating variables. PMID:29706911
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Motorized Recreation Sounds Influence Nature Scene Evaluations: The Role of Attitude Moderators.
Benfield, Jacob; Taff, B D; Weinzimmer, David; Newman, Peter
2018-01-01
Soundscape assessment takes many forms, including letting the consequences of the soundscape be an indicator of soundscape quality or value. As a result, much social science research has been conducted to better quantify problem soundscapes and the subsequent effects on humans exposed to them. Visual evaluations of natural environments are one area where research has consistently shown detrimental effects of noisy or anthropogenic soundscapes (e.g., those containing noise from motorized recreation), but the potential moderating role of individual attitudes toward elements within the soundscape has not been sufficiently explored. This study demonstrates that both pro-motorized recreation and pro-motorized recreation management attitudes can alter the effect of motorized recreation noise on scenic evaluations in opposing directions. Pro-recreation attitudes lessen the effect of the soundscape, while pro-management attitudes heighten the negative effect of anthropogenic sounds on scenic evaluation. The implications for other areas of soundscape research, especially with regard to soundscape quality assessment through experienced outcomes, are discussed, including possible strategies for prioritizing known or relevant moderating variables.
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Motorized Recreation Sounds Influence Nature Scene Evaluations: The Role of Attitude Moderators
Directory of Open Access Journals (Sweden)
Jacob Benfield
2018-04-01
Full Text Available Soundscape assessment takes many forms, including letting the consequences of the soundscape be an indicator of soundscape quality or value. As a result, much social science research has been conducted to better quantify problem soundscapes and the subsequent effects on humans exposed to them. Visual evaluations of natural environments are one area where research has consistently shown detrimental effects of noisy or anthropogenic soundscapes (e.g., those containing noise from motorized recreation, but the potential moderating role of individual attitudes toward elements within the soundscape has not been sufficiently explored. This study demonstrates that both pro-motorized recreation and pro-motorized recreation management attitudes can alter the effect of motorized recreation noise on scenic evaluations in opposing directions. Pro-recreation attitudes lessen the effect of the soundscape, while pro-management attitudes heighten the negative effect of anthropogenic sounds on scenic evaluation. The implications for other areas of soundscape research, especially with regard to soundscape quality assessment through experienced outcomes, are discussed, including possible strategies for prioritizing known or relevant moderating variables.
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Combining gene prediction methods to improve metagenomic gene annotation
Directory of Open Access Journals (Sweden)
Rosen Gail L
2011-01-01
Full Text Available Abstract Background Traditional gene annotation methods rely on characteristics that may not be available in short reads generated from next generation technology, resulting in suboptimal performance for metagenomic (environmental samples. Therefore, in recent years, new programs have been developed that optimize performance on short reads. In this work, we benchmark three metagenomic gene prediction programs and combine their predictions to improve metagenomic read gene annotation. Results We not only analyze the programs' performance at different read-lengths like similar studies, but also separate different types of reads, including intra- and intergenic regions, for analysis. The main deficiencies are in the algorithms' ability to predict non-coding regions and gene edges, resulting in more false-positives and false-negatives than desired. In fact, the specificities of the algorithms are notably worse than the sensitivities. By combining the programs' predictions, we show significant improvement in specificity at minimal cost to sensitivity, resulting in 4% improvement in accuracy for 100 bp reads with ~1% improvement in accuracy for 200 bp reads and above. To correctly annotate the start and stop of the genes, we find that a consensus of all the predictors performs best for shorter read lengths while a unanimous agreement is better for longer read lengths, boosting annotation accuracy by 1-8%. We also demonstrate use of the classifier combinations on a real dataset. Conclusions To optimize the performance for both prediction and annotation accuracies, we conclude that the consensus of all methods (or a majority vote is the best for reads 400 bp and shorter, while using the intersection of GeneMark and Orphelia predictions is the best for reads 500 bp and longer. We demonstrate that most methods predict over 80% coding (including partially coding reads on a real human gut sample sequenced by Illumina technology.
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Directory of Open Access Journals (Sweden)
Cohn Zachary A
2007-06-01
Full Text Available Abstract Background Cartilage plays a fundamental role in the development of the human skeleton. Early in embryogenesis, mesenchymal cells condense and differentiate into chondrocytes to shape the early skeleton. Subsequently, the cartilage anlagen differentiate to form the growth plates, which are responsible for linear bone growth, and the articular chondrocytes, which facilitate joint function. However, despite the multiplicity of roles of cartilage during human fetal life, surprisingly little is known about its transcriptome. To address this, a whole genome microarray expression profile was generated using RNA isolated from 18–22 week human distal femur fetal cartilage and compared with a database of control normal human tissues aggregated at UCLA, termed Celsius. Results 161 cartilage-selective genes were identified, defined as genes significantly expressed in cartilage with low expression and little variation across a panel of 34 non-cartilage tissues. Among these 161 genes were cartilage-specific genes such as cartilage collagen genes and 25 genes which have been associated with skeletal phenotypes in humans and/or mice. Many of the other cartilage-selective genes do not have established roles in cartilage or are novel, unannotated genes. Quantitative RT-PCR confirmed the unique pattern of gene expression observed by microarray analysis. Conclusion Defining the gene expression pattern for cartilage has identified new genes that may contribute to human skeletogenesis as well as provided further candidate genes for skeletal dysplasias. The data suggest that fetal cartilage is a complex and transcriptionally active tissue and demonstrate that the set of genes selectively expressed in the tissue has been greatly underestimated.
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Gene2Function: An Integrated Online Resource for Gene Function Discovery
Directory of Open Access Journals (Sweden)
Yanhui Hu
2017-08-01
Full Text Available One of the most powerful ways to develop hypotheses regarding the biological functions of conserved genes in a given species, such as humans, is to first look at what is known about their function in another species. Model organism databases and other resources are rich with functional information but difficult to mine. Gene2Function addresses a broad need by integrating information about conserved genes in a single online resource.
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Radionuclide reporter gene imaging
Energy Technology Data Exchange (ETDEWEB)
Min, Jung Joon [School of Medicine, Chonnam National Univ., Gwangju (Korea, Republic of)
2004-04-01
Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate model validation as well as allow for clinical monitoring of human diseases.
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Radionuclide reporter gene imaging
International Nuclear Information System (INIS)
Min, Jung Joon
2004-01-01
Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate model validation as well as allow for clinical monitoring of human diseases
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Gene Fusion Markup Language: a prototype for exchanging gene fusion data.
Kalyana-Sundaram, Shanker; Shanmugam, Achiraman; Chinnaiyan, Arul M
2012-10-16
An avalanche of next generation sequencing (NGS) studies has generated an unprecedented amount of genomic structural variation data. These studies have also identified many novel gene fusion candidates with more detailed resolution than previously achieved. However, in the excitement and necessity of publishing the observations from this recently developed cutting-edge technology, no community standardization approach has arisen to organize and represent the data with the essential attributes in an interchangeable manner. As transcriptome studies have been widely used for gene fusion discoveries, the current non-standard mode of data representation could potentially impede data accessibility, critical analyses, and further discoveries in the near future. Here we propose a prototype, Gene Fusion Markup Language (GFML) as an initiative to provide a standard format for organizing and representing the significant features of gene fusion data. GFML will offer the advantage of representing the data in a machine-readable format to enable data exchange, automated analysis interpretation, and independent verification. As this database-independent exchange initiative evolves it will further facilitate the formation of related databases, repositories, and analysis tools. The GFML prototype is made available at http://code.google.com/p/gfml-prototype/. The Gene Fusion Markup Language (GFML) presented here could facilitate the development of a standard format for organizing, integrating and representing the significant features of gene fusion data in an inter-operable and query-able fashion that will enable biologically intuitive access to gene fusion findings and expedite functional characterization. A similar model is envisaged for other NGS data analyses.
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Zhou, Jindan; Rudd, Kenneth E
2013-01-01
EcoGene (http://ecogene.org) is a database and website devoted to continuously improving the structural and functional annotation of Escherichia coli K-12, one of the most well understood model organisms, represented by the MG1655(Seq) genome sequence and annotations. Major improvements to EcoGene in the past decade include (i) graphic presentations of genome map features; (ii) ability to design Boolean queries and Venn diagrams from EcoArray, EcoTopics or user-provided GeneSets; (iii) the genome-wide clone and deletion primer design tool, PrimerPairs; (iv) sequence searches using a customized EcoBLAST; (v) a Cross Reference table of synonymous gene and protein identifiers; (vi) proteome-wide indexing with GO terms; (vii) EcoTools access to >2000 complete bacterial genomes in EcoGene-RefSeq; (viii) establishment of a MySql relational database; and (ix) use of web content management systems. The biomedical literature is surveyed daily to provide citation and gene function updates. As of September 2012, the review of 37 397 abstracts and articles led to creation of 98 425 PubMed-Gene links and 5415 PubMed-Topic links. Annotation updates to Genbank U00096 are transmitted from EcoGene to NCBI. Experimental verifications include confirmation of a CTG start codon, pseudogene restoration and quality assurance of the Keio strain collection.
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Zhou, Jindan; Rudd, Kenneth E.
2013-01-01
EcoGene (http://ecogene.org) is a database and website devoted to continuously improving the structural and functional annotation of Escherichia coli K-12, one of the most well understood model organisms, represented by the MG1655(Seq) genome sequence and annotations. Major improvements to EcoGene in the past decade include (i) graphic presentations of genome map features; (ii) ability to design Boolean queries and Venn diagrams from EcoArray, EcoTopics or user-provided GeneSets; (iii) the genome-wide clone and deletion primer design tool, PrimerPairs; (iv) sequence searches using a customized EcoBLAST; (v) a Cross Reference table of synonymous gene and protein identifiers; (vi) proteome-wide indexing with GO terms; (vii) EcoTools access to >2000 complete bacterial genomes in EcoGene-RefSeq; (viii) establishment of a MySql relational database; and (ix) use of web content management systems. The biomedical literature is surveyed daily to provide citation and gene function updates. As of September 2012, the review of 37 397 abstracts and articles led to creation of 98 425 PubMed-Gene links and 5415 PubMed-Topic links. Annotation updates to Genbank U00096 are transmitted from EcoGene to NCBI. Experimental verifications include confirmation of a CTG start codon, pseudogene restoration and quality assurance of the Keio strain collection. PMID:23197660
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Dong, Xinran; Hao, Yun; Wang, Xiao; Tian, Weidong
2016-01-11
Pathway or gene set over-representation analysis (ORA) has become a routine task in functional genomics studies. However, currently widely used ORA tools employ statistical methods such as Fisher's exact test that reduce a pathway into a list of genes, ignoring the constitutive functional non-equivalent roles of genes and the complex gene-gene interactions. Here, we develop a novel method named LEGO (functional Link Enrichment of Gene Ontology or gene sets) that takes into consideration these two types of information by incorporating network-based gene weights in ORA analysis. In three benchmarks, LEGO achieves better performance than Fisher and three other network-based methods. To further evaluate LEGO's usefulness, we compare LEGO with five gene expression-based and three pathway topology-based methods using a benchmark of 34 disease gene expression datasets compiled by a recent publication, and show that LEGO is among the top-ranked methods in terms of both sensitivity and prioritization for detecting target KEGG pathways. In addition, we develop a cluster-and-filter approach to reduce the redundancy among the enriched gene sets, making the results more interpretable to biologists. Finally, we apply LEGO to two lists of autism genes, and identify relevant gene sets to autism that could not be found by Fisher.
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Obayashi, Takeshi; Kinoshita, Kengo
2010-05-01
Gene coexpression analyses are a powerful method to predict the function of genes and/or to identify genes that are functionally related to query genes. The basic idea of gene coexpression analyses is that genes with similar functions should have similar expression patterns under many different conditions. This approach is now widely used by many experimental researchers, especially in the field of plant biology. In this review, we will summarize recent successful examples obtained by using our gene coexpression database, ATTED-II. Specifically, the examples will describe the identification of new genes, such as the subunits of a complex protein, the enzymes in a metabolic pathway and transporters. In addition, we will discuss the discovery of a new intercellular signaling factor and new regulatory relationships between transcription factors and their target genes. In ATTED-II, we provide two basic views of gene coexpression, a gene list view and a gene network view, which can be used as guide gene approach and narrow-down approach, respectively. In addition, we will discuss the coexpression effectiveness for various types of gene sets.
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DEFF Research Database (Denmark)
Johansson, Tove; Nylund, S.; Olesen, Niels Jørgen
2001-01-01
, M, G and L genes it was determined that transcription start and stop codons were conserved between virus 903/87 and the vesiculo viruses. Virus 903/87 has no open reading frame coding for a non-virion gene between the glycoprotein and the polymerase gene. Phylogenetic studies based on rhabdovirus...
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Gautier, Aude; Le Gac, Florence; Lareyre, Jean-Jacques
2011-02-01
The gonadal soma-derived factor (GSDF) belongs to the transforming growth factor-β superfamily and is conserved in teleostean fish species. Gsdf is specifically expressed in the gonads, and gene expression is restricted to the granulosa and Sertoli cells in trout and medaka. The gsdf gene expression is correlated to early testis differentiation in medaka and was shown to stimulate primordial germ cell and spermatogonia proliferation in trout. In the present study, we show that the gsdf gene localizes to a syntenic chromosomal fragment conserved among vertebrates although no gsdf-related gene is detected on the corresponding genomic region in tetrapods. We demonstrate using quantitative RT-PCR that most of the genes localized in the synteny are specifically expressed in medaka gonads. Gsdf is the only gene of the synteny with a much higher expression in the testis compared to the ovary. In contrast, gene expression pattern analysis of the gsdf surrounding genes (nup54, aff1, klhl8, sdad1, and ptpn13) indicates that these genes are preferentially expressed in the female gonads. The tissue distribution of these genes is highly similar in medaka and zebrafish, two teleostean species that have diverged more than 110 million years ago. The cellular localization of these genes was determined in medaka gonads using the whole-mount in situ hybridization technique. We confirm that gsdf gene expression is restricted to Sertoli and granulosa cells in contact with the premeiotic and meiotic cells. The nup54 gene is expressed in spermatocytes and previtellogenic oocytes. Transcripts corresponding to the ovary-specific genes (aff1, klhl8, and sdad1) are detected only in previtellogenic oocytes. No expression was detected in the gonocytes in 10 dpf embryos. In conclusion, we show that the gsdf gene localizes to a syntenic chromosomal fragment harboring evolutionary conserved genes in vertebrates. These genes are preferentially expressed in previtelloogenic oocytes, and thus, they
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Baker, Richard H; Narechania, Apurva; Johns, Philip M; Wilkinson, Gerald S
2012-08-19
Gene duplication provides an essential source of novel genetic material to facilitate rapid morphological evolution. Traits involved in reproduction and sexual dimorphism represent some of the fastest evolving traits in nature, and gene duplication is intricately involved in the origin and evolution of these traits. Here, we review genomic research on stalk-eyed flies (Diopsidae) that has been used to examine the extent of gene duplication and its role in the genetic architecture of sexual dimorphism. Stalk-eyed flies are remarkable because of the elongation of the head into long stalks, with the eyes and antenna laterally displaced at the ends of these stalks. Many species are strongly sexually dimorphic for eyespan, and these flies have become a model system for studying sexual selection. Using both expressed sequence tag and next-generation sequencing, we have established an extensive database of gene expression in the developing eye-antennal imaginal disc, the adult head and testes. Duplicated genes exhibit narrower expression patterns than non-duplicated genes, and the testes, in particular, provide an abundant source of gene duplication. Within somatic tissue, duplicated genes are more likely to be differentially expressed between the sexes, suggesting gene duplication may provide a mechanism for resolving sexual conflict.
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Ledley, F D; McNamee, L M; Uzdil, V; Morgan, I W
2014-02-01
This report examines the commercialization of gene therapy in the context of innovation theories that posit a relationship between the maturation of a technology through its life cycle and prospects for successful product development. We show that the field of gene therapy has matured steadily since the 1980s, with the congruent accumulation of >35 000 papers, >16 000 US patents, >1800 clinical trials and >$4.3 billion in capital investment in gene therapy companies. Gene therapy technologies comprise a series of dissimilar approaches for gene delivery, each of which has introduced a distinct product architecture. Using bibliometric methods, we quantify the maturation of each technology through a characteristic life cycle S-curve, from a Nascent stage, through a Growing stage of exponential advance, toward an Established stage and projected limit. Capital investment in gene therapy is shown to have occurred predominantly in Nascent stage technologies and to be negatively correlated with maturity. Gene therapy technologies are now achieving the level of maturity that innovation research and biotechnology experience suggest may be requisite for efficient product development. Asynchrony between the maturation of gene therapy technologies and capital investment in development-focused business models may have stalled the commercialization of gene therapy.
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Directory of Open Access Journals (Sweden)
Emily J. Parker
2013-08-01
Full Text Available The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse. This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.
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Huang, Xuena; Gao, Yangchun; Jiang, Bei; Zhou, Zunchun; Zhan, Aibin
2016-01-15
As invasive species have successfully colonized a wide range of dramatically different local environments, they offer a good opportunity to study interactions between species and rapidly changing environments. Gene expression represents one of the primary and crucial mechanisms for rapid adaptation to local environments. Here, we aim to select reference genes for quantitative gene expression analysis based on quantitative Real-Time PCR (qRT-PCR) for a model invasive ascidian, Ciona savignyi. We analyzed the stability of ten candidate reference genes in three tissues (siphon, pharynx and intestine) under two key environmental stresses (temperature and salinity) in the marine realm based on three programs (geNorm, NormFinder and delta Ct method). Our results demonstrated only minor difference for stability rankings among the three methods. The use of different single reference gene might influence the data interpretation, while multiple reference genes could minimize possible errors. Therefore, reference gene combinations were recommended for different tissues - the optimal reference gene combination for siphon was RPS15 and RPL17 under temperature stress, and RPL17, UBQ and TubA under salinity treatment; for pharynx, TubB, TubA and RPL17 were the most stable genes under temperature stress, while TubB, TubA and UBQ were the best under salinity stress; for intestine, UBQ, RPS15 and RPL17 were the most reliable reference genes under both treatments. Our results suggest that the necessity of selection and test of reference genes for different tissues under varying environmental stresses. The results obtained here are expected to reveal mechanisms of gene expression-mediated invasion success using C. savignyi as a model species. Copyright © 2015 Elsevier B.V. All rights reserved.
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Cloning and selection of reference genes for gene expression ...
African Journals Online (AJOL)
Full length mRNA sequences of Ac-β-actin and Ac-gapdh, and partial mRNA sequences of Ac-18SrRNA and Ac-ubiquitin were cloned from pineapple in this study. The four genes were tested as housekeeping genes in three experimental sets. GeNorm and NormFinder analysis revealed that β-actin was the most ...
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Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling
Directory of Open Access Journals (Sweden)
Guo Zheng
2006-01-01
Full Text Available Abstract Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network to address the underlying regulations of genes that can span any unit(s of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex
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Inverse gene-for-gene interactions contribute additively to tan spot susceptibility in wheat.
Liu, Zhaohui; Zurn, Jason D; Kariyawasam, Gayan; Faris, Justin D; Shi, Gongjun; Hansen, Jana; Rasmussen, Jack B; Acevedo, Maricelis
2017-06-01
Tan spot susceptibility is conferred by multiple interactions of necrotrophic effector and host sensitivity genes. Tan spot of wheat, caused by Pyrenophora tritici-repentis, is an important disease in almost all wheat-growing areas of the world. The disease system is known to involve at least three fungal-produced necrotrophic effectors (NEs) that interact with the corresponding host sensitivity (S) genes in an inverse gene-for-gene manner to induce disease. However, it is unknown if the effects of these NE-S gene interactions contribute additively to the development of tan spot. In this work, we conducted disease evaluations using different races and quantitative trait loci (QTL) analysis in a wheat recombinant inbred line (RIL) population derived from a cross between two susceptible genotypes, LMPG-6 and PI 626573. The two parental lines each harbored a single known NE sensitivity gene with LMPG-6 having the Ptr ToxC sensitivity gene Tsc1 and PI 626573 having the Ptr ToxA sensitivity gene Tsn1. Transgressive segregation was observed in the population for all races. QTL mapping revealed that both loci (Tsn1 and Tsc1) were significantly associated with susceptibility to race 1 isolates, which produce both Ptr ToxA and Ptr ToxC, and the two genes contributed additively to tan spot susceptibility. For isolates of races 2 and 3, which produce only Ptr ToxA and Ptr ToxC, only Tsn1 and Tsc1 were associated with tan spot susceptibility, respectively. This work clearly demonstrates that tan spot susceptibility in this population is due primarily to two NE-S interactions. Breeders should remove both sensitivity genes from wheat lines to obtain high levels of tan spot resistance.
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Gene Overexpression Resources in Cereals for Functional Genomics and Discovery of Useful Genes
Directory of Open Access Journals (Sweden)
Kiyomi Abe
2016-09-01
Full Text Available Identification and elucidation of functions of plant genes is valuable for both basic and applied research. In addition to natural variation in model plants, numerous loss-of-function resources have been produced by mutagenesis with chemicals, irradiation, or insertions of transposable elements or T-DNA. However, we may be unable to observe loss-of-function phenotypes for genes with functionally redundant homologs, and for those essential for growth and development. To offset such disadvantages, gain-of-function transgenic resources have been exploited. Activation-tagged lines have been generated using obligatory overexpression of endogenous genes by random insertion of an enhancer. Recent progress in DNA sequencing technology and bioinformatics has enabled the preparation of genomewide collections of full-length cDNAs (fl-cDNAs in some model species. Using the fl-cDNA clones, a novel gain-of-function strategy, Fl-cDNA OvereXpressor gene (FOX-hunting system, has been developed. A mutant phenotype in a FOX line can be directly attributed to the overexpressed fl-cDNA. Investigating a large population of FOX lines could reveal important genes conferring favorable phenotypes for crop breeding. Alternatively, a unique loss-of-function approach Chimeric REpressor gene Silencing Technology (CRES-T has been developed. In CRES-T, overexpression of a chimeric repressor, composed of the coding sequence of a transcription factor (TF and short peptide designated as the repression domain, could interfere with the action of endogenous TF in plants. Although plant TFs usually consist of gene families, CRES-T is effective, in principle, even for the TFs with functional redundancy. In this review, we focus on the current status of the gene-overexpression strategies and resources for identifying and elucidating novel functions of cereal genes. We discuss the potential of these research tools for identifying useful genes and phenotypes for application in crop
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Gene therapy for ocular diseases.
Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao
2011-05-01
The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.
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Empirical study of supervised gene screening
Directory of Open Access Journals (Sweden)
Ma Shuangge
2006-12-01
Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.
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Genome-Wide Comparative Gene Family Classification
Frech, Christian; Chen, Nansheng
2010-01-01
Correct classification of genes into gene families is important for understanding gene function and evolution. Although gene families of many species have been resolved both computationally and experimentally with high accuracy, gene family classification in most newly sequenced genomes has not been done with the same high standard. This project has been designed to develop a strategy to effectively and accurately classify gene families across genomes. We first examine and compare the performance of computer programs developed for automated gene family classification. We demonstrate that some programs, including the hierarchical average-linkage clustering algorithm MC-UPGMA and the popular Markov clustering algorithm TRIBE-MCL, can reconstruct manual curation of gene families accurately. However, their performance is highly sensitive to parameter setting, i.e. different gene families require different program parameters for correct resolution. To circumvent the problem of parameterization, we have developed a comparative strategy for gene family classification. This strategy takes advantage of existing curated gene families of reference species to find suitable parameters for classifying genes in related genomes. To demonstrate the effectiveness of this novel strategy, we use TRIBE-MCL to classify chemosensory and ABC transporter gene families in C. elegans and its four sister species. We conclude that fully automated programs can establish biologically accurate gene families if parameterized accordingly. Comparative gene family classification finds optimal parameters automatically, thus allowing rapid insights into gene families of newly sequenced species. PMID:20976221
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Molecular transformation, gene cloning, and gene expression systems for filamentous fungi
Gold, Scott E.; Duick, John W.; Redman, Regina S.; Rodriguez, Rusty J.
2001-01-01
This chapter discusses the molecular transformation, gene cloning, and gene expression systems for filamentous fungi. Molecular transformation involves the movement of discrete amounts of DNA into cells, the expression of genes on the transported DNA, and the sustainable replication of the transforming DNA. The ability to transform fungi is dependent on the stable replication and expression of genes located on the transforming DNA. Three phenomena observed in bacteria, that is, competence, plasmids, and restriction enzymes to facilitate cloning, were responsible for the development of molecular transformation in fungi. Initial transformation success with filamentous fungi, involving the complementation of auxotrophic mutants by exposure to sheared genomic DNA or RNA from wt isolates, occurred with low transformation efficiencies. In addition, it was difficult to retrieve complementing DNA fragments and isolate genes of interest. This prompted the development of transformation vectors and methods to increase efficiencies. The physiological studies performed with fungi indicated that the cell wall could be removed to generate protoplasts. It was evident that protoplasts could be transformed with significantly greater efficiencies than walled cells.
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Directory of Open Access Journals (Sweden)
Qiusheng Kong
Full Text Available Watermelon is one of the major Cucurbitaceae crops and the recent availability of genome sequence greatly facilitates the fundamental researches on it. Quantitative real-time reverse transcriptase PCR (qRT-PCR is the preferred method for gene expression analyses, and using validated reference genes for normalization is crucial to ensure the accuracy of this method. However, a systematic validation of reference genes has not been conducted on watermelon. In this study, transcripts of 15 candidate reference genes were quantified in watermelon using qRT-PCR, and the stability of these genes was compared using geNorm and NormFinder. geNorm identified ClTUA and ClACT, ClEF1α and ClACT, and ClCAC and ClTUA as the best pairs of reference genes in watermelon organs and tissues under normal growth conditions, abiotic stress, and biotic stress, respectively. NormFinder identified ClYLS8, ClUBCP, and ClCAC as the best single reference genes under the above experimental conditions, respectively. ClYLS8 and ClPP2A were identified as the best reference genes across all samples. Two to nine reference genes were required for more reliable normalization depending on the experimental conditions. The widely used watermelon reference gene 18SrRNA was less stable than the other reference genes under the experimental conditions. Catalase family genes were identified in watermelon genome, and used to validate the reliability of the identified reference genes. ClCAT1and ClCAT2 were induced and upregulated in the first 24 h, whereas ClCAT3 was downregulated in the leaves under low temperature stress. However, the expression levels of these genes were significantly overestimated and misinterpreted when 18SrRNA was used as a reference gene. These results provide a good starting point for reference gene selection in qRT-PCR analyses involving watermelon.
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Directory of Open Access Journals (Sweden)
Mario Fruzangohar
Full Text Available The primary means of classifying new functions for genes and proteins relies on Gene Ontology (GO, which defines genes/proteins using a controlled vocabulary in terms of their Molecular Function, Biological Process and Cellular Component. The challenge is to present this information to researchers to compare and discover patterns in multiple datasets using visually comprehensible and user-friendly statistical reports. Importantly, while there are many GO resources available for eukaryotes, there are none suitable for simultaneous, graphical and statistical comparison between multiple datasets. In addition, none of them supports comprehensive resources for bacteria. By using Streptococcus pneumoniae as a model, we identified and collected GO resources including genes, proteins, taxonomy and GO relationships from NCBI, UniProt and GO organisations. Then, we designed database tables in PostgreSQL database server and developed a Java application to extract data from source files and loaded into database automatically. We developed a PHP web application based on Model-View-Control architecture, used a specific data structure as well as current and novel algorithms to estimate GO graphs parameters. We designed different navigation and visualization methods on the graphs and integrated these into graphical reports. This tool is particularly significant when comparing GO groups between multiple samples (including those of pathogenic bacteria from different sources simultaneously. Comparing GO protein distribution among up- or down-regulated genes from different samples can improve understanding of biological pathways, and mechanism(s of infection. It can also aid in the discovery of genes associated with specific function(s for investigation as a novel vaccine or therapeutic targets.http://turing.ersa.edu.au/BacteriaGO.
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Alu Elements as Novel Regulators of Gene Expression in Type 1 Diabetes Susceptibility Genes?
Kaur, Simranjeet; Pociot, Flemming
2015-07-13
Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate genes to identify embedded Alu elements within these genes. We observed significant enrichment of Alu elements within the T1D genes (p-value genes harboring Alus revealed significant enrichment for immune-mediated processes (p-value genes harboring inverted Alus (IRAlus) within their 3' untranslated regions (UTRs) that are known to regulate the expression of host mRNAs by generating double stranded RNA duplexes. Our in silico analysis predicted the formation of duplex structures by IRAlus within the 3'UTRs of T1D genes. We propose that IRAlus might be involved in regulating the expression levels of the host T1D genes.
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Directory of Open Access Journals (Sweden)
Roger Andrew J
2003-06-01
Full Text Available Abstract Background Lateral gene transfer can introduce genes with novel functions into genomes or replace genes with functionally similar orthologs or paralogs. Here we present a study of the occurrence of the latter gene replacement phenomenon in the four gene families encoding different classes of glutamate dehydrogenase (GDH, to evaluate and compare the patterns and rates of lateral gene transfer (LGT in prokaryotes and eukaryotes. Results We extend the taxon sampling of gdh genes with nine new eukaryotic sequences and examine the phylogenetic distribution pattern of the various GDH classes in combination with maximum likelihood phylogenetic analyses. The distribution pattern analyses indicate that LGT has played a significant role in the evolution of the four gdh gene families. Indeed, a number of gene transfer events are identified by phylogenetic analyses, including numerous prokaryotic intra-domain transfers, some prokaryotic inter-domain transfers and several inter-domain transfers between prokaryotes and microbial eukaryotes (protists. Conclusion LGT has apparently affected eukaryotes and prokaryotes to a similar extent within the gdh gene families. In the absence of indications that the evolution of the gdh gene families is radically different from other families, these results suggest that gene transfer might be an important evolutionary mechanism in microbial eukaryote genome evolution.
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Radiotechnologies and gene therapy
International Nuclear Information System (INIS)
Xia Jinsong
2001-01-01
Gene therapy is an exciting frontier in medicine today. Radiologist will make an uniquely contribution to these exciting new technologies at every level by choosing sites for targeting therapy, perfecting and establishing routes of delivery, developing imaging strategies to monitor therapy and assess gene expression, developing radiotherapeutic used of gene therapy
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Piscopo, Sara-Pier; Drouin, Guy
2014-05-01
Gene conversions are nonreciprocal sequence exchanges between genes. They are relatively common in Saccharomyces cerevisiae, but few studies have investigated the evolutionary fate of gene conversions or their functional impacts. Here, we analyze the evolution and impact of gene conversions between the two genes encoding 2-deoxyglucose-6-phosphate phosphatase in S. cerevisiae, Saccharomyces paradoxus and Saccharomyces mikatae. Our results demonstrate that the last half of these genes are subject to gene conversions among these three species. The greater similarity and the greater percentage of GC nucleotides in the converted regions, as well as the absence of long regions of adjacent common converted sites, suggest that these gene conversions are frequent and occur independently in all three species. The high frequency of these conversions probably result from the fact that they have little impact on the protein sequences encoded by these genes.
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Mind the gap: the transition to hospital consultant.
Westerman, Michiel
2014-06-01
Thesis defended on the 19th of December 2012 at the faculty of Medicine of the VU University Amsterdam. Promotors: Professor Fedde Scheele MD, PhD, (VUmc Amsterdam) and Professor Albert Scherpbier MD, PhD (University of Maastricht). Copromotors: Pim Teunissen, MD, PhD (University of Maastricht) and Carl Siegert MD, PhD (St. Lucas Andreas Hospital, Amsterdam).
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Effect of probiotics on broiler meat quality
African Journals Online (AJOL)
STORAGESEVER
2009-08-04
Aug 4, 2009 ... características químicas e presença de Salmonella spp na carne. [tese]. Botucatu (SP): Universidade Estadual Paulista. Corrêa GSS, Gomes AVC, Corrêa AB, Salles AS (2000). Desempenho de frangos de corte alimentados com diferentes promotores de crescimento. In:Reunião Anual da SBZ, Viçosa. p.
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Investigation of the bond strength between the photo-sensitive polymer SU-8 and gold
DEFF Research Database (Denmark)
Nordström, Maria; Johansson, Alicia; Sánchez Noguerón, E.
2005-01-01
adhesion promotors between the SU-8 and Au; (ii) the influence of the processing sequence, keeping either Au or SU-8 as the bottom layer; (iii) the importance of the UV exposure dosage of the SU-8. For comparison, also the bond strength between SU-8 and other materials was measured. For SU-8 and Au without...
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Investigation of the bond strength between the photo-sensitive polymer SU-8 and Au
DEFF Research Database (Denmark)
Nordstrom, Maria; Johansson, Alicia; Sanches-Noguerón, E.
2004-01-01
promotors between the SU-8 and Au (ii) the effect of the processing sequence, either keeping SU-8 as bottum layer or Au (iii) varying the UV exposure dosage of the SU-8. For comparison, also the bond strength between SU-8 and other materials was measured. We report on bond strength of 4.8 +/- 1.2 MPa...
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Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data
Directory of Open Access Journals (Sweden)
Bing Jiang
2017-01-01
Full Text Available Gastric cancer is one of the most severe complex diseases with high morbidity and mortality in the world. The molecular mechanisms and risk factors for this disease are still not clear since the cancer heterogeneity caused by different genetic and environmental factors. With more and more expression data accumulated nowadays, we can perform integrative analysis for these data to understand the complexity of gastric cancer and to identify consensus players for the heterogeneous cancer. In the present work, we screened the published gene expression data and analyzed them with integrative tool, combined with pathway and gene ontology enrichment investigation. We identified several consensus differentially expressed genes and these genes were further confirmed with literature mining; at last, two genes, that is, immunoglobulin J chain and C-X-C motif chemokine ligand 17, were screened as novel gastric cancer associated genes. Experimental validation is proposed to further confirm this finding.
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Evolving chromosomes and gene regulatory networks
Indian Academy of Sciences (India)
Aswin
Genes under H NS control can be. (a) regulated by H NS. (b) regulated by H NS and StpA. Because backup by StpA is partial. Page 19. Gene expression level. H NS regulated xenogenes. Other genes. Page 20 ... recollect: H&NS silences highl transcribable genes. Gene expression level unilateral. Other genes epistatic ...
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Gene therapy and reproductive medicine.
Stribley, John M; Rehman, Khurram S; Niu, Hairong; Christman, Gregory M
2002-04-01
To review the literature on the principles of gene therapy and its potential application in reproductive medicine. Literature review. Gene therapy involves transfer of genetic material to target cells using a delivery system, or vector. Attention has primarily focused on viral vectors. Significant problems remain to be overcome including low efficacy of gene transfer, the transient expression of some vectors, safety issues with modified adenoviruses and retroviruses, and ethical concerns. If these issues can be resolved, gene therapy will be applicable to an increasing spectrum of single and multiple gene disorders, as the Human Genome Project data are analyzed, and the genetic component of human disease becomes better understood. Gynecologic gene therapy has advanced to human clinical trials for ovarian carcinoma, and shows potential for the treatment of uterine leiomyomata. Obstetric applications of gene therapy, including fetal gene therapy, remain more distant goals. Concerns about the safety of human gene therapy research are being actively addressed, and remarkable progress in improving DNA transfer has been made. The first treatment success for a genetic disease (severe combined immunodeficiency disease) has been achieved, and ongoing research efforts will eventually yield clinical applications in many spheres of reproductive medicine.
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Identification of Candidate B-Lymphoma Genes by Cross-Species Gene Expression Profiling
Tompkins, Van S.; Han, Seong-Su; Olivier, Alicia; Syrbu, Sergei; Bair, Thomas; Button, Anna; Jacobus, Laura; Wang, Zebin; Lifton, Samuel; Raychaudhuri, Pradip; Morse, Herbert C.; Weiner, George; Link, Brian; Smith, Brian J.; Janz, Siegfried
2013-01-01
Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as a gene discovery tool in liver, breast, lung, prostate and other cancers, but has been largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We used global gene expression profiles of DLBCL-like tumors that arose spontaneously in Myc-transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the human DLBCL transcriptome. The human and mouse lymphomas were found to have 60 concordantly deregulated genes in common, including 8 genes that Cox hazard regression analysis associated with overall survival in a published landmark dataset of DLBCL. Genetic network analysis of the 60 genes followed by biological validation studies indicate FOXM1 as a candidate DLBCL and BL gene, supporting a number of studies contending that FOXM1 is a therapeutic target in mature B cell tumors. Our findings demonstrate the value of the “mouse filter” for genomic studies of human B-lineage neoplasms for which a vast knowledge base already exists. PMID:24130802
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Anti-EGFR immunonanoparticles containing IL12 and salmosin genes for targeted cancer gene therapy.
Kim, Jung Seok; Kang, Seong Jae; Jeong, Hwa Yeon; Kim, Min Woo; Park, Sang Il; Lee, Yeon Kyung; Kim, Hong Sung; Kim, Keun Sik; Park, Yong Serk
2016-09-01
Tumor-directed gene delivery is of major interest in the field of cancer gene therapy. Varied functionalizations of non-viral vectors have been suggested to enhance tumor targetability. In the present study, we prepared two different types of anti-EGF receptor (EGFR) immunonanoparticles containing pDNA, neutrally charged liposomes and cationic lipoplexes, for tumor-directed transfection of cancer therapeutic genes. Even though both anti-EGFR immunonanoparticles had a high binding affinity to the EGFR-positive cancer cells, the anti-EGFR immunolipoplex formulation exhibited approximately 100-fold higher transfection to the target cells than anti-EGFR immunoliposomes. The lipoplex formulation also showed a higher transfection to SK-OV-3 tumor xenografts in mice. Thus, IL12 and/or salmosin genes were loaded in the anti-EGFR immunolipoplexes and intravenously administered to mice carrying SK-OV-3 tumors. Co-transfection of IL12 and salmosin genes using anti-EGFR immunolipoplexes significantly reduced tumor growth and pulmonary metastasis. Furthermore, combinatorial treatment with doxorubicin synergistically inhibited tumor growth. These results suggest that anti-EGFR immunolipoplexes containing pDNA encoding therapeutic genes could be utilized as a gene-transfer modality for cancer gene therapy.
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cis sequence effects on gene expression
Directory of Open Access Journals (Sweden)
Jacobs Kevin
2007-08-01
Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.
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Combining many interaction networks to predict gene function and analyze gene lists.
Mostafavi, Sara; Morris, Quaid
2012-05-01
In this article, we review how interaction networks can be used alone or in combination in an automated fashion to provide insight into gene and protein function. We describe the concept of a "gene-recommender system" that can be applied to any large collection of interaction networks to make predictions about gene or protein function based on a query list of proteins that share a function of interest. We discuss these systems in general and focus on one specific system, GeneMANIA, that has unique features and uses different algorithms from the majority of other systems. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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The role of gene-gene interaction in the prediction of criminal behavior.
Boutwell, Brian B; Menard, Scott; Barnes, J C; Beaver, Kevin M; Armstrong, Todd A; Boisvert, Danielle
2014-04-01
A host of research has examined the possibility that environmental risk factors might condition the influence of genes on various outcomes. Less research, however, has been aimed at exploring the possibility that genetic factors might interact to impact the emergence of human traits. Even fewer studies exist examining the interaction of genes in the prediction of behavioral outcomes. The current study expands this body of research by testing the interaction between genes involved in neural transmission. Our findings suggest that certain dopamine genes interact to increase the odds of criminogenic outcomes in a national sample of Americans. Copyright © 2014 Elsevier Inc. All rights reserved.
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Homology-dependent Gene Silencing in Paramecium
Ruiz, Françoise; Vayssié, Laurence; Klotz, Catherine; Sperling, Linda; Madeddu, Luisa
1998-01-01
Microinjection at high copy number of plasmids containing only the coding region of a gene into the Paramecium somatic macronucleus led to a marked reduction in the expression of the corresponding endogenous gene(s). The silencing effect, which is stably maintained throughout vegetative growth, has been observed for all Paramecium genes examined so far: a single-copy gene (ND7), as well as members of multigene families (centrin genes and trichocyst matrix protein genes) in which all closely related paralogous genes appeared to be affected. This phenomenon may be related to posttranscriptional gene silencing in transgenic plants and quelling in Neurospora and allows the efficient creation of specific mutant phenotypes thus providing a potentially powerful tool to study gene function in Paramecium. For the two multigene families that encode proteins that coassemble to build up complex subcellular structures the analysis presented herein provides the first experimental evidence that the members of these gene families are not functionally redundant. PMID:9529389
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Using RNA-Seq data to select refence genes for normalizing gene expression in apple roots
Gene expression in apple roots in response to various stress conditions is a less-explored research subject. Reliable reference genes for normalizing quantitative gene expression data have not been carefully investigated. In this study, the suitability of a set of 15 apple genes were evaluated for t...
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Gene amplification in carcinogenesis
Directory of Open Access Journals (Sweden)
Lucimari Bizari
2006-01-01
Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.
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Salmond, G P; Lutkenhaus, J F; Donachie, W D
1980-01-01
We report the identification, cloning, and mapping of a new cell envelope gene, murG. This lies in a group of five genes of similar phenotype (in the order murE murF murG murC ddl) all concerned with peptidoglycan biosynthesis. This group is in a larger cluster of at least 10 genes, all of which are involved in some way with cell envelope growth. Images PMID:6998962
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Yang, Jun; Hou, Ziming; Wang, Changjiang; Wang, Hao; Zhang, Hongbing
2018-04-23
Adamantinomatous craniopharyngioma (ACP) is an aggressive brain tumor that occurs predominantly in the pediatric population. Conventional diagnosis method and standard therapy cannot treat ACPs effectively. In this paper, we aimed to identify key genes for ACP early diagnosis and treatment. Datasets GSE94349 and GSE68015 were obtained from Gene Expression Omnibus database. Consensus clustering was applied to discover the gene clusters in the expression data of GSE94349 and functional enrichment analysis was performed on gene set in each cluster. The protein-protein interaction (PPI) network was built by the Search Tool for the Retrieval of Interacting Genes, and hubs were selected. Support vector machine (SVM) model was built based on the signature genes identified from enrichment analysis and PPI network. Dataset GSE94349 was used for training and testing, and GSE68015 was used for validation. Besides, RT-qPCR analysis was performed to analyze the expression of signature genes in ACP samples compared with normal controls. Seven gene clusters were discovered in the differentially expressed genes identified from GSE94349 dataset. Enrichment analysis of each cluster identified 25 pathways that highly associated with ACP. PPI network was built and 46 hubs were determined. Twenty-five pathway-related genes that overlapped with the hubs in PPI network were used as signatures to establish the SVM diagnosis model for ACP. The prediction accuracy of SVM model for training, testing, and validation data were 94, 85, and 74%, respectively. The expression of CDH1, CCL2, ITGA2, COL8A1, COL6A2, and COL6A3 were significantly upregulated in ACP tumor samples, while CAMK2A, RIMS1, NEFL, SYT1, and STX1A were significantly downregulated, which were consistent with the differentially expressed gene analysis. SVM model is a promising classification tool for screening and early diagnosis of ACP. The ACP-related pathways and signature genes will advance our knowledge of ACP pathogenesis
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Caracausi, Maria; Piovesan, Allison; Antonaros, Francesca; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara
2017-09-01
The ideal reference, or control, gene for the study of gene expression in a given organism should be expressed at a medium‑high level for easy detection, should be expressed at a constant/stable level throughout different cell types and within the same cell type undergoing different treatments, and should maintain these features through as many different tissues of the organism. From a biological point of view, these theoretical requirements of an ideal reference gene appear to be best suited to housekeeping (HK) genes. Recent advancements in the quality and completeness of human expression microarray data and in their statistical analysis may provide new clues toward the quantitative standardization of human gene expression studies in biology and medicine, both cross‑ and within‑tissue. The systematic approach used by the present study is based on the Transcriptome Mapper tool and exploits the automated reassignment of probes to corresponding genes, intra‑ and inter‑sample normalization, elaboration and representation of gene expression values in linear form within an indexed and searchable database with a graphical interface recording quantitative levels of expression, expression variability and cross‑tissue width of expression for more than 31,000 transcripts. The present study conducted a meta‑analysis of a pool of 646 expression profile data sets from 54 different human tissues and identified actin γ 1 as the HK gene that best fits the combination of all the traditional criteria to be used as a reference gene for general use; two ribosomal protein genes, RPS18 and RPS27, and one aquaporin gene, POM121 transmembrane nucleporin C, were also identified. The present study provided a list of tissue‑ and organ‑specific genes that may be most suited for the following individual tissues/organs: Adipose tissue, bone marrow, brain, heart, kidney, liver, lung, ovary, skeletal muscle and testis; and also provides in these cases a representative
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The evolution of milk casein genes from tooth genes before the origin of mammals.
Kawasaki, Kazuhiko; Lafont, Anne-Gaelle; Sire, Jean-Yves
2011-07-01
Caseins are among cardinal proteins that evolved in the lineage leading to mammals. In milk, caseins and calcium phosphate (CaP) form a huge complex called casein micelle. By forming the micelle, milk maintains high CaP concentrations, which help altricial mammalian neonates to grow bone and teeth. Two types of caseins are known. Ca-sensitive caseins (α(s)- and β-caseins) bind Ca but precipitate at high Ca concentrations, whereas Ca-insensitive casein (κ-casein) does not usually interact with Ca but instead stabilizes the micelle. Thus, it is thought that these two types of caseins are both necessary for stable micelle formation. Both types of caseins show high substitution rates, which make it difficult to elucidate the evolution of caseins. Yet, recent studies have revealed that all casein genes belong to the secretory calcium-binding phosphoprotein (SCPP) gene family that arose by gene duplication. In the present study, we investigated exon-intron structures and phylogenetic distributions of casein and other SCPP genes, particularly the odontogenic ameloblast-associated (ODAM) gene, the SCPP-Pro-Gln-rich 1 (SCPPPQ1) gene, and the follicular dendritic cell secreted peptide (FDCSP) gene. The results suggest that contemporary Ca-sensitive casein genes arose from a putative common ancestor, which we refer to as CSN1/2. The six putative exons comprising CSN1/2 are all found in SCPPPQ1, although ODAM also shares four of these exons. By contrast, the five exons of the Ca-insensitive casein gene are all reminiscent of FDCSP. The phylogenetic distribution of these genes suggests that both SCPPPQ1 and FDCSP arose from ODAM. We thus argue that all casein genes evolved from ODAM via two different pathways; Ca-sensitive casein genes likely originated directly from SCPPPQ1, whereas the Ca-insensitive casein genes directly differentiated from FDCSP. Further, expression of ODAM, SCPPPQ1, and FDCSP was detected in dental tissues, supporting the idea that both types of caseins
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Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster
Directory of Open Access Journals (Sweden)
Jakobek Judy L
2007-07-01
Full Text Available Abstract Background The biosynthesis of aflatoxin (AF involves over 20 enzymatic reactions in a complex polyketide pathway that converts acetate and malonate to the intermediates sterigmatocystin (ST and O-methylsterigmatocystin (OMST, the respective penultimate and ultimate precursors of AF. Although these precursors are chemically and structurally very similar, their accumulation differs at the species level for Aspergilli. Notable examples are A. nidulans that synthesizes only ST, A. flavus that makes predominantly AF, and A. parasiticus that generally produces either AF or OMST. Whether these differences are important in the evolutionary/ecological processes of species adaptation and diversification is unknown. Equally unknown are the specific genomic mechanisms responsible for ordering and clustering of genes in the AF pathway of Aspergillus. Results To elucidate the mechanisms that have driven formation of these clusters, we performed systematic searches of aflatoxin cluster homologs across five Aspergillus genomes. We found a high level of gene duplication and identified seven modules consisting of highly correlated gene pairs (aflA/aflB, aflR/aflS, aflX/aflY, aflF/aflE, aflT/aflQ, aflC/aflW, and aflG/aflL. With the exception of A. nomius, contrasts of mean Ka/Ks values across all cluster genes showed significant differences in selective pressure between section Flavi and non-section Flavi species. A. nomius mean Ka/Ks values were more similar to partial clusters in A. fumigatus and A. terreus. Overall, mean Ka/Ks values were significantly higher for section Flavi than for non-section Flavi species. Conclusion Our results implicate several genomic mechanisms in the evolution of ST, OMST and AF cluster genes. Gene modules may arise from duplications of a single gene, whereby the function of the pre-duplication gene is retained in the copy (aflF/aflE or the copies may partition the ancestral function (aflA/aflB. In some gene modules, the
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Zhang, Ruijie; Lv, Wenhua; Luan, Meiwei; Zheng, Jiajia; Shi, Miao; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Shang, Zhenwei; Duan, Lian; Jiang, Yongshuai
2015-11-24
Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.
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Biedler, James K; Tu, Zhijian
2010-07-08
The maternal zygotic transition marks the time at which transcription from the zygotic genome is initiated and a subset of maternal RNAs are progressively degraded in the developing embryo. A number of early zygotic genes have been identified in Drosophila melanogaster and comparisons to sequenced mosquito genomes suggest that some of these early zygotic genes such as bottleneck are fast-evolving or subject to turnover in dipteran insects. One objective of this study is to identify early zygotic genes from the yellow fever mosquito Aedes aegypti to study their evolution. We are also interested in obtaining early zygotic promoters that will direct transgene expression in the early embryo as part of a Medea gene drive system. Two novel early zygotic kinesin light chain genes we call AaKLC2.1 and AaKLC2.2 were identified by transcriptome sequencing of Aedes aegypti embryos at various time points. These two genes have 98% nucleotide and amino acid identity in their coding regions and show transcription confined to the early zygotic stage according to gene-specific RT-PCR analysis. These AaKLC2 genes have a paralogous gene (AaKLC1) in Ae. aegypti. Phylogenetic inference shows that an ortholog to the AaKLC2 genes is only found in the sequenced genome of Culex quinquefasciatus. In contrast, AaKLC1 gene orthologs are found in all three sequenced mosquito species including Anopheles gambiae. There is only one KLC gene in D. melanogaster and other sequenced holometabolous insects that appears to be similar to AaKLC1. Unlike AaKLC2, AaKLC1 is expressed in all life stages and tissues tested, which is consistent with the expression pattern of the An. gambiae and D. melanogaster KLC genes. Phylogenetic inference also suggests that AaKLC2 genes and their likely C. quinquefasciatus ortholog are fast-evolving genes relative to the highly conserved AaKLC1-like paralogs. Embryonic injection of a luciferase reporter under the control of a 1 kb fragment upstream of the AaKLC2.1 start
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Directory of Open Access Journals (Sweden)
Tu Zhijian
2010-07-01
Full Text Available Abstract Background The maternal zygotic transition marks the time at which transcription from the zygotic genome is initiated and a subset of maternal RNAs are progressively degraded in the developing embryo. A number of early zygotic genes have been identified in Drosophila melanogaster and comparisons to sequenced mosquito genomes suggest that some of these early zygotic genes such as bottleneck are fast-evolving or subject to turnover in dipteran insects. One objective of this study is to identify early zygotic genes from the yellow fever mosquito Aedes aegypti to study their evolution. We are also interested in obtaining early zygotic promoters that will direct transgene expression in the early embryo as part of a Medea gene drive system. Results Two novel early zygotic kinesin light chain genes we call AaKLC2.1 and AaKLC2.2 were identified by transcriptome sequencing of Aedes aegypti embryos at various time points. These two genes have 98% nucleotide and amino acid identity in their coding regions and show transcription confined to the early zygotic stage according to gene-specific RT-PCR analysis. These AaKLC2 genes have a paralogous gene (AaKLC1 in Ae. aegypti. Phylogenetic inference shows that an ortholog to the AaKLC2 genes is only found in the sequenced genome of Culex quinquefasciatus. In contrast, AaKLC1 gene orthologs are found in all three sequenced mosquito species including Anopheles gambiae. There is only one KLC gene in D. melanogaster and other sequenced holometabolous insects that appears to be similar to AaKLC1. Unlike AaKLC2, AaKLC1 is expressed in all life stages and tissues tested, which is consistent with the expression pattern of the An. gambiae and D. melanogaster KLC genes. Phylogenetic inference also suggests that AaKLC2 genes and their likely C. quinquefasciatus ortholog are fast-evolving genes relative to the highly conserved AaKLC1-like paralogs. Embryonic injection of a luciferase reporter under the control of a
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Investigation of ANGPTL3 expression, exon sequence and promotor ...
African Journals Online (AJOL)
like proteins, has been demonstrated to affect lipid metabolism by inhibiting the activity of lipoprotein lipase (LPL). Objective: To compare the ANGPTL3 mRNA and protein expression, exon mutation and promoter district CpG island methylation ...
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A estética como factor promotor da aprendizagem
Directory of Open Access Journals (Sweden)
Fátima Maria BEZERRA BARBOSA
2012-02-01
Full Text Available La reflexión filosófica sobre el arte, lo hermoso, lo bueno, lo verdadero y su capacidad de promover el desarrollo humano es un tema que remonta a Platón en la cultura occidental. Considerando que la educación debe ser entendida como un fenómeno integral, que abarca no sólo las dimensiones intelectuales sino también las dimensiones sensibles, la intuición y el raciocinio, las capacidades imaginativas y creativas, el «saber ser» y el «saber estar» parejas del «conocer» y del «saber hacer», pensamos que es incuestionable la importancia de la estética en el fenómeno educativo. El objetivo de este trabajo es demostrar la importancia de la educación estética como motor fundamental de desarrollo humano y, en este sentido, como catalizador de la motivación y del aprendizaje, para que, a través de la imaginación y de la creatividad, sea posible la innovación en la construcción de vías alternativas para un mundo más humano y placentero.
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Xi, Zhenxiang; Liu, Liang; Davis, Charles C
2015-11-01
The development and application of coalescent methods are undergoing rapid changes. One little explored area that bears on the application of gene-tree-based coalescent methods to species tree estimation is gene informativeness. Here, we investigate the accuracy of these coalescent methods when genes have minimal phylogenetic information, including the implementation of the multilocus bootstrap approach. Using simulated DNA sequences, we demonstrate that genes with minimal phylogenetic information can produce unreliable gene trees (i.e., high error in gene tree estimation), which may in turn reduce the accuracy of species tree estimation using gene-tree-based coalescent methods. We demonstrate that this problem can be alleviated by sampling more genes, as is commonly done in large-scale phylogenomic analyses. This applies even when these genes are minimally informative. If gene tree estimation is biased, however, gene-tree-based coalescent analyses will produce inconsistent results, which cannot be remedied by increasing the number of genes. In this case, it is not the gene-tree-based coalescent methods that are flawed, but rather the input data (i.e., estimated gene trees). Along these lines, the commonly used program PhyML has a tendency to infer one particular bifurcating topology even though it is best represented as a polytomy. We additionally corroborate these findings by analyzing the 183-locus mammal data set assembled by McCormack et al. (2012) using ultra-conserved elements (UCEs) and flanking DNA. Lastly, we demonstrate that when employing the multilocus bootstrap approach on this 183-locus data set, there is no strong conflict between species trees estimated from concatenation and gene-tree-based coalescent analyses, as has been previously suggested by Gatesy and Springer (2014). Copyright © 2015 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Taketo Wakai
Full Text Available Transcriptional negative regulation of the proteolytic system of Lactobacillus helveticus CM4 in response to amino acids seems to be very important for the control of antihypertensive peptide production; however, it remains poorly understood. A 26-kDa protein with N-terminal cystathionine β-synthase domains (CBS domain protein, which seems to be involved in the regulatory system, was purified by using a DNA-sepharose bound 300-bp DNA fragment corresponding to the upstream regions of the six proteolytic genes that are down-regulated by amino acids. The CBS domain protein bound to a DNA fragment corresponding to the region upstream of the pepV gene in response to branched chain amino acids (BCAAs. The expression of the pepV gene in Escherichia coli grown in BCAA-enriched medium was repressed when the CBS domain protein was co-expressed. These results reveal that the CBS domain protein acts as a novel type of BCAA-responsive transcriptional regulator (BCARR in L. helveticus. From comparative analysis of the promoter regions of the six proteolysis genes, a palindromic AT-rich motif, 5'-AAAAANNCTWTTATT-3', was predicted as the consensus DNA motif for the BCARR protein binding. Footprint analysis using the pepV promotor region and gel shift analyses with the corresponding short DNA fragments strongly suggested that the BCARR protein binds adjacent to the pepV promoter region and affects the transcription level of the pepV gene in the presence of BCAAs. Homology search analysis of the C-terminal region of the BCARR protein suggested the existence of a unique βαββαβ fold structure that has been reported in a variety of ACT (aspartate kinase-chorismate mutase-tyrA domain proteins for sensing amino acids. These results also suggest that the sensing of BCAAs by the ACT domain might promote the binding of the BCARR to DNA sequences upstream of proteolysis genes, which affects the gene expression of the proteolytic system in L. helveticus.
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Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer
DEFF Research Database (Denmark)
Jensen, Lars Henrik; Kuramochi, Hidekazu; Crüger, Dorthe Gylling
2011-01-01
promoter was only detected in 14 samples and only at a low level with no correlation to gene expression. MSH2 gene expression was not a prognostic factor for overall survival in univariate or multivariate analysis. The gene expression of MSH2 is a potential quantitative marker ready for further clinical...
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Enhanced gene ranking approaches using modified trace ratio algorithm for gene expression data
Directory of Open Access Journals (Sweden)
Shruti Mishra
Full Text Available Microarray technology enables the understanding and investigation of gene expression levels by analyzing high dimensional datasets that contain few samples. Over time, microarray expression data have been collected for studying the underlying biological mechanisms of disease. One such application for understanding the mechanism is by constructing a gene regulatory network (GRN. One of the foremost key criteria for GRN discovery is gene selection. Choosing a generous set of genes for the structure of the network is highly desirable. For this role, two suitable methods were proposed for selection of appropriate genes. The first approach comprises a gene selection method called Information gain, where the dataset is reformed and fused with another distinct algorithm called Trace Ratio (TR. Our second method is the implementation of our projected modified TR algorithm, where the scoring base for finding weight matrices has been re-designed. Both the methods' efficiency was shown with different classifiers that include variants of the Artificial Neural Network classifier, such as Resilient Propagation, Quick Propagation, Back Propagation, Manhattan Propagation and Radial Basis Function Neural Network and also the Support Vector Machine (SVM classifier. In the study, it was confirmed that both of the proposed methods worked well and offered high accuracy with a lesser number of iterations as compared to the original Trace Ratio algorithm. Keywords: Gene regulatory network, Gene selection, Information gain, Trace ratio, Canonical correlation analysis, Classification
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Characterization of the MLO gene family in Rosaceae and gene expression analysis in Malus domestica.
Pessina, Stefano; Pavan, Stefano; Catalano, Domenico; Gallotta, Alessandra; Visser, Richard G F; Bai, Yuling; Malnoy, Mickael; Schouten, Henk J
2014-07-22
Powdery mildew (PM) is a major fungal disease of thousands of plant species, including many cultivated Rosaceae. PM pathogenesis is associated with up-regulation of MLO genes during early stages of infection, causing down-regulation of plant defense pathways. Specific members of the MLO gene family act as PM-susceptibility genes, as their loss-of-function mutations grant durable and broad-spectrum resistance. We carried out a genome-wide characterization of the MLO gene family in apple, peach and strawberry, and we isolated apricot MLO homologs through a PCR-approach. Evolutionary relationships between MLO homologs were studied and syntenic blocks constructed. Homologs that are candidates for being PM susceptibility genes were inferred by phylogenetic relationships with functionally characterized MLO genes and, in apple, by monitoring their expression following inoculation with the PM causal pathogen Podosphaera leucotricha. Genomic tools available for Rosaceae were exploited in order to characterize the MLO gene family. Candidate MLO susceptibility genes were identified. In follow-up studies it can be investigated whether silencing or a loss-of-function mutations in one or more of these candidate genes leads to PM resistance.
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Systematic Search for Gene-Gene Interaction Effect on Prostate Cancer Risk
2013-07-01
Systematic Search for Gene-Gene Interaction 5a. CONTRACT NUMBER Effect on Prostate Cancer Risk 5b. GRANT NUMBER W81XWH-09-1-0488 5c. PROGRAM...Supported by this grant ) 1. Tao S, Wang Z, Feng J, Hsu FC, Jin G, Kin ST, Zhang Z, Gronberg H, Zheng, SL, Isaacs WB, XU J, Sun J. A Genome-Wide Search for...order interactions among estrogen- metabolism genes in sporadic breast cancer. Am J Hum Genet, 69, 138-47. 48. Marchini, J., Donnelly, P. and Cardon
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[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].
Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin
2017-02-10
Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.
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Directory of Open Access Journals (Sweden)
Elízabeth Contreras
2011-07-01
Abstract Cassava is a staple food for more than a billion people. One of the major diseases of cassava which could compromise food security is known as cassava bacterial blight, caused by the bacterium Xanthomonas axonopodis pv. manihotis (Xam. The RXam2 resistance gene candidate encodes a protein with Nucleotide Binding Site and Leucine Rich Repeats domains, and colocalizes with a QTL (Quantitative Trait Loci that accounts for 61.6% of the resistance to the Xam strain CIO151. In this work we sequenced 1816 bp corresponding to a partial sequence of this gene in three cassava varieties with the aim of having a preliminary overview of the degree of Single Nucleotide Polymorphisms (SNPs. The sequenced regions included 507 bp of the promotor and 1309 bp of the coding sequence. It was possible to identify five and 31 intravarietal SNPs in MCOL2246 and TMS60444, respectively. In addition, the number of SNPs between varieties was 44, 34 and 23 for MCOL2246-TMS60444, TMS60444-SG107-35 and MCOL2246-SG107-35, respectively. The largest number of SNPs was located in the promoter region -500 to -300 bp. This study may help to develop alternatives to identify SNPs in a more diverse group of cassava varieties, and possibly associate them with resistance/susceptible phenotypes. Key words: Cassava; resistance; polymorphisms; SNP.
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Yamada, Yuma; Ishikawa, Takuya; Harashima, Hideyoshi
2017-08-01
Mitochondria have their own gene expression system that is independent of the nuclear system, and control cellular functions in cooperation with the nucleus. While a number of useful technologies for achieving nuclear transgene expression have been reported, only a few have focused on mitochondria. In this study, we validated the utility of an artificial mitochondrial DNA vector with a virus promoter on mitochondrial transgene expression. We designed and constructed pCMV-mtLuc (CGG) that contains a CMV promotor derived from Cytomegalovirus and an artificial mitochondrial genome with a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system. Nluc luciferase activity measurements showed that the pCMV-mtLuc (CGG) efficiently produced the Nluc luciferase protein in human HeLa cells. Moreover, we optimized the mitochondrial transfection of pCMV-mtLuc (CGG) using a MITO-Porter system, a liposome-based carrier for mitochondrial delivery via membrane fusion. As a result, we found that transfection of pCMV-mtLuc (CGG) by MITO-Porter modified with the KALA peptide (cationic amphipathic cell-penetrating peptide) showed a high mitochondrial transgene expression. The developed mitochondrial transgene expression system represents a potentially useful tool for the fields of nanoscience and nanotechnology for controlling the intracellular microenvironment via the regulation of mitochondrial function and promises to open additional innovative research fields of study. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Synthetic sustained gene delivery systems.
Agarwal, Ankit; Mallapragada, Surya K
2008-01-01
Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.
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Gene transfer therapy in vascular diseases.
McKay, M J; Gaballa, M A
2001-01-01
Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of
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Tian, Feng-Xia; Zang, Jian-Lei; Wang, Tan; Xie, Yu-Li; Zhang, Jin; Hu, Jian-Jun
2015-01-01
Aldehyde dehydrogenases (ALDHs) constitute a superfamily of NAD(P)+-dependent enzymes that catalyze the irreversible oxidation of a wide range of reactive aldehydes to their corresponding nontoxic carboxylic acids. ALDHs have been studied in many organisms from bacteria to mammals; however, no systematic analyses incorporating genome organization, gene structure, expression profiles, and cis-acting elements have been conducted in the model tree species Populus trichocarpa thus far. In this study, a comprehensive analysis of the Populus ALDH gene superfamily was performed. A total of 26 Populus ALDH genes were found to be distributed across 12 chromosomes. Genomic organization analysis indicated that purifying selection may have played a pivotal role in the retention and maintenance of PtALDH gene families. The exon-intron organizations of PtALDHs were highly conserved within the same family, suggesting that the members of the same family also may have conserved functionalities. Microarray data and qRT-PCR analysis indicated that most PtALDHs had distinct tissue-specific expression patterns. The specificity of cis-acting elements in the promoter regions of the PtALDHs and the divergence of expression patterns between nine paralogous PtALDH gene pairs suggested that gene duplications may have freed the duplicate genes from the functional constraints. The expression levels of some ALDHs were up- or down-regulated by various abiotic stresses, implying that the products of these genes may be involved in the adaptation of Populus to abiotic stresses. Overall, the data obtained from our investigation contribute to a better understanding of the complexity of the Populus ALDH gene superfamily and provide insights into the function and evolution of ALDH gene families in vascular plants.
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Directory of Open Access Journals (Sweden)
Feng-Xia Tian
Full Text Available Aldehyde dehydrogenases (ALDHs constitute a superfamily of NAD(P+-dependent enzymes that catalyze the irreversible oxidation of a wide range of reactive aldehydes to their corresponding nontoxic carboxylic acids. ALDHs have been studied in many organisms from bacteria to mammals; however, no systematic analyses incorporating genome organization, gene structure, expression profiles, and cis-acting elements have been conducted in the model tree species Populus trichocarpa thus far. In this study, a comprehensive analysis of the Populus ALDH gene superfamily was performed. A total of 26 Populus ALDH genes were found to be distributed across 12 chromosomes. Genomic organization analysis indicated that purifying selection may have played a pivotal role in the retention and maintenance of PtALDH gene families. The exon-intron organizations of PtALDHs were highly conserved within the same family, suggesting that the members of the same family also may have conserved functionalities. Microarray data and qRT-PCR analysis indicated that most PtALDHs had distinct tissue-specific expression patterns. The specificity of cis-acting elements in the promoter regions of the PtALDHs and the divergence of expression patterns between nine paralogous PtALDH gene pairs suggested that gene duplications may have freed the duplicate genes from the functional constraints. The expression levels of some ALDHs were up- or down-regulated by various abiotic stresses, implying that the products of these genes may be involved in the adaptation of Populus to abiotic stresses. Overall, the data obtained from our investigation contribute to a better understanding of the complexity of the Populus ALDH gene superfamily and provide insights into the function and evolution of ALDH gene families in vascular plants.
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Wang, Ying; Ding, Jun; Daniell, Henry; Hu, Haiyan; Li, Xiaoman
2012-09-01
Chloroplasts play critical roles in land plant cells. Despite their importance and the availability of at least 200 sequenced chloroplast genomes, the number of known DNA regulatory sequences in chloroplast genomes are limited. In this paper, we designed computational methods to systematically study putative DNA regulatory sequences in intergenic regions near chloroplast genes in seven plant species and in promoter sequences of nuclear genes in Arabidopsis and rice. We found that -35/-10 elements alone cannot explain the transcriptional regulation of chloroplast genes. We also concluded that there are unlikely motifs shared by intergenic sequences of most of chloroplast genes, indicating that these genes are regulated differently. Finally and surprisingly, we found five conserved motifs, each of which occurs in no more than six chloroplast intergenic sequences, are significantly shared by promoters of nuclear-genes encoding chloroplast proteins. By integrating information from gene function annotation, protein subcellular localization analyses, protein-protein interaction data, and gene expression data, we further showed support of the functionality of these conserved motifs. Our study implies the existence of unknown nuclear-encoded transcription factors that regulate both chloroplast genes and nuclear genes encoding chloroplast protein, which sheds light on the understanding of the transcriptional regulation of chloroplast genes.
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Screening Reliable Reference Genes for RT-qPCR Analysis of Gene Expression in Moringa oleifera.
Deng, Li-Ting; Wu, Yu-Ling; Li, Jun-Cheng; OuYang, Kun-Xi; Ding, Mei-Mei; Zhang, Jun-Jie; Li, Shu-Qi; Lin, Meng-Fei; Chen, Han-Bin; Hu, Xin-Sheng; Chen, Xiao-Yang
2016-01-01
Moringa oleifera is a promising plant species for oil and forage, but its genetic improvement is limited. Our current breeding program in this species focuses on exploiting the functional genes associated with important agronomical traits. Here, we screened reliable reference genes for accurately quantifying the expression of target genes using the technique of real-time quantitative polymerase chain reaction (RT-qPCR) in M. oleifera. Eighteen candidate reference genes were selected from a transcriptome database, and their expression stabilities were examined in 90 samples collected from the pods in different developmental stages, various tissues, and the roots and leaves under different conditions (low or high temperature, sodium chloride (NaCl)- or polyethyleneglycol (PEG)- simulated water stress). Analyses with geNorm, NormFinder and BestKeeper algorithms revealed that the reliable reference genes differed across sample designs and that ribosomal protein L1 (RPL1) and acyl carrier protein 2 (ACP2) were the most suitable reference genes in all tested samples. The experiment results demonstrated the significance of using the properly validated reference genes and suggested the use of more than one reference gene to achieve reliable expression profiles. In addition, we applied three isotypes of the superoxide dismutase (SOD) gene that are associated with plant adaptation to abiotic stress to confirm the efficacy of the validated reference genes under NaCl and PEG water stresses. Our results provide a valuable reference for future studies on identifying important functional genes from their transcriptional expressions via RT-qPCR technique in M. oleifera.
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Gene expression profiles in skeletal muscle after gene electrotransfer
DEFF Research Database (Denmark)
Hojman, Pernille; Zibert, John R; Gissel, Hanne
2007-01-01
BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...
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Targeted cancer gene therapy : the flexibility of adenoviral gene therapy vectors
Rots, MG; Curiel, DT; Gerritsen, WR; Haisma, HJ
2003-01-01
Recombinant adenoviral vectors are promising reagents for therapeutic interventions in humans, including gene therapy for biologically complex diseases like cancer and cardiovascular diseases. In this regard, the major advantage of adenoviral vectors is their superior in vivo gene transfer
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Link-based quantitative methods to identify differentially coexpressed genes and gene Pairs
Directory of Open Access Journals (Sweden)
Ye Zhi-Qiang
2011-08-01
Full Text Available Abstract Background Differential coexpression analysis (DCEA is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance. Results We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links. Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis. Conclusions This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum.
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Learning Gene Regulatory Networks Computationally from Gene Expression Data Using Weighted Consensus
Fujii, Chisato
2015-04-16
Gene regulatory networks analyze the relationships between genes allowing us to un- derstand the gene regulatory interactions in systems biology. Gene expression data from the microarray experiments is used to obtain the gene regulatory networks. How- ever, the microarray data is discrete, noisy and non-linear which makes learning the networks a challenging problem and existing gene network inference methods do not give consistent results. Current state-of-the-art study uses the average-ranking-based consensus method to combine and average the ranked predictions from individual methods. However each individual method has an equal contribution to the consen- sus prediction. We have developed a linear programming-based consensus approach which uses learned weights from linear programming among individual methods such that the methods have di↵erent weights depending on their performance. Our result reveals that assigning di↵erent weights to individual methods rather than giving them equal weights improves the performance of the consensus. The linear programming- based consensus method is evaluated and it had the best performance on in silico and Saccharomyces cerevisiae networks, and the second best on the Escherichia coli network outperformed by Inferelator Pipeline method which gives inconsistent results across a wide range of microarray data sets.