975 resultados para Transcriptional profile


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AbstractOBJECTIVEDescribing the profile of victims and assaults by gunshot, where the outcome was death.METHODAn ecological study conducted in the city of Maceió/AL, in 2012. Data were collected from the death statements. The variables studied were: the death circumstances, gender, age, marital status, place, date, time, month and proportion according to the occurring neighborhood.RESULTSThe homicide mortality rate was 65.2 per 100,000 inhabitants, with 130.6 per 100,000 men and 7.8 per 100,000 women. Of the total number of homicides, 93.6% of the victims were men. The age group between 15 and 29 years of age was the most affected, with 68.8%. In 97.6% of cases the death occurred at the site of aggression, 74.1% in the streets. In relation to the date, 54.2% of cases occurred between Friday and Sunday. 59.7% of the homicides were concentrated in seven neighborhoods.CONCLUSIONThe map of violence presented shows heterogeneous areas for the occurrence of assaults with firearms, characterizing the existing urban inequality in violence distribution.

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Ambient light conditions trigger both developmental transitions, such as the induction of flowering, and a suite of adaptive responses, exemplified by the shade-avoidance syndrome. These responses are initiated by three families of photoreceptors that are conserved in all higher plants: the phototropins, cryptochromes and phytochromes (phyA--phyE, cry1--cry3, phot1 and phot2 in Arabidopsis). Molecular genetic studies performed mainly in Arabidopsis indicate that photon capture by these light sensors usually initiates rapid changes in the gene expression profile, leading to plant adaptation to their environment. Interestingly, numerous transcription factors are early targets of light regulation, both at the transcriptional and post-transcriptional levels.

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Two distinct, TATA box-containing promoters regulate the transcriptional activity of the Xenopus vitellogenin A1 gene. These two promoters are of different strength and are separated by 1.8 kilobase pairs of untranslated sequence. Estrogen receptor (ER) and its ligand, 17beta-estradiol, induce the activity of both promoters. The estrogen response elements (EREs) are located proximal to the downstream i promoter while no ERE-like sequences have been identified in the vicinity of the upstream io promoter. We show here, that transcriptional activity of the upstream io promoter is Sp1-dependent. Moreover, we demonstrate that estrogen inducibility of the io promoter results from functional interactions between the io bound Sp1 and the ER bound at the proximity of i. Functional interactions between Sp1 and ER do not require the presence of a TATA box for transcriptional activation, as is demonstrated using the acyl-CoA oxidase promoter. The relative positions that ER and Sp1 occupy with respect to the initiation site determines whether these two transcription activators can synergize for transcription initiation.

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Given the current economic environment, high-growth companies are particularly relevant for their contribution to employment generation and wealth.This paper discusses the results of a survey that was conducted in order to gain a deeper understanding of high-growth cooperatives through analyzing their financial profiles and then identifying key contributing factors to their growth. To do this, we compared this particular sample with other cooperatives and other high-growth mercantile companies.The results show the main drivers related to high-growth companies success. They are the competitive advantages based on the surveyed group, modern management techniques, quality and productivity, innovation and internationalization. Additionally, we have observed some financial strengths and weaknesses. In this sense, they are under capitalized companies with an unbalanced growth.

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Summary Mood disorders are among the most prevalent, psychosocial^ debilitating, chronic and relapsing forms of psychiatric illnesses. Despite considerable advances in their characterization, the heterogeneous nature of susceptibility factors and patient's symptoms could account for the lack of totally effective and remissive treatment. The neurobiological hypothesis of mood disorders etiology has evolved since the monoamine and neurotrophin theories and current evidence is pointing toward their integration in a broader polygenic epistatic model resulting in defective neuroplasticity of circuitries involved in emotion processing. Consequently, the unraveling of molecular underpinning pathways involved in neuronal plasticity, commonly altered among mood disorder syndromes and symptoms, should shed light on their etiology and provide new drug target. The transcription factor CREB has been critically involved in the long-lasting forms of neuronal plasticity and in the regulation of several mood disorders susceptibility genes. In addition, altered CREB activity has been associated with mood disorders pathophysiology and pharmacotherapy. Interestingly, the newly-identified protein CREB-regulated transcription coactivator 1 (CRTC1) was shown by previous studies in the laboratory to be a neuroactivity- dependent cAMP and calcium sensor, a potent activator of CREB-dependent transcription and involved in neuroplasticity mechanisms associated with long-term synaptic potentiation. Furthermore, the major mood disorder susceptibility gene Bdnf was suggested to be transcriptional regulated by CRTC1. Therefore, we aimed to investigate a role for CRTC1 in mood disorders by generating and characterizing a Crtcl deficient mouse model at the behavioral and molecular levels. Interestingly, their comprehensive characterization revealed a behavioral profile mirroring several major symptoms comorbid in mood disorders, including altered social interactions, aggressive behaviors, obesity, psychomotor retardation, increased emotional response to stress, decreased sexual drive and depression-like behaviors. To investigate the molecular mechanisms underlying these pathological behaviors and the implication of CRTC1 in the regulation of CREB-regulated genes in vivo, we also quantified transcript levels of several relevant CREB-regulated susceptibility genes in brain structures involved in the pathophysiology of mood disorders. Strikingly, we found the underexpression of primary components of the neurotrophin system: Bdnf and its cognate receptor TrkB, a marked decrease in the Nr4a family of transcription factors, implicated in neuroplasticity and associated with dopamine-related disorders, as well as in several other relevant CREB regulated genes. Moreover, neurochemical analysis revealed that Crtcl null mice presented alteration in prefrontal cortical monoamine turnover as well as in hippocampal and accumbal serotonin levels, similarly associated with mood disorders etiology and pharmacotherapy. Together, the present thesis supports the involvement of CRTC1 pathway hypofunction in the pathogenesis of mood disorders and specifically in pathological aggression, obesity and depression-related behavior comorbidities. Ultimately, CRTC1 may represent an interesting antidepressant, antiaggressive or mood stabilizer drug target candidate through the modulation of major CREB regulated susceptibility genes. Les troubles de l'humeur comptent parmi les maladies psychiatriques les plus prévalentes, psychosocialement débilitantes, chroniques et avec le plus grand risque de rechute. Malgré de considérable avancées dans leur caractérisation, la nature hétérogène des facteurs de susceptibilité et des symptômes présentés par les patients, semble justifier l'absence de traitement entraînant une rémission complète de la maladie. L'hypothèse de l'étiologie neurobiologique des troubles de l'humeur a évolué depuis la théorie des monoamines et des neurotrophines. Actuellement, elle tend à les englober dans un modèle polygénique épistatique induisant une déficience de la neuroplasticité des circuits impliqué dans la régulation des émotions. Par conséquent, il apparaît particulièrement relevant de caractériser des voies moléculaires impliquées dans la plasticité neuronale, communément altérées parmi les différents syndromes et symptômes des maladies de l'humeur, afin d'améliorer leur compréhension ainsi que de proposer de nouvelles cibles thérapeutiques potentielles. Le facteur de transcription CREB a été de façon répétée et cohérente impliqué dans les mécanismes à long terme de la plasticité neuronale, ainsi que dans la régulation de plusieurs gènes de susceptibilité aux maladies de l'humeur. De plus, une altération dans l'activité de CREB a été impliqué dans leur étiologie et pharmacothérapie. De façon intéressante, des résultats préliminaires sur la protéine récemment découverte CREB-regulated transcription coactivator 1 (CRTC1) ont indiqué que son activation était dépendante de l'activité neuronale, qu'il était un senseur du calcium et de l'AMPc, ainsi qu'un coactivateur de CREB requis et puissant impliqué dans les mécanismes de plasticité neuronale associés à la potentialisation à long terme. En outre, des résultats ont suggéré que le gène majeur de susceptibilité Bdnf est régulé par CRTC1. Ainsi, notre objectif a été d'investiguer un rôle éventuel de CRTC1 dans les maladies de l'humeur en générant et caractérisant une lignée de souris déficiente pour Crtcl, tant au niveau comportemental que moléculaire. De façon intéressante, leur caractérisation détaillée a révélé un profil comportemental reflétant de nombreux aspects des maladies de l'humeur incluant une altération des interactions sociales, une agression pathologique, l'obésité, un retard psychomoteur, une réponse émotionnelle au stress accrue, une diminution de la motivation sexuelle, et des comportements reliés à la dépression. Afin d'investiguer les mécanismes moléculaires sous- jacents cette altération du comportement, ainsi que l'implication de CRTC1 dans l'expression des gènes régulés par CREB in vivo, nous avons quantifié les niveaux de transcrits de plusieurs gènes de susceptibilité régulés par CREB et impliqués dans la physiopathologie des maladies de l'humeur. Remarquablement, nous avons trouvé la sous-expression de composants primordiaux du système neurotrophique: Bdnf et son récepteur TrkB, une diminution majeure de la famille des facteurs de transcription Nr4a, impliqués dans la neuroplasticité et associés à des désordres liés à la dopamine, ainsi que de nombreux autres gènes relevants régulés par CREB. De plus, une analyse neurochimique a révélé que les souris déficientes pour Crtcî présentent une altération du turn-over des monoamines du cortex préfrontal ainsi que des niveaux hippocampaux et accumbaux de sérotonine, associés de façon similaire dans l'étiologie et la pharmacothérapie des maladies de l'humeur. Vue dans son ensemble, la présente thèse supporte l'implication d'une sous-régulation de la voie de CRTCI dans la pathogenèse des maladies de l'humeur ainsi que dans la comorbidité de l'agression pathologique, l'obésité et la dépression. En conclusion, CRTCI pourrait représenter une cible médicamenteuse intéressante aux propriétés antidépressante, antiagressive ou stabilisatrice de l'humeur au travers de la modulation de gènes de susceptibilité majeurs régulés par CREB.

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The sequence profile method (Gribskov M, McLachlan AD, Eisenberg D, 1987, Proc Natl Acad Sci USA 84:4355-4358) is a powerful tool to detect distant relationships between amino acid sequences. A profile is a table of position-specific scores and gap penalties, providing a generalized description of a protein motif, which can be used for sequence alignments and database searches instead of an individual sequence. A sequence profile is derived from a multiple sequence alignment. We have found 2 ways to improve the sensitivity of sequence profiles: (1) Sequence weights: Usage of individual weights for each sequence avoids bias toward closely related sequences. These weights are automatically assigned based on the distance of the sequences using a published procedure (Sibbald PR, Argos P, 1990, J Mol Biol 216:813-818). (2) Amino acid substitution table: In addition to the alignment, the construction of a profile also needs an amino acid substitution table. We have found that in some cases a new table, the BLOSUM45 table (Henikoff S, Henikoff JG, 1992, Proc Natl Acad Sci USA 89:10915-10919), is more sensitive than the original Dayhoff table or the modified Dayhoff table used in the current implementation. Profiles derived by the improved method are more sensitive and selective in a number of cases where previous methods have failed to completely separate true members from false positives.

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Summary.  Background:  Severe stroke carries high rates of mortality and morbidity. The aims of this study were to determine the characteristics of patients who initially presented with severe ischemic stroke, and to identify acute and subacute predictors of favorable clinical outcome in these patients. Methods:  An observational cohort study, Acute Stroke Registry and Analysis of Lausanne (ASTRAL), was analyzed, and all patients presenting with severe stroke - defined as a National Institute of Health Stroke Scale score of ≥ 20 on admission - were compared with all other patients. In a multivariate analysis, associations with demographic, clinical, pathophysiologic, metabolic and neuroimaging factors were determined. Furthermore, we analyzed predictors of favorable outcome (modified Rankin scale score of ≤ 3 at 3 months) in the subgroup of severe stroke patients. Results:  Of 1915 consecutive patients, 243 (12.7%) presented with severe stroke. This was significantly associated with cardio-embolic stroke mechanism (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.19-2.54), unknown stroke onset (OR 2.35, 95% CI 1.14-4.83), more neuroimaging signs of early ischemia (mostly computed tomography; OR 2.65, 95% CI 1.79-3.92), arterial occlusions on acute imaging (OR 27.01, 95% CI 11.5-62.9), fewer chronic radiologic infarcts (OR 0.43, 95% CI 0.26-0.72), lower hemoglobin concentration (OR 0.97, 95% CI 0.96-0.99), and higher white cell count (OR 1.05, 95% CI 1.00-1.11). In the 68 (28%) patients with favorable outcomes despite presenting with severe stroke, this was predicted by lower age (OR 0.94, 95% CI 0.92-0.97), preceding cerebrovascular events (OR 3.00, 95% CI 1.01-8.97), hypolipemic pretreatment (OR 3.82, 95% CI 1.34-10.90), lower acute temperature (OR 0.43, 95% CI 0.23-0.78), lower subacute glucose concentration (OR 0.74, 95% CI 0.56-0.97), and spontaneous or treatment-induced recanalization (OR 4.51, 95% CI 1.96-10.41). Conclusions:  Severe stroke presentation is predicted by multiple clinical, radiologic and metabolic variables, several of which are modifiable. Predictors in the 28% of patients with favorable outcome despite presenting with severe stroke include hypolipemic pretreatment, lower acute temperature, lower glucose levels at 24 h, and arterial recanalization.

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Background: Most cases of neuroretinitis (NR) are idiopathic or due to cat scratch disease and occur as a single episode but a subgroup of patients experience recurrent attacks with cumulative visual loss. We reviewed our cases of NR to better characterize the clinical features of these subgroups in an effort to predict the risk of recurrence. Methods: Retrospective study of NR patients from a single institution. Sixty-seven patients were divided into three groups: 22 cases due to cat scratch disease (CSD-NR), 24 with idiopathic neuroretinitis (I-NR) and 21 (23 eyes) with recurrent neuroretinitis (R-NR). Results: Preceding systemic symptoms, predominantly central visual field (VF) loss and the combination of poor acuity with small relative afferent pupillary defect at presentation were common features of CSD-NR. There were no cases of recurrent CSD-NR. In the first attack of R-NR, the magnitude of VF loss at presentation was greater compared to the other two groups. While 39% of R-NR had a pattern of VF loss other than a central or cecocentral scotoma, only 13.6% of CSD-NR and 17% of I-NR showed this pattern. Visual recovery was least substantial for the R-NR group (average gain of 3.7 lines of Snellen acuity vs. 5 and 6.4 lines for CSD-NR and I-NR, respectively, and an average gain in VF score of 5.1 in the R-NR group compared to 8.2 and 11.5 for the other two groups). Conclusion: The main predictive factors for recurrence are absence of systemic symptoms, significant VF loss at presentation, particularly loss outside the central 30°, and less substantial visual recovery.

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The recent discovery of lipid-activatable transcription factors that regulate the genes controlling lipid metabolism and adipogenesis has provided insight into the way that organisms sense and respond to lipid levels. Identification of the signaling pathways in which these receptors are involved will help us to understand the control of energy balance and the molecular defects underlying its disorders.

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The plant hormones auxin and brassinosteroid are both essential regulators of plant growth and known to influence both cell division and cell elongation in various developmental contexts. These physiological effects of auxin and brassinosteroid have been known for many years. Based on observations from external simultaneous application of both hormones to plant tissues, it has been suggested that they act in an interdependent and possibly synergistic manner. Recent work in the model plant Arabidopsis thaliana suggests that, at the molecular level, auxin-brassinosteroid synergism manifests itself in the regulation of the expression of common target genes. However, whether this reflects genuine hormone pathway-dependent crosstalk modulation of the transcription machinery or rather indirect effects of hormone action on other cellular activities, such as hormone biosynthesis or the polar transport of auxin, is not entirely clear. This article reviews the evidence for transcriptional crosstalk between auxin and brassinosteroid and its molecular basis.

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Human activities have resulted in the release and introduction into the environment of a plethora of aromatic chemicals. The interest in discovering how bacteria are dealing with hazardous environmental pollutants has driven a large research community and has resulted in important biochemical, genetic, and physiological knowledge about the degradation capacities of microorganisms and their application in bioremediation, green chemistry, or production of pharmacy synthons. In addition, regulation of catabolic pathway expression has attracted the interest of numerous different groups, and several catabolic pathway regulators have been exemplary for understanding transcription control mechanisms. More recently, information about regulatory systems has been used to construct whole-cell living bioreporters that are used to measure the quality of the aqueous, soil, and air environment. The topic of biodegradation is relatively coherent, and this review presents a coherent overview of the regulatory systems involved in the transcriptional control of catabolic pathways. This review summarizes the different regulatory systems involved in biodegradation pathways of aromatic compounds linking them to other known protein families. Specific attention has been paid to describing the genetic organization of the regulatory genes, promoters, and target operon(s) and to discussing present knowledge about signaling molecules, DNA binding properties, and operator characteristics, and evidence from regulatory mutants. For each regulator family, this information is combined with recently obtained protein structural information to arrive at a possible mechanism of transcription activation. This demonstrates the diversity of control mechanisms existing in catabolic pathways.

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Esta tese centra-se em aspectos relevantes do inglês como uma língua universal, no actual contexto globalizado e examina possíveis mudanças relacionadas com o seu uso, em especial no continente africano, particularmente no caso de Cabo Verde, no sentido de ponderar eventuais alternativas nas pedagogias linguísticas no ensino desta língua que impliquem uma adaptação à realidade contemporânea. Uma vez que, nos nossos tempos, o inglês é a língua de eleição para a comunicação intercultural entre povos com várias experiências culturais e linguísticas, o conhecimento deste idioma torna-se, a cada dia que passa, impreterível e indispensável, na interacção intercultural. Em África, as funções desempenhadas pelo inglês são complexas; além da língua inglesa ser usada para comunicação entre etnias, com o estatuto de língua franca, também tem o papel de preservar a identidade nacional e de estabelecer a unidade entre os povos da mesma nação. Por conseguinte, é de considerar talvez ainda com mais pertinência, a adopção de uma nova filosofia de pedagogia de ensino que permita dotar os seus cidadãos de capacidades que lhes possibilitem comunicar de forma inteligível com povos de outras culturas e línguas. O primeiro capítulo aborda aspectos teóricos relacionados com a expansão, comunicação e mudança associadas à língua inglesa e suas implicações no ensino em países onde esta não é língua nativa (L1). O segundo capítulo reflecte, em primeiro lugar, sobre a situação linguística em África e as línguas francas predominantes no continente, incluindo a língua inglesa. Considera também questões relacionadas com o multilinguismo e a identidade, bem como assuntos relacionados com as implicações da diversidade linguística para a educação dos povos africanos.

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Background and Objectives: To specify which of the documented cognitive and emotional deficits characterize adolescents with conduct disorder (CD) compared with high-risk controls. Methods: High-risk adolescent males with and without CD were compared on intellectual efficiency, cognitive flexibility, impulsivity, alexithymia, and cognitive coping strategies. Substance use was controlled for in analyses. Results: Both groups showed normal intellectual efficiency and cognitive flexibility, as weil as heightened alexithymia and bebavioral impulsivity. Youths with CD evidenced more self-defeating and black-and-white tbinking under stress, and more acting-out under negative affect, than those without CD. Conclusions: Deficits specifie to CD resided in facets of emotional functioning and cognitive coping that might be targeted by a coping skills intervention.

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A report by the Iowa Epidemiological Outcome Workgroup showing the substance use epidemiological profile for the state of Iowa. The data shows the consumption patterns and consequences of adults and youths, males and females in Iowa.