The Evolution of Modularity in the Mammalian Skull I: Morphological Integration Patterns and Magnitudes

Morphological integration refers to the modular structuring of inter-trait relationships in an organism, which could bias the direction and rate of morphological change, either constraining or facilitating evolution along certain dimensions of the morphospace. Therefore, the description of patterns and magnitudes of morphological integration and the analysis of their evolutionary consequences are central to understand the evolution of complex traits. Here we analyze morphological integration in the skull of several mammalian orders, addressing the following questions: are there common patterns of inter-trait relationships? Are these patterns compatible with hypotheses based on shared development and function? Do morphological integration patterns and magnitudes vary in the same way across groups? We digitized more than 3,500 specimens spanning 15 mammalian orders, estimated the correspondent pooled within-group correlation and variance/covariance matrices for 35 skull traits and compared those matrices among the orders. We also compared observed patterns of integration to theoretical expectations based on common development and function. Our results point to a largely shared pattern of inter-trait correlations, implying that mammalian skull diversity has been produced upon a common covariance structure that remained similar for at least 65 million years. Comparisons with a rodent genetic variance/covariance matrix suggest that this broad similarity extends also to the genetic factors underlying phenotypic variation. In contrast to the relative constancy of inter-trait correlation/covariance patterns, magnitudes varied markedly across groups. Several morphological modules hypothesized from shared development and function were detected in the mammalian taxa studied. Our data provide evidence that mammalian skull evolution can be viewed as a history of inter-module parcellation, with the modules themselves being more clearly marked in those lineages with lower overall magnitude of integration. The implication of these findings is that the main evolutionary trend in the mammalian skull was one of decreasing the constraints to evolution by promoting a more modular architecture.

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 +/- A 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO(2 max)). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 +/- A 1 mu M) and G4 (14.2 +/- A 0.6 mu M) and between G2 (20.1 +/- A 1.7 mu M) and G4 (14.2 +/- A 0.6 mu M). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 +/- A 1.2 mu M) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity

Caloric restriction is the most effective non-genetic intervention to enhance lifespan known to date. A major research interest has been the development of therapeutic strategies capable of promoting the beneficial results of this dietary regimen. In this sense, we propose that compounds that decrease the efficiency of energy conversion, such as mitochondrial uncouplers, can be caloric restriction mimetics. Treatment of mice with low doses of the protonophore 2,4-dinitrophenol promotes enhanced tissue respiratory rates, improved serological glucose, triglyceride and insulin levels, decrease of reactive oxygen species levels and tissue DNA and protein oxidation, as well as reduced body weight. Importantly, 2,4-dinitrophenol-treated animals also presented enhanced longevity. Our results demonstrate that mild mitochondrial uncoupling is a highly effective in vivo antioxidant strategy, and describe the first therapeutic intervention capable of effectively reproducing the physiological, metabolic and lifespan effects of caloric restriction in healthy mammals.

Metabolismo da homocisteína e defeitos do tubo neural : um estudo bioquímico e molecular no sul do Brasil

Os defeitos de fechamento de tubo neural constituem uma das malformações mais freqüentes na espécie humana, apresentando alta morbi-mortalidade. Sua etiologia é considerada multifatorial, estando envolvidos fatores genéticos e ambientais. Estes fatores estão relacionados principalmente com o metabolismo da homocisteína. Realizamos um estudo de caso-controle com o objetivo de estudar os fatores bioquímicos e genéticos relacionados ao DTN na nossa população. Em pares de afetados com DTN e suas mães e pares de pacientes normais e suas mães foram avaliados dosagem de folato, vitamina B12, homocisteína e polimorfismos da enzima metileno tetraidrofolato redutase (MTHFR), C677T e A1298C. A dosagem de folato nos casos foi 11,37 ng/mL(±6,72) e nos controles 5,64 ng/mL(±4,16) (p<0,001). O folato sérico das mães foi 7,27 ng/mL (±4,48) e 3,90 ng/mL (±1,77) nas mães controles (p<0,001). A média de dosagem de vitamina B12 foi de 641,88 pg/mL ((±262,21) nos casos e 743,27 pg/mL (±433,52) nos controles (p= 0,205). A média de dosagem de vitamina B12 nas mães dos casos foi 354,75 pg/mL (±142,06) e 465,25 pg/mL (±194,91) nas mães controles (p=0,004). O nível de homocisteína plasmático médio foi 6,89 μmol/L(±4,48) para os casos e 5,41 μmol/L (±2,55) para os controles (p=0,099). Nas mães dos casos a dosagem média de homocisteína foi 7,23 μmol/L (±2,64) e 7,00 μmol/L (±2,24) nas mães controles (p=0,666). Não houve diferença entre a freqüência dos genótipos C677T e A1298C da MTHFR nos casos e controles e suas mães. Para o polimorfismo C677T as freqüências dos alelo C e T foram respectivamente 0,6585 e 0,3414 nos pacientes com DTN; 0,6590 e 0,3410 nos controles; 0,6460 e 0,3540 nas mães dos casos e 0,6136 e 0,3860 nas mães controles. Para o polimorfismo A1298C as freqüências dos alelos A e C foram respectivamente 0,7436 e 0,2564 nos pacientes com DTN; 0,7610 e 0,2390 nos controles; 0,8055 e 0,1945 nas mães dos casos e 0,8065 e 0,1935 nas mães controles. Identificamos que indivíduos homozigotos 677TT apresentam um maior nível de homocisteína e este é inversamente relacionado com os níveis de vitamina B12. Estes achados sugerem que uma alteração metabólica relacionada ao metabolismo da homocisteína e principalmente devido à diminuição da vitamina B12 seja um fator de risco para DTN na nossa população.

A qualidade no serviço de advocacia empresarial: um estudo de caso

° objetivo deste estudo exploratório foi o de investigar a percepção da qualidade no serviço de advocacia empresarial. Para tanto foi realizado um estudo de caso, envolvendo uma organização de grande porte e uma sociedade de advogados que lhe presta serviços de assessoria jurídica, ambos com sede no estado do Rio de Janeiro. Os dados foram obtidos a partir de entrevistas em profundidade com profissionais de ambos os lados, tendo em vista o forte caráter de interação inerente ao serviço estudado e, também, buscando-se identificar eventuais discrepâncias relativas aos critérios de julgamento quanto à sua qualidade. Os resultados indicam que o processo de avaliação da qualidade de serviços tende a apresentar traços distintos na sociedade brasileira devido às peculiaridades de seu sistema cultural. Especificamente quanto ao serviço de advocacia empresarial, restou claro que as expectativas do cliente desempenham um papel relevante para a percepção de sua qualidade, e que fatores não técnicos, ou de natureza funcional, também possuem grande influência no processo.

Estudo dos fatores genéticos de risco para o infarto agudo do miocárdio em idade precoce

O mecanismo patogênico mais importante no IAM é a oclusão trombótica de uma artéria coronariária no local de ruptura de uma placa aterosclerótica. Recentemente, diversos estudos têm investigado a associação entre o IAM e fatores genéticos protrombóticos. O presentetrabalho é um estudo tipo caso-controle a fim de avaliar o efeito de diversos polimorfismos genéticos em um grupo de pacientes com IAM antes dos 60 anos de idade. Foram investigados 283 pacientes e 93 indivíduos controles, todos caucasóides e sem diferenças quanto à proporção sexual e idade média entre os grupos.

Estudos sobre o conceito de inteligência e suas implicações

O objetivo deste trabalho é demonstrar que o conceito de inteligência apresenta implicações ideológicas. Para tal fim foi realizado um estudo das principais medidas e teorias sobre a inteligência. A partir deste estudo verificou-se que: 1) As medidas mais sofisticadas precederam as teorias mais formalizadas. A inteligência é um conceito que surgiu de um pólo muito mais técnico que teórico; 2) O primeiro teste padronizado de inteligência foi elaborado a pedido das autoridades escolares francesas. Segundo Althusser (1976), a instituição escolar é um aparelho idelógico do estado, tendo como finalidade garantir que a classe dominante exerça o seu domínio. 3) A fidedignidade é a expressão da conservaçao. O QI não varia com o tempo porque os testes foram construídos para este fim. 4) O critério de validação de um teste de inteligência, direta ou indiretamente, é o sucesso escolar. Desta forma não é necessário um teste para separar alunos brilhantes dos não brilhantes; basta que sejam usadas as notas obtidas pelos alunos nos exames escolares. 5) Algumas variáveis foram, relacionadas com o QI. Especial atenção foi dada à relação entre raça e QI. Foram apresentadas posições que atribuem a fatores genéticos a diferença de QI entre as raças, posições que atribuem esta diferença a fatores ambientais e um terceiro grupo que atribuem a mesma diferença a fatores genéticos-ambientais. 6) As teses geneticistas foram e são acusadas de serem ideológicas, pois, atribuindo-se diferenças a fatores genéticos, elimina-se a possibilidade de questionar o meio social (Caráter conservador da ideologia). 7) As teses ambientalistas também são ideológicas por aceitarem como verdadeira sua concepção, excluindo-se o componente genético. (Caráter deformante da ideologia). 8) As provas experimentais não podem resolver estas questões. Adotar uma ou outra posição é uma questão de valor. A partir do anteriormente exposto fica claro que o objetivo do trabalho não é optar por ou defender uma entre as explicações das diferenças relativas ao QI e, sim, mostrar que tais explicações assumem um caráter ideológico.

Determinantes do fluxo de fundos de investimento no Brasil

Nesse trabalho, procuramos identificar fatores sistemáticos que expliquem uma variação significativa nos fluxos destinados às diversas categorias de fundos de investimento brasileiros, a partir de análises de uma amostra de dados agregados de captações e resgates nesses produtos. O estudo buscou avaliar a existência de padrões de comportamento comuns aos investidores de fundos locais através da análise da migração de fluxos entre as diversas classes de fundos. Foram inicialmente tratados os fatores não comportamentais conhecidos que impactam o fluxo dos fundos, a variável dependente. Esses fatores conhecidos foram apurados através de uma revisão dos trabalhos acadêmicos dos mercados internacional e local. Após esse tratamento foi aplicado o método de decomposição de valores singulares (SVD - Singular Value Decomposition), com o objetivo de avaliarmos os efeitos comportamentais agrupados dos investidores. A decomposição em valores singulares sugere como principais fatores comuns comportamentos de entrada e saída de fundos em massa e migrações entre as classes de fundos de menor e as de maior risco, o que Baker e Wurgler (2007) chamaram de demanda especulativa, e que, segundo esses e outros autores pesquisados, poderia ser interpretada como uma proxy do sentimento dos investidores. Guercio e Tkac (2002) e Edelen et al. (2010), encontraram em suas pesquisas evidências da diferença de comportamento entre investidores de atacado e de varejo, o que foi detectado para a classes de fundos de Renda Variável no caso do presente estudo sobre o mercado brasileiro. O entendimento das variações na tolerância a risco dos investidores de fundos de investimento pode auxiliar na oferta de produtos mais compatíveis com a demanda. Isso permitiria projetar captações para os produtos com base nas características dessa oferta, o que também desenvolvemos nessa pesquisa para o caso das categorias de fundos Multimercado e Renda variável, através de um modelo de espaço de estados com sazonalidade determinística e inicialização SVD. O modelo proposto nesse trabalho parece ter conseguido capturar, na amostra avaliada (2005-2008), um comportamento que se manteve fora da amostra (2009-2011), validando, ao menos na amostra considerada, a proposta de extração dos componentes principais agregados do comportamento dos investidores de fundos brasileiros.

Coevolução e as práticas isomórficas de gestão: um estudo sobre os processos de mudanças institucionais no Instituto Federal de Educação, Ciência e Tecnologia do RN

The Federal Institution for Education, Science and Technology, in its historical path, has been living different changes. The transformations occurred along the way have been determined by coercive forces from the institutional environment, which has became more and more broad and complex throughout the time, obtaining diverse characteristics and new elements such as non institutional factors1 which started to contribute with the other changes. In this context, this work aims to study the isomorphic practices of the managers in the institutional changes process of the IFRN in 1998 and 2008, as of a theoretical coevolutionary perspective (CHILD; RODRIGUES; LEWIN; CARROL; VOLBERDA, 2003). This theory brings a new point of view for the organization analysis to the organizational studies, since it offers a non deterministic and non linear lection of the evolution process, which means, a coevolution. Thus, the organizations and their institutional and non institutional environment auto evolve, auto organize and auto reproduce. Therefore, the institutional and non institutional factors of the macro environment keep a continuous interdependence relationship with the organizations. For the means of this study, it is important to understand that is impossible to comprehend the object, the isomorphic practices, without considering that the previous institutional changes and its evolutions, its continuations and discontinuations, important in the coevolution process. As such, to call upon the institutional historical track is a fundamental aspect to materialize this study, for the recursive movement is indeed present in the coevolution. Another important point to make this research effective is that it is not possible to abdicate from the hologramatic view2 of this study, which considers the object, the isomorphic practices, part of the whole and this whole is also in the parts, therefore it is impossible to comprehend the object of study outside the context where it belongs. With this, as of the objective previously proposed, it is necessary to describe the characteristics of coevolution of the institutional changes related in 1998 and 2008; analyze the dynamic of the isomorphic mechanisms in its respective institutional change process; and describe the lessons learned which the isomorphic practices left to the IFRN, regarding its benefits and difficulties. All these transformations happened through coercive forces3 of the institutional environment. As of the Nineties, these forces became stronger, the environment became broader and more complex, with the emergency of new environmental factors. This study proposed to study the managing process and its practices, related to the micro environment, although it is required to articulate these actions, the demands and requirements from the macro environment. To make this research effective, semi structured interviews have been conducted with the managers who participated in both institutional change processes. In the results analysis, it has been possible to verify the particularity of each change, the one from 1998 with a strong normative action of the managers against coercive forces from the government for the search of recognition and the institutional legitimation and the one in 2008, which has been characterized by the normative action by managers in agreement with the coercive forces from the government, in favor of the government policy for the technological professional education. However, the results analysis it is possible to notice the evidence of a belonging feeling from the interviewed managers

Caracterização comportamental e distribuição de neurônios inibitórios em um modelo animal de autismo induzido por ácido valpróico

Autism comprises a heterogeneous group of neurodevelopmental disorders that affects the brain maturation and produces sensorial, motor, language and social interaction deficits in early childhood. Several studies have shown a major involvement of genetic factors leading to a predisposition to autism, which are possibly affected by environmental modulators during embryonic and post-natal life. Recent studies in animal models indicate that alterations in epigenetic control during development can generate neuronal maturation disturbances and produce a hyper-excitable circuit, resulting in typical symptoms of autism. In the animal model of autism induced by valproic acid (VPA) during rat pregnancy, behavioral, electrophysiological and cellular alterations have been reported which can also be observed in patients with autism. However, only a few studies have correlated behavioral alterations with the supposed neuronal hyper-excitability in this model. The aim of this project was to generate an animal model of autism by pre-natal exposure to VPA and evaluate the early post-natal development and pre-puberal (PND30) behavior in the offspring. Furthermore, we quantified the parvalbumin-positive neuronal distribution in the medial prefrontal cortex and Purkinje cells in the cerebellum of VPA animals. Our results show that VPA treatment induced developmental alterations, which were observed in behavioral changes as compared to vehicle-treated controls. VPA animals showed clear behavioral abnormalities such as hyperlocomotion, prolonged stereotipies and reduced social interaction with an unfamiliar mate. Cellular quantification revealed a decrease in the number of parvalbumin-positive interneurons in the anterior cingulate cortex and in the prelimbic cortex of the mPFC, suggesting an excitatory/inhibitory unbalance in this animal model of autism. Moreover, we also observed that the neuronal reduction occurred mainly in the cortical layers II/III and V/VI. We did not detect any change in the density of Purkinje neurons in the Crus I region of the cerebellar cortex. Together, our results strengthens the face validity of the VPA model in rats and shed light on specific changes in the inhibitory circuitry of the prefrontal cortex in this autism model. Further studies should address the challenges to clarify particular electrophysiological correlates of the cellular alterations in order to better understand the behavioral dysfunctions

Associação entre polimorfismos funcionais nos genes da MMP-7 e MMP-9 e o perfil clinicopatológico do carcinoma epidermóide de língua

Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the squamous cell carcinoma of the tongue

Tontura em idosos institucionalizados da cidade do NATAL/RN: Um estudo caso-controle em vestibulopatas e não-vestibulopatas

the institutionalized elderly presents for being more fragile a lot of body balance s changes, which can induce falls and health frailty. One of the consequences of it is the appearance of dizziness, vestibular or not. This study aims to identify the risk factors related to dizziness in institutionalized elderly, with and without vestibular disorders, in the city of Natal-RN. Method: a case-control study realized in 12 regulated by Health Surveillance Long Term Care Institutions for the elderly in Natal-RN. Elected seniors with good cognitive level and able to walk, totaling 115 individuals, and of these, 102 were selected according to the presence of dizziness in the last year (n = 51) and their controls (n = 51), paired by sex and age. The 51 elderly patients with dizziness were divided into 3 groups case: case one, for elderly with dizziness and without vestibulopathy (n=38); case two, for elderly with dizziness and vestibulopathy (n=13) and case three, for all the seniors with dizziness, or added to the case 1 case 2 (n=51). The 51 seniors who served as controls were also divided into three groups, according to the number of individuals of each case: control 1, n = 38, control 2, n = 13 control and 3 (sum of 1 control with control 2), n = 51. As possible risk factors were analyzed variables related to characteristics of the institution, to the habits of life of older people and those concerned with the health of the elderly. For statistical analysis, we used the chi-square or Fisher exact test for a significance level of 5% and calculating the association magnitude between variables by measuring the Odds Ratio. Results: as risk factors for dizziness without vestibular disorders were found the presence of hypertension and cardiovascular disease, as well as the presence of three or more disorders for elderly and use of gastric protector drugs. For the elderly group from case two were found no associated risk factor. For elderly patients with dizziness in the case group three, we observed the same risk factors found for the elderly in the case group one, plus the presence of osteoarthritis pathology, which was also significant for this group. Conclusion: dizziness in institutionalized elderly is associated with systemic common diseases in this age group and the vestibulopathy presents itself as pathology on an isolated way, not being possible, with our data, associate it with non-risk factors

A study of familial stuttering

Here we study 13 families with stuttering. of the 13 families, 9 were persistent stutterers and 4 were recovered stutterers. In the 9 families with persistent stuttering, 24 were male and 10 were females. of the 4 families with recovered stutterers, 17 were male and 3 were female. of the 17 males, 12 were persistent stutterers and 5 recovered after adolescence. All females were recovered stutterers. We conclude with a short discussion of recent molecular Studies. (c) 2006 Wiley-Liss, Inc.

Identification of a Microdeletion at the 7q33-q35 Disrupting the CNTNAP2 Gene in a Brazilian Stuttering Case

Speech and language disorders are some of the most common referral reasons to child development centers accounting for approximately 40% of cases. Stuttering is a disorder in which involuntary repetition, prolongation, or cessation of the sound precludes the flow of speech. About 5% of individuals in the general population have a stuttering problem, and about 80% of the affected children recover naturally. The causal factors of stuttering remain uncertain in most cases; studies suggest that genetic factors are responsible for 70% of the variance in liability for stuttering, whereas the remaining 30% is due to environmental effects supporting a complex cause of the disorder. The use of high-resolution genome wide array comparative genomic hybridization has proven to be a powerful strategy to narrow down candidate regions for complex disorders. We report on a case with a complex set of speech and language difficulties including stuttering who presented with a 10Mb deletion of chromosome region 7q33-35 causing the deletion of several genes and the disruption of CNTNAP2 by deleting the first three exons of the gene. CNTNAP2 is known to be involved in the cause of language and speech disorders and autism spectrum disorder and is in the same pathway as FOXP2, another important language gene, which makes it a candidate gene for causal studies speech and language disorders such as stuttering. (C) 2010 Wiley-Liss, Inc.

Prevenção de conflitos médico-legais no exercício da medicina

Os conflitos médico-legais que ocorrem no exercício da Cirurgia e da Medicina são motivos de preocupação não só no meio médico, mas também na sociedade como um todo, pois se de um lado geram um maior desgaste emocional ao médico, por outro, os pacientes estão sendo rejeitados. As causas desses conflitos são muitas, envolvendo fatores não assistenciais, como o sistema de saúde distorcido e desorganizado, a falta de participação da sociedade e do médico na melhoria desse sistema, o aparelho formador que lança no mercado grande número de jovens médicos despreparados para o exercício dessa nobre profissão, além da falta do ensino continuado. A solução para esses conflitos não poderá ser por meio de simples criação de leis, e nem pela negativa da existência do erro médico, que ocorre numa freqüência até maior do que os próprios conflitos. Todavia, pode-se afirmar que é muito importante melhorar a relação médico-paciente. É necessário, ainda, que o médico conheça a fundo seus deveres de conduta e que, principalmente, se abstenha de praticar abusos do poder. A sociedade deve também entender que a saúde não é uma questão exclusiva dos médicos e que deve lutar pela melhoria das condições dos níveis de vida.