Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

Objective: Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness, Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. Methods: We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found. Results: Pathogenic mutations in GJB2 and GJB6 genes were detected in 41 individuals (13.7%), and 80.5% (33/41) presented these mutations in homozygosis or compound heterozygosis, thus explaining their hearing defect. The c.35delG in the GJB2 gene was the most frequent mutation (37/300; 12.4%), detected in 23% familial and 6.2% the sporadic cases. The second most frequent mutation (1%; 3/300) was the del(GJB6- D13S1830), always found associated with the c.35delG mutation. Nineteen different sequence variations were found in the GJB2 gene. In addition to the c.35delG mutation, nine known pathogenic alterations were detected 0 67delT, p.Trp24X, p.Val37lle, c.176_191del16, c.235delC, p.Leu90Pro, p.Arg127His, c.509insA, and p.Arg184Pro, Five substitutions had been previously considered benign polymorphisms: c.-15C>T, p.Val27lle, p.Met34hr, p.Ala40Ala, and p.Gly160Ser. Two previously reported Mutations of unknown pathogenicity were found (p.Lys168Arg, and c.684C>A), and two novel substitutions, p.Leu81Val (c.G241C) and p.Met195Val (c.A583G), both in heterozygosis without an accompanying mutation in the other allele. None of these latter four variants of undefined status was present in a sample of 100 hearing controls. Conclusions: The present study demonstrates that Mutations in the GJB2 gene and del(GJB6 D13S1830) are important causes of hearing impairment in Brazil, thus justifying their screening in a routine basis. The diversity of variants in our sample reflects the ethnic heterogeneity of the Brazilian population.

Genetic typing of Trypanosoma cruzi isolates from different hosts and geographical areas of western Venezuela

A total of 72 Trypanosoma cruzi isolates from different hosts and geographical regions of western Venezuela, where Chagas disease is endemic, were typed using ribosomal and mini-exon gene markers. The isolates were obtained from wild, peridomestic and domestic sources including triatomine-bugs, human acute chagasic patients and other mammals. Results showed that T. cruzi two major phylogenetic lineages, T. cruzi I and T. cruzi II were present. However, a remarkable predominance of T. cruzi I (96%) over T. cruzi II (4%) was observed. The present results suggest that in western Venezuela circulation of both T. cruzi I and T. cruzi II isolates is independent from the source of isolation and the geographical area where they occur, with predominance of T. cruzi I. The epidemiological significance of the present results is discussed.

Rapport från en studieresa till Portugal 26/11-1/12 1991

Föreliggande rapport innehåller minnesanteckningar från en studieresa till Portugal 25/11- 2/121991. Syftet var framförallt att diskutera CPC-teknologi för solvärmeändamål med Manuel Collares-Pereira, CCE, Lissabon, inför ett fortsatt arbete med att utveckla CPC-teknologi i Sverige. Även andra institut och anläggningar besöktes och beskrivs i rapporten.

Composição corporal, somatótipo, actividade física e aptidão física, em crianças e adolescentes, em diferentes contextos de participação desportiva

Face ao crescente problema do sedentarismo, a actividade física assume um papel preponderante no combate a este flagelo. Neste sentido, o presente trabalho integra três estudos, em diferentes contextos de participação desportiva, e com os seguintes objectivos: no primeiro estudo, determinar se há diferenças na composição corporal e no somatótipo, em crianças e adolescentes; no segundo estudo, recorrendo à amostra anterior, determinar se há diferenças na aptidão física; e no terceiro estudo, analisar a relação entre os níveis de actividade física habitual, os indicadores de adiposidade e os níveis de aptidão, numa sub-amostra. A amostra foi constituída, nos dois primeiros estudos, por 465 sujeitos, com uma idade média de 13,72±1,64, e no terceiro estudo, por 36 sujeitos, com uma idade média de 15,25±1,03. As características somáticas foram avaliadas segundo o protocolo de Claessens et al. (1990). O índice de massa corporal (IMC) foi obtido pela razão entre o peso (kg) e a altura ao quadrado (m2). No cálculo da percentagem de massa gorda (% MG) recorreu-se às equações de Slaughter et al. (1988). O somatótipo foi avaliado segundo o método antropométrico de Heath-Carter (Carter & Heath, 1990). A aptidão física foi avaliada através das baterias de testes ‘Eurofit’ (Adam et al., 1988) e ‘Prudential Fitnessgram’ (Cooper Institute for Aerobic Research, 1992) e a actividade física por acelerometria (‘Computer Science and Applications’, Inc.). Os resultados do primeiro estudo indicam que não existem diferenças significativas (p > 0,05) na composição corporal e no somatótipo, em função da participação desportiva, enquanto o segundo estudo refere diferenças (p < 0,05), na aptidão física associada à saúde. No terceiro estudo, as crianças e os adolescentes cumprem com as recomendações internacionais de actividade física. De igual forma, a actividade física exibe uma relação negativa com os indicadores de adiposidade e positiva com a aptidão física associada à saúde.

Fatores de risco individuais e familiares no desenvolvimento da pré-eclâmpia

Preeclampsia is a spectral disease, with different clinical forms which can evolve with severe multisystemic complications. This present study aimed to determine the risk factors associated with preeclampsia (PE); to validate the existence of aggregation of hypertensive disease in families of women with preeclampsia and verify the existence of association between polymorphisms in the VEGF gene and level of VEGF and its soluble receptor (sFlt1). A case-control study was performed (n = 851). Genotyping of VEGF was performed and serum levels of VEGF and sFlt1 were measured by ELISA. It was observed that 38% of mothers (173, 455) of a case of preeclampsia and 30.8% (78 of 361) of controls had history of hypertension (p <0.0001). Similarly, when examining the history of maternal preeclampsia, we observed that 14.6% (48 of 328) of mothers of women with preeclampsia and 9.6% (12 of 294) of mothers of controls had a history of preeclampsia (p = 0.0001). As for maternal history of preeclampsia, we found that 5.1% (15 of 295) of cases and 3.6% (7 of 314) of controls had a history of preeclampsia (p = 0.0568). Sisters of women with preeclampsia also had a history of hypertensive disease in 9% (41 of 455) versus 6.6% (13 of 361), p = 0.002. Similarly when examining the history of preeclampsia in sisters, it was observed that 22.7% (57 of 251) of a sister of case versus 11.4% (26 of 228) of controls had a history of preeclampsia (P = 0.0011). We observed a decrease in free VEGF in the serum of patients (P <0.05) and increased soluble VEGF receptor. There was no association between polymorphisms in the VEGF gene and preeclampsia. The data obtained in this work validate that hypertensive disease in mothers and sisters with preeclampsia are risk factors for preeclampsia. The risk of illness in the family is higher according to disease severity. High incidence of preeclampsia can be assumed by the high incidence of this disease among the controls. Significant differences between the frequency of preeclampsia in mothers of cases and controls indicate familial factors. Work is being conducted with the to eventually perform genome wide association studies to identify susceptibility loci

Comparison of micronized whole soybeans to common protein sources in dry dog and cat diets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O ideário modernizador do governo graccho cardoso (1922-26) e a reforma da instrução pública de 1924 em Sergipe

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Anurans of the sandy coastal plains of the Lagamar Paulista, state of São Paulo, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lima beans production and economic revenue as function of organic and mineral fertilization

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Insulin signaling proteins in pancreatic islets of insulin-resistant rats induced by glucocorticoid

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Os objetivos do laboratório didático na visão dos alunos do curso de Licenciatura em Física da UNESP-Bauru

Há mais de cinqüenta anos, existe a preocupação em se definir os objetivos para o laboratório didático, revisando currículos e buscando ações mais localizadas e orientadas de acordo com o avanço crescente de conhecimentos das concepções alternativas de vários tópicos da Física por parte dos alunos, levando-se em conta as dificuldades específicas enfrentadas por eles no processo ensino-aprendizagem. Podem-se identificar duas linhas filosóficas que norteiam o processo ensino-aprendizagem com relação aos objetivos do laboratório didático. Uma linha defende que para sedimentar os conceitos expostos em aulas teóricas é necessária a prática em laboratório. A outra linha defende que o alvo da prática em laboratório deveria ser a obtenção e análise de dados, levando-se em conta a teoria aprendida. Atualmente, se percebe um crescimento por parte de profissionais que entendem haver uma necessidade de planejar, definir e hierarquizar objetivos detalhados, além de propiciar atividades que favoreçam de acordo com cada classe dentro da linha filosófica a que se identifica o profissional, não se esquecendo que ainda existem profissionais que não aceitam essa postura. Dentro desta perspectiva, foi aplicado um questionário a trinta alunos do curso de Licenciatura em Física da UNESP-Bauru, que já cursaram as cinco disciplinas práticas básicas do curso. Os alunos pontuaram de acordo com a sua visão dos objetivos reais frente aos objetivos ideais do laboratório didático. Os resultados mostraram que o laboratório didático vem cumprindo seu papel na opinião dos alunos do curso de Licenciatura em Física.

Estudo da expressão imuno-histoquímica das MMPs -2, -7, -9 e -26 e TIMPs -1 e -2 em adenomas pleomórficos e carcinomas adenóides císticos de glândulas salivares menores

The balance between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) has been related to various physiological and pathological processes, including salivary gland morphogenesis and tumor invasion and metastasis processes. Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) respectively represent benign and malignant neoplasias of salivary glands. Although they share the same cell origin, they present distinct biological behavior. The aim of this study was to compare the immunohistochemical expression of MMPs -2, -7, -9 and -26, and of TIMPs -1 and -2, in cases of PA and ACC of minor salivary glands. Twenty cases of PA and twenty cases of ACC were assessed according to the presence, intensity and location of MMPs and TIMPs in the tumor parenchyma. Most of the PAs and ACCs presented a high expression of MMP -2, -7, -9 and -26 and of TIMP -1 and -2, predominantly located in tumor cells. There was no significant difference in the expression of MMPs -2 (p=0.359), -7 (p=0.081) and -26 (p=0.553), as well as of TIMPs -1 (p=0.657) and -2 (p=0.248), between the parenchyma of PAs and ACCs. However, MMP-9 showed a significant difference of expression between the two tumors, with the ACC showing more intense marking for this gelatinase (p=0.041). The strong expression of MMP-9 observed in the parenchyma suggests that this gelatinase may play an important role in the biological behavior of these tumors. On the other hand, although there was no significant difference between the marking of MMP -2, 7 and 26 in the studied tumors, the data, when analyzed as a whole, suggest that these proteases may take part in the process of tissue remodeling in both tumors, but do not present a direct relation with the pattern of aggressiveness of ACC. Nonetheless, matrilisins may indirectly influence the behavior of this tumor due to their capacity of activating MMP-9, strongly expressed in the parenchyma of ACC