Mechanisms of ring chromosome formation, ring instability and clinical consequences

Background The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients. Methods Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization). Results The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV). Conclusions We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).

1031-1034delTAAC (Leu125Stop): a novel familial UBE3A mutation causing Angelman syndrome in two siblings showing distinct phenotypes

Background More than 50 mutations in the UBE3A gene (E6-AP ubiquitin protein ligase gene) have been found in Angelman syndrome patients with no deletion, no uniparental disomy, and no imprinting defect. Case Presentation We here describe a novel UBE3A frameshift mutation in two siblings who have inherited it from their asymptomatic mother. Despite carrying the same UBE3A mutation, the proband shows a more severe phenotype whereas his sister shows a milder phenotype presenting the typical AS features. Conclusions We hypothesized that the mutation Leu125Stop causes both severe and milder phenotypes. Potential mechanisms include: i) maybe the proband has an additional problem (genetic or environmental) besides the UBE3A mutation; ii) since the two siblings have different fathers, the UBE3A mutation is interacting with a different genetic variant in the proband that, by itself, does not cause problems but in combination with the UBE3A mutation causes the severe phenotype; iii) this UBE3A mutation alone can cause either typical AS or the severe clinical picture seen in the proband.

Evolução histórica dos Anais Brasileiros de Dermatologia

Nesta edição especial para o centenário da Sociedade Brasileira de Dermatologia, os autores fazem uma retrospectiva da dermatologia brasileira impressa, desde os primórdios, evidenciando a dermatologia descritiva com ricas discussões, ilustrações e propagandas de medicações muito utilizadas na época, como o bismuto no tratamento da sífilis, antes da descoberta da penicilina. Esta revisão chega até os dias atuais, quando as publicações nos Anais Brasileiros de Dermatologia entraram na era da modernidade eletrônica, científica e também de layout.

Caminhos da integralidade: adolescentes e jovens na atenção primária à saúde

Adolescentes e jovens constituem importante desafio para a construção da integralidade na Atenção Primária à Saúde (APS). Isso se deve à complexa apreensão e resposta ao conjunto de suas necessidades de saúde, decorrentes do processo de crescimento e desenvolvimento, próprio da fase, mas, sobretudo, dos aspectos socioculturais relacionados. O presente estudo buscou reconhecer alcances e limites em como o princípio da integralidade vem sendo operado em uma Unidade Básica de Saúde. Embora tenha sido possível identificar uma efetiva percepção da especificidade necessária à atenção à saúde desse grupo, também se verificaram importantes limitações relacionadas à construção de projetos de cuidado capazes de integrar as diversas finalidades do trabalho no cotidiano da Unidade, com destaque para a insuficiência de interações profissionais e setoriais, e fragilidades na comunicação de profissionais entre si e de profissionais e usuários.

Necessidades de saúde da pessoa com deficiência: a perspectiva dos sujeitos por meio de histórias de vida

Este trabalho teve como objetivo identificar as necessidades de saúde das pessoas com deficiência, pela ótica dos sujeitos. Realizou-se um estudo qualitativo, por meio da técnica da história de vida; foram incluídas pessoas com deficiência física, auditiva e visual, congênita e adquirida, e com atendimento no SUS. Discutiu-se: a vivência da deficiência; independência, autonomia e apoio; acesso e direitos; sentidos das intervenções; ações e estratégias. Em relação às necessidades de saúde, foram elencados onze eixos: Acesso; Apoio psicossocial; Aspectos gerais de saúde; Autonomia e independência; Dispensação de equipamentos e dispositivos de tecnologia assistiva; Informação/orientação; Prevenção/diagnóstico precoces; Reconhecimento e garantia de direitos; (Re)Encontro com atividades significativas; Validação e ajuda na construção de estratégias próprias de enfrentamento; Vínculo com profissional de saúde. Verifica-se que as necessidades identificadas pelos sujeitos incluem aspectos específicos da assistência em saúde, mas englobam outras dimensões, indicando a importância de ações integrais e intersetoriais.

Comensalidade e cuidado: meninas-jovens-mulheres órfãs no contexto de HIV/Aids

O "monopólio da cozinha", histórica e culturalmente, é atribuído às mulheres, mães. Para cuidar da família, elas elegem alimentos, compram, cozinham e os servem. Sustentam a comensalidade. Em contextos de HIV/Aids, onde há perda da mãe, as filhas tornam-se responsáveis por esses cuidados. O que pensam as meninas do papel de cuidadoras com o qual, prematuramente, deparam-se? O que dizem seus irmãos sobre isso? Realizamos entrevistas semidirigidas com 14 jovens órfãos. Os dados foram analisados pela proposta de Mills (2009). As jovens não demonstram insatisfação por executarem novas tarefas, mas deploram o fato de impedirem o estudo e a vida além-casa. Seus irmãos entendem a lida da cozinha como coisa de mulher e, por isso, dificilmente colaboram. Essas jovens necessitam de cuidados direcionados à situação vulnerável em que vivem. As políticas de Saúde Pública poderiam pleitear macroestruturas que atuassem sobre essa demanda.

Sobre o objeto da Fonoaudiologia

Este trabalho tematiza a questão do objeto em Fonoaudiologia, discute a pretensa unidade do campo e aponta a inexorabilidade de sua divisão para a concretização de seu estatuto científico. Para fazê-lo assume a linguagem em seus processos patológicos sob a instância da clínica como seu objeto, mas indica a necessidade de se desnaturalizar a linguagem, redefinindo-a como instância simbólica de subjetivação. Isto a afasta definitivamente da Audiologia, aqui entendida como ramificação das ciências ditas biológicas, e do reducionismo a que tem sido submetida ao ser concebida apenas como prática. Por outro lado, instaura o fonoaudiólogo como clínico terapeuta, comprometido com a linguagem de seu paciente e sua cura. Reconhece, ainda, outra paternidade para a Fonoaudiologia, indicando a Lingüística e a Psicanálise - quando adotam as mesmas concepções de sujeito e de linguagem - como lugares de peculiar interesse na constituição do saber fonoaudiológico. Uma vez realocada a Fonoaudiologia terá, diante de sí, a tarefa de reconhecer a clínica como seu espaço privilegiado de problematização de questões, das quais a primeira será o enfrentamento da constituição de seu método clínico. Finalmente, alerta-se o fonoaudiólogo para a ameaça de nova dominação caso não se marque a distinção entre as formas de interpretação que identificam a clínica fonoaudiológica e a particularizam em relação à clínica psicanalítica.

BDNF gene polymorphism, cognition and symptom severity in a Brazilian population-based sample of first-episode psychosis subjects

OBJECTIVE: To investigate the influence of brain-derived neurotrophic factor (BDNF) gene variations on cognitive performance and clinical symptomatology in first-episode psychosis (FEP). METHODS: We performed BDNF val66met variant genotyping, cognitive testing (verbal fluency and digit spans) and assessments of symptom severity (as assessed with the PANSS) in a population-based sample of FEP patients (77 with schizophreniform psychosis and 53 with affective psychoses) and 191 neighboring healthy controls. RESULTS: There was no difference in the proportion of Met allele carriers between FEP patients and controls, and no significant influence of BDNF genotype on cognitive test scores in either of the psychosis groups. A decreased severity of negative symptoms was found in FEP subjects that carried a Met allele, and this finding reached significance for the subgroup with affective psychoses (p < 0.01, ANOVA). CONCLUSIONS: These results suggest that, in FEP, the BDNF gene Val66Met polymorphism does not exert a pervasive influence on cognitive functioning but may modulate the severity of negative symptoms.

Feeding habits of the atlantic spotted dolphin, Stenella frontalis, in southeastern Brazil

This study presents new information on the feeding habits of the Atlantic spotted dolphins, Stenella frontalis, in the Western South Atlantic. Nine stomach contents of S. frontalis incidentally caught in fishing operations conducted by the gillnet fleet based on main harbour of Cananéia (25°00'S; 47°55'W), southeastern Brazil, were analyzed. These specimens were captured between 2005 and 2007. A total of 1 422 cephalopod beaks, 147 otoliths and three crustaceans were recovered from the stomach contents. The dolphins assessed preyed on at least eight different fish species of the families Trichiuridae, Carangidae, Sparidae, Merluccidae, Engraulidae, Sciaenidae, Congridae and Scombridae, five cephalopod species of the families Loliginidae, Sepiolidae, Tremoctopodidae and Thysanoteuthidae, and one shrimp species of the Penaeidae family. Based on the analysis of the Index of Relative Importance (IRI), the Atlantic cutlassfish, Trichiurus lepturus, was the most important fish species represented. Of the cephalopods, the squid Doryteuthis plei was by far the most representative species. Several items were reported for the first time as prey of the S. frontalis: Xiphopenaeus kroyeri, Tremoctopus violaceus, Semirossia tenera, Merluccius hubbsi, Pagrus pagrus and Paralonchurus brasiliensis. S. frontalis presented teuthophagous and ichthyofagous feeding habits, with apparent predominance of the first, and preyed mainly on pelagic and demersal items.

Comparative analysis of shell occupation by two southern populations of the hermit crab Loxopagurus loxochelis (Decapoda, Diogenidae)

The present study aimed to comparatively verify the relation between the hermit crabs and the shells they use in two populations of Loxopagurus loxochelis. Samples were collected monthly from July 2002 to June 2003, at Caraguatatuba and Ubatuba Bay, São Paulo, Brazil. The animals sampled had their sex identified, were weighed and measured; their shells were identified, measured and weighed, and their internal volume determined. To relate the hermit crab's characteristics and the shells' variables, principal component analysis (PCA) and a regression tree were used. According to the PCA analysis, the three gastropod shells most frequently used by L. loxochelis varied in size. The regression tree successfully explained the relationship between the hermit crab's characteristics and the internal volume of the inhabited shell. It can be inferred that the relationship between the morphometry of an individual hermit crab and its shell is not straightforward and it is impossible to explain only on the basis of direct correlations between the body's and the shell's attributes. Several factors (such as the morphometry and the availability of the shell, environmental conditions and inter- and intraspecific competition) interact and seem to be taken into consideration by the hermit crabs when they choose a shell, resulting in the diversified pattern of shell occupancy shown here and elsewhere.

Abrasividade pendular e a resistência mecânica das rochas

Esse trabalho emprega o método para avaliar a abrasividade proposto por Golovanevskiy e Bearman (2008). Esse método, ensaio de abrasão por impacto deslizante (Gouging Abrasion Test), é realizado em condições de alta tensão/alto impacto de desgaste. O método consiste de uma ponteira cilíndrica com uma ponta cônica de 90º, que, em trajetória pendular, atinge uma amostra de rocha com energia de impacto de 300 J e velocidade da ordem de 5,2 m/s. O Gouging Abrasion Index (Gi) é calculado como sendo a média do diâmetro da ponta cônica, após desgaste, em milímetros e o resultado é multiplicado por 10. Esse trabalho verificou a adequabilidade do Gouging Abrasion Test, para um pequeno número de amostras de rocha, que representam, qualitativamente, os principais tipos de rocha encontrados em trabalhos de corte, perfuração e britagem no Brasil, e a sua correlação com outros ensaios consagrados como a resistência à compressão, o desgaste Amsler e a dureza Knoop. Essa análise mostrou alta correlação entre Gi e a dureza Knoop (R² = 0,94), baixa correlação com o desgaste

Anomalous diffusion evidenced by particle tracking at high frame rates.

Diffusion is a common phenomenon in nature and generally is associated with a system trying to reach a local or a global equilibrium state, as a result of highly irregular individual particle motion. Therefore it is of fundamental importance in physics, chemistry and biology. Particle tracking in complex fluids can reveal important characteristics of its properties. In living cells, we coat the microbead with a peptide (RGD) that binds to integrin receptors at the plasma membrane, which connects to the CSK. This procedure is based on the hypothesis that the microsphere can move only if the structure where it is attached move as well. Then, the observed trajectory of microbeads is a probe of the cytoskeleton (CSK), which is governed by several factors, including thermal diffusion, pressure gradients, and molecular motors. The possibility of separating the trajectories into passive and active diffusion may give information about the viscoelasticity of the cell structure and molecular motors activity. And also we could analyze the motion via generalized Stokes-Einstein relation, avoiding the use of any active techniques. Usually a 12 to 16 Frames Per Second (FPS) system is used to track the microbeads in cell for about 5 minutes. Several factors make this FPS limitation: camera computer communication, light, computer speed for online analysis among others. Here we used a high quality camera and our own software, developed in C++ and Linux, to reach high FPS. Measurements were conducted with samples for 10£ and 20£ objectives. We performed sequentially images with different intervals, all with 2 ¹s exposure. The sequences of intervals are in milliseconds: 4 5 ms (maximum speed) 14, 25, 50 and 100 FPS. Our preliminary results highlight the difference between passive and active diffusion, since the passive diffusion is represented by a Gaussian in the distribution of displacements of the center of mass of individual beads between consecutive frames. However, the active process, or anomalous diffusion, shows as long tails in the distribution of displacements.

Model for the Dynamics of the Cytoskeleton.

Particle tracking of microbeads attached to the cytoskeleton (CSK) reveals an intermittent dynamic. The mean squared displacement (MSD) is subdiffusive for small Δt and superdiffusive for large Δt, which are associated with periods of traps and periods of jumps respectively. The analysis of the displacements has shown a non-Gaussian behavior, what is indicative of an active motion, classifying the cells as a far from equilibrium material. Using Langevin dynamics, we reconstruct the dynamic of the CSK. The model is based on the bundles of actin filaments that link themself with the bead RGD coating, trapping it in an harmonic potential. We consider a one- dimensional motion of a particle, neglecting inertial effects (over-damped Langevin dynamics). The resultant force is decomposed in friction force, elastic force and random force, which is used as white noise representing the effect due to molecular agitation. These description until now shows a static situation where the bead performed a random walk in an elastic potential. In order to modeling the active remodeling of the CSK, we vary the equilibrium position of the potential. Inserting a motion in the well center, we change the equilibrium position linearly with time with constant velocity. The result found exhibits a MSD versus time ’tau’ with three regimes. The first regime is when ‘tau’ < ‘tau IND 0’, where ‘tau IND 0’ is the relaxation time, representing the thermal motion. At this regime the particle can diffuse freely. The second regime is a plateau, ‘tau IND 0’ < ‘tau’ < ‘tau IND 1’, representing the particle caged in the potential. Here, ‘tau IND 1’ is a characteristic time that limit the confinement period. And the third regime, ‘tau’ > ‘tau IND 1’, is when the particles are in the superdiffusive behavior. This is where most of the experiments are performed, under 20 frames per second (FPS), thus there is no experimental evidence that support the first regime. We are currently performing experiments with high frequency, up to 100 FPS, attempting to visualize this diffusive behavior. Beside the first regime, our simple model can reproduce MSD curves similar to what has been found experimentally, which can be helpful to understanding CSK structure and properties.

Lipid and glucose profiles of dairy buffaloes during lactation and dry period

The purpose of this study was to analyze the influence of lactation and dry period in the constituents of lipid and glucose metabolism of buffaloes. One hundred forty-seven samples of serum and plasma were collected between November 2009 and July 2010, from properties raising Murrah, Mediterranean and crossbred buffaloes, located in the State of Sao Paulo, Brazil. Biochemical analysis was obtained by determining the contents of serum cholesterol, triglycerides, beta-hydroxybutyrate (β-HBO), non-esterified fatty acids (NEFA) and plasma glucose. Values for arithmetic mean and standard error mean were calculated using the SAS procedure, version 9.2. Tests for normality of residuals and homogeneity of variances were performed using the SAS Guide Data Analysis. Data were analyzed by ANOVA using the SAS procedure Glimmix. The group information (Lactation), Farm and Age were used in the statistical models. Means of groups were compared using Least Square Means (LSMeans) of SAS, where significant difference was observed at P ≤ 0.05. It was possible to conclude that buffaloes during peak lactation need to metabolize body reserves to supplement the lower amounts of bloodstream lipids, when they remain in negative energy balance. In the dry period, there were significant changes in the lipid profile, characterized by decrease of nutritional requirements, with consequent improvement in the general conditions of the animals.