Aberrant transcript produced by a splice donor site deletion in the TECTA gene is associated with autosomal dominant deafness in a Brazilian family

We ascertained a Brazilian family with nine individuals affected by autosomal dominant nonsyndromic sensorineural hearing loss. The bilateral hearing loss affected mainly mid-high frequencies, was apparently stable with an early onset. Microsatellites close to the DFNA8/DFNA12 locus, which harbors the TECTA gene, showed significant multipoint lod scores (32) close to marker D11S4107. Sequencing of the exons and exon-intron boundaries of the TECTA gene in one affected subject revealed the deletion c.5383 + 5delGTGA in the 5' end of intron 16, that includes the last two bases of the donor splice site consensus sequence. This mutation segregates with deafness within the family. To date, 33 different TECTA mutations associated with autossomal dominant hearing loss have been described. Among them is the mutation reported herein, first described by Hildebrand et al. (2011) in a UK family. The audioprofiles from the UK and Brazilian families were similar. In order to investigate the transcripts produced by the mutated allele, we performed cDNA analysis of a lymphoblastoid cell line from an affected heterozygote with the c.5383 + 5delGTGA and a noncarrier from the same family. The analysis allowed us to identify an aberrant transcript with skipping of exon 16, without affecting the reading frame. One of the dominant TECTA mutations already described, a synonymous substitution in exon 16 (c.5331 G<A), was also shown to affect splicing resulting in an aberrant transcript lacking exon 16. Despite the difference in the DNA level, both the synonymous substitution in exon 16 (c.5331 G<A) and the mutation described herein affect splicing of exon 16, leading to its skipping. At the protein level they would have the same effect, an in-frame deletion of 37 amino-acids (p.S1758Y/G1759_N1795del) probably leading to an impaired function of the ZP domain. Thus, like the TECTA missense mutations associated with dominant hearing loss, the c5383 + 5delGTGA mutation does not have an inactivating effect on the protein. (C) 2012 Elsevier B.V. All rights reserved.

Discourse and bipolar disorder: Narrative therapy on northeast Brazil

Background: The expression 'bipolar disorder' refers to any of several psychological disorders of mood that alternate episodes of depression and mania. Also called manic depression or manic-depressive illness, it is a relatively common but unknown pathology that brings some stigmas for patients and provokes deleterious effects for their lives. This research aimed to comprehend actions, behaviors and emotions involved with bipolar disorder, through narratives of patient's personal and familiar histories. Methods: We surveyed 30 patients from a psychiatric service located in Aparecida, Paraiba, Brazil. Selected patients had bipolar disorder according to DSM-IV. For data collection, we used non-structured interview, approaching specific aspects related to bipolar disorder. Quantitative and qualitative analysis were done and Hamilton Rating Scale for Depression (HAMD) was used. Results: Most of patients presented depressive actions associated with moderate euphoria. 11 of them related familiar history of psychopathology. Mania and hippomania were prevalent on male gender, while psychotic symptoms overlay ate female. Conclusion: Patients lack a translation of behavioral and temperamental processes to minimize harm caused to their lives.

Lipopolysaccharide administration in the dominant mouse destabilizes social hierarchy

Sickness behavior is a set of behavioral changes that are part of an adaptive strategy to overcome infection. Mice that interact with conspecifics displaying sickness behavior also show relevant behavioral changes. In this work we sought to determine the role of sickness behavior display by a dominant mouse as a promoter of hierarchy instability. We treated the dominant mouse within a dyad with lipopolysaccharide (LPS) (400 mu g/kg, i.p.) for three consecutive days and assessed social dominance behavior. Since elder animals display increased inflammatory responses and the behaviors toward conspecifics are influenced by kinship we also assessed whether kinship and age, might influence sickness related hierarchy instability. Our results show that administration of LPS in the dominant mouse promotes social instability within a dyad, and indicates that this instability could be influenced by kinship and age. (C) 2012 Elsevier B.V. All rights reserved.

Scientific metaphors in the journalistic discourse

Scientific education and divulgation not only amplify people's vocabulary and repertory of scientific concepts but, at the same time, promote the diffusion of certain conceptual and cognitive metaphors. Here we describe this process and propose a classification in terms of visible, invisible, basic and derived metaphors. We focus our attention on physical metaphors applied to psychological and socio-economical phenomena, by studying two exemplar cases through an exhaustive exam of the online content of large Brazilian journalistic portals. Finally, we present implications and suggestions from Lakiff and Johnson's cognitive metaphor theory for the scientific education and divulgation process.

Homophobic discourse in blogs: Weaving of violence and network

This article aims at analyzing the effects of meaning installed in the discursive space of a blog, especially a formulation of discriminatory nature which was posted in November, 2011 and considerably discussed in other discursive spaces on the Internet. By means of French Discourse Analysis, we sought to track the memory networks and the ideological effects that are at play in the discourse on homosexuals posted by browsers-subjects and how they update the meanings already there in order to install effects of prejudice and hatred. Our interest is also to catch the meanings of violence inscribed in the electronic network and analyze the functioning of the language in motion in this space bordered by the imaginary in which it is possible to say anything. Hence, by means of the analyses performed in this study, we observed these effects of the subject's full freedom when he/she subscribes to the electronic network without fear of any punishment of any order. The discourses of intolerance and hatred posted on the blog by the subject give voice to a discursive confrontation observed by marks of agreement or indignation, supported by the discursive memory. Thus, we observed the interruption of regularities that break up with a supposed linearity in the discourse, putting the contradiction and the heterogeneous nature of the sayings on the net in motion.

Penetrance rate estimation in autosomal dominant conditions

Accurate estimates of the penetrance rate of autosomal dominant conditions are important, among other issues, for optimizing recurrence risks in genetic counseling. The present work on penetrance rate estimation from pedigree data considers the following situations: 1) estimation of the penetrance rate K (brief review of the method); 2) construction of exact credible intervals for K estimates; 3) specificity and heterogeneity issues; 4) penetrance rate estimates obtained through molecular testing of families; 5) lack of information about the phenotype of the pedigree generator; 6) genealogies containing grouped parent-offspring information; 7) ascertainment issues responsible for the inflation of K estimates.

Structuring depressive discourse: A descriptive narrative process

This study aimed to evaluate the importance of a descriptive narrative process of the significance involved in a depressive phenomenon. The research population consisted of 324 adult and adolescent patients of both genders, located in the central area of the city of Paraiba, for clinical and psychological health care. For surveyed patients, suffering and or psychological pain were the most common complaints. A sample of 159 patients was taken, including male and female adolescents and adults. Data were collected through a narrative interview. Shutz' procedure was used for information analysis. The obtained data offered the opportunity to review concepts, discuss life history and listen to narrative positioning episodes of manifested depression. The narratives were considered to be a determinant factor to consider inherent conflicts.

Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C > A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.

GATA3 and a dominant regulatory gene expression profile discriminate operational tolerance in human transplantation

Some organ-transplanted patients achieve a state of "operational tolerance" (01) in which graft function is maintained after the complete withdrawal of immunosuppressive drugs. We used a gene panel of regulatory/inflammatory molecules (FOXP3, GATA3, 100, TGFB1, TGFBR1/TBX21, TNF and IFNG) to investigate the gene expression profile in peripheral blood mononuclear cells of renal-transplanted individuals experiencing OT compared to transplanted individuals not displaying OT and healthy individuals (HI). OT subjects showed a predominant regulatory (REG) profile with higher gene expression of GATA3, FOXP3, TGFB1 and TGFB receptor 1 compared to the other groups. This predominant REG gene expression profile displayed stability over time. The significant GATA3 gene and protein expressions in OT individuals suggest that a Th2 deviation may be a relevant pathway to OT. Moreover, the capacity of the REG/INFLAMMA gene panel to discriminate OT by peripheral blood analysis indicates that this state has systemic repercussions. (C) 2011 Elsevier Inc. All rights reserved.

Mutation Spectrum in the Large GTPase Dynamin 2, and Genotype-Phenotype Correlation in Autosomal Dominant Centronuclear Myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT. Hum Mutat 33: 949-959, 2012. (C) 2012 Wiley Periodicals, Inc.

Degree of multicollinearity and variables involved in linear dependence in additive-dominant models

The objective of this work was to assess the degree of multicollinearity and to identify the variables involved in linear dependence relations in additive-dominant models. Data of birth weight (n=141,567), yearling weight (n=58,124), and scrotal circumference (n=20,371) of Montana Tropical composite cattle were used. Diagnosis of multicollinearity was based on the variance inflation factor (VIF) and on the evaluation of the condition indexes and eigenvalues from the correlation matrix among explanatory variables. The first model studied (RM) included the fixed effect of dam age class at calving and the covariates associated to the direct and maternal additive and non-additive effects. The second model (R) included all the effects of the RM model except the maternal additive effects. Multicollinearity was detected in both models for all traits considered, with VIF values of 1.03 - 70.20 for RM and 1.03 - 60.70 for R. Collinearity increased with the increase of variables in the model and the decrease in the number of observations, and it was classified as weak, with condition index values between 10.00 and 26.77. In general, the variables associated with additive and non-additive effects were involved in multicollinearity, partially due to the natural connection between these covariables as fractions of the biological types in breed composition.