Pea rms6 mutants exhibit increased basal branching

Our studies on two branching mutants of pea (Pisum sativum L.) have identified a further Ramosus locus, Rms6, with two recessive or partially recessive mutant alleles: rms6-1 (type line S2-271) and rms6-2 (type line K586). Mutants rms6-1 and rms6-2 were derived from dwarf and tall cultivars, Solara and Torsdag, respectively. The rms6 mutants are characterized by increased branching from basal nodes. In contrast, mutants rms1 through rms5 have increased branching from both basal and aerial (upper stem) nodes. Buds at the cotyledonary node of wild-type (WT) plants remain dormant but in rms6 plants these buds were usually released from dormancy. Their growth was either subsequently inhibited, sometimes even prior to emergence above ground, or they grew into secondary stems. The mutant phenotype was strongest for rms6-1 on the dwarf background. Although rms6-2 had a weak single-mutant phenotype, the rms3-1 rms6-2 double mutant showed clear transgression and an additive branching phenotype, with a total lateral length almost 2-fold greater than rms3-1 and nearly 5-fold greater than rms6-2 . Grafting studies between WT and rms6-1 plants demonstrated the primary action of Rms6 may be confined to the shoot. Young WT and rms6-1 shoots had similar auxin levels, and decapitated plants had a similar magnitude of response to applied auxin. Abscisic acid levels were elevated 2-fold at node 2 of young rms6-1 plants. The Rms6 locus mapped to the R to Gp segment of linkage group V (chromosome 3). The rms6 mutants will be useful for basic research and also have possible agronomical value.

Shoot control of hypernodulation and aberrant root formation in the har1-1 mutant of Lotus japonicus

The har1-1 mutant of Lotus japonicus B-129-S9 Gifu is characterized by two phenotypes: greater than normal nodulation (hypernodulation) and significantly inhibited root growth in the presence of its microsymbiont Mesorhizobium loti strain NZP2235. We demonstrate that the two traits co-segregate, suggesting a single genetic alteration involving developmental pleiotropy. A cross between the mutant and genotype Funakura (with wild-type root and nodule morphology) demonstrated Mendelian recessive segregation of both phenotypes (root and nodule) in 216 F2 individuals. Using DNA-amplification fingerprinting polymorphisms in Gifu har1-1 and Funakura, the mutant locus was positioned between two markers at about 7 and 13 cM distance. Reciprocal hypocotyl grafting of shoots and roots showed that the hypernodulation and reduced root phenotypes are both predominantly controlled by the shoot.

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy

Mental retardation and epilepsy often occur together. They are both heterogeneous conditions with acquired and genetic causes. Where causes are primarily genetic, major advances have been made in unraveling their molecular basis. The human X chromosome alone is estimated to harbor more than 100 genes that, when mutated, cause mental retardation(1). At least eight autosomal genes involved in idiopathic epilepsy have been identified(2), and many more have been implicated in conditions where epilepsy is a feature. We have identified mutations in an X chromosome-linked, Aristaless-related, homeobox gene (ARX), in nine families with mental retardation (syndromic and nonspecific), various forms of epilepsy, including infantile spasms and myoclonic seizures, and dystonia. Two recurrent mutations, present in seven families, result in expansion of polyalanine tracts of the ARX protein. These probably cause protein aggregation, similar to other polyalanine(3) and polyglutamine(4) disorders. In addition, we have identified a missense mutation within the ARX homeodomain and a truncation mutation. Thus, it would seem that mutation of ARX is a major contributor to X-linked mental retardation and epilepsy.

A case of myoepithelial carcinoma displaying biallelic inactivation of the tumour suppressor gene APC in a patient with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene. It is characterised by the appearance of hundreds to thousands of colorectal adenomas in adolescence and the subsequent development of colorectal cancer. Various extracolonic malignancies are associated with FAP, including desmoids and neoplasms of the stomach, duodenum, pancreas, liver, and brain. We present a family affected by FAP with an exon 14 APC mutation displaying two rare extracolonic lesions, a hepatoblastoma and a myoepithelial carcinoma. The hepatoblastoma was found in a male patient aged 2 years. The second lesion, a myoepithelial carcinoma of the right cheek, was found in a female patient aged 14 years. Inactivation of the normal APC allele was demonstrated in this lesion by loss of heterozygosity analysis, thus implicating APC in the initiation or progression of this neoplasm. This is the first reported case of this lesion in a family affected by FAP.

No Major Schizophrenia Locus Detected on Chromosome 1q in a Large Multicenter Sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators

SOX transcription factors perform a remarkable variety of important roles in vertebrate development, either activating or repressing specific target genes through interaction with different partner proteins. Surprisingly, these interactions are often mediated by the conserved, DNA-binding HMG domain, raising questions as to how each factor's specificity is generated. We propose a model whereby non-HMG domains may influence partner protein selection and/or binding stability.

Sox18 mutations in the ragged mouse alleles ragged-like and opossum

The ragged (Ra) spontaneous mouse mutant is characterised by abnormalities in its coat and cardiovascular system. Four alleles are known and we have previously described mutations in the transcription factor gene Sox18 in the Ra and Ra-J alleles. We report here Sox18 mutations in the remaining two ragged alleles, opossum (Ra-op) and ragged-like (Ragl). The single-base deletions cause a C-terminal frameshift, abolishing transcriptional trans-activation and impairing interaction with the partner protein MEF2C. The nature of these mutations, together with the near-normal phenotype of Sox18-null mice, suggests that the ragged mutant SOX18 proteins act in a dominant-negative fashion. The four ragged mutants represent an allelic series that reveal SOX18 structure-function relationships and implicate related SOX proteins in cardiovascular and hair follicle development. (C) 2003 Wiley-Liss, Inc.

Etiology of ovarian failure in blepharophimosis ptosis epicanthus inversus syndrome: FOXL2 is a conserved, early-acting gene in vertebrate ovarian development

Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a human disorder caused by mutations in the forkhead transcription factor gene FOXL2 and is characterized by facial dysmorphology combined in some cases with ovarian failure. To better understand the role of FOXL2 in the etiology of ovarian failure in BPES, we examined its expression in embryonic ovaries of mice, chickens, and red-eared slider turtles, representatives of three phylogenetically distant vertebrate groups that have different mechanisms of sex determination. Expression of Foxl2 was detected in early ovaries of all three species around the time of sex determination and was associated with both somatic and germ cell populations in mice. Expression was sexually dimorphic in all cases. Sequence analysis of turtle and chicken FoxL2 orthologues indicated an unusually high degree of structural conservation during evolution. FoxL2 was found to be autosomal in chickens, and therefore unlikely to represent the dominant ovarian-determining gene that has been postulated to exist as a possible explanation for female heterogamety in birds. Our observations suggest that BPES may result from early abnormalities in regulating the development of the fetal ovary, rather than premature degeneration of the postnatal or adult ovary. Further, our results suggest that FOXL2 is a highly conserved early regulator of vertebrate ovarian development.

SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro

Sox8 is a member of the Sox family of developmental transcription factor genes and is closely related to Sox9, a key gene in the testis determination pathway in mammals. Like Sox9, Sox8 is expressed in the developing mouse testis around the time of sex determination, suggesting that it might play a role in regulating the expression of testis-specific genes. An early step in male sex differentiation is the expression of anti-Mullerian hormone (AMH) in Sertoli cells. Expression of the Amh gene during sex differentiation requires the interaction of several transcription factors, including SF1, SOX9, GATA4, WT1, and DAX1. Here we show that SOX8 may also be involved in regulating the expression of Amh. Expression of Sox8 begins just prior to that of Amh at 12 days post coitum (dpc) in mouse testes and continues beyond 16 dpc in Sertoli cells. In vitro assays showed that SOX8 binds specifically to SOX binding sites within the Amh minimal promoter and, like SOX9, acts synergistically with SF1 through direct protein-protein interaction to enhance Amh expression, albeit at lower levels compared with SOX9. SOX8 and SOX9 appear to have arisen from a common ancestral gene and may have retained some common functions during sexual development. Our data provide the first evidence that SOX8 may partially compensate for the reduced SOX9 activity in campomelic dysplasia and substitute for Sox9 where Sox9 is either not expressed or expressed too late to be involved in sex determination or regulation of Amh expression.

Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis

Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p

Effect of alcohol on iron storage diseases of the liver

The consumption of excess alcohol in patients with liver iron storage diseases, in particular the iron-overload disease hereditary haemochromatosis (HH), has important clinical consequences. HH, a common genetic disorder amongst people of European descent, results in a slow, progressive accumulation of excess hepatic iron. If left untreated, the condition may lead to fibrosis, cirrhosis and primary hepatocellular carcinoma. The consumption of excess alcohol remains an important cause of hepatic cirrhosis and alcohol consumption itself may lead to altered iron homeostasis. Both alcohol and iron independently have been shown to result in increased oxidative stress causing lipid peroxidation and tissue damage. Therefore, the added effects of both toxins may exacerbate the pathogenesis of disease and impose an increased risk of cirrhosis. This review discusses the concomitant effects of alcohol and iron on the pathogenesis of liver disease. We also discuss the implications of co-existent alcohol and iron in end-stage liver disease.

Control of familial and renal cardiac diseases in English bull terriers: How to repair a damaged breed?

Control recommendations are presented for four genetic or familial diseases that cause significant morbidity and mortality in affected English Bull Terriers. Bull Terrier polycystic kidney disease is an autosomal dominant disease diagnosed by detecting a minimum of three renal cysts, with cysts present in both kidneys, and similarly affected family members to confirm the inherited nature of the cysts. Bull Terrier hereditary nephritis is an autosomal dominant disease diagnosed in otherwise normal animals with urinary protein: creatinine ratios persistently >0.3 and no significant urinary sediment, a family history of the disease, and characteristic glomerular basement membrane lesions. Mitral valve myxomatous degeneration and left ventricular outflow tract obstruction in Bull Terriers are familial diseases diagnosed by auscultating characteristic murmurs in affected animals. Excluding animals with these clinical signs from the breeding pool will reduce the prevalence rates of these diseases, however maintenance of an effective population size is also important. Providing breeders with information on genetics, including the risks associated with inbreeding and the benefits of outcrossing, is likely to improve canine breeding practices, thus increasing fitness and fecundity of these purebred dogs.

O bebê surdo na educação infantil : um olhar sobre inclusão e práticas pedagógicas

Este estudo teve como objetivo analisar como ocorre a inclusão de dois bebês surdos (de 1 ano) na educação infantil de um Centro Municipal de Educação Infantil (CMEI) do município de Vitória/ES. Como aporte teórico foi utilizada a perspectiva Histórico-Cultural do desenvolvimento humano, sob a perspectiva que o sujeito se constitui nas relações sociais, como um ser ativo que transforma e é transformado nessas relações. Nesse contexto, o desenvolvimento implica a relação com o outro e a mediação da linguagem, meio de comunicação e de constituição do pensamento. Assim, no caso dos bebês surdos, destaca-se a LIBRAS como língua privilegiada que deve ser apropriada por eles e ensinada no cotidiano da educação infantil. Como opção metodológica, desenvolvemos um estudo de caso de inspiração etnográfica, por entendermos que essa metodologia permite atender apropriadamente ao objetivo do estudo. Para a coleta de dados, adotamos recursos como observação participante, registro em diário de campo, entrevistas semiestruturadas com os sujeitos participantes da pesquisa e análise documental. Na análise dos dados, tomamos como eixos de análise: as concepções dos profissionais a respeito da inclusão, surdez e do trabalho com os bebês surdos; o cuidado e a educação dos bebês surdos e as atividades lúdicas na sala dos bebês. As análises indicam que muitos profissionais têm dúvidas a respeito da inclusão e que a falta do conhecimento da LIBRAS por parte de muitos profissionais, leva à utilização de outros recursos de comunicação, como os gestos. A vivência e interação em LIBRAS entre as crianças e a maior parte dos profissionais da escola com os bebês surdos torna-se um desafio, sobressaindo a necessidade de mais profissionais com o conhecimento da LIBRAS para atender às crianças surdas em diferentes espaços no cotidiano da educação infantil, na perspectiva de potencializar o seu desenvolvimento e a constituição de sua identidade. Todavia, os profissionais da escola são movidos pela preocupação com a inclusão e o aprendizado da LIBRAS, esforçando-se no sentido de buscar novas formas de trabalho para/com as crianças surdas. Além disso, o empenho da equipe bilíngue na estruturação do cotidiano da educação infantil merece destaque, não só pelo trabalho que faz enquanto equipe bilíngue, mas pelo incentivo e auxílio aos outros profissionais.

Cultura, Consumo e Diferença : estudo com um grupo de surdos em Vitória-ES

Tanto pessoas diferentes, como culturas diferentes, quanto percepções diferentes produzem significados de consumo particulares, sejam esses referentes a determinado grupo de pessoas, sejam relacionados a uma cultura ou a seletividade de percepção de cada um de nós. Nessa perspectiva, cultura, consumo e diferença são analisados através de situações específicas de consumo de um grupo de surdos em Vitória-ES. Tal escolha deveu-se a ausência de estudos dentro da área da Administração que se ocupem do tema surdez, uma vez que a discussão sobre a surdez vem ganhando cada vez mais espaço, dentro e fora da esfera acadêmica. A busca aqui se realiza pela reflexão acerca da ausência do sentido da audição não pelas abordagens clínicas, médicas ou terapêuticas, mas aproximando-se dos estudos sociais interpretativistas (THOMA, 2008; STROBEL, 2008; SÁ, 2006). O intento é buscar compreender de que forma esses consumidores forjam suas relações sociais através do consumo de bens e serviços. Para tal análise, realizouse pesquisa bibliográfica sobre o consumo por uma perspectiva antropológica (ROCHA, 2000, 2005; MILLER, 2002; MCCRACKEN, 2003). A partir de então, aproximou-se da perspectiva cultural proposta pelos estudos surdos, na busca pela compreensão do consumo como mediador de relações e construtor de significações. Através de inspiração etnográfica com a utilização de observação direta e entrevistas informais (MALINOWSKI, 1978; GEERTZ, 1989; MAGNANI, 2002, 2003), o campo de pesquisa se desenvolveu a partir dos eventos, encontros, discussões e passeios realizados pelo grupo de surdos. Com estes, foi possível vivenciar algumas situações de consumo que envolvem do uso de transporte coletivo à encontros informais. Viu-se que das relações sociais forjadas pelos surdos e ouvintes emergem sujeitos-chaves que atuam na construção coletiva do grupo. Também identificou-se possibilidades de compreensão do consumidor através das abordagens política, médico/terapêutica e religiosa, além de artefatos que permeiam o grupo estudado. Deixou-se como sugestão para pesquisas futuras, dentre outras, a busca pela utilização da etnografia para a compreensão de grupos de consumidores, pela compreensão da relação entre a surdez e bens específicos de consumo, além da possibilidade de utilizar as perspectivas elencadas nesse trabalho em outras situações, com o intuito de alargar o universo de possibilidade de compreensão dos surdos.

Inclusão ideal e inclusão real : estudo de caso com professoras de crianças surdas em uma escola regular de João Pessoa – PB

O presente estudo tem como objetivo analisar as condições de inclusão educacional de crianças surdas em uma escola regular, a partir dos relatos de professoras que vivenciam essa prática. Para coletar informações a esse respeito, foram realizadas junto às participantes entrevistas de caráter semi-estruturado. No tratamento a esses dados foram descritas as condições de inclusão existentes na escola (campo de pesquisa), como também os significados elaborados pelas participantes acerca do aluno surdo e da inclusão do mesmo na escola regular. Os dados foram coletados em uma amostra de cinco professoras de classes regulares que possuem alunos surdos. Esses dados foram submetidos a uma análise de conteúdo manual dos mesmos no modelo de Bardin (2002). Os resultados apontam para uma visão predominantemente negativa das condições de inclusão oferecidas pela escola, consideradas como inadequadas. Isto é agravado pela insuficiência em termos de capacitação dos professores para o trabalho inclusivo. Observa-se, pois, do ponto de vista das participantes, a existência de uma discrepância entre os modelos legal e real de inclusão das crianças surdas em escola regular, que se manifesta em diversos aspectos da prática pedagógica nesse contexto.