zyg-11and cul-2 promote the metaphase to anaphase transition and M phase exit of meiosis II and prevent polarity establishment in C.elegans

Résumé Les mécanismes qui coordonnent la progression du cycle cellulaire lors de la méiose avec les événements du développement embryonnaire précoce, y compris la formation des axes de polarité embryonnaire, sont peu compris. Dans le zygote du vers Caenorhabditis elegans, les premiers signes de polarité Antéro-Postérieur (A-P) embryonnaire apparaissent après que la méiose soit terminée. La nature des protéines et des mécanismes moléculaires qui cassent la symétrie du zygote n'est pas connue. Nous démontrons que zyg-11 et cul-2 promeuvent la transition métaphase - anaphase et la sortie de la phase M lors de la seconde division méiotique. Nos résultats indiquent que ZYG-11 agit comme unité recrutant le substrat d'une ligase E3 comprennant CUL-2. Nos résultats montrent aussi que le délai de sortie de la phase M dépend de l'accumulation de la Cyclin B, CYB-3. Nous démontrons que dans des embryons zyg-11(RNAi) ou cul-2(RNAi), une polarité inversée est établie lors du délai de méiosis II. Enfin nous montrons que les défauts de cycle cellulaire et ceux de polarité peuvent être séparés. De plus, nous faisons apparaitre que l'établissement d'une polarité inversée pendant le délai de méiose II des embryons zyg-11(RNAi), comme l'établissement de la A-P polarité des embryons sauvage ne semblent pas requérir les microtubules. Nous montrons également les premiers résultats d'un crible deux hybrides ainsi qu'un crible génomique qui vise à identifier des gènes dont l'inactivation augmente ou supprime les défauts de mutants pour le gène zyg-11, afin d'identifier les gènes qui intéragissent avec ZYG-11 pour assumer ses deux fonctions séparables. Par conséquent, nos trouvailles suggèrent un modèle selon lequel ZYG-11 est une sous-unité qui recrute les substrats d'une ligase E3 basée sur CUL-2 qui promeut la progression du cycle cellulaire et empêche l'établissement de la polarité pendant la méiose II, et où le centrosome agit comme la clé qui polarise l'embryon à la fin de la méiose. Summary The mechanisms that couple meiotic cell cycle progression to subsequent developmental events, including specification of embryonic axes, are poorly understood. In the one cell stage embryos of Caenorhabditis elegans, the first signs of Antero-Posterior (A-P) polarity appear after meiosis completion. A centrosome ¬derived component breaks symmetry of the embryo, but the molecular nature of this polarity signal is not known. We established that zyg-11 and cul-2 promote the metaphase to anaphase transition and M phase exit at meiosis II. Our results indicate that ZYG-11 acts as a substrate recruitment subunit of a CUL-2-based E3 ligase. Moreover, we find that the delayed meiosis II exit of embryos lacking zyg-11 is caused by accumulation of the B-type cyclin, CYB-3. We demonstrate that inverted A-P polarity is established during the meiosis II delay in zyg-11(RNAi) and cul¬2(RNAi) embryos. Importantly, we demonstrate that the polarity defects following zyg-11 or cul-2 inactivation can be uncoupled from the cell cycle defects. Furthermore, we found that microtubules appear dispensable for inverted polarity during the meiosis II delay in zyg-11(RNAi) embryos, as well as for A-P polarity during the first mitotic cell cycle in wild-type embryos. We also show the initial results from a comprehensive yeast two hybrid, as well as an RNAi-based functional genomic enhancer and suppressor screen, that may lead to identification of proteins that interact with zyg-11 to ensure the two functions. Our findings suggest a model in which ZYG-11 is a substrate recruitment subunit of an CUL-2-based E3 ligase that promotes cell cycle progression and prevents polarity establishment during meiosis II, and in which the centrosome acts as a cue to polarize the embryo along the AP axis after exit from the meiotic cell cycle.

Formação do vínculo na implantação do Programa Saúde da Família numa Unidade Básica de Saúde

Este estudo objetivou conhecer as estratégias de formação do vínculo entre usuários e profissionais do Programa de Saúde da Família (PSF) de uma unidade básica em Fortaleza-CE. Estudo descritivo de natureza qualitativa, realizado nos meses de agosto e setembro de 2007 em Fortaleza-Ceará-Brasil. Os informantes do estudo foram os 12 profissionais das equipes de saúde da família. Os dados foram coletados por meio de entrevista e organizados na forma de categorização das falas dos sujeitos, com base na técnica do Discurso do Sujeito Coletivo e analisados com a literatura. Foram respeitadas as questões éticas inerentes a estudos com seres humanos. Os profissionais compreendem vínculo como relacionamento, cumplicidade e confiança. Acreditam que organização do serviço, compromisso e respeito são indispensáveis para a consolidação deste processo, que pode ser formado com grupos, acolhimento e visita domiciliar. Ressalta-se a importância da formação do vínculo no Programa Saúde da Família como estratégia para uma melhor assistência à saúde.

Curso Técnico de Enfermagem do PROFAE - Ceará: uma análise sob a óptica dos egressos

Este estudo objetivou analisar o curso Técnico em Enfermagem do PROFAE, sob a perspectiva dos egressos, vislumbrando o reconhecimento dos pontos fortes e as dificuldades decorrentes do desenvolvimento do curso. Estudo descritivo-exploratório de natureza qualitativa, desenvolvido com os egressos da Escola de Saúde Pública do Ceará. Foram realizados dois grupos focais, com 21 egressos, em maio e junho de 2007. Utilizou-se a análise de conteúdo para a compreensão das falas. Evidenciou-se que o curso proporcionou aquisição de conhecimentos, transformando a vida dos participantes, passando a ser agente de mudança no contexto de trabalho. Foram analisados a qualidade do currículo, a metodologia, o material didático disponibilizado pela instituição, bem como a atuação do corpo docente. Como pontos frágeis citaram-se a limitação do campo de estágio, duração do curso e gerenciamento de ajuda de custo. Entende-se que a avaliação representa um aspecto importante para o curso, ensejando o aperfeiçoamento da proposta.

Introducing a new MRI classification of lumbar spinal stenosis based on cross-sectional morphology of the dural sac : 37

Introduction: Measures of the degree of lumbar spinal stenosis (LSS) such as antero-posterior diameter of the canal, and dural sac cross sectional area vary, and do not correlate with symptoms or results of surgery. We created a grading system, comprised of seven categories, based on the morphology of the dural sac and its contents as seen on T2 axial images. The categories take into account the ratio of rootlet/ CSF content. Grade A indicates no significant compression, grade D is equivalent to a total myelograhic block. We compared this classification with commonly used criteria of severity of stenosis. Methods: Fifty T2 axial MRI images taken at disc level from 27 symptomatic LSS patients undergoing decompressive surgery were classified twice by two radiologists and three spinal surgeons working at different institutions and countries. Dural sac cross-sectional surface area and AP diameter of the canal were measured both at disc and pedicle level from DICOM images using OsiriX software. Intraand inter-observer reliability were assessed using Cohen's, Fleiss' kappa statistics, and t test. Results: For the morphological grading the average intra-and inter observer kappas were 0.76 and 0.69+, respectively, for physicians working in the study originating country. Combining all observers the kappa values were 0.57 ± 0.19. and 0.44 ± 0.19, respectively. AP diameter and dural sac cross-sectional area measurements showed no statistically significant differences between observers. No correlation between morphological grading and AP diameter or dural sac crosssectional areawas observed in 13 (26%) and 8 cases (16%), respectively. Discussion: The proposed morphological grading relies on the identification of the dural sac and CSF better seen on full MRI series. This was not available to the external observers, which might explain the lower overall kappa values. Since no specific measurement tools are needed the grading suits everyday clinical practice and favours communication of degree of stenosis between practising physicians. The absence of a strict correlation with the dural sac surface suggests that measuring the surface alone might be insufficient in defining LSS as it is essentially a mismatch between the spinal canal and its contents. This grading is now adopted in our unit and further studies concentrating on relation between morphology, clinical symptoms and surgical results are underway.

Lämpökuvaus laadunvarmistustyökaluna talonrakentamisessa

Tutkimuksen tavoitteena oli luoda NCC Rakennus Oy:lle uusi lämpökuvaus-toimintamalli, joka mahdollistaa rakentamisen ja rakennusten työvaiheiden laadunvarmistamisen entistä tehokkaammin. Tutkimuksessa käsiteltiin lämpökuvauksen perusteita, lämpökuvaustoiminnan roolia yrityksen laatujärjestelmässä ja erityispiirteitä eri työlajien laadunvarmistuksessa. Tutkimuksessa keskityttiin uudishankkeisiin toimitilarakentamisessa, asunto-, takuu- ja korjauspuolen aiheita käsiteltiin yleisesti. Insinöörityön lähdemateriaalina käytettiin lämpökuvaus- ja rakennuskirjallisuutta, yleisiä rakennusmääräyksiä ja -ohjeita, haastatteluja ja lämpökuvausraportteja. Teoriaosuuden jälkeen selvitettiin NCC:n kokemuksia lämpökuvauksesta ja kohteissa havaituista lämpöteknisistä ongelmakohdista. Kokeellisia lämpökuvauksia suoritettiin lämpökuvausolosuhteiden salliessa yhteensä seitsemässä toimitilakohteessa, yhdessä rivitalokohteessa, julkisivusaneerauskohteen 14:sta kerrostaloasunnossa ja yhdessä yksityisessä paritaloasunnossa. Toimintamalli osoittautui erittäin tarpeelliseksi ja tehokkaaksi rakennusten lämpöteknisen tiiveyden ja talotekniikan lämmitysjärjestelmien toiminnan varmistamisessa. Toistuvien lämpökuvausten aikana selvisi mittauslaitteiston ominaisuuksien merkitys, aputyökalujen ja tutkimusajan tarve sekä työnaikaisen lämpökuvausraportin rakenne. Insinöörityön tuloksena syntyi lämpökuvauksen avuksi toimintamalli, josta selviää rakennusvaiheittain lämpökuvauksen vaikutustapa, paikka, tiedonkulku, lämpökuvauksessa toistuvat vaiheet, osapuolet, tehtävät ja työkalut. Lämpökuvauksen avuksi luotiin aputyökaluja, jotka ovat avaintyölajien lämpökuvausohjekortit sekä suunnittelussa ja kuvaustilanteessa käytettävä apumateriaali kuten lämpökuvauksen tilauspohja, käyttäjätiedote, mittauspöytäkirja- pohja ja valmiit lämpötilaindeksien mukaiset pintalämpötilojen ohjearvotaulukot.

Do orthopaedic shoes improve local dynamic stability of gait? An observational study in patients with chronic foot and ankle injuries.

BACKGROUND: Complex foot and ankle fractures, such as calcaneum fractures or Lisfranc dislocations, are often associated with a poor outcome, especially in terms of gait capacity. Indeed, degenerative changes often lead to chronic pain and chronic functional limitations. Prescription footwear represents an important therapeutic tool during the rehabilitation process. Local Dynamic Stability (LDS) is the ability of locomotor system to maintain continuous walking by accommodating small perturbations that occur naturally during walking. Because it reflects the degree of control over the gait, LDS has been advocated as a relevant indicator for evaluating different conditions and pathologies. The aim of this study was to analyze changes in LDS induced by orthopaedic shoes in patients with persistent foot and ankle injuries. We hypothesised that footwear adaptation might help patients to improve gait control, which could lead to higher LDS: METHODS: Twenty-five middle-aged inpatients (5 females, 20 males) participated in the study. They were treated for chronic post-traumatic disabilities following ankle and/or foot fractures in a Swiss rehabilitation clinic. During their stay, included inpatients received orthopaedic shoes with custom-made orthoses (insoles). They performed two 30s walking trials with standard shoes and two 30s trials with orthopaedic shoes. A triaxial motion sensor recorded 3D accelerations at the lower back level. LDS was assessed by computing divergence exponents in the acceleration signals (maximal Lyapunov exponents). Pain was evaluated with Visual Analogue Scale (VAS). LDS and pain differences between the trials with standard shoes and the trials with orthopaedic shoes were assessed. RESULTS: Orthopaedic shoes significantly improved LDS in the three axes (medio-lateral: 10% relative change, paired t-test p < 0.001; vertical: 9%, p = 0.03; antero-posterior: 7%, p = 0.04). A significant decrease in pain level (VAS score -29%) was observed. CONCLUSIONS: Footwear adaptation led to pain relief and to improved foot & ankle proprioception. It is likely that that enhancement allows patients to better control foot placement. As a result, higher dynamic stability has been observed. LDS seems therefore a valuable index that could be used in early evaluation of footwear outcome in clinical settings.

Rouva Päätoimittaja Maija-Liisa Heini 4/2 1972

Kirje 4.2.1972

Assessment of a new MRI classification of spinal stenosis based on cross-sectional morphology of the dural sac : FM2

Introduction: Quantitative measures of degree of lumbar spinal stenosis (LSS) such as antero-posterior diameter of the canal or dural sac cross sectional area vary widely and do not correlate with clinical symptoms or results of surgical decompression. In an effort to improve quantification of stenosis we have developed a grading system based on the morphology of the dural sac and its contents as seen on T2 axial images. The grading comprises seven categories ranging form normal to the most severe stenosis and takes into account the ratio of rootlet/CSF content. Material and methods: Fifty T2 axial MRI images taken at disc level from twenty seven symptomatic lumbar spinal stenosis patients who underwent decompressive surgery were classified into seven categories by five observers and reclassified 2 weeks later by the same investigators. Intra- and inter-observer reliability of the classification were assessed using Cohen's and Fleiss' kappa statistics, respectively. Results: Generally, the morphology grading system itself was well adopted by the observers. Its success in application is strongly influenced by the identification of the dural sac. The average intraobserver Cohen's kappa was 0.53 ± 0.2. The inter-observer Fleiss' kappa was 0.38 ± 0.02 in the first rating and 0.3 ± 0.03 in the second rating repeated after two weeks. Discussion: In this attempt, the teaching of the observers was limited to an introduction to the general idea of the morphology grading system and one example MRI image per category. The identification of the dimension of the dural sac may be a difficult issue in absence of complete T1 T2 MRI image series as it was the case here. The similarity of the CSF to possibly present fat on T2 images was the main reason of mismatch in the assignment of the cases to a category. The Fleiss correlation factors of the five observers are fair and the proposed morphology grading system is promising.

Fru Chefredaktören Maija-Liisa Heini 4.2.1972

Kirje