Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish

Background: In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh) signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish. Results: Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1 protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation. Conclusion: Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling

Fracture of the tibial baseplate in bicompartmental knee arthroplasty

Introduction. Bicompartmental knee arthroplasty (BKA) addresses combined medial and patellofemoral compartment osteoarthritis, which is relatively common, and has been proposed as a bridge between unicompartmental and total knee arthroplasty (TKA). Case Presentation. We present the case report of a young active man treated with BKA after unsuccessful conservative therapy. Four years later, loosening with fracture of the tibial baseplate was identified and the patient was revised to TKA. Discussion. Although our case is only the second fractured tibial baseplate to be reported, we believe that the modular titanium design, with two fixation pegs, is too thin to withstand daily cyclic loading powers. Light daily routine use, rather than high-impact sports, is therefore advised. Failures may also be related to the implant being an early generation and known to be technically complex, with too few implant sizes. We currently use TKA for the treatment of medial and patellofemoral compartment osteoarthritis

The interactional origins of foreigner talk : municipal employees and foreign workers

Contains fulltext : 3867.pdf (publisher's version ) (Open Access

Gruppenzusammensetzung und Interaktion bei kooperativem lernen in Mathematik

Kernfrage dieses Forschungsprojekts ist die Bedeutung von Individuellen-, Kleingruppen- und Klassenvariablen für kognitive und affektive Lernergebnisse in Mathematik von Schülern der Sekundarstufe.Selected paper, originally presented at the International Convention Utrecht 1-4 July, 1992 of the International Association of Co-operation in Education (IASCE), Co-chaired by Prof. dr. Elizabeth Cohen, Stanford University & prof. dr. Jan Terwel, Utrecht University

Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm

Laminin-111 (α1β1γ1) is a member of the Laminin family of extra-cellular matrix proteins that comprises 16 members, components of basement membranes. Laminin-111, one of the first Laminin proteins synthesised during embryogenesis, is required for basement membrane deposition and has essential roles in tissue morphogenesis and patterning. Yet, the mechanisms controlling Laminin-111 expression are poorly understood. We generated a zebrafish transgenic reporter line that reproduces faithfully the expression pattern of lama1, the gene encoding Laminin α1, and we used this reporter line to investigate lama1 transcriptional regulation. Our findings established that lama1 expression is controlled by intronic enhancers, including an enhancer directing expression in the paraxial mesoderm, anterior spinal cord and hindbrain, located in intron 1. We show that Hedgehog signalling is necessary and sufficient for lama1 transcription in the paraxial mesoderm and identify putative Gli/Zic binding sites that may mediate this control. These findings uncover a conserved role for Hedgehog signalling in the control of basement membrane assembly via its transcriptional regulation of lama1, and provide a mechanism to coordinate muscle cell fate specification in the zebrafish embryo

Different Slopes for Different Folks: Socioeconomic and Racial/Ethnic Disparities in Asthma and Hay Fever among 173,859 U.S. Men and Women.

Although allergic diseases such as asthma and hay fever are a major cause of morbidity in industrialized countries, most studies have focused on patterns of prevalence among children and adolescents, with relatively few studies on variations in prevalence by race/ethnicity and socioeconomic position among adults. Our study examined racial/ethnic and socioeconomic patterns in the prevalence of asthma overall, asthma with hay fever, asthma without hay fever, and hay fever overall, in a population of 173,859 women and men in a large prepaid health plan in northern California. Using education as a measure of socioeconomic position, we found evidence of a positive gradient for asthma with hay fever with increasing level of education but an inverse gradient for asthma without hay fever. Hay fever was also strongly associated with education. Compared with their White counterparts, Black women and men were more likely to report asthma without hay fever, and Black women were less likely to have asthma with hay fever. Asian men were also more likely to report asthma with hay fever, and Asian women and men were much more likely to have hay fever. Racial/ethnic disparities in prevalence of allergic diseases were largely independent of education. We discuss implications for understanding these social inequalities in allergic disease risk in relation to possible differences in exposure to allergens and determinants of immunologic susceptibility and suggest directions for future research

Altered expression of an ankyrin-repeat protein results in leaf abnormalities, necrotic lesions, and the elaboration of a systemic signal

Summary: The PR-like proteins, class I β-1,3-glucanase (GLU I) and chitinase (CHN I), are induced as part of a stereotypic response that can provide protection against viral, bacterial, and fungal pathogens. We have identified two Nicotiana plumbaginifolia ankyrin-repeat proteins, designated $$\underline{G}$$ lucanohydrolase $$\underline{B}$$ inding $$\underline{P}$$ roteins (GBP) 1 and 2, that bind GLU I and CHN I both in vitro and when expressed in yeast cells. Sense as well as antisense transformants of tobacco carrying the GBP1 gene elaborated graft-transmissible acropetally moving signals that induced the downward curling of young leaves. This phenotype was associated with reduced starch, sucrose, and fructose accumulation; the formation of necrotic lesions; and, the induction of markers for the hypersensitive response. GBP1/2 are members of a conserved $$\underline{P}$$ lant-specific $$\underline{Ank}$$ yrin- repeat (PANK) family that includes proteins implicated in carbohydrate allocation, reactive oxygen metabolism, hypersensitive cell death, rapid elicitor responses, virus pathogenesis, and auxin signaling. The similarity in phenotype of PANK transformants and transformants altered in carbohydrate metabolism leads us to propose that PANK family members are multifunctional proteins involved in linking plant defense responses and carbohydrate metabolis