UME6 is a central component of a developmental regulatory switch controlling meiosis-specific gene expression.

The UME6 gene of Saccharomyces cerevisiae was identified as a mitotic repressor of early meiosis-specific gene expression. It encodes a Zn2Cys6 DNA-binding protein which binds to URS1, a promoter element needed for both mitotic repression and meiotic induction of early meiotic genes. This paper demonstrates that a complete deletion of UME6 causes not only vegetative derepression of early meiotic genes during vegetative growth but also a significant reduction in induction of meiosis-specific genes, accompanied by a severe defect in meiotic progression. After initiating premeiotic DNA synthesis the vast majority of cells (approximately 85%) become arrested in prophase and fail to execute recombination; a minority of cells (approximately 15%) complete recombination and meiosis I, and half of these form asci. Quantitative analysis of the same early meiotic transcripts that are vegetatively derepressed in the ume6 mutant, SPO11, SPO13, IME2, and SPO1, indicates a low level of induction in meiosis above their vegetative derepressed levels. In addition, the expression of later meiotic transcripts, SPS2 and DIT1, is significantly delayed and reduced. The expression pattern of early meiotic genes in ume6-deleted cells is strikingly similar to that of early meiotic genes with promoter mutations in URS1. These results support the view that UME6 and URS1 are part of a developmental switch that controls both vegetative repression and meiotic induction of meiosis-specific genes.

Structural features of the invariant chain fragment CLIP controlling rapid release from HLA-DR molecules and inhibition of peptide binding.

The invariant chain (Ii) prevents binding of ligands to major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum and during intracellular transport. Stepwise removal of the Ii in a trans-Golgi compartment renders MHC class II molecules accessible for peptide loading, with CLIP (class II-associated Ii peptides) as the final fragment to be released. Here we show that CLIP can be subdivided into distinct functional regions. The C-terminal segment (residues 92-105) of the CLIP-(81-105) fragment mediates inhibition of self- and antigenic peptide binding to HLA-DR2 molecules. In contrast, the N-terminal segment CLIP-(81-98) binds to the Staphylococcus aureus enterotoxin B contact site outside the peptide-binding groove on the alpha 1 domain and does not interfere with peptide binding. Its functional significance appears to lie in the contribution to CLIP removal: the dissociation of CLIP-(81-105) is characterized by a fast off-rate, which is accelerated at endosomal pH, whereas in the absence of the N-terminal CLIP-(81-91), the off-rate of C-terminal CLIP-(92-105) is slow and remains unaltered at low pH. Mechanistically, the N-terminal segment of CLIP seems to prevent tight interactions of CLIP side chains with specificity pockets in the peptide-binding groove that normally occurs during maturation of long-lived class II-peptide complexes.

Multiple loci govern the bone marrow-derived immunoregulatory mechanism controlling dominant resistance to autoimmune orchitis.

The existence of immunoregulatory genes conferring dominant resistance to autoimmunity is well documented. In an effort to better understand the nature and mechanisms of action of these genes, we utilized the murine model of autoimmune orchitis as a prototype. When the orchitis-resistant strain DBA/2J is crossed with the orchitis-susceptible strain BALB/cByJ, the F1 hybrid is completely resistant to the disease. By using reciprocal radiation bone marrow chimeras, the functional component mediating this resistance was mapped to the bone marrow-derived compartment. Resistance is not a function of either low-dose irradiation- or cyclophosphamide (20 mg/kg)-sensitive immunoregulatory cells, but can be adoptively transferred by primed splenocytes. Genome exclusion mapping identified three loci controlling the resistant phenotype. Orch3 maps to chromosome 11, whereas Orch4 and Orch5 map to the telomeric and centromeric regions of chromosome 1, respectively. All three genes are linked to a number of immunologically relevant candidate loci. Most significant, however, is the linkage of Orch3 to Idd4 and Orch5 to Idd5, two susceptibility genes which play a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese diabetic mouse.

Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.

Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum of AOD is characterized by the development of anti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model of AOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on the mechanisms of self-tolerance that are relevant to disease pathogenesis. Previous studies indicate that the principal mechanisms involved in AOD susceptibility are genetically controlled and govern developmental processes associated with the induction and maintenance of peripheral tolerance. We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, including scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt.

Strategic knowledge serendipity and arbitrage & intellectual venture capitalists: An emerging breed of knowledge entrepreneurs; and Part II: Global and Local (GloCal) knowledge logistics for innovation and competitiveness. ACES Working Papers, August 2009

Strategic Knowledge: While entrepreneurship may occur as a natural result of personal drive, it occurs most often, most robustly and is most sustainable in an environment designed to encourage it. Potential entrepreneurs become active entrepreneurs when the conditions are most supportive of their commercial opportunities and their business thus helping channel the two key qualities they exhibit as individuals obsessed maniacs and clairvoyant oracles (Carayannis, GWU Lectures, 2000-2005) and (Carayannis et at, 2003a) towards the generation of sustainable wealth. So far, entrepreneurial scholars who turn into intellectual venture capitalists by founding knowledge-driven companies remain one of the least explored specie in the territory of entrepreneurship. GloCal: The increasing engagement of firms within global knowledge and production networks and their ability to source knowledge globally as well as locally (GloCally), for the development of innovation capacities will shape the future of UK's knowledge resources and its role in the global economy. Practices such as off-shoring R&D activities are widely adopted, creating challenging, and not very well understood, issues related to cross-country and inter-firm knowledge and technology flows. We seek to address the internationalisation and networking of research and innovation activities, including the roles and strategies of enterprises, universities, research centres, governments in a cross-country and inter-sectoral way, to assess the impact and the implications for sustaining and enhancing the competitiveness of UK firms and other British knowledge producers and users.

Global and local (GloCal) knowledge logistics for innovation and competitiveness. ACES Working Papers, August 2010

The increasing engagement of firms within global knowledge and production networks and their ability to source knowledge globally as well as locally (GloCally), for the development of innovation capacities will shape the future of UK's knowledge resources and its role in the global economy. Practices such as off-shoring R&D activities are widely adopted, creating challenging, and not very well understood, issues related to cross-country and inter-firm knowledge and technology flows. We seek to address the internationalisation and networking of research and innovation activities, including the roles and strategies of enterprises, universities, research centres, governments in a cross-country and inter-sectoral way, to assess the impact and the implications for sustaining and enhancing the competitiveness of UK firms and other British knowledge producers and users.

Controlling Hox gene expression and activity to build the vertebrate axial skeleton

It has long been known that Hox genes are central players in patterning the vertebrate axial skeleton. Extensive genetic studies in the mouse have revealed that the combinatorial activity of Hox genes along the anterior-posterior body axis specifies different vertebral identities. In addition, Hox genes were instrumental for the evolutionary diversification of the vertebrate body plan. In this review, we focus on fundamental questions regarding the intricate mechanisms controlling Hox gene activity. In particular, we discuss the functional relevance of the precise timing of Hox gene activation in the embryo. Moreover, we provide insight into the epigenetic regulatory mechanisms that are likely to control this process and are responsible for the maintenance of spatially restricted Hox expression domains throughout embryonic development. We also analyze how specific features of each Hox protein may contribute to the functional diversity of Hox family. Altogether, the work reviewed here further supports the notion that the Hox program is far more complex than initially assumed. Exciting new findings will surely emerge in the years ahead.

Anwendungen von Fuzzy Logic im Controlling

Die wesentliche Aufgabe des Controllings besteht darin, dem Management aufbereitete Informationen zur Verfügung zu stellen. Die zu verarbeitenden Informationen liegen allerdings nicht immer in der gewünschten Genauigkeit vor. Trotz dieser Unschärfe muss eine Beschreibung stattfinden, um eine Entscheidungsfindung zu realsieren. Eine Möglichkeit ist der hier vorgestellte wissensbasierte Ansatz der Fuzzy Logic. Anhand von drei Controllinginstrumenten wird in der vorliegenden Arbeit das Anwendungspotential der Fuzzy Logic im Controlling bewertet.

Guidance for controlling asbestos-containing materials in buildings.

Mode of access: Internet.

Expeditionary logistics : --a strategic plan for Navy and Marine Corps 21st century logistics.

Mode of access: Internet.

Evaluation of measures for controlling sediment and nutrient losses from irrigated areas /

Mode of access: Internet.