709 research outputs found

    Is de vrijloopstal haalbaar in Nederland?

    Get PDF
    Vrijloopstallen zijn stallen, waarin de koe vrij kan rondlopen. Ze hebben geen ligboxen. De koeien lopen en liggen op een zachte bodem. De stal biedt kansen voor het dierenwelzijn en de diergezondheid. In het buitenland zijn ervaringen met bodems van compost, zand en gedroogde mest. Voor het Productschap Zuivel en het ministerie van LNV is een haalbaarheidsstudie gedaan naar de mogelijkheden in Nederlan

    Moderne huisvesting melkvee

    Get PDF
    Brochure met praktische adviezen om de melkveehouder op een overzichtelijke en prikkelende manier te informeren over een goede huisvesting van melkvee waarmee het welzijn van de koeien verbeterd kan worden. Er wordt nader ingegaan op regelgeving en subsidies, erfinrichting, de uitvoering van de ligboxenstal, het melken en stalsysteme

    Redirected evolution of a proline-based tautomerase:New tools for carboligation reactions

    Get PDF
    Enzymes are highly specialized catalysts, used by all living organisms to catalyze chemical reactions necessary to sustain life. Although enzymes in the course of evolution became highly specialized catalysts towards one specific chemical reaction, many enzymes are capable of catalyzing one or more unnatural reactions. These promiscuous reactions can be highly interesting, especially when the product of a promiscuous reaction forms a facile building block for the synthesis of particular pharmaceuticals. The focus of this thesis is the enzyme 4-oxalocrotonate tautomerase, which is capable of catalyzing several highly interesting carbon-carbon bond-forming reactions. The products of these reactions can be used to synthesize gamma-aminobutyric-acid analogues (GABA analogues), a highly important class of pharmaceuticals. Via extensive mutagenesis and by means of a novel color-based screenings method, enzyme variants were identified that were able to catalyze these reactions much quicker and moreover would almost exclusively synthesize the desired enantiomer. These improved enzyme variants were combined with other enzymes and a chemical catalyst in one pot, showing that all steps in this novel synthesis route could be performed without intermediate purification. Although this synthesis route needs to be further improved before it can be applied industrially, it highlights the exciting opportunities available to search for new enzyme variants and develop new sustainable catalysts that could applied in the synthesis of pharmaceuticals

    RNA elements directing in vivo assembly of the 7SK/MePCE/Larp7 transcriptional regulatory snRNP

    Get PDF
    Through controlling the nuclear level of active positive transcription elongation factor b (P-TEFb), the 7SK small nuclear RNA (snRNA) functions as a key regulator of RNA polymerase II transcription. Together with hexamethylene bisacetamide-inducible proteins 1/2 (HEXIM1/2), the 7SK snRNA sequesters P-TEFb into transcriptionally inactive ribonucleoprotein (RNP). In response to transcriptional stimulation, the 7SK/HEXIM/P-TEFb RNP releases P-TEFb to promote polymerase II-mediated messenger RNA synthesis. Besides transiently associating with HEXIM1/2 and P-TEFb, the 7SK snRNA stably interacts with the La-related protein 7 (Larp7) and the methylphosphate capping enzyme (MePCE). In this study, we used in vivo RNA-protein interaction assays to determine the sequence and structural elements of human 7SK snRNA directing assembly of the 7SK/MePCE/Larp7 core snRNP. MePCE interacts with the short 5'-terminal G1-U4/U106-G111 helix-tail motif and Larp7 binds to the 3'-terminal hairpin and the following U-rich tail of 7SK. The overall RNA structure and some particular nucleotides provide the information for specific binding of MePCE and Larp7. We also demonstrate that binding of Larp7 to 7SK is a prerequisite for in vivo recruitment of P-TEFb, indicating that besides providing stability for 7SK, Larp7 directly participates in P-TEFb regulation. Our results provide further explanation for the frequently observed link between Larp7 mutations and cancer development

    In Situ Acetaldehyde Synthesis for Carboligation Reactions

    Get PDF
    The enzyme 4-oxalocrotonate tautomerase (4-OT) can promis-cuously catalyze various carboligation reactions using acetalde-hyde as a nucleophile. However, the highly reactive nature ofacetaldehyde requires intricate handling, which can impede itsusage in practical synthesis. Therefore, we investigated threeenzymatic routes to synthesize acetaldehyde in situ in one-potcascade reactions with 4-OT. Two routes afforded practicalacetaldehyde concentrations, using an environmental pollu-tant,trans-3-chloroacrylic acid, or a bio-renewable, ethanol, asstarting substrate. These routes can be combined with 4-OTcatalyzed Michael-type additions and aldol condensations inone pot. This modular systems biocatalysis methodology pro-vides a stepping stone towards the development of larger arti-ficial metabolic networks for the practical synthesis of impor-tant chemical synthons

    Prediction of outcome in autoimmune hepatitis and variant syndromes

    Get PDF
    In general the prognosis of treated autoimmune hepatitis is comparable to the general population. The knowledge on risk factors predicting long term survival is still limited. Better knowledge on risk factors can lead to tailored treatment of patients in the future, preventing side effects in patients currently overtreated and preventing disease progression in patients currently undertreated.At diagnosis age, ethnicity, cirrhosis and ALT level were the main predictors for long-term survival. During treatment ALT level but not IgG level was associated with long-term survival. In patients presenting with acute or acute severe AIH improvement of liver function within 2 weeks after start of treatment was the main predictor for survival. In patients with AIH-PBC variant syndrome more patients than the guidelines indicate are treated with a combination of immunosupression and ursodeoxycholic acid.New treatment options are urgently needed in AIH which requires a better understanding of changes in the immune system. To our suprise complement did not play a role in autoimmune hepatitis. Using B-cell related cytokines, patients could be divided into immunological subgroups with each a different presentation, treatment response and outcome.LUMC / Geneeskund

    Dihydrolipoic acid reduces cytochrome b561 proteins.

    Get PDF
    Cytochrome b561 (Cyt-b561) proteins constitute a family of trans-membrane proteins that are present in a wide variety of organisms. Two of their characteristic properties are the reducibility by ascorbate (ASC) and the presence of two distinct b-type hemes localized on two opposite sides of the membrane. Here we show that the tonoplast-localized and the putative tumor suppressor Cyt-b561 proteins can be reduced by other reductants than ASC and dithionite. A detailed spectral analysis of the ASC-dependent and dihydrolipoic acid (DHLA)-dependent reduction of these two Cyt-b561 proteins is also presented. Our results are discussed in relation to the known antioxidant capability of DHLA as well as its role in the regeneration of other antioxidant compounds of cells. These results allow us to speculate on new biological functions for the trans-membrane Cyt-b561 proteins

    Corporate social responsibility of African and Middle East mobile operators towards climate change and the potential impact of its carbon footprint

    Get PDF
    Research report, presented to the SBL Unisa, Midrand.The current and future anticipated changes in the earth’s climate are a concern that has captured business’s and governments’ global attention. Climate change and its potential impacts cannot be ignored as there is ample evidence that global warming is indeed the result of anthropogenic greenhouse gas emissions. The mobile operator in Africa and the Middle East (ME) operates on continents and in parts of the world, predicted by scientists as the most vulnerable to the effects of climate change. The mobile operator in Africa and the Middle East is moreover an emitter of significant amounts of CO2 and this exacerbates the serious environmental climate change problem that humankind faces. This research paper addresses the Corporate Social Responsibility of African and Middle East (ME) mobile operators, and its Carbon Footprint. The main objectives of the research are to identify strategic risks and opportunities and the implications for the mobile operator and to determine its Greenhouse Gas emissions. The performance against targets and plans to reduce GHG emissions are also reviewed. The research is based on the questionnaire of the Carbon Disclosure Project (CDP) initiative. A shortened and modified version of the CDP was designed and emailed to two major mobile telecom operators both operating in Africa and the Middle East. It is postulated that the telecommunications industry is at an inflection point where significant changes must take place in the way energy requirements are managed. This in turn could have a positive effect on reducing its carbon footprint, benefit corporate reputation and at the same time earn “green miles” in the subscriber’s minds. The research reached the main conclusion that the mobile operators’ investigated do not yet have strategies, systems and reporting in place to be counted as “good corporate citizens” concerning their environmental responsibility. The research further concluded that a proactive strategic intent is a necessity to achieve this goal. In short: The Corporate Social Responsibility of African and Middle East mobile operators indeed has a positive effect on its Carbon Footprint.M.B.L.Graduate School of Business Leadershi
    corecore