Hochschule Bonn-Rhein-Sieg
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The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation
No full textIsovaleric acidemia (IVA), due to isovaleryl-CoA dehydrogenase (IVD) deficiency, results in the accumulation of isovaleryl-CoA, isovaleric acid and secondary metabolites. The increase in these metabolites decreases mitochondrial energy production and increases oxidative stress. This contributes to the neuropathological features of IVA. A general assumption in the literature exists that glycine N-acyltransferase (GLYAT) plays a role in alleviating the symptoms experienced by IVA patients through the formation of N-isovalerylglycine. GLYAT forms part of the phase II glycine conjugation pathway in the liver and detoxifies excess acyl-CoA’s namely benzoyl-CoA. However, very few studies support GLYAT as the enzyme that conjugates isovaleryl-CoA to glycine. Furthermore, GLYATL1, a paralogue of GLYAT, conjugates phenylacetyl-CoA to glutamine. Therefore, GLYATL1 might also be a candidate for the formation of N-isovalerylglycine. Based on the findings from the literature review, we proposed that GLYAT or GLYATL1 can form N-isovalerylglycine in IVA patients. To test this hypothesis, we performed an in-silico analysis to determine which enzyme is more likely to conjugate isovaleryl-CoA with glycine using AutoDock Vina. Thereafter, we performed in vitro validation using purified enzyme preparations. The in-silico and in vitro findings suggested that both enzymes could form N-isovaleryglycine albeit at lower affinities than their preferred substrates. Furthermore, an increase in glycine concentration does not result in an increase in N-isovalerylglycine formation. The results from the critical literature appraisal, in-silico, and in vitro validation, suggest the importance of further investigating the reaction kinetics and binding behaviors between these substrates and enzymes in understanding the pathophysiology of IVA
Ordnung zur Regelung der Zugangsprüfung für im Ausland qualifizierte Studienbewerberinnen und Studienbewerber (Zugangsprüfungsordnung) an der Hochschule Bonn-Rhein-Sieg vom 19.10.2023
Get PDFFaktor Mensch: Risiko und Chance: Informationssicherheitsbewusstsein in medizinischen Einrichtungen – Expertenansichten (Teil 2)
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Data Cart: A Privacy Pattern for Personal Data Management in Organizations
No full textThe European General Data Protection Regulation requires the implementation of Technical and Organizational Measures (TOMs) to reduce the risk of illegitimate processing of personal data. For these measures to be effective, they must be applied correctly by employees who process personal data under the authority of their organization. However, even data processing employees often have limited knowledge of data protection policies and regulations, which increases the likelihood of misconduct and privacy breaches. To lower the likelihood of unintentional privacy breaches, TOMs must be developed with employees’ needs, capabilities, and usability requirements in mind. To reduce implementation costs and help organizations and IT engineers with the implementation, privacy patterns have proven to be effective for this purpose. In this chapter, we introduce the privacy pattern Data Cart, which specifically helps to develop TOMs for data processing employees. Based on a user-centered design approach with employees from two public organizations in Germany, we present a concept that illustrates how Privacy by Design can be effectively implemented. Organizations, IT engineers, and researchers will gain insight on how to improve the usability of privacy-compliant tools for managing personal data
Dynamics and durability of HIV-1 neutralization are determined by viral replication
No full textHuman immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4+ T cell counts <200 µl-1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response
Strategic brand innovation – an explorative study of up- and downstream brand innovation practices in SME wineries
No full textImproving insect conservation management through insect monitoring and stakeholder involvement
Get PDFIn recent years, the decline of insect biodiversity and the imminent loss of provided ecosystem functions and services has received public attention and raised the demand for political action. The complex, multi-causal contributors to insect decline require a broad interdisciplinary and cross-sectoral approach that addresses ecological and social aspects to find sustainable solutions. The project Diversity of Insects in Nature protected Areas (DINA) assesses insect communities in 21 nature reserves in Germany, and considers interactions with plant diversity, pesticide exposure, spatial and climatic factors. The nature reserves border on agricultural land, to investigate impacts on insect diversity. Part of the project is to obtain scientific data from Malaise traps and their surroundings, while another part involves relevant stakeholders to identify opportunities and obstacles to insect diversity conservation. Our results indicate a positive association between insect richness and biomass. Insect richness was negatively related to the number of stationary pesticides (soil and vegetation), pesticides measured in ethanol, the amount of area in agricultural production, and precipitation. Our qualitative survey along with stakeholder interviews show that there is general support for insect conservation, while at the same time the stakeholders expressed the need for more information and data on insect biodiversity, as well as flexible policy options. We conclude that conservation management for insects in protected areas should consider a wider landscape. Local targets of conservation management will have to integrate different stakeholder perspectives. Scientifically informed stakeholder dialogues can mediate conflicts of interests, knowledge, and values to develop mutual conservation scenarios
Erträge geraten von zwei Seiten unter Druck: Eine Analyse der Margen-Entwicklung in der Fleischbranche zeigt die existentiellen Herausforderungen
No full textEine Untersuchung der Margen-Entwicklung in der Fleischbranche kommt zu einem eindeutigen Ergebnis: Der Lebensmitteleinzelhandel profitiert weit mehr als die anderen Teile der Wertschöpfungskette von den steigenden Preisen
Qualitative and quantitative study of the motor freewheel on the dynamic behavior of an eBike drive unit
No full textHeutzutage werden alternative Mobilitätslösungen immer wichtiger. Dabei haben eBikes ihr Potential längst unter Beweis gestellt. Der zugehörige Markt ist über die letzten 10 Jahre enorm gewachsen und gleichermaßen auch die Erwartungen an das Produkt, wie bspw. eine Fahrt ohne störende Vibrationen und Geräusche zu haben. Der Motorfreilauf leistet dabei einen maßgeblichen Einfluss auf das dynamische Verhalten. In diesem Beitrag soll daher eine methodische Vorgehensweise vorgestellt werden, um mittels Versuch und Simulation den Einfluss des Motorfeilaufs auf das dynamische Verhalten der eBike Antriebseinheit zu bestimmen