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Lifestyle interventions including meal replacement are suitable for prevention and treatment of obesity and type-2-diabetes. Since leptin is involved in weight regulation, we hypothesised that a meal replacement-based lifestyle intervention would reduce leptin levels more effectively than lifestyle intervention alone. In the international, multicentre, randomised-controlled ACOORH-trial (Almased-Concept-against-Overweight-and-Obesity-and-Related- Health-Risk), overweight or obese participants with metabolic syndrome criteria (n = 463) were randomised into two groups and received telemonitoring devices and nutritional advice. The intervention group additionally used a protein-rich, low-glycaemic meal replacement. Data were collected at baseline, after 1, 3, 6, and 12 months. All datasets providing leptin data (n = 427) were included in this predefined subanalysis. Serum leptin levels significantly correlated with sex, body mass index, weight, and fat mass at baseline (p < 0.0001). Stronger leptin reduction has been observed in the intervention compared to the control group with the lowest levels after 1 month of intervention (estimated treatment difference −3.4 µg/L [1.4; 5.4] for females; −2.2 µg/L [1.2; 3.3] for males; p < 0.001 each) and was predictive for stronger reduction of body weight and fat mass (p < 0.001 each) over 12 months. Strongest weight loss was observed after 6 months (−5.9 ± 5.1 kg in females of the intervention group vs. −2.9 ± 4.9 kg in the control group (p < 0.0001); −6.8 ± 5.3 kg vs. −4.1 ± 4.4 kg (p = 0.003) in males) and in those participants with combined leptin and insulin decrease. A meal replacement-based lifestyle intervention effectively reduces leptin which is predictive for long-term weight loss.
Die Fundmeldungen in Band 34 von Botanik und Naturschutz in Hessen stammen von: Dirk Bönsel, Martin De Jong, Klaus Dühr, Uta Engel, Benjamin Feller, Christian Feuring, Thomas Gregor, Arthur Händler, Karsten Horn, Diemut Klärner, Julia Kruse, Eric Martiné, Hasko Friedrich Nesemann, Kai Uwe Nierbauer, Uwe Raabe, Susanne Raehse, Felix Reischmann, Bernd Sauerwein, Petra Schmidt, Fabian Schrauth, Christof Nikolaus Schröder, Helmut Siebert, Michael Thieme, Otto Wacker und Rüdiger Wittig.
Zwei traditionelle Wirkungsbereiche von Intellektuellen, die politische Medienöffentlichkeit und das akademische Feld, unterliegen seit über drei Jahrzehnten anhaltenden strukturellen Veränderungen. Diese gelten vielfach als Ursache einer tiefen Krise oder sogar des Verschwindens der Intellektuellen. Doch um welche Veränderungen geht es dabei genau, und wie restrukturieren sie die gegenwärtige Rolle und Funktion von Intellektuellen? Zur Beantwortung dieser Fragen entwickelt der Beitrag einen Ansatz, der die struktur- und erfahrungsbezogenen Bedingungen intellektueller Praxis fokussiert und historisch vergleichend analysiert. Um eine Vergleichsfolie zu gewinnen, wird die intellektuelle Praxis Theodor W. Adornos analysiert. Dabei zeigt sich, dass Adorno die charakteristischen Widersprüche öffentlichen und akademischen intellektuellen Engagements methodisch aufrechterhielt, indem er eine Position des „Dazwischen“ reklamierte. Vor diesem Hintergrund werden seit den 1970er-Jahren forcierte strukturelle Veränderungen der Medienöffentlichkeit und des akademischen Feldes als Prozesse der „Vereindeutigung“ interpretiert, die eine widerspruchsaffine intellektuelle Praxis erschweren. In der Folge lassen sich eine ausgeweitete kommerzielle sowie eine eingeschränkte akademische Intellektuellenpraxis beobachten, die jeweils politisch wirksame Interventionen begrenzen.
Gene therapy (GT) is becoming a realistic treatment option for patients with haemophilia. Outside clinical trials, the complexity and potential complications of GT will pose unprecedented challenges to haemophilia care centres.AIM: To explore the potential use of electronic tools to improve the delivery of GT under real-world conditions.METHODS: Considering the hub-and-spoke model, the GTH working group on GT considered the entire patient pathway and reached consensus on requirements for an integrative software tool to secure documenting and sharing information between treaters, pharmacies and patients.RESULTS: Six steps of the gene therapy process were identified, each requiring completion of the previous step as a prerequisite for entry. The responsibilities of GT dosing and follow-up treatment centres, read/write access rules, and the minimum data set were outlined. Data contributed by patients through mobile devices was also considered.CONCLUSION: Important information needs to be shared between patients and treatment centres in a real-world GT hub-and-spoke model. Collecting and sharing this information in well-organised electronic applications will not only improve patient care but also enable national and international data collection in clinical registries...
Phenotypical screening is a widely used approach in drug discovery for the identification of small molecules with cellular activities. However, functional annotation of identified hits often poses a challenge. The development of small molecules with narrow or exclusive target selectivity such as chemical probes and chemogenomic (CG) libraries, greatly diminishes this challenge, but non-specific effects caused by compound toxicity or interference with basic cellular functions still pose a problem to associate phenotypic readouts with molecular targets. Hence, each compound should ideally be comprehensively characterized regarding its effects on general cell functions. Here, we report an optimized live-cell multiplexed assay that classifies cells based on nuclear morphology, presenting an excellent indicator for cellular responses such as early apoptosis and necrosis. This basic readout in combination with the detection of other general cell damaging activities of small molecules such as changes in cytoskeletal morphology, cell cycle and mitochondrial health provides a comprehensive time-dependent characterization of the effect of small molecules on cellular health in a single experiment. The developed high-content assay offers multi-dimensional comprehensive characterization that can be used to delineate generic effects regarding cell functions and cell viability, allowing an assessment of compound suitability for subsequent detailed phenotypic and mechanistic studies.
A toolbox for the generation of chemical probes for Baculovirus IAP Repeat containing proteins
(2022)
E3 ligases constitute a large and diverse family of proteins that play a central role in regulating protein homeostasis by recruiting substrate proteins via recruitment domains to the proteasomal degradation machinery. Small molecules can either inhibit, modulate or hijack E3 function. The latter class of small molecules led to the development of selective protein degraders, such as PROTACs (PROteolysis TArgeting Chimeras), that recruit protein targets to the ubiquitin system leading to a new class of pharmacologically active drugs and to new therapeutic options. Recent efforts have focused on the E3 family of Baculovirus IAP Repeat (BIR) domains that comprise a structurally conserved but diverse 70 amino acid long protein interaction domain. In the human proteome, 16 BIR domains have been identified, among them promising drug targets such as the Inhibitors of Apoptosis (IAP) family, that typically contain three BIR domains (BIR1, BIR2, and BIR3). To date, this target area lacks assay tools that would allow comprehensive evaluation of inhibitor selectivity. As a consequence, the selectivity of current BIR domain targeting inhibitors is unknown. To this end, we developed assays that allow determination of inhibitor selectivity in vitro as well as in cellulo. Using this toolbox, we have characterized available BIR domain inhibitors. The characterized chemical starting points and selectivity data will be the basis for the generation of new chemical probes for IAP proteins with well-characterized mode of action and provide the basis for future drug discovery efforts and the development of PROTACs and molecular glues.