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"Münster, Max"
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A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction
Dengue virus causes approximately 96 million symptomatic infections annually, manifesting as dengue fever or occasionally as severe dengue
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,
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. There are no antiviral agents available to prevent or treat dengue. Here, we describe a highly potent dengue virus inhibitor (JNJ-A07) that exerts nanomolar to picomolar activity against a panel of 21 clinical isolates that represent the natural genetic diversity of known genotypes and serotypes. The molecule has a high barrier to resistance and prevents the formation of the viral replication complex by blocking the interaction between two viral proteins (NS3 and NS4B), thus revealing a previously undescribed mechanism of antiviral action. JNJ-A07 has a favourable pharmacokinetic profile that results in outstanding efficacy against dengue virus infection in mouse infection models. Delaying start of treatment until peak viraemia results in a rapid and significant reduction in viral load. An analogue is currently in further development.
The small molecule JNJ-A07 interferes with the interaction between the NS3 and NS4B proteins of dengue virus and reduces the viral load in mice even when first administered at peak viraemia.
Journal Article
Floral homeotic genes were recruited from homologous MADS-box genes preexisting in the common ancestor of ferns and seed plants
Flowers sensu lato are short, specialized axes bearing closely aggregated sporophylls. They are typical for seed plants (spermatophytes) and are prominent in flowering plants sensu stricto (angiosperms), where they often comprise an attractive perianth. There is evidence that spermatophytes evolved from gymnosperm-like plants with a fern-like mode of reproduction called progymnosperms. It seems plausible, therefore, that the stamens/carpels and pollen sacs/nucelli of spermatophytes are homologous to fern sporophylls and sporangia, respectively. However, the exact mode and molecular basis of early seed and flower evolution is not yet known. Comparing flower developmental control genes to their homologs from lower plants that do not flower may help to clarify the issue. We have isolated and characterized MADS-box genes expressed in gametophytes and sporophytes of the fern Ceratopteris. The data indicate that at least two different MADS-box genes homologous to floral homeotic genes existed in the last common ancestor of contemporary vascular plants, some descendants of which underwent multiple duplications and diversifications and were recruited into novel developmental networks during the evolution of floral organs
Journal Article
Aus der Wiedertaeuferzeit in Münster
Aber so große Erbitterung auch die Zwangseinziehung des Goldes und Silbers damals im April und Mai, als Jan noch einfacher Prophet war, hervorgerufen haben mochte, eine offene Empörung hatte noch nicht stattgefunden. Diese trat erst ein, als Jan Ende Juli dazu schritt, die Vielweiberei als offizielle, staatliche Eheform einzuführen. Es kann nicht genug betont werden, daß dieser verhängnisvolle Schritt die Entwicklung der Wiedertäufer …
Magazine Article
Aus der Wiedertaeuferzeit in Münster
Wer weiß heute noch viel von den Wiedertäufern in Münster? Vielleicht einige Gelehrte und ein paar Geschichtsfreunde in der alten lindenumgebenen Bischofsstadt. Vielleicht auch sonst jemand, dem einmal bei einem Besuche Münsters das Fehlen der Kircbturmspitzen aufgefallen ist, und der sich dann hat erzählen lassen, daß hier einmal ein Schneider, Jean von Leiden, sich anderthalb Jahre als König aufgespielt hat, 15 Frauen sein eigen nannte, …
Magazine Article
Postural dependency of the cerebral venous outflow
We have shown that predominance of the jugular veins in cerebrovenous drainage is limited to the supine position. In the erect position, the vertebral venous system represents the major outflow pathway.
Journal Article
Mixed-methods process evaluation of a proactive approach to healthcare in Parkinson’s disease—ParkProReakt: a protocol of a hybrid efficacy-implementation study
IntroductionPeople with Parkinson’s disease (PwPD) experience a wide range of motor and non-motor symptoms that have a significant impact on their health and quality of life. Effective care management for PwPD involves monitoring symptoms at home, involving specialised multidisciplinary care providers and enhancing self-management skills. This study protocol describes the process evaluation within a randomised clinical trial to assess the implementation and its impact on patient health outcomes of ParkProReakt—a proactive, multidisciplinary, digitally supported care model for community-dwelling PwPD.Methods and analysisThe hybrid efficacy-implementation study will assess key implementation outcomes using the Medical Research Council framework for complex interventions alongside a randomised controlled trial. A combination of quantitative and qualitative methods will be used to assess process data from care providers and patients. The main process outcomes are fidelity, dose, feasibility and context. Context will be analysed through semistructured interviews and focus groups using the Consolidated Framework of Implementation Research. To elucidate potential facilitators and barriers to implementation and to gain deeper insights into the efficacy outcome data, quantitative and qualitative process data will be integrated at an interpretative level using mixed methods. In addition to process evaluation, potential indirect mechanisms of impact will be measured.Ethics and disseminationEthical approval for this study was obtained from the responsible state medical ethics committees in Hesse and Hamburg, Germany. Results will be communicated to the funding body and disseminated through scientific publications.Trial registrationThis study was registered with the German Registry for Clinical Studies (DRKS)—number: DRKS00031092.
Journal Article
ParkProReakt—evaluation of a proactive approach to healthcare in Parkinson’s disease: a study protocol for a randomised controlled trial
IntroductionThe complexity of Parkinson’s disease (PD) symptoms and the necessity for individualised, multidisciplinary and digital health technology-based care are widely acknowledged; however, access to specialist care remains limited, particularly in rural areas. Current healthcare systems are frequently ill-equipped to deliver timely, personalised interventions. In response to these challenges, the ParkProReakt project aims to enhance PD care through a proactive, technology-enabled, multidisciplinary approach designed to improve patient health-related quality of life (HRQoL) and alleviate caregiver burden.Methods and analysisA randomised controlled trial will assess the efficacy and cost-effectiveness of ParkProReakt—a proactive, multidisciplinary, digitally supported care model for community-dwelling people with Parkinson’s disease (PwPD)—compared with standard care. We will recruit a total of 292 PwPD and their informal caregivers living in two diverse regions in Germany. The primary outcome measure will be patients’ HRQoL as measured by the Parkinson’s Disease Questionnaire, obtained at baseline, monthly and at completion of participation. Secondary outcomes comprise patients’ subjective well-being, incidence or change of long-term care needs, global cognition and disease progression, utilisation of healthcare services, including hospitalisations, caregiver burden and healthcare costs. Statistical analysis will include t-tests for HRQoL changes, general linear model for confounders and multilevel models for centre effects. Secondary outcomes and cost-effectiveness (incremental cost-effectiveness ratio) will be analysed similarly using R and SPSS.Ethics and disseminationThe study protocol has been approved by the Ethics Committees of the Medical Associations of Hesse and Hamburg. The results of our study will be reported to the funding body and disseminated through scientific publications and presentations at national and international conferences.Trial registration numberThis study was registered with the German Registry for Clinical Studies (DRKS) in both German and English; number: DRKS00031092.
Journal Article
Pediatric Precursor B-Cell Lymphoblastic Malignancies: From Extramedullary to Medullary Involvement
B-cell lymphoblastic lymphoma (BCP-LBL) and B-cell acute lymphoblastic leukemia (BCP-ALL) are the malignant counterparts of immature B-cells. BCP-ALL is the most common hematological malignancy in childhood, while BCP-LBL accounts for only 1% of all hematological malignancies in children. Therefore, BCP-ALL has been well studied and treatment protocols have changed over the last decades, whereas treatment for BCP-LBL has stayed roughly the same. Clinical characteristics of 364 pediatric patients with precursor B-cell malignancies were studied, consisting of BCP-LBL (n = 210) and BCP-ALL (n = 154) patients. Our results indicate that based on the clinical presentation of disease, B-cell malignancies probably represent a spectrum ranging from complete isolated medullary disease to apparent complete extramedullary disease. Hepatosplenomegaly and peripheral blood involvement are the most important discriminators, as both seen in 80% and 95% of the BCP-ALL patients and in 2% of the BCP-LBL patients, respectively. In addition, we show that the overall survival rates in this cohort differ significantly between BCP-LBL and BCP-ALL patients aged 1–18 years (p = 0.0080), and that the outcome for infants (0–1 years) with BCP-LBL is significantly decreased compared to BCP-LBL patients of all other pediatric ages (p < 0.0001).
Journal Article