Biocrates Life Sciences (Austria)

Physical education (PE) is often considered an ideal setting for the promotion of physical activity (PA) among adolescents and for the encouragement of an active lifestyle in adulthood. In order to achieve this goal, however, it is necessary to foster a positive attitude towards PE. The present study examined attitudes towards and the perceived importance of PE among Austrian adolescents. A total of 3011 adolescents (47.5% female) between 10 and 17 years of age completed a standardized questionnaire during regular school hours. In addition, body weight and height were measured. Overall, 78.5% stated that PE is important to them and 84.3% believed that PE positively affects their health and well-being. PE also motivated 68.4% of the participants to engage in leisure time PA, and 69.9% would like to have daily PE. Further, 91.0% reported a good relationship with their PE teacher while 68.6% considered themselves to be good at sports. Nevertheless, there was a significant decline in the perceived value of PE with increasing age, and among girls, as well as those with excess body weight, perceived PE to be less important. As these groups are particularly vulnerable for low PA levels, it is important to provide challenging and enjoyable experiences that foster a positive attitude towards PE. Ensuring positive experiences throughout students' school careers could play a key role in promoting an active lifestyle later in life.

BackgroundRespiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease among infants and young children worldwide, especially in low- and middle-income countries (LMICs). RSM01 is a novel, highly potent, half-life-extended anti-RSV monoclonal antibody (mAb) candidate primarily being developed for LMICs. Here we present the preclinical characterisation and results of a phase 1 trial of RSM01.MethodsPreclinical characterisation of RSM01 was conducted using in-vitro neutralization assays and cotton rat models.In the first-in-human, double-blind, phase 1 trial, 56 healthy adults were randomised 6:1 within dose cohorts to receive a single dose of RSM01 (n = 48) or placebo (n = 8): 300 mg intravenously (IV), 300 mg intramuscularly (IM) or 1000 mg IV (parallel cohorts), 3000 mg IV, and an expansion cohort of 600 mg IM. Systemic solicited adverse events (AEs) were assessed through day 7; unsolicited AEs were collected through day 151. Pharmacokinetics and anti-drug antibodies (ADA) to RSM01 were assessed using immunoassays. A population pharmacokinetics model predicted paediatric pharmacokinetics parameters using allometric scaling and age-specific population weight statistics of North American and African infants.ResultsRSM01 exhibited highly potent neutralizing activity in the single ng/mL range (0.7–6.4) against diverse RSV-A and RSV-B isolates in vitro. RSM01 also demonstrated prophylactic efficacy in cotton rat models with both RSV subtypes. In the phase 1 clinical trial, the most common unsolicited AEs were COVID-19 (2/48), headache (2/48), and nausea (2/48), all in RSM01-treated participants. The only systemic solicited AEs reported were headache (5/48) and tiredness (2/48) in participants receiving RSM01. No serious AEs or deaths were reported. The half-life of RSM01 was 78 days with dose-proportional increases in Tmax and AUClast after IV administration. Among RSM01-treated participants, 2/48 were ADA positive at baseline, and 1/48 seroconverted to ADA-positive post-baseline.ConclusionsRSM01 is a highly potent, half-life-extended, RSV-neutralising mAb candidate that was shown to be well tolerated in healthy adults. The rate of ADA to RSM01 was low. The long half-life of RSM01 and pharmacokinetics profile support further development of RSM01 as a potential single dose per season prophylaxis to prevent RSV disease in infants.Trial registrationClinicaltrials.gov NCT05118386, Nov 12, 2021.

Abstract Protein kinases act as central molecular switches in the control of cellular functions. Alterations in the regulation and function of protein kinases may provoke diseases including cancer. In this study we investigate the conformational states of such disease-associated kinases using the high sensitivity of the Kinase Conformation (KinCon)-reporter system. We first track BRAF-kinase activity conformation changes upon melanoma drug binding. Second, we also use the KinCon reporter technology to examine the impact of regulatory protein interactions on LKB1-kinase tumor suppressor functions. Third, we explore the conformational dynamics of RIP-kinases in response to TNF-pathway activation and small molecule interactions. Finally, we show that CDK4/6 interactions with regulatory proteins alter conformations which remain unaffected in the presence of clinically applied inhibitors. Apart from its predictive value, the KinCon technology helps to identify cellular factors that impact drug efficacies. The understanding of the structural dynamics of full-length protein kinases when interacting with small molecule inhibitors or regulatory proteins is crucial for designing more effective therapeutic strategies.

It was the aim of this study to design charge converting lipid nanoparticles (LNP) via a microfluidic mixing technique used for the preparation and coating of LNP. LNP consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE), and various cationic surfactants were prepared at diverging flow rate ratios (FRR) via microfluidic mixing. Utilizing a second chip in the microfluidic set-up, LNP were coated with polyoxyethylene (9) nonylphenol monophosphate ester (PNPP). LNP were examined for their stability in different physiologically relevant media as well as for hemolytic and cytotoxic effects. Finally, phosphate release and charge conversion of PNPP-coated LNP were evaluated after incubation with alkaline phosphatase and on Caco2-cells. LNP produced at an FRR of 5:1 exhibited a size between 80 and 150 nm and a positive zeta potential. Coating with PNPP within the second chip led to LNP exhibiting a negative zeta potential. After incubation with 1 U/ml alkaline phosphatase for 4 h, zeta potential of the LNP containing 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP) as cationic component shifted from − 35 mV to approximately + 5 mV. LNP prepared with other cationic surfactants remained slightly negative after enzymatic phosphate cleavage. Manufacturing of LNP containing PNPP and DOTAP via connection of two chips in a microfluidic instrument proves to show efficient change in zeta potential from negative to positive after incubation with alkaline phosphatase.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1007/s13346-024-01538-5.

Abstract Soils are the foundation of agricultural production, ecosystem functioning and human well‐being. Bridging soil knowledge gaps and improving the knowledge system is crucial to meet the growing EU soil policy ambitions in the face of climate change and the ongoing trend in soil degradation. The objective of this article is to assess the current state of knowledge, knowledge use and knowledge gaps concerning sustainable soil management in Europe. This study is based on interviews with 791 stakeholders and 254 researchers and on a comprehensive review of >1800 documents carried out under the European Joint Programme on agricultural soils. Despite differences in stakeholder groups, the conclusions are rather consistent and complementary. We identified major knowledge gaps with respect to (1) soil carbon stocks, (2) soil degradation and fertility and (3) strategies for improved soil management. Transcending these three areas, particularly the loss of soil organic carbon, peatland degradation and soil compaction, are most critical, thus, we stress the urgency of developing more models and monitoring programmes on soils. Stakeholders further report that insufficient transfer of existing soil research findings to practitioners is a hindrance to the adoption of sustainable soil management practices. In addition to knowledge production, soil knowledge gaps may be addressed by considering seven recommendations from the stakeholders: (1) raising awareness, (2) strengthening knowledge brokers, (3) improving relevance of research activities and resource allocation for land users, (4) peer‐to‐peer communication, (5) targeting advice and information, (6) improving knowledge access, and (7) providing incentives. We argue that filling and bridging knowledge gaps should be a priority for policymakers and the insights provided in the article may help prioritise research and dissemination needs enabling a transition to more sustainable soil management in Europe.

Ion mobility spectrometry-mass spectrometry (IMS-MS) is experiencing rapid growth in proteomic studies, driven by its enhancements in dynamic range and throughput, increasing the quantitation precision, and the depth of proteome coverage. The core principle of ion mobility spectrometry is to separate ions in an inert gas under the influence of an electric field based on differences in drift time. This minireview provides an introduction to IMS operation modes and a description of advantages and limitations is presented. Moreover, the principles of trapped IMS-MS (TIMS-MS), including parallel accumulation-serial fragmentation are discussed. Finally, emerging applications linked to TIMS focusing on sample throughput (in clinical proteomics) and sensitivity (single-cell proteomics) are reviewed, and the possibilities of intact protein analysis are discussed.

The increasing prevalence of unhealthy lifestyle choices contribute to almost all chronic conditions negatively affecting individual and public health. As the most beneficial preventative solution, a healthy lifestyle focusing on the dual approach of physical activity (PA) and a healthful diet is highly recommended. Considering the growing number of people interested in sustainable, plant-based diets, it seems crucial to analyze lifestyle behaviors with a special focus on diet type to delve deeper into the unenthusiastic health status among young populations. Therefore, this multidisciplinary study aims to survey and scale health behaviors with a special focus on the prevalence of traditional and vegetarian diets in connection with PA levels among Austrian pupils (10–19 years), teachers and principals in secondary education levels I and II. Following a cross-sectional design, sociodemographic and school-related data along with a complete profile of lifestyle behaviors, including detailed information regarding diet, PA, sports & exercise, and other health-related behaviors, were collected using online-based questionnaires. A total number of 8,845 children/adolescents (~1.2% of the eligible 771,525 Austrian secondary school pupils) and 1,350 adults (~1.5% of total eligible 89,243 Austrian teachers/principals) participated in the study. As this is the first investigation to explore the prevalence of veganism/vegetarianism amongst a large group of pupils, the present study will add an important contribution to overcome the lack of knowledge on PA, sports & exercise linked to healthy alternative diets. With a sustainable healthy lifestyle, a healthy transition from childhood to adulthood occurs, which can result in growing healthier functioning generations at all social levels. As a study protocol, the present article is intended to present comprehensive details of the study design, objectives, and the associated analytical procedures of the “From Science 2 School” study.