32 research outputs found

    Framework and baseline examination of the German National Cohort (NAKO)

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    The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5

    The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

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    The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)

    The role of manufacturing in affecting the social dimension of sustainability

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    The High Resolution Imaging Science Experiment (HiRISE) during MRO’s Primary Science Phase (PSP)

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    Temperature effects on three downy brome \u3cem\u3e(Bromus tectorum)\u3c/em\u3e seed collections inoculated with the fungal pathogen \u3cem\u3ePyrenophora semeniperda\u3c/em\u3e

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    Downy brome (Bromus tectorum L., syn. cheatgrass) is a winter annual grass that invades North American cropping, forage, and rangeland systems. Control is often difficult to achieve, because B. tectorum has a large seedbank, which results in continuous propagule pressure. Pyrenophora semeniperda (Brittlebank and Adam) Shoemaker, a soilborne fungal pathogen, has been investigated as a biological control for B. tectorum, because it can kill seeds that remain in the seedbank, thereby reducing propagule pressure. Temperature influences P. semeniperda and has not been investigated in the context of seeds collected from different B. tectorum locations, that may vary in susceptibility to infection. We compared the effects of temperature (13, 17, 21, 25 C) and B. tectorum seed locations (range, crop, subalpine) with different mean seed weights on infection rates of P. semeniperda using a temperature-gradient table. Infection differed by seed location (P \u3c 0.001) and temperature (P \u3c 0.001), with lighter-weight seeds (i.e., range and subalpine) more susceptible to P. semeniperda infection. Infection increased as temperature increased and was higher at 21 C (66.7 ± 6.7%) and 25 C (73.3 ± 6.0%). Germination was affected by seed location (P \u3c 0.001) and temperature (P = 0.019). Germination was highest for the crop seed location (45.4 ± 4.2%) and overall decreased at higher temperatures (21 and 25 C). Our results suggest that B. tectorum seeds from a crop location are less affected by P. semeniperda than those from range and subalpine locations. Moreover, this demonstrates a temperature-dependent effect on all populations
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