Recombinant expression and purification of the 2,5-diketocamphane 1,2-monooxygenase from the camphor metabolizing Pseudomonas putida strain NCIMB 10007

Three different Baeyer-Villiger monooxygenases (BVMOs) were reported to be involved in the camphor metabolism by Pseudomonas putida NCIMB 10007. During (+)-camphor degradation, 2,5-diketocamphane is formed serving as substrate for the 2,5-diketocamphane 1,2-monooxygenase. This enzyme is encoded on the CAM plasmid and depends on the cofactors FMN and NADH and hence belongs to the group of type II BVMOs. We have cloned and recombinantly expressed the oxygenating subunit of the 2,5-diketocamphane 1,2-monooxygenase (2,5-DKCMO) in E. coli followed by His-tag-based affinity purification. A range of compounds representing different BVMO substrate classes were then investigated, but only bicyclic ketones were converted by 2,5-DKCMO used as crude cell extract or after purification. Interestingly, also (-)-camphor was oxidized, but conversion was about 3-fold lower compared to (+)-camphor. Moreover, activity of purified 2,5-DKCMO was observed in the absence of an NADH-dehydrogenase subunit

The effect of word semantic transparency on Chinese lexical unitisation: a window into lexical learning and organisation

Word semantic transparency (ST) refers to the extent that word constituents are semantically transparent (T) or opaque (O) to whole-word meaning. Bimorphemic compound words (compounds) may be fully opaque (OO), partially opaque (TO or OT), or fully transparent (TT). The word-superiority effect (WSE) describes the superior recognition of word constituents in a word, as opposed to a nonword, context. Chinese compounds comprise two written characters with a natural space between compound constituents. It has been shown that Chinese compounds with at least an opaque constituent patterned together and displayed a larger WSE (more word-like) than TT compounds. This corroborated with results obtained with English compounds when a space was artificially inserted between compound constituents. The present study further examined the modulatory effect of ST on the Chinese WSE by transposing the order of constituent characters; the familiar form of the canonical compounds was disrupted, delaying word recognition until at least the initial constituent (now second character) was processed. Expectedly, OO items appeared more word-like than TT items. However, partially opaque items were not as word-like as OO items, especially when the T constituent was the final constituent (now first character). Taken together with previous results, the effect of ST on Chinese whole-word lexical unitisation appears graded but with a bias toward unitisation wherever there is an opaque element. These results provided a window into how lexical learning and representation is sensitive to language-specific, script-related variations

The relation between science achievement and general cognitive abilities in large-scale assessments

Although large-scale assessments (LSA) of school achievement claim to measure domain-specific achievement, they have been criticized for primarily measuring domain-general abilities. Numerous studies provide evidence that LSA of mathematical achievement as well as verbal achievement cover both general cognitive abilities (GCA) and domain-specific achievement dimensions. We extend previous research by analyzing a standards-oriented and literacy-oriented LSA in the domain of science to determine the relation of these two assessment types with domain-general abilities. While literacy-oriented assessments focus on the knowledge and skills students need to meet the demands of modern societies, standards-oriented assessments focus on national educational standards and curricula. A sample of 1722 students worked on three assessments: (a) the PISA scientific literacy assessment; (b) a standards-oriented assessment based on the German National Educational Standards in biology, chemistry, and physics developed by the Institute for Educational Quality Improvement (IQB); and (c) a GCA test. Comparisons of competing structural models showed that models differentiating between domain-specific achievement and GCA best represented the structure of the assessments. Furthermore, standards-oriented and literacy-oriented LSAs in science shared common variance with GCA but also comprised specific variance. In addition to a factor representing students' GCA, we identified a science literacy-oriented and two standards-oriented factors. Relations with school grades in various STEM and non-STEM subjects were mixed and only partly provided evidence for the specificity of science LSAs. Our findings are important for understanding and interpreting results of LSAs in the contexts of GCA and science. We discuss our outcomes with respect to educational monitoring practices

German health interview and examination survey for adults (DEGS) - design, objectives and implementation of the first data collection wave

Background: The German Health Interview and Examination Survey for Adults (DEGS) is part of the recently established national health monitoring conducted by the Robert Koch Institute. DEGS combines a nationally representative periodic health survey and a longitudinal study based on follow-up of survey participants. Funding is provided by the German Ministry of Health and supplemented for specific research topics from other sources. Methods/design: The first DEGS wave of data collection (DEGS1) extended from November 2008 to December 2011. Overall, 8152 men and women participated. Of these, 3959 persons already participated in the German National Health Interview and Examination Survey 1998 (GNHIES98) at which time they were 18–79 years of age. Another 4193 persons 18–79 years of age were recruited for DEGS1 in 2008–2011 based on two-stage stratified random sampling from local population registries. Health data and context variables were collected using standardized computer assisted personal interviews, self-administered questionnaires, and standardized measurements and tests. In order to keep survey results representative for the population aged 18–79 years, results will be weighted by survey-specific weighting factors considering sampling and drop-out probabilities as well as deviations between the design-weighted net sample and German population statistics 2010. Discussion: DEGS aims to establish a nationally representative data base on health of adults in Germany. This health data platform will be used for continuous health reporting and health care research. The results will help to support health policy planning and evaluation. Repeated cross-sectional surveys will permit analyses of time trends in morbidity, functional capacity levels, disability, and health risks and resources. Follow-up of study participants will provide the opportunity to study trajectories of health and disability. A special focus lies on chronic diseases including asthma, allergies, cardiovascular conditions, diabetes mellitus, and musculoskeletal diseases. Other core topics include vaccine-preventable diseases and immunization status, nutritional deficiencies, health in older age, and the association between health-related behavior and mental health

M4 Safety and tolerability of BN82451B in huntington’s disease

Background BN82451B is a small, orally active molecule with good CNS penetration. Preclinical studies in tgHD R6/2 mice suggested improved motor function and prolonged survival. In addition antidyskinetic activity was observed in other models. The proposed mechanisms of action (MOA) are (1) antiexcytotoxic due to a sodium channel blocking potential, (2) antioxidant, (3) anti-inflammatory due to a cyclooxygenase (COX) inhibitory potential and (4) mitochondrial protective. Aims The primary objective of this phase 2a study (NCT02231580) is to investigate the safety and tolerability of BN82451B bid versus placebo for 28 days in male HD subjects. Secondary objectives include assessment of pharmacokinetics and of pharmacodynamics via the effects on quantitative motor (Q-Motor) measures. UHDRS subscales are implemented as exploratory measures. Methods Subjects: We intend to recruit 30 male HD subjects. 24 receive BN82451B and 6 placebo. The study is conducted in an inpatient setting at a single phase I unit in Germany. Design A sequential design was chosen to enable dose escalation starting with 40 mg bid with a potential maximum dose of 80 mg bid. Three subsequent cohorts of 10 patients each are randomised with different starting doses. Subjects in group one are treated with 40 mg bid for 14 days and may be increased to 60 mg bid the subsequent 14 days. In group 2, subjects may first receive 60 mg bid with possible increase to 80 mg bid. Group 3 subjects may receive 80 mg bid for 28 days. Dose increases in the consecutive groups are subject to approval by a Data Review Committee (DRC). The decision to increase the dose in individual patient will be based on the investigator’s judgement. Results Results of the study are expected for Q4/2016. Conclusions Recruitment in this trial is difficult as in-patient periods of nearly one month are logistically challenging. Safety data will be available soon and pharmacodynamics readouts such as Q-motor measures may help to guide decisions on the further path of development of BN82451B