Medium- and short-chain dehydrogenase/reductase gene and protein families: The SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes

Short-chain dehydrogenases/reductases (SDRs) constitute a large family of NAD(P)(H)-dependent oxidoreductases, sharing sequence motifs and displaying similar mechanisms. SDR enzymes have critical roles in lipid, amino acid, carbohydrate, cofactor, hormone and xenobiotic metabolism as well as in redox sensor mechanisms. Sequence identities are low, and the most conserved feature is an α/β folding pattern with a central beta sheet flanked by 2–3 α-helices from each side, thus a classical Rossmannfold motif for nucleotide binding. The conservation of this element and an active site, often with an Asn-Ser-Tyr-Lys tetrad, provides a platform for enzymatic activities encompassing several EC classes, including oxidoreductases, epimerases and lyases. The common mechanism is an underlying hydride and proton transfer involving the nicotinamide and typically an active site tyrosine residue, whereas substrate specificity is determined by a variable C-terminal segment. Relationships exist with bacterial haloalcohol dehalogenases, which lack cofactor binding but have the active site architecture, emphasizing the versatility of the basic fold in also generating hydride transfer-independent lyases. The conserved fold and nucleotide binding emphasize the role of SDRs as scaffolds for an NAD(P)(H) redox sensor system, of importance to control metabolic routes, transcription and signalling

Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions

BACKGROUND: VS38c is a monoclonal antibody that recognises a rough endoplasmic reticulum (rER) intracellular antigen termed cytoskeleton-linking membrane protein 63. rER is typically found in viable tumour cells and is abundant in osteosarcoma cells. The aim of this study was to determine the diagnostic and prognostic utility of VS38c in the histological assessment of osteosarcoma and other bone tumours/tumour-like leisons. METHODS: Immunohistochemical staining with VS38c was carried out on formalin-fixed specimens of osteosarcoma (pre/post-chemotherapy) and a wide range of benign and malignant bone lesions. In addition, VS38c staining of cultures of MG63 and Sa0S2 osteosarcoma cell cultures. (±cisplatin and actinomycin D-treatment) was analysed. RESULTS: VS38c strongly stained tumour cells in all low-grade and high-grade osteosarcomas and in undifferentiated sarcomas and high-grade chondrosarcomas. There was little or no VS38c staining of low-grade chondrosarcomas or chordomas and variable staining of Ewing sarcomas. Osteoblasts in benign bone-forming tumours and mononuclear stromal cells in chondroblastomas, giant cell tumours and non-ossifying fibromas strongly stained for VS38c. VS38c staining was absent in cisplatin and actinomycin D treated Sa0S2 and MG63 cells. In specimens of osteosarcoma post-neoadjuvant therapy, VS38c staining was absent in most morphologically necrotic areas of tumor although some cells with pyknotic nuclei stained for VS38c in these areas. Most tumour cells exhibiting atypical nuclear forms were not stained by VS38c. CONCLUSIONS: Our findings show that VS38c is a sensitive but not specific diagnostic marker of osteosarcoma. Staining with VS38c identifies viable osteosarcoma cells, a feature which may be useful in the assessment of percentage tumour necrosis post-neoadjuvant chemotherapy

Akzeptanz von Tiergesundheitsplänen bei Landwirten – Ergebnisse einer Befragung bei 60 Betrieben

In organic farming the ambitious claims in enhancing and keeping animal health are often not realised. The implementation of animal health plans should clear this deficit effectively. Experiences with British and Danish herd health plans showed that the acceptance of plans is an essential part for its successful transfer into practice. But anyhow, this aspect has not been regarded sufficiently. To avoid similar mistakes like done in former institution tests a social study is integrated into German projects that deal with the implementation of animal health plans in poultry, dairy, and pig hus-bandry. To get more information about the acceptance, the study requires farmers’ attitudes to herd health plans, the motivation to animal health and financial and work capabilities as well

Lack of clustering in low-redshift 21-cm intensity maps cross-correlated with 2dF galaxy densities

We report results from 21-cm intensity maps acquired from the Parkes radio telescope and cross-correlated with galaxy maps from the 2dF galaxy survey. The data span the redshift range $0.057<z<0.098$ and cover approximately 1,300 square degrees over two long fields. Cross correlation is detected at a significance of $5.18\sigma$. The amplitude of the cross-power spectrum is low relative to the expected dark matter power spectrum, assuming a neutral hydrogen (HI) bias and mass density equal to measurements from the ALFALFA survey. The decrement is pronounced and statistically significant at small scales. At $k\sim1.5$ $h \mathrm{Mpc^{-1}}$, the cross power spectrum is more than a factor of 6 lower than expected, with a significance of $14.8\,\sigma$. This decrement indicates either a lack of clustering of neutral hydrogen (HI), a small correlation coefficient between optical galaxies and HI, or some combination of the two. Separating 2dF into red and blue galaxies, we find that red galaxies are much more weakly correlated with HI on $k\sim1.5$ $h \mathrm{Mpc^{-1}}$ scales, suggesting that HI is more associated with blue star-forming galaxies and tends to avoid red galaxies.Comment: 12 pages, 3 figures; fixed typo in meta-data title and paper author

Structural Basis for Substrate Specificity in Human Monomeric Carbonyl Reductases

Carbonyl reduction constitutes a phase I reaction for many xenobiotics and is carried out in mammals mainly by members of two protein families, namely aldo-keto reductases and short-chain dehydrogenases/reductases. In addition to their capacity to reduce xenobiotics, several of the enzymes act on endogenous compounds such as steroids or eicosanoids. One of the major carbonyl reducing enzymes found in humans is carbonyl reductase 1 (CBR1) with a very broad substrate spectrum. A paralog, carbonyl reductase 3 (CBR3) has about 70% sequence identity and has not been sufficiently characterized to date. Screening of a focused xenobiotic compound library revealed that CBR3 has narrower substrate specificity and acts on several orthoquinones, as well as isatin or the anticancer drug oracin. To further investigate structure-activity relationships between these enzymes we crystallized CBR3, performed substrate docking, site-directed mutagenesis and compared its kinetic features to CBR1. Despite high sequence similarities, the active sites differ in shape and surface properties. The data reveal that the differences in substrate specificity are largely due to a short segment of a substrate binding loop comprising critical residues Trp229/Pro230, Ala235/Asp236 as well as part of the active site formed by Met141/Gln142 in CBR1 and CBR3, respectively. The data suggest a minor role in xenobiotic metabolism for CBR3. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

Preschool children's health and its association with parental education and individual living conditions in East and West Germany

BACKGROUND: Social inequalities in health exist globally and are a major public health concern. This study focus on a systematic investigation into the associations between health indicators, living conditions and parental educational level as indicator of the social status of 6-year-old children living in West and East Germany in the decade after re-unification. Explanations of observed associations between parental education and health indicators were examined. METHODS: All boys and girls entering elementary school and living in predefined areas of East and West Germany were invited to participate in a series of cross-sectional surveys conducted between 1991 and 2000. Data of 28,888 German children with information on parental education were included in the analysis. Information about educational level of the parents, individual living conditions, symptoms and diagnoses of infectious diseases and allergies were taken from questionnaire. At the day of investigation, atopic eczema was diagnosed by dermatologists, blood was taken for the determination of allergen-specific immuno-globulin E, height and weight was measured and lung function tests were done in subgroups. Regression analysis was applied to investigate the associations between the health indicators and parental educational level as well as the child's living conditions. Gender, urban/rural residency and year of survey were used to control for confounding. RESULTS: Average response was 83% in East Germany and 71% in West Germany. Strong associations between health indicators and parental education were observed. Higher educated parents reported more diagnoses and symptoms than less educated. Children of higher educated parents were also more often sensitized against grass pollen or house dust mites, but had higher birth weights, lower airway resistance and were less overweight at the age of six. Furthermore, most of the health indicators were significantly associated with one or more living conditions such as living as a single child, unfavourable indoor air, damp housing condition, maternal smoking during pregnancy or living near a busy road. The total lung capacity and the prevalence of an atopic eczema at the day of investigation were the only health indicators those did not show associations with any of the predictor variables. CONCLUSION: Despite large differences in living conditions and evidence that some poor health outcomes were directly associated with poor living conditions, only few indicators demonstrated poorer health in social disadvantaged children. These were in both parts of Germany increased levels of overweight, higher airway resistance and, in East Germany only, reduced height in children with lower educated parents compared to those of higher education. In both East and West Germany, higher prevalence of airway symptoms was associated with a damp housing condition, and lower birth weight, reduced height and increased airway resistance at the age of six were associated with maternal smoking during pregnancy. The latter explained to a large extent the difference in birth weight and airway resistance between the educational groups

Ginzburg-Landau functional for nearly antiferromagnetic perfect and disordered Kondo lattices

Interplay between Kondo effect and trends to antiferromagnetic and spin glass ordering in perfect and disordered bipartite Kondo lattices is considered. Ginzburg-Landau equation is derived from the microscopic effective action written in three mode representation (Kondo screening, antiferromagnetic correlations and spin liquid correlations). The problem of local constraint is resolved by means of Popov-Fedotov representation for localized spin operators. It is shown that the Kondo screening enhances the trend to a spin liquid crossover and suppresses antiferromagnetic ordering in perfect Kondo lattices and spin glass ordering in doped Kondo lattices. The modified Doniach's diagram is constructed, and possibilities of going beyond the mean field approximation are discussed.Comment: 18 pages, RevTeX, 7 EPS figures include

Factors Affecting European Farmers’Participation in Biodiversity Policies

This article reports the major findings from an interdisciplinary research project that synthesises key insights into farmers’ willingness and ability to co-operate with biodiversity policies. The results of the study are based on an assessment of about 160 publications and research reports from six EU member states and from international comparative research.We developed a conceptual framework to systematically review the existent literature relevant for our purposes. This framework provides a common structure for analysing farmers’ perspectives regarding the introduction into farming practices of measures relevant to biodiversity. The analysis is coupled and contrasted with a survey of experts. The results presented above suggest that it is important to view support for practices oriented towards biodiversity protection not in a static sense – as a situation determined by one or several influencing factors – but rather as a process marked by interaction. Financial compensation and incentives function as a necessary, though clearly not sufficient condition in this process

Crossover from the chiral to the standard universality classes in the conductance of a quantum wire with random hopping only

The conductance of a quantum wire with off-diagonal disorder that preserves a sublattice symmetry (the random hopping problem with chiral symmetry) is considered. Transport at the band center is anomalous relative to the standard problem of Anderson localization both in the diffusive and localized regimes. In the diffusive regime, there is no weak-localization correction to the conductance and universal conductance fluctuations are twice as large as in the standard cases. Exponential localization occurs only for an even number of transmission channels in which case the localization length does not depend on whether time-reversal and spin rotation symmetry are present or not. For an odd number of channels the conductance decays algebraically. Upon moving away from the band center transport characteristics undergo a crossover to those of the standard universality classes of Anderson localization. This crossover is calculated in the diffusive regime.Comment: 22 pages, 9 figure

Assessment of technological options and economical feasibility for cyanophycin biopolymer and high-value amino acid production

Major transitions can be expected within the next few decades aiming at the reduction of pollution and global warming and at energy saving measures. For these purposes, new sustainable biorefinery concepts will be needed that will replace the traditional mineral oil-based synthesis of specialty and bulk chemicals. An important group of these chemicals are those that comprise N-functionalities. Many plant components contained in biomass rest or waste stream fractions contain these N-functionalities in proteins and free amino acids that can be used as starting materials for the synthesis of biopolymers and chemicals. This paper describes the economic and technological feasibility for cyanophycin production by fermentation of the potato waste stream Protamylasse™ or directly in plants and its subsequent conversion to a number of N-containing bulk chemicals