syn-Benzene dioxides: chemoenzymatic synthesis from 2,3-cis-dihydrodiol derivatives of monosubstituted benzenes and their application in the synthesis of regioisomeric 1,2- and 3,4-cis-dihydrodiols and 1,4-dioxocins

cis-2,3-Dihydrodiol metabolites of monosubstituted halobenzenes and toluene have been used as synthetic precursors of the corresponding 3,4-cis-dihydrodiols. Enantiopure syn-benzene dioxide intermediates were reduced to the 3,4-cis-dihydrodiols and thermally racemised via the corresponding 1,4-dioxocins. The syn-benzene dioxide-1,4-dioxocin valence tautomeric equilibrium ratio was found to be dependent on the substituent position. The methodology has also been applied to the synthesis of both enantiomers of the 1,2-(ipso)- and 3,4-cis-dihydrodiols of toluene. This chemoenzymatic approach thus makes available, for the first time, all three possible cis-dihydrodiol regioisomers of a monosubstituted benzene.

Information gathering and decision making about resource value in animal contests

Contestants are predicted to adjust the cost of a fight in line with the perceived value of the resource and this provides a way of determining whether the resource has been assessed. An assessment of resource value is predicted to alter an animal's motivational state and we note different methods of measuring that state. We provide a categorical framework in which the degree of resource assessment may be evaluated and also note limitations of various approaches. We place studies in six categories: (1) cases of no assessment, (2) cases of internal state such as hunger influencing apparent value, (3) cases of the contestants differing in assessment ability, (4) cases of mutual and equal assessment of value, (5) cases where opponents differ in resource value and (6) cases of particularly complex assessment abilities that involve a comparison of the value of two resources. We examine the extent to which these studies support game theory predictions and suggest future areas of research. (C) 2008 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Acute and chronic effects of dietary fatty acids on cholecystokinin expression, storage and secretion in enteroendocrine STC-1 cells

Cholecystokinin (CCK) is a peptide hormone secreted from the I-cells of the intestine and it has important physiological actions related to appetite regulation and satiety. In this study we used STC-1 cells to investigate the effects of common dietary-derived fatty acids (FAs) on I-cell secretory function and metabolism. We extend earlier studies by measuring the acute and chronic effects of 11 FAs on CCK secretion, cellular CCK content, CCK mRNA levels, cellular DNA synthesis, cellular viability and cytotoxicity. FAs were selected in order to assess the importance of chain length, degree of saturation, and double bond position and conformation. The results demonstrate that secretory responses elicited by dietary FAs are highly selective. For example, altering the conformation of a double bond from cis to trans (i.e. oleic acid versus elaidic acid) completely abolishes CCK secretion. Lauric acid appears to adversely affect I-cell metabolism and arachidonic acid suppresses DNA synthesis. Our studies reveal for the first time that conjugated linoleic acid isoforms are particularly potent CCK secretagogues, which also boost intracellular stores of CCK. These actions of conjugated linoleic acid may explain satiating actions observed in dietary intervention studies.

The effect of slurry storage and anaerobic-digestion on survival of pathogenic bacteria

The decline in viable numbers of Salmonella typhimurium, Yersinia enterocolitica and Listeria monocytogenes in beef cattle slurry is temperature-dependent; they decline more rapidly at 17-degrees-C than at 4-degrees-C. Mesophilic anaerobic digestion caused an initial rapid decline in the viable numbers of Escherichia coli, Salm. typhimurium, Y. enterocolitica and L. monocytogenes. This was followed by a period in which the viable numbers were not reduced by 90%. The T90 values of E. coli, Salm. typhimurium and Y. enterocolitica ranged from 0.7 to 0.9 d during batch digestion and 1.1 to 2-5 d during semi-continuous digestion. Listeria monocytogenes had a significantly higher mean T90 value during semi-continuous digestion (35.7 d) than batch digestion (12.3 d). Anaerobic digestion had little effect in reducing the viable numbers of Campylobacter jejuni.

Examining acute and chronic effects of short- and long-chain fatty acids on peptide YY (PYY) gene expression, cellular storage and secretion in STC-1 cells

PURPOSE: Peptide YY (PYY) is a gastrointestinal hormone with physiological actions regulating appetite and energy homoeostasis. The cellular mechanisms by which nutrients stimulate PYY secretion from intestinal enteroendocrine cells are still being elucidated.r/>r/>METHODS: This study comprehensively evaluated the suitability of intestinal STC-1 cells as an in vitro model of PYY secretion. PYY concentrations (both intracellular and in culture media) with other intestinal peptides (CCK, GLP-1 and GIP) demonstrated that PYY is a prominent product of STC-1 cells. Furthermore, acute and chronic PYY responses to 15 short (SCFAs)- and long-chain (LCFAs) dietary fatty acids were measured alongside parameters for DNA synthesis, cell viability and cytotoxicity.r/>r/>RESULTS: We found STC-1 cells to be reliable secretors of PYY constitutively releasing PYY into cell culture media (but not into non-stimulatory buffer). We demonstrate for the first time that STC-1 cells produce PYY mRNA transcripts; that STC-1 cells produce specific time- and concentration-dependent PYY secretory responses to valeric acid; that linoleic acid and conjugated linoleic acid 9,11 (CLA 9,11) are potent PYY secretagogues; and that chronic exposure of SCFAs and LCFAs can be detrimental to STC-1 cells.r/>r/>CONCLUSIONS: Our studies demonstrate the potential usefulness of STC-1 cells as an in vitro model for investigating nutrient-stimulated PYY secretion in an acute setting. Furthermore, our discovery that CLA directly stimulates L-cells to secrete PYY indicates another possible mechanism contributing to the observed effects of dietary CLA on weight loss.

Stability studies of the metabolites of nitrofuran antibiotics during storage and cooking

Nitrofuran antibiotics cannot be used in food production within the European Union because of their potential health risks to consumers. The recent discovery of their widespread use in global food industries and the finding of semicarbazide in baby food as a result of packaging contamination have focused attention on the toxicity and stability of these drugs and their metabolites. The stability of the nitrofuran marker residues 3-amino-2-oxazolidinone (AOZ), 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ), 1-aminohydantoin (AHD) and semicarbazide (SEM) were tested. Muscle and liver of nitrofuran treated pigs were cooked by frying, grilling, roasting and microwaving. Between 67 and 100% of the residues remained after cooking, demonstrating that these metabolites are largely resistant to conventional cooking techniques and will continue to pose a health risk. The concentration of metabolites in pig muscle and liver did not drop significantly during 8 months of storage at -20 degrees C. Metabolite stock and working standard solutions in methanol were also stable for 10 months at 4 degrees C. Only a 10 ng ml(-1) solution of SEM showed a small drop in concentration over this extended storage period.

Assessing family members' satisfaction with information sharing and communication during Hospital care at the end of life

Context: Despite the fact that most deaths occur in hospital, problems remain with how patients and families experience care at the end of life when a death occurs in a hospital. Objectives: (1) assess family member satisfaction with information sharing and communication, and (2) examine how satisfaction with information sharing and communication is associated with patient factors. Methods: Using a cross-sectional survey, data were collected from family members of adult patients who died in an acute care organization. Correlation and factor analysis were conducted, and internal consistency assessed using Cronbach's alpha. Linear regression was performed to determine the relationship among patient variables and satisfaction on the Information Sharing and Communication (ISC) scale. Results: There were 529 questionnaires available for analysis. Following correlation analysis and the dropping of redundant and conceptually irrelevant items, seven items remained for factor analysis. One factor was identified, described as information sharing and communication, that explained 76.3% of the variance. The questionnaire demonstrated good content and reliability (Cronbach's alpha 0.96). Overall, family members were satisfied with information sharing and communication (mean total satisfaction score 3.9, SD 1.1). The ISC total score was significantly associated with patient gender, the number of days in hospital before death, and the hospital program where the patient died. Conclusions: The ISC scale demonstrated good content validity and reliability. The ISC scale offers acute care organizations a means to assess the quality of information sharing and communication that transpires in care at the end of life. © Copyright 2013, Mary Ann Liebert, Inc.

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 1: Development of a potent and CNS penetrant [3.1.0]-based lead

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach that provided a robust intellectual property position, in lieu of a traditional, expensive HTS campaign. Members within this new [3.1.0]​-​based series displayed excellent GlyT1 potency, selectivity, free fraction, CNS penetration and efficacy in a preclin. model of schizophrenia (prepulse inhibition)​. r/>

The Map of Connections 3.1: Unofficial and previously unmapped Irish border crossings

I charted unofficial border-crossings along Ireland's border, those not found on any other map. r/>r/>During many surveys of Ireland's border I discovered that it is often perforated. Gates are set in hedgerows for the convenience of farmers, stepping stones and community-built bridges span rivers, walkers’ routes and muddy by-ways go wherever they please. These kinds of connections have always been there, although I think it is fair to say that their numbers have increased during the Peace Process. Roads blocked or cratered during the Troubles are being re-connected at a rate too fast for the Ordnance Survey to keep up with. On the local level cross-border movement is quietly happening, unchecked and often unmapped, until now. r/>r/>This map attempts to throw the borderline in perpendicular, showing it as a place of connection rather than division.

A Dual Role for Lecithin:Cholesterol Acyltransferase (EC 2.3.1.43) in Lipoprotein Oxidation

Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme involved in lipoprotein metabolism. It mediates the transesterification of free cholesterol to cholesteryl ester in an apoprotein A-I-dependent process. We have isolated purified LCAT from human plasma using anion-exchange chromatography and characterized the extracted LCAT in terms of its molecular weight, molar absorption coefficient, and enzymatic activity. The participation of LCAT in the oxidation of very low density lipoproteins (VLDL) and low-density lipoproteins (LDL) was examined by supplementing lipoproteins with exogenous LCAT over a range of protein concentrations. LCAT-depleted lipoproteins were also prepared and their oxidation kinetics examined. Our results provide evidence for a dual role for LCAT in lipoprotein oxidation, whereby it acts in a dose-responsive manner as a potent pro-oxidant during VLDL oxidation, but as an antioxidant during LDL oxidation. We believe this novel pro-oxidant effect may be attributable to the LCAT-mediated formation of oxidized cholesteryl ester in VLDL, whereas the antioxidant effect is similar to that of chain-breaking antioxidants. Thus, we have demonstrated that the high-density lipoprotein-associated enzyme LCAT may have a significant role to play in lipoprotein modification and hence atherogenesis. (C) 2007 Elsevier Inc. All rights reserved.

Information sharing and reporting systems in the UK and Ireland: Professional barriers to reporting child maltreatment concerns

Across the UK recent policy developments have focused on improved information sharing and inter-agency cooperation. Professional non-reporting of child maltreatment concerns has been consistently highlighted as a problem in a range of countries and the research literature indicates that this can happen for a variety of reasons. Characteristics such as the type of abuse and the threshold of evidence available are key factors, as are concerns that reporting will damage the professional-client relationship. Professional discipline can also impact on willingness to report, as can personal beliefs about abuse, attitudes towards child protection services and experiences of court processes. Research examining the role of organisational factors in information sharing and reporting emphasises the importance of training and there are some positive indications that training can increase professional awareness of reporting processes and requirements and help to increase knowledge of child abuse and its symptoms. Nonetheless, this is a complex issue and the need for training to go beyond simple awareness raising is recognised. In order to tackle non-reporting in a meaningful way, childcare professionals need access to on-going multidisciplinary training which is specifically tailored to address the range of different factors which impact on reporting attitudes and behaviours.