Descriptors for Pentane-2,4-dione and Its Derivatives

We have used equations for partition coefficients of compounds from water and the gas phase to various solvents to obtain descriptors for pentane-2,4-dione and 21 of its derivatives. These descriptors can then be used to estimate further partition coefficients into a wide variety of solvents. The descriptors also yield information about the properties of pentane-2,4-dione and its derivatives. Pentane-2,4-dione and its alkyl derivatives are quite polar, with substantial hydrogen bond basicity but with no hydrogen bond acidity. In contrast 1,1,1-trifluoropentane-2,4-dione and hexafluoropentan-2,4-dione have significant hydrogen bond acidities

Design of Lipid-Based Nanocarriers via Cation Modulation of Ethanol-Interdigitated Lipid Membranes

Short-chain alcohols (i.e., ethanol) can induce membrane interdigitation in saturated-chain phosphatidylcholines (PCs). In this process, alcohol molecules intercalate between phosphate heads, increasing lateral separation and favoring hydrophobic interactions between opposing acyl chains, which interpenetrate forming an interdigitated phase. Unraveling mechanisms underlying the interactions between ethanol and model lipid membranes has implications for cell biology, biochemistry, and for the formulation of lipid-based nanocarriers. However, investigations of ethanol–lipid membrane systems have been carried out in deionized water, which limits their applicability. Here, using a combination of small- and wide-angle X-ray scattering, small-angle neutron scattering, and all-atom molecular dynamics simulations, we analyzed the effect of varying CaCl2 and NaCl concentrations on ethanol-induced interdigitation. We observed that while ethanol addition leads to the interdigitation of bulk phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers in the presence of CaCl2 and NaCl regardless of the salt concentration, the ethanol-induced interdigitation of vesicular DPPC depends on the choice of cation and its concentration. These findings unravel a key role for cations in the ethanol-induced interdigitation of lipid membranes in either bulk phase or vesicular form

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Fate of liposomes in presence of phospholipase C and D: from atomic to supramolecular lipid arrangement

Understanding the origins of lipid membrane bilayer rearrangement in response to external stimuli is an essential component of cell biology and the bottom-up design of liposomes for biomedical applications. The enzymes phospholipase C and D (PLC and PLD) both cleave the phosphorus–oxygen bonds of phosphate esters in phosphatidylcholine (PC) lipids. The atomic position of this hydrolysis reaction has huge implications for the stability of PC-containing self-assembled structures, such as the cell wall and lipid-based vesicle drug delivery vectors. While PLC converts PC to diacylglycerol (DAG), the interaction of PC with PLD produces phosphatidic acid (PA). Here we present a combination of small-angle scattering data and all-atom molecular dynamics simulations, providing insights into the effects of atomic-scale reorganization on the supramolecular assembly of PC membrane bilayers upon enzyme-mediated incorporation of DAG or PA. We observed that PC liposomes completely disintegrate in the presence of PLC, as conversion of PC to DAG progresses. At lower concentrations, DAG molecules within fluid PC bilayers form hydrogen bonds with backbone carbonyl oxygens in neighboring PC molecules and burrow into the hydrophobic region. This leads initially to membrane thinning followed by a swelling of the lamellar phase with increased DAG. At higher DAG concentrations, localized membrane tension causes a change in lipid phase from lamellar to the hexagonal and micellar cubic phases. Molecular dynamics simulations show that this destabilization is also caused in part by the decreased ability of DAG-containing PC membranes to coordinate sodium ions. Conversely, PLD-treated PC liposomes remain stable up to extremely high conversions to PA. Here, the negatively charged PA headgroup attracts significant amounts of sodium ions from the bulk solution to the membrane surface, leading to a swelling of the coordinated water layer. These findings are a vital step toward a fundamental understanding of the degradation behavior of PC lipid membranes in the presence of these clinically relevant enzymes, and toward the rational design of diagnostic and drug delivery technologies for phospholipase-dysregulation-based diseases

Motion dazzle and camouflage as distinct anti-predator defenses.

BACKGROUND: Camouflage patterns that hinder detection and/or recognition by antagonists are widely studied in both human and animal contexts. Patterns of contrasting stripes that purportedly degrade an observer's ability to judge the speed and direction of moving prey ('motion dazzle') are, however, rarely investigated. This is despite motion dazzle having been fundamental to the appearance of warships in both world wars and often postulated as the selective agent leading to repeated patterns on many animals (such as zebra and many fish, snake, and invertebrate species). Such patterns often appear conspicuous, suggesting that protection while moving by motion dazzle might impair camouflage when stationary. However, the relationship between motion dazzle and camouflage is unclear because disruptive camouflage relies on high-contrast markings. In this study, we used a computer game with human subjects detecting and capturing either moving or stationary targets with different patterns, in order to provide the first empirical exploration of the interaction of these two protective coloration mechanisms. RESULTS: Moving targets with stripes were caught significantly less often and missed more often than targets with camouflage patterns. However, when stationary, targets with camouflage markings were captured less often and caused more false detections than those with striped patterns, which were readily detected. CONCLUSIONS: Our study provides the clearest evidence to date that some patterns inhibit the capture of moving targets, but that camouflage and motion dazzle are not complementary strategies. Therefore, the specific coloration that evolves in animals will depend on how the life history and ontogeny of each species influence the trade-off between the costs and benefits of motion dazzle and camouflage.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Duodenal enteroglucagonoma revealed by differential comparison of serum and tissue glucagon reactivity with Siemens' Double Glucagon Antibody and DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report demonstrates that the differential immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>compared to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>allow for pathologic distinction of enteral versus pancreatic glucagonoma.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian man was diagnosed with a duodenal enteroglucagonoma following presentation with obstructive jaundice. He had a low serum glucagon level using Siemens' <it>Double Antibody Glucagon</it>, a clinical syndrome consistent with glucagon hypersecretion. A periampullary mass biopsy proved to be a neuroendocrine tumor, with positive immunohistochemical reactivity to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon</it>.</p> <p>Conclusions</p> <p>Differential comparison of the immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>and DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>discerns enteroglucagon from pancreatic glucagon.</p

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

A randomised feasibility study to investigate the impact of education and the addition of prompts on the sedentary behaviour of office workers

Abstract Background Office workers have been identified as being at risk of accumulating high amounts of sedentary time in prolonged events during work hours, which has been associated with increased risk of a number of long-term health conditions. There is some evidence that providing advice to stand at regular intervals during the working day, and using computer-based prompts, can reduce sedentary behaviour in office workers. However, evidence of effectiveness, feasibility and acceptability for these types of intervention is currently limited. Methods A 2-arm, parallel group, cluster-randomised feasibility trial to assess the acceptability of prompts to break up sedentary behaviour was conducted with office workers in a commercial bank (n = 21). Participants were assigned to an education only group (EG) or prompt and education group (PG). Both groups received education on reducing and breaking up sitting at work, and the PG also received hourly prompts, delivered by Microsoft Outlook over 10 weeks, reminding them to stand. Objective measurements of sedentary behaviour were made using activPAL monitors worn at three time points: baseline, in the last 2 weeks of the intervention period and 12 weeks after the intervention. Focus groups were conducted to explore the acceptability of the intervention and the motivations and barriers to changing sedentary behaviour. Results Randomly generated, customised prompts, delivered by Microsoft Outlook, with messages about breaking up sitting, proved to be a feasible and acceptable way of delivering prompts to office workers. Participants in both groups reduced their sitting, but changes were not maintained at follow-up. The education session seemed to increase outcome expectations of the benefits of changing sedentary behaviour and promote self-regulation of behaviour in some participants. However, low self-efficacy and a desire to conform to cultural norms were barriers to changing behaviour. Conclusions Prompts delivered by Microsoft Outlook were a feasible, low-cost way of prompting office workers to break up their sedentary behaviour, although further research is needed to determine whether this has an additional impact on sedentary behaviour, to education alone. The role of cultural norms, and promoting self-efficacy, should be considered in the design of future interventions. Trial registration This study was registered retrospectively as a clinical trial on ClinicalTrials.gov (ID no. NCT02609282 ) on 23 March 2015

Structure–activity relationships on the odor detectability of homologous carboxylic acids by humans

We measured concentration detection functions for the odor detectability of the homologs: formic, acetic, butyric, hexanoic, and octanoic acids. Subjects (14 ≤ n ≤ 18) comprised young (19–37 years), healthy, nonsmoker, and normosmic participants from both genders. Vapors were delivered by air dilution olfactometry, using a three-alternative forced-choice procedure against carbon-filtered air, and an ascending concentration approach. Delivered concentrations were established by gas chromatography (flame ionization detector) in parallel with testing. Group and individual olfactory functions were modeled by a sigmoid (logistic) equation from which two parameters are calculated: C, the odor detection threshold (ODT) and D, the steepness of the function. Thresholds declined with carbon chain length along formic, acetic, and butyric acid where they reached a minimum (ODTs = 514, 5.2, and 0.26 ppb by volume, respectively). Then, they increased for hexanoic (1.0 ppb) and octanoic (0.86 ppb) acid. Odor thresholds and interindividual differences in olfactory acuity among these young, normosmic participants were lower than traditionally thought and reported. No significant effects of gender on odor detectability were observed. The finding of an optimum molecular size for odor potency along homologs confirms a prediction made by a model of ODTs based on a solvation equation. We discuss the mechanistic implications of this model for the process of olfactory detection

Further development of the Children’s Mathematics Anxiety Scale UK (CMAS-UK) for ages 4–7 years

There are currently many mathematics anxiety rating scales designed typically for adult and older children populations, yet there remains a lack of assessment tools for younger children ( 0.45) and high internal consistency (α = 0.88). A single factor model of Online Mathematics Anxiety was related to the experience of an entire mathematics lesson, from first entering the classroom to completing a task. A significant negative correlation was observed between the CMAS-UK and mathematics performance scores, suggesting that children who score high for mathematics anxiety tend to score to perform less well on a mathematics task. Subsequent confirmatory factor analysis was conducted to test a range of module structures; the shortened 19-item CMAS-UK was found to have similar model indices as the 26-item model, resulting in the maintenance of the revised scale. To conclude, the 19-item CMAS-UK provides a reliable assessment of children’s mathematics anxiety and has been shown to predict mathematics performance. This research points towards the origins of mathematics anxiety occurring when number is first encountered and supports the utility of the CMAS-UK. Subsequent research in the area should consider and appropriately define an affective component that may underlie mathematics anxiety at older ages. Mathematics anxiety relates to more complex procedures that elude the experiences of younger children and may instead be the result of number-based experiences in the early years of education.N/