bluuebunny/crossref_metadata_2025 huggingface dataset:
Regret and the rationality of choices
Authors: Bourgeois-Gironde Sacha
Published: December 2009

Regret helps to optimize decision behaviour. It can be defined as a rational emotion. Several recent neurobiological studies have confirmed the interface between emotion and cognition at which regret is located and documented its role in decision behaviour. These data give credibility to the incorporation of regret in decision theory that had been proposed by economists in the 1980s. However, finer distinctions are required in order to get a better grasp of how regret and behaviour influence each other. Regret can be defined as a predictive error signal but this signal does not necessarily transpose into a decision-weight influencing behaviour. Clinical studies on several types of patients show that the processing of an error signal and its influence on subsequent behaviour can be dissociated. We propose a general understanding of how regret and decision-making are connected in terms of regret being modulated by rational antecedents of choice. Regret and the modification of behaviour on its basis will depend on the criteria of rationality involved in decision-making. We indicate current and prospective lines of research in order to refine our views on how regret contributes to optimal decision-making.
Molecular replacement withMOLREP
Authors: Vagin Alexei , Teplyakov Alexei
Published: December 2009

MOLREPis an automated program for molecular replacement that utilizes a number of original approaches to rotational and translational search and data preparation. Since the first publication describing the program,MOLREPhas acquired a variety of features that include weighting of the X-ray data and search models, multi-copy search, fitting the model into electron density, structural superposition of two models and rigid-body refinement. The program can run in a fully automatic mode using optimized parameters calculated from the input data.
Overcoming merohedral twinning in crystals of bacteriorhodopsin grown in lipidic mesophase
Authors: Borshchevskiy Valentin , Efremov Rouslan , Moiseeva Ekaterina , Büldt Georg , Gordeliy Valentin
Published: December 2009

Twinning is one of the most common crystal-growth defects in protein crystallography. There are neither efficient rational approaches for the growth of nontwinned protein crystals nor are there examples of systematic studies of the dependence of the twinning-ratio distribution on crystallization conditions. The description of the twinning phenomenon has been covered even less for membrane-protein crystals and is non-existent for crystals grown using lipidic phases (in meso). In the present work, possibilities for overcoming merohedral twinning are investigated for crystals of the membrane protein bacteriorhodopsin (bR) grownin meso. It is shown that traditional crystallization additives are not effective in the case of thein mesocrystallization of bR. The twinning ratio was determined for 310 crystals grown under different crystallization conditions. A correlation of the twinning ratio with the growth rate of the crystals was observed. Slow growth indicated that crystals had a noticeable chance of avoiding twinning. Model calculations were performed in order to rationalize this observation. The calculations confirmed the experimental observation that most crystals consist of two twin domains and showed that under this condition small changes in the probability of twin-domain formation lead to dramatic changes in the number of nontwinned crystals, which explains why slow crystal growth results in a considerable number of nontwinned crystals.
The X-ray structure ofSalmonella typhimuriumuridine nucleoside phosphorylase complexed with 2,2′-anhydrouridine, phosphate and potassium ions at 1.86 Å resolution
Authors: Lashkov Alexander A. , Zhukhlistova Nadezhda E. , Gabdoulkhakov Azat H. , Shtil Alexander A. , Efremov Roman G. , Betzel Christian , Mikhailov Al'bert M.
Published: December 2009

Uridine nucleoside phosphorylase is an important drug target for the development of anti-infective and antitumour agents. The X-ray crystal structure ofSalmonella typhimuriumuridine nucleoside phosphorylase (StUPh) complexed with its inhibitor 2,2′-anhydrouridine, phosphate and potassium ions has been solved and refined at 1.86 Å resolution (Rcryst= 17.6%,Rfree= 20.6%). The complex of human uridine phosphorylase I (HUPhI) with 2,2′-anhydrouridine was modelled using a computational approach. The model allowed the identification of atomic groups in 2,2′-anhydrouridine that might improve the interaction of future inhibitors withStUPh andHUPhI.
Pim‐3 protects against hepatic failure in D‐galactosamine (D‐GalN)‐sensitized rats
Authors: Liu L.‐M. , Zhang J.‐X. , Wang X.‐P. , Guo H.‐X. , Deng H. , Luo J.
Published: December 2009

Eur J Clin Invest 2010; 40 (2): 127–138

Background  Fulminant hepatic failure (FHF) has a high mortality resulted from massive hepatic apoptosis and haemorrhage necrosis; it is required to develop a valid therapy directed towards hepatocyte protection and regeneration. Pim‐3, a hepatic growth stimulator, belongs to the serine/threonine kinase Pim‐family that has been implicated in gp130‐mediated induction of cell proliferation, protection from apoptosis downstream of Signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor‐A‐dependent vasculogenesis and angiogenesis, thus is suggested to possibly play a role in the tissue repair of FHF.

Materials and methods  Male Wistar rats received simultaneous intraperitoneal injections of lipopolysaccharide (LPS) (100 μg kg−1) and D‐galactosamine (D‐GalN) (600 mg kg−1). One day prior to LPS/D‐GalN administration, naked plasmid or Ringer’s solution was injected via tail vein by hydrodynamics‐based procedure.

Results  Exogenous Pim‐3 gene protected against LPS/D‐GalN‐induced lethality with survival rate of more than 80% and improved the hepatic pathomorphism. The fractions of hepatic apoptotic‐positive cells and the levels of caspase‐3 activity were markedly lower in Pim‐3‐pretreated rats. Furthermore, exogenous Pim‐3 significantly inhibited expression of tumour necrosis factor‐α and interleukin‐1β in the liver, declined p53 and inducible nitric oxide synthase mRNAs levels, but elevated levels of Bcl‐2 protein, an anti‐apoptosis member of Bcl‐2 family, in the liver. Exogenous Pim‐3, however, showed little effect on expression of Bax, a pro‐apoptosis member of Bcl‐2 family.

Conclusions  Pim‐3 gene could protect rats from FHF by inhibiting liver apoptosis and improving inflammatory response of liver tissues, which could be associated with inhibiting expression of inflammatory mediators and promoting expression of anti‐apoptosis protein Bcl‐2.
Efficacy and safety of pegylated interferon alpha‐2a therapy for chronic hepatitis C in HIV‐infected patients with haemophilia
Authors: ZHANG R.‐F. , SUN H.‐Q. , HUANG Q. , WANG J.‐R. , ZHANG X.‐X. , LIU X.‐N. , MA Q. , LU H.‐Z.
Published: December 2009

Summary.  The objective of this study was to evaluate the efficacy and safety of pegylated interferon (PEG‐IFN) alpha‐2a monotherapy in a cohort of Chinese haemophilic patients co‐infected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and undergoing highly active antiretroviral drugs therapy. Twenty‐two (n = 22) patients with CD4 lymphocyte counts over 200 cells μL−1 were treated with 180 μg of PEG‐IFN alpha‐2a subcutaneously once in a week for 48 weeks. HCV load (HCV RNA), HIV load (HIV RNA) and CD4 lymphocyte counts were measured at baseline and 4, 12, 24, 48 and 72 weeks after initiation of anti‐HCV therapy. Efficacy and safety were analysed according to baseline CD4 status (≥350 cells μL−1). Significant HCV‐RNA decreases (>1 log10 copies mL−1) were observed through week 72 after PEG‐INF alpha‐2a monotherapy across both CD4 strata. CD4 status was not associated with treatment outcomes as evaluated using rapid viral response rate (P = 0.655), early viral response rate (P = 0.387), end‐of‐treatment viral response rate (P = 1.000) or sustained viral response rate (SVR, P = 0.674). A sustained virological response was achieved in nine patients (41%), five with genotype 2a (83%) and four with genotype 1b (25%, P = 0.023). SVR was HCV genotype dependent. Eleven patients required a dose reduction in PEG‐IFN alpha‐2a. PEG‐IFN alpha‐2a monotherapy could be considered as a safe and effective option for the treatment of HCV infection in HIV patients with haemophilia, particularly in resource‐limited settings. While higher CD4 lymphocyte counts resulted in greater HCV‐RNA reduction, HCV genotype was a predictor for sustained virological response.
Defining and measuring ecological specialization
Authors: Devictor Vincent , Clavel Joanne , Julliard Romain , Lavergne Sébastien , Mouillot David , Thuiller Wilfried , Venail Patrick , Villéger Sébastien , Mouquet Nicolas
Published: December 2009

1.  Ecological specialization is one of the main concepts in ecology and conservation. However, this concept has become highly context‐dependent and is now obscured by the great variability of existing definitions and methods used to characterize ecological specialization.

2.  In this study, we clarify this concept by reviewing the strengths and limitations of different approaches commonly used to define and measure ecological specialization. We first show that ecological specialization can either be considered as reflecting species’ requirements or species’ impacts. We then explain how specialization depends on species‐specific characteristics and on local and contingent environmental constraints. We further show why and how ecological specialization should be scaled across spatial and temporal scales, and from individuals to communities.

3.  We then illustrate how this review can be used as a practical toolbox to classify widely used metrics of ecological specialization in applied ecology, depending on the question being addressed, the method used, and the data available.

4.
 Synthesis and applications. Clarifying ecological specialization is useful to make explicit connections between several fields of ecology using the niche concept. Defining this concept and its practical metrics is also a crucial step to better formulate predictions of scientific interest in ecology and conservation. Finally, understanding the different facets of ecological specialization should facilitate to investigate the causes and consequences of biotic homogenization and to derive relevant indicators of biodiversity responses to land‐use changes.
Quantifying aphid predation: the mealy plum aphid Hyalopterus pruni in California as a case study
Authors: Latham Daniel R. , Mills Nicholas J.
Published: December 2009

1. Generalist insect predators provide an important ecosystem service in the regulation of agricultural pests. However, the role of predation in the dynamics of aphid populations has been difficult to quantify as any change in aphid density results from a balance between two opposing processes, aphid recruitment through reproduction and aphid mortality through predation.

2. Our goal in this study was to determine the degree to which aphid consumption by naturally occurring densities of aphidophagous predators is responsible for observed seasonal changes in aphid densities. We quantified consumptive predation using a mechanistic approach that incorporates the balance between aphid recruitment and mortality. We used the mealy plum aphid Hyalopterus pruni in Prunus domestica plum orchards as a model system.

3. Our approach was to compare two quantities: a demographic‐based estimate of predation and an observation‐based estimate of predation. The demographic‐based estimate used a simple model of aphid population growth and predation. It estimates the mortality that must have occurred to give rise to observed changes in aphid densities between sample dates. The model uses independent estimates of aphid population growth rate in the absence of predation. The observation‐based estimate combined field data on predator densities in plum orchards with stage‐ and species‐specific per capita predation rates estimated from field observation.

4. Predation may have reduced the rate at which mealy plum aphid populations increased early in the season and rebounded from mid‐season declines, but was not sufficient to prevent high aphid densities or to accelerate rates of decline later in the season. Moreover, predation at naturally occurring densities did not appear sufficient to drive the directional changes in mealy plum aphid densities at any point through the season.

5.
Synthesis and applications. Our study shows that natural densities of generalist predators can be too low to provide effective biological control services for an aphid pest. Generalist aphid predators could provide more effective control if early‐season densities were increased through augmentative releases or encouragement of crop colonization, but the commercial viability of these options remains to be tested.
Tropical dry forest trees and the relationship between local abundance and geographic range
Authors: Williams John N. , Viers Joshua H. , Schwartz Mark W.
Published: December 2009

Aim  To test the macroecological principle that a positive relationship exists between local abundance and geographic range size for tree communities in the tropical dry forest.

Location  Two tropical dry forest (TDF) regions on the Pacific coast of Mexico: one near Chamela, Jalisco; the other near Huatulco, Oaxaca.

Methods  We recorded species presence and relative abundance of trees and lianas from over 40 locales in each of the study regions using transects across an elevational gradient. We then compared the field data with occurrence data from national and online databases to examine how local patterns of abundance relate to putative geographic range areas and latitudinal breadth.

Results  We found no significant correlation between abundance and range size. Overall, many more locally abundant species had small ranges than large ones. We found that most species occupy the majority of the TDF range north of Colombia, and those species present in South America occupy the majority of that continent’s TDF range as well. This pattern was independent of local abundance. We also found no relationship between range size and local niche breadth as measured by elevation, or between local abundance and distance to the range centre.

Main conclusions  The macroecological tenet that posits a positive correlation between local abundance and geographic range size does not appear to hold for TDF trees. The finding that many locally abundant species had narrow ranges also suggests that dry forest endemics may be particularly well adapted to local conditions and make important contributions to community structure. We hypothesize that the absence of abundant species with large ranges is due to opposing environmental constraints that prevent a species from thriving everywhere.
The discomfort of an evidence‐based prescribing decision
Authors: Lewis Penny J. , Tully Mary P.
Published: December 2009

Rationale, aims and objectives  Prescribing decisions are not always based on published clinical research; social and environmental influences can sometimes drive such decisions. However, little is known about this topic in prescribing in secondary care. The aim of this study was to explore such influences by asking doctors to discuss their uncomfortable prescribing decisions in secondary care.

Methods  Forty‐eight doctors, of varying grades from four hospitals, were selected for in‐depth qualitative interviews, which included the critical incident technique. Doctors were asked to remember any uncomfortable prescribing decisions and these ‘incidents’ were discussed, enabling the researcher to unpack the more subconscious influences on the decision to prescribe. Interviews were tape‐recorded and transcribed verbatim. A grounded theory approach to data analysis was taken.

Results  All doctors had previously been uncomfortable when attempting to practise in accordance with evidence‐based medicine. Locating, critically appraising and applying the evidence to individual patients were frequent causes of discomfort. Many doctors struggled with uncomfortable decisions that were influenced by non‐research evidence, such as prior experience or expert opinion. This appeared, in part, because of these doctors' skewed notions that EBM condemns clinical experience as illegitimate evidence.

Conclusions  Incorporating the research evidence into prescribing decisions was associated with much discomfort by secondary care doctors. Greater efforts should also be placed towards developing the model of EBM, so that it fits more explicitly with how medicine is currently practised. Perhaps more importantly, educators need to reinforce what EBM is and what it is not to all concerned in the delivery of health care.
Gonadotrophin‐Releasing Hormone (GnRH) Exerts Stimulatory Effects on GnRH Neurones in Intact Adult Male and Female Mice
Authors: Han S.‐K. , Lee K. , Bhattarai J. P. , Herbison A. E.
Published: December 2009

There is substantial evidence for a role of the neuropeptide gonadotrophin‐releasing hormone (GnRH) in the regulation of GnRH neurone secretion but how this is achieved is not understood. We examined here the effects of GnRH on the electrical excitability and intracellular calcium concentration ([Ca2+]i) of GnRH neurones in intact adult male and female mice. Perforated‐patch electrophysiological recordings from GnRH‐green fluorescent protein‐tagged GnRH neurones revealed that 3 nm–3 μm GnRH evoked gradual approximately 3 mV depolarisations in membrane potential from up to 50% of GnRH neurones in male and female mice. The depolarising effect of GnRH was observed on approximately 50% of GnRH neurones throughout the oestrous cycle. However, at pro‐oestrus alone, GnRH was also found to transiently hyperpolarise approximately 30% of GnRH neurones. Both hyperpolarising and depolarising responses were maintained in the presence of tetrodotoxin. Calcium imaging studies undertaken in transgenic GnRH‐pericam mice showed that GnRH suppressed [Ca2+]i in approximately 50% of GnRH neurones in dioestrous and oestrous mice. At pro‐oestrus, 25% of GnRH neurones exhibited a suppressive [Ca2+]i response to GnRH, whereas 17% were stimulated. These results demonstrate that nm to μm concentrations of GnRH exert depolarising actions on approximately 50% of GnRH neurones in males and females throughout the oestrous cycle. This is associated with a reduction in [Ca2+]i. At pro‐oestrus, however, a further population of GnRH neurones exhibit a hyperpolarising response to GnRH. Taken together, these studies indicate that GnRH acts predominantly as a neuromodulator at the level of the GnRH cell bodies to exert a predominant excitatory influence upon GnRH neurones in intact adult male and female mice.
Root cortical aerenchyma improves the drought tolerance of maize (Zea mays L.)
Authors: ZHU JINMING , BROWN KATHLEEN M. , LYNCH JONATHAN P.
Published: December 2009

Root cortical aerenchyma (RCA) reduces root respiration in maize by converting living cortical tissue to air volume. We hypothesized that RCA increases drought tolerance by reducing root metabolic costs, permitting greater root growth and water acquisition from drying soil. To test this hypothesis, recombinant inbred lines with high and low RCA were observed under water stress in the field and in soil mesocosms in a greenhouse. In the field, lines with high RCA had 30% more shoot biomass at flowering compared with lines with low RCA under water stress. Root length density in deep soil was significantly greater in the high RCA lines compared with the low RCA lines. Mid‐day leaf relative water content in the high RCA lines was 10% greater than in the low RCA lines under water stress. The high RCA lines averaged eight times the yield of the low RCA lines under water stress. In mesocosms, high RCA lines had less seminal root respiration, deeper rooting, and greater shoot biomass compared with low RCA lines under water stress. These results support the hypothesis that RCA is beneficial for drought tolerance in maize by reducing the metabolic cost of soil exploration.
Signal transduction in Mimosa pudica: biologically closed electrical circuits
Authors: VOLKOV ALEXANDER G. , FOSTER JUSTIN C. , MARKIN VLADISLAV S.
Published: December 2009

Biologically closed electrical circuits operate over large distances in biological tissues. The activation of such circuits can lead to various physiological and biophysical responses. Here, we analyse the biologically closed electrical circuits of the sensitive plant Mimosa pudica Linn. using electrostimulation of a petiole or pulvinus by the charged capacitor method, and evaluate the equivalent electrical scheme of electrical signal transduction inside the plant. The discharge of a 100 µF capacitor in the pulvinus resulted in the downward fall of the petiole in a few seconds, if the capacitor was charged beforehand by a 1.5 V power supply. Upon disconnection of the capacitor from Ag/AgCl electrodes, the petiole slowly relaxed to the initial position. The electrical properties of the M. pudica were investigated, and an equivalent electrical circuit was proposed that explains the experimental data.
X‐chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts
Authors: Bottema R. W. B. , Kerkhof M. , Reijmerink N. E. , Koppelman G. H. , Thijs C. , Stelma F. F. , Smit H. A. , Brunekreef B. , Van Schayck C. P. , Postma D. S.
Published: December 2009

To cite this article: Bottema RWB, Kerkhof M, Reijmerink NE, Koppelman GH, Thijs C, Stelma FF, Smit HA, Brunekreef B, van Schayck CP, Postma DS. X‐chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts. Allergy 2010; 65: 865–874.

Background:  The Forkhead Box P3 (FOXP3) gene, located on the X‐chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single‐nucleotide polymorphisms (SNPs) of FOXP3 are associated with atopy development in childhood.

Methods:  Seven SNPs in FOXP3 were genotyped in 3062 children (51% boys) participating in the Allergenic study, which consists of three Dutch birth cohorts (PIAMA, PREVASC and KOALA). Association of FOXP3 SNPs with total serum IgE and sensitisation (presence of specific serum IgE to egg, milk, and indoor, i.e. house‐dust mite, cat, and/or dog allergens) was investigated at ages 1, 2, 4, and 8. Analysis of variance and logistic regression were performed, stratified for gender.

Results:  Our most consistent finding was observed for sensitisation to egg and indoor allergens. In girls, five FOXP3 SNPs (rs5906761, rs2294021, rs2294019, rs6609857 and rs3761548) were significantly associated with sensitisation to egg at ages 1 and 2 and with sensitisation to indoor allergens at age 2 (P < 0.05), but not at 4 and 8, a finding that was observed across the three cohorts. Rs5906761 and rs2294021 were associated with remission of sensitisation to food allergens in boys, as tested in the PIAMA cohort.

Conclusion:  This is the first study showing across three cohorts that X‐chromosomal FOXP3 genotypes may contribute to development of sensitisation against egg and indoor allergens in girls in early childhood. In addition, an association with remission of sensitisation to food allergens existed in boys only.
Towards evidence‐based medicine in specific grass pollen immunotherapy
Authors: Calderon M. , Mösges R. , Hellmich M. , Demoly P.
Published: December 2009

To cite this article: Calderon M, Mösges R, Hellmich M, Demoly P. Towards evidence‐based medicine in specific grass pollen immunotherapy. Allergy 2010; 65: 420–434.

When initiating grass pollen immunotherapy for seasonal allergic rhinoconjunctivitis, specialist physicians in many European countries must choose between modalities of differing pharmaceutical and regulatory status. We applied an evidence‐based medicine (EBM) approach to commercially available subcutaneous and sublingual Gramineae grass pollen immunotherapies (SCIT and SLIT) by evaluating study design, populations, pollen seasons, treatment doses and durations, efficacy, quality of life, safety and compliance. After searching MEDLINE, Embase and the Cochrane Library up until January 2009, we identified 33 randomized, double‐blind, placebo‐controlled trials (including seven paediatric trials) with a total of 440 specific immunotherapy (SIT)‐treated subjects in seven trials (0 paediatric) for SCIT with natural pollen extracts, 168 in three trials (0 paediatric) for SCIT with allergoids, 906 in 16 trials (five paediatric) for natural extract SLIT drops, 41 in two trials (one paediatric) for allergoid SLIT tablets and 1605 in five trials (two paediatric) for natural extract SLIT tablets. Trial design and quality varied significantly within and between SIT modalities. The multinational, rigorous trials of natural extract SLIT tablets correspond to a high level of evidence in adult and paediatric populations. The limited amount of published data on allergoids prevented us from judging the level of evidence for this modality.
Specific immunotherapy suppresses Th2 responses via modulating TIM1/TIM4 interaction on dendritic cells
Authors: Zhao C.‐Q. , Li T.‐L. , He S.‐H. , Chen X. , An Y.‐F. , Wu W.‐K. , Zhou X.‐H. , Li P. , Yang P.‐C.
Published: December 2009

To cite this article: Zhao C‐Q, Li T‐L, He S‐H, Chen X, An Y‐F, Wu W‐K, Zhou X‐H, Li P, Yang P‐C. Specific immunotherapy suppresses Th2 responses via modulating TIM1/TIM4 interaction on dendritic cells. Allergy 2010; 65: 986–995

Background:  Specific immunotherapy (SIT) is the only curable remedy for allergic disorders currently; however, the underlying mechanism is not fully understood yet. This study aimed to elucidate the mechanism of SIT on suppressing TIM4 (T cell immunoglobulin mucin domain molecule 4) expression in dendritic cells (DCs) and modulating the skewed T helper 2 (Th2) responses in patients with airway allergy.

Methods:  Twenty patients with allergic rhinitis (AR) were treated with SIT for 3 months. Before and after SIT, the expression of TIM4 in peripheral DC and TIM1 in Th2 cells was examined. The role of Fc gamma receptor (FcγR) I and II in modulating the expression of TIM4 in DCs was investigated.

Results:  The interaction of TIM1/TIM4 played a critical role in sustaining the polarization status of Th2 cells in AR patients. Cross‐linking FcγRI by antigen/IgG complexes increased the production of TIM4 by dendritic cells via upregulating tumor necrosis factor‐alpha in DCs. Exposure to microbial products promoted the expression of FcγRI in DCs that further increased the expression of TIM4. Exposure to specific antigens alone upregulated the expression of FcγRII in DCs, that suppressed the expression of TIM4.

Conclusions:  We conclude that SIT suppresses the skewed Th2 responses via disrupting the interaction of TIM1/TIM4 in antigen‐specific Th2 cells.
Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor‐related neurotoxicity after hematopoietic stem cell transplantation
Authors: Yanagimachi Masakatsu , Naruto Takuya , Tanoshima Reo , Kato Hiromi , Yokosuka Tomoko , Kajiwara Ryosuke , Fujii Hisaki , Tanaka Fumiko , Goto Hiroaki , Yagihashi Tatsuhiko , Kosaki Kenjiro , Yokota Shumpei
Published: December 2009

Yanagimachi M, Naruto T, Tanoshima R, Kato H, Yokosuka T, Kajiwara R, Fujii H, Tanaka F, Goto H, Yagihashi T, Kosaki K, Yokota S. Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor‐related neurotoxicity after hematopoietic stem cell transplantation.  Clin Transplant 2010: 24: 855–861. © 2009 John Wiley & Sons A/S.

Abstract:  Background:  One severe side effect of calcineurin inhibitors (CNIs: such as cyclosporine [CsA] and tacrolimus [FK506]) is neurotoxicity. CNIs are substrates for CYP3A5 and P‐glycoprotein (P‐gp), encoded by ABCB1 gene. In the present study, we hypothesized that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI‐related neurotoxicity.

Methods:  The effects of the polymorphisms, such as CYP3A5 A6986G, ABCB1 C1236T, G2677T/A, and C3435T, associated with CNI‐related neurotoxicity were evaluated in 63 patients with hematopoietic stem cell transplantation.

Results:  Of the 63 cases, 15 cases developed CNI‐related neurotoxicity. In the CsA patient group (n = 30), age (p = 0.008), hypertension (p = 0.017), renal dysfunction (p < 0.001), ABCB1 C1236T (p < 0.001), and G2677T/A (p = 0.014) were associated with neurotoxicities. The CC genotype at ABCB1 C1236T was associated with it, but not significantly so (p = 0.07), adjusted for age, hypertension, and renal dysfunction. In the FK506 patient group (n = 33), CYP3A5 A6986G (p < 0.001), and ABCB1 C1236T (p = 0.002) were associated with neurotoxicity. At least one A allele at CYP3A5 A6986G (expressor genotype) was strongly associated with it according to logistic regression analysis (p = 0.01; OR, 8.5; 95% CI, 1.4–51.4).

Conclusion:  The polymorphisms in CYP3A5 and ABCB1 genes were associated with CNI‐related neurotoxicity. This outcome is probably because of CYP3A5 or P‐gp functions or metabolites of CNIs.
Psychosocial evaluation of Chinese living related kidney donors
Authors: Zhao Wen‐Yu , Zeng Li , Zhu You‐Hua , Wang Li‐Ming , Zhou Mei‐Sheng , Han Shu , Zhang Lei
Published: December 2009

Zhao W‐Y, Zeng L, Zhu Y‐H, Wang L‐M, Zhou M‐S, Han S, Zhang L. Psychosocial evaluation of Chinese living related kidney donors.  Clin Transplant 2010: 24: 766–771. © 2009 John Wiley & Sons A/S.

Abstract:  Background:  Although living kidney transplantation has numerous advantages over cadaveric transplantation, donor apprehension remains a problem. This study investigated psychosocial features and quality of life in Chinese living kidney donors after transplantation procedures.

Methods:  Participants were 84 donors interviewed during follow‐up after donation. Sociodemographic characteristics were evaluated by a 22‐item questionnaire. Social support, quality of life, depression, and anxiety were objectively measured with the Social Support Rating Scale for Chinese, the Short‐Form 36 Health Survey, the modified Beck Depression Inventory, and the Self‐Rating Anxiety Scale questionnaire, respectively.

Results:  All donors volunteered without pressure from families or recipients. Altruistic motives were the main impetus for donation, and donors had good social support. Living transplantation affected donors’ quality of life, with a slight negative effect on some physical aspects. There were no major depressive or anxiety disorders following donation.

Conclusions:  Living kidney donation was a generally positive experience without evidence of major psychological disturbance. However, considering the limited size and duration of our study, we recommend careful follow‐up of all donors. We also recommend provision of social support services and removal of financial disincentives for donors.
Testing whether the epidural works: too time consuming?
Authors: LARSSON J. , GORDH T. E.
Published: December 2009

Background: When using epidural anaesthesia (EDA) for pain relief after major surgery, a failure rate of 10% is common. A crucial step in improving the care of patients with EDA is to define the position of the epidural catheter. The aim of this study was to investigate how much time it takes to determine whether the block is sufficient by assessing the extent of loss of cold sensation before induction of anaesthesia.

Methods: One hundred patients listed for abdominal surgery were included in the study. After an epidural catheter had been inserted and an intrathecal or an intravenous position had been made unlikely by the use of a test dose, the patient was given a bolus dose of local anaesthetic plus an opioid in the epidural catheter. The epidural block was tested every 2 min, starting at 5 min and ending at 15 min. When at least four segments were blocked bilaterally, the testing was stopped, the time was noted and the patient was anaesthetised.

Results: An epidural block was demonstrated after 5–6 min in 37 patients, after 7–8 min in 43 additional patients and after 9–10 min in 15 patients. In one patient, it took 12 min and in three patients, it took 15 min. In two patients, no epidural block could be demonstrated.

Conclusion: Testing an epidural anaesthetic before the induction of anaesthesia takes only 5–10 extra minutes. Knowing whether the catheter is correctly placed means better quality of care, giving the anaesthetist better prerequisites for taking care of the patient post‐operatively.
Increased opportunity for sexual conflict promotes harmful males with elevated courtship frequencies
Authors: CRUDGINGTON H. S. , FELLOWS S. , SNOOK R. R.
Published: December 2009

Mating systems have a profound influence on the probability of conflict occurring between the sexes. Promiscuity is predicted to generate sexual conflict, thereby driving the evolution of male traits that harm females, whereas monogamy is expected to foster reproductive cooperation, thus rendering such traits redundant. We tested these predictions using experimentally evolved Drosophila pseudoobscura subject to different mating systems. Female survival was not influenced by the mating system treatment of her partner. However, females continuously housed with males evolving under elevated opportunities for female promiscuity produced fewer total progeny, but a relatively greater number of progeny early in their lives, than females housed with males evolving under obligate monogamy. We also found that promiscuous males courted females more frequently than monogamous males. Variation in male courtship frequency and progeny production patterns among treatments reinforces the critical importance of mating system variation for sexual conflict, during both pre‐ and post‐copulatory interactions.
Impact of cocaine on adult hippocampal neurogenesis in an animal model of differential propensity to drug abuse
Authors: García‐Fuster M. J. , Perez J. A. , Clinton S. M. , Watson S. J. , Akil H.
Published: December 2009

Hippocampal plasticity (e.g. neurogenesis) likely plays an important role in maintaining addictive behavior and/or relapse. This study assessed whether rats with differential propensity to drug‐seeking behavior, bred Low‐Responders (bLR) and bred High‐Responders (bHR) to novelty, show differential neurogenesis regulation after cocaine exposure. Using specific immunological markers, we labeled distinct populations of adult stem cells in the dentate gyrus at different time‐points of the cocaine sensitization process; Ki‐67 for newly born cells, NeuroD for cells born partway, and 5‐bromo‐2′‐deoxyuridine for older cells born prior to sensitization. Results show that: (i) bHRs exhibited greater psychomotor response to cocaine than bLRs; (ii) acute cocaine did not alter cell proliferation in bLR/bHR rats; (iii) chronic cocaine decreased cell proliferation in bLRs only, which became amplified through the course of abstinence; (iv) neither chronic cocaine nor cocaine abstinence affected the survival of immature neurons in either phenotype; (v) cocaine abstinence decreased survival of mature neurons in bHRs only, an effect that paralleled the greater psychomotor response to cocaine; and (vi) cocaine treatment did not affect the ratio of neurons to glia in bLR/bHR rats as most cells differentiated into neurons in both lines. Thus, cocaine exerts distinct effects on neurogenesis in bLR vs. bHR rats, with a decrease in the birth of new progenitor cells in bLRs and a suppression of the survival of new neurons in bHRs, which likely leads to an earlier decrease in formation of new connections. This latter effect in bHRs could contribute to their enhanced degree of cocaine‐induced psychomotor behavioral sensitization.
Dopamine modulation of excitatory currents in the striatum is dictated by the expression of D1 or D2 receptors and modified by endocannabinoids
Authors: André Véronique M. , Cepeda Carlos , Cummings Damian M. , Jocoy Emily L. , Fisher Yvette E. , William Yang X. , Levine Michael S.
Published: December 2009

Striatal medium‐sized spiny neurons (MSSNs) receive glutamatergic inputs modulated presynaptically and postsynaptically by dopamine. Mice expressing the gene for enhanced green fluorescent protein as a reporter gene to identify MSSNs containing D1 or D2 receptor subtypes were used to examine dopamine modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in slices and postsynaptic N‐methyl‐d‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) currents in acutely isolated cells. The results demonstrated dopamine receptor‐specific modulation of sEPSCs. Dopamine and D1 agonists increased sEPSC frequency in D1 receptor‐expressing MSSNs (D1 cells), whereas dopamine and D2 agonists decreased sEPSC frequency in D2 receptor‐expressing MSSNs (D2 cells). These effects were fully (D1 cells) or partially (D2 cells) mediated through retrograde signaling via endocannabinoids. A cannabinoid 1 receptor (CB1R) agonist and a blocker of anandamide transporter prevented the D1 receptor‐mediated increase in sEPSC frequency in D1 cells, whereas a CB1R antagonist partially blocked the decrease in sEPSC frequency in D2 cells. At the postsynaptic level, low concentrations of a D1 receptor agonist consistently increased NMDA and AMPA currents in acutely isolated D1 cells, whereas a D2 receptor agonist decreased these currents in acutely isolated D2 cells. These results show that both glutamate release and postsynaptic excitatory currents are regulated in opposite directions by activation of D1 or D2 receptors. The direction of this regulation is also specific to D1 and D2 cells. We suggest that activation of postsynaptic dopamine receptors controls endocannabinoid mobilization, acting on presynaptic CB1Rs, thus modulating glutamate release differently in glutamate terminals projecting to D1 and D2 cells.
Additive actions of the cannabinoid and neuropeptide Y systems on adiposity and lipid oxidation
Authors: Zhang L. , Lee N. J. , Nguyen A. D. , Enriquez R. F. , Riepler S. J. , Stehrer B. , Yulyaningsih E. , Lin S. , Shi Y. C. , Baldock P. A. , Herzog H. , Sainsbury A.
Published: December 2009

Aims: Energy homeostasis is regulated by a complex interaction of molecules and pathways, and new antiobesity treatments are likely to require multiple pharmacological targeting of anorexigenic or orexigenic pathways to achieve effective loss of excess body weight and adiposity. Cannabinoids, acting via the cannabinoid‐1 (CB1) receptor, and neuropeptide Y (NPY) are important modulators of feeding behaviour, energy metabolism and body composition. We investigated the interaction of CB1 and NPY in the regulation of energy homeostasis, hypothesizing that dual blockade of CB1 and NPY signalling will induce greater weight and/or fat loss than that induced by single blockade of either system alone.

Methods: We studied the effects of the CB1 antagonist Rimonabant on food intake, body weight, body composition, energy metabolism and bone physiology in wild‐type (WT) and NPY knockout (NPY−/−) mice. Rimonabant was administered orally at 10 mg/kg body weight twice per day for 3 weeks. Oral Rimonabant was delivered voluntarily to mice via a novel method enabling studies to be carried out in the absence of gavage‐induced stress.

Results: Mice with dual blockade of CB1 and NPY signalling (Rimonabant‐treated NPY−/− mice) exhibited greater reductions in body weight and adiposity than mice with single blockade of either system alone (Rimonabant‐treated WT or vehicle‐treated NPY−/− mice). These changes occurred without loss of lean tissue mass or bone mass. Furthermore, Rimonabant‐treated NPY−/− mice showed a lower respiratory exchange ratio than that seen in Rimonabant‐treated WT or vehicle‐treated NPY−/− mice, suggesting that this additive effect of dual blockade of CB1 and NPY involves promotion of lipid oxidation. On the other hand, energy expenditure and physical activity were comparable amongst all treatment groups. Interestingly, Rimonabant similarly and transiently reduced spontaneous and fasting‐induced food intake in WT and NPY−/− mice in the first hour after administration only, suggesting independent regulation of feeding by CB1 and NPY signalling. In contrast, Rimonabant increased serum corticosterone levels in WT mice, but this effect was not seen in NPY−/− mice, indicating that NPY signalling may be required for effects of CB1 on the hypothalamo‐pituitary‐adrenal axis.

Conclusions: Dual blockade of CB1 and NPY signalling leads to additive reductions in body weight and adiposity without concomitant loss of lean body mass or bone mass. An additive increase in lipid oxidation in dual CB1 and NPY blockade may contribute to the effect on adiposity. These findings open new avenues for more effective treatment of obesity via dual pharmacological manipulations of the CB1 and NPY systems.
Deconstructing morphology
Authors: Scholtz Gerhard
Published: December 2009

Scholtz, G. 2010. Deconstructing morphology. —Acta Zoologica (Stockholm) 91: 44–63

Morphology as the science of form is, in particular, related to the overwhelming diversity of animal forms. Due to its long pre‐Darwinian tradition, organismic morphology is partly burdened by ahistorical typological views. On the other hand, the study of organismic form has always implied concepts of transformation, which helped to pave the way for evolutionary theories. This contradictory history and the fact that we need words to describe organismic form lead in many cases to morphological concepts implying a mixture of structural, functional, developmental, ecological, typological, and evolutionary aspects in current morphological approaches. Because these mixed views lead to contradictory and misleading interpretations of animal form, I stress the need to deconstruct morphological concepts at all levels. I propose a morphology that analyses transformation of animal forms strictly at the structural level in combination with genealogical thinking. Function and other biological aspects of form should be considered in an independent second analytical step. A comparative pattern approach, including developmental patterns, of animal structure in an evolutionary framework allows for the analysis of morphological change, in particular, phylogenetic reconstructions, homology assessment, and the recognition of evolutionary independent morphological units.
What are the learning affordances of 3‐D virtual environments?
Authors: Dalgarno Barney , Lee Mark J. W.
Published: December 2009

This article explores the potential learning benefits of three‐dimensional (3‐D) virtual learning environments (VLEs). Drawing on published research spanning two decades, it identifies a set of unique characteristics of 3‐D VLEs, which includes aspects of their representational fidelity and aspects of the learner–computer interactivity they facilitate. A review of applications of 3‐D VLEs is presented, leading to the identification of a series of learning affordances of such environments. These affordances include the facilitation of tasks that lead to enhanced spatial knowledge representation, greater opportunities for experiential learning, increased motivation/engagement, improved contextualisation of learning and richer/more effective collaborative learning as compared to tasks made possible by 2‐D alternatives. The authors contend that the continued development of and investment in 3‐D games, simulations and virtual worlds for educational purposes should be considered contingent on further investigation into the precise relationships between the unique characteristics of 3‐D VLEs and their potential learning benefits. To this end, they conclude by proposing an agenda or ‘roadmap’ for future research that encompasses empirical studies aimed at exploring these relationships, as well as those aimed at deriving principles and guidelines to inform the design, development and use of 3‐D virtual environments for learning.
Supporting authors in the development of task‐based learning in serious virtual worlds
Authors: Bellotti Francesco , Berta Riccardo , De Gloria Alessandro , Primavera Ludovica
Published: December 2009

Serious virtual worlds (SVWs) represent a great opportunity for learning and should embed a lot of high‐quality contextualised information so that the player can take the most from his or her exploration of the environment. This requires defining new methodologies and tools for effective production. We have investigated this issue in implementing a couple of SVWs and abstracted a conceptual framework relying on the task‐based learning pedagogical theory. The model defines games set in realistic SVWs enriched with embedded educational tasks. Tasks are simple trial activities that embody units of knowledge. The player can discover them in his or her SVW exploration and interact with them in order to construct meaning, build lasting memories and deepen understanding of the featured item(s). The model involves pedagogical task annotation—which allows decoupling the tasks, which can be reused in different VWs from the definition of their delivery strategy in the context of a specific VW, which is specified by the VW designer and automatically managed by the run‐time engine. This approach simplifies the authoring work. The visual Creative Toolkit (CT) we have developed is being used for producing contents for the 15 reconstructed cultural cities that will be featured in the first version of the Travel in Europe VW. The paper described the overall framework and the details of the CT. It also presented an implemented example, briefly discussing the methodology we have followed for developing cultural heritage content.
Deception and defection from ethical norms in market relationships: a general analytic framework
Authors: Keep William W. , Schneider Gary P.
Published: December 2009

Market relationships built on trust and governed by commonly accepted ethical norms are generally viewed as economically positive and beneficial to both parties; however, such relationships are occasionally the situs of a variety of unexpected and ethically questionable behaviours. This study examines the narratives provided by participants who share their experience as an exchange partner in a market relationship or as a close observer of an exchange partner in a market relationship to identify the use of short‐term deceptions and ethics defections in managing these relationships. The data demonstrate a number of instances in which one exchange partner is willing to deceive another. Situations identified include deceiving current customers, new customers, current suppliers, governmental bodies, and employees and managers for the purposes of: protecting an existing relationship, pursuing a new relationship, ensuring product or service quality, and exerting control over a relationship. This research develops a general analytic framework for the occurrence of deception and defection from ethical norms in market relationships from elements of the study participants' narrative reports. This framework can be used by future researchers to design studies that examine the specific antecedents of these behaviours.