bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential targeting of components of the dystrophin complex to the postsynaptic membrane
Authors: Marchand Sophie , Stetzkowski‐Marden Françoise , Cartaud Jean
Published: July 2009

Accumulating evidence points to the participation of dystroglycan in the clustering of nicotinic acetylcholine receptors at the neuromuscular junction [Côtéet al.. (1999) Nature Genet., 3, 338–342]. Dystroglycan is part of a multimolecular complex, either associated with dystrophin (the dystrophin‐associated protein complex) at the sarcolemma or with utrophin (the utrophin‐associated protein complex) at the neuromuscular junction. Understanding the assembly of this complex at the developing synapse led us to investigate, in Torpedo electrocyte, the intracellular routing and the targeting of several of its components, including dystroglycan, syntrophin, dystrophin and dystrobrevin. We previously demonstrated that acetylcholine receptors and rapsyn, the 43‐kDa receptor‐associated protein at the synapse, are cotargeted to the postsynaptic membrane via the exocytic pathway [Marchand et al.. (2000) J. Neurosci., 20, 521–528]. Using cell fractionation, immunopurification and immuno‐electron microscope techniques, we show that β‐dystroglycan, an integral glycoprotein that constitutes the core of the dystrophin‐associated protein complex localized at the innervated membrane, is transported together with acetylcholine receptor and rapsyn in post‐Golgi vesicles en route to the postsynaptic membrane. Syntrophin, a peripheral cytoplasmic protein of the complex, associates initially with these exocytic vesicles. Conversely, dystrophin and dystrobrevin were absent from these post‐Golgi vesicles and associate directly with the postsynaptic membrane. This study provides the first evidence for a separate targeting of the various components of the dystrophin‐associated protein complex and a step‐by‐step assembly at the postsynaptic membrane.
p35/cdk5 binds and phosphorylates β‐catenin and regulates β‐catenin/presenilin‐1 interaction
Authors: Kesavapany Sashi , Lau Kwok‐Fai , McLoughlin Declan M. , Brownlees Janet , Ackerley Steven , Leigh P. Nigel , Shaw Christopher E. , Miller Christopher C. J.
Published: July 2009

The neuronal cyclin‐dependent kinase p35/cdk5 comprises a catalytic subunit (cdk5) and an activator subunit (p35). To identify novel p35/cdk5 substrates, we utilized the yeast two‐hybrid system to screen for human p35 binding partners. From one such screen, we identified β‐catenin as an interacting protein. Confirmation that p35 binds to β‐catenin was obtained by using glutathione S‐transferase (GST)–β‐catenin fusion proteins that interacted with both endogenous and transfected p35, and by showing that β‐catenin was present in p35 immunoprecipitates. p35 and β‐catenin also displayed overlapping subcellular distribution patterns in cells including neurons. Finally, we demonstrated that p35/cdk5 phosphorylates β‐catenin. β‐catenin also binds to presenilin‐1 and altered β‐catenin/presenilin‐1 interactions may be mechanistic in Alzheimer's disease (AD). Abnormal p35/cdk5 activity has also been suggested to contribute to AD. We therefore investigated how modulation of p35/cdk5 activity influenced β‐catenin/presenilin‐1 interactions. Inhibition of p35/cdk5 with roscovitine did not alter the steady state levels of either β‐catenin or presenilin‐1 but reduced the amount of presenilin‐1 bound to β‐catenin. Thus, p35/cdk5 binds and phosphorylates β‐catenin and regulates its binding to presenilin‐1. The findings reported here therefore provide a novel molecular framework to connect p35/cdk5 with β‐catenin and presenilin‐1 in AD.
The integration of parallel and serial processing mechanisms in visual search: evidence from eye movement recording
Authors: Maioli Claudio , Benaglio Irene , Siri Simona , Sosta Katiuscia , Cappa Stefano
Published: July 2009

We examined timing and scanning paths of eye movements during a visual search task, in which subjects had to detect, as quickly as possible, the presence or absence of a target among distractors [Q‐like element among O stimuli (QvsO) and vice‐versa (OvsQ)]. According to an influential theory [Treisman, A. & Gelade, G. (1980) Cognitive Psychol, 12, 97–136; Treisman, A. & Sato, S. (1990) J. Exp. Psychol. Hum. Percept. Perform., 16, 459–478], only tasks yielding nonflat search functions (OvsQ) involve focal attention. Alternative models propose that all kinds of visual search are resolved by a biased competitive process, working in parallel across the visual field. Data show that QvsO and OvsQ tasks are characterized by quantitative rather than by qualitative differences in search strategy. No differences between the two tasks were found regarding either the percentage of saccades foveating single stimulus items or the timing of the button response with respect to the onset of the last foveation saccade within a trial. Furthermore, the number of saccades made during search predicted very accurately the time required to accomplish the task and fixation times were independent of the number of stimulus items. On the basis of our results there is no reason to postulate the occurrence of shifts of visuospatial attention, other than those associated with the executions of saccadic eye movements, which are driven by a parallel feature analysis of the visual scene, in both types of search tasks. A time‐limited competitive model for attentive target identification, in which both parallel (competitive) and serial (attentive) processing mechanisms are integrated, can account for these findings, providing a unified conceptual framework for all kinds of visual search.
Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study
Authors: Buccino G. , Binkofski F. , Fink G. R. , Fadiga L. , Fogassi L. , Gallese V. , Seitz R. J. , Zilles K. , Rizzolatti G. , Freund H.‐J.
Published: July 2009

Functional magnetic resonance imaging (fMRI) was used to localize brain areas that were active during the observation of actions made by another individual. Object‐ and non‐object‐related actions made with different effectors (mouth, hand and foot) were presented. Observation of both object‐ and non‐object‐related actions determined a somatotopically organized activation of premotor cortex. The somatotopic pattern was similar to that of the classical motor cortex homunculus. During the observation of object‐related actions, an activation, also somatotopically organized, was additionally found in the posterior parietal lobe. Thus, when individuals observe an action, an internal replica of that action is automatically generated in their premotor cortex. In the case of object‐related actions, a further object‐related analysis is performed in the parietal lobe, as if the subjects were indeed using those objects. These results bring the previous concept of an action observation/execution matching system (mirror system) into a broader perspective: this system is not restricted to the ventral premotor cortex, but involves several somatotopically organized motor circuits.
NAAG inhibits KCl‐induced [3H]‐GABA release via mGluR3, cAMP, PKA and L‐type calcium conductance
Authors: Zhao Jing , Ramadan Epolia , Cappiello Marisa , Wroblewska Barbara , Bzdega Tomasz , Neale Joseph H.
Published: July 2009

The peptide neurotransmitter,N‐acetylaspartylglutamate (NAAG), is a selective agonist at the type 3 metabotropic glutamate receptor (mGluR3) where it acts to decrease cAMP levels. Rat cortical interneurons express both NAAG and glutamic acid decarboxylase, as well as mGluR3 mRNA. In the presence of ionotropic glutamate receptor antagonists, both NAAG and the group II metabotropic glutamate receptor agonist, DCG‐IV, reduced the calcium‐dependent, KCl‐induced [3H]‐GABA release from rat cortical neurons by 35%. This release process was unaffected by tetrodotoxin. The group II antagonist, ethyl glutamate, reversed the effects of DCG‐IV and NAAG. The mGluR3‐selective antagonist, β‐N‐acetylaspartylglutamate, reversed the effect of NAAG. While pretreatment of cortical neurons with forskolin alone did not significantly affect KCl‐stimulated [3H]‐GABA‐release, forskolin abolished the inhibition of release produced by NAAG. The protein kinase A inhibitor, H‐89, decreased [3H]‐GABA release while NAAG produced no additional inhibition in the presence of H‐89. In contrast, the protein kinase C inhibitor, Ro 31–8220, had no effect on KCl‐stimulated release, nor did it affect the inhibition of release produced by NAAG. The L‐type calcium channel blocker, nifedipine, also inhibited the release of [3H]‐GABA and coapplication with NAAG resulted in no significant additional inhibition of release. These data support the hypothesis that the inhibition of KCl‐stimulated [3H]‐GABA release by NAAG is mediated via presynaptic mGluR3 on GABAergic cortical neurons and that this effect is obtained by decreasing cAMP with a consequent decrease in protein kinase A activity and L‐type calcium channel conductance.
Differential development of selectivity for faces and bodies in the fusiform gyrus
Authors: Peelen Marius V. , Glaser Bronwyn , Vuilleumier Patrik , Eliez Stephan
Published: July 2009

Viewing faces or bodies activates category‐selective areas of visual cortex, including the fusiform face area (FFA), fusiform body area (FBA), and extrastriate body area (EBA). Here, using fMRI, we investigate the development of these areas, focusing on the right FFA and FBA. Despite the overlap of functionally defined FFA and FBA (54%–75% overlap), we found that these regions developed along different trajectories. With age (7–32 years old), the FFA gradually increased in size and selectivity, and was significantly larger and more face‐selective in adults than children. By contrast, the size and selectivity of the FBA did not correlate with age, and were equivalent in children and adults. Whereas in adults the FFA and FBA were comparable in size, in children the FBA was on average 70% larger than the FFA. These findings suggest that, in children, the fusiform gyrus is predominantly selective for bodies, with commensurate face‐selective responses apparent later in development. Moreover, differences in the development of the FFA and FBA indicate that overlapping functional brain areas, supported by the same anatomical structure, can develop along different trajectories.
AUTHORIZING PSYCHIATRIC RESEARCH: PRINCIPLES, PRACTICES AND PROBLEMS
Authors: CHONG SIOW ANN , HUXTABLE RICHARD , CAMPBELL ALASTAIR
Published: July 2009

Psychiatric research is advancing rapidly, with studies revealing new investigative tools and technologies that are aimed at improving the treatment and care of patients with psychiatric disorders. However, the ethical framework in which such research is conducted is not as well developed as we might expect. In this paper we argue that more thought needs to be given to the principles that underpin research in psychiatry and to the problems associated with putting those principles into practice. In particular, we comment on some of the difficulties posed by the twin imperatives of ensuring that we respect the autonomy and interests of the research subject and, at the same time, enable potentially beneficial psychiatric research to flourish. We do not purport to offer a blueprint for the future; we do, however, seek to advance the debate by identifying some of the key questions to which better answers are required.
WHY MORAL PHILOSOPHERS ARE NOT AND SHOULD NOT BE MORAL EXPERTS
Authors: ARCHARD DAVID
Published: July 2009

Professional philosophers are members of bioethical committees and regulatory bodies in areas of interest to bioethicists. This suggests they possess moral expertise even if they do not exercise it directly and without constraint. Moral expertise is defined, and four arguments given in support of scepticism about their possession of such expertise are considered and rejected: the existence of extreme disagreement between moral philosophers about moral matters; the lack of a means clearly to identify moral experts; that expertise cannot be claimed in that which lacks objectivity; and that ordinary people do not follow the advice of moral experts.

I offer a better reason for scepticism grounded in the relation between moral philosophy and common‐sense morality: namely that modern moral philosophy views even a developed moral theory as ultimately anchored in common‐sense morality, that set of basic moral precepts which ordinary individuals have command of and use to regulate their own lives.

Even if moral philosophers do nevertheless have a limited moral expertise, in that they alone can fully develop a set of moral judgments, I sketch reasons – grounded in the values of autonomy and of democracy – why moral philosophers should not wish non‐philosophers to defer to their putative expertise.
EQUALITY AND THE TREATMENT‐ENHANCEMENT DISTINCTION
Authors: HOLTUG NILS
Published: July 2009

In From Chance to Choice, Allen Buchanan, Dan Brock, Norman Daniels and Daniel Wikler propose a new way of defending the moral significance of the distinction between genetic treatments and enhancements. They develop what they call a ‘normal function model’ of equality of opportunity and argue that it offers a ‘limited’ defence of this distinction. In this article, I critically assess their model and the support it (allegedly) provides for the treatment‐enhancement distinction. First, I argue that there is a troubling tension in the normal function model. Secondly, I argue that neither of the rationales invoked by Buchanan et al. really serves to justify this model or the results they seek to derive from it with respect to the significance of the distinction between treatments and enhancements.
Leadership Styles as Predictors of Self‐reported and Observed Workplace Bullying
Authors: Hoel Helge , Glasø Lars , Hetland Jørn , Cooper Cary L. , Einarsen Ståle
Published: July 2009

The connection between leadership or management style, on the one hand, and perceptions of bullying, on the other, has received little attention within bullying research. Hence, the aim of this study is to examine the relationship between subordinates' ratings of their immediate superiors' behaviours, and both perceived exposure and claims of observations of bullying at work. Based on a sampling process which emphasized randomness and representativeness, the responses from 5288 respondents in Great Britain taking part in a nationwide study on psychosocial issues at work were included in the analysis. Bullying correlated with all four leadership styles measured. Yet, ‘non‐contingent punishment’ emerged as the strongest predictor of self‐perceived exposure to bullying, while autocratic leadership was the strongest predictor of observed bullying. Hence, while observers particularly associate bullying with autocratic or tyrannical leader behaviour, targets relate bullying more to non‐contingent punishment, i.e. an unpredictable style of leadership, where punishment is meted out or delivered on leaders' own terms, independent of the behaviour of subordinates. In addition, laissez‐faire leadership emerged as a predictor of self‐reported as well as observed bullying. Thus, leadership styles seem to play an important but complex role in the bullying process.
Who We Are Affects How We Do: The Financial Benefits of Organizational Identification
Authors: Millward Lynne J. , Postmes Tom
Published: July 2009

One ultimate test of the material value of identification in an organizational context is whether it relates to productivity. In this rare study of a business team in a global consumer goods company, we demonstrate a sales benefit of organizational identification when correcting for systematic between‐unit differences in sales. Findings also question the theoretical and practical meaning of ‘proximity’ in accounting for salience variations in identification – the best predictor of sales was the degree of identification with the superordinate business unit. Findings shed light on the scientific as well as managerial and business utility of the organizational identity concept.
Short‐term versus Long‐term Impact of Managers: Evidence from the Football Industry
Authors: Hughes Mathew , Hughes Paul , Mellahi Kamel , Guermat Cherif
Published: July 2009

Studies into the impact of top manager change on organization performance have revealed inconsistent findings. Using longitudinal data over a 12‐year period on football organizations, we test for the short‐term and long‐term effects of manager change in comparison to the tenures of incumbent top managers. We find that long incumbent tenures are associated with performance far above the average. But when looking at change events, contrary to theoretical expectations, we find that change in the short term leads to a brief reprieve in poor performance only for performance to deteriorate in the long term as underlying weaknesses once again take hold. Our findings reveal the illusion of a short‐term reprieve and the long‐term consequences of this illusion. We map several implications for research and practice from our work.
Counting Chicks Before They Hatch
Authors: White David J. , Ho Lucy , Freed-Brown Grace
Published: July 2009

Here we show that demands associated with brood parasitism have favored sophisticated cognitive abilities in female brown-headed cowbirds. We discovered that cowbirds can use the rate at which eggs are added to a nest across days to assess the readiness of the nest for incubation, which would allow them to synchronize laying with the host and avoid nests where incubation has most likely commenced. In three experiments, cowbirds investigated and laid eggs in artificial nests that differed in the number of eggs they contained. Across days, we added eggs to nests at different rates to simulate differences in the timing of reproduction of the hosts. Cowbirds avoided a nest if the number of eggs that had been added was less than the number of days that had elapsed. The ability of females to remember egg number and compare changes in egg number across days allows them to select nests most suitable for parasitism.
Non‐parametric Tests for Recurrent Events under Competing Risks
Authors: DAUXOIS JEAN‐YVES , SENCEY SOPHIE
Published: July 2009

Abstract.  We consider a data set on nosocomial infections of patients hospitalized in a French intensive care facility. Patients may suffer from recurrent infections of different types and they also have a high risk of death. To deal with such situations, a model of recurrent events with competing risks and a terminal event is introduced. Our aim was to compare the occurrence rates of two types of events. For this purpose, we propose two tests: one to detect if the occurrence rate of a given type of event increases with time; a second to detect if the instantaneous probability of experiencing an event of a given type is always greater than the one of another type. The asymptotic properties of the test statistics are derived and Monte Carlo methods are used to study the power of the tests. Finally, the procedures developed are applied to the French nosocomial infections data set.
Empirical Likelihood Confidence Intervals for Response Mean with Data Missing at Random
Authors: XUE LIUGEN
Published: July 2009

Abstract.  A kernel regression imputation method for missing response data is developed. A class of bias‐corrected empirical log‐likelihood ratios for the response mean is defined. It is shown that any member of our class of ratios is asymptotically chi‐squared, and the corresponding empirical likelihood confidence interval for the response mean is constructed. Our ratios share some of the desired features of the existing methods: they are self‐scale invariant and no plug‐in estimators for the adjustment factor and asymptotic variance are needed; when estimating the non‐parametric function in the model, undersmoothing to ensure root‐n consistency of the estimator for the parameter is avoided. Since the range of bandwidths contains the optimal bandwidth for estimating the regression function, the existing data‐driven algorithm is valid for selecting an optimal bandwidth. We also study the normal approximation‐based method. A simulation study is undertaken to compare the empirical likelihood with the normal approximation method in terms of coverage accuracies and average lengths of confidence intervals.
Preschoolers' Attachment to Mother and Risk for Adjustment Problems in Kindergarten: Can Teachers Make a Difference?
Authors: Buyse Evelien , Verschueren Karine , Doumen Sarah
Published: July 2009

Based on attachment theory, two aims were addressed. Firstly, we tested whether close teacher–child relationships may buffer children who are less securely attached to their mothers against negative outcomes, such as aggressive behavior. Secondly, our study evaluated whether teacher sensitivity may protect less securely attached children against forming less close relationships with their teachers. In a sample of 127 children, mother–child attachment was observed in preschool. In kindergarten, teacher sensitivity was observed, and teacher–child closeness and child aggressive behavior were rated by the teacher. Results of multilevel hierarchical regression analyses first showed that with high teacher–child closeness, less securely attached children are no longer at risk for more aggressive behavior. Secondly, it was found that with high teacher sensitivity, less securely attached children are no longer at risk for developing less close relationships with their teachers.
Understanding adolescent mental health: the influence of social processes, doing gender and gendered power relations
Authors: Landstedt Evelina , Asplund Kenneth , Gillander Gådin Katja
Published: July 2009

Despite a well‐documented gender pattern in adolescent mental health, research investigating possible explanatory factors from a gender‐theoretical approach is scarce. This paper reports a grounded theory study based on 29 focus groups. The aim was to explore 16‐ to 19‐year‐old students’ perceptions of what is significant for mental health, and to apply a gender analysis to the findings in order to advance understanding of the gender pattern in adolescent mental health. Significant factors were identified in three social processes categories, including both positive and negative aspects: (1) social interactions, (2) performance and (3) responsibility. Girls more often experienced negative aspects of these processes, placing them at greater risk for mental health problems. Boys’ more positive mental health appeared to be associated with their low degree of responsibility‐taking and beneficial positions relative to girls. Negotiating cultural norms of femininity and masculinity seemed to be more strenuous for girls, which could place them at a disadvantage with regard to mental health. Social factors and processes (particularly responsibility), gendered power relations and constructions of masculinities and femininities should be acknowledged as important for adolescent mental health.
Exploring stigma: medical knowledge and the stigmatisation of parents of children diagnosed with autism spectrum disorder
Authors: Farrugia David
Published: July 2009

This paper analyses 12 parent interviews to investigate the stigmatisation of parents of children diagnosed with an autism spectrum disorder. Drawing on poststructural accounts of the relationship between knowledge and subjectivity, the stigma concept is critically interrogated in order to address previous individualistic constructions of stigmatisation and to place stigma within the power dynamics of social control. The results of the study indicate that a child’s diagnosis with an autism spectrum disorder (ASD) is critical for parents to resist stigmatisation. Parents experienced considerable enacted stigma, but successfully resisted felt stigma by deploying medical knowledge to articulate unspoiled subject positions. The institutionalisation of medical knowledge within the autism community was critical to this process. Resistance to enacted stigma was successful to the degree that medical constructions of deviance deployed by parents were accepted by others, notably those in power within institutions. It is concluded that poststructural accounts of subjectivity and social control provide a useful way of conceptualising stigmatisation. An acceptance of the painful nature of stigma as lived experience co‐exists with an emphasis on the constantly negotiated nature of embodied subjectivity as a contingent social process to illustrate the conditions for active resistance to stigmatisation.
Biographical disruption, abruption and repair in the context of Motor Neurone Disease
Authors: Locock Louise , Ziebland Sue , Dumelow Carol
Published: July 2009

Concepts of biographical disruption and repair have been widely applied to chronic illness, but not terminal illness. This paper examines the relevance of these concepts to motor neurone disease (MND), a progressive neurological condition characterised by loss of mobility, speech and ability to breathe or swallow. Survival is usually between two and five years, and some die within a few months. The condition thus lies at the boundary between chronic and terminal illness. Narrative interviews were conducted with 35 people living with MND and 11 family carers; analysis exploredhowpeople constructed their accounts as well aswhatthey said. As well as accounts of biographical disruption, we identified a distinctive sense that the diagnosis is a ‘death sentence’ and life is already over, which we term ‘biographical abruption’. We also found instances of biographical repair, as participants sought to make sense of their remaining life, restore normality and control, and find new meaning and identity.
The case of the vanishing patient? Image and experience
Authors: Blaxter Mildred
Published: July 2009

It has been argued that the new technologies of medicine privilege the image over the actual body and its experience, so that the patients themselves may ‘vanish’ behind the images. A case study is used to explore this from the patient’s point of view. What evidence is there that alienation or other dysfunctional effects can actually happen? In this example of the high‐tech medicine of lung cancer treatment, it was demonstrable that the process of diagnosis was not only dependent on, but also in some ways distorted by, the reliance on technologies. It was not necessarily true, however, that the machines and the images themselves proved alienating to the patient, or produced a feeling of disembodiment. It was the system in which they were used, their translation into records and decisions, which was deeply alienating, with only lip‐service paid to the principles of patient‐centredness or the inclusion of the patient as a partner in decision making. Features of the contemporary British health service which seem to foster this are discussed.
South Carolina indigo, European textiles, and the British Atlantic economy in the eighteenth century
Authors: NASH R. C.
Published: July 2009

Europe's indigo imports grew rapidly from the 1720s, but the mid‐century wars (1739–48, 1756–63) had a devastating effect on the European textile industries and hence on the indigo trade. Britain's indigo market, however, boomed in wartime on the bases of prize indigo captured from France and Spain and of indigo imported from South Carolina. The rise of South Carolina's trade from the mid‐1740s was not caused, as the historiography claims, by its monopoly of the British market—such a monopoly never existed—but because the depression in South Carolina's major staple, rice, compelled a remodelling of the South Carolina plantation system, which produced an elastic supply of indigo. Carolina indigo was blighted by a poor reputation, not, as is usually argued, because British merchants maligned unfairly its quality, but because Carolina planters failed to achieve consistent production standards. Carolina indigo nevertheless succeeded in displacing French and Spanish indigo in the British and in some continental markets, reflecting the demand for cheap dyestuffs from manufacturers of low‐cost textiles, the fastest‐growing sectors of the European textile industries at the onset of industrialization.
Urban population in late medieval England: the evidence of the lay subsidies
Authors: RIGBY STEPHEN H.
Published: July 2009

Was there a growth in the proportion of the population living in England's towns in the later middle ages? Uncertainty about national population trends and about the taxation multipliers needed to arrive at population totals has made it difficult to answer this question. A direct comparison of the proportion of taxpayers that was urban in 1377 and 1524 suggests that the urban share of population was static or may even have declined in this period. However, such decline provides no simple index of urban prosperity or decay: a decline in urbanization could be the product of rural buoyancy rather than of urban recession.
Criteria for initiating highly active antiretroviral therapy and short‐term immune response among HIV‐1‐infected patients in Côte d'Ivoire
Authors: Diabaté S , Alary M
Published: July 2009

Objectives

The aims of this study were to determine the predictors of CD4 count below 200 cells/μL and to propose an algorithm for antiretroviral therapy initiation; and to assess the determinants of immune response to highly active antiretroviral therapy (HAART) in Côte d'Ivoire.

Methods

A total of 615 consecutive patients attending an HIV/AIDS day hospital were enrolled in the study. We constructed a score system based on the results of a multivariate logistic regression analysis of the predictors of CD4 count <200 cells/μL with the intention of proposing an algorithm able to accurately designate patients eligible for HAART. We also identified factors associated with a short‐term increase in CD4 count >50 cells/μL after HAART initiation.

Results

Total lymphocyte count <1200 cells/μL (P<0.0001), lower haemoglobin levels (P<0.0001), and Centers for Disease Control and Prevention (CDC) clinical stages C (P=0.005) and B (P=0.045), as compared with stage A, were associated with CD4 count <200 cells/μL. Nonetheless, no accurate algorithm for HAART initiation was found. Three hundred and three of the 615 patients were treated. Of these 303 patients, 79.5% showed an increase of >50 cells/μL in CD4 count 6 months after HAART initiation (median increase 128 cells/μL). Adherence ≥95% (P=0.022) and increase in absolute total lymphocyte count during follow‐up (P<0.0001) were associated with a short‐term positive immune response.

Conclusions

Our results support the effectiveness of generic drug combinations in sub‐Saharan Africa. In order to enhance the management of HIV disease in sub‐Saharan Africa, efforts should target the development of low‐cost CD4 cell count laboratory tests.
High rates of active hepatitis B and C co‐infections in HIV‐1 infected Cameroonian adults initiating antiretroviral therapy
Authors: Laurent C , Bourgeois A , Mpoudi‐Ngolé E , Kouanfack C , Ciaffi L , Nkoué N , Mougnutou R , Calmy A , Koulla‐Shiro S , Ducos J , Delaporte E
Published: July 2009

Objectives

To investigate the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA in HIV‐infected patients initiating antiretroviral therapy in Cameroon.

Methods

Baseline blood samples from 169 patients were tested retrospectively for hepatitis B surface antigens (HBsAg), anti‐hepatitis B core (anti‐HBc), anti‐HCV and – if HBsAg or anti‐HCV result was positive or indeterminate – for HBV DNA or HCV RNA, respectively, using the Cobas Ampliprep/Cobas TaqMan quantitative assay (Roche Diagnostics GmbH, Mannheim, Germany).

Results

HBV DNA was detected in 14 of the 18 patients with positive or indeterminate HBsAg results [8.3% of the total study population, 95% confidence interval (CI) 4.6–13.5]. The median HBV viral load was 2.47 × 107 IU/mL [interquartile range (IQR) 3680–1.59 × 108; range 270 to >2.2 × 108]. Twenty‐one patients (12.4%, 95% CI 7.9–18.4) were found with HCV RNA (all with positive HCV serology). The median HCV viral load was 928 000 IU/mL (IQR 178 400–2.06 × 106; range 640–5.5 × 106). No patient was co‐infected with HBV and HCV. In multivariate analysis, HCV co‐infection was associated with greater age [≥45 years vs. <45 years, odds ratio (OR) 11.89, 95% CI 3.49–40.55, P<0.001] and abnormal serum alanine aminotransferase level [≥1.25 × upper limit of normal (ULN) vs. <1.25 × ULN, OR 7.81, 95% CI 1.54–39.66, P=0.01]; HBV co‐infection was associated with abnormal serum aspartate aminotransferase level (OR 4.33, 95% CI 1.32–14.17, P=0.02).

Conclusions

These high rates of active HBV and HCV co‐infections in HIV‐positive Cameroonian patients requiring antiretroviral therapy underline the need to promote: (i) screening for HBV and HCV before treatment initiation; (ii) accessibility to tenofovir (especially in HBV‐endemic African countries); and (iii) accessibility to treatment for HBV and HCV infections.
A 5‐year longitudinal follow‐up study of serological responses to 23‐valent pneumococcal polysaccharide vaccination among patients with HIV infection who received highly active antiretroviral therapy*
Authors: Hung C‐C , Chang S‐Y , Su C‐T , Chen Y‐Y , Chang S‐F , Yang C‐Y , Liu W‐C , Wu C‐H , Chang S‐C
Published: July 2009

Background

Long‐term antibody responses to 23‐valent pneumococcal polysaccharide vaccine (PPV) among HIV‐infected patients receiving highly active antiretroviral therapy (HAART) are rarely investigated.

Methods

Antibody responses to three pneumococcal capsular polysaccharides [Pneumococcal polysaccharide (PPS) 14, 19F and 23F] were assessed among 169 HIV‐infected patients who received HAART and 23‐valent PPV. Patients were stratified into four groups according to CD4 count at vaccination: group 1, CD4<100 cells/μL (n=35); group 2, CD4 100–199 cells/μL (n=36); group 3, CD4 200–349 cells/μL (n=34); and group 4, CD4≥350 cells/μL (n=64). The proportion of patients who achieved increases in antibody titres of twofold or greater from baseline values (responders) was compared among the four groups of patients for five consecutive years after vaccination.

Results

The proportion of responders to the three serotypes was significantly lower among patients in group 1 compared with those in the other three groups during yearly follow‐up. Much faster loss of antibody responses was observed in group 1, although the rate of decline varied with the serotypes studied in the four groups. Compared with the nonresponders, more responders had CD4 counts >100 cells/μL at vaccination and achieved better virological suppression throughout the 5‐year period, while the absolute increases of CD4 cell counts after HAART were not statistically significantly different.

Conclusions

Despite continued increases in CD4 cell counts after HAART, the proportion of HIV‐infected patients who maintained antibody responses to PPV declined significantly over the 5‐year follow‐up period, especially among those who had CD4 counts <100 cells/μL at vaccination and who failed to achieve virological suppression.
Autosomal dominant cerebellar ataxia: frequency analysis and clinical characterization of 45 families from Portugal
Authors: Vale J. , Bugalho P. , Silveira I. , Sequeiros J. , Guimarães J. , Coutinho P.
Published: July 2009

Background and purpose:  The relative frequency of the different autosomal dominant cerebellar ataxia (ADCA) varies widely amongst different geographic locations. Here we describe a series of 45 ADCA families from Portugal.

Methods:  Patients with progressive cerebellar dysfunction of autosomal dominant transmission underwent a clinical examination protocol and genetic testing for spinocerebellar ataxia (SCA)1 to Machado‐Joseph disease (MJD)/SCA3, SCA6, SCA7, SCA10, SCA12, SCA17 and dentatorubral‐pallidoluysian atrophy (DRPLA). We registered the clinical characteristics and frequency of each type of ataxia.

Results:  MJD/SCA3 was the most frequent ADCA (26 families, 57.8% of all families), followed by DRPLA (5 families, 11.2%), SCA7 (2 families, 4.4%), SCA2 and SCA1 (1 family each, 2.2% each); 10 families (22.2%) had no molecular diagnosis. SCA1 and SCA7 patients had African ancestry. DRPLA patients had Portuguese ancestry and were characterized by prominent anticipation and a variable combination of epilepsy, extra‐pyramidal symptoms and dementia. Ophtalmoparesis, slow saccades and retinopathy were most distinctive of SCA3, SCA2 and SCA7 cases, respectively.

Conclusions:  MJD/SCA3 was the most common ADCA in this group of families. The high frequency of DRPLA and presence of SCA1 and SCA7 cases was unexpected. The presence of these rarer ADCA types probably reflects migration phenomena, posing a challenge for differential diagnosis.
Predator behaviour and morphology mediates the impact of an invasive species: cane toads and death adders in Australia
Authors: Phillips B. L. , Greenlees M. J. , Brown G. P. , Shine R.
Published: July 2009

The arrival of an invasive species can have severe impacts on native species. The extent of the impact, as well as the speed at which native species may mount an adaptive response, depend upon the correlation between impact and the individual phenotypes of the native species. Strong correlation between phenotype and impact within the native species raises the possibility of rapid adaptive response to the invader. Here, we examine the impact of a dangerous newly arrived prey species (the highly toxic cane toad Bufo marinus) on naïve predators (death adders Acanthophis praelongus) in northern Australia. During laboratory trials and field radiotracking, toads killed 48% of the adders we studied. Long‐term monitoring of the population also suggests a massive decline (>89%) in recent years concurrent with the arrival of toads. Variation in snake physiology (resistance to toad toxin) had little bearing on snake survival in the field. Snake behaviour (tendency to attack toads) and morphology (body size and head size), however, were strong predictors of snake survival. Smaller snakes with relatively small heads, and snakes that were unwilling to attack toads in the laboratory, had much higher survival rates in the field. These results show that toads have a massive impact on death adder populations, but that snake phenotypes strongly mediate this impact. Thus natural selection is operating on these adder populations and an adaptive response is a possibility. If these adders can rapidly shift toad‐relevant morphological and behavioural traits (either through plastic or evolved means), they will ultimately face a lowered impact from this toxic invader.
An elevational shift of cryophilous bryophytes in the last century – an effect of climate warming?
Authors: Bergamini Ariel , Ungricht Stefan , Hofmann Heike
Published: July 2009

Aim To investigate altitudinal range shifts of bryophytes in Switzerland by comparing recent altitudinal distributions with historical distributions derived from herbarium specimens.

Location Switzerland, covering 41,285 km2in Central Europe.

Methods We used a dataset of 8520 herbarium specimens of 61 bryophyte species and compared altitudinal data between the two periods 1880–1920 and 1980–2005. The records we used were not specifically sampled for climatological analyses, but originate from non‐systematic fieldwork by various collectors. Historical and recent records were distributed all over Switzerland with occurrences in all major biogeographical areas. To account for different sampling efforts in the two time periods, different subsampling procedures were applied.

Results Overall, we found a significant mean increase in altitude of 89 ± 29 m which was mainly driven by the cryophilous species (+222 ± 50 m). The mean increase in altitude of cryophilous species corresponds to a decadal upward shift of 24 m. The upper range limit of cryophilous species also increased by 189 ± 55 m, but there was no effect on the lower range limit. For intermediate and thermophilous species neither mean, nor upper or lower range limits changed. However, the proportion of records of thermophilous to cryophilous species increased considerably at lower altitudes, but levelled off above approximately 1800 m.

Main conclusions We conclude that cryophilous bryophytes are expanding their range to higher elevations in Switzerland and that at lower elevations, a slow extinction process is going on, probably as a result of climate warming trends. The observed decadal upward shifts of cryophilous species closely match those reported from vascular plants in Europe and those expected, given recent estimates of climate warming trends. We emphasize that herbaria provide valuable data that can be used to detect ongoing changes in the distribution of species.
Mechanisms involved in the regional haemodynamic effects of intermedin (adrenomedullin 2) compared with adrenomedullin in conscious rats
Authors: Jolly L , March JE , Kemp PA , Bennett T , Gardiner SM
Published: July 2009

Background and purpose: Intermedin (IMD) is a newly identified member of the calcitonin family of peptides that shares structural and functional homology with adrenomedullin (AM).In vivocardiovascular effects of AM have been described, but relatively little is known of thein vivoactions of IMD. The purpose of this study was to compare the regional haemodynamic effects of IMD with those of AM in conscious rats, and investigate possible underlying mechanisms.

Experimental approach: Measurements of blood pressure, heart rate and renal, mesenteric and hindquarters haemodynamics were made in conscious, chronically‐instrumented rats.

Key results: IMD caused tachycardia and vasodilatation in all three vascular beds, associated with modest hypotension. At an equimolar dose (1 nmol·kg−1), most of the cardiovascular effects of IMD were greater than those of AM. The AM receptor antagonist, AM22–52, was equally effective in attenuating the renal and mesenteric vasodilator effects of IMD (1 nmol·kg−1) and AM (3 nmol·kg−1), but inhibition of NO synthase was more effective at reducing the vasodilator effects of IMD than AM. Vascular KATPchannel blockade with U‐37883A did not inhibit the vasodilator effects of either peptide.

Conclusions and implications: In vivo, the regional haemodynamic profile of IMD resembles that of AM, and some of the vasodilator effects of IMD are mediated by AM receptors and NO, but not by KATPchannels. The cardiovascular effects of AM have been implicated in various pathological conditions, but whether or not endogenous IMD fulfils a similar role remains to be determined.
Prevention of arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen
Authors: Chang Kuo‐Chu , Liang Jin‐Tung , Tsai Pei‐Shan , Wu Ming‐Shiou , Hsu Kwan‐Lih
Published: July 2009

Background and purpose: Our team previously demonstrated that diabetes induces a deterioration in vascular dynamics, in parallel with the enhanced formation of advanced glycation end products. The aim of this study was to determine whether prevention of the arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen.

Experimental approach: Diabetes was induced in rats by a single tail vein injection with 55 mg·kg−1steptozotocin (STZ). After induction of hyperglycaemia, animals were treated for 8 weeks with pyridoxamine (1 g·L−1in drinking water) and compared with the age‐matched untreated diabetic controls. Pulse wave reflection along the vasculature was derived using the impulse response function of the filtered aortic input impedance spectra.

Key results: Treatment of this experimental diabetes with pyridoxamine resulted in a significant increase in wave transit time and a decrease in wave reflection factor, indicating that pyridoxamine attenuates the diabetes‐induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, pyridoxamine therapy ameliorated the diabetes‐related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Glycation‐derived modification of aortic collagen was also found to be attenuated by administration of pyridoxamine to the STZ‐induced diabetic rats.

Conclusions and implications: Pyridoxamine imparts significant protection against the diabetes‐induced deterioration in pulsatile arterial load imposed on the heart, at least partly through inhibition of the formation of advanced glycation end products and their accumulation on aortic collagen of the STZ‐treated rats.
Endogenous cannabinoids induce fever through the activation of CB1 receptors
Authors: Fraga D , Zanoni CIS , Rae GA , Parada CA , Souza GEP
Published: July 2009

Background and purpose:  The effects of centrally administered cannabinoids on body core temperature (Tc) and the contribution of endogenous cannabinoids to thermoregulation and fever induced by lipopolysaccharide (LPS) (Sigma Chem. Co., St. Louis, MO, USA) were investigated.

Experimental approach:  Drug‐induced changes in Tc of male Wistar rats were recorded over 6 h using a thermistor probe (Yellow Springs Instruments 402, Dayton, OH, USA) inserted into the rectum.

Key results:  Injection of anandamide [(arachidonoylethanolamide (AEA); Tocris, Ellisville, MO, USA], 0.01–1 µg i.c.v. or 0.1–100 ng intra‐hypothalamic (i.h.), induced graded increases in Tc (peaks 1.5 and 1.6°C at 4 h after 1 µg i.c.v. or 10 ng i.h.). The effect of AEA (1 µg, i.c.v.) was preceded by decreases in tail skin temperature and heat loss index (values at 1.5 h: vehicle 0.62, AEA 0.48). Bell‐shaped curves were obtained for the increase in Tc induced by the fatty acid amide hydrolase inhibitor [3‐(3‐carbamoylphenyl)phenyl] N‐cyclohexylcarbamate (Cayman Chemical Co., Ann Arbor, MI, USA) (0.001–1 ng i.c.v.; peak 1.9°C at 5 h after 0.1 ng) and arachidonyl‐2‐chloroethylamide (ACEA; Tocris) (selective CB1 agonist; 0.001–1 µg i.c.v.; peak 1.4°C 5 h after 0.01 µg), but (R,S)‐(+)‐(2‐Iodo‐5‐nitrobenzoyl)‐[1‐(1‐methyl‐piperidin‐2‐ylmethyl)‐1H‐indole‐3‐yl] methanone (Tocris) (selective CB2 agonist) had no effect on Tc. AEA‐induced fever was unaffected by i.c.v. pretreatment with 6‐Iodo‐2‐methyl‐1‐[2‐(4‐morpholinyl)ethyl]‐1H‐indole‐3‐yl](4‐methoxyphenyl) methanone (Tocris) (selective CB2 antagonist), but reduced by i.c.v. pretreatment with N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251; Tocris) (selective CB1 antagonist). AM251 also reduced the fever induced by ACEA or LPS.

Conclusions and implications:  The endogenous cannabinoid AEA induces an integrated febrile response through activation of CB1 receptors. Endocannabinoids participate in the development of the febrile response to LPS constituting a target for antipyretic therapy.