bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergence Rates and Asymptotic Standard Errors for Markov Chain Monte Carlo Algorithms for Bayesian Probit Regression
Authors: Roy Vivekananda , Hobert James P.
Published: August 2007

Consider a probit regression problem in which Y1, …, Yn are independent Bernoulli random variables such that Pr(Yi=1)=Φ(xiTβ) where xi is a p-dimensional vector of known covariates that are associated with Yi, β is a p-dimensional vector of unknown regression coefficients and Φ(·) denotes the standard normal distribution function. We study Markov chain Monte Carlo algorithms for exploring the intractable posterior density that results when the probit regression likelihood is combined with a flat prior on β. We prove that Albert and Chib's data augmentation algorithm and Liu and Wu's PX-DA algorithm both converge at a geometric rate, which ensures the existence of central limit theorems for ergodic averages under a second-moment condition. Although these two algorithms are essentially equivalent in terms of computational complexity, results of Hobert and Marchev imply that the PX-DA algorithm is theoretically more efficient in the sense that the asymptotic variance in the central limit theorem under the PX-DA algorithm is no larger than that under Albert and Chib's algorithm. We also construct minorization conditions that allow us to exploit regenerative simulation techniques for the consistent estimation of asymptotic variances. As an illustration, we apply our results to van Dyk and Meng's lupus data. This example demonstrates that huge gains in efficiency are possible by using the PX-DA algorithm instead of Albert and Chib's algorithm.
Functional Clustering and Identifying Substructures of Longitudinal Data
Authors: Chiou Jeng-Min , Li Pai-Ling
Published: August 2007

A functional clustering (FC) method, k-centres FC, for longitudinal data is proposed. The k-centres FC approach accounts for both the means and the modes of variation differentials between clusters by predicting cluster membership with a reclassification step. The cluster membership predictions are based on a non-parametric random-effect model of the truncated Karhunen–Loève expansion, coupled with a non-parametric iterative mean and covariance updating scheme. We show that, under the identifiability conditions derived, the k-centres FC method proposed can greatly improve cluster quality as compared with conventional clustering algorithms. Moreover, by exploring the mean and covariance functions of each cluster, thek-centres FC method provides an additional insight into cluster structures which facilitates functional cluster analysis. Practical performance of the k-centres FC method is demonstrated through simulation studies and data applications including growth curve and gene expression profile data.
Controlling the Reinforcement in Bayesian Non-Parametric Mixture Models
Authors: Lijoi Antonio , Mena Ramsés H. , Prünster Igor
Published: August 2007

The paper deals with the problem of determining the number of components in a mixture model. We take a Bayesian non-parametric approach and adopt a hierarchical model with a suitable non-parametric prior for the latent structure. A commonly used model for such a problem is the mixture of Dirichlet process model. Here, we replace the Dirichlet process with a more general non-parametric prior obtained from a generalized gamma process. The basic feature of this model is that it yields a partition structure for the latent variables which is of Gibbs type. This relates to the well-known (exchangeable) product partition models. If compared with the usual mixture of Dirichlet process model the advantage of the generalization that we are examining relies on the availability of an additional parameter σ belonging to the interval (0,1): it is shown that such a parameter greatly influences the clustering behaviour of the model. A value of σ that is close to 1 generates a large number of clusters, most of which are of small size. Then, a reinforcement mechanism which is driven by σ acts on the mass allocation by penalizing clusters of small size and favouring those few groups containing a large number of elements. These features turn out to be very useful in the context of mixture modelling. Since it is difficult to specify a priori the reinforcement rate, it is reasonable to specify a prior for σ. Hence, the strength of the reinforcement mechanism is controlled by the data.
On Bayesian analysis of nonlinear continuous‐time autoregression models
Authors: Stramer O. , Roberts G. O.
Published: August 2007

Abstract.  This article introduces a method for performing fully Bayesian inference for nonlinear conditional autoregressive continuous‐time models, based on a finite skeleton of observations. Our approach uses Markov chain Monte Carlo and involves imputing data from times at which observations are not made. It uses a reparameterization technique for the missing data, and because of the non‐Markovian nature of the models, it is necessary to adopt an overlapping blocks scheme for sequentially updating segments of missing data. We illustrate the methodology using both simulated data and a data set from the S & P 500 index.
Citizenship of the European Union—A Legal Analysis
Authors: Jacobs Francis G.
Published: August 2007

Abstract:  The aim of this article is to present a legal analysis of the concept of citizenship of the EU. This concept was considered by some to be embryonic in the original Community Treaties, but was first expressly incorporated into the Treaties by the Treaty on European Union, signed at Maastricht on 7 February 1992. In the case‐law of the European Court of Justice, which has given citizenship a content going beyond the express Treaty provisions, the concept is closely related to other basic concepts, including free movement of persons, the prohibition of discrimination on grounds of nationality and the protection of fundamental rights. This article seeks to review the case‐law, to disentangle citizenship from other related concepts, and to determine what added value citizenship has brought to the Treaties and what the potential and the proper limits of the concept might be.
The Scope of Article 12 EC: Some Remarks on the Influence of European Citizenship
Authors: Epiney Astrid
Published: August 2007

Abstract:  According to European Court of Justice (ECJ) case‐law, the scope of application of the EC Treaty is engaged under the following conditions when the free movement of persons has been established: a cross‐border connection is given; the Union citizen concerned resides legally in the host Member State; and the measure in question or the regulation has a connection with the residence or facilitates it. This condition will regularly be fulfilled since nearly every (national) regulation has a direct or indirect effect on the stay. A general link to primary or secondary law is, on the other hand, not necessary. Secondary law, however, can be significant in connection with the lawful residence. Even if partly vehement critiques have been formulated against this approach of the ECJ, it is convincing with regard to the aim of guaranteeing the free movement to European citizens.
European Union Citizenship: Writing the Future
Authors: Kostakopoulou Dora
Published: August 2007

Abstract:  EU citizenship has matured as an institution, owing to a number of important interventions by the European Court of Justice and legislative initiatives, such as the Citizenship Directive 2004/38/EC, which has recently entered into force. In this article, I critically examine minimalist and cosmopolitan conceptions of European citizenship and argue that once we dispense with the preoccupation of assigning primacy to a specific level of citizenship and establishing some kind of hierarchy among them, we can begin to address the questions and issues that really matter. Among these are the future governance of citizenship and the design of a more inclusive, multilayered and multicultural conception of citizenship. European citizenship entails a number of fruitful ideas for a more ambitious transition to a post‐national tableau and can be the prototype for institutional experimentation on citizenship on a global scale.
‘Caminante, no hay camino, se hace camino al andar’1: EU Citizenship, Direct Democracy and Treaty Ratification
Authors: Cheneval Francis
Published: August 2007

Abstract:  This article argues that obligatory, simultaneous, and simple Treaty ratification by referenda is the next step in the consolidation of the political core of European citizenship. In the first part, general remarks about the special nature of EU citizenship highlight the relevance of referenda on EU Treaties for EU citizenship. In the second part, the normative and empirical case in favour of direct democracy is put forward. It is followed by the assessment of direct democracy in European integration as we have known it so far. The practice is irreversible and gaining in momentum. But it is in need of substantial reform due to procedural dysfunctions and discriminatory consequences for the citizens. Section V relates this result to a legal analysis of EU citizenship. The suppression of the discriminatory consequences of the Treaty ratification procedure is necessary from a legal point of view, but it cannot be expected from the ‘judicial incrementalism’ that has characterised the development of EU citizenship regarding free movement and residence. In section VI, the conclusions of the previous sections are drawn into the final proposal of obligatory, simultaneous and simple Treaty reform by referenda in all Member States. At the end, five counter‐arguments to the proposal are discussed.
How can one be European? Reflections on the Pillars of European Civic Identity
Authors: Magnette Paul
Published: August 2007

Abstract:  The citizenship of the EU is not only a set of rights, but also of civic behaviours and representations. In this article, I analyse these moral and sociological foundations of EU citizenship, stressing the limits of classic interpretations in terms of ‘identification to’ or ‘support for’ the EU. Instead, I suggest reading the evolution of EU citizenship as a process of political recognition. Such an analytical framework, inspired by recent works of Axel Honneth and Paul Ricoeur, leads one to understand this process as a threefold evolution: critical assessment of one's own national identity; transformation of the perception of other nationalities; and identification to the EU. Such a reading also compels us to pay attention to the limits of these processes: mutual recognition is an unending process which does not exclude the persistence of nationalistic reactions, hegemonic temptation and the revival of xenophobic attitudes vis‐à‐vis other Member States and third countries. I conclude that any project to render EU identity thicker needs to take care of the risk of jeopardising the fragile acquis.
Successful treatment of periungual warts using photodynamic therapy: a pilot study
Authors: Schroeter CA , Kaas L , Waterval JJ , Bos PM , Neumann HAM
Published: August 2007

Aim  The aim of this pilot study was an investigation on photodynamic therapy (PDT) whether it is a good alternative for treating periungual and subungual warts of the hands.

Study design  Twenty patients (mean age: 30.5 years) with a total of 40 periungual and subungual warts were treated with PDT. A photosensitizer, 20%δ‐aminolevulinic acid was applied on the warts. After a mean incubation time of 4.6 h (SD: 1.2), the warts were irradiated with the VersaLight® for 5–30 min (15.2 ± 4.3 min).

Results  After a mean of 4.5 treatments a mean clearance of 100% was achieved in 90% of the patients. One patient (5%) showed a clearance of 50% and another showed no improvement. The subungual or periungual location of the wart had no influence on the number of treatments or end result (P > 0.05). There were two recurrences during the mean follow‐up period of 5.9 months (SD: 7.6). Besides mainly pain and hyperpigmentation, most treatments had no side‐effects.

Conclusion  PDT can offer a good alternative for treating periungual warts of the hands. Larger studies are indicated.
Development and validation of a questionnaire to evaluate how a cosmetic product for oily skin is able to improve well‐being in women
Authors: Segot‐Chicq E , Compan‐Zaouati D , Wolkenstein P , Consoli S , Rodary C , Delvigne V , Guillou V , Poli F
Published: August 2007

Background  Skin diseases are known to negatively affect self‐image and to have detrimental psychosocial effects. Oily skin is a cosmetic skin problem that women often describe as ‘invalidating’.

Objective  To develop and validate a questionnaire to assess the psychological and psychosocial effects of oily skin condition in women and the outcome of a targeted cosmetic skincare treatment.

Methods  We developed and validated a concise 18‐item questionnaire [oily skin self‐image questionnaire (OSSIQ)] to assess perception, behavioural, and emotional consequences associated with oily skin condition. The questionnaire was then used to assess the effects of a skincare treatment for oily skin and compare them with sebum level measurements.

Results  The 18‐item questionnaire clearly distinguished the oily skin group from the control group. Responsiveness, reliability, and construct validity showed satisfactory performance. The questionnaire provided a relevant assessment of the psychological benefits associated with the skincare programme.

Conclusion  The OSSIQ is a valid tool that can be used to monitor the benefits of cosmetic skincare treatments
What Factors are Related to a Negative Outcome of Self‐Injurious Behaviour During Childhood in Pervasive Developmental Disorders?
Authors: Baghdadli A. , Picot M. C. , Pry R. , Michelon C. , Burzstejn C. , Lazartigues A. , Aussilloux C.
Published: August 2007

Aim To explore the factors related to the outcome of self‐injurious behaviour (SIB) in children with pervasive developmental disorders (PDD).

Method Children with PDD were assessed on individual and environmental variables at time 1 and 3 years later. A questionnaire about the presence or absence of SIB was also administered at both times in order to examine the early course of SIB.

Results Our findings suggest an association between a negative outcome and several aspects of the children’s behaviour. Children with a negative outcome differed from the others in having greater speech impairment, more cognitive and adaptive deficits, and more severe signs of autism. When these variables were entered into a multivariate model for predicting the outcome of SIB, only speech deficits (ORa3.5, CI 95% 1.13–13.4) and autism severity (ORa1.1, CI 95% 1.03–1.18) were significant risk factors.

Discussion The importance of these findings for improving our understanding of SIB is discussed.
Specialist Versus Generic Models of Psychiatry Training and Service Provision for People with Intellectual Disabilities
Authors: Jess Gillian , Torr Jennifer , Cooper Sally‐Ann , Lennox Nicholas , Edwards Nicole , Galea Jennifer , O’Brien Gregory
Published: August 2007

Background  Models of service provision and professional training differ between countries. This study aims to investigate a specialist intellectual disabilities model and a generic mental health model, specifically comparing psychiatrists’ knowledge and competencies, and service quality and accessibility in meeting the mental health needs of people with intellectual disabilities.

Method  Data were collected from consultant and trainee psychiatrists within a specialist intellectual disabilities model (UK) and a generic mental health model (Australia).

Results  The sample sizes were 294 (UK) and 205 (Australia). Statistically significant differences were found, with UK participants having positive views about the specialist intellectual disabilities service model they worked within, demonstrating flexible and accessible working practices and service provision, responsive to the range of mental health needs of the population with intellectual disabilities, and providing a wide range of treatments and supports. The UK participants were knowledgeable, well trained and confident in their work. They wanted to work with people with intellectual disabilities. In all of these areas, the converse was found from the Australian generic mental health service model.

Conclusions  The specialist intellectual disabilities model of service provision and training has advantages over the generic mental health model.
Genetic quality of individuals impacts population dynamics
Authors: Reed D. H. , Nicholas A. C. , Stratton G. E.
Published: August 2007

Ample evidence exists that an increase in the inbreeding level of a population reduces the value of fitness components such as fecundity and survival. It does not follow, however, that these decreases in the components of fitness impact population dynamics in a way that increases extinction risk, because virtually all species produce far more offspring than can actually survive. We analyzed the effects of the genetic quality (mean fitness) of individuals on the population growth rate of seven natural populations in each of two species of wolf spider in the genus Rabidosa, statistically controlling for environmental factors. We show that populations of different sizes, and different inbreeding levels, differ in population dynamics for both species. Differences in population growth rates are especially pronounced during stressful environmental conditions (low food availability) and the stressful environment affects smaller populations (<500 individuals) disproportionately. Thus, even in an invertebrate with an extremely high potential growth rate and strong density‐dependent mortality rates, genetic factors contribute directly to population dynamics and, therefore, to extinction risk. This is only the second study to demonstrate an impact of the genetic quality of individual genotypes on population dynamics in a wild population and the first to document strong inbreeding–environment interactions for fitness among populations. Endangered species typically exist at sizes of a few hundred individuals and human activities degrade habitats making them innately more stressful (e.g. global climate change). Therefore, the interaction between genetic factors and environmental stress has important implications for efforts aimed at conserving the Earth's biodiversity.
Assessing the efficacy of reintroduction programmes by modelling adult survival: the example of Hermann's tortoise
Authors: Bertolero A. , Oro D. , Besnard A.
Published: August 2007

Although reintroduction programmes are often implemented for recovering animal populations, projects seldom monitor the long‐term survival of released animals. In addition, although many releases may occur in the same area, little is known about how the survival of successive release batches is affected by the presence of conspecifics and density dependence. Here, we use multi‐state capture–recapture modelling (combining information from recaptures and recoveries) to analyse the survival of two batches of Hermann's tortoise Testudo hermanni hermanni released in a 10‐year interval and monitored for 18 years at the Ebro Delta (western Mediterranean). We also tested whether the released animals experienced lower survival (i.e. a release cost) before becoming familiar with the new environment. Although we used a hard‐release method, neither group experienced a short‐term release cost. Annual survival of both groups differed and was not negatively affected by density‐dependent factors. Annual survivorship of the first group of released tortoises was constant and very high (0.945, se=0.011), and similar to that estimated from several natural populations. The presence of a terrestrial predator in 1 year (before the release of the second group) significantly decreased the survival of tortoises (0.819, se=0.073). Strikingly, survival of the second batch was significantly lower than that of the first group after the first years of release (0.775, se=0.049). Although survivorship for the first group suggested that habitat quality was high, the second group seemed not to acclimate well to the new environment, possibly due to the presence of resident tortoises. From a management perspective, reintroduction programmes of the Hermann's tortoise are a successful strategy for its recovery. Nevertheless, it seems advisable to avoid: (1) the release of tortoises at the core of well‐established populations and (2) areas with a high density of predators, which can jeopardize the reintroduction success, especially when the number of released individuals is small.
Contribution of endothelial cells to organogenesis: a modern reappraisal of an old Aristotelian concept
Authors: Crivellato E. , Nico B. , Ribatti D.
Published: August 2007

It is well established that many tissue‐derived factors are involved in blood vessel formation, but evidence is now emerging that endothelial cells themselves represent a crucial source of instructive signals to non‐vascular tissue cells during organ development. Thus, endothelial cell signalling is currently believed to promote fundamental cues for cell fate specification, embryo patterning, organ differentiation and postnatal tissue remodelling. This review article summarizes some of the recent advances in our understanding of the role of endothelial cells as effector cells in organ formation.
Beyond drinking: the role of wine in the life of the UK consumer
Authors: Ritchie Caroline
Published: August 2007

Since the development of wine sales via supermarkets in the UK in the 1970s wine consumption has more than doubled so now the UK is the largest wine import market (by value) in the world. Wine is now consumed by approximately 61% of the UK adult population on a regular basis. For many social wine consumption has become part of their lifestyle. Given the international importance of the UK wine market, plus the increasing incorporation of wine into regular consumption behaviour, it is remarkable how few academic studies have been undertaken into the consumption behaviour of moderate, social UK wine consumers. This paper aims to start developing that knowledge, thus adding to our understanding of consumer behaviour in general. The results show that consumers use wine in very sophisticated ways via purchasing, gifting and consumption. The findings also show that social interaction with wine varies significantly, dependant upon occasion and environment. Behaviour also varies if the purchase, as gift and/or for consumption, is perceived as a private or public activity. This paper places UK wine consumer behaviour within a social context, and is able to show that all consumers display a range of behaviours in relation to wine which are situation and occasion dependant.
Individualism and the ‘new tourism’: a perspective on emulation, personal control and choice
Authors: Voase Richard
Published: August 2007

Changes can be identified in patterns of Western tourism over recent decades. The changes are linked with the theorized cultural shift from modern to postmodern. The discourse of change points to a shift in emphasis from the designated resort environment to a proliferation of individuated experiences. Analysts are apt to link these changes to a growth in individualism and individualistic expression. This study argues that the new tourists' real needs are to discover a new form of the collective. The argument is constructed drawing on the work of Veblen and Bourdieu. The final diagnosis draws on the work of Foucault.
The binding and phosphorylation of Thr231 is critical for Tau’s hyperphosphorylation and functional regulation by glycogen synthase kinase 3β
Authors: Lin Yuh‐Te , Cheng Jiin‐Tsuey , Liang Li‐Ching , Ko Chiung‐Yuan , Lo Yuk‐Keung , Lu Pei‐Jung
Published: August 2007

Neuropathological hallmarks of Alzheimer’s disease are extracellular senile plaques and intracellular neurofibrillary lesions. The neurofibrillary lesions mainly consist of the hyperphosphorylated microtubule‐associated protein Tau predominantly expressed in the axon of CNS neurons. Hyperphosphorylation of Tau negatively affects its binding to tubulin and decreases the capacity to promote microtubule assembly. Among a number of proline‐directed kinases capable of phosphorylating paired helical filament‐Tau, glycogen synthase kinase 3β (GSK3β) was first identified as a Tau protein kinase I and has been demonstrated to phosphorylate Tau both in vivo and in vitro. However, the phosphorylation mechanism of Tau by GSK3β remained unclear. In this study, we show that the T231 is the primary phosphorylation site for GSK3β and the Tau227–237 (AVVRTPPKSPS) derived from Tau containing T231P232 motif is identified as the GSK3β binding site with high affinity of a Kd value 0.82 ± 0.16 μmol/L. Our results suggest that direct binding and phosphorylation of T231P232 motif by GSK3β induces conformational change of Tau and consequentially alters the inhibitory activity of its N‐terminus that allows the phosphorylation of C‐terminus of Tau by GSK3β. Furthermore, hyperphosphorylation reduces Tau’s ability to promote tubulin assembly and to form bundles in N18 cells. T231A mutant completely abolishes Tau phosphorylation by GSK3β and retains the ability to promote tubulin polymerization and bundle formation. Taken together, these results suggest that phosphorylation of T231 by GSK3β may play an important role in Tau’s hyperphosphorylation and functional regulation.
Functional and immunocytochemical evidence for the expression and localization of the secretory pathway Ca2+‐ATPase isoform 1 (SPCA1) in cerebellum relative to other Ca2+ pumps
Authors: Sepúlveda M. Rosario , Berrocal María , Marcos Daniel , Wuytack Frank , Mata Ana M.
Published: August 2007

Membrane fractions of pig cerebellum show Ca2+‐ATPase activdity and Ca2+ transport due to the presence of the secretory pathway Ca2+‐ATPase (SPCA). The SPCA1 isoform shows a wide distribution in the neurons of pig cerebellum, where it is found in the Golgi complex of the soma of Purkinje, stellate, basket and granule cells, and also in more distal components of the secretory pathway associated with a synaptic localization such as in cerebellar glomeruli. The SPCA1 may be involved in loading the Golgi complex and the secretory vesicles of these specific neuronal cell types with Ca2+ and also Mn2+. This study of the cellular and subcellular localization of SPCA1 pumps relative to the sarco(endo) plasmic reticulum Ca2+‐ATPase and plasma membrane Ca2+‐ATPase pumps hints to a possible specific role of SPCA1 in controlling the luminal secretory pathway Ca2+ (or Mn2+) levels as well as the local cytosolic Ca2+ levels. In addition, it helps to specify the zones that are most vulnerable to Ca2+ and/or Mn2+ dyshomeostasis, a condition that is held responsible of an increasing number of neurological disorders.
Peroxisome proliferator‐activated receptor‐alpha is required for the neurotrophic effect of oleic acid in neurons
Authors: Bento‐Abreu André , Tabernero Arantxa , Medina José M.
Published: August 2007

Oleic acid synthesized by astrocytes behaves as a neurotrophic factor for neurons, up‐regulating the molecular markers of axonal and dendritic outgrowth, growth‐associated protein 43 and microtubule‐associated protein 2. In this work, the nature of the receptor involved in this neurotrophic effect was investigated. As oleic acid has been reported to be a ligand and activator of the peroxisome proliferator‐activated receptor (PPAR), we focus on this family of receptors. Our results show that PPARα, β/δ, and γ are expressed in neurons in culture. However, only the agonists of PPARα, Wy14643, GW7647 and oleoylethanolamide, promoted neuronal differentiation, while PPAR β/δ and γ agonists did not modify neuronal differentiation. Consequently, we investigated the involvement of PPARα (Nr1c1) in oleic acid‐induced neuronal differentiation. Our results indicate that oleic acid activates PPARα in neurons. In addition, the effect of oleic acid on neuronal morphology, growth‐associated protein 43 and microtubule‐associated protein 2 expression decreases in neurons after PPARα has been silenced by small interfering RNA. Taken together, our results suggest that PPARα could be the receptor for oleic acid in neurons, further broadening the range of functions attributed to this family of transcription factors. Although several works have reported that PPARα could be involved in neuroprotection, the present work provides the first evidence suggesting a role of PPARα in neuronal differentiation.
Pituitary adenylate cyclase‐activating polypeptide induces translocation of its G‐protein‐coupled receptor into caveolin‐enriched membrane microdomains, leading to enhanced cyclic AMP generation and neurite outgrowth in PC12 cells
Authors: Zhang Weishi , Duan Wei , Cheung Nam Sang , Huang Zhili , Shao Ke , Li Qiu‐Tian
Published: August 2007

Pituitary adenylate cyclase‐activating polypeptide (PACAP), a member of the secretin/glucagon/vasoactive intestinal peptide family expressed throughout the nervous system, binds to the PACAP‐specific G‐protein‐coupled receptor family members to promote both neuronal differentiation and survival. Although the PACAP receptor is known to activate its effector protein, adenylate cyclase (AC), and thus enhance cAMP generation, the molecular mechanism utilized by the receptor to activate AC is lacking. Here, we show that PACAP induces neurite outgrowth in PC12 cells by induction of translocation of the PACAP type 1 receptor (PAC1R) into caveolin‐enriched Triton X‐100‐insoluble microdomains, leading to stronger PAC1R‐AC interaction and elevated cAMP production. Moreover, we demonstrate that translocation of PAC1R is blocked by various treatments that selectively disrupt caveolae. As a result, intracellular cAMP level is decreased and consequently the PACAP‐induced neurite outgrowth retarded. In contrast, addition of exogenous ganglioside GM1 to the cells shows the opposite effects. These results therefore identify the PACAP‐induced translocation of its G‐protein‐coupled receptor into caveolae, where both AC and the regulating G‐proteins reside, as the key molecular event in activating AC and inducing cAMP‐mediated differentiation of PC12 cells.
The expression of L‐type voltage‐gated calcium channels in retinal photoreceptors is under circadian control
Authors: Ko Michael L. , Liu Yilin , Dryer Stuart E. , Ko Gladys Y.‐P.
Published: August 2007

Photoreceptors are non‐spiking neurons, and their synapses mediate the continuous release of neurotransmitters under the control of L‐type voltage‐gated calcium channels (VGCCs). Photoreceptors express endogenous circadian oscillators that play important roles in regulating photoreceptor physiology and function. Here, we report that the L‐type VGCCs in chick cone photoreceptors are under circadian control. The L‐type VGCC currents are greater when measured during the subjective night than during the subjective day. Using antibodies against the VGCCα1C and VGCCα1D subunits, we found that the immunofluorescence intensities of both VGCCα1C and VGCCα1D in photoreceptors are higher during the subjective night. However, the mRNA levels of VGCCα1D, but not VGCCα1C, are rhythmic. Nocturnal increases in L‐type VGCCs are blocked by manumycin A, PD98059, and KN93, which suggest that the circadian output pathway includes Ras, Erk, and calcium‐calmodulin dependent kinase II. In summary, four independent lines of evidence show that the L‐VGCCs in cone photoreceptors are under circadian control.
Collapsin response mediator protein‐2 hyperphosphorylation is an early event in Alzheimer’s disease progression
Authors: Cole Adam R. , Noble Wendy , Aalten Lidy van , Plattner Florian , Meimaridou Rena , Hogan Dale , Taylor Margaret , LaFrancois John , Gunn‐Moore Frank , Verkhratsky Alex , Oddo Salvatore , LaFerla Frank , Giese K. Peter , Dineley Kelly T. , Duff Karen , Richardson Jill C. , Yan Shi Du , Hanger Diane P. , Allan Stuart M. , Sutherland Calum
Published: August 2007

Collapsin response mediator protein 2 (CRMP2) is an abundant brain‐enriched protein that can regulate microtubule assembly in neurons. This function of CRMP2 is regulated by phosphorylation by glycogen synthase kinase 3 (GSK3) and cyclin‐dependent kinase 5 (Cdk5). Here, using novel phosphospecific antibodies, we demonstrate that phosphorylation of CRMP2 at Ser522 (Cdk5‐mediated) is increased in Alzheimer’s disease (AD) brain, while CRMP2 expression and phosphorylation of the closely related isoform CRMP4 are not altered. In addition, CRMP2 phosphorylation at the Cdk5 and GSK3 sites is increased in cortex and hippocampus of the triple transgenic mouse [presenilin‐1 (PS1)M146VKI; Thy1.2‐amyloid precursor protein (APP)swe; Thy1.2tauP301L] that develops AD‐like plaques and tangles, as well as the double (PS1M146VKI; Thy1.2‐APPswe) transgenic mouse. The hyperphosphorylation is similar in magnitude to that in human AD and is evident by 2 months of age, ahead of plaque or tangle formation. Meanwhile, there is no change in CRMP2 phosphorylation in two other transgenic mouse lines that display elevated amyloid β peptide levels (Tg2576 and APP/amyloid β‐binding alcohol dehydrogenase). Similarly, CRMP2 phosphorylation is normal in hippocampus and cortex of Tau(P301L) mice that develop tangles but not plaques. These observations implicate hyperphosphorylation of CRMP2 as an early event in the development of AD and suggest that it can be induced by a severe APP over‐expression and/or processing defect.
A rapid oxidation and persistent decrease in the vesicular monoamine transporter 2 after methamphetamine
Authors: Eyerman David J. , Yamamoto Bryan K.
Published: August 2007

Methamphetamine (METH) produces long‐term decreases in markers of dopamine (DA) terminals in animals and humans. A decrease in the function of the vesicular monoamine transporter 2 (VMAT2) has been associated with damage to striatal DA terminals caused by METH; however, a possible mechanism for this decrease in VMAT2 function has not been defined. The current study showed that METH caused a rapid decrease to 68% of controls in VMAT2 protein immunoreactivity of the vesicular fraction from striatal synaptosomes within 1 h after a repeated high‐dose administration regimen of METH. This decrease was associated with a 75% increase in nitrosylation of VMAT2 protein in the synaptosomal fraction as measured by nitrosocysteine immunoreactivity of VMAT2 protein. The rapid decreases in VMAT2 persisted when evaluated 7 days later and were illustrated by decreases in VMAT2 immunoreactivity and DA content of the vesicular fraction to 34% and 51% of control values, respectively. The decreases were blocked or attenuated by prior injections of the neuronal nitric oxide synthase inhibitor,S‐methyl‐l‐thiocitrulline. These studies demonstrate that METH causes a rapid neuronal nitric oxide synthase‐dependent oxidation of VMAT2 and long‐term decreases in VMAT2 protein and function. The results also suggest that surviving DA terminals after METH exposure may have a compromised capacity to buffer cytosolic DA concentrations and DA‐derived oxidative stress.
NO‐induced neuroprotection in ischemic preconditioning stimulates mitochondrial Mn‐SOD activity and expression via RAS/ERK1/2 pathway
Authors: Scorziello A. , Santillo M. , Adornetto A. , Dell’Aversano C. , Sirabella R. , Damiano S. , Canzoniero L.M.T. , Renzo G.F. Di , Annunziato L.
Published: August 2007

To identify the transductional mechanisms responsible for the neuroprotective effect of nitric oxide (NO) during ischemic preconditioning (IPC), we investigated the effects of this gaseous mediator on mitochondrial Mn‐superoxide dismutase (Mn‐SOD) expression and activity. In addition, the possible involvement of Ras/extracellular‐regulated kinase (ERK) ERK1/2 pathway in preserving cortical neurons exposed to oxygen and glucose deprivation (OGD) followed by reoxygenation was also examined. Ischemic preconditioning was obtained by exposing neurons to a 30‐min sublethal OGD (95% N2 and 5% CO2). Then, after a 24‐h interval, neurons were exposed to 3 h of OGD followed by 24 h of reoxygenation (OGD/Rx). Our results revealed that IPC reduced cytochrome c (cyt c) release into the cytosol, improved mitochondrial function, and decreased free radical production. Moreover, it induced an increase in nNOS expression and NO production and promoted ERK1/2 activation. These effects were paralleled by an increase in Mn‐SOD expression and activity that persisted throughout the following OGD phase. When the neurons were treated with L‐NAME, a well known NOS inhibitor, the increase in Mn‐SOD expression occurring during IPC was reduced and, as a result, IPC‐induced neuroprotection was prevented. Similarly, when ERK1/2 was inhibited by its selective inhibitor PD98059, the increase in Mn‐SOD expression observed during IPC was almost completely abolished. As a result, its neuroprotective effect on cellular survival was thwarted. The present findings indicate that during IPC the increase in Mn‐SOD expression and activity are paralleled by NO production. This suggests that NO neuroprotective role occurs through the stimulation of Mn‐SOD expression and activity. In particular, NO via Ras activation stimulates downstream ERK1/2 cascade. This pathway, in turn, post‐transcriptionally activates Mn‐SOD expression and activity, thus promoting neuroprotection during preconditioning.
Activation of phospholipase C pathways by a synthetic chondroitin sulfate‐E tetrasaccharide promotes neurite outgrowth of dopaminergic neurons
Authors: Sotogaku Naoki , Tully Sarah E. , Gama Cristal I. , Higashi Hideho , Tanaka Masatoshi , Hsieh‐Wilson Linda C. , Nishi Akinori
Published: August 2007

In dopaminergic neurons, chondroitin sulfate (CS) proteoglycans play important roles in neuronal development and regeneration. However, due to the complexity and heterogeneity of CS, the precise structure of CS with biological activity and the molecular mechanisms underlying its influence on dopaminergic neurons are poorly understood. In this study, we investigated the ability of synthetic CS oligosaccharides and natural polysaccharides to promote the neurite outgrowth of mesencephalic dopaminergic neurons and the signaling pathways activated by CS. CS‐E polysaccharide, but not CS‐A, ‐C or ‐D polysaccharide, facilitated the neurite outgrowth of dopaminergic neurons at CS concentrations within the physiological range. The stimulatory effect of CS‐E polysaccharide on neurite outgrowth was completely abolished by its digestion into disaccharide units with chondroitinase ABC. Similarly to CS‐E polysaccharide, a synthetic tetrasaccharide displaying only the CS‐E sulfation motif stimulated the neurite outgrowth of dopaminergic neurons, whereas a CS‐E disaccharide or unsulfated tetrasaccharide had no effect. Analysis of the molecular mechanisms revealed that the action of the CS‐E tetrasaccharide was mediated through midkine‐pleiotrophin/protein tyrosine phosphatase ζ and brain‐derived neurotrophic factor/tyrosine kinase B receptor pathways, followed by activation of the two intracellular phospholipase C (PLC) signaling cascades: PLC/protein kinase C and PLC/inositol 1,4,5‐triphosphate/inositol 1,4,5‐triphosphate receptor signaling leading to intracellular Ca2+ concentration‐dependent activation of Ca2+/calmodulin‐dependent kinase II and calcineurin. These results indicate that a specific sulfation motif, in particular the CS‐E tetrasaccharide unit, represents a key structural determinant for activation of midkine, pleiotrophin and brain‐derived neurotrophic factor‐mediated signaling, and is required for the neuritogenic activity of CS in dopaminergic neurons.
Effects of Learning about Gender Discrimination on Adolescent Girls' Attitudes Toward and Interest in Science
Authors: Weisgram Erica S. , Bigler Rebecca S.
Published: August 2007

Gender discrimination has contributed to the gender imbalance in scientific fields. However, research on the effects of informing adolescent girls about gender discrimination in these fields is rare and controversial. To examine the consequences of learning about gender-based occupational discrimination, adolescent girls ( n = 158, ages 11 to 14) were randomly assigned to either (a) a standard intervention program aimed at increasing girls' interest in science or (b) a nearly identical program that included information about gender discrimination. Girls' interest in, and attitudes toward, science were assessed using a pre/post design. Only girls who learned about gender discrimination showed increases in science self-efficacy and belief in the value of science; interest in scientific fields was unaffected by the intervention programs. Theoretical and educational implications are discussed.
Exopolymeric substances of sulfate‐reducing bacteria: Interactions with calcium at alkaline pH and implication for formation of carbonate minerals
Authors: BRAISSANT O. , DECHO A. W. , DUPRAZ C. , GLUNK C. , PRZEKOP K. M. , VISSCHER P. T.
Published: August 2007

Sulfate‐reducing bacteria (SRB) have been recognized as key players in the precipitation of calcium carbonate in lithifying microbial communities. These bacteria increase the alkalinity by reducing sulfate ions, and consuming organic acids. SRB also produce copious amounts of exopolymeric substances (EPS). All of these processes influence the morphology and mineralogy of the carbonate minerals. Interactions of EPS with metals, calcium in particular, are believed to be the main processes through which the extracellular matrix controls the precipitation of the carbonate minerals. SRB exopolymers were purified from lithifying mat and type cultures, and their potential role in CaCO3 precipitation was determined from acid‐base titrations and calcium‐binding experiments. Major EPS characteristics were established using infrared spectroscopy and gas chromatography to characterize the chemical functional groups and the sugar monomers composition. Our results demonstrate that all of the three SRB strains tested were able to produce large amounts of EPS. This EPS exhibited three main buffering capacities, which correspond to carboxylic acids (pKa = 3.0), sulfur‐containing groups (thiols, sulfonic and sulfinic acids – pKa = 7.0–7.1) and amino groups (pKa = 8.4–9.2). The calcium‐binding capacity of these exopolymers in solution at pH 9.0 ranged from 0.12gCa gEPS−1–0.15 gCa gEPS−1. These results suggest that SRB could play a critical role in the formation of CaCO3 in lithifying microbial mats. The unusually high sulfur content, which has not been reported for EPS before, indicates a possible strong interaction with iron. In addition to changing the saturation index through metabolic activity, our results imply that SRB affect the rock record through EPS production and its effect on the CaCO3 precipitation. Furthermore, EPS produced by SRB may account for the incorporation of metals (e.g. Sr, Fe, Mg) associated with carbonate minerals in the rock record.
Loss of pregnancy‐associated plasma protein A extends lifespan in mice
Authors: Conover Cheryl A. , Bale Laurie K.
Published: August 2007

Genetic deletion in mice of pregnancy‐associated plasma protein A (PAPP‐A), a recently identified metalloproteinase in the insulin‐like growth factor system, extends by 30–40% both mean and maximum lifespan with no reduction in food intake or secondary endocrine abnormalities. Furthermore, these mice have markedly reduced incidence of spontaneous tumors. The findings implicate PAPP‐A as a critical regulator of lifespan and age‐related diseases, and suggest PAPP‐A as a possible target to promote longevity.
Reliability of knee extension and flexion measurements using the Con‐Trex isokinetic dynamometer
Authors: Maffiuletti Nicola A. , Bizzini Mario , Desbrosses Kevin , Babault Nicolas , Munzinger Urs
Published: August 2007

The aim of this study was to evaluate the reliability of isokinetic and isometric assessments of the knee extensor and the flexor muscle function using the Con‐Trex isokinetic dynamometer. Thirty healthy subjects (15 males, 15 females) were tested and retested 7 days later for maximal strength (isokinetic peak torque, work, power and angle of peak torque as well as isometric maximal voluntary contraction torque and rate of torque development) and fatigue (per cent loss and linear slope of torque and work across a series of 20 contractions). For both the knee extensor and the flexor muscle groups, all strength data – except angle of peak torque – demonstrated moderate‐to‐high reliability, with intraclass correlation coefficients (ICC) higher than 0·86. The highest reliability was observed for concentric peak torque of the knee extensor muscles (ICC = 0·99). Test–retest reliability of fatigue variables was moderate for the knee extensor (ICC range 0·84–0·89) and insufficient‐to‐moderate for the knee flexor muscles (ICC range 0·78–0·81). The more reliable index of muscle fatigue was the linear slope of the decline in work output. These findings establish the reliability of isokinetic and isometric measurements using the Con‐Trex machine.
Calibrated photoplethysmographic estimation of digital pulse volume and arterial compliance
Authors: Raamat Rein , Jagomägi Kersti , Talts Jaak
Published: August 2007

Digital pulse volume and arterial compliance have been estimated by using the finger arterial pressure and volume waveforms when performing measurements at rest and during local cold exposure in 17 volunteers. The amplitude‐based algorithm determines compliance as a ratio of finger volume and pressure pulses. Cooling was conducted by immersion of the contra‐lateral arm in water at 11°C for 2 min. Continuous non‐invasive finger blood pressure was measured by the Finapres monitor, while the finger volume pulses were recorded by the UT9201 physiograph, which provides a photoplethysmographic registration of volume changes in a large range of transmural pressures (Ptransm). The photoplethysmographic signal was calibrated by applying a graded modulation to the cuff. The study demonstrated that contra‐lateral arm cooling induced a statistically significant (P<0·001) reduction in the digital arterial compliance at Ptransm ≈ 0 as well as at Ptransm = 50 mmHg. The median compliance diminished during cooling from 0·67 mm3 mmHg−1 to the level of 55% at Ptransm ≈ 0, and from 0·14 mm3 mmHg−1 to the level of 42% at Ptransm = 50 mmHg respectively. The observed changes were mostly due to the reduction in the pulse volume. Digital arterial pressure and volume waveforms recorded by the Finapres monitor combined with a calibrated photoplethysmograph can be used in estimating the absolute values of the dynamic compliance of finger arteries. A quantitative estimation instead of the non‐calibrated recording of the digital pulse volume allows shortening the variability and widening the scope of finger arterial compliance measurements.
Experimental Investigation of the Static Behaviour of a Hole Drilled Steel Plate Reinforced with a Composite Patch
Authors: Tsouvalis N. G. , Mirisiotis L. S.
Published: August 2007

Abstract:  This paper presents an experimental investigation of the efficiency of a carbon/epoxy composite patch for reinforcing a steel plate with a central hole, loaded in static tension. Patches were laminated on one‐side of the steel plate using the conventional hand lay‐up method. Common, low cost composite materials were used, in an effort to assess the effectiveness of a repair or reinforcement that could be executed in situ in the harsh marine environment of a ship by properly trained crew personnel. Various methods were investigated for the steel surface preparation before patch lamination and corresponding roughness measurements were performed. Strains were monitored at three different positions of the specimens. Despite the low stiffness ratio of the patch reinforcements, experimental measurements indicated an extension of the linear response of the specimens, a smoother transition to plasticity and an increase in the failure load ranging from 30% to 50%.