bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of supplementary foods by Australian magpies Gymnorhina tibicen: Implications for wildlife feeding in suburban environments
Authors: O’LEARY REBECCA , JONES DARRYL N.
Published: March 2006

Abstract  The provision of foods to wild birds is an extremely common practice among householders throughout the Western world. Nonetheless, concerns over potential impacts of the practice are currently being raised, including the possibility that some species may become reliant on human‐provided food. We compared the foraging and breeding ecology of pairs of fed and unfed Australian magpies Gymnorhina tibicen living in suburban environments in Brisbane, Queensland, Australia. Detailed behavioural observations of both foraging and chick provisioning were made for males and females of both groups throughout the breeding season. Natural foods dominated the diets of both fed and unfed magpies, making up 76% and 92% of all items consumed respectively. During the morning, fed magpies obtained fewer food items during ground foraging than did unfed birds, apparently because they visited suburban feeding stations more often during the early part of the day. At other times, the amount of food items obtained during foraging was similar for both fed and unfed birds. Magpies utilizing suburban feeding stations started all breeding activities significantly earlier than unfed magpies, except during the fledgling phase. Both fed and unfed magpie parents provisioned their chicks predominantly with natural food. Magpies were not reliant or dependent on supplementary food provided by wildlife feeders at any time during the breeding season. Although many magpies did utilize suburban feeding stations extensively, they continued to forage for and provision their chicks with natural food.
Mussel beds on different types of structures support different macroinvertebrate assemblages
Authors: PEOPLE J.
Published: March 2006

Abstract  Artificial structures, such as seawalls, pilings and pontoons, are common features of urban estuaries. They replace natural structures or add to the amount of hard substratum in an area and provide habitats for many fish and invertebrates. Previous work has concentrated on fish or on the invertebrates that occupy the primary substratum of artificial structures. Mussels often grow on different types of structures (pontoons, pilings, seawalls and natural reefs) and provide a secondary substratum for other organisms to inhabit. Counting and identifying organisms associated with mussel beds is traditionally done to species level, which is very time‐consuming. To save time, organisms in this study were identified to coarse levels of taxonomic resolution (a mix of taxa, such as class, order, family and genus), which showed similar patterns to those when particularly speciose and abundant groups were identified to species. This study tests hypotheses that the distribution and abundance of mobile and sessile organisms that inhabit mussel beds will differ among natural and various types of artificial structures. When the associated assemblages of mussel beds from different types of structures and from different locations were examined, assemblages varied according to the type of structure they inhabited and its location. Assemblages associated with mussels on pontoons differed consistently from those on other types of structures. Patterns in the assemblages were also consistent through time. These data show that the types and amounts of artificial structures added to an environment can affect the types, distribution and abundances of organisms living in biogenic habitats.
Roost tree characteristics determine use by the white‐striped freetail bat (Tadarida australis, Chiroptera: Molossidae) in suburban subtropical Brisbane, Australia
Authors: RHODES MONIKA , WARDELL‐JOHNSON GRANT
Published: March 2006

Abstract  We examined factors affecting roost tree selection by the white‐striped freetail bat Tadarida australis (Chiroptera: Molossidae), a large insectivorous bat in suburban Brisbane, Australia. We compared biophysical characteristics associated with 34 roost trees and 170 control trees of similar diameter, height and tree senescence characters. Roost trees used by the white‐striped freetail bat had significantly higher numbers of hollows in the trunk and branches (P < 0.003) and were more likely to contain a large trunk cavity with an internal diameter of >30 cm (P < 0.001) than control trees. These trees also accommodated more species of hollow‐using fauna (P = 0.005). When comparing roost trees with control trees of similar diameters and heights, roost trees were on average at a later stage of tree senescence (P < 0.001). None of the roost trees were found in the large forest reserves fringing the Brisbane metropolitan area despite these areas being used for foraging by the white‐striped freetail bat. Although all tree locations in this study were in modified landscapes, roost trees tended to be surrounded by groups of trees and undergrowth. Roost trees provide important habitat requirements for hollow‐using fauna in suburban, rural and forested environments.
Modelling the occurrence of rainbow lorikeets (Trichoglossus haematodus) in Melbourne
Authors: SHUKUROGLOU PAVLINA , MCCARTHY MICHAEL A.
Published: March 2006

Abstract  Over the previous three decades, the rainbow lorikeet (Trichoglossus haematodus Family Psittacidae) has increased in urbanized areas of Australia. To help understand the nature of this increase, we investigated the influence of road density, tree cover and season on the occurrence of the rainbow lorikeet in the Melbourne region. Bayesian logistic regression was used to construct models to predict the occurrence of rainbow lorikeets, using Birds Australia atlas data at 207 2‐ha sites. The results demonstrate a strong relationship between tree cover and urbanization and the distribution of the species. The best model incorporated quadratic terms for road density and tree cover, and interaction terms, as well as season as a categorical variable. Probability of occurrence of rainbow lorikeets was highest at medium tree cover (40% to 70% of the site covered) and medium road density (9% to 12% of the surrounding area covered by roads). There was a close correspondence between the predictions of the model and new observations from bird surveys conducted at randomly selected field sites. The increased abundance of the species in urban areas has occurred despite a paucity of hollows that would act as suitable nesting sites, suggesting that only a small proportion of the population is breeding in these areas.
Microsatellites for ecologists: a practical guide to using and evaluating microsatellite markers
Authors: Selkoe Kimberly A. , Toonen Robert J.
Published: March 2006

Recent improvements in genetic analysis and genotyping methods have resulted in a rapid expansion of the power of molecular markers to address ecological questions. Microsatellites have emerged as the most popular and versatile marker type for ecological applications. The rise of commercial services that can isolate microsatellites for new study species and genotype samples at reasonable prices presents ecologists with the unprecedented ability to employ genetic approaches without heavy investment in specialized equipment. Nevertheless, the lack of accessible, synthesized information on the practicalities and pitfalls of using genetic tools impedes ecologists’ ability to make informed decisions on using molecular approaches and creates the risk that some will use microsatellites without understanding the steps needed to evaluate the quality of a genetic data set. The first goal of this synthesis is to provide an overview of the strengths and limitations of microsatellite markers and the risks, cost and time requirements of isolating and using microsatellites with the aid of commercial services. The second goal is to encourage the use and consistent reporting of thorough marker screening to ensure high quality data. To that end, we present a multistep screening process to evaluate candidate loci for inclusion in a genetic study that is broadly targeted to both novice and experienced geneticists alike.
Evaluating the Characteristics of Corporate Boards Associated with Layoff Decisions
Authors: Yawson Alfred
Published: March 2006

The paper evaluates the characteristics of corporate boards associated with layoff decisions using a large sample of UK firms suffering performance declines over the period 1994–2003. The results show that firms are less likely to respond to performance declines with employee layoffs when they have large boards. Further analysis shows that layoff decisions are positively associated with the proportion of outside directors and directors’ remuneration. The findings provide some support to the recommendations of the Cadbury Report (1992) and Higgs Review (2003) on the importance of the structure and composition of board of directors in the corporate governance process.
Governance System Effectiveness Following the Crisis: the case of Korean business group headquarters
Authors: Chang James Jinho , Shin Hyun‐Han
Published: March 2006

Various corporate governance initiatives were adopted in Korea following a major corporate governance failure, identified as a direct cause of the Asian Financial Crisis of 1997–1998. Our findings indicate that, before the crisis, the likelihood of replacing poorly performing CEOs was not related to business group (chaebol) affiliation. However, after the Asian Financial Crisis, we find CEO turnover sensitivity to performance is greater in chaebol firms than in stand‐alone firms. These findings indicated improved monitoring following reforms initiated by the Korean government, NGOs and other capital market participants. These findings have implications for the effectiveness of corporate governance in US firms following governance restructuring imposed by the SEC, the government and various market participants.
Boards of Directors of Publicly‐Held Companies in Brazil: profile and implications for minority shareholders
Authors: Saito Richard , Dutra Marcos Galileu Lorena
Published: March 2006

We analyse the profile of the boards of directors of 142 Brazilian publicly‐held companies in 1999. Directors were divided into four distinct categories, following Bhagat and Black (2000 Working Paper no. 143, Columbia Law School) criteria for the US market. Our survey analyses the degree of independence of directors in relation to their respective controlling shareholders. Our results indicate that the controlling shareholders’ representatives largely dominate the boards. One intriguing finding is that minority shareholders do not use the mechanisms at their disposal to elect directors. There seems to be low interest by non‐controlling shareholders in participating in shareholders’ meetings, and consequently in selecting representatives for the board of directors. This could partly be explained by the lack of proxy voting mechanisms.
The Implementation of Corporate Governance Principles in an Emerging Economy: a critique of the situation in Cyprus
Authors: Krambia‐Kapardis Maria , Psaros Jim
Published: March 2006

When the Cyprus economy was booming in the 1990s, key issues emanating from sound corporate governance, such as accountability, transparency and effective independent boards were not deemed important. However, largely as a result of the Cyprus stock exchange collapse of 2000, this view changed. In September 2002, due to the collapse, the Cyprus Stock Exchange implemented a Corporate Governance Code predicated largely on Anglo‐Saxon principles of corporate governance.

This paper reports the result of a study into levels of compliance with the Code by companies listed on the Cyprus Stock Exchange. The findings indicate that only a small minority complied with all significant aspects of the Code, and the vast majority did not comply with any. While the Code was well intended, the intended reforms do not appear to have significantly improved corporate governance. This is perhaps not surprising, given that the Cyprus equity markets and corresponding legislative support pertaining to corporate governance are in their infancy. In addition, some typical free market controls (e.g. low degree of concentration of ownership, reliable and timely information flows and opportunities for investor diversification) that facilitate international institutional investment do not exist in Cyprus. This suggests that the introduction of a Corporate Governance Code in Cyprus, or other developing economies, is likely to have only minimal impact unless it is supported by other initiatives. However, recent developments in Cyprus relating to greater education as to the benefits of corporate governance, as well as more stringent listing rules for companies lacking aspects of corporate governance, suggest that Cyprus is making serious endeavours to improve the corporate governance of its listed companies.
Wavelet-based Functional Mixed Models
Authors: Morris Jeffrey S. , Carroll Raymond J.
Published: March 2006

Increasingly, scientific studies yield functional data, in which the ideal units of observation are curves and the observed data consist of sets of curves that are sampled on a fine grid. We present new methodology that generalizes the linear mixed model to the functional mixed model framework, with model fitting done by using a Bayesian wavelet-based approach. This method is flexible, allowing functions of arbitrary form and the full range of fixed effects structures and between-curve covariance structures that are available in the mixed model framework. It yields nonparametric estimates of the fixed and random-effects functions as well as the various between-curve and within-curve covariance matrices. The functional fixed effects are adaptively regularized as a result of the non-linear shrinkage prior that is imposed on the fixed effects’ wavelet coefficients, and the random-effect functions experience a form of adaptive regularization because of the separately estimated variance components for each wavelet coefficient. Because we have posterior samples for all model quantities, we can perform pointwise or joint Bayesian inference or prediction on the quantities of the model. The adaptiveness of the method makes it especially appropriate for modelling irregular functional data that are characterized by numerous local features like peaks.
Nonparametric Methods for Solving the Berkson Errors-in-Variables Problem
Authors: Delaigle Aurore , Hall Peter , Qiu Peihua
Published: March 2006

It is common, in errors-in-variables problems in regression, to assume that the errors are incurred ‘after the experiment’, in that the observed value of the explanatory variable is an independent perturbation of its true value. However, if the errors are incurred ‘before the experiment’ then the true value of the explanatory variable equals a perturbation of its observed value. This is the context of the Berkson model, which is increasingly attracting attention in parametric and semiparametric settings. We introduce and discuss nonparametric techniques for analysing data that are generated by the Berkson model. Our approach permits both random and regularly spaced values of the target doses. In the absence of data on dosage error it is necessary to propose a distribution for the latter, but we show numerically that our method is robust against that assumption. The case of dosage error data is also discussed. A practical method for smoothing parameter choice is suggested. Our techniques for errors-in-variables regression are shown to achieve theoretically optimal convergence rates.
Generalized Linear Array Models with Applications to Multidimensional Smoothing
Authors: Currie I. D. , Durban M. , Eilers P. H. C.
Published: March 2006

Data with an array structure are common in statistics, and the design or regression matrix for analysis of such data can often be written as a Kronecker product. Factorial designs, contingency tables and smoothing of data on multidimensional grids are three such general classes of data and models. In such a setting, we develop an arithmetic of arrays which allows us to define the expectation of the data array as a sequence of nested matrix operations on a coefficient array. We show how this arithmetic leads to low storage, high speed computation in the scoring algorithm of the generalized linear model. We refer to a generalized linear array model and apply the methodology to the smoothing of multidimensional arrays. We illustrate our procedure with the analysis of three data sets: mortality data indexed by age at death and year of death, spatially varying microarray background data and disease incidence data indexed by age at death, year of death and month of death.
Variance Stabilization for a Scalar Parameter
Authors: DiCiccio Thomas J. , Monti Anna Clara , Alastair Young G.
Published: March 2006

We present a variance stabilizing transformation for inference about a scalar parameter that is estimated by a function of a multivariate M-estimator. The transformation proposed is automatic, computationally simple and can be applied quite generally. Though it is based on an intuitive notion and entirely empirical, the transformation is shown to have an appropriate justification in providing variance stabilization when viewed from both parametric and nonparametric perspectives. Further, the transformation repairs deficiencies of existing methods for variance stabilization. The transformation proposed is illustrated in a range of examples, and its effectiveness to yield confidence limits having low coverage error is demonstrated in a numerical example.
Functional Clustering by Bayesian Wavelet Methods
Authors: Ray Shubhankar , Mallick Bani
Published: March 2006

We propose a nonparametric Bayes wavelet model for clustering of functional data. The wavelet-based methodology is aimed at the resolution of generic global and local features during clustering and is suitable for clustering high dimensional data. Based on the Dirichlet process, the nonparametric Bayes model extends the scope of traditional Bayes wavelet methods to functional clustering and allows the elicitation of prior belief about the regularity of the functions and the number of clusters by suitably mixing the Dirichlet processes. Posterior inference is carried out by Gibbs sampling with conjugate priors, which makes the computation straightforward. We use simulated as well as real data sets to illustrate the suitability of the approach over other alternatives.
Democratizing the workplace through professionalization of human resource development*
Authors: Hatcher Tim
Published: March 2006

This article critically examines democratizing the workplace through the professionalization of HRD. The primary question the article seeks to explore is to what extent can a democratic profession potentially minimize undemocratic workplaces. Drawing from several conceptual and research bodies of literature, including democracy and democratic workplaces, globalization and sociology of professions, this article describes democracy and how professions can enhance its growth.
Choice, diversity and ‘false consciousness’ in women's careers
Authors: Caven Val
Published: March 2006

The central theme of this paper is that contemporary literature concerning women's careers is based on assumptions held by researchers and not actually on views held by women themselves. Many feminist researchers are guilty of assuming ‘false consciousness’ on the part of their subjects by explaining these women as being victims of gender or patriarchal systems instead of making a mindful decision founded on choice. The empirical work draws on in‐depth interviews with 39 women architects. Of the 39 women interviewed, 20 had adopted alternative ways of working in the sense that they had rejected the conventional career within an organization. Their reasons for this were diverse and ranged from wanting to combine child or elder care with work; involvement in local politics; wanting time for further study or sporting activities; as well as just not wanting to work full‐time. In short, this research demonstrates that work is not always a central interest in the lives of individuals and supports Hakim's view of heterogeneity among women.
Critically challenging some assumptions in HRD
Authors: O'Donnell David , McGuire David , Cross Christine
Published: March 2006

This paper sets out to critically challenge five interrelated assumptions prominent in the (human resource development) HRD literature. These relate to: the exploitation of labour in enhancing shareholder value; the view that employees are co‐contributors to and co‐recipients of HRD benefits; the distinction between HRD and human resource management; the relationship between HRD and unitarism; and the relationship between HRD and organizational and learning cultures. From a critical modernist perspective, it is argued that these can only be adequately addressed by taking a point of departure from the particular state of the capital–labour relation in time, place and space. HRD, of its nature, exists in a continuous state of dialectical tension between capital and labour – and there is much that critical scholarship has yet to do in informing practitioners about how they might manage and cope with such tension.
Incorporating Serotypes into Family Based Association Studies Using the MFG Test
Authors: Minassian S. L. , Palmer C. G. S. , Turunen J. A. , Paunio T. , Lönnqvist J. , Peltonen L. , Woodward J. A. , Sinsheimer J. S.
Published: March 2006

Family based association tests are widely used to detect genetic effects. The focus of this paper is the maternal‐fetal genotype (MFG) incompatibility test, a family based association test which can be used to detect genetic effects that contribute to disease, including alleles in the child that increase disease risk, maternal alleles that increase disease risk in the child, and maternal‐fetal genotype incompatibilities. Consideration of incomplete data resulting from using serotypes could expand the power of the MFG test for detecting genetic effects. Serotypes may be all that are available in certain families, or preferred because of convenience or low cost, and thus a modification of the MFG test will allow optimal use of such data. The modified MFG likelihood can accommodate the incomplete data that result from using serotypes rather than the corresponding codominant genotypes. The modified MFG test was evaluated with serotypes and genotypes from families with members affected with schizophrenia. In addition, simulation studies were performed. Results of the data analyses and simulation studies showed that serotypes can be used to augment genotypes within a sample, to increase power to detect effects when the candidate gene produces serotypes.
Forage selection by mule deer: does niche breadth increase with population density?
Authors: Nicholson M. C. , Bowyer R. T. , Kie J. G.
Published: March 2006

Effects of population density of mule deer Odocoileus hemionus on forage selection were investigated by comparing diet characteristics of two subpopulations of deer in southern California, USA, that differed in population density during winter. Quality of diet for deer, as indexed by faecal crude protein, was higher at the low‐density site than at the high‐density site in winter, when deer densities were different. Quality of diet was similar in summer when both areas had comparable densities of deer. Both outcomes are consistent with predictions from density‐dependent selection of diets by deer. Dietary niche breadth, however, differed in a manner opposite to predictions of niche theory based on diet selection under an ideal‐free distribution. During winter, when differences in density between the two study sites were pronounced, niche breadth along the dietary axis in the low‐density area was twice that of the high‐density site. Generalist herbivores feeding primarily on low‐quality browse at high population density in winter would be expected to increase their dietary breadth by feeding on additional species of plants as they depleted their food supply. Mule deer in our study, however, decreased the breadth of their dietary niche as population density increased. We hypothesize that by rapidly eliminating high‐quality forages from an area by heavy grazing, deer at higher population densities narrowed their dietary niche. Theoretical models for changes in niche dimensions, including the ideal‐free distribution, need to consider such empirical outcomes.
Efficiency of strip‐ and line‐transect surveys of African savanna mammals
Authors: Ogutu J. O. , Bhola N. , Piepho H.‐P. , Reid R.
Published: March 2006

Effective management and conservation of wildlife populations require reliable estimates of population size, which can be difficult and costly to obtain. We evaluated how precision in estimates of herd size and abundance varies with sample size and strip width using two field surveys and bootstrap resampling of the field data. We also examined precision under distance sampling and evaluated the cost‐effectiveness of both survey techniques. Precision in estimates of abundance increased with increasing sample size and varied with strip width independently of sample size. The hazard rate key function was best for five species in two surveys with contrasting visibility conditions. Precision in density was more sensitive to the number of herds sighted than to variation in herd size and effective strip width for distance sampling. Strip counts produced lower abundance estimates but higher precision than distance sampling. We estimated that distance sampling would cost about US$3.1 km−1of transect. Strip counts deserve serious consideration for surveys of species that occur at high densities and form large, loose agglomerations but distance methods are suitable for species occurring at moderate to low densities in areas where visibility varies substantially. Distance sampling may thus need to be supplemented by strip counts to efficiently estimate densities of rare, abundant and highly clustered multi‐species assemblages of African savanna mammals. In small areas, it may often prove necessary to conduct several surveys to obtain adequate sample sizes for distance models.
Age‐specific resource investment strategies: evidence from female Richardson's ground squirrels (Spermophilus richardsonii)
Authors: Broussard D. R. , Michener G. R. , Dobson F. S.
Published: March 2006

To avoid a possible cost to their future survival and/or reproduction, individuals must balance their somatic and reproductive investments. The van Noordwijk and De Jong model of resource investment predicts that investments into reproduction and soma can vary among individuals of a population based on the variation in the total amount of energy that individuals acquire. With principal components analysis (PCA), we created two axes of life history for female Richardson's ground squirrels Spermophilus richardsonii: an index of total energy investment (PC1) and an index of investment tactic (PC2). Using these indices, we examined patterns of resource allocation to reproductive and somatic investments. Because yearling female Richardson's ground squirrels complete growth to adult size during pregnancy and early lactation, their somatic needs exceed those of older, fully grown females. Therefore, we predicted that yearlings would show more evidence of a tradeoff between reproductive and somatic investments compared with older females. Both yearling and older females invested four to five times more mass into their litters than into their own body mass. With increasing total investment, yearling females increased investment in both reproduction and themselves, whereas older females invested relatively more in reproduction than themselves. Regardless of age, females that emerged heavier from hibernation invested fewer resources into themselves and more into their litters. Variation in total energy investment and investment tactic indices was similar for yearling and older females. Contrary to our prediction, however, yearling females showed positive associations between reproductive and somatic investments, whereas older females exhibited showed no significant association between reproductive and somatic investments.
Photoreceptive organs in larvae of Spionidae (Annelida) and Sipuncula
Authors: Radashevsky V. I. , Migotto A. E.
Published: March 2006

A pair of spherical unpigmented ocelli in addition to pigmented eyes have been observed in the anterior part of the prostomium in larvae of more than 40 species of Spionidae examined alive with light microscopy. Ocelli become visible in larvae at the one‐ to three‐segment stage, increase in size as growth proceeds, and probably disintegrate in the course of metamorphosis because they were not observed in adults and settled juveniles. One pair of transparent, spherical bodies is also found in the anterior part of the head of planktotrophic pelagosphera larvae of Sipuncula. These bodies are in a similar position and have a similar appearance and size to unpigmented ocelli in Spionidae larvae. A pair of epidermal invaginations, densely covered with short cilia, is also observed antero‐laterally in the head in pelagospheras of one species. These invaginations appear similar to the nuchal organs present in many polychaete larvae. Photoreceptive organs so far reported for sipunculan larvae comprise only pigmented eyes. Unpigmented ocelli and nuchal organs have never been reported in pelagospheras. Further ultrastructural investigations on sipunculan larvae are encouraged to clarify the composition, function and morphogenesis of transparent, spherical bodies and ciliated invaginations in the anterior part of the head. Such investigations may help to better understand the nature of photoreceptive structures and nuchal organs in Sipuncula, and also contribute to phylogenetic hypotheses regarding relationships of the Sipuncula and Annelida.
Inter‐ and intracellular interactions of Nogo: new findings and hypothesis
Authors: Teng Felicia Y. H. , Ling Belinda M. T. , Tang Bor Luen
Published: March 2006

The molecule Nogo has captured the imagination of many as a possible key player, and therefore therapeutic target, in the pathological settings of central nervous system (CNS) injury and degenerative pathology. Found in both glial cells and neurons, the endogenous, physiological role of Nogo is as yet unknown. Recently reported targeted disruption of the Nogo gene did not result in any obvious neuro‐anatomical or neurological phenotype. Compared with wild‐type mice, Nogo‐deficient mice also did not exhibit a truly convincing enhancement in their ability to regenerate CNS neurons upon injury. Does the molecule have any important physiological function at all? Other recent discoveries of new interacting partners of Nogo at the mitochondria and the CNS paranode suggest intriguing links to the modulation of apoptosis and developmental organization or signalling at the axoglial junction.
GABAB receptors in 5‐HT transporter‐ and 5‐HT1A receptor‐knock‐out mice: further evidence of a transduction pathway shared with 5‐HT1A receptors
Authors: La Cour Clotilde Mannoury , Hanoun Naïma , Melfort Maxette , Hen René , Lesch Klaus‐Peter , Hamon Michel , Lanfumey Laurence
Published: March 2006

The functional properties of GABAB receptors were examined in the dorsal raphe nucleus (DRN) and the hippocampus of knock‐out mice devoid of the 5‐HT transporter (5‐HTT–/–) or the 5‐HT1A receptor (5‐HT1A–/–). Electrophysiological recordings in brain slices showed that the GABAB receptor agonist baclofen caused a lower hyperpolarization and neuronal firing inhibition of DRN 5‐HT cells in 5‐HTT–/– versus 5‐HTT+/+ mice. In addition, [35S]GTP‐γ‐S binding induced by GABAB receptor stimulation in the DRN was approximately 40% less in these mutants compared with wild‐type mice. In contrast, GABAB receptors appeared functionally intact in the hippocampus of 5‐HTT–/–, and in both this area and the DRN of 5‐HT1A‐knock‐out mice. The unique functional changes of DRN GABAB receptors closely resembled those of 5‐HT1A autoreceptors in 5‐HTT–/– mice, further supporting the idea that both receptor types are coupled to a common pool of G‐proteins in serotoninergic neurons.
Caspase‐mediated proteolysis of the polyglutamine disease protein ataxin‐3
Authors: Berke Sarah J Shoesmith , Schmied Francisca A Flores , Brunt Ewout R. , Ellerby Lisa M. , Paulson Henry L.
Published: March 2006

Spinocerebellar ataxia type‐3, also known as Machado‐Joseph Disease, is one of many inherited neurodegenerative disorders caused by polyglutamine‐encoding CAG repeat expansions in otherwise unrelated disease genes. Polyglutamine disorders are characterized by disease protein misfolding and aggregation; often within the nuclei of affected neurons. Although the precise mechanism of polyglutamine‐mediated cell death remains elusive, evidence suggests that proteolysis of polyglutamine disease proteins by caspases contributes to pathogenesis. Using cellular models we now show that the endogenous spinocerebellar ataxia type‐3 disease protein, ataxin‐3, is proteolyzed in apoptotic paradigms, resulting in the loss of full‐length ataxin‐3 and the corresponding appearance of an approximately 28‐kDa fragment containing the glutamine repeat. Broad‐spectrum caspase inhibitors block ataxin‐3 proteolysis and studies suggest that caspase‐1 is a primary mediator of cleavage. Site‐directed mutagenesis experiments eliminating three, six or nine potential caspase cleavage sites in the protein suggest redundancy in the site(s) at which cleavage can occur, as previously described for other disease proteins; but also map a major cleavage event to a cluster of aspartate residues within the ubiquitin‐binding domain of ataxin‐3 near the polyglutamine tract. Finally, caspase‐mediated cleavage of expanded ataxin‐3 resulted in increased ataxin‐3 aggregation, suggesting a potential role for caspase‐mediated proteolysis in spinocerebellar ataxia type‐3 pathogenesis.
Uptake and transport of high‐density lipoprotein (HDL) and HDL‐associated α‐tocopherol by an in vitro blood–brain barrier model
Authors: Balazs Zoltan , Panzenboeck Ute , Hammer Astrid , Sovic Andrea , Quehenberger Oswald , Malle Ernst , Sattler Wolfgang
Published: March 2006

The present study aimed to investigate pathways that contribute to uptake and transcytosis of high‐density lipoproteins (HDLs) and HDL‐associated α‐tocopherol (αTocH) across an in vitro model of the blood–brain barrier (BBB). In primary porcine brain capillary endothelial cells HDL‐associated αTocH was taken up in 10‐fold excess of HDL holoparticles, indicating efficient selective uptake, a pathway mediated by scavenger receptor class B, type I (SR‐BI). SR‐BI was present in caveolae of brain capillary endothelial cells and expressed almost exclusively at the apical membrane. Disruption of caveolae with methyl‐β‐cyclodextrin (CDX) resulted in (mis)sorting of SR‐BI to the basolateral membrane. Immunohistochemistry of porcine brain cryosections revealed SR‐BI expression on brain capillary endothelial cells and presumably astrocytic endfeet. HDL‐associated [14C]αTocH taken up by brain capillary endothelial cells was recovered in sucrose gradient fractions containing the majority of cellular caveolin‐1, the major caveolae‐associated protein. During mass transfer studies using αTocH‐enriched HDL, approximately 50% of cellular αTocH was recovered with the bulk of cellular caveolin‐1 and SR‐BI. Efflux experiments revealed that a substantial amount of cell‐associated [14C]αTocH could be mobilized into the culture medium. In addition, apical‐to‐basolateral transport of HDL holoparticles and HDL‐associated αTocH was saturable. Results from the present study suggest that part of cerebral apolipoprotein A‐I and αTocH originates from plasma HDL transcytosed across the BBB and that caveolae‐located SR‐BI facilitates selective uptake of HDL‐associated αTocH at the BBB.
Modulating huntingtin half‐life alters polyglutamine‐dependent aggregate formation and cell toxicity
Authors: Kaytor Michael D. , Wilkinson Keith D. , Warren Stephen T.
Published: March 2006

A common finding among the expanded polyglutamine disorders is intracellular protein aggregates. Although the precise role of these aggregates in the disease process is unclear, they are generally ubiquitinated, implicating the ubiquitin–proteasome pathway in neuronal degeneration. To investigate the mechanism of aggregate formation, we have developed a cell culture model to express huntingtin designed to have an altered degradation rate through the ubiquitin‐dependent N‐end rule pathway. We fused the first 171 amino acids of huntingtin, containing either a pathogenic or normal polyglutamine tract, to the enhanced green fluorescent protein (EGFP). The half‐life of soluble huntingtin‐EGFP was dependent on the degradation signal and the polyglutamine tract length. However, once huntingtin‐EGFP with a pathogenic tract had aggregated, the protein was extremely stable. Huntingtin‐EGFP with a pathogenic glutamine tract and a shorter half‐life displayed a delayed onset of aggregate formation and was more toxic to transfected cells. These data suggest that rapid clearance through the ubiquitin–proteasome pathway slows aggregate formation, yet increases cellular toxicity. Polyglutamine‐induced neurotoxicity may therefore be triggered by non‐aggregated protein, and aggregate formation itself may be a cellular defense mechanism.
N‐linked glycosylation sites of the motor protein prestin: effects on membrane targeting and electrophysiological function
Authors: Matsuda Keiji , Zheng Jing , Du Guo‐Guang , Klöcker Nikolaj , Madison Laird D. , Dallos Peter
Published: March 2006

Prestin is a motor protein of outer hair cells (OHC) that plays a crucial role in mammalian hearing. Prestin is a putative N‐glycoprotein with three potential N‐linked glycosylation sites. It is not known whether glycosylation affects the function and activity of prestin. Therefore, the effects of N‐glycosylation were investigated by producing single‐point (N163Q and N166Q) or double‐point mutations (NN163/166QQ and NN163/166AA) at putative N‐glycosylation sites. Further, treatment with tunicamycin or glycopeptidase‐F was used to determine the consequences of removing N‐linked glycosylation in wild‐type prestin. We determined the effects of these manipulations on prestin's cell surface expression, molecular mass, glycosylation pattern, and electrophysiological properties in different cell‐types. Data indicate that prestin is a glycoprotein with N‐linked glycosylation sites at N163 and N166. N163 and N166 may have differential programs for synthesis and trimming of the glycans. The N166 site appears to have greater extent of glycosylation than its companion. N‐linked glycosylation is not required for plasma membrane targeting of prestin. Both glycosylated and deglycosylated prestin demonstrate non‐linear capacitance, a signature of prestin's motor function. Compared to glycosylated prestin, the fully de‐glycosylated protein has altered electrophysiological function, with a change in membrane potential at most effective charge transfer to more depolarized values. These data suggest that glycosylation of prestin may quantitatively affect OHC electromotility.
Specific molecular alterations in the norpA‐encoded phospholipase C of Drosophila and their effects on electrophysiological responses in vivo
Authors: Yoon Jaeseung , Leung Hung‐Tat , Lee Seunghee , Geng Chaoxian , Kim Younkyung , Baek Kwanghee , Pak William L.
Published: March 2006

A large number of mutants in the norpA gene, which encodes the phospholipase C (PLC) involved in Drosophila phototransduction, is available for the investigation of the effects of specific amino acid substitutions in PLC on biochemical and electrophysiological properties of these mutants. Of the 47 norpA mutants screened for PLC protein content, all but one (H43) displayed drastically decreased amounts of the protein suggesting that almost any mutational alteration has a deleterious effect on the integrity of the protein. Three new amino acids were identified in the catalytic domains X and Y that are important for PLC catalytic activity and the generation of photoreceptor responses (ERG). One of them was found substituted in H43, which showed a low specific PLC activity, a pronounced decrease in ERG sensitivity, and a wild‐type‐like response termination time. The response termination times obtained from three mutants was found to be approximately inversely proportional to the amount of PLC. In addition, we show that (i) the specific PLC activity is a key factor determining the photoreceptor sensitivity; (ii) the catalytic activity and response termination are separable functions of PLC; and (iii) a mutation in the putative Gα‐interacting C2 domain causes a preferentially strong defect in latency.
Clearing amyloid through the blood–brain barrier
Authors: Zlokovic Berislav V.
Published: March 2006

According to the amyloid hypothesis, accumulation of amyloid β‐peptide (Aβ) in the brain is the primary pathogenic event in Alzheimer's disease (AD). Recent evidence indicates that Aβ within the intravascular space is linked to Aβ deposited in the brain suggesting that transport of Aβ between the brain, blood and cerebrospinal fluid, and across the blood–brain barrier, regulates brain Aβ. Thus, understanding Aβ exchanges between brain and blood, and vice versa, and developing transport‐based systemic Aβ‐lowering strategies may provide new important insights into pathogenesis and therapeutic control of AD.
Accumulation of protein O‐GlcNAc modification inhibits proteasomes in the brain and coincides with neuronal apoptosis in brain areas with high O‐GlcNAc metabolism
Authors: Liu Kan , Paterson Andrew J. , Zhang Fengxue , McAndrew Joanne , Fukuchi Ken‐Ichiro , Wyss J. Michael , Peng Ling , Hu Yong , Kudlow Jeffrey E.
Published: March 2006

All tissues contain the enzymes that modify and remove O‐GlcNAc dynamically from nucleocytoplasmic proteins. These enzymes have been shown to play a role in the control of transcription, vesicular trafficking and, more recently, proteasome function. Modification by O‐GlcNAc of the 19S cap of the proteasome inhibits proteasomal function. Transcripts of both O‐GlcNAc transferase and O‐GlcNAcase are very abundant in the brain, with the highest concentrations in hippocampal neurons and Purkinje cells. When the on‐rate of modification is favored over the off‐rate by intraventricular administration of a drug, streptozocin, these areas of the brain display the most rapid accumulation of O‐GlcNAc. Cerebral proteasome function is reduced and ubiquitin and p53 accumulate in these brain regions, with the subsequent activation of a p53‐dependent transgene and the endogenous Mdm2 gene. Later, some hippocampal cells, but not Purkinje cells, undergo apoptosis. These observations suggest that the O‐GlcNAc system may participate in neurodegeneration, particularly in the hippocampus.
Alterations in ionotropic glutamate receptor subunits during binge cocaine self‐administration and withdrawal in rats
Authors: Tang Wenxue , Wesley Michael , Freeman Willard M. , Liang Bill , Hemby Scott E.
Published: March 2006

Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in glutamatergic function in brain regions associated with reinforcement. Previous studies have examined ionotropic glutamate receptor (iGluR) subunit protein level changes following acute and chronic experimenter‐administered cocaine or after withdrawal periods from experimenter‐administered cocaine. To evaluate whether alterations in expression of iGluRs are associated with cocaine reinforcement, protein levels were assessed after binge (8 h/day, 15 days; 24‐h access, days 16–21) cocaine self‐administration and following 2 weeks of abstinence from this binge. Western blotting was used to compare levels of iGluR protein expression (NR1–3B, GluR1–7, KA2) in the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) of rats. iGluR subunits were altered in a time‐dependent manner in all brain regions studied; however, selective alterations in certain iGluR subtypes appeared to be associated with binge cocaine self‐administration and withdrawal in a region‐specific manner. In the SN and VTA, alterations in iGluR protein levels compared with controls occurred only following binge access, whereas in the striatum and PFC, iGluR alterations occurred with binge access and following withdrawal. In the NAc, GluR2/3 levels were increased following withdrawal compared with binge access, and were the only changes observed in this region. Because subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long‐term biochemical and behavioral effects of cocaine.
Bone morphogenetic proteins and neurotrophins provide complementary protection of septal cholinergic function during phosphatase inhibitor‐induced stress
Authors: Nonner Doris , Panickar Kiran , Barrett Ellen F. , Barrett John N.
Published: March 2006

Cultures of embryonic rat septum were exposed for 24–48 h to 2–5 nm okadaic acid (OA), an inhibitor of pp1A and pp2A phosphatases. This stress killed approximately 75% of neurons. A neurotrophin (NT) combination (nerve growth factor and brain‐derived neurotrophic factor, each 100 ng/mL) plus a bone morphogenetic protein (BMP6 or BMP7, 5 nm) reduced the death of both cholinergic and non‐cholinergic neurons, and preserved choline acetyltransferase (ChAT) activity assayed 2–6 days post‐stress. This NT + BMP combination preserved ChAT activity better than either NTs or BMPs alone, and was effective even if trophic factor addition was delayed until 12 h after stress onset. A general caspase inhibitor (qVD‐OPH, 10 µg/mL) also increased survival of stressed cholinergic neurons, but its protection of ChAT activity was shorter lived than that produced by the NT + BMP combination. Neither the NT + BMP combination nor the caspase inhibitor reduced the OA‐induced increase in tau phosphorylation. These findings indicate that NTs and BMPs have synergistic protective effects against an OA stress, and suggest that at least some of these protective effects occur upstream of caspase activation.
Modulatory action of RFamide‐related peptides on acid‐sensing ionic channels is pH dependent: the role of arginine
Authors: Ostrovskaya O. , Moroz L. , Krishtal O.
Published: March 2006

Acid‐sensing ionic channels (ASICs) are involved in such functions of the sensory nervous system as mechanoreception, nociception and perception of acid taste. Phe‐Met‐Arg‐Phe amide‐related (FMRFa‐related) peptides in µm concentrations slow down the rate of ASICs desensitization. Here we report that this effect is strongly pH dependent: the lower the pH used to activate ASICs, the larger is the modulatory effect of Arg‐Phe amide‐related (RFa‐related) peptides. Pre‐application of the peptides results in a change to the desensitization kinetics of the ASICs‐operated current from monoexponential to biexponential: the fast component retains the control kinetics, whereas the slow one is induced by the peptide. The lower the pH, the larger is the slow component, whereas there is practically no modulation at pH 6.6. Phe‐Met‐Val‐Phe amide (FMVFa), which has neutral valine instead of arginine, similarly modulates the kinetics of ASICs, but does not reveal pH dependence of this action. Thus, positively charged arginine regulates the access of the RFa‐related peptides to the modulatory site. We suggest that the pH dependence of the modulatory action of RFa‐related peptides can be associated with the interaction of a positively charged arginine with histidine residues in the molecule of ASIC.