bluuebunny/crossref_metadata_2025 huggingface dataset:
Females Mated without Sperm Transfer Maintain High Sexual Receptivity in the Wolf Spider Schizocosa malitiosa
Authors: Aisenberg Anita , Costa Fernando G.
Published: June 2005

The mating of the Neotropical lycosid Schizocosa malitiosa is long and complex, involving intense genital stimulation and copulatory courtship. This suggests functions other than just insemination. Previous data indicated that mated females of this species are less sexually receptive than virgins. We hypothesise that copulatory characteristics presented by males during prolonged copulations could be responsible for subsequent female sexual reluctance, and may be selected by cryptic female choice. Our objective was to examine the influence of copulatory behaviour on subsequent female sexual receptivity in S. malitiosa, isolating it from the effects of sperm transfer per se. For this purpose, we obtained males without sperm in their copulatory organs (palpal bulbs), and prevented them from charging their palps by sealing their genital pores immediately after their last moult (treated males). Virgin females were separated into three groups: (i) females exposed once to normal males, (ii) females exposed twice to normal males, and (iii) females exposed first to treated and second to normal males. The results showed that, 3 d after their first mating, females first mated with untreated males were frequently refractory to remating, whereas all those first mated with treated males were receptive. Copulations performed by treated males showed some differences from those performed by normal males, but maintained the basic behavioural pattern with abundant sexual stimulation. The presence of sperm fluids in the female receptacles appears to be the most likely factor generating female remating reluctance. Males may manipulate female responses using receptivity inhibiting substances in their sperm, like those described for insects. Females would first ensure sperm supply, becoming more choosy afterwards. All females, whether mated once or twice, generated similar numbers of progeny, indicating no relationship between number of matings and number of spiderlings.
Co‐Occurrence of Preference Functions and Acceptance Thresholds in Female Choice: Mate Discrimination in the Lesser Wax Moth
Authors: Brandt LaRoy S.E. , Ludwar Bjorn Ch. , Greenfield Michael D.
Published: June 2005

Basic economic models adapted from foraging theory predict that decisions in mate choice may be determined either by ‘best‐of‐n’ preference functions or by sequential rules incorporating acceptance thresholds. However, in some species, more complex determinations that incorporate versions of both protocols are found. To understand the functions of co‐occurring protocols, we studied mating decisions in the lesser wax moth, Achroia grisella (Lepidoptera: Pyralidae), an acoustic species in which females prefer males, the advertisement songs of which are delivered at relatively high ‘pulse‐pair’ rates. In addition to this preference, A. grisella females avoid mating with a male, the song of which does not exceed a minimum pulse‐pair rate, and they hold to this criterion even when no other singing males are present and regardless of song amplitude. Thus, mating decisions are not simply based on acoustic power (pulse‐pair rate × amplitude). We recorded male songs and female responses in an A. grisella population and found that male pulse‐pair rates showed a median of 87/s and ranged from 50 to 115/s, while female acceptance thresholds for male song showed a median of 60/s and ranged from 30 to 105/s. The distributions of thresholds were approximately normal and were not significantly skewed toward the right. Male song rates declined slightly with age, but female thresholds remained stable over the adult lifespan. Both the male and female traits showed significant repeatability within individuals. Whereas phylogenetic inference indicates that hearing in pyralid moths originated as a means of avoiding predation by insectivorous bats, the specific distribution of female acceptance thresholds suggests that currently this protocol does not primarily function to preclude inappropriate, and potentially lethal, responses to bat echolocations: pulse rates in the searching‐phase echolocations used by either aerial‐hawking or substrate‐gleaning bats mostly range from 10 to 20/s, and the lack of positive skew in the distribution of thresholds indicates an absence of directional selection from the left. Rather, we infer that thresholds augment preference functions in A. grisella by precluding mating with males which are markedly inferior in a critical song character. In general, co‐occurring protocols may be important where population density fluctuates markedly, as preference functions may be ineffective in preventing mating with inferior males when density is low.
Information on Resource Quality Mediates Aggression between Male Madagascar Hissing Cockroaches,Gromphadorhina portentosa(Dictyoptera: Blaberidae)
Authors: Guerra Patrick A. , Mason Andrew C.
Published: June 2005

Male Madagascar hissing cockroaches,Gromphadorhina portentosaSchaum (Dictyoptera: Blaberidae) have a well‐defined dominance hierarchy that has been assumed to explain the outcome of most competitive interactions. We studied whether males of this species would alter their level of aggression towards unfamiliar rivals as a function of changing resource availability and value – two factors that are key to aggression levels in non‐hierarchical species. We quantified male aggression as three variables (aggressive state – behaviours measured by their duration; aggressive act – behaviours measured by their frequency of occurrence; aggressive latency – the latency to first aggressive behaviour, either state or act) and tested for any context‐specific variation within each by manipulating both territorial status (males were either residents or intruders) and access to mates (female present or absent). Both the presence of a female and territorial status affected male aggression towards rivals as measured by duration of aggressive state. Highest levels of aggression were displayed by residents when a female was present. These results show that inter‐male aggression inG. portentosais tuned to the immediate expected payoff from fighting, and not exclusively aimed at establishing dominance relationships (which can affect future payoffs).
The Influence of Long‐chain Polyunsaturated Fatty Acids on Total Lipid Fatty Acid Composition of a Canine Mastocytoma Cell Line
Authors: Seidel A. , Gueck T. , Fuhrmann H.
Published: June 2005

Cutaneous mast cells are considered as key immune effectors in the pathogenesis of canine atopic dermatitis (CAD). These cells release immediate‐phase and late‐phase mediators of inflammation. Dietary fatty acids are incorporated in cellular membranes and seem to influence mediator production and release. A dietary intervention with n6‐ and n3‐fatty acids is thought to alleviate clinical symptoms in atopic dogs. The purpose of this study was to examine the effects of n6‐ and n3‐fatty acids on the fatty acid composition of canine mastocytoma cells (C2) as a possible model for CAD. The C2 was cultured in a basic medium called Dulbecco's modified Eagle's medium (DEH) or with additional 14 μmlinoleate (C18:2n6, DEH–LA),γ‐linolenate (C18:3n6, DEH–GLA), arachidonate (C20:4n6, DEH–AA),α‐linolenate (C18:3n3, DEH–LnA), eicosapentaenoate (C20:5n3, DEH–EPA) or docosahexaenoate (C22:6n3, DEH–DHA). Cell growth was examined for 11 days in all media. Cell growth increased from days 1 to 8 and decreased thereafter in all media conditions. The fatty acids supplied did not influence cell growth. The cells were harvested after 8 days for fatty acid analysis. The fatty acid composition was determined by gas chromatography after extraction and trans‐esterification of the lipids. The added fatty acids increased the concentration of these fatty acids in C2 differently (LA 4.9‐fold, GLA 6.9‐fold, AA 6‐fold, LNA 9.3‐fold, EPA 6.5‐fold and DHA 8.4‐fold). Furthermore, elongated and Δ6‐desaturated products of the corresponding fatty acids were significantly elevated. However, Δ5‐desaturated products were not measurable. These results let us assume that C2 has no measurable activity of the Δ5‐desaturase. In case the low activity of Δ5‐desaturase is one of the mechanisms underlying the pathogenesis of CAD, C2 seems to be an adequate model for investigations in CAD.
Effect of Orally Administered Omeprazole on Abomasal Luminal pH in Dairy Calves Fed Milk Replacer*
Authors: Ahmed A. F. , Constable P. D. , Misk N. A.
Published: June 2005

The objective of this study was to determine whether oral administration of omeprazole, a proton‐pump inhibitor, increased abomasal luminal pH in calves fed milk replacer. Four male dairy calves with cannulae in the abomasal body suckled milk replacer (60 ml/kg body weight every 12 h) and were administered a non‐enteric‐coated omeprazole (4 mg/kg body weight every 24 h) in a paste formulation for five successive days. Abomasal luminal pH was continuously measured using miniature glass pH electrodes. On the first day of omeprazole administration, there was a significant (P < 0.05) increase in mean 24‐h pH from 2.89 to 4.17. The mean 24‐h pH on days 2, 3, 4 and 5 of omeprazole administration were 3.85, 4.02, 3.97 and 3.39 respectively. We conclude that oral administration of non‐enteric‐coated omeprazole increased abomasal luminal pH in calves fed milk replacer, but that the effect may decrease over time.
Dose‐dependent Effects of Resistant Potato Starch in the Diet on Intestinal Skatole Formation and Adipose Tissue Accumulation in the Pig
Authors: Lösel D. , Claus R.
Published: June 2005

Resistant starch (RS) intake leads to a reduction of apoptosis in the pig colon and thus to a reduction of skatole in the carcass. To determine the minimal amount of RS which is required for the effect, diets with varying amounts (20, 30 and 40%) of RS were fed to barrows and gilts. Controls were fed instead with 55% pre‐gelatinized starch. Skatole was determined after slaughter in distal colon content and in adipose tissue (flare fat and belly fat). Resistant starch led to a dose‐dependent reduction of skatole in the gut content from 134 μg/g dry matter (controls) to 4.8 μg/g in the 40% group. Flare fat concentrations were decreased from 159 to 20 ng/g fat and belly fat concentrations from 64 to 16 ng/g fat. Strategies to improve sensorial quality by feeding RS continuously or for only 1 week prior to slaughter are discussed.
Alpha‐1‐acid Glycoprotein Inhibits Phorbol Ester‐induced but not Fc‐Receptor‐induced Generation of Reactive Oxygen Species in Bovine Peripheral Blood Neutrophils
Authors: Stakauskas R. , Leibold W. , Pieskus J. , Mironova L. , Schuberth H.‐J.
Published: June 2005

Alpha‐1‐acid glycoprotein (AGP) is an acute‐phase protein with anti‐inflammatory and immunomodulating properties. AGP is described as a potent inhibitor of the production of reactive oxygen species (ROS) in human neutrophils. However, published reports about the mechanism of inhibition are conflicting. The influence of bovine AGP on the production of ROS by bovine peripheral blood polymorphonuclear leucocytes (PMN) was studied using a highly sensitive method approaching its inhibitory mechanism. ROS production in PMN was induced with phorbol 12‐myristate 13‐acetate (PMA) or opsonized Staphylococcus aureus bacteria. ROS generation was quantified and evaluated by flow cytometry. AGP efficiently suppressed PMA, but did not opsonize bacteria‐induced ROS generation in vitro. The suppressive effect was concentration‐dependent and adversely proportional to PMA concentration. The selective inhibitory potential of AGP in comparison with ovalbumin (OVA) and bovine serum albumin (BSA) showed that ROS inhibition was not a mere protein effect. ROS production was suppressed only if AGP and PMA were simultaneously present with PMN. Pre‐incubation of PMN with AGP did not alter the PMN response to PMA. Moreover, AGP could not suppress ROS production after pre‐stimulation of PMN with PMA. Human and bovine AGP did not differ in their inhibitory potential to the PMA‐induced ROS production in bovine, human and equine PMN. The results show that AGP does not modulate bovine neutrophil functions directly, but acts as a scavenger of PMA.
Is Metoclopramide an Alternative to Tramadol in Management of Post‐operative Pain? An Experimental Study*
Authors: Ceyhan A. , Ustun H. , Altunatmaz K. , Ide T. , Unal N.
Published: June 2005

In this study, metoclopramide was compared with other pharmacological agents for preventing post‐operative pain. Sixty Sprague–Dawley male rats, weighing 310–345 g were included in the study; 1 cm surgical incision, including skin, facia, and muscle was made to the plantar surface of rear foot of all anaesthetized rats. Rats were randomized into four groups. In group 1 (group S) 2 cm3 saline, in group 2 (group M) 2 cm3 metoclopramide (5 mg/kg) in group 3 (group T) 2 cm3 tramadol (45 mg/kg), in group 4 (group M + T) half doses of group M and group T was given intraperitoneally. Post‐operative pain was assessed after 2 h, first and second days of incision. Post‐operative pain scores were found to be significantly lower in group M, group T and group M + T when compared with the control group. But there was no significant difference between these groups. We concluded that metoclopramide, with low cost, fewer side‐effects and being significantly effective for preventing post‐operative pain, can be an alternative to tramadol.
Giant Cell Tumour of Bone in a Cat with Extraskeletal Metastases: Pathological and Immunohistochemical Study
Authors: Ferreras M. C. , Fuertes M. , Pérez V. , Benavides J. , García‐Pariente C. , Reyes L. E. , García‐Marín J. F.
Published: June 2005

A case of giant cell tumour of bone (GCTb) in the lung and in a subcutaneous mass located in the right flank, with a probable primary origin in the mid‐diaphysis of the right tibia, was described in a 8‐year‐old female cat. Numerous multinucleated giant cells were homogeneously distributed among a population of ovoid or spindle‐shaped mononuclear cells. All of them were positive for vimentin suggesting a mesenchymal origin. Spindle‐shaped tumour cells resemble fibroblastic cells, showing collagen fibres in their vicinity. Ovoid mononuclear cells are similar to macrophages, with a cytoplasm rich in electron‐dense lysosomes. Multinucleated giant cells appear morphologically similar to osteoclasts. These findings are supported for the positive reaction to tartrate‐resistant acid phosphatase (TRAP) and lysozyme, encountered only in ovoid and multinucleated giant cells. No immunoreactivity against human oestrogen receptors was observed in the nuclei of any neoplastic cells.
Genetic Evaluation of Elbow Angles as Predictors of Elbow Dysplasia in German Shepherd Dogs
Authors: Janutta V. , Hamann H. , Klein S. , Tellhelm B. , Distl O.
Published: June 2005

Elbow angles were measured in X‐rays of both elbows to elucidate the usefulness of such data for selecting against elbow dysplasia (ED) in German shepherd dogs. These measurements record the size, proportions and alignments of the anconeal process (PA), the radius (RA), the olecranon (OL), and the ulnar trochlear notch (UL). The reference system for evaluating the information content of the measurements was the score for ED (ED‐SV) as recommended by the International Elbow Working Group. Data from 2645 X‐rayed dogs born from 1998 to 2001 in 1331 kennels were analysed by using residual maximum likelihood procedures to estimate heritabilities, additive genetic correlations and residual correlations. The pedigree file included 11 426 dogs and contained ancestors for up to six generations. ED‐SV was significantly influenced by sex, by age within sex and by month of birth. The elbow angles were significantly influenced by the month and year of birth, X‐ray positioning of the dog's forelimbs, angle of elbow flection, litter size and number of dogs X‐rayed by the veterinary practitioners. The following heritability estimates were found:h2 = 0.18 ± 0.04 for ED;h2 = 0.76 ± 0.04 for OL;h2 = 0.52 ± 0.05 for PA;h2 = 0.50 ± 0.04 for UL; andh2 = 0.39 ± 0.04 for RA. The additive genetic correlations of ED‐SV with three elbow angles (OL, UL and RA) were close to zero. A higher additive genetic correlation to ED‐SV was found only for PA, for whichrg = 0.31. The distributions of predicted breeding values for susceptibility to ED were not affected by regarding the elbow angles as additional traits in the multivariate prediction procedure. Measurements of elbow angles were thus shown to be unsuitable for use in selection programmes against ED in German shepherd dogs.
Mitochondrial Damage as an Early Event of Monensin‐induced Cell Injury in Cultured Fibroblasts L929
Authors: Souza A. C. , Machado F. S. , Celes M. R. N. , Faria G. , Rocha L. B. , Silva J. S. , Rossi M. A.
Published: June 2005

The present study was designed to identify, submicroscopically, the primary organelle or target structure for monensin in cultured murine fibroblasts L929. In addition, the effect of the drug on cell size and surface membranes of the cells were analysed; cellular proliferation, collagen secretion, and necrosis and apoptosis were re‐evaluated. At the lowest concentration of monensin the foremost ultrastructural alteration occurred in the mitochondria, characterized by increased matrix density with disorganized and less distinct crystae. Incubation with monensin at higher concentrations resulted in severe mitochondrial damage and marked dilatation of the Golgi apparatus and rough endoplasmic reticulum cisternae. Fibroblasts exposed to higher concentrations of monensin were enlarged with decreased number of filopodia and hollows in the surface membrane. Moreover, monensin inhibited the cell proliferation, increased immunohistochemical positiveness for collagen type I in a dose‐dependent manner, and, at high concentrations, caused cell necrosis whereas apoptosis was not induced. Taken together, these results show that monensin induces early mitochondrial damage, possibly causing an energy deficit that led to inhibition of fibroblasts proliferation and accumulation of collagen causing dilatation of Golgi apparatus and rough endoplasmic reticulum. Moreover, the mitochondrial damage would also explain the monensin‐induced necrosis.
World Risk Society and War against Terror
Authors: Spence Keith
Published: June 2005

I interpret the ‘war against terror’, declared following September 11 2001, as adopting concepts drawn from the work of Ulrich Beck, as a projection of world risk society. Despite its global character, war against terror is constructed through outmoded vocabularies of national security and sovereignty, within which the reasoned negotiation of risk is marginalized. This exclusion contributes to the intensification rather than reduction of terror and terrorism. In so doing the moment of violence inscribed within the concept of the political resurfaces in the constitution of war against terror, Homeland Security, and the identities and anxieties that they reproduce. Contrary to Slavoj Žižek's claim that risk society is incapable of resolving the dilemmas that it exposes, Beck's approach cuts across established ideological and methodological boundaries, anticipating key transformations of discourse required to address the prevailing global predicament through the vocabularies and logic of cosmopolitan risk, rather than those of absolute security, terror and war.
Before, during and after: Realism, Reflexivity and Ethnography
Authors: Roberts John Michael , Sanders Teela
Published: June 2005

In this paper we argue that what is missing from many ethnographic accounts is a recognition that dilemmas inevitably emerge for the researcher before they make contact with the research setting, during the process of ethnographic research, and subsequently in the lengthy time taken to unravel the theoretical importance of the research after the fieldwork has ended. Using a comparison of two ethnographies as case studies, and by recourse to a realist methodology, such dilemmas are, we argue, overdetermined by many non-observable social structures that influence the everyday research process. We argue that specific mechanisms determine both the process and the outcome of the ethnographic journey in the before, during and after stages of research. For example we demonstrate how biography and the wider process of institutional knowledge production are two key resources that influence research practice. We use the term pragmatic realism as a means to reflect upon some of the connections between the dilemmas of research and real structures in these three stages.
Learning Democratic Reason: The Adult Education Project of Jürgen Habermas
Authors: Brookfield Stephen
Published: June 2005

The work of Jürgen Habermas is often cited in adult educational literature as underpinning dialogic traditions and practices central to the field. But to many adult educators the density of Habermas's analysis and complexity of his language limit his influence on their practice. This article's intent is to render a comprehensive analysis of the totality of Habermas's work that demonstrates its enduring applicability for the adult education movement's traditional concern with developing in learners and citizens the critical reasoning necessary to democracy. In so doing the author relies strongly on Habermas's own words (rather than on secondary interpretations of these) and attempts to communicate Habermas's complex ideas in an accessible manner.
Historical and Contemporary Explorations of the Social Change and Spiritual Directions of Adult Education
Authors: English Leona M.
Published: June 2005

This article addresses twin purposes of adult education: education for social change and education for spiritual growth. In reviewing the historical roots for both purposes, as well as emergent contemporary interests, the author makes the case that renewed attention is being, and ought to be, given to these purposes both by academics and by practitioners. The author argues that mining the field's history for its underlying inspirations and foci (read: purposes) may indeed be one way to address present struggles and to offer a way forward for adult education. Attention is given to key events in our present-day thinking and to the repository of adult education history, in order to explicate the long commitment of adult educators to spiritual and social change concerns.
Smith'sSentiments(1759) and Wright'sPassions(1601): the beginnings of sociology
Authors: Barbalet Jack
Published: June 2005

Treatments of sources of Adam Smith's sociological theory of the self and associated ideas inThe Theory of Moral Sentimentstypically refer to classical antecedents or the work of his teacher Francis Hutcheson or his contemporary David Hume. During the seventeenth century, however, many books on the passions were published in London that arguably constitute an important but neglected source of Smith's treatment of moral sentiments. These works are largely forgotten today but at the time were widely read. They are not philosophical, partly devotional and predominantly psychological. Although Smith does not refer to these works his argument resembles theirs in many places. The importance of the seventeenth‐century books on the passions, apart from their role in the history of psychology, is their bearing on contemporary economic practices. In this paper the connections between Smith and one of these books, Thomas Wright'sThe Passions of the Minde in Generall, are indicated.
Symbolic interactionism and the concept of power
Authors: Dennis Alex , Martin Peter J.
Published: June 2005

Symbolic interactionism is often represented as a perspective which is limited by its restriction to ‘micro’ aspects of social organization. As such, it is allegedly unable to adequately conceptualize ‘macro’ phenomena such as social structure, patterns of inequality, and power. Such a view is routinely presented in undergraduate textbooks. This paper contests such a view through a consideration of the concept of power. We argue that the interactionist research tradition does show a fundamental concern with power phenomena, and that a reconsideration of the concept is timely in light of theoretical developments in sociology more generally. An increasing concern with the analysis of culture, the continuing influence of Foucault, the development of feminist perspectives, and the emerging consensus around neo‐Weberian thought have all contributed to a renewal of interest in themes long ago explored by interactionists. As examples we suggest that interactionist studies in the fields of deviance and education have been concerned above all with the authoritative imposition of consequential identities, i.e., with the social processes through which power is enacted and institutionalized in real situations. Such developments have led some to argue that interactionism has now been incorporated into the mainstream of sociology. We conclude, however, by arguing that such a view runs the risk of granting to orthodox sociological thought a legitimacy which is analytically unwarranted, and which fails to recognize the alternative theoretical and philosophical foundations of symbolic interactionist thought.
Choosing Buddhism in Australia: towards a traditional style of reflexive spiritual engagement1
Authors: Phillips Tim , Aarons Haydn
Published: June 2005

There has been little dedicated sociological research on the appeal Buddhism holds for many individuals in the West. It is suggested that this absence reflects a current tendency within the discipline to highlight a new age approach to spiritual involvement and to overlook other optional styles of engagement. Such a pattern of study is concerning because the propensity to privilege the new age style would seem to be less an outcome of a coherent research agenda than a result of the currency that the idea of postmodern religion has come to assume in theoretical accounts of spiritual transformation in contemporary societies. Using data from a modest quantitative survey, the study investigates spiritual style among a sample of Australians who have developed an interest in Buddhist practice and belief. The results point to the prevalence of a traditional approach to involvement, whereby the individual decides to engage solely with Buddhism for the long duration. Given its possession of these qualities, the research goes on to examine the social patterning of spiritual commitment. The findings suggest that comprehending the social restrictions to any kind of involvement is a more pressing sociological question than explaining social divergences among the engaged.
Reciprocity in relationships: socio‐economic and health influences on intergenerational exchanges between Third Age parents and their adult children in Great Britain
Authors: Grundy Emily
Published: June 2005

In this paper data from a nationally representative British longitudinal study are used to analyse exchanges of support between Third Age parents (aged 55–75) and their adult children. Results show that between two thirds and three quarters of parents in this age group were involved in some sort of exchange relationship with at least one of their children. Generally, more Third Age parents were providers than recipients of help, but there was a strong reciprocal element to intergenerational exchange with, for example, married parents who provided support to at least one child being twice as likely as those who did not to receive support from a child, after allowance for a range of relevant parental and child characteristics. Parental characteristics associated with higher probability of providing help included higher income, home ownership and being married or widowed rather than divorced. Higher income and home ownership were, however, negatively associated with odds of receiving help from a child, again after adjustment for other co‐variates, suggesting socio‐economic differences in the balance of support exchanges. Children seem responsive to parental needs in that receipt of help from a child was positively associated with older parental age and with parental disability. The paper shows that in Britain, as in the USA, the balance of intergenerational exchanges involving Third Age adults is downward rather than upward, in contravention of depictions of older adults as ‘burdens’ on younger generations. Current demographic and social changes are, it is argued, likely to increase support demands from adult children to Third Age parents in coming decades.
2004 American Sociological Association Presidential address: For public sociology*
Authors: Burawoy Michael
Published: June 2005

Responding to the growing gap between the sociological ethos and the world we study, the challenge of public sociology is to engage multiple publics in multiple ways. These public sociologies should not be left out in the cold, but brought into the framework of our discipline. In this way we make public sociology a visible and legitimate enterprise, and, thereby, invigorate the discipline as a whole. Accordingly, if we map out the division of sociological labor, we discover antagonistic interdependence among four types of knowledge: professional, critical, policy, and public. In the best of all worlds the flourishing of each type of sociology is a condition for the flourishing of all, but they can just as easily assume pathological forms or become victims of exclusion and subordination. This field of power beckons us to explore the relations among the four types of sociology as they vary historically and nationally, and as they provide the template for divergent individual careers. Finally, comparing disciplines points to the umbilical chord that connects sociology to the world of publics, underlining sociology's particular investment in the defense of civil society, itself beleaguered by the encroachment of markets and states.
Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease
Authors: Pineda José R. , Canals Josep M , Bosch Miquel , Adell Albert , Mengod Guadalupe , Artigas Francesc , Ernfors Patrik , Alberch Jordi
Published: June 2005

Dysfunction of dopaminergic neurons may contribute to motor impairment in Huntington's disease. Here, we study the role of brain‐derived neurotrophic factor (BDNF) in alterations of the nigrostriatal system associated with transgenics carrying mutant huntingtin. Using huntingtin‐BDNF+/– double‐mutant mice, we analyzed the effects of reducing the levels of BDNF expression in a model of Huntington's disease (R6/1). When compared with R6/1 mice, these mice exhibit an increased number of aggregates in the substantia nigra pars compacta. In addition, reduction of BDNF expression exacerbates the dopaminergic neuronal dysfunction seen in mutant huntingtin mice, such as the decrease in retrograde labelling of dopaminergic neurons and striatal dopamine content. However, mutant huntingtin mice with normal or lowered BDNF expression show the same decrease in the anterograde transport, number of dopaminergic neurons and nigral volume. In addition, reduced BDNF expression causes decreased dopamine receptor expression in mutant huntingtin mice. Examination of changes in locomotor activity induced by dopamine receptor agonists revealed that, in comparison with R6/1 mice, the double mutant mice exhibit lower activity in response to amphetamine, but not to apomorphine. In conclusion, these findings demonstrate that the decreased BDNF expression observed in Huntington's disease exacerbates dopaminergic neuronal dysfunction, which may participate in the motor disturbances associated with this neurodegenerative disorder.
The antimicrobial peptide rCRAMP is present in the central nervous system of the rat
Authors: Bergman Peter , Termén Stefan , Johansson Linda , Nyström Lisbeth , Arenas Ernest , Jonsson Ann‐Beth , Hökfelt Tomas , Gudmundsson Gudmundur H. , Agerberth Birgitta
Published: June 2005

The brain is protected against invading pathogens by the blood–brain barrier, and also by its own innate defence system consisting of microglia and neurons in a coordinated network. Antimicrobial peptides are a part of the innate immune system at epithelial surfaces, and may also have important functions in the brain. Recently, we characterized the rat homologue of the human cathelicidin LL‐37, designated rCRAMP. Here we present several lines of evidence for this peptide being expressed in rat CNS. (1) A peptide/protein extract of rat brain is active against bacteria in a salt‐dependent manner. (2) Western blot analysis demonstrates the presence of rCRAMP in rat brain extract. (3) rCRAMP peptide and mRNA are present mainly in specific CNS regions (olfactory bulb, cerebellum, medulla oblongata and spinal cord). (4) rCRAMP‐like immunoreactivity is detected in olfactory bulb, cerebellum and spinal cord by immunohistochemistry. (5) Moreover, the transcript of rCRAMP is detected in primary cultures from hippocampus, striatum, cerebellum and spinal cord, as shown with RT–PCR and Southern blot analyses. In addition, the rCRAMP peptide exhibits in vitro activity against the neuropathogenic bacterium Neisseria meningitidis. Taken together, these data suggest that the cathelicidin rCRAMP may play a role in the innate immunity of the CNS.
Green tea polyphenol (–)‐epigallocatechin‐3‐gallate induces neurorescue of long‐term serum‐deprived PC12 cells and promotes neurite outgrowth
Authors: Reznichenko L. , Amit T. , Youdim M. B. H. , Mandel S.
Published: June 2005

Our previous studies have shown that the green tea polyphenol (–)‐epigallocatechin‐3‐gallate (EGCG) prevents neuronal cell death caused by several neurotoxins. The present study sought to determine the neuroprotective effect of EGCG when it is administered after the induction of cell damage (‘neurorescue’). In an attempt to imitate a progressive mode of death, PC12 cells were initially subjected to serum‐starvation conditions for a period of 1 or 3 days before administration of EGCG (0.1–10 µm) for up to 3 days. In spite of the high percentage of cell death, single or repetitive administration of EGCG (1 µm) significantly attenuated cell death. The neurorescue effect of EGCG was abolished by pre‐treatment with the protein kinase C inhibitor GF109203X (2.5 µm), suggesting the involvement of the protein kinase C pathway in neurorescue by the drug. This is consistent with the rapid (15 min) translocation of the protein kinase C alpha isoform to the cell membrane in response to EGCG. The correlative neurite outgrowth activity of EGCG on PC12 cells may also contribute to its neurorescue effect. The present findings suggest that EGCG may have a positive impact on aging and neurodegenerative diseases to retard or perhaps even reverse the accelerated rate of neuronal degeneration.
Loaded dopamine is preferentially stored in the halo portion of PC12 cell dense core vesicles
Authors: Sombers L. A. , Maxson M. M. , Ewing A. G.
Published: June 2005

Large dense core vesicles in rat pheochromocytoma cells are morphologically distinct from dense core vesicles in mast and chromaffin cells in that the dense core occupies a much smaller fraction of the vesicular volume, allowing for a much larger vesicular clear space, or halo. In this work, we present evidence indicating that upon treatment with L‐DOPA the majority of the dopamine loaded into these vesicles is preferentially compartmentalized into the halo portion of the vesicle. Amperometry was used to monitor release of loaded neurotransmitter from cells in both isotonic and hypertonic extracellular conditions, with the latter condition causing inhibition of dense core dissociation. In combination with this we have used transmission electron microscopy to determine the morphological characteristics of dense core vesicles before and after treatment with L‐DOPA in solutions of varied osmolarity. The results provide a more complete understanding of the complex interaction of molecules within dense core vesicles, suggesting that newly loaded dopamine is located in the halo of the vesicle. This finding has fundamental significance for studies of neurotransmitter release from dense core vesicles, as the core appears to have a function involving more than simple storage of neurotransmitter and associated molecules, and the often overlooked vesicular halo appears to be an important storage compartment for neurotransmitter.
Mild prenatal protein malnutrition increases α2C‐adrenoceptor density in the cerebral cortex during postnatal life and impairs neocortical long‐term potentiation and visuo‐spatial performance in rats
Authors: Soto‐Moyano Rubén , Valladares Luis , Sierralta Walter , Pérez Hernán , Mondaca Mauricio , Fernández Victor , Burgos Héctor , Hernández Alejandro
Published: June 2005

Mild reduction in the protein content of the mother's diet from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but leads to significant enhancements in the concentration and release of cortical noradrenaline during early postnatal life. Since central noradrenaline and some of its receptors are critically involved in long‐term potentiation (LTP) and memory formation, this study evaluated the effect of mild prenatal protein malnutrition on the α2C‐adrenoceptor density in the frontal and occipital cortices, induction of LTP in the same cortical regions and the visuo‐spatial memory. Pups born from rats fed a 25% casein diet throughout pregnancy served as controls. At day 8 of postnatal age, prenatally malnourished rats showed a threefold increase in neocortical α2C‐adrenoceptor density. At 60 days‐of‐age, α2C‐adrenoceptor density was still elevated in the neocortex, and the animals were unable to maintain neocortical LTP and presented lower visuo‐spatial memory performance. Results suggest that overexpression of neocortical α2C‐adrenoceptors during postnatal life, subsequent to mild prenatal protein malnutrition, could functionally affect the synaptic networks subserving neocortical LTP and visuo‐spatial memory formation.
Hyposmolarity‐induced ErbB4 phosphorylation and its influence on the non‐receptor tyrosine kinase network response in cultured cerebellar granule neurons
Authors: Lezama Ruth , Ortega Arturo , Ordaz Benito , Pasantes‐Morales Herminia
Published: June 2005

Exposure of cultured cerebellar granule neurons (24 h serum‐starved) during 3 min to 30% hyposmotic medium activated the tyrosine kinase receptor ErbB4 in the absence of its ligand. Hyposmolarity also activated the non‐receptor tyrosine kinases, Src, focal adhesion kinase (FAK), extracellular signal‐regulated protein kinase (ERK)1/2, and the tyrosine kinase target phosphatidyl‐inositol‐3‐kinase (PI3K). The hyposmotic‐induced activation of these kinases required the prior phosphorylation of ErbB4 as shown by the effect of ErbB4 blockade with AG213 reducing by 85–95% the phosphorylation of FAK and ERK1/2, by 74% and 36% that of PI3K and Src, respectively. These results suggest a key role of ErbB4 as a signal integrator of events associated with hyposmolarity. PI3K seems to be an important connecting element in the signaling network evoked by the hyposmolarity/ErbB4 activation as: (i) the p85 regulatory subunit of PI3K co‐immunoprecipitates with ErbB4 and with FAK; (ii) PI3K blockade with wortmannin reduced the hyposmotic activation of FAK (90%) and ERK1/2 (84–91%). Inhibition of Src with PP2 reduced ErbB4 phosphorylation and inhibited the subsequent cytosolic kinase activation with the same potency as ErbB4 blockade. These results point to Src and ErbB4 and as early targets of the hyposmotic stimulus and osmosignaling. The functional significance for cell volume regulation of the ErbB4‐Src‐PI3K signaling cascade is indicated by the 48–66% decrease of the hyposmotic taurine efflux observed by inhibition of these kinases.
Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10
Authors: Moon Younghye , Lee Kun Ho , Park June‐Hee , Geum Dongho , Kim Kyungjin
Published: June 2005

Chronic exposure to the pesticide rotenone induces a selective degeneration of nigrostriatal dopaminergic neurons and reproduces the features of Parkinson's disease in experimental animals. This action is thought to be relevant to its inhibition of the mitochondrial complex I, but the precise mechanism of this suppression in selective neuronal death is still elusive. Here we investigate the mechanism of dopaminergic neuronal death mediated by rotenone in primary rat mesencephalic neurons. Low concentrations of rotenone (5–10 nm) induce the selective death of dopaminergic neurons without significant toxic effects on other mesencephalic cells. This cell death was coincident with apoptotic events including capsase‐3 activation, DNA fragmentation, and mitochondrial membrane depolarization. Pretreatment with coenzyme Q10, the electron transporter in the mitochondrial respiratory chain, remarkably reduced apoptosis as well as the mitochondrial depolarization induced by rotenone, but other free radical scavengers such as N‐acetylcysteine, glutathione, and vitamin C did not. Furthermore, the selective neurotoxicity of rotenone was mimicked by the mitochondrial protonophore carbonyl cyanide 4‐(trifluoromethoxy) phenylhydrazone (FCCP), a cyanide analog that effectively collapses a mitochondrial membrane potential. These data suggest that mitochondrial depolarization may play a crucial role in rotenone‐induced selective apoptosis in rat primary dopaminergic neurons.
Protein tyrosine nitration in rat brain is associated with raft proteins, flotillin‐1 and α‐tubulin: effect of biological aging
Authors: Dremina Elena S. , Sharov Victor S. , Schöneich Christian
Published: June 2005

Protein 3‐nitrotyrosine (3‐NY) immunoreactivity of rat brain homogenate was localized to a ca. 50 kDa protein band by western blot (WB) analysis. The nitrated proteins were localized to the raft fraction obtained by centrifugation of the homogenate in a sucrose density gradient, which contained specific raft markers such as flotillin‐1 and caveolin‐1. Purification of the nitrated raft proteins either by a combination of reversed‐phase high‐performance liquid chromatography (HPLC) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS–PAGE) or by immunoprecipitation (IP) with protein‐ and modification‐specific antibodies coupled to WB and HPLC‐electrospray ionization‐tandem mass spectrometry (ESI–‐MS/MS) analysis allowed us to identify two proteins modified by 3‐NY: flotillin‐1 and α‐tubulin. Both α‐ and β‐tubulin were detected in the rat brain raft fraction as abundant proteins, which co‐immunoprecipitate with flotillin‐1 and caveolin‐1. Importantly, some protein–protein interactions in rafts were disrupted in 3‐NY‐containing proteins, e.g. caveolin‐1 was dissociated from a complex with flotillin‐1 and α‐tubulin. The analysis of age dependencies did not show any significant change in protein nitration and expression of flotillin‐1 and α‐tubulin, but a decrease in the brain caveolin‐1 level for old (34 months) versus young (6 months) rats. The putative mechanism of nitric oxide synthase (NOS) activity regulation by the level of caveolin expression and raft protein–protein interactions is discussed.
Direct visualization of mitochondrial zinc accumulation reveals uniporter‐dependent and ‐independent transport mechanisms
Authors: Malaiyandi Latha M. , Vergun Olga , Dineley Kirk E. , Reynolds Ian J.
Published: June 2005

Current evidence suggests that zinc kills neurons by disrupting energy production, specifically by inhibiting mitochondrial function. However it is unclear if the inhibitory effect requires zinc accumulation, and if so, precisely how zinc enters mitochondria. Here, using fluorescence microscopy to visualize individual rat brain mitochondria, we detected matrix zinc uptake using the fluorophore FluoZin‐3. Fluorescence increased rapidly in mitochondria treated with micromolar free zinc, and was quickly returned to baseline by membrane permeant chelation. Zinc uptake occurred through the calcium uniporter, because depolarization or uniporter blockade reduced fluorescence changes. However, increased fluorescence under these conditions suggests that zinc can enter through a uniporter‐independent pathway. Fluorescence steadily declined over time and was unaffected by acidification or phosphate depletion, suggesting that zinc precipitation is not a mechanism for reducing matrix zinc. Uniporter blockade with ruthenium red also did not change the rate of zinc loss. Instead, zinc appears to exit the matrix through a novel efflux pathway not yet identified. Interestingly, dye‐loaded mitochondria showed no fluorescence increase after treatment with strong oxidants, arguing against oxidant‐labile intra‐mitochondrial zinc pools. This study is the first to directly demonstrate zinc accumulation in individual mitochondria and provides insight about mechanisms mediating mitochondrial zinc uptake and efflux.
Modification by the tissue plasminogen activator–plasmin system of morphine‐induced dopamine release and hyperlocomotion, but not anti‐nociceptive effect in mice
Authors: Nagai Taku , Kamei Hiroyuki , Ito Mina , Hashimoto Kazuki , Takuma Kazuhiro , Nabeshima Toshitaka , Yamada Kiyofumi
Published: June 2005

The extracellular serine protease tissue plasminogen activator (tPA) that converts plasminogen into plasmin is abundantly expressed throughout the central nervous system. We have recently demonstrated that the tPA–plasmin system participates in the rewarding and locomotor‐stimulating effects of morphine by acutely regulating morphine‐induced dopamine release in the nucleus accumbens (NAc). In the present study, we examined the effects of microinjections of plasminogen activator inhibitor‐1 (PAI‐1), tPA or plasmin into the NAc on morphine‐induced dopamine release, hyperlocomotion and anti‐nociceptive effects in ICR mice. A single morphine treatment resulted in an increase in protein levels of PAI‐1 in the NAc. Microinjection of PAI‐1 into the NAc dose‐dependently reduced morphine‐induced dopamine release and hyperlocomotion. In contrast, microinjection of tPA into the NAc significantly potentiated morphine‐induced dopamine release and hyperlocomotion without affecting basal levels. Furthermore, microinjection of plasmin enhanced morphine‐induced dopamine release, but did not modify the hyperlocomotion induced by morphine. The intracerebroventricular injection of PAI‐1, tPA and plasmin at high doses had no effect on the anti‐nociceptive effects of morphine. These results suggest that the tPA–plasmin system is involved in the regulation of morphine‐induced dopamine release and dopamine‐dependent behaviors but not the anti‐nociceptive effects of morphine.
NT3 inhibits FGF2‐induced neural progenitor cell proliferation via the PI3K/GSK3 pathway
Authors: Jin Lu , Hu Xinhua , Feng Linyin
Published: June 2005

Neurotrophin 3 (NT3), a member of the neurotrophin family, antagonizes the proliferative effect of fibroblast growth factor 2 (FGF2) on cortical precursors. However, the mechanism by which NT3 inhibits FGF2‐induced neural progenitor (NP) cell proliferation is unclear. Here, using an FGF2‐dependent rat neurosphere culture system, we found that NT3 inhibits both FGF2‐induced neurosphere growth and bromodeoxyuridine (BrdU) incorporation in a dose‐dependent manner. U0126, a mitogen‐activated protein kinase kinase 1/2 (MEK1/2) inhibitor, and LY294002, a phosphatidylinositol 3‐kinase (PI3K) inhibitor, both inhibited FGF2‐induced BrdU incorporation, suggesting that the extracellular signal‐regulated kinase1/2 (ERK1/2) and PI3K pathways are required for FGF2‐induced NP cell proliferation. NT3 significantly inhibited FGF2‐induced phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β), a downstream kinase of Akt, whereas phosphorylation of ERK1/2 was unaffected. The inhibitory effect of NT3 on FGF2‐induced NP cell proliferation was abolished by LY294002, and treatment with SB216763, a specific GSK3 inhibitor, antagonized the NT3 effect, rescuing both neurosphere growth and BrdU incorporation. Moreover, experiments with anti‐NT3 antibody revealed that endogenous NT3 also plays a role in inhibiting FGF2‐induced NP cell proliferation, and that anti‐NT3 antibody enhanced phospho‐Akt and phospho‐GSK3β levels in the presence of FGF2. These findings indicate that FGF2‐induced NP cell proliferation is inhibited by NT3 via the PI3K/GSK3 pathway.