bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of different plant parts to study N2 fixation with 15N techniques in field‐grown red clover (Trifolium pratense)
Authors: Huss‐Danell Kerstin , Chaia Eugenia
Published: August 2005

Red clover, Trifolium pratense L., is the dominant forage legume in Sweden and is usually harvested twice per year, once in June and once in August. Two 15N‐based methods –15N isotopic dilution (ID) and 15N natural abundance (NA) – were used to study N2 fixation from spring until first harvest in late June, from first to second harvest in late August, and from second harvest until first frost in autumn in Umeå, Sweden. The material studied comprized three neighbouring fields carrying a first year ley, a second year ley and a third year ley. For the 15N ID method, small amounts of highly enriched 15N‐nitrate were added to experimental plots. The non‐legumes in the plots, essentially Phleum pratense L. together with Festuca pratensis L., served as reference plants for both the ID and 15N NA measurements. Dry matter, N and 15N were separately analysed in leaves (laminae), stems (including petioles), stubble and roots. The proportion of N derived from air (pNdfa) was then calculated for each plant part and for whole plants. Estimates of the proportion of N derived from N2 fixation (pNdfa) were always very high, usually ≥0.8. Generally, estimates of pNdfa obtained by the ID and NA methods were similar, but the ID method gave higher estimates of pNdfa than the NA method when the highest N2 fixation levels were recorded, at the August harvest. Regression analyses suggest that estimates of pNdfa in leaves could provide useful indications of pNdfa in shoots and whole T. pratense plants, thus avoiding the need for time‐consuming root analyses.
20 Questions on Adaptive Dynamics
Authors: WAXMAN D. , GAVRILETS S.
Published: August 2005

Adaptive Dynamics is an approach to studying evolutionary change when fitness is density or frequency dependent. Modern papers identifying themselves as using this approach first appeared in the 1990s, and have greatly increased up to the present. However, because of the rather technical nature of many of the papers, the approach is not widely known or understood by evolutionary biologists. In this review we aim to remedy this situation by outlining the methodology and then examining its strengths and weaknesses. We carry this out by posing and answering 20 key questions on Adaptive Dynamics. We conclude that Adaptive Dynamics provides a set of useful approximations for studying various evolutionary questions. However, as with any approximate method, conclusions based on Adaptive Dynamics are valid only under some restrictions that we discuss.
On the Weight‐bearing Function of the Medial Coronoid Process in Dogs
Authors: Breit S. , Künzel W. , Seiler S.
Published: August 2005

The shape of and proportions between the surface areas of the medial coronoid process (MCP) and the fovea of the radial head were determined in 88 juvenile dogs and 146 adult dogs grouped as giant, large, mid‐sized, chondrodystrophic, or small dogs. Thereby, the longitudinal (length) and transverse (width) extension of the MCP and fovea of the radial head have been measured. Original values were used to describe changes of the parameters attributed to growth. Normalized values (i.e. values expected in case of a width of the fovea of the radial head of 20 mm) were used to determine potential differences between constitutional types. All original values increased during growth (P < 0.05) except for the width and length of the MCP in chondrodystrophic and small breeds. Normalized values revealed a proportional decrease in width and length of the MCP during growth (P < 0.05) compared with the radial head. In adults, the normalized MCP was widest in giant dogs followed by large, mid‐sized, small, and chondrodystrophic breeds. The MCP was also longest in giant dogs but shortest in large and chondrodystrophic dogs with those of large dogs being significantly (P < 0.05) shorter than those in giant, mid‐sized and small dogs. Present results suggest that a deficiency in length‐growth of the MCP – which has been present especially in large dogs – results in smaller humeral contact areas and decreased weight‐bearing capacity of the MCP. Because loading forces acting on the MCP increase with body weight, the condition noted in large dogs might increase the risk of fragmentation of the MCP in these.
Dependence of the timing system regulating the onset of gastrulation on cytoplasmic, but not nuclear, activities in the Xenopus embryo
Authors: Takagi Makoto , Shimoda Taiki , Shinagawa Atsunori
Published: August 2005

This study examines the properties of the timer that regulates the onset of gastrulation in the Xenopus embryo. Pre‐gastrulation embryos were exposed to aphidicolin, vinblastine, 6‐dimethylaminopurine (6‐DMAP) or urethane. Embryos exposed to aphidicolin or vinblastine for 0.5–2 h before the presumptive onset of gastrulation, began gastrulation at the same time as control embryos. However, those exposed to 6‐DMAP or urethane commenced gastrulation significantly later than controls. In 6‐DMAP‐ and urethane‐treated embryos, the onset of gastrulation was retarded by approximately 25% and 120%, respectively. 6‐DMAP and urethane, but not vinblastine, also lowered the rate of nuclear doubling by 30% and 120%, respectively, in late‐blastula to early‐gastrula embryos. 6‐DMAP and urethane also lowered the rate of cleavage and cleavage‐relevant cytoplasmic cycling by 30% and 80%, respectively, in cleavage‐stage embryos. We propose that cytoplasmic activities that can be retarded by 6‐DMAP and urethane, but not aphidicolin or vinblastine, may be responsible for regulating the onset of gastrulation in Xenopus embryos.
The molecular basis and prospects in pancreatic development
Authors: Kume Shoen
Published: August 2005

Studies on the signaling mechanism that control the specification of endoderm‐derived organs have only recently begun. While many studies revealed genes involved in the differentiation, growth and morphogenesis of the pancreas through studies of mutant mice, still little is known about how endoderm give rise to specific domains. Although many genes are known to have a role in pancreatic differentiation, growth and morphogenesis, few genes are known to take part in the specification of the pancreas so far. Hallmarks as well as gene markers for early development of the pancreas, which are however still very limited, will be useful for dissecting early events in pancreatic specification. Here, I give a summary on the origin of the dorsal and ventral pancreatic progenitors, signals for inductions, and genes so far known to function in pancreatic differentiation. I also give a future prospect in the use of ES cells and other experimental models, towards a comprehensive understanding of gene networks in the progenitor cells or intermediate cell types which arise during various stages of differentiation.
Unlocking the opportunity of tight glycaemic control
Authors: Scherbaum Werner A.
Published: August 2005

Numerous attempts have been made to develop novel routes of insulin delivery that are both effective and tolerable. Of all the potential non‐invasive delivery options, pulmonary delivery is the most clinically viable. Early studies demonstrate that the inhaled insulin is rapidly absorbed and is closer to biological insulin than standard subcutaneous insulin (SC). To date, inhaled insulin (Exubera®) has been clinically assessed in more than 3500 patients with type 1 or type 2 diabetes, some treated for more than 7 years. Several phase 3 studies of 24‐week duration have demonstrated comparable glycosylated haemoglobin (HbA1c) control in patients with type 1 diabetes treated with Exubera® vs. SC insulin. Similar results have also been recorded in patients with type 2 diabetes. Furthermore, Exubera® has shown clinical superiority to oral agent regimens in patients with type 2 diabetes who failed to achieve their target HbA1c using lifestyle modification and oral agents. Exubera® was well tolerated and treatment satisfaction was high, with Exubera® being the preferred insulin therapy in all studies. The results of these trials, and others, suggest that Exubera® may be a valuable tool to help a wide variety of patients with type 1 or type 2 diabetes reach their recommended goals for glycaemic control, irrespective of their current therapy.
How many branchiopod crustacean species are there? Quantifying the components of underestimation
Authors: Adamowicz Sarah J. , Purvis Andy
Published: August 2005

Aims  For the crustacean class Branchiopoda, we estimated global species richness, assessed the reliability of relative diversity estimates among higher taxa and made predictions about the kinds of species remaining to be described.

Location  Global.

Methods  We calculated correction factors to account for three different sources of diversity underestimation, analysed taxonomic patterns of species descriptions over time and tested possible correlates of description date.

Results  Our work suggests that there are c. 2.1 times more branchiopod species in nature than the c. 1180 currently described. The largest correction factor was at the scale of single biogeographical regions, mainly attributed to poor knowledge of species diversity within described morphospecies. Relative diversity estimates among major taxonomic groups are apparently quite reliable, with diversity differences greater than 1.5‐fold robust to the heterogeneity of the taxonomic process. Current knowledge of branchiopod diversity is biased towards species with large geographical ranges, whereas body size and higher taxonomic group were only weak predictors of description date.

Main conclusions  A proper understanding of species boundaries in nature, which is greatly aided by molecular studies, is key in accurately estimating species richness for invertebrate groups. However, we suggest that while many species remain to be described, numbers of presently described species are still useful for macroevolutionary studies of diversification when interpreted with caution.
Macroecological correlates and spatial patterns of anuran description dates in the Brazilian Cerrado
Authors: Diniz‐Filho José Alexandre F. , Bastos Rogério Pereira , Rangel Thiago F. L. V. B. , Bini Luis M. , Carvalho Priscilla , Silva Rodrigo J.
Published: August 2005

Aim To quantify the relationship between the description dates of anuran species in the Brazilian Cerrado and some macroecological traits, and to verify the spatial patterns of average description dates and their correlation with human occupation and biodiversity knowledge.

Location Brazilian Cerrado (South America).

Methods The average date of description of 131 species of anurans found in 181 cells overlaying the Brazilian Cerrado was recorded. Description date was regressed across species on body size and geographical range size. Phylogenetic effects that could bias the significance tests of the multiple regression model of description dates on macroecological traits were taken into account using a phylogenetic subtraction method in which families and genera were classificatory factors in a nested two‐way analysis of variance (anova) model. We also conducted a spatial analysis of the average description date that was estimated for each cell. This cell‐based metric was regressed on human population size, the year of foundation of the municipalities and the number of inventories undertaken in each cell. The influence of spatial autocorrelation patterns was taken into account by using the geographically effective number of degrees of freedom.

Results The number of new species being discovered in the Brazilian Cerrado has been increasing, especially over the last 50 years. Cross‐species analyses indicated that description dates were negatively correlated with body size and geographical range size, taking phylogenetic effects into account. Even after controlling for the spatial structures in all variables, average description date was positively correlated with human population in geographical space, but because of multicolinearity structure in the data, it was not possible to quantify the independent influence of human population and number of inventories on description date.

Conclusions As found in previous papers, large‐bodied and widely distributed species are likely to be described first. Species yet to be discovered are probably small‐bodied and with narrow distributions, more restricted to the Cerrado biome. Also, the explicit spatial approach showed that the average description date is spatially correlated with total human population and biodiversity knowledge in the Cerrado region. Our findings suggest that incorporating human population density into the reserve design algorithms, which has usually been done to avoid or minimize conservation conflicts, may also produce good results because this will preserve many places where most of the non‐described species will probably be found in the future.
Sensitivity and response of northern hemisphere altitudinal and polar treelines to environmental change at landscape and local scales
Authors: Holtmeier Friedrich‐Karl , Broll Gabriele
Published: August 2005

The sensitivity and response of northern hemisphere altitudinal and polar treelines to environmental change are increasingly discussed in terms of climate change, often forgetting that climate is only one aspect of environmental variation. As treeline heterogeneity increases from global to regional and smaller scales, assessment of treeline sensitivity at the landscape and local scales requires a more complex approach than at the global scale. The time scale (short‐, medium‐, long‐term) also plays an important role when considering treeline sensitivity. The sensitivity of the treeline to a changing environment varies among different types of treeline. Treelines controlled mainly by orographic influences are not very susceptible to the effects of warming climates. Greatest sensitivity can be expected in anthropogenic treelines after the cessation of human activity. However, tree invasion into former forested areas above the anthropogenic forest limit is controlled by site conditions, and in particular, by microclimates and soils. Apart from changes in tree physiognomy, the spontaneous advance of young growth of forest‐forming tree species into present treeless areas within the treeline ecotone and beyond the tree limit is considered to be the best indicator of treeline sensitivity to environmental change. The sensitivity of climatic treelines to climate warming varies both in the local and regional topographical conditions. Furthermore, treeline history and its after‐effects also play an important role. The sensitivity of treelines to changes in given factors (e.g. winter snow pack, soil moisture, temperature, evaporation, etc.) may vary among areas with differing climatic characteristics. In general, forest will not advance in a closed front but will follow sites that became more favourable to tree establishment under the changed climatic conditions.
A Contrast of HRM and TQM Approaches to Performance Management: Some Evidence*
Authors: Soltani Ebrahim , Van Der Meer Robert , Williams Terry M.
Published: August 2005

Using a survey, this paper provides information about the current state of performance management (appraisal) from a sample of UK‐based EFQM‐affiliated organizations. It particularly focuses on several critical issues of performance management in the context of TQM including: the effectiveness of TQM programmes; the rationale for performance management; degree of internal consistency between TQM assumptions and performance management systems; and the relationship among performance management, effectiveness of TQM programmes, employee satisfaction and overall organization performance. Although the fundamental precepts advocated by founders of TQM appear to be in conflict with performance management practices, however, the article argues that, rather than being contradictory, both can add value to the operations of the other in the interest of the organization as a whole. More precisely, the paper explains how a successful TQM strategy requires a rethinking and changing the organization's performance management system, otherwise it is highly likely to result in a disaster. To conclude, the survey evidence is used, combined with previous literature, to discuss the implications of these results for designing a contextually appropriate performance management for TQM and in the interest of the future research on TQM and HRM.
Performance Decline and Turnaround in Public Organizations: A Theoretical and Empirical Analysis*
Authors: Jas Pauline , Skelcher Chris
Published: August 2005

Public sector performance is currently a significant issue for management practice and policy, and especially the turnaround of those organizations delivering less than acceptable results. Theories of organizational failure and turnaround derive largely from the business sector and require adaptation to the public service. The performance of public organizations is more complex to measure, is related to institutional norms, and the idea of ‘failure’ is problematic. Empirical findings from a real‐time, longitudinal study of poorly performing English local authorities are used to develop an initial theory of performance failure and turnaround suited to public organizations. The paper argues that the typical performance of public organizations over time is cyclical. Where cognition and leadership capability are absent, organizations fail to self‐initiate turnaround. In this situation authoritative external intervention is necessary. The strategies applied are principally concerned with building a leadership capability that engages senior politicians and managers in order to overcome inertia and collective action problems. The theory is presented in the form of seven propositions that provide a basis for further research across the public sector.
REASON‐EXPLANATION AND THE CONTENTS OF THE MIND
Authors: Tanney Julia
Published: August 2005

This paper takes a close look at the kinds of considerations we use to reach agreement in our ordinary (non‐philosophical and non‐theoretical) judgments about a person's reasons for acting, and the following theses are defended. First, considering the circumstances in which the action occurs is often enough to remove our puzzlement as to why someone acts as she does. Second, in those situations where we do need to enquire about the agent's state of mind, this does not, in the normal case, lead us to look for hidden, inner events that are candidates for the causes of her action. Finally, even though there are cases in which the agent's introspections, reflections, and deliberations are relevant to our search for reasons, such cases do not lend support to the idea that reasons are hidden or inner causes of action. This suggests a problem for most philosophical accounts of what it is to act for reasons and for most philosophical accounts of the nature of mental states.
Local Model Uncertainty and Incomplete-Data Bias (With Discussion)
Authors: Copas John , Eguchi Shinto
Published: August 2005

Problems of the analysis of data with incomplete observations are all too familiar in statistics. They are doubly difficult if we are also uncertain about the choice of model. We propose a general formulation for the discussion of such problems and develop approximations to the resulting bias of maximum likelihood estimates on the assumption that model departures are small. Loss of efficiency in parameter estimation due to incompleteness in the data has a dual interpretation: the increase in variance when an assumed model is correct; the bias in estimation when the model is incorrect. Examples include non-ignorable missing data, hidden confounders in observational studies and publication bias in meta-analysis. Doubling variances before calculating confidence intervals or test statistics is suggested as a crude way of addressing the possibility of undetectably small departures from the model. The problem of assessing the risk of lung cancer from passive smoking is used as a motivating example.
Estimating the Proportion of True Null Hypotheses, with application to DNA Microarray Data
Authors: Langaas Mette , Lindqvist Bo Henry , Ferkingstad Egil
Published: August 2005

We consider the problem of estimating the proportion of true null hypotheses, π0, in a multiple-hypothesis set-up. The tests are based on observed p-values. We first review published estimators based on the estimator that was suggested by Schweder and Spjøtvoll. Then we derive new estimators based on nonparametric maximum likelihood estimation of the p-value density, restricting to decreasing and convex decreasing densities. The estimators of π0 are all derived under the assumption of independent test statistics. Their performance under dependence is investigated in a simulation study. We find that the estimators are relatively robust with respect to the assumption of independence and work well also for test statistics with moderate dependence.
From Chicago to Santiago: Neoliberalism and Social Security Privatization in Chile
Authors: BORZUTZKY SILVIA
Published: August 2005

This article examines the ideology and principles that inspired the privatization of social security in Chile during the Pinochet regime. The article highlights the role of the state in the establishment of a fully funded, defined contribution system, as well as the importance of the transmission of ideas from the halls of the University of Chicago to Chile's centers of power. In the case of Chile, the ideas of freedom espoused by Milton Friedman and Frederick von Hayek were applied by a repressive authoritarian regime that violated human and political rights. Furthermore, these ideas served to legitimize a political and economic system based on the deprivation of freedom. Although social security reform was a critical component of a revolution going on in Chile in the 1970s, the ultimate purpose of this article is to show that the effects of this reform are by no means limited to Chile. The Chilean reform has been adopted by countries in Latin America and other parts of the world, and it has critically affected those societies as well. The article shows that the establishment of the fully funded, defined contribution system has been very costly, both for the state and the insured, while coverage has dramatically declined. The article concludes that the market economic reforms have enhanced only the freedom of those who could take advantage of the new economy, and that few of the promises made during the Pinochet regime by the neoliberal economists came true.
Effects of familial risk factors and place of birth on the risk of autism: a nationwide register‐based study
Authors: Lauritsen Marlene Briciet , Pedersen Carsten Bøcker , Mortensen Preben Bo
Published: August 2005

Background:  The etiology of autism is unknown. A strong genetic component has been detected but non‐genetic factors may also be involved in the etiology.

Methods:  We used data from the Danish Psychiatric Central Register and the Danish Civil Registration System to study some risk factors of autism, including place of birth, parental place of birth, parental age, family history of psychiatric disorders, and paternal identity.

Results:  A total of 943,664 children younger than ten years were followed from 1994 to 2001; of those, 818 children developed autism. The highest risks of autism were found in siblings of children with autism, or Asperger‘s syndrome and other pervasive developmental disorders (PDDs), with relative risks of 22 and 13, respectively. The relative risk of autism in the child was about twice as high if the mother had been diagnosed with a psychiatric disorder. The risk of autism was associated with increasing degree of urbanisation of the child's place of birth and with increasing paternal, but not maternal, age. An increased relative risk of 1.4 was found if the mother was born outside Europe, and in children of parents who were born in different countries.

Conclusions:  The highest risk of autism was found in families with a history of autism, or Asperger‘s syndrome and other PDDs in siblings, supporting the commonly accepted knowledge that genetic factors are involved in the etiology of autism.
Response reversal and children with psychopathic tendencies: success is a function of salience of contingency change
Authors: Budhani S. , Blair R.J.R.
Published: August 2005

Background:  Previous work has inconsistently reported difficulties with response reversal/extinction in children with psychopathic tendencies.

Method:  We tested the hypothesis that the degree of impairment seen in children with psychopathic tendencies is a function of the salience of contingency change. We investigated the performance of children with psychopathic tendencies on a novel probabilistic response reversal task involving four conditions with gradated reward–punishment contingencies (100–0, 90–10, 80–20 and 70–30; i.e., for the 100–0 contingency, responding to one object is always rewarded while responding to the other is always punished).

Results:  In line with predictions, the impairment seen in the children with psychopathic tendencies was an inverse function of the salience of the contingency change.

Conclusions:  We suggest that this data is consistent with suggestions of subtle orbital frontal cortex impairment in children with psychopathic tendencies.
The role of marital discord and parenting in relations between parental problem drinking and child adjustment
Authors: Keller Peggy S. , Mark Cummings E. , Davies Patrick T.
Published: August 2005

Background:  Research suggests that children exposed to parental drinking problems are at risk for maladjustment. However, the potential impact of drinking problems in a community sample and the processes involved in the relationship between parental drinking and child outcomes have rarely been examined.

Method:  A community sample of 235 mothers and fathers of kindergarten children completed measures of problem drinking symptoms, family functioning and child adjustment.

Results:  Model tests indicate that problem drinking was associated with greater marital conflict, and that marital conflict was related to ineffective parenting which was in turn related to poorer child adjustment.

Conclusions:  Even in a community sample, parental problem drinking behaviors are associated with reduced family functioning that relates to child outcomes.
Selected executive skills in adolescents with recent first episode major depression
Authors: Kyte Zoë A. , Goodyer Ian M. , Sahakian Barbara J.
Published: August 2005

Background:  To investigate whether recent first episode major depression in adolescence is characterised by selected executive difficulties in attentional flexibility, behavioural inhibition and decision‐making.

Methods:  Selected executive functions were compared in adolescents with recent (past year) first episode major depression (n = 30) and community controls (n = 49). Three computerised tests within the CANTAB battery were completed by all subjects (the Intra‐Dimensional, Extra‐Dimensional Set‐Shifting task, the Affective Go, No‐Go task, and the Decision‐Making task).

Results:  Compared with controls, recently depressed cases displayed a bias towards negative stimuli with fewer errors on sad words as well as being more accurate in their responses to sad targets on the Affective Go, No‐Go task. Cases also made faster decisions in the context of betting more of their available points compared to controls, as indexed by the Decision‐Making task. These results were not influenced by age, gender, IQ, recent mood, severity of depression, medication or comorbidity.

Conclusions:  Adolescents with recent first episode major depression show greater attention towards sad stimuli and more impulsive behaviour when making decisions. They were able to switch attentional set to neutral stimuli. This study demonstrates that computerised tests for measuring executive functions can be successfully deployed in adolescents, and suggests that specific patterns of neuropsychological functions may be relatively compromised in first episode major depression. These, together with their underlying neural substrates, deserve further investigation within this age range.
The borderline personality diagnosis in adolescents: gender differences and subtypes
Authors: Bradley Rebekah , Zittel Conklin Carolyn , Westen Drew
Published: August 2005

Background:  This study aimed to identify personality features characterizing adolescent girls and boys with borderline personality disorder (BPD) and to see whether meaningful patterns of heterogeneity exist among adolescents diagnosed with the disorder.

Methods:  Two hundred and ninety‐four randomly selected doctoral‐level clinicians described adolescent patients using Axis II rating scales and the Shedler–Westen Assessment Procedure‐200 for Adolescents (SWAP‐200‐A). We used the SWAP‐200‐A to provide empirically derived descriptions of female and male adolescents meeting DSM‐IV criteria for BPD (who differed substantially in their profiles), and used Q‐factor analysis to identify naturally occurring groupings of female patients based on shared personality features.

Results:  The symptoms and phenomenology of adolescent girls with BPD are similar to those of adults. Adolescent boys meeting BPD criteria have a more aggressive, disruptive, antisocial presentation. Although Ns did not permit further analysis of the data on adolescent boys, Q‐analysis isolated four clinically coherent subgroups of girls with BPD: high‐functioning internalizing, histrionic, depressive internalizing, and angry externalizing.

Conclusions:  BPD in female adolescents resembles DSM‐IV BPD as defined for adults. The operating characteristics of the DSM‐IV criteria for adolescent boys require further investigation. Empirically derived subgroups are similar to those identified in recent research with adult females. Differences across subgroups on internalizing and externalizing Child Behavior Checklist (CBCL) scales provide preliminary data on the validity of subgroups and raise questions about the place of BPD among internalizing and externalizing spectrum disorders.
Annotation: Economic evaluations of child and adolescent mental health interventions: a systematic review
Authors: Romeo Renée , Byford Sarah , Knapp Martin
Published: August 2005

Background: Recognition has grown over recent years of the need for economic information on the impacts of child and adolescent mental health problems and the cost‐effectiveness of interventions.

Methods: A range of electronic databases were examined using a predefined search strategy to identify economic studies which focused on services, pharmacological interventions and other treatments for children and adolescents with a diagnosed mental health problem or identified as at risk of mental illness. Published studies were included in the review if they assessed both costs and outcomes, with cost‐effectiveness being the primary interest. Studies meeting the criteria for inclusion were assessed for quality.

Results: There are still relatively few economic evaluations in this field. Behavioural disorders have been given relatively greater attention in economic evaluations of child and adolescent mental health. These studies tentatively suggest child behavioural gains and parent satisfaction from parent and child training programmes, although the cost‐effectiveness of the location of delivery for behavioural therapies is less clear. In general, the quality of economic evaluations was limited by small sample sizes, constrained measurement of costs, narrow perspectives and over‐simple statistical and econometric methods.

Conclusion: Economic evaluations in the field of child and adolescent mental health interventions are few in number and generally poor in quality, although the number of studies being undertaken now appears to be rising.
Glial cell line‐derived neurotrophic factor‐induced signaling in Schwann cells
Authors: Iwase T. , Jung C. G. , Bae H. , Zhang M. , Soliven B.
Published: August 2005

Glial cell line‐derived neurotrophic factor (GDNF), a known survival factor for neurons, has recently been shown to stimulate the migration of Schwann cells (SCs) and to enhance myelination. GDNF exerts its biological effects by activating the Ret tyrosine kinase in the presence of glycosylphosphatidylinositol‐linked receptor, GDNF family receptor (GFR) α1. In Ret‐negative cells, the alternative transmembrane coreceptor is the 140‐kDa isoform of neural cell adhesion molecule (NCAM) associated with a non‐receptor tyrosine kinase Fyn. We confirmed that GDNF, GFRα1 and NCAM are expressed in neonatal rat SCs. We found that GDNF induces an increase in the partitioning of NCAM and heparan sulfate proteoglycan agrin into lipid rafts and that heparinase inhibits GDNF‐signaling in SCs. In addition to activation of extracellular signal‐regulated kinases, and phosphorylation of cAMP response element binding protein, we found that cAMP‐dependent protein kinase A and protein kinase C are involved in GDNF‐mediated signaling in SCs. Although GDNF did not promote the differentiation of purified SCs into the myelinating phenotype, it enhanced myelination in neuron–SC cocultures. We conclude that GDNF utilizes NCAM signaling pathways to regulate SC function prior to myelination and at early stages of myelin formation.
Neuronal transmission stimulates the phosphorylation of Kv1.4 channel at Ser229 through protein kinase A1
Authors: Tao Yanmei , Zeng Rui , Shen Bin , Jia Jiemin , Wang Yizheng
Published: August 2005

Phosphorylation of voltage‐gated K+ channels (Kv) is involved in regulation of neuronal excitability, synaptic plasticity and neuronal survival. Among Kv channels expressed in the CNS, Kv1.4 is located in the soma, dendrite and axon terminus of neurones in most regions of the brain. Here, we show that Ser229 found within the highly conserved T1 domain of Kv1.4 in cultured rat cortical neurones is phosphorylated by protein kinase A (PKA), as demonstrated by in vitro protein kinase assay and Western blotting with a polyclonal antibody specific against phosphorylated Ser229. Glutamate, high concentrations of K+ or K+ channel blockers known to increase neurotransmission all stimulated the phosphorylation of Kv1.4 at Ser229 via N‐methyl‐d‐aspartate (NMDA), but not α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐proprionic acid (AMPA) receptor, whereas tetradotoxin (TTX), known to block neuronal transmission, and depletion of extracellular Ca2+ inhibited phosphorylation induced by tetraethylammonium (TEA), a non‐selective K+ channel blocker. Mutation of Ser229 to Ala229 enhanced the current density. Taken together, elevation of the neuronal transmission stimulates the phosphorylation of Kv1.4 at Ser229 via the Ca2+ influx through NMDA receptor. Thus, it is possible that neuronal transmission regulates neuronal excitability partially through the phosphorylation of Kv1.4S229.
Progenitor cell injury after irradiation to the developing brain can be modulated by mild hypothermia or hyperthermia
Authors: Fukuda Aya , Fukuda Hirotsugu , Jönsson Marie , Swanpalmer Janos , Hertzman Sven , Lannering Birgitta , Björk‐Eriksson Thomas , Màrky Ildikó , Blomgren Klas
Published: August 2005

Ionizing radiation induced acute cell death in the dentate gyrus subgranular zone (SGZ) and the subventricular zone (SVZ). Hypomyelination was also observed. The effects of mild hypothermia and hyperthermia for 4 h after irradiation (IR) were studied in postnatal day 9 rats. One hemisphere was irradiated with a single dose of 8 Gy and animals were randomized to normothermia (rectal temperature 36°C for 4 h), hypothermia (32°C for 4 h) or hyperthermia (39°C for 4 h). Cellular injury, e.g. chromatin condensation and nitrotyrosine formation, appeared to proceed faster when the body temperature was higher. Caspase‐3 activation was more pronounced in the hyperthermia group and nuclear translocation of p53 was less pronounced in the hypothermia group 6 h after IR. In the SVZ the loss of nestin‐positive progenitors was more pronounced (48%) and the size was smaller (45%) in the hyperthermia group 7 days post‐IR. Myelination was not different after hypo‐ or hyperthermia. This is the first report to demonstrate that hypothermia may be beneficial and that hyperthermia may aggravate the adverse side‐effects after radiation therapy to the developing brain.
Functions and pathophysiological roles of phospholipase D in the brain
Authors: Klein Jochen
Published: August 2005

Ten years after the isoforms of mammalian phospholipase D (PLD), PLD1 and 2, were cloned, their roles in the brain remain speculative but several lines of evidence now implicate these enzymes in basic cell functions such as vesicular trafficking as well as in brain development. Many mitogenic factors, including neurotransmitters and growth factors, activate PLD in neurons and astrocytes. Activation of PLD downstream of protein kinase C seems to be a required step for astroglial proliferation. The characteristic disruption of the PLD signaling pathway by ethanol probably contributes to the delay of brain growth in fetal alcohol syndrome. The post‐natal increase of PLD activities concurs with synapto‐ and myelinogenesis in the brain and PLD is apparently involved in neurite formation. In the adult and aging brain, PLD activity has antiapoptotic properties suppressing ceramide formation. Increased PLD activities in acute and chronic neurodegeneration as well as in inflammatory processes are evidently due to astrogliosis and may be associated with protective responses of tissue repair and remodeling. ARF‐regulated PLD participates in receptor endocytosis as well as in exocytosis of neurotransmitters where PLD seems to favor vesicle fusion by modifications of the shape and charge of lipid membranes. Finally, PLD activities contribute free choline for the synthesis of acetylcholine in the brain. Novel tools such as RNA interference should help to further elucidate the roles of PLD isoforms in brain physiology and pathology.
Roles of transmembrane domain 2 and the first intracellular loop in human noradrenaline transporter function: pharmacological and SCAM analysis
Authors: Sucic Sonja , Bryan‐Lluka Lesley J.
Published: August 2005

The aim was to investigate the roles of transmembrane domain 2 and the adjacent region of the first intracellular loop in determining human noradrenaline transporter (hNET) function by pharmacological and substituted‐cysteine accessibility method (SCAM) analyses. It was first necessary to establish a suitable background NET for SCAM. Alanine mutants of endogenous hNET cysteines, hC86A, hC131A and hC339A, were examined and showed no marked effects on expression or function. hNET and the mutants were also resistant to methanethiosulfonate (MTS), ethylammonium (MTSEA) and MTStrimethylammonium (MTSET). Hence, wild‐type hNET is an appropriate background for production of cysteine mutants for SCAM. Pharmacological investigation showed that all mutants except hT99C and hL109C showed reduced cell‐surface expression, while all except hM107C showed a reduction in functional activity. The mutations did not markedly affect the apparent affinities of substrates, but apparent affinities of cocaine were decreased 7‐fold for hP97C and 10‐fold for hF101C and increased 12‐fold for hY98C. [3H]Nisoxetine binding affinities were decreased 13‐fold for hP97C and 5‐fold for hF101C. SCAM analysis revealed that only hL102C was sensitive to 1.25 mmMTSEA, and this sensitivity was protected by noradrenaline, nisoxetine and cocaine. The results suggest that this region of hNET is important for interactions with antidepressants and cocaine, but it is probably not involved in substrate translocation mechanisms.
Nerve growth factor‐induced expression of the GTP cyclohydrolase I gene via Ras/MEK pathway in PC12D cells
Authors: Ito Takehito , Suzuki Takahiro , Ichinose Hiroshi
Published: August 2005

Neurotrophins are essential for the development and survival of the catecholaminergic neurons. GTP cyclohydrolase I (GCH) is the first and rate‐limiting enzyme in the biosynthesis of 5,6,7,8‐tertahydrobiopterin (BH4), the required cofactor for tyrosine hydroxylase. Previously, we reported that TH requires the Ras/mitogen‐activated protein kinase kinase (MEK) pathway for its induction by nerve growth factor (NGF). Here, we examined intracellular signals required for NGF‐induced expression of the GCH gene in PC12D cells. The activity of GCH was increased up to 5‐fold after the NGF treatment, and the increase was repressed by pretreatment with U0126, an MEK1/2 inhibitor, but not with protein kinase A (PKA), phosphoinositide 3‐kinase (PI3K), p38 mitogen‐activated protein kinase (MAPK), and c‐Jun NH2‐terminal kinase (JNK) inhibitors. Induction of GCH mRNA by NGF was also abolished by pretreatment with U0126. The human GCH promoter activity was significantly enhanced by NGF treatment. Deletion analysis showed that the 465‐bp 5′‐flanking region is responsible for NGF‐enhanced promoter activity. These data suggest that the Ras–MEK pathway is required for coordinate expression of the GCH and TH genes induced by neurotrophins.
An unusual case of dementia: a case of paraneoplastic limbic encephalitis secondary to a non‐small cell lung cancer
Authors: WOOD Alice , LOCKINGTON Timothy
Published: August 2005

This case report accounts the history of a 71‐year‐old man who presented with a 1‐month history of cognitive decline, the diagnosis of which was only made at post‐mortem, and was found to be paraneoplastic limbic encephalitis secondary to an unsuspected non‐small cell lung cancer. The epidemiology, clinical and pathological features of paraneoplastic limbic encephalitis are then discussed, as are potential mechanisms by which the condition may be produced.
Senile depression with olfactory reference syndrome: a psychopathological review
Authors: KOBAYASHI Toshiyuki , KATO Satoshi
Published: August 2005

Olfactory reference syndrome (ORS) is a psychiatric condition characterized by a persistent preoccupation with body odor and is regarded as a common clinical entity known as jiko‐shu‐kyofu or jiko‐shu‐sho in published Japanese medical reports. However, the condition has not been assigned appropriate significance in recent operational diagnostic criteria. While adolescent patients with ORS seem to nosologically range from patients with obsessive–compulsive disorder to patients with schizophrenia, ORS is likely to be observed in depressive patients during presenile and senile periods. In this paper, two elderly patients with depression and ORS are presented and the relationship between depression and ORS is discussed from the viewpoint of psychopathology. The first case involved a 60‐year‐old woman with depression who complained that she was emitting a decaying body odor. Six years prior to this episode, she had been plagued by typical depression with inhibition; in the next phase of her illness, she manifested little inhibition, but developed ORS, which was effectively treated with clomipramine. The second case was an 88‐year‐old woman with depression and mild senile dementia who was placed in a nursing home for the elderly. After a delirium‐like episode, she became depressed and complained that she was emitting a bad body odor. Clomipramine was efficacious in providing relief from her symptoms. These case studies show two aspects of the relation between depression and ORS. First, ORS appears to arise from the ambiguity surrounding the onset of depressive delusion, in line with S. Kato's discussion of the ‘semantic horizon of evil’. Second, ORS appears to be equivalent to the mixed state defined by T. Miyamoto as ‘the matrix of both mania and depression’.
Caloric Restriction and Caloric Restriction Mimetics: Current Status and Promise for the Future
Authors: Roth George S.
Published: August 2005

Dietary caloric restriction is the most reproducible means of extending longevity and maintaining health and vitality. It has been shown to be relevant to a wide rage of species, including primates. Examination of key markers of the calorically restricted phenotype, such as plasma insulin, dehydroepiandrosterone sulfate, and body temperature, suggest that they may predict longevity in humans as well. However, most people would be unwilling or unable to adopt the 30% to 40% reduction in food intake necessary to achieve optimal health and longevity benefits. For this reason, a number of laboratories are pursuing caloric restriction mimetics: ways to achieve the benefits of restriction without eating less. This approach will undoubtedly remain a major focus of biogerontolgy for the foreseeable future.
Telomere Biology in Aging and Cancer
Authors: Wright Woodring E. , Shay Jerry W.
Published: August 2005

It is thought that a limited investment by the body in many types of maintenance and repair causes aging. Cell turnover is one mechanism of replacing damaged cells, and cell division thus contributes to good repair, but the number of times cells can divide is limited to form a barrier against cancer. Precancerous cells must divide many times to accumulate all of the mutations needed to become malignant. Limiting the number of times they can divide helps prevent cancer. The mechanism for counting cell divisions lies in structures at the ends of the chromosomes called telomeres that shorten with every division, eventually causing cell aging. This shortening can be prevented and cells immortalized using the enzyme telomerase, which can elongate telomeres. Immortalizing all of the cells in the body might increase repair but would remove the barrier to malignancy and would probably cause premature death from cancer in many cases, although the ability to immortalize cells opens up enormous opportunities for using normal cells for therapeutic purposes in localized areas. Eventually, once better controls and treatments for cancer are available, cellular rejuvenation by manipulating telomeres may reduce some of the physiological declines that accompany aging. Such treatments should increase health span, but because replicative aging represents only one of many processes that may contribute to overall human aging, modest increases in life span are expected at best.
Determinants of the Level of Knowledge Application: A Knowledge‐Based and Information‐Processing Perspective*
Authors: Song Michael , Van Der Bij Hans , Weggeman Mathieu
Published: August 2005

Knowledge application is of key importance in the development of successful new products. Knowledge application refers to an organization's timely response to technological change by utilizing the knowledge and technology generated into new products and processes. This study uses the knowledge‐based theory of the firm and considers its roots in the information‐processing approach to organization theory to identify and structure potential antecedents of knowledge application.

This study develops four hypotheses concerning antecedents of knowledge application. The hypotheses are tested using data collected from 277 high‐technology firms. Empirical results indicate that a long‐term orientation supported by a research and development (R&D) budget, formal rewards, and information technology directly increases the level of knowledge application, while R&D co‐location indirectly increases the level of knowledge application. It is surprising to find that an increase in the level of organizational redundancy reduces the level of knowledge application. The findings also suggest that information technologies, lead‐user, and supplier networks do not appear to significantly influence organizational redundancy.