bluuebunny/crossref_metadata_2025 huggingface dataset:
A general autoimmunity gene (PTPN22) is not associated with inflammatory bowel disease in a British population
Authors: Prescott N. J. , Fisher S. A. , Onnie C. , Pattni R. , Steer S. , Sanderson J. , Forbes A. , Lewis C. M. , Mathew C. G.
Published: September 2005

A single‐nucleotide polymorphism (C1858T) causing an amino acid substitution (R620W) in the lymphoid protein tyrosine phosphatase gene PTPN22 has been implicated in type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, juvenile idiopathic arthritis and Hashimoto's thyroiditis, thus revealing a general role for this gene in autoimmune disease. We investigated the association of the C1858T variant in an additional autoimmune disease population by performing a case‐control study of 514 British individuals with inflammatory bowel disease (IBD) [294 with Crohn's disease (CD) and 220 with ulcerative colitis (UC)] and 374 normal controls. No significant differences in genotype or allele frequencies were observed between IBD, CD or UC and controls, indicating that PTPN22 does not influence risk of IBD.
Contrasting effects of long distance seed dispersal on genetic diversity during range expansion
Authors: Bialozyt R. , Ziegenhagen B. , Petit R. J.
Published: September 2005

Currently many attempts are made to reconstruct the colonization history of plant species after the last ice age. A surprising finding is that during the colonization phase genetic diversity did not decrease as much as expected. In this paper we examine whether long distance seed dispersal events could play a role in the unexpected maintenance of genetic diversity during range expansion. This study is based on simulations carried out with a maternally inherited haploid locus using a cellular automaton. The simulations reveal a close relationship between the frequency of long distance seed dispersal events and the amount of genetic diversity preserved during colonization. In particular, when the colonized region is narrow, a complete loss of genetic diversity results from the occurrence of very rare long distance dispersal (LDD) events. We call this phenomenon the ‘embolism effect’. However, slightly higher rates of LDD events reverse this effect, up to the point that diversity is better preserved than in a pure diffusion model. This phenomenon is linked to the reorganization of the genetic structure during colonization and is called the ‘reshuffling effect’.
Variation in synonymous codon use and DNA polymorphism within the Drosophila genome
Authors: Bierne N. , Eyre-walker A.
Published: September 2005

A strong negative correlation between the rate of amino-acid substitution and codon usage bias in Drosophila has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. To further explore this possibility we have investigated polymorphism and divergence at three kinds of sites: synonymous, nonsynonymous and intronic in relation to codon bias in D. melanogaster and D. simulans. We confirmed that protein evolution is one of the main explicative parameters for interlocus codon bias variation (r2∼ 40%). However, intron or synonymous diversities, which could have been expected to be good indicators of local interference [here defined as the additional increase of drift due to selection on tightly linked sites, also called ‘genetic draft’ by Gillespie (2000)] did not covary significantly with codon bias or with protein evolution. Concurrently, levels of polymorphism were reduced in regions of low recombination rates whereas codon bias was not. Finally, while nonsynonymous diversities were very well correlated between species, neither synonymous nor intron diversities observed in D. melanogaster were correlated with those observed in D. simulans. All together, our results suggest that the selective constraint on the protein is a stable component of gene evolution while local interference is not. The pattern of variation in genetic draft along the genome therefore seems to be instable through evolutionary times and should therefore be considered as a minor determinant of codon bias variance. We argue that selective constraints for optimal codon usage are likely to be correlated with selective constraints on the protein, both between codons within a gene, as previously suggested, and also between genes within a genome.
A comparison of methods to estimate cross-environment genetic correlations
Authors: Astles P. A. , Moore A. J. , Preziosi R. F.
Published: September 2005

Advanced techniques for quantitative genetic parameter estimation may not always be necessary to answer broad genetic questions. However, simpler methods are often biased, and the extent of this determines their usefulness. In this study we compare family mean correlations to least squares and restricted error maximum likelihood (REML) variance component approaches to estimating cross-environment genetic correlations. We analysed empirical data from studies where both types of estimates were made, and from studies in our own laboratories. We found that the agreement between estimates was better when full-sib rather than half-sib estimates of cross-environment genetic correlations were used and when mean family size increased. We also note biases in REML estimation that may be especially important when testing to see if correlations differ from 0 or 1. We conclude that correlations calculated from family means can be used to test for the presence of genetic correlations across environments, which is sufficient for some research questions. Variance component approaches should be used when parameter estimation is the objective, or if the goal is anything other than determining broad patterns.
Differences in Wheat Cultivar Response to N Supply. I: Differences in Grain Yield Formation
Authors: Diekmann F. , Fischbeck G.
Published: September 2005

Two‐year field trials with winter wheat cultivars Batis and Toronto were conducted in Southern Bavaria, Germany, to investigate the possible causes of cultivar differences in response to N supply varying in total amount and time of application. Cultivar‐related differences in grain yields were observed in treatments with low and medium N supply. High doses of N supply resulted in grain yield adjustment or grain yield advantage for cv. Toronto. The results of this study revealed a consistent, genotypic pattern in response to N fertilization in spite of strong seasonal effects. Systematic modifications in canopy growth rates in response to N supply were of particular relevance and a main factor for differences in tillering intensity resulting in modified stand densities. In the present study, cultivar differences in spike development and interactions with N supply related more to abortion than to initiation processes for number of spikelets and number of flowers per spikelet. High grain density (grains per m2) of cv. Toronto was evident during reproduction stages even under conditions of medium N supply. However, decreased growth rates during the later part of grain filling in combination with low 1000 grain weight, which was barely modified by N fertilization, allowed only partial utilization of this potential. It is assumed that sink limitations were of particular relevance for grain yield development in cv. Toronto, while cv. Batis combined a less intense response to N supply with more stability in the development of grain yield components.
Differences in Wheat Cultivar Response to Nitrogen Supply. II: Differences in N‐Metabolism‐Related Traits
Authors: Diekmann F. , Fischbeck G.
Published: September 2005

Two‐year field trials with winter wheat cultivars Batis and Toronto were conducted in Southern Bavaria, Germany, to investigate the possible causes of cultivar differences in response to N supply varying in total amount and time of application. The results revealed cultivar‐related differences in response to N fertilization in all parameters included in this study. Amount and timing of N fertilization was a strong indicator of N uptake into canopies and three phases of cultivar differentiation became apparent. Cultivar differences in N content were most clearly expressed during early growth stages, but distinctive differences in canopy N uptake were observed during later growth stages. Nitrate reductase activity, water‐soluble carbohydrates (WSC), and plant nitrate content varied in response to N supply within cultivar‐specific patterns that included reversals in cultivar ranking during canopy development, and provided additional indications for elevated intensity of N metabolism in cv. Toronto when compared with cv. Batis. Apart from such differences Batis partially compensated for delayed N uptake in earlier phases during the latter part of grain filling, presumably due to differences in root system development. Cultivar differences in regression of tillering, stand density, grains per ear and grain density (grains m−2) on a number of N metabolism‐related parameters have been determined. They contribute considerably to the understanding of cultivar differences in grain yield components, as presented in an earlier communication. For 1000 grain weight, least affected from N supply within each year, large differences between years seemed to relate to differences in WSC content observed between heading and flowering, whereas cultivar differences in the level of grain N content and reaction to N supply were more directly determined by differences in N uptake and remobilization, and possibly enhanced by sink limitations of Toronto in grain size development.
Dietary lutein and fat interact to modify macrophage properties in chicks hatched from carotenoid deplete or replete eggs
Authors: Selvaraj R. K. , Koutsos E. A. , Calvert C. C. , Klasing K. C.
Published: September 2005

Two experiments were conducted to study the interaction between dietary lutein and fat levels in broiler chicks hatched from lutein depleted (Experiment I) and repleted (Experiment II) eggs. In both experiments, a 2 × 3 factorial arrangement of treatments resulted in six dietary treatments (fat at 3% and 6% and lutein at 0, 25 and 50 mg/kg feed) that were fed for 23 days to 18 birds per treatment (in three replications). In Experiment I, the anti‐dinitrophenyl‐keyhole‐lympet‐hemocyanin (anti‐DNP‐KLM) serum antibody response at day 22 and macrophage phagocytotic index at day 17 did not differ among treatment groups (p > 0.05). The concavalin A and phytohaemagglutinin‐P lymphocyte proliferation index at day 19 was greater in birds fed 50 mg of lutein and 3% fat than in birds fed all other diets (p < 0.05). Independent of the level of dietary fat, dietary lutein increased macrophage (day 23) nitrite production measured 46 h after in vitro stimulation with LPS (p < 0.05). Among the birds fed lutein at 25 or 50 mg/kg feed, birds fed 3% fat had higher LPS–induced nitrite production compared to the birds fed 6% fat after 46 (p = 0.014) or 70 h (p < 0.001). In Experiment II, macrophage nitrite production was measured at 54 h after LPS stimulation on days 11, 15, 19 and 23. An interaction between dietary lutein and fat levels on nitrite production was observed on day 19 (p = 0.012), where macrophages from birds fed 0 mg lutein and 3% fat had the highest nitrite production (p = 0.012). Macrophages from birds fed lutein at 25 and 50 mg/kg diet and 3% fat had higher (p = 0.012) nitrite production than birds fed 6% fat. Thus, in birds hatched from lutein deplete and replete eggs, modulation of macrophage nitrite production by lutein is dependent on the level of dietary fat.
Aggressive Lennert's lymphoma: Report of three cases in comparison to non‐aggressive Lennert's lymphoma
Authors: Kitamura Atsuko , Yamashita Yoriko , Sato Yuji , Hasegawa Yuichi , Kojima Hiroshi , Nagasawa Toshiro , Mori Naoyoshi
Published: September 2005

The present article describes three cases of Lennert's lymphoma exhibiting aggressive clinical courses. These cases were accompanied by disseminated intravascular coagulation (DIC) or hemophagocytic syndrome (HPS). These cases were compared to non‐aggressive type of Lennert's lymphoma. Of the three cases, two demonstrated involvement of the liver and the other possessed bone marrow involvement. In one patient, while a lymph node biopsy revealed Lennert's lymphoma histologically, a liver biopsy obtained 2 months later revealed a high‐grade large cell cytotoxic T‐cell lymphoma. Two of these cases showed HPS and the other exhibited DIC. All patients died within 1 year of diagnosis, with the shortest survival period being 1.5 months. Immunohistochemically, lymphoma cells were CD8+, CD4‐, granzyme B+, and T‐cell intracellular antigen‐1 (TIA‐1)+, showing a cytotoxic T‐cell phenotype. Two cases demonstrated positive reactivity for Epstein–Barr virus in lymphoma cells by in situ hybridization. These cases were compared with eight cases of non‐aggressive Lennert's lymphoma. In comparison to non‐aggressive disease, these three cases displayed a higher percentage of Ki‐67‐positive cells. In conclusion it was found that a subset of Lennert's lymphoma cases share common features with high‐grade cytotoxic T‐cell lymphoma, indicating that Lennert's lymphoma may be part of the spectrum of cytotoxic T‐cell lymphoma.
Incidental in vivo detection of an epithelioid hemangioendothelioma of the mitral valve
Authors: Val‐Bernal J. Fernando , García‐Alberdi Eva , Gutierrez J. Antonio , Garijo M. Francisca
Published: September 2005

Valvular epithelioid hemangioendotheliomas (EHE) are exceptional. To the authors’ knowledge only four cases have been reported. Herein is described an EHE incidentally detected in the mitral valve of a 69‐year‐old woman with chronic rheumatic valvular heart disease. The 0.4 cm lesion was situated in the anterior leaflet and was discovered in the pathological study after mitral valve replacement. The patient was alive and well 6 months after operation. Review of the literature including the present report, revealed that the mean age was 60.2 years (range, 49–69 years). Symptomatic patients had clinical features of valvular disease or embolism. Each of the four cardiac valves can be affected. Mean tumor size was 2.4 cm (range, 0.4–8 cm). In 40% of cases the EHE was an incidental finding at autopsy or in a removed valve. In two cases the involved cusp was affected by chronic rheumatic disease. In conclusion, EHE is a rare lesion that can be an incidental finding and it should be considered in the differential diagnosis of valve tumors. Although EHE can present a histologically benign appearance, the correct pathological diagnosis is clinically important because the lesion can be potentially malignant. Regular follow up is suggested due to this potential.
Multiple gastrointestinal stromal tumors with a germline c‐kit mutation
Authors: Kim Hyun Jung , Lim Sung‐Jig , Park Kyeongmee , Yuh Young Jin , Jang Se J. , Choi Jene
Published: September 2005

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder; thus far, only seven families have been reported with c‐kit germline mutations. Presented herein is a case of multiple intestinal GIST in a 38‐year‐old man with a germline mutation of the c‐kit gene. Operative specimens of the jejunal segment and multiple wedge resection specimens included approximately 30 masses, ranging in size from 1.0 to 6.0 cm. Microscopically, the tumors were composed of CD117‐positive spindle/epitheloid cells with variable numbers of mitotic counts, a characteristic of GIST. The mitotic rate increased to more than 5/50 high‐power fields. Interestingly, marked hypertrophy of the myenteric plexus with CD117‐positive cells was identified in the intestinal segment. By polymerase chain reaction–single‐strand conformation polymorphism analysis and direct DNA sequencing, a heterozygous c‐kit missense mutation at nucleotide 1676 of codon 559 (T → C, Val → Ala), part of the juxtamembrane domain, was detected in the normal tissue. The same mutation was homozygous in the tumor samples. The present case is the first proven case of multiple GIST with a c‐kit germline mutation in Korea and is distinguishable from other reported germ‐line c‐kit mutations because the same 1676 T → C missense mutation occurs in the normal allele as well as the affected allele, although the significance of the identical mutations remains to be investigated.
Post‐liver transplantation de novo hepatitis with overlap features
Authors: Keaveny Andrew P. , Gordon Fredric D. , Khettry Urmila
Published: September 2005

The development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults. Reported herein is a case that is best characterized as post‐LT de novo hepatitis with features of autoimmune hepatitis (AIH)–primary biliary cirrhosis (PBC) overlap. A 56‐year‐old man underwent LT for decompensated liver disease secondary to non‐alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 months after LT. Sequential liver transplant biopsy findings were confusing and shared findings seen with both AIH and PBC. Although standard autoimmune serological tests were negative, a dramatic biochemical response was observed to a regimen consisting of prednisone, mycophenolate mofetil, and ursodeoxycholic acid added to maintainance tacrolimus. The donor was histocompatibility leukocyte antigen, DR4, positive, a haplotype associated with the development of AIH–PBC overlap syndrome. In conclusion the authors believe that this may be a case of post‐LT de novo overlap syndrome of AIH‐PBC, a novel ‘autoimmune‐type’ response.
PQBP‐1 is expressed predominantly in the central nervous system during development
Authors: Qi Yunglong , Hoshino Masataka , Wada Yo‐ichi , Marubuchi Shigeki , Yoshimura Natsue , Kanazawa Ichiro , Shinomiya Ken‐ichi , Okazawa Hitoshi
Published: September 2005

Mutations of PQBP‐1 (polyglutamine binding protein‐1) have been shown recently to cause human mental retardation accompanied by microcephaly at a high frequency. As a first step towards understanding the molecular basis of this developmental anomaly, we analysed developmental expression of PQBP‐1 by in situ hybridization, immunohistochemsitry and Western blot analysis. Although it had been shown by Northern blot analysis that PQBP‐1 mRNA is expressed in multiple organs in adult mice, our present results revealed that PQBP‐1 mRNA and protein are dominantly expressed in the central nervous system (CNS) in embryos and in newborn mice. The mean expression level of PQBP‐1 reaches a peak around birth and is down‐regulated in adulthood. Furthermore, the expression pattern in the CNS changes remarkably following birth. PQBP‐1 mRNA in the cerebral cortex is high in embryos but it rapidly decreases after birth. PQBP‐1 mRNA increases in external and internal granular cell layers of the cerebellum from postnatal day 1 (P1) to P5. In addition, expression in the subventricular zone, where neurogenesis occurs, was high from P5 to adulthood. Collectively, these findings suggest that PQBP‐1 might be involved in neuronal proliferation and/or maturation. These ideas may be relevant to the insufficient growth of brain structure reported in PQBP‐1‐linked human mental retardation.
Life‐threatening hypokalaemia on a low‐carbohydrate diet associated with previously undiagnosed primary hypoaldosteronism
Authors: Advani A. , Taylor R.
Published: September 2005

Background  Low‐carbohydrate diets are popular and fashionable for weight loss despite lack of evidence about long‐term effects. Many individuals attempting to lose weight have hypertension, especially those with diabetes, and the prevalence of hyperaldosteronism among hypertensive patients is higher than previously recognized. We present a patient with Type 2 diabetes and previously undiagnosed hyperaldosteronism who developed life‐threatening hypokalaemia while following a low‐carbohydrate diet.

Case Report  A 60‐year‐old man with diet‐treated Type 2 diabetes and hypertension presented with generalized muscle weakness and serum potassium of 1.9 mmol/l. He had succeeded in losing three and a half stones during the previous 4 months by adhering strictly to a low‐carbohydrate diet. HbA1c was 4.8% and plasma aldosterone:renin ratios were elevated suggestive of increased aldosterone secretion. On a low‐calorie mixed diet serum potassium levels were maintained in the low‐normal range over the following 165 days. The adrenals were normal on CT scanning and blood pressure responded dramatically to the addition of spironolactone on day 212 (125/83 mmHg).

Conclusions  The prevalence of primary hyperaldosteronism in the hypertensive population, based on elevation of plasma renin:aldosterone ratio, is approximately 6%. The majority of these people are normokalaemic and remain undiagnosed. However, when carbohydrate intake is restricted such individuals are at increased risk of potentially life‐threatening metabolic derangements.
Visual Cognition Influences Early Vision
Authors: Lee Hyunkyu , Vecera Shaun P.
Published: September 2005

A partly occluded visual object is perceptually filled in behind the occluding surface, a process known as amodal completion or visual interpolation. Previous research focused on the image-based properties that lead to amodal completion. In the present experiments, we examined the role of a higher-level visual process—visual short-term memory (VSTM)—in amodal completion. We measured the degree of amodal completion by asking participants to perform an object-based attention task on occluded objects while maintaining either zero or four items in visual working memory. When no items were stored in VSTM, participants completed the occluded objects; when four items were stored in VSTM, amodal completion was halted (Experiment 1). These results were not caused by the influence of VSTM on object-based attention per se (Experiment 2) or by the specific location of to-be-remembered items (Experiment 3). Items held in VSTM interfere with amodal completion, which suggests that amodal completion may not be an informationally encapsulated process, but rather can be affected by high-level visual processes.
Visual Memory Decay Is Deterministic
Authors: Gold Jason M. , Murray Richard F. , Sekuler Allison B. , Bennett Patrick J. , Sekuler Robert
Published: September 2005

After observers see an object or pattern, their visual memory of what they have seen decays slowly over time. Nearly all current theories of vision assume that decay of short-term memory occurs because visual representations are progressively and randomly corrupted as time passes. We tested this assumption using psychophysical noise-masking methods, and we found that visual memory decays in a completely deterministic fashion. This surprising finding challenges current ideas about visual memory and sets a goal for future memory research: to characterize the deterministic “forgetting function” that describes how memories decay over time.
The Meaning of the Mask Matters
Authors: Dux Paul E. , Coltheart Veronika
Published: September 2005

The rapid serial visual presentation (RSVP) experiment reported here investigated the role of conceptual interference in the attentional blink (AB). Subjects were presented with RSVP streams that contained five stimuli: Target 1, a distractor, Target 2, a second distractor, and a symbol mask. Target 1 was a green letter, Target 2 was a red letter, and the distractors were either white letters or white digits. The stimuli were presented in a font typically seen on the face of a digital watch. Thus, “S” and “O” were identical to “5” and “0,” respectively. This allowed us to present streams that were conceptually different even though featurally identical: The two letter targets were followed by distractors that were recognized either as “5” and “0” or as “S” and “O.” The AB was substantially attenuated when subjects were told the distractors were digits rather than letters. This result indicates that conceptual interference plays a role in the AB.
Hypnotic Disgust Makes Moral Judgments More Severe
Authors: Wheatley Thalia , Haidt Jonathan
Published: September 2005

Highly hypnotizable participants were given a posthypnotic suggestion to feel a flash of disgust whenever they read an arbitrary word. They were then asked to rate moral transgressions described in vignettes that either did or did not include the disgust-inducing word. Two studies show that moral judgments can be made more severe by the presence of a flash of disgust. These findings suggest that moral judgments may be grounded in affectively laden moral intuitions.
Data Dependent Endogeneity Correction in Cointegrated Panels*
Authors: Westerlund Joakim
Published: September 2005

This paper examines the small‐sample performance of several information based criteria that can be employed to facilitate data dependent endogeneity correction in estimation of cointegrated panel regressions. The Monte Carlo evidence suggests that the criteria generally perform well but that there are differences of practical importance. In particular, the evidence suggests that, although the estimators of the cointegration vectors generally perform well, the criterion with best small‐sample performance also leads to the best performing estimator.
Temporal lobe epileptic activity mimicking dementia: a case report
Authors: Tombini M. , Koch G. , Placidi F. , Sancesario G. , Marciani M. G. , Bernardi G.
Published: September 2005

Epileptic activity is an underdiagnosed cause that can determine a disruption of memory and cognitive performance, leading an incorrect diagnosis of dementia. We report a 68‐year‐old man, referred with a 5‐year history of subtle behavioral changes and a subjective memory impairment, who was admitted to our department because of recurrent episodes of confusional state lasting from 1 week. Neuropsychological evaluation demonstrated a marked impairment of all cognitive domains examined. Electroencephalogram (EEG) recording showed frequent almost continuous sharp waves localized on the bilateral posterior temporal regions with mild right side predominance. Treatment with phenytoin reversed his cognitive dysfunction and behavioral disturbances. We presume that ictal temporal lobe epileptiform activity is the cause of his confusional episodes and cognitive dysfunction, showing an electroclinical picture of complex partial status epilepticus. However, we hypothesize that the interictal discharges and ictal and postictal effects of subclinical seizures could be involved in the behavioral changes and memory impairment complained by our patient in the last years.
Inhibition of IL‐6 overproduction by steroid treatment before transsternal thymectomy for myasthenia gravis: does it help stabilize perioperative condition?
Authors: Endo S. , Hasegawa T. , Sato Y. , Otani S. , Saito N. , Tetsuka K. , Tezuka Y. , Sohara Y.
Published: September 2005

Overproduction of interleukin (IL)‐6 plays an important role in the pathophysiology of myasthenia gravis (MG), and thymectomy can cause myasthenic crisis because of surgically induced overproduction of IL‐6. Preoperative steroid therapy is beneficial in preventing MG crisis during the perioperative period. The purpose of this study was to clarify the effect of preoperative steroid therapy on proinflammatory mediators during the perioperative period of transsternal thymectomy for MG. The study group comprised 20 consecutive MG patients undergoing transsternal thymectomy during the period March 2002 through March 2004. Seventeen of these patients received dose‐escalated steroid therapy before thymectomy (steroid treatment group) and three did not (non‐steroid treatment group). Serum concentrations of C‐reactive protein (CRP) and IL‐6 were determined during the perioperative period; clinical outcomes were reviewed, and the results were compared between the two groups. Peak serum IL‐6 and CRP concentrations were significantly lower in the steroid treatment group than in the non‐steroid treatment group. Amongst perioperative variables subjected to multiple regression analysis, preoperative steroid treatment were found to be the most significant independent predictor of inhibited IL‐6 production on postoperative day 1. No postoperative respiratory failure occurred in the steroid treatment group, but it did occur in the non‐steroid treatment group. Preoperative steroid therapy can ameliorate IL‐6 overproduction and may help stabilize the patient's postoperative condition.
EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy
Authors: Lauria G. , Cornblath D. R. , Johansson O. , McArthur J. C. , Mellgren S. I. , Nolano M. , Rosenberg N. , Sommer C.
Published: September 2005

Skin biopsy has become a widely used tool to investigate small calibre sensory nerves including somatic unmyelinated intraepidermal nerve fibres (IENF), dermal myelinated nerve fibres, and autonomic nerve fibres in peripheral neuropathies and other conditions. Different techniques for tissue processing and nerve fibre evaluation have been used. In March 2004, a Task Force was set up under the auspices of the European Federation of Neurological Societies (EFNS) with the aim of developing guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathies. We searched the Medline database from 1989, the year of the first publication describing the innervation of human skin using immunostaining with anti‐protein‐gene‐product 9.5 (PGP 9.5) antibodies, to 31 March 2005. All pertinent papers were rated according to the EFNS guidance. The final version of the guidelines was elaborated after consensus amongst members of the Task Force was reached. For diagnostic purposes in peripheral neuropathies, we recommend performing a 3‐mm punch skin biopsy at the distal leg and quantifying the linear density of IENF in at least three 50‐μm thick sections per biopsy, fixed in 2% PLP or Zamboni's solution, by bright‐field immunohistochemistry or immunofluorescence with anti‐PGP 9.5 antibodies (level A recommendation). Quantification of IENF density closely correlated with warm and heat‐pain threshold, and appeared more sensitive than sensory nerve conduction study and sural nerve biopsy in diagnosing small‐fibre sensory neuropathy. Diagnostic efficiency and predictive values of this technique were very high (level A recommendation). Confocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation. In future, the diagnostic yield of dermal myelinated nerve fibre quantification and of sweat gland innervation should be addressed. Longitudinal studies of IENF density and regeneration rate are warranted to correlate neuropathological changes with progression of neuropathy and to assess the potential usefulness of skin biopsy as an outcome measure in peripheral neuropathy trials (level B recommendation). In conclusion, punch skin biopsy is a safe and reliable technique (level A recommendation). Training in an established cutaneous nerve laboratory is recommended before using skin biopsy as a diagnostic tool in peripheral neuropathies. Quality control at all levels is mandatory.
Towards Improving Medical Care for People with Intellectual Disability Living in the Community: Possibilities of Integrated Care
Authors: Jansen D. E. M. C. , Krol B. , Groothoff J. W. , Post D.
Published: September 2005

Background  Ongoing deinstitutionalization has resulted in several problems in medical care delivery to people with intellectual disability, such as an increased workload for general practitioners (GPs) and a lack of active co‐ordination and co‐operation between healthcare professionals. A major consequence is the incidence of untreated yet treatable medical conditions. An integrated care approach may provide a means for better co‐ordination and delivery of care. The aim is to review recent integrated care initiatives and their significance for people with intellectual disability.

Method  A literature search was conducted to trace relevant literature on integrated care for people with intellectual disability published between 1995 and 2003.

Results  Although integrated care appears to offer potential for eliminating fragmentation and discontinuity in medical care for people with intellectual disability and for reducing GP workload, there are few published studies which have evaluated its implementation with people with intellectual disability.

Conclusions  Even though the potential advantages of integrated care are well known, the applicability of this approach for people with intellectual disability has still to be demonstrated.
Responses of Female Fire‐Setters with Mild and Borderline Intellectual Disabilities to a Group Intervention
Authors: Taylor John L. , Robertson Alison , Thorne Ian , Belshaw Tracy , Watson Angela
Published: September 2005

Background  This report describes a cognitive behavioural group intervention for women with mild and borderline intellectual disabilities detained in a secure hospital setting because of their fire‐setting behaviour. The study aimed to examine participants’ motivations for setting fires, their responses to an intervention designed specifically for this group and to monitor their progress over an extended follow‐up period.

Methods  A number of fire‐specific and clinical assessments were administered before the intervention started and immediately after it concluded to examine trends in the group data. Detailed case study material was collected in order to describe participants’ engagement in and reactions to the treatment process, and their status at 2‐year follow‐up.

Results  The intervention successfully engaged participants in the therapy process, all of whom completed the programme. Scores on measures related to fire‐related treatment targets and clinical measures pertinent to motivations for fire‐setting generally improved following the intervention. There were no reports of participants setting any fires 2 years after the intervention programme was completed.

Conclusions  The group intervention appeared to be acceptable and beneficial to study participants. This pilot study needs to be extended into a more robust evaluation of this approach with this group.
Anatomy of melancholia: focus on hypothalamic–pituitary–adrenal axis overactivity and the role of vasopressin
Authors: Dinan Timothy G. , Scott Lucinda V.
Published: September 2005

Overactivity of the hypothalamic–pituitary–adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin‐releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down‐regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.
Anatomical perspectives on adult neural stem cells
Authors: Watts C. , McConkey H. , Anderson L. , Caldwell M.
Published: September 2005

The concept of stem cells within the adult brain is not new. However, only recently have scientific techniques become sufficiently advanced to identify them although this remains problematic and the technology is still developing. Nevertheless, it is now generally recognized that stem cells are restricted to two germinal regions within the intact brain. From here they can migrate to specific destinations where they integrate with existing circuitry. Their identity remains controversial but a growing body of evidence suggests it may have an astrocytic phenotype. Within the germinal regions the stem cells are confined to a niche environment and are capable of responding to environmental signals generated locally in an autocrine or paracrine fashion. The niche environment is also modulated by more generalized systemic and physiological activity. These observations are exciting in their own right and form the basis of this review. They are also beginning to alter how we think about neural injury and disease and to impact on the development of novel therapies.
Stem cells, progenitors and myelin repair
Authors: Zhao Chao , Fancy Stephen P. J. , Magy Laurent , Urwin Joanna E. , Franklin Robin J. M.
Published: September 2005

Remyelination, the process by which new myelin sheaths are restored to demyelinated axons, represents one of the most compelling examples of adult multipotent progenitor cells contributing to regeneration of the injured central nervous system (CNS). This process can occur with remarkable efficiency in both clinical disease, such as multiple sclerosis, and in experimental models, revealing an impressive ability of the adult CNS to repair itself. However, the inconsistency of remyelination in multiple sclerosis, and the loss of axonal integrity that results from its failure, makes enhancement of remyelination an important therapeutic objective. Identifying potential targets will depend on a detailed understanding of the cellular and molecular mechanisms of remyelination. In this article we address two important issues. First, we consider the nature of the cell or cells that respond to demyelination and generate new oligodendrocytes, identifying current areas of uncertainty and addressing the role of adult CNS stem and progenitor cells. Second, we discuss the concept of adult progenitor activation following demyelination, focusing on the increased expression of (1) olig transcription factors, (2) bone morphogenetic proteins and (3) fyn, a member of the src‐family of tyrosine kinases.
Role of radial glia in cytogenesis, patterning and boundary formation in the developing spinal cord
Authors: McDermott Kieran W. , Barry Denis S. , McMahon Siobhan S.
Published: September 2005

Radial glial fibres provide a transient scaffold and impose constraints in the developing central nervous system (CNS) that facilitate cell migration and axon growth. Recent reports have raised doubts about the distinction between radial glia and precursor cells by demonstrating that radial glia are themselves neuronal progenitor cells in the developing cortex, indicating a dual role for radial glia in both neurogenesis and migration guidance. Radial glia shift toward exclusive generation of astrocytes after neurogenesis has ceased. Radial progenitor cell differentiation and lineage relationships in CNS development are complex processes depending on genetic programming, cell–cell interaction and microenvironmental factors. In the spinal cord, radial cells that arise directly from the neuroepithelium have been identified. At least in the spinal cord, these radial cells appear to be the precursors to radial glia. It remains unknown whether radial glial cells or their precursors, the radial cells, or both can give rise to neurons in the spinal cord. Radial glial cells are also important in regulating the axon out‐growth and pathfinding processes that occur during white matter patterning of the developing spinal cord.
Sami self‐determination in the making?*
Authors: Semb Anne Julie
Published: September 2005

Abstract.The article discusses whether principles of territorial or non‐territorial jurisdiction ought to guide the future distribution of decision‐making power between the Norwegian Sami Parliament and the Norwegian Parliament. It argues that an acceptable distribution of powers must satisfy two normative criteria: first, decision‐making power ought to be distributed on the basis of individuals' desire to be politically associated with some people rather than with others. Second, a normatively defensible distribution of decision‐making power must ensure that those who are subject to the jurisdiction of a particular body have the right to vote in elections for, and thus have the possibility to affect the composition of, that particular body. The article concludes that a non‐territorial principle for distribution of decision‐making power provides a more fruitful point of departure for discussions of the future status of the Sami Parliament in the Norwegian political system than do notions of territorial jurisdiction.
Nationalism and nostalgia: the case of radical Basque nationalism*
Authors: Muro Diego
Published: September 2005

Abstract.This article argues that the myth of the Golden Age is a key mobilising element within radical Basque nationalism. By using an ethno‐symbolist approach, this article argues that nostalgia, a catchword for looking back, usually relates to an idealised past. It then proceeds to explain how ETA in particular has domesticated the past to justify its political violence which is currently exalted as a means of honouring the fighting spirit of their ancestors. From this perspective, violence is presented as a redemptive act that can stop the decay of the Basque nation and bring a new political future in which the inspiring ancient virtues will be rediscovered. This nostalgic gaze upon the past continually ‘reminds’ radical Basque nationalists of an imaginary, yet familiar, past which can only be regained by using revolutionary violence.
Amniotic fluid brain‐specific proteins are biomarkers for spinal cord injury in experimental myelomeningocele
Authors: Petzold A. , Stiefel D. , Copp A. J.
Published: September 2005

Myelomeningocele (MMC), the most severe form of spina bifida (SB), causes neurological deficit. Injury to the spinal cord is thought to begin in utero. We investigated whether brain‐specific proteins (BSPs) would enable us to monitor the development of MMC‐related tissue damage during pregnancy in an animal model with naturally occurring SB (curly tail/loop tail mouse; n = 256). Amniotic fluid levels of neurofilament heavy chain (NfH), glial acidic fibrillary protein (GFAP) and S100B were measured by standard ELISA techniques. The amniotic fluid levels of all BSPs were similar in SB and control mice on embryonic day (E) 12.5 and 14.5, whereas a significant increase was observed for GFAP in SB mice on E16.5. Levels of all BSPs were significantly increased in SB mice on E18.5. The rapid increase in GFAP, paralleled by a moderate increase in NfH and S100B, suggests that spinal cord damage starts to accelerate around E16.5. The macroscopic size of the MMC was related to NfH level on E16.5 and E18.5, suggesting that axonal degeneration is most severe in large MMC. Amniotic fluid BSP measurements may provide important information for balancing the risks and benefits to mother and child of in utero surgery for MMC.
Ethanol disrupts cell cycle regulation in developing rat cortex interaction with transforming growth factor β1
Authors: Siegenthaler Julie A. , Miller Michael W.
Published: September 2005

Ethanol is a potent teratogenic agent that disrupts several aspects of neuronogenesis, including the proliferation rate of cortical precursors. With regard to corticogenesis, possible targets of ethanol toxicity include soluble factors, like transforming growth factor β1 (TGFβ1), that regulate cortical growth and cell cycle proteins that control the kinetics of the cell cycle. The effect of ethanol on normal cell proliferation and TGFβ1‐regulated cell proliferation in the developing cortex was assessed using an organotypic slice culture model. Ethanol elongated the cell cycle, possibly through a decrease in the expression of G1 cell cycle protein cyclin D1. Further, ethanol exposure antagonized the anti‐proliferative action of TGFβ1 and blocked TGFβ1‐dependent increases in cell cycle inhibitor p21. Collectively, this evidence suggests that disruption of appropriate cell cycle protein expression and inhibition of TGFβ1 activity are potential mechanisms underlying the effect of ethanol on cortical development.
Rapid WAVE dynamics in dendritic spines of cultured hippocampal neurons is mediated by actin polymerization
Authors: Pilpel Yair , Segal Menahem
Published: September 2005

The Wiskott–Aldrich syndrome protein family Verprolin‐homologous protein (WAVE) complex has been proposed to link Rho GTPase activity with actin polymerization but its role in neuronal plasticity has never been documented. We now examined the presence, distribution and dynamics of WAVE3 in cultured hippocampal neurons. WAVE3 was localized to dendritic spines via its N‐terminal domain. Green fluorescent protein (GFP)‐tagged WAVE3 clusters demonstrate an F‐actin‐dependent high rate of local motility. Constitutive Rac activation translocates WAVE3 (via the N‐terminus), to the leading edge of lamellipodia. Also, spinogenesis is associated with actin‐based motility of the WAVE3 protein. Brain specific WAVE1 showed similar localization and effects on spine density. Cytoplasmic fragile X mental retardation protein interacting protein (CYFIP) and non‐catalytic region of tyrosine kinase adaptor protein 1 (NCK‐1), proteins that are assumed to complex with WAVE, have a somewhat similar cellular distribution and motility. We propose that the WAVE complex is a downstream effector of the Rac signaling cascade, localized to sites of novel synaptic contacts by means of its N‐terminal domain, to guide local actin polymerization needed for morphological plasticity of neurons.
Karyotypes of two American field crickets: Gryllus rubens and Gryllus sp. (Orthoptera: Gryllidae)
Authors: YOSHIMURA Aya
Published: September 2005

The karyotypes of Gryllus rubens (Scudder) and Gryllus sp. collected in the US were studied using conventional Giemsa staining and two differential staining methods. Both species had a chromosome complement of 2n = 28 + XX/XO, and the X chromosome was large and metacentric. In addition, nucleolus organizer regions (NOR) were detected in the short arm of one pair in the two species, and the NOR showed variation in size. The two species had species‐specific chromosome configuration and C‐banding patterns. In Gryllus sp., the chromosome configuration showed polymorphism in size and type among individuals, and the distal C‐bands of Gryllus sp. were larger than those of G. rubens.
Vertical and seasonal variation in the abundance and the species richness of Attelabidae and Cantharidae (Coleoptera) in a suburban mixed forest
Authors: LEKSONO Amin Setyo , NAKAGOSHI Nobukazu , TAKADA Kenta , NAKAMURA Koji
Published: September 2005

A continuous sampling of canopy beetles was carried out to determine variation in the abundance and the species richness of the Attelabidae and Cantharidae in a suburban mixed forest. Changes in the abundance and the species richness were monitored in three vertical strata of the forest from May to November in 1999, using yellow and blue water pan traps. The results showed significant variation in the abundance and the species richness of Attelabidae and Cantharidae between the layers, trap colors and seasons. Rare species were found in the bottom and middle layers, but were absent in the upper layer. In contrast, common species were more abundant in the upper layer than in the lower layers. The yellow traps had better trapping efficiency than the blue traps for both families, with the exception of an attelabid species, Cycnotrachelus reolofsi, which was more abundant in the blue traps. The abundance and the species richness were generally greater in spring than in summer. In spring, the abundance was consistently highest in the yellow traps in the upper layer. Season and layer were determinant factors in the species composition of the Attelabidae, while only season explained variation in species composition of the Cantharidae.