bluuebunny/crossref_metadata_2025 huggingface dataset:
Parasitism shaping host life‐history evolution: adaptive responses in a marine gastropod to infection by trematodes
Authors: FREDENSBORG B. L. , POULIN R.
Published: November 2005

Variation in life‐history strategies among conspecific populations indicates the action of local selective pressures; recently, parasitism has been suggested as one of these local forces.

Effects of trematode infections on reproductive effort, juvenile growth, size at maturity and susceptibility were investigated among different natural populations of the marine gastropod Zeacumantus subcarinatus, Sowerby 1855.

Reproductive effort was not higher in uninfected snails from populations experiencing a high trematode prevalence, but females from high prevalence populations produced significantly larger offspring compared with their conspecifics from other populations.

Juvenile growth rate was significantly higher in laboratory‐raised snails originating from females in a high prevalence population compared with other populations.

Size at maturity, determined by the appearance of functional gonads, was significantly and negatively related to trematode prevalence, and positively related to mean snail size, across 10 populations in the study area.

There was no evidence of different host resistance against trematodes in sentinel snails from high and low prevalence populations exposed to the same infection pressure in the field.

Our results strongly indicate that Z. subcarinatus adapt to trematodes by reaching maturity early, thereby maximizing their chance of reproducing in populations experiencing a high prevalence of infection by castrating trematodes.
Corticosterone Actions on the Hippocampal Brain‐Derived Neurotrophic Factor Expression are Mediated by Exon IV Promoter
Authors: Hansson A. C. , Sommer W. H. , Metsis M. , Strömberg I. , Agnati L. F. , Fuxe K.
Published: November 2005

Brain‐derived neurotrophic factor (BDNF) expression is strongly regulated by adrenocorticosteroids via activated gluco‐ and mineralocorticoid receptors. Four separate promoters are located upstream of the BDNF noncoding exons I to IV and may thus be involved in adrenocorticosteroid‐mediated gene regulation. In adrenalectomised rats, corticosterone (10 mg/kg s.c.) induces a robust down‐regulation of both BDNF mRNA and protein levels in the hippocampus peaking at 2–8 h. To study the role of the individual promoters in the corticosterone response, we employed exon‐specific riboprobe in situ hybridisation as well as real‐time polymerase chain reaction (PCR) in the dentate gyrus. We found a down‐regulation, mainly of exon IV and the protein‐coding exon V, in nearby all hippocampal subregions, but exon II was only down‐regulated in the dentate gyrus. Exon I and exon III transcripts were not affected by corticosterone treatment. The results could be confirmed with real‐time PCR in the dentate gyrus. It appears as if the exon IV promoter is the major target for corticosterone‐mediated transcriptional regulation of BDNF in the hippocampus.
Two processivity clamp interactions differentially alter the dual activities of UmuC
Authors: Beuning Penny J. , Sawicka Dorota , Barsky Daniel , Walker Graham C.
Published: November 2005

DNA polymerases of the Y family promote survival by their ability to synthesize past lesions in the DNA template. One Escherichia coli member of this family, DNA pol V (UmuC), which is primarily responsible for UV‐induced and chemically induced mutagenesis, possesses a canonical β processivity clamp‐binding motif. A detailed analysis of this motif in DNA pol V (UmuC) showed that mutation of only two residues in UmuC is sufficient to result in a loss of UV‐induced mutagenesis. Increased levels of wild‐type β can partially rescue this loss of mutagenesis. Alterations in this motif of UmuC also cause loss of the cold‐sensitive and β‐dependent synthetic lethal phenotypes associated with increased levels of UmuD and UmuC that are thought to represent an exaggeration of a DNA damage checkpoint. By designing compensatory mutations in the cleft between domains II and III in β, we restored UV‐induced mutagenesis by a UmuC β‐binding motif variant. A recent co‐crystal structure of the ‘little finger’ domain of E. coli pol IV (DinB) with β suggests that, in addition to the canonical β‐binding motif, a second site of pol IV (303VWP305) interacts with β at the outer rim of the dimer interface. Mutational analysis of the corresponding motif in UmuC showed that it is dispensable for induced mutagenesis, but that alterations in this motif result in loss of the cold‐sensitive phenotype. These two β interaction sites of UmuC affect the dual functions of UmuC differentially and indicate subtle and sophisticated polymerase management by the β clamp.
Mating type regulation of cellular tolerance to DNA damage is specific to the DNA post‐replication repair and mutagenesis pathway
Authors: Barbour Leslie , Xiao Wei
Published: November 2005

In order to help further define DNA post‐replication repair (PRR), a conditional synthetic lethal screen was employed to identify new genes involved in the PRR pathway. A synthetic lethal screen with the mms2 mutation resulted in the recovery of two suppressor mutations responsible for regulating PRR. The recovered suppressors are the mating type genes and SIR3. Indeed, controlled expression of both mating type genes or deletion of SIR3 rescued the conditional synthetic lethal mutant phenotypes. Furthermore, comprehensive analyses suggest that mating type heterozygosity confers tolerance to a broad range of DNA damage, and that this effect is limited to all PRR pathway mutations, but does not apply to base excision repair, nucleotide excision repair or recombination repair mutants. In addition, the tolerance conferred to PRR mutants as a result of mating type heterozygosity is dependent on a functional homologous recombination but not the non‐homologous end‐joining pathway. Thus, mating type status appears to be responsible for signalling DNA content and possibly cell cycle stage, allowing the cell to select the most efficient means to repair the DNA damage.
Cloning, functional expression and primary characterization of Vibrio parahaemolyticus K+/H+ antiporter genes in Escherichia coli
Authors: Radchenko Martha V. , Waditee Rungaroon , Oshimi Sawako , Fukuhara Masahiro , Takabe Teruhiro , Nakamura Tatsunosuke
Published: November 2005

The regulation of internal Na+ and K+ concentrations is important for bacterial cells, which, in the absence of Na+ extrusion systems, cannot grow in the presence of high external Na+. Likewise, bacteria require K+ uptake systems when the external K+ concentration becomes too low to support growth. At present, we have little knowledge of K+ toxicity and bacterial outward‐directed K+ transport systems. We report here that high external concentrations of K+ at alkaline pH are toxic and that bacteria require K+ efflux and/or extrusion systems to avoid excessive K+ accumulation. We have identified the first example of a bacterial K+(specific)/H+ antiporter, Vp‐NhaP2, from Vibrio parahaemolyticus. This protein, a member of the cation : proton antiporter‐1 (CPA1) family, was able to mediate K+ extrusion from the cell to provide tolerance to high concentrations of external KCl at alkaline pH. We also report the discovery of two V. parahaemolyticus Na+/H+ antiporters, Vp‐NhaA and Vp‐NhaB, which also exhibit a novel ion specificity toward K+, implying that they work as Na+(K+)/H+ exchangers. Furthermore, under specific conditions, Escherichia coli was able to mediate K+ extrusion against a K+ chemical gradient, indicating that E. coli also possesses an unidentified K+ extrusion system(s).
Domains of group A streptococcal M protein that confer resistance to phagocytosis, opsonization and protection: implications for vaccine development
Authors: McArthur Jason D. , Walker Mark J.
Published: November 2005

Streptococcus pyogenes (group A streptococcus) colonizes skin and throat tissues resulting in a range of benign and serious human diseases. Opsonization and phagocytosis are important defence mechanisms employed by the host to destroy group A streptococci. Antisera against the cell‐surface M protein, of which over 150 different types have been identified, are opsonic and contribute to disease protection. In this issue of Molecular Microbiology, Sandin and colleagues have comprehensively analysed the regions of M5 protein that contribute to phagocytosis resistance and opsonization. Human plasma proteins bound to M5 protein B‐ and C‐repeats were shown to block opsonization, an observation that needs to be carefully considered for the development of M protein‐derived vaccines. While safe and efficacious human group A streptococcal vaccines are not commercially available, candidate M protein‐derived vaccines have shown promise in murine vaccine models and a recent phase 1 human clinical trial.
The Bacillus subtilis spore coat protein interaction network
Authors: Kim Hosan , Hahn Marlene , Grabowski Paul , McPherson Derrell C. , Otte Michele M. , Wang Rong , Ferguson Caitlin C. , Eichenberger Patrick , Driks Adam
Published: November 2005

Bacterial spores are surrounded by a morphologically complex, mechanically flexible protein coat, which protects the spore from toxic molecules. The interactions among the over 50 proteins that make up the coat remain poorly understood. We have used cell biological and protein biochemical approaches to identify novel coat proteins in Bacillus subtilis and describe the network of their interactions, in order to understand coat assembly and the molecular basis of its protective functions and mechanical properties. Our analysis characterizes the interactions between 32 coat proteins. This detailed view reveals a complex interaction network. A key feature of the network is the importance of a small subset of proteins that direct the assembly of most of the coat. From an analysis of the network topology, we propose a model in which low‐affinity interactions are abundant in the coat and account, to a significant degree, for the coat's mechanical properties as well as structural variation between spores.
Mcm2 labelling of balloon cells in focal cortical dysplasia
Authors: Thom M. , Martinian L. , Sisodiya S. M. , Cross J. H. , Williams G. , Stoeber K. , Harkness W. , Harding B. N.
Published: November 2005

Balloon cells (BC) are the prominent and defining cellular component of type IIB Focal Cortical Dysplasia (FCD), a common cause of focal epilepsy in patients undergoing surgical treatment. BC are considered immature cells of uncommitted cellular differentiation having immunophenotypical characteristics of both neurones and glia. They are often located in the lower cortical layers and white matter underlying the dysplastic cortex, suggesting migratory arrest during development. We investigated the proliferative potential of BC in 15 cases of FCD from patients with a wide range of ages using immunohistochemistry for Mcm2 (mini chromosome maintenance protein) and Ki67. In the majority of cases, BC showed Mcm2 nuclear positivity. In addition, cells with intermediate neuronal‐glial characteristics were labelled whilst the dysmorphic or hypertrophic pyramidal neuronal components of FCD were not. Ki67 labelled only occasional BC. These findings support the view that BC cells represent a pool of less differentiated glial cells with proliferative capacity which may have potential for delayed neuronal differentiation. Furthermore, as Mcm2 specifically identifies BC populations, this marker may be of diagnostic value in the subtyping of FCD lesions in patients with epilepsy.
Structure–function analysis of the plasma membrane‐ localized Arabidopsis defense component ACD6
Authors: Lu Hua , Liu Yang , Greenberg Jean T.
Published: November 2005

The ACCELERATED CELL DEATH 6 (ACD6) protein, composed of an ankyrin‐repeat domain and a predicted transmembrane region, is a necessary positive regulator of Arabidopsis defenses. ACD6 overexpression confers enhanced disease resistance by priming stronger and quicker defense responses during pathogen infection, plant development or treatment with an agonist of the key defense regulator salicylic acid (SA). Modulation of ACD6 affects both SA‐dependent and SA‐independent defenses. ACD6 localizes to the plasma membrane and is an integral membrane protein with a cytoplasmic ankyrin domain. An activated version of ACD6 with a predicted transmembrane helix mutation called ACD6‐1 has the same localization and overall topology as the wild‐type protein. A genetic screen for mutants that suppress acd6‐1‐conferred phenotypes identified 17 intragenic mutations of ACD6. The majority of these mutations reside in the ankyrin domain and in predicted transmembrane helices, suggesting that both ankyrin and transmembrane domains are important for ACD6 function. One mutation (S638F) also identified a key residue in a putative loop between two transmembrane helices. This mutation did not alter the stability or localization of ACD6, suggesting that S635 is a critical residue for ACD6 function. Based on structural modeling, two ankyrin domain mutations are predicted to be in surface‐accessible residues. As ankyrin repeats are protein interaction modules, these mutations may disrupt protein–protein interactions. A plausible scenario is that information exchange between the ankyrin and transmembrane domains is involved in activating defense signaling.
Histochemical staining and quantification of plant mitochondrial respiratory chain complexes using blue‐native polyacrylamide gel electrophoresis
Authors: Sabar Mohammed , Balk Janneke , Leaver Christopher J.
Published: November 2005

Our knowledge of the respiratory chain and associated defects depends on the study of the multisubunit protein complexes in the inner mitochondrial membrane. Functional analysis of the plant mitochondrial respiratory chain has been successfully achieved by a combination of blue‐native polyacrylamide gel electrophoresis (BN‐PAGE) for separation of the protein complexes, and in‐gel histochemical staining of the enzyme activities. We have optimized this powerful technique by determining linear ranges of amount of protein and enzyme activity for each respiratory complex. Time courses of the in‐gel enzyme activities were also performed to determine optimal reaction times. Using the in‐gel activity staining method we have previously shown decreased activity of complex V (F1F0‐ATPase) in male‐sterile sunflowers (Sabar et al., 2003). Here we have identified unique supercomplexes comprising complex IV (cytochrome c oxidase) in sunflower mitochondria. This method therefore represents a reliable tool for the diagnosis of respiratory dysfunction. In addition, the wider application of BN‐PAGE in combination with enzyme activity staining is discussed.
Genetic diversity of herbicide‐resistant and ‐susceptible Avena fatua populations in North Dakota and Minnesota
Authors: MENGISTU L W , MESSERSMITH C G , CHRISTOFFERS M J
Published: November 2005

Genetic diversity within and among 20 herbicide‐resistant (HR) and 16 herbicide‐susceptible (HS) Avena fatua multi‐field populations was determined using 82 polymorphic loci resulting from two intersimple sequence repeat (ISSR) primers and one long‐primer random amplified polymorphic DNA (LP‐RAPD) primer. Collections from the Red River Valley of North Dakota and Minnesota, sampled in 1964 and 2000, represented A. fatua populations before and after intensive exposure to herbicides. A 1995 collection from south‐west North Dakota represented A. fatua exposed to low herbicide selection. Despite differences in years of herbicide exposure among collections, both HR and HS populations from every collection maintained nearly similar levels of ISSR and RAPD diversity. Genetic differentiation among populations (GST) varied from 11% to 13% among HR populations and from 9% to 16% among HS populations, indicating that 84–91% of total variation remained within HS or within HR populations. Minimal difference in gene diversity between HR and HS is consistent with multiple origins of resistance, where HR A. fatua most likely evolved from diverse founding individuals.
Quality of life instrument for Turkish people with skin diseases
Authors: Gurel Mehmet Salih , Yanik Medaim , Simsek Zeynep , Kati Mahmut , Karaman Ahmet
Published: November 2005

Background and objective  To develop a new, short, self‐administrated subjective quality of life (QOL) instrument for Turkish people with skin diseases.

Patients and methods  The 11‐item questionnaire of QOL instrument was developed from 200 consecutive dermatological patients’ replies. The reliability and validity of the instrument was tested on data gathered from 278 patients with skin diseases attending a dermatology outpatient department and 49 normal subjects. Construct validity was assessed by an exploratory factor analyses and comparisons between patients rated severe and not severe, as well as between normal and patient groups. Reliability was assessed from the internal consistency of the scales and the correlations were made between scores from a 7–10‐day retest by using intraclass correlation coefficient.

Results  Factor analyses found six separate dimensions of QOL involving skin disease: social life, emotional life, daily activity, symptoms, cognitive life and sexual life. In addition, 81.3% of common variance was explained by the above factors, all of which correlated with the scale scores of the instrument. The instrument scales were internally consistent (Cronbach's α= 0.77–0.84) and scale scores were reproducible after 7–10 days (ICC = 0.63–0.88). Significantly, correlations between scale scores and physician's assessment of the severity of the skin disease were found. Significant differences between diagnostic groups were observed with higher scores for patients with psoriasis, urticaria and acne than those with eczema in the emotional life domain (P < 0.05). In the sexual life domain, however, the eczema group had higher scores than patients with psoriasis, urticaria or acne (P < 0.01).

Conclusion  The instrument provides valid and reliable assessments of QOL in Turkish patients with skin disease.
Ultrasonographical evaluation of the Achilles’ tendon in psoriasis patients
Authors: Özçakar Levent , Çetin Alp , Ínanici Fatma , Kaymak Bayram , Gürer Cansel Köse , Kölemen Fikret
Published: November 2005

Background  Psoriasis is a common dermatological disease with erythematous plaques where articular and extra articular findings (tenosynovitis and enthesitis) may well accompany. The aim of this current study was to evaluate the Achilles’ tendon of psoriasis patients with ultrasonography.

Methods  The study comprised 30 psoriasis patients and 20 healthy controls. Ankle ultrasonography was performed with posterior approach, the joint in neutral or in a little dorsiflexed position. The statistical analysis was carried out with a Student's t‐test and Spearman correlation tests.

Results  The mean values of Achilles’ tendon thickness of two groups were compared: the psoriatic group was found to have thicker tendon measurements (P = 0.00). The tendons of the patients with radiologically proven enthesopathy were found to be even thicker (P = 0.001).

Conclusions  We encourage the use of diagnostic ultrasonography for evaluation of enthesopathy manifestations in psoriasis patients as an adjunct to conventional methods owing to its convenience and promising results.
Familial aquagenic acrokeratoderma: case reports and review of the literature
Authors: Saray Yasemin , Seçkin Deniz
Published: November 2005

In recent years, a number of authors have described the development of palmar or palmoplantar keratoderma after brief exposure to water. Herein, we report a father and son with this condition, which we prefer to call aquagenic acrokeratoderma. These cases are interesting because they mark the first documentation of this entity in males. Also, they provide further evidence of familial occurrence.
Bullous variant of Sweet's syndrome
Authors: Voelter‐Mahlknecht Susanne , Bauer Jürgen , Metzler Gisela , Fierlbeck Gerhard , Rassner Gernot
Published: November 2005

A 69‐year‐old woman presented to our clinic as an emergency with erythematous, well‐circumscribed plaques, which were partly vesicular, on her extremities and in her armpits, and additionally hemorrhagic blisters on both her palms and her fingers (Fig. 1a), which had developed 2 days after the first appearance of the skin lesions. The rapid onset of the lesions (within a few hours) and the pain associated with them were extremely troublesome to the patient. On admission she complained of fever, tiredness and being easily fatigued. Because of a urinary tract infection 1 month prior to admission, trospiumchloride was given. On clinical examination, body temperature was found to be above 38 °C and infraclavicular lymph nodes were enlarged but not tender.

(a) Bullae on the patient's right hand. (b) Multiple partly confluent vesicles with neutrophilic granulocytes intraepidermally and a dense interstitial perivascular infiltration of neutrophilic granulocytes and lymphomononuclear cells (H&E, ×200)

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Normal or negative laboratory tests included blood counts, liver and kidney parameters, electrolytes and infection screen. Laboratory examination demonstrated minor leukocytosis and absolute neutrophilia (white blood cell count 10 440 cells/µL, neutrophils 8030 cells/µL). X‐ray screening, abdominal ultrasound and laboratory investigations were all normal.

There was no response to antibiotics when erythromycine was given. However, there was a good response to systemic corticosteroids. The patient was treated with a low dosage of prednisolone, beginning at 50 mg/day, which was then tapered off. Skin lesions resolved within 7 days.

Histology from a lesion on the patient's left forearm showed a dense interstitial inflammatory infiltration consisting predominantly of neutrophilic granulocytes from the subepidermal layer to the middle of the reticular dermis. Inflammatory cells penetrated into both blood vessels and vessel walls; vasculitis was not prominent. In the lower dermis, perivascular infiltrations of lymphomononuclear cells were found. In addition, intraepidermally multiple partly confluent vesicles, with inclusions of neutrophilic granulocytes, were found, confirming the diagnosis of this rare variant of an acute febrile neutrophilic dermatosis (Fig. 1b).
Diagnostic clinical features of pentazocine‐induced ulcers
Authors: Prasad H. R. Y. , Khaitan Binod K. , Ramam M. , Sharma Vinod K. , Pandhi Ravinder K. , Agarwal Saurabh , Dhawan Anju , Jain Raka , Singh Manoj K.
Published: November 2005

Background  Pentazocine was introduced in 1967 as a “non‐narcotic, nonaddicting” analgesic. However, the abuse potential of this medication was soon recognized, and cutaneous and muscular complications of pentazocine abuse have been reported.

Methods  Demographic and clinical data on 10 patients with pentazocine‐induced ulcers attending the Dermatology Outpatient Department of the All India Institute of Medical Sciences (AIIMS), New Delhi, India between November 2000 and October 2002 have been compiled.

Results  Ten patients with pentazocine‐induced ulcers were seen at AIIMS between November 2000 and October 2002, six of whom were female. The average age of these patients was 32 years. The duration of the complaints ranged from 10 days to 7 years (average 17.5 months). Nine of the 10 patients had past history of painful medical conditions for which they had received pentazocine injections. All the patients presented with deep ulcers and sinuses over the accessible sites. The margins of these ulcers were hyperpigmented and indurated. Six patients had scars along the superficial vein access sites. Three patients had puffy‐hand syndrome, while two had muscle contractures. No underlying psychiatric disorders were found in any of these patients. Urine screening for pentazocine was positive in two patients. Antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA) and antibody against DNA (antidsDNA) tests and screening for infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative in all patients.

Conclusions  Pentazocine abuse can be suspected from cutaneous findings, even when the patient does not volunteer a history of self‐medication. Recognition of the condition will prevent misdirected investigations and treatment. The patient should be encouraged to seek treatment for drug dependence.
Heritability of corticosterone response and changes in life history traits during selection in the zebra finch
Authors: Evans Matthew R. , Roberts Mark L. , Buchanan Katherine L. , Goldsmith Arthur R.
Published: November 2005

Vertebrates respond to environmental stressors through the neuro-endocrine stress response, which involves the production of glucocorticoids. We have selected independent, duplicate divergent lines of zebra finches for high, low and control corticosterone responses to a mild stressor. This experiment has shown that over the first four generations, the high lines have demonstrated a significant realized heritability of about 20%. However, the low lines have apparently not changed significantly from controls. This asymmetry in response is potentially because of the fact that all birds appear to be showing increased adaptation to the environment in which they are housed, with significant declines in corticosterone response in control lines as well as low lines. Despite the existence of two- to threefold difference in mean corticosterone titre between high and low lines, there were no observed differences in testosterone titre in adult male birds from the different groups. In addition, there were no consistent, significant differences between the lines in any of the life history variables measured – number of eggs laid per clutch, number of clutches or broods produced per pair, number of fledglings produced per breeding attempt, nor in any of egg, nestling and fledgling mortality. These results highlight the fact that the mechanisms that underlie variation in the avian physiological system can be modified to respond to differences between environments through selection. This adds an additional level of flexibility to the avian physiological system, which will allow it to respond to environmental circumstances.
Predator diversity strengthens trophic cascades in kelp forests by modifying herbivore behaviour
Authors: Byrnes Jarrett , Stachowicz John J. , Hultgren Kristin M. , Randall Hughes A. , Olyarnik Suzanne V. , Thornber Carol S.
Published: November 2005

Although human‐mediated extinctions disproportionately affect higher trophic levels, the ecosystem consequences of declining diversity are best known for plants and herbivores. We combined field surveys and experimental manipulations to examine the consequences of changing predator diversity for trophic cascades in kelp forests. In field surveys we found that predator diversity was negatively correlated with herbivore abundance and positively correlated with kelp abundance. To assess whether this relationship was causal, we manipulated predator richness in kelp mesocosms, and found that decreasing predator richness increased herbivore grazing, leading to a decrease in the biomass of the giant kelp Macrocystis. The presence of different predators caused different herbivores to alter their behaviour by reducing grazing, such that total grazing was lowest at highest predator diversity. Our results suggest that declining predator diversity can have cascading effects on community structure by reducing the abundance of key habitat‐providing species.
Scale‐dependent interactions and community structure on cobble beaches
Authors: van de Koppel Johan , Altieri Andrew H. , Silliman Brian R. , Bruno John F. , Bertness Mark D.
Published: November 2005

Recent theory suggests that scale‐dependent interaction between facilitation and competition can generate spatial structure in ecological communities. The application of this hypothesis, however, has been limited to systems with little underlying heterogeneity. We evaluated this prediction in a plant community along an intertidal stress gradient on cobble beaches in Rhode Island, USA. Prior studies have shown that Spartina alterniflora facilitates a forb‐dominated community higher in the intertidal by modifying the shoreline environment. We tested the hypothesis that, at a smaller scale, Spartina competitively excludes forb species, explaining their marked absence within the lower Spartina zone. Transplant experiments showed forb species grow significantly better in the Spartina zone when neighbours were removed. Removal of the Spartina canopy led to a massive emergence of annual forbs, showing that competition limits local occupation. These findings indicate that interaction of large‐scale facilitation and small‐scale competition drives plant zonation on cobble beaches. This study is the first to provide empirical evidence of scale‐dependent interactions between facilitation and competition spatially structuring communities in heterogeneous environments.
Tariffs and steel: US safeguard actions*
Authors: Greenville Jared , MacAulay T.Gordon
Published: November 2005

A multiproduct spatial equilibrium model of world steel trade is presented in this paper. The model is used to analyse the impacts of the safeguard trade barriers brought about by the USA in order to protect their domestic industry from the so‐called unfair competition. Emphasis is placed on the likely effect on the Australian industry and possible policy responses available to the industry. A case study is made of Australia's three largest export products; namely, slab, hot‐rolled and cold‐rolled steel, which share some substitutability in supply and demand because of the nature of the industry. As a result of the safeguard barriers to steel trade, world steel prices fell and trade shifted away from the USA to other importing regions.
Economic substitution for US wheat food use by class*
Authors: Marsh Thomas L.
Published: November 2005

Wheat for food use is conceptualised as an input into flour production and demand is derived from an industry profit function to quantify price responsiveness and economic substitutability across wheat classes. Price and substitution elasticities are estimated for hard red winter, hard red spring, soft red wheat, soft white winter and durum wheat. In general, hard red winter and spring wheat varieties are much more responsive to their own price than are soft wheat varieties and durum wheat. Substitution elasticities indicate that hard red winter and hard red spring wheat are economic substitutes for milling purposes.
College Choice and Subsequent Earnings: Results Using Swedish Sibling Data*
Authors: Lindahl Lena , Regnér Håkan
Published: November 2005

Using data on 19,000 whole siblings, it is shown that earnings vary significantly among students who have graduated from different colleges. The cross‐section estimates are up to twice the within‐family estimates, indicating that a regression estimator of college effects that does not adjust properly for family characteristics will overestimate the earnings premium of college. This study also shows that the effects of college choice vary between sisters and brothers and that there is a relationship between teacher quality and the college effects. These findings suggest that there is no straightforward interpretation of college in individual earnings equations.
Direct Displacement Effects of Labour Market Programmes*
Authors: Dahlberg Matz , Forslund Anders
Published: November 2005

Using a panel of 250 Swedish municipalities over the period 1987–1996, we examine the direct displacement effects of active labour market programmes (ALMPs). Compared to earlier studies on this topic, we have more and better data. Based on our GMM estimations, we find that there are direct displacement effects from subsidised employment (in the order of approximately 65%), but that there seem to be no (significant) displacement effects from training. This result seems to be robust to several alternative specifications.
Intertemporal Equity and Hartwick's Rule in an Exhaustible Resource Model*
Authors: Buchholz Wolfgang , Dasgupta Swapan , Mitra Tapan
Published: November 2005

In a standard exhaustible resource model, it is known that if, along a competitive path, investment in the augmentable capital good equals the rents on the exhaustible resource (known as Hartwick's rule), then the path is equitable in the sense that the consumption level is constant over time. In this paper, we show the converse of this result: if a competitive path is equitable, then it must satisfy Hartwick's rule.
Regulation and Evolution of Compliance in Common Pool Resources
Authors: Xepapadeas Anastasios
Published: November 2005

The evolution of compliance with regulation and the evolution of a CPR stock are modeled jointly in a setup where replicator dynamics describing compliance with harvesting rules are combined with resource stock dynamics. This evolutionary approach suggests that in long‐run equilibrium, coexistence of both cooperative and non‐cooperative rules is possible under regulation. Stock effects on profits and a certain structure of auditing probabilities could imply the emergence of a limit cycle in areas of low stock levels, as an equilibrium outcome. It might be easier for the regulator to obtain full compliance under precommitment to fixed auditing probabilities.
Health in People with Intellectual Disabilities: Current Knowledge and Gaps in Knowledge
Authors: van Schrojenstein Lantman‐de Valk Henny M. J.
Published: November 2005

Background  The health needs of people with intellectual disabilities have recently received increasing attention.

Method  Based on a review of the 2003 literature, this paper presents an overview of our knowledge on physical, mental and social well‐being in this group.

Results  Physical well‐being is threatened by handicap‐related conditions, syndrome‐related health problems and lifestyle characteristics.

Conclusion  Gaps in knowledge include insufficient evidence on health disparities, the lack of comparability of data on the prevalence of ill heath, lack of expertise in relation to communication problems and the fact that all knowledge is based on research in developed countries, while people with intellectual disabilities in developing countries face the same or even greater health problems. Recommendations concerning evidence, education and empowerment are formulated.
Gene–environment interplay and psychopathology: multiple varieties but real effects
Authors: Rutter Michael , Moffitt Terrie E. , Caspi Avshalom
Published: November 2005

Gene–environment interplay is a general term that covers several divergent concepts with different meanings and different implications. In this review, we evaluate research evidence on four varieties of gene–environment interplay. First, we consider epigenetic mechanisms by which environmental influences alter the effects of genes. Second, we focus on variations in heritability according to environmental circumstances. Third, we discuss what is known about gene–environment correlations. Finally, we assess concepts and findings on the interaction between specific identified genes and specific measured environmental risks. In order to provide an understanding of what may be involved in gene–environment interplay, we begin our presentation with a brief historical review of prevailing views about the role of genetic and environmental factors in the causation of mental disorders, and we provide a simplified account of some of the key features of how genes ‘work’.
A long‐term outcome study of selective mutism in childhood
Authors: Steinhausen Hans‐Christoph , Wachter Miriam , Laimböck Karin , Metzke Christa Winkler
Published: November 2005

Objective:  Controlled study of the long‐term outcome of selective mutism (SM) in childhood.

Method:  A sample of 33 young adults with SM in childhood and two age‐ and gender‐matched comparison groups were studied. The latter comprised 26 young adults with anxiety disorders in childhood (ANX) and 30 young adults with no psychiatric disorders during childhood. The three groups were compared with regard to psychiatric disorder in young adulthood by use of the Composite International Diagnostic Interview (CIDI). In addition, the effect of various predictors on outcome of SM was studied.

Results:  The symptoms of SM improved considerably in the entire SM sample. However, both SM and ANX had significantly higher rates for phobic disorder and any psychiatric disorder than controls at outcome. Taciturnity in the family and, by trend, immigrant status and a severity indicator of SM had an impact on psychopathology and symptomatic outcome in young adulthood.

Conclusion:  This first controlled long‐term outcome study of SM provides evidence of symptomatic improvement of SM in young adulthood. However, a high rate of phobic disorder at outcome points to the fact that SM may be regarded as an anxiety disorder variant.
Hyperbaric oxygen stimulates cell proliferation and normalizes multidrug resistance protein‐2 protein localization in primary rat hepatocytes
Authors: MIZUGUCHI TORU , OSHIMA HIDEKI , IMAIZUMI HITOSHI , KOHARA HIROSHI , KAWAMOTO MASAKI , NOBUOKA TAKAYUKI , KAWASAKI HIROYUKI , HARADA KEISUKE , MASUDA YOSHIKI , KIKKAWA YAMATO , MITAKA TOSHIHIRO , ASAI YASUFUMI , HIRATA KOICHI
Published: November 2005

Hyperbaric oxygen therapy (HBO) has been used for many clinical treatments, including primary liver nonfunction. However, the cellular mechanism by which HBO treatment ameliorates liver function is not understood. Therefore, the purpose of this study was to elucidate this cellular mechanism using primary cultured rat hepatocytes in in vitro studies. Hepatocytes were treated with HBO at 1 day after plating, and the morphological and functional characteristics of bile canaliculi formed in cultured hepatocytes were observed by time‐lapse microscopy. Multidrug resistance protein‐2 localization was observed by confocal laser microscopy. In cultured hepatocytes, the labeling index in the HBO group at 2 days after treatment was significantly higher than that in the control group. In addition, the proliferating cellular nuclear antigen level in the HBO group was significantly higher than that in the control group. The contraction of the bile canaliculi in the HBO group was slower than in the control group and the dilatation of bile canaliculi in the HBO group was much larger than in the control group. Multidrug resistance protein‐2 in the HBO group was localized at the apical membrane. These results show that HBO stimulates hepatocytes to proliferate and HBO normalizes Multidrug resistance protein‐2 localization to the apical membrane, which could dilate bile canaliculi.
Optimization and validation of an ischemic wound model
Authors: GOULD LISA J. , LEONG MIMI , SONSTEIN JOSEPH , WILSON SHELLY
Published: November 2005

Localized tissue ischemia is a key factor in the development and poor prognosis of chronic wounds. Currently, there are no standardized animal models that provide sufficient tissue to evaluate the effect of modalities that may induce angiogenesis, and in vitro models of angiogenesis do not mimic the complexity of the ischemic wound bed. Therefore, we set out to develop a reproducible ischemic model for use in wound‐healing studies. Male Sprague–Dawley rats underwent creation of dorsal bipedicle skin flaps with centrally located excisional wounds. Oxygen tension, wound‐breaking strength, wound area, lactate, and wound vascular endothelial growth factor (VEGF) were compared in flaps measuring 2.5 and 2.0 × 11 cm with and without an underlying silicone sheet. We found that the center of the 2.0 cm flap with silicone remains in the critically ischemic range up to 14 days without tissue necrosis (33±4 vs. 49±6 mmHg in controls). Wound healing and breaking strength were significantly impaired and tissue lactate from the center of this flap was 2.9 times greater than tissue from either nonischemic controls and 2.5 cm flap (0.23±0.05 mg/dL/mg sample vs. 0.09±0.02 and 0.08±0.02, respectively). Vascular endothelial growth factor was 2 times greater than the nonischemic control. This ischemic wound model is relatively inexpensive, easy to perform, reproducible, and reliable. The excisional wounds provide sufficient tissue for biochemical and histologic analysis, and are amenable to the evaluation of topical and systemic therapies that may induce angiogenesis or improve wound healing.
Periictal Dynamic Changes in Benzodiazepine Receptors
Authors: Cascino Gregory D.
Published: November 2005

Seizure-related Short-term Plasticity of Benzodiazepine Receptors in Partial Epilepsy: An [11C]Flumazenil-PET Study

Bouvard S, Costes N, Bonnefoi F, Lavenne F, Mauguiere F, Delforge J, Ryvlin P

Brain 2005;128:1330–1343

We have undertaken a test–retest [11C]flumazenil (FMZ) positron emission tomography (PET) study in 10 drug-resistant epilepsy patients, including six with a mesiotemporal epilepsy (MTE), and 10 normal controls, to investigate seizure-related short-term plasticity of benzodiazepine (BZD) receptors. All subjects underwent two FMZ-PET scans at a 1-week interval. Patients benefited from a concurrent video-EEG monitoring, which allowed determination of the duration of the interictal period (IP) preceding each PET study. Test–retest whole-brain B′max variations, evaluated with a partial-saturation injection protocol, were similarly observed in patients and controls, suggesting a physiologic modulation of BZD receptors. Five (50%) patients, but no controls, also demonstrated clinically significant test–retest FMZ-PET variations in the mesial temporal region. This was observed in all three patients with MTE and no hippocampal atrophy, in whom only the PET study associated with the shortest IP correctly identified the epileptogenic zone. Statistical analysis revealed a significant effect of IP duration on BZD receptor B′max in MTE patients, suggesting that the shorter the IP, the lower the B′max in the epileptogenic hippocampus. FMZ-PET appears to be an interesting tool for investigating both normal and abnormal short-term modulations of the BZD receptor system and should ideally be performed within a few days after a seizure in patients with MTE and a normal MRI.
Pregabalin: The Next New Thing
Authors: Faught Edward
Published: November 2005

Safety and Efficacy of Two Pregabalin Regimens for Add-on Treatment of Partial Epilepsy

Beydoun A, Uthman BM, Kugler AR, Greiner MJ, Knapp LE, Garofalo EA; Pregabalin 1008-009 Study Group

Neurology 2005;64:475–480

Objective

To evaluate the efficacy, tolerability, and safety of two pregabalin regimens administered as adjunctive therapy to that of placebo in patients with medically refractory partial epilepsy.

Methods

A multicenter, double-blind, randomized, parallel-group, placebo-controlled trial was performed. After a prospective 8-week baseline phase, patients were randomized to 12 weeks of double-blind treatment with placebo or pregabalin, 600 mg/day, administered twice daily (BID) or 3 times daily (TID). Primary efficacy was measured as change in seizure frequency from baseline of either pregabalin regimen compared with placebo. Secondary efficacy comparisons included the proportion of patients experiencing ≥50% reduction in seizure frequency (responder rate) and median percentage change from baseline in seizure frequency. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluation. Efficacy and safety analyses were performed on the intent-to-treat (ITT) population.

Results

Pregabalin treatment resulted in seizure frequency reductions: 53% for pregabalin TID ( P ≤ 0.0001) and 44% for pregabalin BID ( P ≤ 0.0001) compared with a 1% increase for placebo. Responder rates were 49% for pregabalin TID and 43% for pregabalin BID compared with 9% for placebo ( P ≤ 0.001). Both pregabalin regimens were similar in efficacy and tolerability. The most common AEs were dizziness, somnolence, and ataxia.

Conclusions

Pregabalin administered at 600 mg/day is safe, generally well tolerated, and efficacious as adjunctive therapy for the treatment of patients with partial seizures, with or without secondary generalizations. This dose can be administered on a twice-daily or 3-times-daily schedule with similar efficacy and tolerability results.
Angelman Syndrome: Need for Further Illumination in the Theater of the Happy Puppet
Authors: Sankar Raman
Published: November 2005

Analysis of the Characteristics of Epilepsy in 37 Patients with the Molecular Diagnosis of Angelman Syndrome

Galvan-Manso M, Campistol J, Conill J, Sanmarti FX

Epileptic Disord 2005;7:19–25

Angelman syndrome is a genetic disorder caused by defects in the maternally inherited imprinted domain located on chromosome 15q11-q13. Most patients with Angelman syndrome have severe mental retardation, characteristic physical appearance, behavioral traits, and severe, early-onset epilepsy. We retrospectively reviewed the medical histories of 37 patients, all with the molecular diagnosis of Angelman syndrome and at least 3 years of follow-up in our neurology department, for further information about their epilepsy: age at onset, type of seizures initially and during follow-up, EEG recordings, treatments, and response. The molecular studies showed 87% deletions de novo; 8% uniparental, paternal disomy; and 5% imprinting defects. The median age at diagnosis was 6.5 years, with 20% having begun to manifest febrile seizures at an average age of 1.9 years. Nearly all (95%) had epilepsy, the majority younger than 3 years (76%). The most frequent seizure types were myoclonic, atonic, generalized tonic–clonic, and atypical absences. At onset, two patients exhibited West syndrome. EEG recordings typical of Angelman syndrome were found in 68%. Normalization of EEG appeared in 12 patients after 9 years. Control of epileptic seizures improved after the age of 8.5 years. The most effective treatments were valproic acid and clonazepam. We conclude that epilepsy was present in nearly all of our cases with Angelman syndrome and that the EEG can be a useful diagnostic tool. On comparing the severity of epilepsy with the type of genetic alteration, we did not find any statistically significant correlations.
Hypoxia Results in GABAergic Channelopathy
Authors: Poolos Nicholas P.
Published: November 2005

AMPA/Kainate Receptor–mediated Downregulation of GABAergic Synaptic Transmission by Calcineurin after Seizures in the Developing Rat Brain

Sanchez RM, Dai W, Levada RE, Lippman JJ, Jensen FE

J Neurosci 2005;25:3442–3451

Hypoxia is the most common cause of perinatal seizures and can be refractory to conventional anticonvulsant drugs, suggesting an age-specific form of epileptogenesis. A model of hypoxia-induced seizures in immature rats reveals that seizures result in immediate activation of the phosphatase calcineurin (CaN) in area CA1 of hippocampus. After seizures, CA1 pyramidal neurons exhibit a downregulation of GABAA receptor (GABAAR)-mediated inhibition that was reversed by CaN inhibitors. CaN activation appears to be dependent on seizure-induced activation of Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), because the upregulation of CaN activation and GABAAR inhibition were attenuated by GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] or Joro spider toxin. GABAAR β2/3 subunit protein was dephosphorylated at 1 h after seizures, suggesting this subunit as a possible substrate of CaN in this model. Finally, in vivo administration of the CaN inhibitor FK-506 significantly suppressed hypoxic seizures, and posttreatment with NBQX (2,3-dihydroxy-6-nitro-7-sulfonylbenzo[ f]quinoxaline) or FK-506 blocked the hypoxic seizure-induced increase in CaN expression. These data suggest that Ca2+-permeable AMPARs and CaN regulate inhibitory synaptic transmission in a novel plasticity pathway that may play a role in epileptogenesis in the immature brain.