bluuebunny/crossref_metadata_2025 huggingface dataset:
Report: Clear cell acanthoma: a rare clinical diagnosis prior to biopsy
Authors: Morrison L. Katie , Duffey Michael , Janik Matthew , Shamma H. Nicholas
Published: September 2010

Background  Clear cell acanthoma is a rare, benign epidermal tumor with a clinical hybrid appearance and a distinct histological one. It is frequently mistaken for other clinical lesions.

Objective  To evaluate the frequency that clear cell acanthoma was listed in the clinical differential diagnosis of histologically confirmed specimens.

Methods  A regional dermatopathology lab database was evaluated from January 1998 through March 2008 for histologically diagnosed cases of clear cell acanthoma. Clinical data that was submitted with these cases including differential diagnoses was analyzed.

Results  During this time period of review, 411 histologically confirmed cases of clear cell acanthoma were identified. This entity was listed as a diagnostic possibility in 11 (2.7%) of the cases.

Conclusion  Clear cell acanthoma was rarely listed amongst the differential diagnosis of biopsy proven specimens. This may be due to a variable clinical appearance with overlapping features of several other lesions making it difficult to distinguish, or an entity that is rare and not frequently suspected. Additional studies with dermatoscopy may help to further delineate the reasons for the low diagnostic sensitivity.
Tropical medicine rounds: Acrodermatitis enteropathica: a review of 29 Tunisian cases
Authors: Kharfi Monia , El Fékih Nadia , Aounallah‐Skhiri Hajer , Schmitt Sébastien , Fazaa Bécima , Küry Sébastien , Kamoun Mohamed Ridha
Published: September 2010

Introduction  Acrodermatitis enteropathica is a rare autosomal recessive disease due to an abnormality in a zinc transporting molecule.

Methods  We conducted a retrospective monocentric study on 29 Tunisian cases of Acrodermatitis enteropathica (AE) treated in our Department of Dermatology in Tunisia, between January 1981 and June 2008.

Results  The age of onset of disorders was between 15 d and 12 months (mean 6.86 ± 3.25 months). The delay of consultation ranged between 15 d and 8 months (mean of 2.8 ± 2.17 months) after onset. Onset of gastrointestinal and psychiatric signs depended significantly on consulting times. Plasma zinc levels ranged between 14 and 88 lg/100 ml (mean 44.86 ± 18.4 lg/100 ml). There was not a significant relation between zincemia and clinical features. Genetic analyses in 13 of our patients showed three different mutations in the SLC39A4 gene: c.1223_1227del (p.Trp411ArgfsX7) in exon 7,c.143T>G (p.Leu48X) in exon 1 and c.1784T>C (p.Gly595Val) in exon 11. No significant genotype‐phenotype correlations could be established.

Conclusion  Acrodermatitis enteropathica is a rare disease which diagnosis is easy. Its biological confirmation is made on a simple dosage of zincemia. However, the diagnosis is not always suggested, and is unfortunately made late. At present, there is a molecular test to detect SLC39A4 mutations.
Review: Identifying potential pitfalls in conventional herpes simplex virus management
Authors: Nguyen Nicholas , Burkhart Craig N. , Burkhart Craig G.
Published: September 2010

In recent years, it has become increasingly clear that genital ulcers from herpes simplex virus (HSV) are associated with HIV acquisition. In light of this evolving synergy in transmission and the availability of effective antiviral therapy, proper diagnosis and management of HSV becomes increasingly important. Unfortunately, conventional HSV management is founded on several popular misconceptions. Herein, we hope to dispel these common misconceptions and expand the current model of herpetic reactivation. By doing so, we aimed to unveil potential pitfalls in current herpetic management.
Diagnostic sensitivity of hepatocellular carcinoma imaging and its application to non‐cirrhotic patients
Authors: Lin Ming‐Tzung , Chen Chao‐Long , Wang Chih‐Chi , Cheng Yu‐Fan , Eng Hock‐Liew , Wang Jing‐Houng , Chiu King‐Wah , Lee Chuan‐Mo , Hu Tsung‐Hui
Published: September 2010

Background and Aims:  The American Association for the Study of Liver Disease issued guidelines that proposed that hepatocellular carcinoma (HCC) can be diagnosed if a mass is larger than 2 cm in a cirrhotic liver and shows typical features of HCC at triphasic liver computed tomography (CT) or dynamic magnetic resonance imaging (MRI). In non‐cirrhotic livers, the criteria were not applicable. The aim of the present study was to retrospectively analyze the sensitivity of imaging by samples of definite HCC postoperatively and test their application to diagnose HCC in non‐cirrhotic livers.

Methods:  From January 2006 to November 2008, a total of 343 pathologically‐diagnosed HCC patients via surgical resection were reviewed. Among the 343 patients, 204 patients had undergone liver CT examination, and 80 patients underwent MRI examination; serum α‐fetoprotein had been checked for all 343 patients prior to operation. The diagnostic sensitivity of HCC by imaging was evaluated and compared in patients with/without cirrhosis by ultrasound and histology.

Results:  The diagnostic sensitivity of HCC by single imaging was approximately 65–80% (liver CT or MRI). A higher sensitivity of HCC diagnosis was found in patients with ultrasound‐diagnosed cirrhosis than non‐cirrhosis, but the difference in sensitivity disappeared after histologically‐cirrhotic validation. The results indicated that regardless of the presence or absence of cirrhosis (histology), a typical vascular pattern could diagnose HCC with equally high sensitivity.

Conclusions:  We provide evidence that the sensitivity of HCC diagnosis by imaging is not influenced by the cirrhotic background. Further study is needed to validate the specificity and accuracy.
Systematic review of hepatocellular adenoma in China and other regions
Authors: Lin Haoming , van den Esschert Jacomina , Liu Chao , van Gulik Thomas M
Published: September 2010

Hepatocellular adenoma (HCA) is a benign liver neoplasm with a risk of spontaneous bleeding and malignant transformation. The aim of this review article is to review all the case reports and case series of patients with HCA from 1998 to 2008 in China and other parts of the world in order to compare clinical presentation, surgical management and outcomes. A search for all reports of HCA in the world literature from 1998 to 2008 was performed. A total of 356 patients were identified, including 191 patients from China, 104 from Europe, 46 from North America, and 15 from South–East Asia. A female predominance was not observed in Chinese patients in contrast to the other regions. Acute/chronic abdominal pain was the main clinical presentation in all regions. Twenty patients were diagnosed with coexistent hepatocellular carcinoma (HCC), and hepatitis B virus infection (HBV) was found among six of them. The management of HCA consisted of resection in most cases. The clinical presentation of HCA in China differed from other parts of the world regarding male predominance and a higher incidence of coexistent HCC in China. This might be the result of the birth control policy in China, limited oral contraceptive use, and the higher incidence of HBV.
Short‐term results of intensive physiotherapy in clubfoot deformity treated with the Ponseti method
Authors: Nilgün Bek , Suat Erel , Engin Şimşek İbrahim , Fatma Uygur , Yakut Yakut
Published: September 2010

Purpose:  We aimed to determine the efficacy of the physical therapy program as an adjunct to the Ponseti technique in the treatment of idiopathic clubfoot. This study was carried out with the presumption of a difference in results between the study group who were included in the physiotherapy program and the control group who performed home exercises.

Patients and method:  Forty affected feet of 29 patients were included in the study. The average ages of the control and study groups were 15.00 ± 21.33 and 20.30 ± 15.78 months, respectively. Passive range of motion of dorsiflexion, plantar flexion, inversion, eversion, rear foot varus angle and forefoot adduction angle were measured and the Dimeglio classification system was utilized in order to determine the severity of clubfoot deformity. Reassessments were carried out for the study group at the end of 1 month's therapy and for the control group during the first month follow‐up.

Results:  Comparison of pre‐ and post‐treatment assessment results revealed a difference in terms of recovery, concerning all parameters except passive inversion values in the study group and for all parameters in the control group (P < 0.05). For study and control group comparisons, since deformity severity was higher in the study group an effect size analysis was carried out. The effect size analysis showed that the change in range of motion of dorsiflexion and Dimeglio and decrease of rear foot varus angle was higher in the study group.

Conclusion:  The results of this study imply that an intensive physiotherapy program may enhance the effectiveness of the Ponseti protocol.
Nebulized hypertonic saline and recombinant human DNase in the treatment of pulmonary atelectasis in newborns
Authors: Dilmen Ugur , Karagol Belma Saygili , Oguz Serife Suna
Published: September 2010

Objective:  The aim of this study was to compare and evaluate the efficacy of nebulized 3% hypertonic saline (HS) and recombinant human DNase (rhDNase) treatment for resolution of persistent atelectasis in newborns.

Study design:  Forty newborns (38 preterms) who did not respond to conventional treatment were enrolled to receive either nebulized 3% HS solution (n = 20) or rhDNase (n = 20) between September 2007 and March 2008. Clinical parameters, oxygen saturation and radiological response (chest X‐ray scoring) were analyzed before and after administration of 3% HS or rhDNase.

Results:  The patients of the nebulized 3% HS solution group improved better chest X‐ray scores parameters than the patients of the rhDNase group: chest X‐ray scores were 5.1 ± 1.9 vs 4.8 ± 1.7 before treatment and 1.0 ± 0.8 vs 2.1 ± 1.4 after treatment (P < 0.001). Resolution time of atelectasis did not differ between the two groups after whole treatment but the percentage of atelectasis resolution after 3 days treatment were 90% (18/20) in the 3% HS group and 70% (14/20) in the rhDNase group. The patients in the 3% HS group improved better also in clinical parameters in comparison to the rhDNase treatment. The difference of oxygen saturation before and after the treatment was 4.6 ± 0.8 in 3% HS group in comparison to 2.6 ± 0.1 in the rhDNase group (P < 0.05). All serum sodium levels were normal in two groups before and after the treatment modalities.

Conclusion:  This is the first study on the usefulness of nebulized 3% hypertonic saline solution in treating newborns with pulmonary atelectasis. In addition, 3% HS solution was a more effective therapeutic option on the basis of clinical and radiological improvement compared to rhDNase treatment in newborns with pulmonary atelectasis.
Staphylococcal scalded skin syndrome in an extremely low‐birth‐weight neonate: Molecular characterization and rapid detection by multiplex and real‐time PCR of methicillin‐resistant Staphylococcus aureus
Authors: Shi Da , Ishii Shiro , Sato Takashi , Yamazaki Hajime , Matsunaga Masamichi , Higuchi Wataru , Takano Tomomi , Yabe Shizuka , Tanaka Kenichi , Yamamoto Tatsuo
Published: September 2010

Background:  Staphylococcal scalded skin syndrome (SSSS), caused by methicillin‐resistant Staphylococcus aureus (MRSA) producing exfoliative toxin (ET), is a life‐threatening infection for neonates in neonatal intensive care units (NICUs). SSSS in extremely low‐birth‐weight (ELBW) neonates is rare. A new class of MRSA (community‐acquired MRSA, CA‐MRSA) has been emerging in the community. The aim of this study was to characterize MRSA from an ELBW neonate with SSSS, and to develop rapid detection methods for SSSS‐associated and emerging pediatric MRSA.

Methods:  An ELBW infant in the NICU developed SSSS on day 16 after birth. Isolated MRSA was genetically characterized and compared with CA‐MRSA from bullous impetigo (biCA‐MRSA), which is positive for the ET and collagen‐adhesin (CNA) genes in many cases, and the Panton‐Valentine leucocidin (PVL) gene rarely. Specific primers and probes for five virulence genes (for ETA, ETB, ETD, PVL, CNA) were designed for multiplex polymerase chain reaction (PCR) and real‐time PCR.

Results:  MRSA strain H5 from SSSS exhibited the genotype (ST91, spa416[t375], agr3, SCCmecIVa, CoaI), and possessed the ETB and CNA genes, similar to ST91 biCA‐MRSA (albeit with a divergence). Multiplex PCR detected the ETB and CNA genes of strain H5, and real‐time PCR detected strain H5 at as low as 102 CFU/mL. The assays were 100% specific and 100% sensitive, for the five virulence genes.

Conclusion:  ETB‐positive ST91 MRSA, which was very similar to ST91 biCA‐MRSA, was isolated from an ELBW infant with SSSS. The multiplex and real‐time PCR assays specifically or quantitatively detected SSSS‐associated and emerging pediatric MRSA.
Methylenetetrahydrofolate reductase C677T polymorphism in patients with Henoch‐Schönlein purpura
Authors: Emre Sevinc , Sirin Aydan , Ergen Arzu , Bilge Ilmay , Sucu Aysegul , Yilmaz Alev , Isbir Turgay
Published: September 2010

Aim:  Associations between several vascular diseases such as Kawasaki disease, venous and arterial thromboembolism, cardiovascular disease, diabetic nephropathy, focal segmental glomerulosclerosis and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been reported. This is a clinical study designed to investigate the possible effects of MTHFR C677T polymorphism on the development of Henoch‐Schönlein purpura (HSP).

Methods:  Forty‐one patients with HSP (25 male/16 female) with a mean age of 7.8 ± 2.9 years were included in the study. The control group consisted of 50 healthy children. MTHFR genotypes were determined by polymerase chain reaction and by Hindf I restriction enzyme analysis and subsequent 3% agarose gel electrophoresis techniques.

Results:  No significant differences were observed in the distribution of MTHFR genotypes or allele frequencies in the HSP cases versus controls. Plasma homocysteine levels and vitamin B12 levels were almost comparable in the HSP patients and control group without a significant difference. Folic acid levels were within normal limits in the HSP cases and the control group, HSP patients' levels being significantly higher than the control group. No significant relationship was present with the MTHFR genotype and plasma homocysteine, vitamin B12 and folic acid levels in HSP patients.

Conclusion:  No association with MTHFR gene polymorphism and homocysteine plasma levels could be found in patients with HSP. The results of this study indicate that other mechanisms should be operative in the development of HSP.
A low fructose diet in the treatment of pediatric obesity: A pilot study
Authors: Maier Ina B. , Stricker Laura , Özel Yelda , Wagnerberger Sabine , Bischoff Stephan C. , Bergheim Ina
Published: September 2010

Background:  Over the last three decades the prevalence of overweight and obesity has increased dramatically among children and adolescents worldwide. As the results of animal and human studies suggest that a diet rich in fructose may be a risk factor for the development of overweight, the aim of the pilot study was to evaluate if a dietary counseling aimed at a moderate reduction of dietary fructose intake (−50% in comparison to intake at baseline) has a positive effect on the body mass index (BMI) of overweight and obese children.

Methods:  Fifteen overweight or obese children aged 5–8 years were included into the 3 month dietary intervention study. At baseline and after 4 and 8 weeks children and their parents were trained to reduce fructose in the children's diet. Anthropometric parameters for calculating BMI and BMI standard deviation scores (BMI‐SDS) as well as nutritional intake were assessed at baseline, after the 12‐week intervention and after 12 week of follow up.

Results:  After the 12‐week intervention children had significantly reduced their total energy, fructose, sucrose and glucose intake. BMI and BMI‐SDS were significantly reduced by 0.68 kg/m2 and 0.21, respectively, at the end of the intervention. At follow up, the BMI‐SDS was significantly lower in comparison to baseline while the BMI was only decreased by trend (P= 0.08).

Conclusions:  The results of our pilot study indicate that counseling aimed towards a moderate reduction of dietary fructose and/or general sugar intake may have a positive effect on BMI in overweight and obese children.
The HYDE 3.1 spatially explicit database of human‐induced global land‐use change over the past 12,000 years
Authors: Klein Goldewijk Kees , Beusen Arthur , van Drecht Gerard , de Vos Martine
Published: September 2010

Aim  This paper presents a tool for long‐term global change studies; it is an update of the History Database of the Global Environment (HYDE) with estimates of some of the underlying demographic and agricultural driving factors.

Methods  Historical population, cropland and pasture statistics are combined with satellite information and specific allocation algorithms (which change over time) to create spatially explicit maps, which are fully consistent on a 5′ longitude/latitude grid resolution, and cover the period 10,000 bc to ad 2000.

Results  Cropland occupied roughly less than 1% of the global ice‐free land area for a long time until ad 1000, similar to the area used for pasture. In the centuries that followed, the share of global cropland increased to 2% in ad 1700 (c. 3 million km2) and 11% in ad 2000 (15 million km2), while the share of pasture area grew from 2% in ad 1700 to 24% in ad 2000 (34 million km2) These profound land‐use changes have had, and will continue to have, quite considerable consequences for global biogeochemical cycles, and subsequently global climate change.

Main conclusions  Some researchers suggest that humans have shifted from living in the Holocene (emergence of agriculture) into the Anthropocene (humans capable of changing the Earth's atmosphere) since the start of the Industrial Revolution. But in the light of the sheer size and magnitude of some historical land‐use changes (e.g. as result of the depopulation of Europe due to the Black Death in the 14th century and the aftermath of the colonization of the Americas in the 16th century) we believe that this point might have occurred earlier in time. While there are still many uncertainties and gaps in our knowledge about the importance of land use (change) in the global biogeochemical cycle, we hope that this database can help global (climate) change modellers to close parts of this gap.
The effect of biodiversity on tree productivity: from temperate to boreal forests
Authors: Paquette Alain , Messier Christian
Published: September 2010

Aim  An important issue regarding biodiversity concerns its influence on ecosystem functioning. Experimental work has led to the proposal of mechanisms such as niche complementarity. However, few attempts have been made to confirm these in natural systems, especially in forests. Furthermore, one of the most interesting unresolved questions is whether the effects of complementarity on ecosystem functioning (EF) decrease in favour of competitive exclusions over an increasing productivity gradient. Using records from permanent forest plots, we asked the following questions. (1) Is tree productivity positively related to diversity? (2) Does the effect of diversity increase in less productive forests? (3) What metric of diversity (e.g. functional or phylogenetic diversity) better relates to tree productivity?

Location  Temperate, mixed and boreal forests of eastern Canada.

Methods  Over 12,000 permanent forest plots, from temperate to boreal forests, were used to test our hypotheses in two steps. (1) Stepwise regressions were used to identify the best explanatory variables for tree productivity. (2) The selected climatic and environmental variables, as well as density and biodiversity indices, were included in a structural equation model where links (paths) between covarying variables are made explicit, making structural equation modelling the best tool to explore such complicated causal networks.

Results  This is the first large‐scale demonstration of a strong, positive and significant effect of biodiversity on tree productivity with control for climatic and environmental conditions. Important differences were noted between the two forest biomes investigated.

Main conclusions  We show for the first time that complementarity may be less important in temperate forests growing in a more stable and productive environment where competitive exclusion is the most probable outcome of species interactions, whereas in the more stressful environment of boreal forests, beneficial interactions between species may be more important. The present work is also a framework for the analysis of large datasets in biodiversity–ecosystem functioning (B‐EF) research.
Asymmetric boundary shifts of tropical montane Lepidoptera over four decades of climate warming
Authors: Chen I‐Ching , Hill Jane K. , Shiu Hau‐Jie , Holloway Jeremy D. , Benedick Suzan , Chey Vun Khen , Barlow Henry S. , Thomas Chris D.
Published: September 2010

Aim  To estimate whether species have shifted at equal rates at their leading edges (cool boundaries) and trailing edges (warm boundaries) in response to climate change. We provide the first such evidence for tropical insects, here examining elevation shifts for the upper and lower boundaries shifts of montane moths. Threats to species on tropical mountains are considered.

Location  Mount Kinabalu, Sabah, Malaysia.

Methods  We surveyed Lepidoptera (Geometridae) on Mount Kinabalu in 2007, 42 years after the previous surveys in 1965. Changes in species upper and lower boundaries, elevational extents and range areas were assessed. We randomly subsampled the data to ensure comparable datasets between years. Estimated shifts were compared for endemic versus more widespread species, and for species that reached their range limits at different elevations.

Results  Species that reached their upper limits at 2500–2700 m (n= 28 species, 20% of those considered) retreated at both their lower and upper boundaries, and hence showed substantial average range contractions (−300 m in elevational extent and −45 km2 in estimated range area). These declines may be associated with changes in cloud cover and the presence of ecological barriers (geological and vegetation transitions) which impede uphill movement. Other than this group, most species (n= 109, 80% of the species considered) expanded their upper boundaries upwards (by an average of 152 m) more than they retreated at their lower boundaries (77 m).

Main conclusions  Without constraints, leading margins shifted uphill faster than trailing margins retreated, such that many species increased their elevational extents. However, this did not result in increases in range area because the area of land available declines with increasing elevation. Species close to a major ecological/geological transition zone on the mountain flank declined in their range areas. Extinction risk may increase long before species reach the summit, even when undisturbed habitats are available.
Health‐Care Reform and ESI: Reconsidering the Relationship Between Employment and Health Insurance
Authors: FLYNN PATRICIA C.
Published: September 2010

The health‐care reform promised by the Patient Protection and Affordable Care Act of March 2010 continues our dependence on a central feature of the American health‐care system: employer‐sponsored insurance (ESI). In this article I will criticize the assumptions regarding market and welfare concerns on which this dependence is based and argue that efforts to mandate ESI ignore both the dynamics of the employment relation and the nature of health‐care needs. A comparison between investing in employee education and investing in employee health will reveal the pragmatic challenges to ESI and the covert appeal to employer beneficence on which ESI rests. This paper argues that relying on ESI to guarantee appropriate care for a significant segment of the population is undesirable and unsustainable from both market and moral perspectives.
Toward a Framework for Achieving a Sustainable Globalization
Authors: PREBLE JOHN F.
Published: September 2010

Widespread trade liberalization and economic integration characterize the current era of globalization. While this approach has resulted in significant job creation, improved living standards, and a wider variety of cheaper consumer goods and services, opponents question if globalization's benefits outweigh the dislocations and downsides that it causes. Protestors are intent on stalling or rolling back globalization's progression and our review of the history of globalization reveals that a backlash is not without precedent. The article carefully examines the myth and reality of these two opposing positions on four key areas of the globalization debate: jobs; inequality and poverty; national sovereignty and cultural diversity; and the natural environment. This information is then utilized to derive a broad set of feasible policy recommendations that could help bring about a more sustainable form of globalization.
Ethical Room for Maneuver: Playground for the Food Business
Authors: POMPE VINCENT , KORTHALS MICHIEL
Published: September 2010

In a world of glossy corporate social responsibility (CSR) reports, the shallowness of the actual CSR results may well be its counterpart. We claim that the possible gaps between aspirations and implementations are due to the company's overrating abilities to deal with the irrational and complex moral world of business. Many academic approaches aim to lift business ethics up to a higher level by enhancing competences but will fail because they are too rationalistic and generalistic to match the pluralistic and situational practice constituted by the mosaic of values and set of constraints. This is demonstrated by describing and analyzing the CSR development of the multinational caterer Sodexo and in particular its Dutch branch. We explain what they do and why they are not successful. We present a new tool named Ethical Room for Maneuver that centers experiences and concrete situations in a playground of inquiry and experiment to enhance abilities to operate in themoral world and to meliorate business and society with more effectiveness.
Carcass removal by scavengers and search accuracy affect bird mortality estimates at power lines
Authors: Ponce C. , Alonso J. C. , Argandoña G. , García Fernández A. , Carrasco M.
Published: September 2010

Bird mortality as a result of collisions with power lines has been of increasing concern in recent decades, but the real impact on bird populations requires an experimental assessment of scavenger removal rates and searcher detection errors. Farmland and steppe birds, two of the most threatened avian groups, have been shown to be particularly vulnerable to collision with power lines, but few removal and detectability studies have been developed in cereal farmland habitats, and none in the Mediterranean region. We conducted five carcass disappearance trials in central Spain by placing 522 corpses of different sizes under power lines, and searching for remains four times during the following month. The influence of several factors was examined using multivariate approach. The accumulated number of carcasses removed by scavengers increased logarithmically, with 32% removed over the 2‐day period after the initial placement, but only 1.5% removed on a daily basis by day 28. Small birds disappeared earlier and at a higher proportion than larger birds. Carcass removal rates were site‐dependent, but were not influenced by carcass density or season. The detection rate increased with the observer's previous experience and carcass size. Carcass counts at power lines notably underestimate bird casualties. Our 4‐week disappearance equations provide a full range of scavenging rates and observer efficiency correction factors for a wide range of bird weights. Fortnightly to monthly search frequencies may be adequate to detect medium‐ to large‐sized corpses, but are insufficient for smaller birds. Finally, all personnel participating in carcass searches should be trained previously in this task.
Evidence that glycogen synthase kinase‐3 isoforms have distinct substrate preference in the brain
Authors: Soutar Marc P. M. , Kim Woo‐Yang , Williamson Ritchie , Peggie Mark , Hastie Charles James , McLauchlan Hilary , Snider William D. , Gordon‐Weeks Phillip R. , Sutherland Calum
Published: September 2010

J. Neurochem. (2010) 115, 974–983.

Mammalian glycogen synthase kinase‐3 (GSK3) is generated from two genes, GSK3α and GSK3β, while a splice variant of GSK3β (GSK3β2), containing a 13 amino acid insert, is enriched in neurons. GSK3α and GSK3β deletions generate distinct phenotypes. Here, we show that phosphorylation of CRMP2, CRMP4, β‐catenin, c‐Myc, c‐Jun and some residues on tau associated with Alzheimer’s disease, is altered in cortical tissue lacking both isoforms of GSK3. This confirms that they are physiological targets for GSK3. However, deletion of each GSK3 isoform produces distinct substrate phosphorylation, indicating that each has a different spectrum of substrates (e.g. phosphorylation of Thr509, Thr514 and Ser518 of CRMP is not detectable in cortex lacking GSK3β, yet normal in cortex lacking GSK3α). Furthermore, the neuron‐enriched GSK3β2 variant phosphorylates phospho‐glycogen synthase 2 peptide, CRMP2 (Thr509/514), CRMP4 (Thr509), Inhibitor‐2 (Thr72) and tau (Ser396), at a lower rate than GSK3β1. In contrast phosphorylation of c‐Myc and c‐Jun is equivalent for each GSK3β isoform, providing evidence that differential substrate phosphorylation is achieved through alterations in expression and splicing of the GSK3 gene. Finally, each GSK3β splice variant is phosphorylated to a similar extent at the regulatory sites, Ser9 and Tyr216, and exhibit identical sensitivities to the ATP competitive inhibitor CT99021, suggesting upstream regulation and ATP binding properties of GSK3β1 and GSK3β2 are similar.
Exogenous protein Hsp70/Hsc70 can penetrate into brain structures and attenuate the severity of chemically‐induced seizures
Authors: Ekimova Irina V. , Nitsinskaya Larisa E. , Romanova Irina V. , Pastukhov Yuri F. , Margulis Boris A. , Guzhova Irina V.
Published: September 2010

J. Neurochem.(2010)115, 1035–1044.

Heat shock protein 70 kDa (Hsp70) possesses a remarkable neuroprotective activity and the results of recent studies demonstrated its efficacy in the attenuation of epileptic seizures. The aim of this study was to explore the effects of a pure Hsp70/Hsc70 preparation delivered to the brain regions involved in generalized seizures induced in rats by intracerebroventricular microinjections of NMDA or systemic injections of pentylenetetrazole. Purified Hsp70/Hsc70 was administered (intracerebroventricular) 2 h before the induction of seizures. Compared to the vehicle‐treated control animals, Hsp70/Hsc70‐pretreated rats demonstrated reduced severity of NMDA‐ and pentylenetetrazole‐induced seizures. To identify the brain structures potentially implicated in the Hsp70/Hsc70‐mediated anticonvulsant effect, we analysed the localization of a fluorescently‐labelled chaperone in the brain. Labelled Hsp70/Hsc70 was found in neurons and terminals of the limbic seizure complex of the brain and was co‐localized in these regions with NMDA receptors, synaptophysin and the GABA‐synthesizing enzyme,L‐glutamic acid decarboxylase 67. An immunoprecipitation assay confirmed interactions between Hsp70 and both synaptophysin andL‐glutamic acid decarboxylase 67 in brain tissue. We suggest that the anticonvulsant effect of exogenous Hsp70/Hsc70 is not only based on its protective capacity but is also related to its ability to modulate GABA neurotransmission, which in turn contributes to the maintenance of the excitatory‐inhibitory balance of the CNS.
Search for the acetylcholine and vesamicol binding sites in vesicular acetylcholine transporter: the region around the lumenal end of the transport channel
Authors: Khare Parul , Mulakaluri Anuprao , Parsons Stanley M.
Published: September 2010

J. Neurochem.(2010)115, 984–993.

Vesicular acetylcholine transporter (VAChT; TC 2.A.1.2.13) mediates storage of acetylcholine (ACh) by synaptic vesicles. A three‐dimensional homology model of VAChT is available, but the binding sites for ACh and the allosteric inhibitor (−)‐trans‐2‐(4‐phenylpiperidino)cyclohexanol (vesamicol) are unknown. In previous work, mutations of invariant W331 in the lumenal beginning of transmembrane helix VIII (TM VIII) of rat VAChT led to as much as ninefold loss in equilibrium affinity for ACh and no loss in affinity for vesamicol. The current work investigates the effects of additional mutations in and around W331 and the nearby lumenal end of the substrate transport channel. Mutants of human VAChT were expressed in the PC12A123.7cell line and characterized using radiolabeled ligands and filtration assays for binding and transport. Properties of a new and a repeat mutation in W331 are consistent with the original observations. Of 16 additional mutations in 13 other residues (Y60 in the beginning of lumenal Loop I/II, F231 in the lumenal end of TM V, W315, M316, K317, in the lumenal end of TM VII, M320, A321, W325, A330 in lumenal Loop VII/VIII, A334 in the lumenal beginning of TM VIII, and C388, C391, F392 in the lumenal beginning of TM X), only A334F impairs binding. This mutation decreases ACh and vesamicol equilibrium binding affinities by 14‐ and 4‐fold, respectively. The current results, combined with previous results, demonstrate existence of a spatial cluster of residues close to vesicular lumen that decreases affinity for ACh and/or vesamicol when the cluster is mutated. The cluster is composed of invariant W331, highly conserved A334, and invariant F335 in TM VIII and invariant C391 in TM X. Different models for the locations of the ACh and vesamicol binding sites relative to this cluster are discussed.
Correlated changes in NMDA receptor phosphorylation, functional activity, and sedation by chronic ethanol consumption
Authors: Wu Peter H. , Coultrap Steven , Browning Michael D. , Proctor William R.
Published: September 2010

J. Neurochem.(2010)115, 1112–1122.

Alcohol abuse leads to tolerance, dependence, and memory impairments that involve excitatory glutamatergic NMDA synaptic transmission. The NMDA receptor (NMDAR) is known to undergo activity‐dependent adaptive functional changes. Since we observed that acute ethanol inhibition of the NMDAR was regulated by protein tyrosine phosphorylation, we investigated the role of protein tyrosine kinases and phosphatases on the NMDAR functions by chronic ethanol treatment. We carried out whole‐cell recording, western blotting, and behavioral righting reflex measurements to assess the impact of chronic ethanol treatment on NMDAR function. Our results indicated that these receptors became resistant to the acute ethanol inhibition following chronic ethanol consumption. This resistance occurred without an increase in the NMDAR subunit expression but was associated with decreases in the levels of phospho‐Y‐1472 NR2B, increases in the levels of STEP33, increases in phospho‐p38 mitogen‐activated protein kinase (pp38 MAPK), and acquisition of tolerance to the sedative effects of ethanol. These data suggested that altered protein tyrosine phosphorylation of the NMDAR subunits significantly contributes to functional changes of this receptor by chronic ethanol ingestion. Therefore, preservation of the integrity of tyrosine phosphorylation mechanisms of the NMDAR may be important in controlling the progression of alcohol tolerance and dependence.
Effect of age on proliferation‐regulating factors in human adult neurogenic regions
Authors: Werry Eryn L. , Enjeti Shilpa , Halliday Glenda M. , Sachdev Perminder S. , Double Kay L.
Published: September 2010

J. Neurochem. (2010) 115, 956–964.

Neurogenesis, the birth of new neurons, continues throughout adulthood in the human subventricular zone (SVZ) and hippocampus. It is not known how levels of putative proliferation‐regulating factors change with age in human adult neurogenic areas. The current project employed ELISAs to investigate changes in levels of putative proliferation‐regulating factors in the healthy human SVZ and dentate gyrus throughout the adult lifespan (18–104 years). Levels of brain‐derived neurotrophic factor, basic fibroblast growth factor and interleukin (IL)‐1β were significantly higher in the hippocampus than in the SVZ and levels of glial‐derived neurotrophic factor and transforming growth factor‐α were significantly higher in the SVZ (p < 0.005), suggesting that factors with predominant influences on neurogenesis differ between the two human adult neurogenic areas. Hippocampal levels of transforming growth factor‐β1 strongly increased with age (n = 9, p < 0.01), whereas hippocampal and SVZ levels of brain‐derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, glial‐derived neurotrophic factor, heparin‐binding epidermal growth factor, insulin‐like growth factor‐1, IL‐1β, IL‐6 and transforming growth factor‐α did not change significantly with age in the SVZ or hippocampus. These findings suggest regulation of the adult neurogenic environment in the human brain may differ over time from that in other species.
Benefits of histone deacetylase inhibitors for acute brain injury: a systematic review of animal studies
Authors: Gibson Claire L. , Murphy Sean P.
Published: September 2010

J. Neurochem. (2010) 115, 806–813.

Drugs that inhibit histone deacetylase (HDAC) activities have enormous potential as neuroprotective agents. We performed a systematic review of controlled animal studies that administered known inhibitors of the zinc‐dependent HDACs before and/or after acute cerebral injury and assessed anatomic/functional outcomes. Relevant studies were found by searching PubMed, Embase and Web of Science. From more than 100 identified publications, those data meeting specific criteria were analyzed using the Cochrane Review Manager software. A beneficial effect of administering HDAC inhibitors was seen in studies involving cerebral ischemia or non‐ischemic models of acute cerebral injury. Specific studies assessed efficacy when drug was administered up to 14 days prior to, and 14 days following, the onset of cerebral injury. This systematic review provides objective evidence of a neuroprotective role for drugs that inhibit HDACs and highlights particular areas that require further experimental investigation.
N‐Methyl‐d‐aspartate receptor subunit‐ and neuronal‐type dependence of excitotoxic signaling through post‐synaptic density 95
Authors: Fan Jing , Vasuta Oana Cristina , Zhang Lily Y. J. , Wang Liang , George Ashley , Raymond Lynn A.
Published: September 2010

J. Neurochem.(2010)115, 1045–1056.

NMDA receptors (NMDARs) mediate excitatory synaptic transmission during repetitive or prolonged glutamate release, playing a critical role in synaptic plasticity or cell death, respectively. Evidence indicates that a major pathway of NMDAR signaling to cell death in cortical and hippocampal neurons requires the scaffolding protein post‐synaptic density 95 (PSD‐95) and activation of neuronal nitric oxide synthase. However, it is not known if this PSD‐95‐dependent pathway contributes to excitotoxicity in other brain regions. It is also unclear whether the neuroprotective effects of Tat‐NR2B9c, a membrane‐permeant peptide that disrupts PSD‐95/NMDAR binding, correlate with uncoupling NR2B‐ and/or NR2A‐type NMDARs from PSD‐95. In this study, we used cultured hippocampal and striatal neurons to test the potency of Tat‐NR2B9c on uncoupling NR2 subunits from PSD‐95 and protecting against NMDA‐induced excitotoxicity. We found that the concentration of Tat‐NR2B9c required to dissociate 50% of PSD‐95 was fourfold lower for NR2B than NR2A in cultured hippocampal and striatal neurons, and that this concentration correlated tightly with protection against NMDA‐induced toxicity in hippocampal neurons without altering NMDAR current. In contrast, NMDAR signaling to cell death in cultured striatal neurons occurred independently of the NR2B/PSD‐95 interaction or neuronal nitric oxide synthase activation. These results will facilitate development of neuronal type‐specific protective therapies.
Retrospectives and Prospectives on Hurricane Katrina: Five Years and Counting
Authors: Comfort Louise K. , Birkland Thomas A. , Cigler Beverly A. , Nance Earthea
Published: September 2010

New Orleans’ recovery from the damage caused by Hurricane Katrina in 2005 reflects a long, complex, contentious process that still is not complete. In this article, the authors explore the key factors that have supported and hindered recovery so far. Initial conditions within the city, the web of policy demands, as well as recent changes in law and procedures for the region are explored using a new model that may be applicable to other severe disasters. Any recovery, the authors conclude, must be anchored within a local context, but only with necessary administrative backing from the wider region and society. Recovery from disaster offers a rare opportunity to rebuild damaged communities into more resilient ones when energy and investment are immediately channeled into the stricken region and focused in a constructive redesign that acknowledges environmental risk. The recovery process then shifts to mitigation and reduction of risk. Hence, cities will be better prepared for the next extreme event, which will surely come.
Revisiting the Motivational Bases of Public Service: Twenty Years of Research and an Agenda for the Future
Authors: Perry James L. , Hondeghem Annie , Wise Lois Recascino
Published: September 2010

How has research regarding public service motivation evolved since James L. Perry and Lois Recascino Wise published their essay “The Motivational Bases of Public Service” 20 years ago? The authors assess subsequent studies in public administration and in social and behavioral sciences as well as evolving definitions of public service motivation. What have we learned about public service motivation during the last two decades? What gaps in our understanding and knowledge have appeared with respect to the three propositions offered by Perry and Wise? This essay charts new directions for public service motivation scholarship to help clarify current research questions, advance comparative research, and enhance our overall understanding of individuals’ public service motives.
A Strategy for Building Public Service Motivation Research Internationally
Authors: Kim Sangmook , Vandenabeele Wouter
Published: September 2010

As public service motivation research grows qualitatively and quantitatively, some scholars question its appropriateness for international applications. This essay sets out a strategy of convergence for international research and measurement approaches. Studies that assess commonalities in public service motivation content internationally are analyzed in order to develop a broader conceptual and more operational definition as well as consequently a more universal public service motivation construct. Public service motives, according to this review, are based on self‐sacrifice and fall into three categories: instrumental, value‐based, and identification. The dimensions of the public service motivation construct are refined along the lines of attraction to public participation, commitment to public values, compassion, and self‐sacrifice. Researchers are urged to include all of its dimensions within their empirical studies to advance contemporary public service motivation studies.
Transformational Leadership and Public Service Motivation: Driving Individual and Organizational Performance
Authors: Paarlberg Laurie E. , Lavigna Bob
Published: September 2010

Despite growing evidence about prosocial motivations and their effects on employee behavior, how can new public service motivation research translate into more effective management practices—which, so far, regrettably remain underdeveloped? Increasingly, public service motivation studies have moved from understanding what motivates public servants to exploring how public service motives influence performance. Similarly, greater attention is now paid to the practices of transformational leadership. Drawing on concepts from transformational leadership, this essay explores how managers can harness the positive aspects of public service motivation to enhance employee and organizational performance and outlines strategies that can help managers incorporate public service motivation values across management systems.
Wakeup Call: Strategic Management, Network Alarms, and Performance
Authors: Walker Richard M. , Andrews Rhys , Boyne George A. , Meier Kenneth J. , O’Toole Laurence J.
Published: September 2010

New empirical evidence suggests that service performance is shaped by the strategies adopted by public organizations and the networking behavior of public managers. Strategy captures two central behavioral aspects of public organizations: the way in which objectives and actions are selected (processes), and an organization’s approach to service delivery (content). Networking is similarly concerned with the behavior of public managers as they interact with others. These twin themes are linked in an integrated study that explores the relationship between strategy, networking, and service performance within a sample of English local governments. The results show that strategy processes based on rational planning offer long‐run positive effects on public services, as does a strategic proactive stance.
Monitoring across Sectors: Examining the Effect of Nonprofit and For‐Profit Contractor Ownership on Performance Monitoring in State and Local Contracts
Authors: Amirkhanyan Anna A.
Published: September 2010

What is the effect of contractors' nonprofit and for‐profit ownership on the scope and nature of performance measurement used by government agencies? Quantitative and qualitative data were generated through semistructured interviews administered to a sample of state and local public agencies and private contractors across five jurisdictions. The findings of this study suggest that monitoring officers working with nonprofit rather than for‐profit contractors are more likely to rely on qualitative performance data and examine equitable access to services, contractors' reputation, and compliance with industry rules and regulations. Although organizational ownership may not be well understood by practitioners, performance appears to be conceptualized differently across sectors. The author calls for a better understanding of the impact of the identified differences in performance measurement on the effectiveness of contract monitoring.
A Report On Reporting: Why Peers Report Integrity and Law Violations in Public Organizations
Authors: De Graaf Gjalt
Published: September 2010

The archives of three bureaus of integrity are analyzed in order to study the reasons for reporting integrity and law violations within public organizations. Peer reporting accounts for only a small percentage of cases; most investigations originate from routine and continuous institutional controls. What are the reasons peers choose to report or not report? A sense of justice is most important, followed by self‐protection and protection of the wrongdoer. The most important reason against coming forward is the reporter’s fear of negative consequences. One surprising rationale for not reporting is that an individual feels responsible for the wrongdoer’s punishment. Six propositions are elicited from this research as well as specific pragmatic recommendations for management procedures to improve reporting of integrity and/or law violations.