bluuebunny/crossref_metadata_2025 huggingface dataset:
Policy Transfer Networks and Collaborative Government: The Case of Social Security Fraud
Authors: Evans Mark , McComb Paul
Published: March 2007

This article makes three central claims. Firstly, it argues that the study of policy transfer provides a rich source for investigating structures and processes of Collaborative Government. For policy transfer is the outcome of collaborative activities between governmental and non-governmental actors. Secondly, it further argues that Collaborative Government can both extend and limit participation; empower and disempower. Thirdly, we draw on previous work (Evans and Davies, 1999), to contend that the policy transfer network approach provides a useful lens for studying this particular structure and process of Collaborative Government. The article explores these three claims through a case study of the emergence and development of a performance measurement and resource allocation programme within the Department of Social Security to counter social security fraud. The case study draws on the insights of the Project Leader and his team.
The National Assembly for Wales and the Promotion of Sustainable Development: Implications for collaborative government and governance
Authors: Bishop Kevin , Flynn Andrew
Published: March 2007

The National Assembly for Wales is unique amongst all levels of modern government in the UK in that it is legally required under section 121(1) of the Government of Wales Act 1998 to make a scheme setting out how it proposes, in the exercise of its functions, to promote sustainable development. This requirement represents a significant challenge for the Assembly in terms of establishing institutional structures and operational processes that will facilitate and promote sustainable development across all of its areas of responsibility. This article explores the background to the duty placed upon the Assembly and the different models that the Assembly may pursue in trying to achieve its goal of sustainable development. It explores the potential for joined-up government within the Assembly and the prospects for new forms of governance in its external links and the interactions between its internal and external processes. The article concludes that the Assembly will be a powerful force for collaborative government and that the requirements of section 121 should reinforce this move towards a new style of collaborative government but that there remains a risk that pragmatic pressures may prompt a return to the traditionally dominant form of economic governance that characterised the former Welsh Office.
Quality Issues in the Public Sector
Authors: Massey Andrew
Published: March 2007

Benchmarking grew out of the concern for measuring performance and quality in the public sector, the latest manifestation of the change that has transformed the way in which the public sector operates. From the TQA movement of the 1980s, benchmarking has emerged in the UK, via the EFQM Excellence Model, as a formidable tool to seek to ascertain and implement best practice. Although originally a model designed for the private sector, the EFQM approach has a highly political aspect to its use and as such must be of legitimate concern for policy theorists. This special edition leads on from a concern with benchmarking to a wider discussion of 'Best Value' and quality issues per se.
Raising the Expectation Interest: New Labour and the Citizen's Charter
Authors: Taylor Ian
Published: March 2007

The Citizen's Charter is essentially a charter for consumers of public services rather than a blueprint for enhancing the constitutional and political rights of the citizen. In the private sector, consumers of goods and services are protected by legislation governing the sales of goods which bestows entitlements upon them, and reinforces their expectation interest. The relationship between purchaser and provider is contractual so that if goods are faulty or the service does not match its description or the expectation of the consumer, there is an entitlement to seek redress in the form of exchange of goods, refund or damages. Whilst most public services cannot be so precise in content and objectives as private goods and services, the Citizen's and service charters nevertheless established an expectation on the part of the consumer that quality, choice, standards and value would be provided and that there would be redress in the form of compensation or, at the very least, an explanation and apology if the service did not meet expectations. Therefore it could be argued that an expectation interest was implicit in the use of a service reflecting the customer's ability to cite the objectives of the relevant charter in a dispute about a service received. This article explores the extent to which there is a legitimate expectation interest for the user of public services and examines how far New Labour's plans for strengthening the Charter enhance that expectation interest by focusing on entitlements of citizenship, as well as consumerism.
The attitudes of Councillors since Widdicombe: a focus on democratic engagement
Authors: Copus Colin
Published: March 2007

The Widdicombe committee's survey of councillors' attitudes towards democracy provided an assessment of how councillors interpret the processes of local representation and their position as representatives. Taking some of Widdicombe's research findings, this article compares it with the results of more recent research into councillors' attitudes. It explores how councillor's view the prospect of enhanced citizen participation in council affairs as an integral part of the local government modernisation agenda. The approach councillors take toward the business of local representation plays an important part in enabling local government to connect, or otherwise, with local communities and indicates the likely success or failure of moves to encourage greater public participation in local government.
Maintaining the digital hub: locating the community technology center in a communication infrastructure
Authors: Hayden Craig , Ball-Rokeach Sandra J.
Published: March 2007

Community technology centers (CTCs) are potentially a critical component in the communication environment of urban communities. They have been investigated extensively as instruments of technology-based public policy and social service capacity-building, yet they have not been subject to research that posits these centers as integral components of larger communication systems essential to civic participation and empowerment. This article describes how communication theory, communication infrastructure theory and community technology centers contribute to solving the inequalities addressed in previous studies of the `digital divide'. The article presents the communication infrastructure theory perspective as a way to reconcile alternative prescriptions for the way in which community technology interventions can lead to positive outcomes for local community-building and social mobility enhancement. This project re-situates the CTC as a communication-centric phenomenon, focusing on the linkages between the community-building capacity of CTCs and their role as an integral component of a community's communication infrastructure.
A cross-cultural comparison of perceptions and uses of mobile telephony
Authors: Campbell Scott W.
Published: March 2007

Drawing from the theoretical orientation of apparatgeist, this article explores the cultural similarities and differences in perceptions and uses of mobile telephony. A sample of college students from Hawaii, Japan, Sweden,Taiwan and the US mainland was surveyed to assess: (1) perceptions of the mobile phone as fashion;

(2) attitudes about mobile phone use in public settings; (3) use of the mobile phone for safety/security; (4) use of the mobile phone for instrumental purposes; and (5) use of the mobile phone for expressive purposes.The results indicate some differences and several similarities among the cultural groupings and help to lay the groundwork for future research and theory-building.
Abnormal hematopoiesis in Gab2 mutant mice
Authors: Zhang Yi , Diaz-Flores Ernesto , Li Geqiang , Wang Zhengqi , Kang Zizhen , Haviernikova Eleonora , Rowe Sara , Qu Cheng-Kui , Tse William , Shannon Kevin M. , Bunting Kevin D.
Published: March 2007

Gab2 is an important adapter molecule for cytokine signaling. Despite its major role in signaling by receptors associated with hematopoiesis, the role of Gab2 in hematopoiesis has not been addressed. We report that despite normal numbers of peripheral blood cells, bone marrow cells, and c-Kit+Lin−Sca-1+ (KLS) cells, Gab2-deficient hematopoietic cells are deficient in cytokine responsiveness. Significant reductions in the number of colony-forming units in culture (CFU-C) in the presence of limiting cytokine concentrations were observed, and these defects could be completely corrected by retroviral complementation. In earlier hematopoiesis, Gab2-deficient KLS cells isolated in vitro responded poorly to hematopoietic growth factors, resulting in an up to 11-fold reduction in response to a cocktail of stem cell factor, flt3 ligand, and thrombopoietin. Gab2-deficient c-Kit+Lin− cells also demonstrate impaired activation of extracellular signal-regulated kinase (ERK) and S6 in response to IL-3, which supports defects in activating the phosphatidylinositol-3 kinase (PI-3K) and mitogen-associated protein kinase (MAPK) signaling cascades. Associated with the early defects in cytokine response, competitive transplantation of Gab2−/− bone marrow cells resulted in defective long-term multilineage repopulation. Therefore, we demonstrate that Gab2 adapter function is intrinsically required for hematopoietic cell response to early-acting cytokines, resulting in defective hematopoiesis in Gab2-deficient mice.
Alanine to Serine Polymorphism at Position 986 of the Calcium-Sensing Receptor Associated with Coronary Heart Disease, Myocardial Infarction, All-Cause, and Cardiovascular Mortality
Authors: März Winfried , Seelhorst Ursula , Wellnitz Britta , Tiran Beate , Obermayer-Pietsch Barbara , Renner Wilfried , Boehm Bernhard O. , Ritz Eberhard , Hoffmann Michael M.
Published: March 2007

Background: Disorders of calcium homeostasis have been implicated in atherosclerosis. The calcium-sensing receptor (CASR) is crucial to the regulation of calcium metabolism. An alanine (A) to serine (S) polymorphism at codon 986 (A986S) of the CASR gene has been associated with higher calcium and osteoporosis; the association with coronary artery disease (CAD) has not been studied.

Methods and Results: We investigated this polymorphism in individuals with CAD (n = 2561), including survivors of myocardial infarction (MI) (n = 1358) compared to 698 controls without angiographic CAD. Compared to AA homozygotes, the prevalence of CAD [multivariate odds ratio 1.25; 95% confidence interval (CI) 1.02–1.54] and previous MI (multivariate odds ratio 1.33; 95% CI 1.06–1.68) was increased in carriers of at least one S-allele. With each S-allele, the prevalence of CAD and MI increased 1.22-fold (95% CI 1.02–1.47) and 1.30-fold (95% CI 1.06–1.60), respectively. Fully adjusted hazard ratios for total and cardiovascular mortality per one S-allele were 1.24 (95% CI 1.05–1.46) and 1.38 (95% CI 1.13–1.67), respectively. In carriers of at least one S-allele, the adjusted hazard ratios for all-cause and cardiovascular death were 1.25 (95% CI 1.04–1.51) and 1.48 (95% CI 1.18–1.86), respectively. These associations were independent of cardiovascular risk factors, calcium and phosphate. The S-allele was associated with higher calcium (P < 0.001) and PTH (P < 0.02), and lower phosphate (P < 0.003) in CAD patients and controls.

Conclusion: Serine at position 986 of CASR may be an independent genetic predictor of angiographic CAD, previous MI, and cardiovascular mortality.
Association of Small Ubiquitin-Like Modifier 4 (SUMO4) Variant, Located in IDDM5 Locus, with Type 2 Diabetes in the Japanese Population
Authors: Noso Shinsuke , Fujisawa Tomomi , Kawabata Yumiko , Asano Katsuaki , Hiromine Yoshihisa , Fukai Aya , Ogihara Toshio , Ikegami Hiroshi
Published: March 2007

Context: Despite distinct differences in the pathogenesis, epidemiological data have indicated familial clustering of type 1 and type 2 diabetes, suggesting a common genetic basis between these two types of diabetes. Few shared susceptibility genes, however, have been reported to date.

Objective: Small ubiquitin-like modifier 4 (SUMO4) has been identified as a candidate gene for the IDDM5 locus and suggested to have possible involvement in immune responses, such as autoimmunity and inflammation. Recent reports demonstrated that a polymorphism with an amino acid substitution (Met55Val) in SUMO4 was associated with type 1 diabetes in Asian populations, although no association was reproduced in subjects of Caucasian descent. The present study aimed to clarify the contribution of SUMO4 to type 2 diabetes susceptibility in the Japanese population.

Subjects: The 753 subjects included 355 cases and 398 control subjects.

Methods: The SUMO4 Met55Val (rs237025) and 001Msp (rs577001) polymorphisms were genotyped.

Results: Strong linkage disequilibrium (D′: 1.0 in each pair of single-nucleotide polymorphisms) across the MAP3K7IP2/SUMO4 region was shown in the Japanese population. The frequency of genotypes with the G allele of the SUMO4 Met55Val polymorphism was significantly higher in patients with type 2 diabetes [odds ratio, 1.46; 95% confidence interval (CI), 1.08–1.93; P = 0.01, χ2 test]. The association was concentrated in patients without insulin therapy (odds ratio, 1.56; 95% CI, 1.13–2.15; P = 0.0072), but not in those with insulin (odds ratio, 1.24; 95% CI, 0.81–1.89; not significant).

Conclusions: These data, together with previous reports, suggest the contribution of the SUMO4 Met55Val polymorphism to both type 1 and type 2 diabetes susceptibility in the Japanese population.
Missense Mutations of Dual Oxidase 2 (DUOX2) Implicated in Congenital Hypothyroidism Have Impaired Trafficking in Cells Reconstituted with DUOX2 Maturation Factor
Authors: Grasberger Helmut , De Deken Xavier , Miot Francoise , Pohlenz Joachim , Refetoff Samuel
Published: March 2007

Dual oxidase 2 (DUOX2), a reduced NAD phosphate:O2 oxidoreductase flavoprotein, is a component of the thyrocyte H2O2 generator required for hormone synthesis at the apical plasma membrane. We recently identified a specific DUOX2 maturation factor (DUOXA2) that is necessary and sufficient for expression of functional DUOX2 in mammalian cell lines. We have now used a DUOXA2 reconstituted system to provide the first characterization of natural DUOX2 missense variants (Q36H, R376W, D506N) at the molecular level, analyzing their impact on H2O2 generation, trafficking, stability, folding, and DUOXA2 interaction. The Q36H and R376W mutations completely prevent routing of DUOX2 to the cell surface. The mutant proteins are predominantly present as core N-glycosylated, thiol-reduced folding intermediates, which are retained by the quality control system within the endoplasmic reticulum (ER) as indicated by increased complexation with the lectin calnexin. D506N displays a partial deficiency phenotype with reduced surface expression of a mutant protein with normal intrinsic activity in generating H2O2. D506N N-glycan moieties are not subject to normal modification in the Golgi apparatus, suggesting that nonnative protein can escape the quality control in the ER. Oxidative folding of DUOX2 in the ER appears to be the rate-limiting step in the maturation of DUOX2, but is not facilitated by DUOXA2. Rather, DUOXA2 allows rapid ER exit of folded DUOX2 or enhanced degradation of mutant DUOX2 proteins not competent for ER exit. DUOXA2 may thus be part of a secondary quality control system specific for DUOX2.
Multiple functions of Snail family genes during palate development in mice
Authors: Murray Stephen A. , Oram Kathleen F. , Gridley Thomas
Published: March 2007

Palate development requires precise regulation of gene expression changes,morphogenetic movements and alterations in cell physiology. Defects in any of these processes can result in cleft palate, a common human birth defect. The Snail gene family encodes transcriptional repressors that play essential roles in the growth and patterning of vertebrate embryos. Here we report the functions of Snail (Snai1) and Slug (Snai2) genes during palate development in mice. Snai2-/- mice exhibit cleft palate, which is completely penetrant on a Snai1 heterozygous genetic background. Cleft palate in Snai1+/- Snai2-/-embryos is due to a failure of the elevated palatal shelves to fuse. Furthermore, while tissue-specific deletion of the Snai1 gene in neural crest cells does not cause any obvious defects, neural-crest-specific Snai1 deletion on a Snai2-/- genetic background results in multiple craniofacial defects, including a cleft palate phenotype distinct from that observed in Snai1+/-Snai2-/- embryos. In embryos with neural-crest-specific Snai1 deletion on a Snai2-/- background, palatal clefting results from a failure of Meckel's cartilage to extend the mandible and thereby allow the palatal shelves to elevate, defects similar to those seen in the Pierre Robin Sequence in humans.
Intracellular pathway of Onconase that enables its delivery to the cytosol
Authors: Rodríguez Montserrat , Torrent Gerard , Bosch Montserrat , Rayne Fabienne , Dubremetz Jean-François , Ribó Marc , Benito Antoni , Vilanova Maria , Beaumelle Bruno
Published: March 2007

Onconase® is an RNase with a very specific property because it is selectively toxic to transformed cells. This toxin is thought to recognize cell surface receptors, and the protection conferred by metabolic poisons against Onconase toxicity indicated that this RNase relies on endocytic uptake to kill cells. Nevertheless, its internalization pathway has yet to be unraveled. We show here that Onconase enters cells using AP-2/clathrin-mediated endocytosis. It is then routed, together with transferrin, to the receptor recycling compartment. Increasing the Onconase concentration in this structure using tetanus toxin light chain expression enhanced Onconase toxicity, indicating that recycling endosomes are a key compartment for Onconase cytosolic delivery. This intracellular destination is specific to Onconase because other (and much less toxic) RNases follow the default pathway to late endosomes/lysosomes. Drugs neutralizing endosomal pH increased Onconase translocation efficiency from purified endosomes during cell-free translocation assays by preventing Onconase dissociation from its receptor at endosomal pH. Consistently, endosome neutralization enhanced Onconase toxicity up to 100-fold. Onconase translocation also required cytosolic ATP hydrolysis. This toxin therefore shows an unusual entry process that relies on clathrin-dependent endocytic uptake and then neutralization of low endosomal pH for efficient translocation from the endosomal lumen to the cytosol.
A Comparison of Antibiotic Use in Children Between Canada and Denmark
Authors: Marra Fawziah , Monnet Dominique L , Patrick David M , Chong Mei , Brandt Christian T , Winters Meghan , Kaltoft Margit S , Tyrrell Gregory J , Lovgren Marguerite , Bowie William R
Published: March 2007

Background:

High rates of antibiotic prescribing in children lead to antibiotic resistance in the community. Surveillance on utilization rates and comparisons with other jurisdictions are methods for benchmarking. Surveillance on antibiotic use is well established in Europe, including Denmark, but until recently, similar data from Canada were lacking.

Objective:

To compare pediatric antibiotic prescribing rates in British Columbia, Canada, with those in Denmark.

Methods:

Population-based data on antibiotic prescriptions from British Columbia and Denmark were obtained from 1999 to 2003 for children less than 15 years of age. Annual trends in prescription rates per 1000 children were analyzed by using generalized linear models for all children less than 15 years of age; they were stratified by age group (0–4, 5–9, 10–14 y) for all antibiotics. Class-specific trends were also evaluated for penicillins, cephalosporins, macrolides, sulfonamides and trimethoprim, tetracyclines, and fluoroquinolones.

Results:

From 1999 to 2003, the overall British Columbia prescription rate was significantly higher than that of Denmark (p < 0.0001) at all age stratifications. In 2003, the British Columbia prescription rate was twice that of Denmark, at 608 versus 385 prescriptions per 1000 children, respectively. In both jurisdictions, the majority of antibiotics used were penicillins (Anatomical Therapeutic Chemical class J01C), However, in British Columbia, most penicillins used were extended-spectrum (83% in 2003); in Denmark, 34% of penicillins used in 2003 were extended-spectrum and 56% were β-lactamase sensitive. In British Columbia, use of penicillins (−4.5%), cephalosporins (−5.5%), trimethoprim/sulfamethoxazole (−36%), and tetracycline (−1.6%) decreased over time, whereas in Denmark, use of penicillins increased by 11% over time and non-penicillin antibiotics remained stable. A significant increase in macrolide consumption was seen in British Columbia due to use of clarithromycin and azithromycin; in contrast, macrolide consumption declined in Denmark.

Conclusions:

Compared with Denmark, the antibiotic prescription rate for children is substantially higher in British Columbia. In addition, there has been a significant increase in the use of macrolides, especially the second-generation agents, in British Columbia compared with the use in Denmark. Further studies are required to delineate reasons for antibiotic prescribing patterns in these 2 jurisdictions.
Cardiology: Post-Cardiothoracic Surgery Atrial Fibrillation: A Review of Preventive Strategies
Authors: Baker William L , White C Michael
Published: March 2007

Objective:

To review the available literature addressing preventive strategies of post-cardiothoracic surgery atrial fibrillation (post-CTS atrial fibrillation).

Data Sources:

Pertinent articles related to the etiology, risk factors, and preventive strategies were identified through a MEDLINE search (1966–March 2007) using the MeSH terms atrial fibrillation, cardiothoracic surgery, cardiac surgery, etiology, neurohormonal, sympathetic, volume, fluid, inflammation, risk factors, operative, pacing, β-adrenergic blockers, amiodarone, sotalol, calcium-channel blockers, magnesium, HMG-CoA reductase inhibitors, statins, fatty acids, PUFA, steroids, and nonsteroidal antiinflammatory drugs.

Study Selection and Data Extraction:

Articles evaluated were limited to human studies, published in the English language, with a Jadad score greater than 3. References of identified articles were reviewed for additional pertinent articles.

Data Synthesis:

Post-CTS atrial fibrillation most commonly occurs on the second or third postoperative day, with an incidence of 20–50%. Etiology theories include neurohormonal activation, volume overload, and inflammation. Studies examining nonpharmacologic therapies have shown that maintenance of the anterior epicardial fat pad is not a viable prophylactic strategy. Biatrial cardiac pacing, especially in combination with amiodarone, is a viable preventive option. Withdrawal of preoperative β-blockers places patients at higher risk for atrial fibrillation; these drugs should be continued postoperatively. Evidence exists supporting the use of amiodarone, sotalol, and magnesium in addition to β-blockers. Since most of these strategies work by attenuating neurohormonal activation, adverse events, including hypotension and bradycardia, are of concern. Adding agents with antiinflammatory properties, including hydroxymethylglutaryl coenzyme A reductase inhibitors or corticosteroids, may prove to be of benefit. Additional studies using novel therapies are needed in addition to established preventive strategies.

Conclusions:

Available evidence supports the continuation of preoperative β-blockers, as well as prophylactic amiodarone, sotalol, and magnesium. Other novel therapies, mostly targeting inflammation, are under investigation and may provide additional strategies.
Basic Fibroblast Growth Factor Modulates Density of Blood Vessels and Preserves Tight Junctions in Organotypic Cortical Cultures of Mice: A NewIn VitroModel of the Blood–Brain Barrier
Authors: Bendfeldt Kerstin , Radojevic Vesna , Kapfhammer Josef , Nitsch Cordula
Published: March 2007

This study was performed to examine the maintenance of blood vesselsin vitroin cortical organotypic slice cultures of mice with special emphasis on basic fibroblast growth factor (FGF-2), which is known to promote angiogenesis and to preserve the integrity of the blood–brain barrier. Slices of neonatal day 3 or 4 mouse brain were maintained for 3, 7, or 10 din vitro(DIV) under standard culture conditions or in the presence of FGF-2. Immunohistochemistry for factor VIII-related antigen or laminin revealed a relative low number of blood vessels under standard conditions. In contrast, moderate FGF-2 concentrations increased the number of vessels: with 0.5 ng/ml FGF-2 it was 1.4-fold higher after DIV 3 or 1.5-fold after DIV 7 compared with controls; with 5 ng/ml it was almost doubled in both cases. With an excess of 50 ng/ml, FGF-2 vessels were reduced after DIV 3 or similar to controls after DIV 7. FGF receptor 1 was preferentially found on endothelial cells; its immunolabeling was reduced in the presence of the ligand. Cell death detected by an ethidium bromide analog or the apoptosis marker caspase-3 was barely detectable during the 10 d culture period. Immunolabeling of the tight junction proteins ZO-1 (zonula occludens protein 1), occludin, claudin-5, and claudin-3 revealed evidence for structural integrity of the blood–brain barrier in the presence of moderate FGF-2 concentrations. In conclusion, FGF-2 maintains blood vesselsin vitroand preserves the composition of the tight junction. Hence, we propose FGF-2-treated organotypic cortical slices as a new tool for mechanistic studies of the blood–brain barrier.
Hippocampal Expression Analyses Reveal Selective Association of Immediate-Early, Neuroenergetic, and Myelinogenic Pathways with Cognitive Impairment in Aged Rats
Authors: Rowe Wayne B. , Blalock Eric M. , Chen Kuey-Chu , Kadish Inga , Wang Daguang , Barrett James E. , Thibault Olivier , Porter Nada M. , Rose Gregory M. , Landfield Philip W.
Published: March 2007

Although expression of some genes is known to change during neuronal activity or plasticity, the overall relationship of gene expression changes to memory or memory disorders is not well understood. Here, we combined extensive statistical microarray analyses with behavioral testing to comprehensively identify genes and pathways associated with aging and cognitive dysfunction. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups based on their Morris water maze performance relative to young-adult (Y) animals. Hippocampal gene expression was assessed in Y, AU, and AI on the fifth (last) day of maze training (5T) or 21 d posttraining (21PT) and in nontrained animals (eight groups total, one array per animal;n= 78 arrays). ANOVA and linear contrasts identified genes that differed from Y generally with aging (differed in both AU and AI) or selectively, with cognitive status (differed only in AI or AU). Altered pathways/processes were identified by overrepresentation analyses of changed genes. With general aging, there was downregulation of axonal growth, cytoskeletal assembly/transport, signaling, and lipogenic/uptake pathways, concomitant with upregulation in immune/inflammatory, lysosomal, lipid/protein degradation, cholesterol transport, transforming growth factor, and cAMP signaling pathways, primarily independent of training condition. Selectively, in AI, there was downregulation at 5T of immediate-early gene, Wnt (wingless integration site), insulin, and G-protein signaling, lipogenesis, and glucose utilization pathways, whereas Notch2 (oligodendrocyte development) and myelination pathways were upregulated, particularly at 21PT. In AU, receptor/signal transduction genes were upregulated, perhaps as compensatory responses. Immunohistochemistry confirmed and extended selected microarray results. Together, the findings suggest a new model, in which deficient neuroenergetics leads to downregulated neuronal signaling and increased glial activation, resulting in aging-related cognitive dysfunction.
Cell-Specific Alterations of T-Type Calcium Current in Painful Diabetic Neuropathy Enhance Excitability of Sensory Neurons
Authors: Jagodic Miljen M. , Pathirathna Sriyani , Nelson Michael T. , Mancuso Stefani , Joksovic Pavle M. , Rosenberg Ethan R. , Bayliss Douglas A. , Jevtovic-Todorovic Vesna , Todorovic Slobodan M.
Published: March 2007

Recent data indicate that T-type Ca2+channels are amplifiers of peripheral pain signals, but their involvement in disorders of sensory neurons such as those associated with diabetes is poorly understood. To address this issue, we used a combination of behavioral, immunohistological, molecular, and electrophysiological studies in rats with streptozotocin (N-[methylnitrosocarbamoil]-d-glucosamine)-induced early diabetic neuropathy. We found that, in parallel with the development of diabetes-induced pain, T-type current density increased by twofold in medium-size cells from L4–L5dorsal root ganglia (DRG) with a depolarizing shift in steady-state inactivation. This not only correlated closely with more prominent afterdepolarizing potentials (ADPs) but also increased cellular excitability manifested as a lower threshold for burst firing in diabetic than in control cells. T-type currents and ADPs were potently inhibited by nickel and enhanced byl-cysteine, suggesting that the CaV3.2 T-type channel isoform was upregulated. Both control and diabetic DRG cells with ADPs stained positively for isolectin B4, but only diabetic cells responded robustly to capsaicin, suggesting enhanced nociceptive function. Because increased excitability of sensory neurons may result in such pathological perceptions of pain as hyperalgesia and allodynia, upregulation of T-type Ca2+currents and enhanced Ca2+entry into these cells could contribute to the development of symptoms in diabetic neuropathy.
The Impact of Input Fluctuations on the Frequency–Current Relationships of Layer 5 Pyramidal Neurons in the Rat Medial Prefrontal Cortex
Authors: Arsiero Maura , Lüscher Hans-Rudolf , Lundstrom Brian Nils , Giugliano Michele
Published: March 2007

The role of irregular cortical firing in neuronal computation is still debated, and it is unclear how signals carried by fluctuating synaptic potentials are decoded by downstream neurons. We examinedin vitrofrequency versus current (f–I) relationships of layer 5 (L5) pyramidal cells of the rat medial prefrontal cortex (mPFC) using fluctuating stimuli. Studies in the somatosensory cortex show that L5 neurons become insensitive to input fluctuations as input mean increases and that theirf–Iresponse becomes linear. In contrast, our results show that mPFC L5 pyramidal neurons retain an increased sensitivity to input fluctuations, whereas their sensitivity to the input mean diminishes to near zero. This implies that the discharge properties of L5 mPFC neurons are well suited to encode input fluctuations rather than input mean in their firing rates, with important consequences for information processing and stability of persistent activity at the network level.
Experience-Specific Functional Modification of the Dentate Gyrus through Adult Neurogenesis: A Critical Period during an Immature Stage
Authors: Tashiro Ayumu , Makino Hiroshi , Gage Fred H.
Published: March 2007

Neural circuits in the dentate gyrus are continuously modified by adult neurogenesis, whose level is affected by the animal's experience. However, it is not known whether this experience-dependent anatomical modification alters the functional properties of the dentate gyrus. Here, using the expression of immediate early gene products, c-fos and Zif268, as indicators of recently activated neurons, we show that previous exposure to an enriched environment increases the total number of new neurons and the number of new neurons responding to reexposure to the same environment. The increase in the density of activated new neurons occurred specifically in response to exposure to the same environment but not to a different experience. Furthermore, we found that these experience-specific modifications are affected exclusively by previous exposure around the second week after neuronal birth but not later than 3 weeks. Thus, the animal's experience within a critical period during an immature stage of new neurons determines the survival and population response of the new neurons and may affect later neural representation of the experience in the dentate gyrus. This experience-specific functional modification through adult neurogenesis could be a mechanism by which new neurons exert a long-term influence on the function of the dentate gyrus related to learning and memory.
Rapid and Intermittent Cotransport of Slow Component-b Proteins
Authors: Roy Subhojit , Winton Matthew J. , Black Mark M. , Trojanowski John Q. , Lee Virginia M.-Y.
Published: March 2007

After synthesis in neuronal perikarya, proteins destined for synapses and other distant axonal sites are transported in three major groups that differ in average velocity and protein composition: fast component (FC), slow component-a (SCa), and slow component-b (SCb). The FC transports mainly vesicular cargoes at average rates of ∼200–400 mm/d. SCa transports microtubules and neurofilaments at average rates of ∼0.2–1 mm/d, whereas SCb translocates ∼200 diverse proteins critical for axonal growth, regeneration, and synaptic function at average rates of ∼2–8 mm/d. Several neurodegenerative diseases are characterized by abnormalities in one or more SCb proteins, but little is known about mechanisms underlying SCb compared with FC and SCa. Here, we use live-cell imaging to visualize and quantify the axonal transport of three SCb proteins, α-synuclein, synapsin-I, and glyceraldehyde-3-phosphate dehydrogenase in cultured hippocampal neurons, and directly compare their transport to synaptophysin, a prototypical FC protein. All three SCb proteins move rapidly but infrequently with pauses during transit, unlike synaptophysin, which moves much more frequently and persistently. By simultaneously visualizing the transport of proteins at high temporal and spatial resolution, we show that the dynamics of α-synuclein transport are distinct from those of synaptophysin but similar to other SCb proteins. Our observations of the cotransport of multiple SCb proteins in single axons suggest that they move as multiprotein complexes. These studies offer novel mechanistic insights into SCb and provide tools for further investigating its role in disease processes.
Involvement of Interferon-γ in Microglial-Mediated Loss of Dopaminergic Neurons
Authors: Mount Matthew P. , Lira Arman , Grimes David , Smith Patrice D. , Faucher Sylvie , Slack Ruth , Anisman Hymie , Hayley Shawn , Park David S.
Published: March 2007

Growing evidence implicates microglia in the loss of dopaminergic neurons in Parkinson's disease (PD). However, factors mediating microglial activation in PD are poorly understood. Proinflammatory cytokines, such as interferon-γ (IFN-γ), orchestrate the actions of microglia. We report here that PD patients express significantly elevated levels of IFN-γ in their blood plasma. After this initial finding, we found thatIFN-γ-deficient mice displayed attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced substantia nigra pars compacta dopaminergic cell loss along with reduced loss of striatal tyrosine hydroxylase and dopamine transporter fiber density. MPTP-induced depletion of striatal dopamine and its metabolite DOPAC (3,4-dihydroxyphenylacetic acid), as well as ΔFosB, a marker of postsynaptic dysfunction, were also attenuated in these knock-out mice. Consistent with the role for IFN-γ in microglial activation, MPTP-induced morphological activation of microglia was abrogated compared with wild-type mice. To examine more mechanistically the role of IFN-γ in microglial activation, we evaluated the interactions between microglia and dopaminergic neurons in anin vitromixed microglia/midbrain neuron rotenone-induced death paradigm. In thisin vitroparadigm, dopaminergic neurons are selectively damaged by rotenone. Exogenous IFN-γ ligand alone and without rotenone resulted in dopaminergic cell loss, but only in the presence of microglia. The addition of an IFN-γ neutralizing antibody attenuated neuronal loss as a result of rotenone treatment. The presence of only wild-type microglia and not those deficient in IFN-γ receptor elicited significant dopaminergic cell loss when exposed to rotenone. Neurons deficient in IFN-γ receptor, however, did not display increased resistance to death. Finally, levels of IFN-γ message increased in microglia in response to rotenone. Together, these data suggest that IFN-γ participates in death of dopaminergic neurons by regulating microglial activity.
Modulation of Gamma and Alpha Activity during a Working Memory Task Engaging the Dorsal or Ventral Stream
Authors: Jokisch Daniel , Jensen Ole
Published: March 2007

Despite extensive experimental work in both animals and humans, the actual role of oscillatory brain activity for working memory maintenance remains elusive. Gamma band activity (30–100 Hz) has been hypothesized to reflect either the maintenance of neuronal representations or changing demands in attention. Regarding posterior alpha activity (8–13 Hz), it is under debate whether it reflects functional inhibition or neuronal processing required for the task. The aim of the present study was to further elucidate the role of oscillatory brain activity in humans using a working memory task engaging either the dorsal or ventral visual stream. We recorded brain activity using magnetoencephalography from subjects performing a delayed-match-to-sample task. Subjects were instructed to remember either the identity or the spatial orientation of shortly presented faces. The analysis revealed stronger alpha power around the parieto-occipital sulcus during retention of face identities (ventral stream) compared with the retention of face orientations (dorsal stream). In contrast, successful retention of face orientations was associated with an increase in gamma power in the occipital lobe relative to the face identity condition. We propose that gamma activity reflects the actual neuronal maintenance of visual representations, whereas the alpha increase is a result of functional inhibition.
Multishell Semiconductor Nanocrystals
Authors: Dorfs Dirk , Eychmüller Alexander
Published: March 2007

In this review article we summarize the progress in research on multishell semiconductor nanocrystals. Three branches are covered: Core–shell–shell (CSS) nanocrystals with a lattice adapting layer which show extraordinarily high emission quantum yields and high photostability, quantum dot quantum well nanocrystals which allow to study interactions across extremely thin semiconductor layers, and “inversed” quantum dot quantum well structures which show two distinct emissions from one sample.
Zeolite-Encaged Iridium Clusters with Hydride Ligands: Characterization by Extended X-Ray Absorption Fine Structure, NMR, and Inelastic Neutron Scattering Vibrational Spectroscopies
Authors: Li Fen , Yu Ping , Hartl Monika , Daemen Luke L. , Eckert Juergen , Gates Bruce C.
Published: March 2007

A family of NaY zeolite-supported iridium clusters was prepared by reductive carbonylation of Ir(CO)2(acac) sorbed in the zeolite pores to form Ir6(CO)16, which was decarbonylated by treatment in He. This method allowed preparation of samples with Ir contents as high as 33.0 wt.%. Extended X-ray absorption fine structure spectra of the decarbonylated samples indicate that the clusters are well approximated as octahedral Ir6 in the zeolite cages. The high loadings of clusters in the zeolite allowed characterization of the hydride ligands on the clusters by 1H NMR spectroscopy and inelastic neutron scattering spectroscopy. These ligands exist on the clusters even in the absence of H2 in the gas phase, presumably equilibrated with OH groups on the zeolite. The data indicate both terminal and bridging hydride ligands on the clusters. The H/Ir atomic ratio is estimated to be approximately 0.01 on the basis of the 1H NMR data and thermogravimetric analysis of the sample.
Cyclic Voltammetry for Predicting Oxidation Process in Heterogeneous Catalysis
Authors: Zhu Junjiang , Yang Xiangguang , Xu Xuelian , Wei Kemei
Published: March 2007

Catalytic reactions with different oxidation process were investigated and correlated to the electrochemical properties of the catalysts. The activity of suprafacial reaction is closely related to the area of redox peak, while that of the intrafacial one is to the match of redox potentials. Accordingly, it is supposed that cyclic voltammetry (CV) measurement could be a means for predicting the oxidation process in heterogeneous catalysis.
Free Volume Nanocavities in PMMA Revealed by Rotational Dephasing of Paraterphenyl in a Transient Grating Experiment
Authors: von Seggern David , Spitz Christian , Menzel Ralf
Published: March 2007

The excited state decay behaviour of p-terphenyl in cyclohexane solution and in a rigid poly(methyl methacrylate) (PMMA) film is reported as measured in a ps polarization dependent transient grating experiment. In both cases, the diffracted intensity shows a biexponential decay. The slower component is attributed to excited state lifetime. In the liquid solution, the faster decay component is described by the hydrodynamical Stokes–Einstein–Debye theory for rotational reorientation under slip boundary conditions. In the rigid matrix it is interpreted in terms of a free volume effect.
The Line of Beauty
Authors: Swaab Peter
Published: March 2007

ABSTRACT The BBC TV adaptation of Alan Hollinghurst's Booker Prize-winning 2004 novel of Aids and Thatcherism was undertaken by Andrew Davies, best known for his version of Pride and Prejudice. Directed by Saul Dibb, The Line of Beauty's depiction of 1980s London is appropriate to both to its source and costume-drama conventions.
The Chinese Side of the Mountain
Authors: Berry Chris
Published: March 2007

ABSTRACT Brokeback Mountain not only differs from most other Westerns by mixing in melodrama, but also uses a very specifically Chinese form of melodrama known as the “family ethics” film. Furthermore, it also draws on another regional subcultural tradition —comics produced for and by straight women but about love between two young men.
Brokering Brokeback: Jokes, Backlashes, and Other Anxieties
Authors: Rich B. Ruby
Published: March 2007

ABSTRACT This essay explores the reception of Brokeback Mountain by film critics, gay viewers, female audiences, television shows, and the blogosphere. By tracing the path of controversies, jokes, and anxieties, this essay argues that hysteria came into play to mask homophobia while, in the gay community, debates etched the limits of contemporary identity politics.
Interpreters and Ideology: From 'Between' to 'Within'
Authors: Pöchhacker Franz
Published: March 2007

Ideology was not an issue in the literature on interpreting until very recently. When the subject of ideology emerged in translation studies in the late 1990s, interpreting researchers were only just beginning to move beyond the traditional concern with (conference) interpreters' psycholinguistic processing skills and cognitive functions to include problems of cross-cultural interaction in their purview. This exploratory paper therefore reviews the development of the interpreting profession from the conceptual vantage point of 'ideology', focusing on the common pejorative, political sense of the term. The positionality of interpreters as agents 'between' ideologies will be traced through the profession's development before some examples will be given of how interpreters, their professional organizations and training institutions have become 'involved' in and with ideology, and to what extent such involvement has been acknowledged. As will be seen, closer examination of the relationship between interpreters and ideology is warranted even on a narrow, political understanding of the term, but especially if ideology is reconceptualized in the broader sense used in recent scholarship.
Translation in Context: Omnibus Review (Nigel Armstrong: Translation, Linguistics, Culture: A French-English Handbook. Lynne Long (ed.): Translation and Religion: Holy Untranslatable? Phyllis Zatlin: Theatrical Translation and Film Adaptation: A Practitioner's View. Gunilla Anderman and Margaret Rogers (eds): In and Out of English: For Better or Worse?)
Authors: Albrecht Neubert
Published: March 2007

This is an omnibus review that deals with the almost simultaneous appearance of four books, each devoted to a significant aspect of translation studies. Each publication purports to contribute to what their authors hold to be essential business of the discipline, and this reviewer fully shares their views regarding the relevance of the questions raised in the four publications. In particular, he thinks that the individual approaches deserve to be seen in unison. This is the reason why the analysis of these four publications has been composed into a single review article, which is also intended to serve several other purposes: (1) to show that the studies, with the exception of the last title, represent integral voices of the now well-established seriesTopics in Translation, also published by Multilingual Matters, (2) to stress that all four books manage to put into the forefront what in a too narrow linguistic view often tends to get overlooked, namely the place of translation, past and present, in real life contexts.
Book Reviews
Authors: Bánhegyi Mátyás , Bakti Mária , Jenei Gabriella , Lengyel István
Published: March 2007

Mona Baker: Translation and Conflict: A Narrative Account; Rita Godijns, Michael Hinderdael (eds.): Directionality in Interpreting. The 'Retour' or the Native?; Krisztina Károly: Lexical Repetition in Text: A Study of the Text-organizing Function of Lexical Repetition in Foreign Language Argumentative Discourse; Ljuba Tarvi: Comparative Translation Assessment: Quantifying Quality
Chlamydia Trachomatis: Milestones in clinical and microbiological diagnostics in the last hundred years
Authors: Budai Irén
Published: March 2007

Chlamydia trachomatis
an obligate intracellular, Gram-negative bacterium is the causative agent of several acute or chronic, local and systemic human diseases such as trachoma, oculogenital and neonatal infections. It was discovered in 1907 by Halberstaedter and von Prowazek who observed it in conjunctival scrapings from an experimentally infected orangutan. In the last hundred years the detection and study of the intracellular pathogens, including chlamydiae, passed through an enormous evolution. This memorial review is dedicated to these important research and diagnostic discoveries and to the scientists who significantly contributed to this evolution starting from the application of simple light microscopy through the cell culture technique, antibiotic susceptibility, antigen and antibody detection, serotyping, to the real-time nucleic acid amplification and restriction fragment lengths polymorphism analysis. Although the majority of these old and new excellent diagnostic methods have been introduced into the rutine practice, the trachoma has remained one of the leading causes of blindness, and oculogenital chlamydial infections still are the most frequent sexually transmitted bacterial diseases, furthermore lymphogranuloma venereum is a disease emerging in the developed countries at the beginning of the 21
st
century.