bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 induction contributes to excitotoxic neuronal death in rat striatum through apoptotic and autophagic mechanisms
Authors: Wang Yan , Dong Xiao‐Xia , Cao Yi , Liang Zhong‐Qin , Han Rong , Wu Jun‐Chao , Gu Zhen‐Lun , Qin Zhen‐Hong 
Published: December 2009

AbstractThe present study sought to investigate mechanisms by which p53 induction contributes to excitotoxic neuronal injury. Rats were intrastriatally administered the N‐methyl‐d‐aspartate (NMDA) receptor agonist quinolinic acid (QA), the changes in the expression of p53 and its target genes involved in apoptosis and autophagy, including p53‐upregulated modulator of apoptosis (PUMA), Bax, Bcl‐2, damage‐regulated autophagy modulator (DRAM) and other autophagic proteins including microtubule‐associated protein 1 light chain 3 (LC3) and beclin 1 were assessed. The contribution of p53‐mediated autophagy activation to apoptotic death of striatal neurons was assessed with co‐administration of the nuclear factor‐kappaB (NF‐κB) inhibitor SN50, the p53 inhibitor Pifithrin‐alpha (PFT‐α) or the autophagy inhibitor 3‐methyladenine (3‐MA). The increased formation of autophagosomes and secondary lysosomes were observed with transmission electron microscope after excitotoxin exposure. QA induced increases in the expression of p53, PUMA, Bax and a decrease in Bcl‐2. These changes were significantly attenuated by pre‐treatment with SN50, PFT‐α or 3‐MA. SN50, PFT‐α or 3‐MA also reversed QA‐induced upregulation of DRAM, the ratio of LC3‐II/LC3‐I and beclin 1 protein levels in the striatum. QA‐induced internucleosomal DNA fragmentation and loss of striatal neurons were robustly inhibited by SN50, PFT‐α or 3‐MA. These results suggest that overstimulation of NMDA receptors can induce NF‐κB‐dependent expression of p53. p53 participates in excitotoxic neuronal death probably through both apoptotic and autophagic mechanisms.
Zn2+ regulates Kv2.1 voltage‐dependent gating and localization following ischemia
Authors: Aras Mandar A. , Saadi Robert A. , Aizenman Elias 
Published: December 2009

AbstractThe delayed‐rectifier K+ channel Kv2.1 exists in highly phosphorylated somatodendritic clusters. Ischemia induces rapid Kv2.1 dephosphorylation and a dispersal of these clusters, accompanied by a hyperpolarizing shift in their voltage‐dependent activation kinetics. Transient modulation of Kv2.1 activity and localization following ischemia is dependent on a rise in intracellular Ca2+and the protein phosphatase calcineurin. Here, we show that neuronal free Zn2+also plays a critical role in the ischemic modulation of Kv2.1. We found that sub‐lethal ischemia in cultured rat cortical neurons led to characteristic hyperpolarizing shifts in K+ current voltage dependency and pronounced dephosphorylation of Kv2.1. Zn2+chelation, similar to calcineurin inhibition, attenuated ischemic induced changes in K+ channel activation kinetics. Zn2+chelation during ischemia also blocked Kv2.1 declustering. Surprisingly, we found that the Zn2+rise following ischemia occurred in spite of calcineurin inhibition. Therefore, a calcineurin‐independent rise in neuronal free Zn2+ is critical in altering Kv2.1 channel activity and localization following ischemia. The identification of Zn2+ in mediating ischemic modulation of Kv2.1 may lead to a better understanding of cellular adaptive responses to injury.
A mental retardation gene, motopsin /neurotrypsin /prss12, modulates hippocampal function and social interaction
Authors: Mitsui Shinichi , Osako Yoji , Yokoi Fumiaki , Dang Mai T. , Yuri Kazunari , Li Yuqing , Yamaguchi Nozomi 
Published: December 2009

AbstractMotopsin is a mosaic serine protease secreted from neuronal cells in various brain regions, including the hippocampus. The loss of motopsin function causes nonsyndromic mental retardation in humans and impairs long‐term memory formation in Drosophila. To understand motopsin’s function in the mammalian brain, motopsin knockout (KO) mice were generated. Motopsin KO mice did not have significant deficits in memory formation, as tested using the Morris water maze, passive avoidance and Y‐maze tests. A social recognition test showed that the motopsin KO mice had the ability to recognize two stimulator mice, suggesting normal social memory. In a social novelty test, motopsin KO mice spent a longer time investigating a familiar mouse than wild‐type (WT) mice did. In a resident–intruder test, motopsin KO mice showed prolonged social interaction as compared with WT mice. Consistent with the behavioral deficit, spine density was significantly decreased on apical dendrites, but not on basal dendrites, of hippocampal pyramidal neurons of motopsin KO mice. In contrast, pyramidal neurons at the cingulate cortex showed normal spine density. Spatial learning and social interaction induced the phosphorylation of cAMP‐responsive element‐binding protein (CREB) in hippocampal neurons of WT mice, whereas the phosphorylation of CREB was markedly decreased in mutant mouse brains. Our results indicate that an extracellular protease, motopsin, preferentially affects social behaviors, and modulates the functions of hippocampal neurons.
Dexmedetomidine: perioperative applications in children
Authors: YUEN VIVIAN MAN YING 
Published: December 2009

SummaryDexmedetomidine is a highly specific and selective alpha‐2‐adrenergic agonist with sedative, anxiolytic, and organ protective effects. Its clinical applications in children include premedication, prevention of emergence delirium, as part of multimodal anesthetic regimen and sedation in the pediatric intensive care unit. Its role in neuroprotection in children undergoing anesthesia should be explored. In this review, various uses of dexmedetomidine are discussed in detail.
Monitoring and impact of fluconazole serum and cerebrospinal fluid concentration in HIV‐associated cryptococcal meningitis‐infected patients
Authors: Manosuthi W , Chetchotisakd P , Nolen TL , Wallace D , Sungkanuparph S , Anekthananon T , Supparatpinyo K , Pappas PG , Larsen RA , Filler SG , Andes D ,   on behalf of the BAMSG 3‐01 Study Team
Published: December 2009

Objectives
The aim of the present study was to assess fluconazole pharmacokinetic measures in serum and cerebrospinal fluid (CSF); and the correlation of these measures with clinical outcomes of invasive fungal infections.Methods
A randomized trial was conducted in HIV‐infected patients receiving three different regimens of fluconazole plus amphotericin B (AmB) for the treatment of cryptococcal meningitis. Regimens included fluconazole 400 mg/day+AmB (AmB+Fluc400) or fluconazole 800 mg/day+AmB (AmB+Fluc800) (14 days followed by fluconazole alone at the randomized dose for 56 days); or AmB alone for 14 days followed by fluconazole 400 mg/day for 56 days. Serum (at 24 h after dosing) and CSF samples were taken at baseline and days 14 and 70 (serum only) for fluconazole measurement, using gas–liquid chromatography.Results
Sixty‐four treated patients had fluconazole measurements: 11 in the AmB group, 12 in the AmB+Fluc400 group and 41 in the AmB+Fluc800 group. Day 14 serum concentration geometric means were 24.7 mg/L for AmB+Fluc400 and 37.0 mg/L for AmB+Fluc800. Correspondingly, CSF concentration geometric means were 25.1 mg/L and 32.7 mg/L. Day 14 Serum and CSF concentrations were highly correlated with AmB+Fluc800 (P<0.001, r=0.873) and AmB+Fluc400 (P=0.005, r=0.943). Increased serum area under the curve (AUC) appears to be associated with decreased mortality at day 70 (P=0.061, odds ratio=2.19) as well as with increased study composite endpoint success at days 42 and 70 (P=0.081, odds ratio=2.25 and 0.058, 2.89, respectively).Conclusion
High fluconazole dosage (800 mg/day) for the treatment of HIV‐associated cryptococcal meningitis was associated with high serum and CSF fluconazole concentration. Overall, high serum and CSF concentration appear to be associated with increased survival and primary composite endpoint success.
Urbanization and Informal Development in China: Urban Villages in Shenzhen
Authors: WANG YA PING , WANG YANGLIN , WU JIANSHENG 
Published: December 2009

AbstractInformal housing and industrial developments in the so‐called urban villages have been key features of the recent Chinese urbanization. In this article we will examine the development of urban villages in one of the most dynamic Chinese cities — Shenzhen. The article first reviews the urbanization and migration process in the region and the emergence of urban villages. It then examines informal housing, commercial and industrial developments in these villages. We analyse the politics of village urbanization and highlight the important relationship between migration and informal village development. We emphasize the contribution made by urban villages in providing affordable housing and jobs for the low‐income population during the rapid urbanization and urge cautious consideration with regard to hasty and large‐scale redevelopment of these villages. We conclude that the development of urban villages is a very important part of the urbanization process.RésuméL’habitat informel et les aménagements commerciaux et industriels dans les villages dits urbains constituent des caractéristiques essentielles de la récente urbanisation chinoise. Cet article examine le développement des villages urbains dans l’une des villes les plus dynamiques: Shenzhen. L’article revient d’abord sur les processus d’urbanisation et de migration dans la région et sur l’émergence des villages urbains. Il s’attache ensuite à l’habitat informel, ainsi qu’aux aménagements commerciaux et industriels, dans ces villages. La politique d’urbanisation des villages est analysée, mettant en évidence le lien important entre migration et aménagement informel des villages. L’étude souligne que les villages urbains fournissent des logements accessibles financièrement et des emplois à la population à faible revenu pendant la phase rapide d’urbanisation, et insiste sur les précautions à prendre vis‐à‐vis d’un réaménagement précipité et à grande échelle de ces villages. La conclusion met en avant combien le développement des villages urbains est important dans le processus d’urbanisation.
Sexually transmitted infections and related sociodemographic factors in Lisbon’s major Venereology Clinic: a descriptive study of the first 4 months of 2007
Authors: Borges da Costa J , Azevedo J , Santo I 
Published: December 2009

AbstractObjectives  To assess the prevalence of sexually transmitted infections (STI) and relationships between them and sociodemographic/behavioural data in the major Venereology Clinic in Lisbon.Methods  Every patient attending this STI clinic for the first time in the first 17 weeks of 2007 was enrolled in this study. Early syphilis, Chlamydia trachomatis infection, gonorrhoea, human immunodeficiency virus (HIV) first diagnosed and genital warts were considered for the study of statistical associations with sociodemographic/behavioural variables or other STI. Data were analysed with an exact significance level of 5%.Results  A total of 743 patients were included. In women (n = 296), the only significant associations found were for C. trachomatis and being non‐Caucasian (OR = 2.13, CI 1.17–3.9) or being younger than 25 years (OR = 1.9, CI 1.31–2.79).Men who have sex with men (176 of the 447 male patients) contributed to 39% of the STI, although more than half of the early syphilis, gonorrhoea and HIV cases were diagnosed in this group.Conclusions  Despite its limitations, our study allows some insight into the relationships between sociodemographic factors and STI in a selected population attending Lisbon’s major Venereology Clinic. The results were similar to those of other European studies and to recent trends in STI, but differ in the association between C. trachomatis infection and non‐Caucasian women, which is similar to cities with significant African minorities. Attention should be given to the associations found between men who have sex with men and STI such as gonorrhoea, syphilis and HIV, as these associations can lead to serious difficulties in the control of HIV infection in Portugal.
Welfare Analysis with a Proxy Consumption Measure: Evidence from a Repeated Experiment in Indonesia*
Authors: Pradhan Menno 
Published: December 2009

AbstractEvery three years, Indonesia fields simultaneously two nationwide surveys which collect consumption data. One collects consumption using 23 questions, the other using 320 questions. Based on a repeated experiment in which the two questionnaires were randomly assigned across households, this paper examines the consequences of using a higher level of aggregation in questioning. A mapping of distribution functions reveals the combined effect of systematic differences in measurement and measurement error. Comparing means by subgroups, the effect of additive measurement error is eliminated, and it is found that using a higher level of aggregation yields a lower consumption measure and that the fraction of underestimation increases as consumption rises. A 1 per cent increase in average consumption increases the fraction by which consumption is underestimated by about 0.4 percentage points. Next, the paper examines the consequences of using the short consumption questionnaire in welfare analysis. Higher relative measurement error in the consumption measure derived from the short questionnaire results in higher poverty estimates even if the poverty line is adjusted to take account of the systematic underestimation. Small differences are found for analysis that is based on the rank the individual holds in the consumption distribution. In gradient analysis, it seems impossible to devise a simple correction factor for the higher consumption elasticities that follow when the short questionnaire is used.
Methodological Innovations in Collecting Spending Data: The HRS Consumption and Activities Mail Survey*
Authors: Hurd Michael , Rohwedder Susann 
Published: December 2009

AbstractIt has traditionally been believed that collecting survey measures of total spending necessarily involved asking a large number of questions, too many for inclusion of a comprehensive spending measure in a general‐purpose survey. In this paper, we report on a supplemental survey to the Health and Retirement Study that took up this challenge. We discuss issues that arise when designing a survey module to collect spending data with strict time constraints, describe how the implementation in the Consumption and Activities Mail Survey (CAMS) played out, and elicit anomalies that more detailed analysis of data quality revealed. We report how we addressed some of these anomalies in subsequent waves of CAMS. Other anomalies required conducting some randomised experiments to find what explains the observed patterns. The results highlight the tension between asking about spending using a long time frame, which exacerbates recall bias, versus using a short time frame, which risks relying on an unrepresentative snapshot of a household's spending to proxy the total for the last 12 months. An important complicating factor in deciding which goods should be put into which time frames is that there is substantial heterogeneity in the frequency of spending across households even for the same category of spending.
The Allocation of Expenditures within the Household: A New Survey*
Authors: Bonke Jens , Browning Martin 
Published: December 2009

AbstractWe report on a data initiative that is designed to address the question of ‘who gets what’ within the household. The data consist of supplements to the Danish Household Expenditure Survey (DHES), which is a traditional nationally representative diary‐based survey of expenditures. We collect supplementary data of two kinds for all couples (with or without children) in the survey. The first set of additional information is that respondents report on the intra‐household allocation of each item of expenditure recorded in the diary. The allowed assignments are ‘the whole family’, ‘the wife’, ‘the husband’, ‘the children’, ‘others’ and ‘not assignable’. The second addition is an extra set of ‘sociological’ questions concerning household financial management, autonomy and family background.We focus on the survey design and give some descriptive statistics from the survey. We also show how the distribution of expenditure on clothing, which is often used to look at intra‐household allocation, is related to the distribution of expenditure on other goods.The paper concludes that it is feasible to collect information on ‘who gets what’ within the household and that some sociological questions provide valuable supplementary information for some issues of interest.
Structure–function relationships of the N‐terminus of receptor activity‐modifying proteins
Authors: Qi Tao , Hay Debbie L 
Published: December 2009

The receptor activity‐modifying proteins (RAMPs) are a family of three single transmembrane proteins that have been identified as accessory proteins to some G‐protein‐coupled receptors (GPCRs). They can regulate their pharmacology, forward trafficking and recycling, depending on the GPCR. The best characterized receptor complexes formed by RAMPs and GPCRs are the calcitonin peptide family receptors. The association of RAMP1 with the calcitonin receptor‐like receptor (CL) constitutes the calcitonin gene‐related peptide receptor, whereas RAMP2 or 3 with CL generates adrenomedullin receptors. In this case, the RAMPs substantially alter the pharmacology and trafficking properties of this GPCR. Amylin receptor subtypes are formed from calcitonin receptor (CTR) interactions with RAMPs. Although the RAMPs themselves are not responsive to calcitonin peptide family ligands, there is clear evidence that they participate in ligand binding, although it is still unclear whether this is by directly participating in binding or through allosteric modulation of CL or CTR. A considerable amount of mutagenesis data have now been generated on RAMPs to try and identify the residues that play a role in ligand interactions, and to also identify which residues in RAMPs interact with CL and CTR. This review will focus on RAMP mutagenesis studies with CL, summarizing and discussing the available data in association with current RAMP models and structures. The data reveal key regions in RAMPs that are important for ligand binding and receptor interactions.This article is part of a themed section on Molecular Pharmacology of GPCR. To view the editorial for this themed section visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00695.x
The accumulation and metabolism of zidovudine in 3T3‐F442A pre‐adipocytes
Authors: Janneh Omar , Owen Andrew , Bray Patrick G. , Back David J. , Pirmohamed Munir 
Published: December 2009

Background and purpose: Cultured pre‐adipocytes accumulate and metabolize zidovudine (ZDV), but its mode of accumulation into these cells is unclear. We investigated the mode of accumulation of [3H]‐ZDV, and the impact of changes in external pH and modulators of drug transporters on its accumulation and metabolism.Experimental approach: The initial rate and steady‐state accumulation of [3H]‐ZDV were measured in 3T3‐F442A cells. P‐glycoprotein (P‐gp) expression was detected by Western blotting. External pH was varied, and modulators of intracellular pH and drug transporters were used to study the mode of accumulation of ZDV. Phosphorylated ZDV metabolites were detected by high‐performance liquid chromatography.Key results: Intracellular accumulation of ZDV was rapid, reaching equilibrium within 20 min; nigericin increased accumulation by 1.9‐fold, but this did not alter the generation of ZDV mono‐, di‐ and triphosphate. The accumulation and metabolism were pH dependent, being maximal at pH 7.4 and least at pH 5.1. Monensin, carbonyl cyanidep‐trifluoromethoxy) phenyl hydrazone, brefeldin A, bafilomycin A1 and concanamycin A increased accumulation; 2‐deoxyglucose, dipyridamole, thymidine and tetraphenylphosphonium inhibited accumulation. The accumulation was saturable; the derivedKdand capacity of binding were 250 nmol per 106cells and 265 nM respectively. 3T3‐F442A cells express P‐gp; inhibitors of P‐gp (XR9576 and verapamil), P‐gp/BCRP (GF120918), multidrug resistance protein (MRP) (MK571) and MRP/OATP (probenecid) increased the accumulation of ZDV. Saquinavir, ritonavir, amprenavir and lopinavir increased accumulation.Conclusions and implications: The accumulation of ZDV in 3T3‐F442A cells was rapid, energy dependent, saturable and pH sensitive. Western blot analysis showed that 3T3‐F442A cells express P‐gp, and direct inhibition assays suggest that ZDV is a substrate of P‐gp and MRP.
Prevalence and Severity of Gait Disorders in Alzheimer's and Non‐Alzheimer's Dementias
Authors: Allan Louise M. , Ballard Clive G. , Burn David J. , Kenny Rose Anne 
Published: December 2009

Objectives: To compare the prevalence, severity, and type of gait and balance disorders in Alzheimer's disease (AD), vascular dementia (VaD), Parkinson's disease with dementia (PDD), dementia with Lewy bodies (DLB), Parkinson's disease without dementia (PD), and age‐matched controls.Design: Cross‐sectional.Setting: Secondary care clinics in geriatric psychiatry, neurology, and geriatrics.Participants: Two hundred forty‐five participants aged 65 and older (AD, n=40; VaD, n=39; PDD, n=46; DLB, n=32; PD, n=46; and controls, n=42).Measurements: Prevalence and severity of gait and balance disorders were assessed using the Tinetti gait and balance scale. The types of gait disorders in each diagnostic group were classified using the Nutt et al. classification.Results: Gait and balance disorders were more common with PDD (93%), VaD (79%), and DLB (75%) than with PD (43%) and AD (25%) and in controls (7%). The risk of gait and balance disorder was higher in the non‐Alzheimer's dementia groups (VaD, PDD, and DLB) than in the AD group (odds ratio=15 (95% confidence interval=6–37). If a gait disorder was present in mild dementia (Cambridge Examination for Mental Disorders of the Elderly cognitive subsection score >65), this was diagnostic of non‐Alzheimer's dementia, with sensitivity of 78% and specificity of 100%. Non‐Alzheimer's dementia groups had worse Tinetti gait and balance scores than the AD group (all P<.001). The types of gait disorders discriminated between non‐Alzheimer's dementias.Conclusion: The findings support the idea that gait and balance assessment may augment the diagnostic evaluation of dementia.