bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis
Authors: Yao Shu‐Qin , Li Zheng‐Zheng , Huang Qing‐Yuan , Li Fang , Wang Zhao‐Wei , Augusto Elisabete , He Jin‐Cai , Wang Xiao‐Tong , Chen Jiang‐Fan , Zheng Rong‐Yuan 
Published: May 2012

AbstractStudies with multiple sclerosis patients and animal models of experimental autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors in modulation of neuroinflammation and brain injury. Although the involvement of the A1 receptor has been recently demonstrated, the role of the adenosine A2A receptor (A2AR) in development of EAE pathology is largely unknown. Using mice with genetic inactivation of the A2A receptor, we provide direct evidence that loss of the A2AR exacerbates EAE pathology in mice. Compared with wild‐type mice, A2AR knockout mice injected with myelin oligodendroglia glycoprotein peptide had a higher incidence of EAE and exhibited higher neurological deficit scores and greater decrease in body weight. A2AR knockout mice displayed increased inflammatory cell infiltration and enhanced microglial cell activation in cortex, brainstem, and spinal cord. In addition, demyelination and axonal damage in brainstem were exacerbated, levels of Th1 cytokines increased, and Th2 cytokines decreased. Collectively, these findings suggest that extracellular adenosine acting at A2ARs triggers an important neuroprotective mechanism. Thus, the A2A receptor is a potential target for therapeutic approaches to multiple sclerosis.
Constitutively active mutant gives novel insights into the mechanism of bitter taste receptor activation
Authors: Pydi Sai Prasad , Bhullar Rajinder Pal , Chelikani Prashen 
Published: May 2012

J. Neurochem. (2012) 122, 537–544.AbstractThe human bitter taste receptors (T2Rs) belong to the G‐protein coupled receptor (GPCR) superfamily. T2Rs share little homology with the large subfamily of Class A G‐protein coupled receptors, and their mechanisms of activation are poorly understood. Guided by biochemical and molecular approaches, we identified two conserved amino acids Gly281.46 and Ser2857.47 present on transmembrane (TM) helices, TM1 and TM7, which might play important roles in T2R activation. Previously, it was shown that naturally occurring Gly511.46 mutations in the dim light receptor, rhodopsin, cause autosomal dominant retinitis pigmentosa, with the mutants severely defective in signal transduction. We mutated Gly281.46 and Ser2857.47 in T2R4 to G28A, G28L, S285A, S285T, and S285P, and carried out pharmacological characterization of the mutants. No major changes in signaling were observed upon mutation of Gly281.46 in T2R4. Interestingly, S285A mutant displayed agonist‐independent activity (approximately threefold over basal wild‐type T2R4 or S285T or S285P). We propose that Ser2857.47 stabilizes the inactive state of T2R4 by a network of hydrogen‐bonds connecting important residues on TM1‐TM2‐TM7. We compare and contrast this hydrogen‐bond network with that present in rhodopsin. Thus far, S285A is the first constitutively active T2R mutant reported, and gives novel insights into T2R activation.
Leucine‐rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin‐like protein
Authors: Niu Jingwen , Yu Mei , Wang Chunyan , Xu Zhiheng 
Published: May 2012

J. Neurochem. (2012) 122, 650–658.AbstractMutations in Leucine‐rich repeat kinase 2 (LRRK2) are the leading causes of genetically inherited Parkinson’s disease (PD) identified so far. The underlying mechanism whereby missense alterations in LRRK2 initiate neurodegeneration remains largely unclear. Mitochondrial dysfunction has been recognized to contribute to the pathogenesis of both sporadic and familial PD. The pathogenic gain‐of‐function mutant form of LRRK2, LRRK2 G2019S, is associated with elevated kinase activity and PD. Here we show that LRRK2 G2019S can cause defects in the morphology and dynamics of mitochondria in cortical neurons. In neurons, endogenous LRRK2 and the mitochondrial fission factor Dynamin like protein 1 (DLP1) interact with and partially co‐localize with each other. DLP1 plays an essential role in LRRK2‐induced mitochondrial fission. In support of this, expression of LRRK2 leads to the translocation of DLP1 from the cytosol to the mitochondria and knockdown of DLP1 expression inhibits LRRK2‐induced mitochondrial fission. In addition, co‐expression of LRRK2 and DLP1 induces mitochondrial clearance. Furthermore, we have found that expression of LRRK2 leads to increased reactive oxygen species levels in cells. Taken together, our results provide insights into the pathobiology of LRRK2 and suggest that LRRK2 G2019S may induce neuronal dysfunction or cell death by disturbing normal mitochondrial fission/fusion dynamics and function.
Functional differences between ATP‐gated human and rat P2X3 receptors are caused by critical residues of the intracellular C‐terminal domain
Authors: Sundukova Mayya , Vilotti Sandra , Abbate Rita , Fabbretti Elsa , Nistri Andrea 
Published: May 2012

J. Neurochem. (2012) 122, 557–567.AbstractATP‐activated P2X3 receptors of sensory ganglion neurons contribute to pain transduction and are involved in chronic pain signaling. Although highly homologous (97%) in rat and human species, it is unclear whether P2X3 receptors have identical function. Studying human and rat P2X3 receptors expressed in patch‐clamped human embryonic kidney (HEK) cells, we investigated the role of non‐conserved tyrosine residues in the C‐terminal domain (rat tyrosine‐393 and human tyrosine‐376) as key determinants of receptor function. In comparison with rat P2X3 receptors, human P2X3 receptors were more expressed and produced larger responses with slower desensitization and faster recovery. In general, desensitization was closely related to peak current amplitude for rat and human receptors. Downsizing human receptor expression to the same level of the rat one still yielded larger responses retaining slower desensitization and faster recovery. Mutating phenylalanine‐376 into tyrosine in the rat receptor did not change current amplitude; yet, it retarded desensitization onset, demonstrating how this residue was important to functionally link these two receptor states. Conversely, removing tyrosine from position 376 strongly down‐regulated human receptor function. The different topology of tyrosine residues in the C‐terminal domain has contrasting functional consequences and is sufficient to account for species‐specific properties of this pain‐transducing channel.
Subcellular localization of regulator of G protein signaling RGS7 complex in neurons and transfected cells
Authors: Liapis Evangelos , Sandiford Simone , Wang Qiang , Gaidosh Gabriel , Motti Dario , Levay Konstantin , Slepak Vladlen Z. 
Published: May 2012

J. Neurochem. (2012) 122, 568–581.AbstractThe R7 family of regulators of G protein signaling (RGS) is involved in many functions of the nervous system. This family includes RGS6, RGS7, RGS9, and RGS11 gene products and is defined by the presence of the characteristic first found in Disheveled, Egl‐10, Pleckstrin (DEP), DEP helical extension (DHEX), Gγ‐like, and RGS domains. Herein, we examined the subcellular localization of RGS7, the most broadly expressed R7 member. Our immunofluorescence studies of retinal and dorsal root ganglion neurons showed that RGS7 concentrated at the plasma membrane of cell bodies, in structures resembling lamellipodia or filopodia along the processes, and at the dendritic tips. At the plasma membrane of dorsal root ganglia neurons, RGS7 co‐localized with its known binding partners R7 RGS binding protein (R7BP), Gαo, and Gαq. More than 50% of total RGS7‐specific immunofluorescence was present in the cytoplasm, primarily within numerous small puncta that did not co‐localize with R7BP. No specific RGS7 or R7BP immunoreactivity was detected in the nuclei. In transfected cell lines, ectopic RGS7 had both diffuse cytosolic and punctate localization patterns. RGS7 also localized in centrosomes. Structure‐function analysis showed that the punctate localization was mediated by the DEP/DHEX domains, and centrosomal localization was dependent on the DHEX domain.
Accuracy, completeness and comprehensiveness of information on pressure ulcers recorded in the patient record
Authors: Thoroddsen Asta , Sigurjónsdóttir Guðrún , Ehnfors Margareta , Ehrenberg Anna 
Published: May 2012

Scand J Caring Sci; 2013; 27; 84–91

Accuracy, completeness and comprehensiveness of information on pressure ulcers recorded in the patient record
Aim:  To describe the accuracy, completeness and comprehensiveness of information on pressure ulcers documented in patient records.Design and setting:  A cross‐sectional descriptive study performed in 29 wards at a university hospital in Iceland. The study included skin assessment of patients and retrospective audits of records of patients identified with pressure ulcers.Participants:  A sample of 219 patients was inspected for signs of pressure ulcers on 1 day in 2008. Records of patients identified with pressure ulcers were audited (n = 45) retrospectively.Results:  The prevalence of pressure ulcers was 21%. Information in patient records lacked accuracy, completeness and comprehensiveness. Only 60% of the identified pressure ulcers were documented in the patient records. The lack of accuracy was most prevalent for stage I pressure ulcers.Conclusions:  The purpose of documentation to record, communicate and support the flow of information in the patient record was not met. The patient records lacked accuracy, completeness and comprehensiveness, which can jeopardise patient safety, continuity and quality of care. The information on pressure ulcers in patient records was found not to be a reliable source for the evaluation of quality in health care. To improve accuracy, completeness and comprehensiveness of data in the patient record, a systematic risk assessment for pressure ulcers and assessment and treatment of existing pressure ulcers based on evidence‐based guidelines need to be implemented and recorded in clinical practice. Health information technology, including the electronic health record with decision support, has shown promising results to facilitate and improve documentation of pressure ulcers.
Impacts of data quality on the setting of conservation planning targets using the species–area relationship
Authors: Metcalfe Kristian , Delavenne Juliette , Garcia Clément , Foveau Aurélie , Dauvin Jean‐Claude , Coggan Roger , Vaz Sandrine , Harrop Stuart R. , Smith Robert J. 
Published: May 2012

AbstractAimThe species–area relationship (SAR) is increasingly being used to set conservation targets for habitat types when designing protected area networks. This approach is transparent and scientifically defensible, but there has been little research on how it is affected by data quality and quantity.LocationEnglishChannel.MethodsWe used a macrobenthic dataset containing 1314 sampling points and assigned each point to its associated habitat type. We then used theSAR‐based approach and tested whether this was influenced by changes in (i) the number of sampling points used to generate estimates of total species richness for each habitat type; (ii) the nonparametric estimator used to calculate species richness; and (iii) the level of habitat classification employed. We then compared our results with targets from a similar national‐level study that is currently being used to identifyMarineConservationZones in theUK.ResultsWe found that targets were affected by all of the tested factors. Sample size had the greatest impact, with specific habitat targets increasing by up to 45% when sample size increased from 50 to 300. We also found that results based on theBootstrap estimator of species richness, which is the most widely used for setting targets, were more influenced by sample size than the other tested estimators. Finally, we found that targets were higher when using broader habitat classification levels or a larger study region. However, this could also be a sample size effect because these larger habitat areas generally contained more sampling points.Main conclusionsHabitat targets based on theSARcan be strongly influenced by sample size, choice of richness estimator and the level of habitat classification. Whilst setting habitat targets using best‐available data should play a key role in conservation planning, further research is needed to develop methods that better account for sampling effort.
Global land use intensity and the endangerment status of mammal species
Authors: Pekin Burak K. , Pijanowski Bryan C. 
Published: May 2012

AbstractAimHuman land use activities are creating a biodiversity crisis. However, it is not clear how species respond to different intensities of land use at a global scale. We used spatial analyses to determine the relationships between human settlements, croplands, rangelands and forests of varying intensities and the endangerment status of mammal species across the globe. In doing so, we sought to assess the role of different land use and land management strategies in global biodiversity conservation.LocationGlobal.MethodsA GIS database with distribution ranges for 4734 Red‐Listed and non‐threatened terrestrial mammal species was obtained from the IUCN and combined with the global anthropogenic biomes dataset, which uses population density class (dense, residential, populated and remote) as a proxy for land use intensity. Ordered logistic regression was used to predict the effect of each land use intensity class on the probability of having a more endangered IUCN status for all mammal species together and for species within major mammal groups separately.ResultsThe probability of having a more endangered status generally increased for mammal species as the proportion of urban settlements, mosaic and cropped ‘villages’, and residential and populated croplands within their distribution ranges increased. In contrast, endangerment probability of mammals decreased with proportion of irrigated, pastoral and rainfed ‘villages’, remote croplands and all rangeland classes. Endangerment probability also decreased with proportion of wildlands and remote forests, but increased with proportion of populated forests for several mammal groups.Main conclusionsUrbanization and high‐intensity crop production pose a significant threat to mammals worldwide. In contrast, rangelands, low‐intensity croplands and certain low‐intensity human settlements may in fact help maintain mammal diversity at global scales. While the area of wild habitat available to species is also highly important for biodiversity conservation, forested lands that are disturbed or over utilized by humans do not benefit and may even endanger species.
Temporal analysis of vascular smooth muscle cell elasticity and adhesion reveals oscillation waveforms that differ with aging
Authors: Zhu Yi , Qiu Hongyu , Trzeciakowski Jerome P. , Sun Zhe , Li Zhaohui , Hong Zhongkui , Hill Michael A. , Hunter William C. , Vatner Dorothy E. , Vatner Stephen F. , Meininger Gerald A. 
Published: May 2012

SummaryA spectral analysis approach was developed for detailed study of time‐resolved, dynamic changes in vascular smooth muscle cell (VSMC) elasticity and adhesion to identify differences in VSMC from young and aged monkeys. Atomic force microscopy (AFM) was used to measure Young’s modulus of elasticity and adhesion as assessed by fibronectin (FN) or anti‐beta 1 integrin interaction with the VSMC surface. Measurements demonstrated that VSMC cells from old vs. young monkeys had increased elasticity (21.6 kPa vs. 3.5 kPa or a 612% increase in elastic modulus) and adhesion (86 pN vs. 43 pN or a 200% increase in unbinding force). Spectral analysis identified three major frequency components in the temporal oscillation patterns for elasticity (ranging from 1.7 × 10−3 to 1.9 × 10−2 Hz in old and 8.4 × 10−4 to 1.5 × 10−2 Hz in young) and showed that the amplitude of oscillation was larger (P < 0.05) in old than in young at all frequencies. It was also observed that patterns of oscillation in the adhesion data were similar to the elasticity waveforms. Cell stiffness was reduced and the oscillations were inhibited by treatment with cytochalasin D, ML7 or blebbistatin indicating the involvement of actin–myosin‐driven processes. In conclusion, these data demonstrate the efficacy of time‐resolved analysis of AFM cell elasticity and adhesion measurements and that it provides a uniquely sensitive method to detect real‐time functional differences in biomechanical and adhesive properties of cells. The oscillatory behavior suggests that mechanisms governing elasticity and adhesion are coupled and affected differentially during aging, which may link these events to changes in vascular stiffness.
Direct democracy and regional integration: Citizens' perceptions of treaty implications and the Irish reversal on Lisbon
Authors: GARRY JOHN 
Published: May 2012

AbstractAnalyses of voting in European Union referendums typically distinguish between ‘second‐order’ effects and the impact of substantive ‘issues’. In order to explain change in referendum outcome, two types of substantive issues are distinguished in this article. Focusing on Irish voting in the Lisbon Treaty referendums and using data from post‐referendum surveys, it is found that perceptions of treaty implications outperform underlying attitudes to EU integration in predicting vote choice at both referendums, and perceptions of treaty implications are strong predictors of vote change between the referendums. The findings have broadly positive implications for normative assessments of the usefulness of direct democracy as a tool for legitimising regional integration advance.
A Sumatriptan Iontophoretic Transdermal System for the Acute Treatment of Migraine
Authors: Goldstein Jerome , Smith Timothy R. , Pugach Neil , Griesser Jim , Sebree Terri , Pierce Mark 
Published: May 2012

Objective.— Gastrointestinal symptoms, such as nausea and vomiting, occur almost universally at one time or another in patients during a migraine attack. One third of patients who experience migraine‐related nausea report that this symptom interferes with their ability to take oral medications. The sumatriptan iontophoretic transdermal system (NuPathe Inc., Conshohocken, PA, USA) uses proprietary technology to circumvent the gastrointestinal tract while delivering triptan therapy. This phase III randomized, double‐blind, placebo‐controlled trial evaluated the efficacy and tolerability of this system for the acute treatment of migraine.Methods.— Patients were randomized to treat a single moderate‐to‐severe migraine attack with the sumatriptan iontophoretic transdermal system or placebo. The primary end point was the proportion of patients who were headache pain‐free 2 hours after patch activation. Other end points included the proportions of patients who reported headache pain relief, and freedom from nausea, photophobia, and phonophobia; rescue medication use; and tolerability.Results.— Four hundred sixty‐nine patients were treated. Significantly more patients treated with the sumatriptan iontophoretic transdermal system compared with placebo experienced freedom from headache pain, nausea, photophobia, and phonophobia 2 hours after patch activation, experienced rapid and sustained headache pain relief, and used less rescue medication. Treatment‐emergent adverse events were reported by 50% and 44% of patients treated with the sumatriptan iontophoretic transdermal system and placebo, respectively. Most events were transient mild‐to‐moderate application‐site reactions.Conclusions.— The sumatriptan iontophoretic transdermal system is effective and well tolerated, and may be particularly useful in patients with migraine‐related gastrointestinal symptoms such as nausea.
Efficacy of Transcranial Direct Current Stimulation and Repetitive Transcranial Magnetic Stimulation for Treating Fibromyalgia Syndrome: A Systematic Review
Authors: Marlow Nicole M. , Bonilha Heather S. , Short E. Baron 
Published: May 2012

AbstractObjective:  To systematically review the literature to date applying repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for patients with fibromyalgia syndrome (FMS).Method:  Electronic bibliography databases screened included PubMed, Ovid MEDLINE, PsychINFO, CINAHL, and Cochrane Library. The keyword “fibromyalgia” was combined with (“transcranial” and “stimulation”) or “TMS” or “tDCS” or “transcranial magnetic stimulation” or “transcranial direct current stimulation”.Results:  Nine of 23 studies were included; brain stimulation sites comprised either the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC). Five studies used rTMS (high‐frequency‐M1: 2, low‐frequency‐DLPFC: 2, high‐frequency‐DLPFC: 1), while 4 applied tDCS (anodal‐M1: 1, anodal‐M1/DLPFC: 3). Eight were double‐blinded, randomized controlled trials. Most (80%) rTMS studies that measured pain reported significant decreases, while all (100%) tDCS studies with pain measures reported significant decreases. Greater longevity of significant pain reductions was observed for excitatory M1 rTMS/tDCS.Conclusion:  Studies involving excitatory rTMS/tDCS at M1 showed analogous pain reductions as well as considerably fewer side effects compared to FDA apaproved FMS pharmaceuticals. The most commonly reported side effects were mild, including transient headaches and scalp discomforts at the stimulation site. Yearly use of rTMS/tDCS regimens appears costly ($11,740 to 14,507/year); however, analyses to apapropriately weigh these costs against clinical and quality of life benefits for patients with FMS are lacking. Consequently, rTMS/tDCS should be considered when treating patients with FMS, particularly those who are unable to find adequate symptom relief with other therapies. Further work into optimal stimulation parameters and standardized outcome measures is needed to clarify associated efficacy and effectiveness.
Managing Employee Compliance with Information Security Policies: The Critical Role of Top Management and Organizational Culture*
Authors: Hu Qing , Dinev Tamara , Hart Paul , Cooke Donna 
Published: May 2012

ABSTRACTWe develop an individual behavioral model that integrates the role of top management and organizational culture into the theory of planned behavior in an attempt to better understand how top management can influence security compliance behavior of employees. Using survey data and structural equation modeling, we test hypotheses on the relationships among top management participation, organizational culture, and key determinants of employee compliance with information security policies. We find that top management participation in information security initiatives has significant direct and indirect influences on employees’ attitudes towards, subjective norm of, and perceived behavioral control over compliance with information security policies. We also find that the top management participation strongly influences organizational culture which in turn impacts employees’ attitudes towards and perceived behavioral control over compliance with information security policies. Furthermore, we find that the effects of top management participation and organizational culture on employee behavioral intentions are fully mediated by employee cognitive beliefs about compliance with information security policies. Our findings extend information security research literature by showing how top management can play a proactive role in shaping employee compliance behavior in addition to the deterrence oriented remedies advocated in the extant literature. Our findings also refine the theories about the role of organizational culture in shaping employee compliance behavior. Significant theoretical and practical implications of these findings are discussed.