bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytosolic Receptor Melanoma Differentiation–Associated Protein 5 Mediates Preconditioning-Induced Neuroprotection Against Cerebral Ischemic Injury
Authors: Gesuete Raffaella , Christensen Sara N. , Bahjat Frances R. , Packard Amy E.B. , Stevens Susan L. , Liu Mingyue , Salazar Andres M. , Stenzel-Poore Mary P. 
Published: November 2015

Background and Purpose—

Preconditioning with poly-
l
-lysine and carboxymethylcellulose (ICLC) provides robust neuroprotection from cerebral ischemia in a mouse stroke model. However, the receptor that mediates neuroprotection is unknown. As a synthetic double-stranded RNA, poly-ICLC may bind endosomal Toll-like receptor 3 or one of the cytosolic retinoic acid–inducible gene-I–like receptor family members, retinoic acid–inducible gene-I, or melanoma differentiation–associated protein 5. Activation of these receptors culminates in type I interferons (IFN-α/β) induction—a response required for poly-ICLC–induced neuroprotection. In this study, we investigate the receptor required for poly-ICLC–induced neuroprotection.

Methods—
Toll-like receptor 3, melanoma differentiation–associated protein 5-, and IFN-promoter stimulator 1–deficient mice were treated with poly-ICLC 24 hours before middle cerebral artery occlusion. Infarct volume was measured 24 hours after stroke to identify the receptor signaling pathways involved in protection. IFN-α/β induction was measured in plasma samples collected 6 hours after poly-ICLC treatment. IFN-β–deficient mice were used to test the requirement of IFN-β for poly-ICLC–induced neuroprotection. Mice were treated with recombinant IFN-α-A to test the role of IFN-α as a potential mediator of neuroprotection.

Results—
Poly-ICLC induction of both neuroprotection and systemic IFN-α/β requires the cytosolic receptor melanoma differentiation–associated protein 5 and the adapter molecule IFN-promoter stimulator 1, whereas it is independent of Toll-like receptor 3. IFN-β is not required for poly-ICLC–induced neuroprotection. IFN-α treatment protects against stroke.

Conclusions—
Poly-ICLC preconditioning is mediated by melanoma differentiation–associated protein 5 and its adaptor molecule IFN-promoter stimulator 1. This is the first evidence that a cytosolic receptor can mediate neuroprotection, providing a new target for the development of therapeutic agents to protect the brain from ischemic injury.
Exploring the Predictability of 30-Day Extreme Precipitation Occurrence Using a Global SST–SLP Correlation Network
Authors: Lu Mengqian , Lall Upmanu , Kawale Jaya , Liess Stefan , Kumar Vipin 
Published: November 2015

Abstract
Correlation networks identified from financial, genomic, ecological, epidemiological, social, and climatic data are being used to provide useful topological insights into the structure of high-dimensional data. Strong convection over the oceans and the atmospheric moisture transport and flow convergence indicated by atmospheric pressure fields may determine where and when extreme precipitation occurs. Here, the spatiotemporal relationship among sea surface temperature (SST), sea level pressure (SLP), and extreme global precipitation is explored using a graph-based approach that uses the concept of reciprocity to generate cluster pairs of locations with similar spatiotemporal patterns at any time lag. A global time-lagged relationship between pentad SST anomalies and pentad SLP anomalies is investigated to understand the linkages and influence of the slowly changing oceanic boundary conditions on the development of the global atmospheric circulation. This study explores the use of this correlation network to predict extreme precipitation globally over the next 30 days, using a logistic principal component regression on the strong global dipoles found between SST and SLP. Predictive skill under cross validation and blind prediction for the occurrence of 30-day precipitation that is higher than the 90th percentile of days in the wet season is indicated for the selected global regions considered.
An Initial Study on Climate Change Fingerprinting Using the Reflected Solar Spectra
Authors: Jin Zhonghai , Sun Moguo 
Published: November 2015

Abstract
Attribution of averaged spectral variation over large spatial and temporal scales to different climate variables is central to climate change fingerprinting. Using 10 years of satellite data for simulation, the authors generate a group of observation-based spectral fingerprints and a time series of monthly mean reflectance spectra over the ocean in five large latitude regions and globally. Next, these fingerprints and the interannual variation spectra are used to retrieve the interannual changes in the relevant climate variables to test the concept of using the spectral fingerprinting approach for climate change attribution. Comparing the fingerprinting retrieval of climate variable change to the actual underlying variable change, the RMS differences between the two are less than twice as large as the monthly variability for all variables in all regions. Instances where larger errors are observed correspond to those variables with large nonlinear radiative response, such as the cloud optical depth and the ice particle size. Using the linear fingerprinting approach and accounting for the nonlinear radiative error in fingerprints results in significantly higher retrieval accuracy; the RMS errors are reduced to less than the monthly variability for nearly all variables, indicating the profound impact of the nonlinear error on fingerprinting retrieval. Another important finding is that if the cloud fraction is known a priori, the retrieval accuracy in cloud optical depth would be improved substantially. Moreover, a better retrieval for the water vapor amount and aerosol optical depth can be achieved from the clear-sky data only. The test results demonstrate that climate change fingerprinting based on reflected solar benchmark spectra is possible.
A Direct Determination of the World Ocean Barotropic Circulation
Authors: Colin de Verdière Alain , Ollitrault Michel 
Published: November 2015

AbstractThe time-mean Argo float displacements and the World Ocean Atlas 2009 temperature–salinity climatology are used to obtain the total, top to bottom, mass transports. Outside of an equatorial band, the total transports are the sum of the vertical integrals of geostrophic- and wind-driven Ekman currents. However, these transports are generally divergent, and to obtain a mass conserving circulation, a Poisson equation is solved for the streamfunction with Dirichlet boundary conditions at solid boundaries. The value of the streamfunction on islands is also part of the unknowns. This study presents and discusses an energetic circulation in three basins: the North Atlantic, the North Pacific, and the Southern Ocean. This global method leads to new estimations of the time-mean western Eulerian boundary current transports maxima of 97 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) at 60°W for the Gulf Stream, 84 Sv at 157°E for the Kuroshio, 80 Sv for the Agulhas Current between 32° and 36°S, and finally 175 Sv for the Antarctic Circumpolar Current at Drake Passage. Although the large-scale structure and boundary of the interior gyres is well predicted by the Sverdrup relation, the transports derived from the wind stress curl are lower than the observed transports in the interior by roughly a factor of 2, suggesting an important contribution of the bottom torques. With additional Argo displacement data, the errors caused by the presence of remaining transient terms at the 1000-db reference level will continue to decrease, allowing this method to produce increasingly accurate results in the future.
Differences between Nonprecipitating Tropical and Trade Wind Marine Shallow Cumuli
Authors: Ghate Virendra P. , Miller Mark A. , Zhu Ping 
Published: November 2015

Abstract
Marine nonprecipitating cumulus topped boundary layers (CTBLs) observed in a tropical and in a trade wind region are contrasted based on their cloud macrophysical, dynamical, and radiative structures. Data from the Atmospheric Radiation Measurement (ARM) observational site previously operating at Manus Island, Papua New Guinea, and data collected during the deployment of ARM Mobile Facility at the island of Graciosa, in the Azores, were used in this study. The tropical marine CTBLs were deeper, had higher surface fluxes and boundary layer radiative cooling, but lower wind speeds compared to their trade wind counterparts. The radiative velocity scale was 50%–70% of the surface convective velocity scale at both locations, highlighting the prominent role played by radiation in maintaining turbulence in marine CTBLs. Despite greater thicknesses, the chord lengths of tropical cumuli were on average lower than those of trade wind cumuli, and as a result of lower cloud cover, the hourly averaged (cloudy and clear) liquid water paths of tropical cumuli were lower than the trade wind cumuli. At both locations ~70% of the cloudy profiles were updrafts, while the average amount of updrafts near cloud base stronger than 1 m s−1 was ~22% in tropical cumuli and ~12% in the trade wind cumuli. The mean in-cloud radar reflectivity within updrafts and mean updraft velocity was higher in tropical cumuli than the trade wind cumuli. Despite stronger vertical velocities and a higher number of strong updrafts, due to lower cloud fraction, the updraft mass flux was lower in the tropical cumuli compared to the trade wind cumuli. The observations suggest that the tropical and trade wind marine cumulus clouds differ significantly in their macrophysical and dynamical structures.
The meaning and making of union delegate networks
Authors: Peetz David , Murray Georgina , Muurlink Olav , May Maggie 
Published: November 2015

AbstractNetworks are a subject of growing research interest. Yet union networks, particularly networks of delegates, and ways to build them, are still poorly understood. This is a study of the meaning that workplace union delegates assign to networks of support. It explores the characteristics of effective delegate and union networks and influences upon them. Effective networks are a combination of strong and weak ties, such that delegates sometimes do not recognise they are part of a network. Our three-stage research methodology involved delegate focus groups, a paper-based self-completion questionnaire of recently trained delegates (N=473) and a follow-up telephone survey (N=145). It found that organisers were key to creation of internal workplace networks (although they did not necessarily establish them) and in providing a bridge for delegates with external networks. They were the key support person for many delegates. Networks took a variety of forms. Only a minority were formalised. A majority were mainly internal to the workplace. Social media were rarely used, with little intention of using them more, and were, we suspect, underutilised.
Evaluating the appropriateness of a community pharmacy model for a colorectal cancer screening program in Catalonia (Spain)
Authors: Santolaya M , Aldea M , Grau J , Estrada M , Barau M , Buron A , Francesc M , Castell A , Rodriguez C , Gascón P , Rius P , Guayta-Escolies R ,   on behalf of the PROCOLON research group (all members of this group are listed in Author Note)
Published: November 2015

Background The traditional model of community pharmacy has changed, with patients, caregivers and consumers having access to many cognitive services other than the traditional dispensing and supply of medicines. In December 2009, a population-based colorectal cancer screening program started in Barcelona, introducing the community pharmacist and the professional expertise of the pharmacist into the organisational model. Aim To evaluate the program implementation process in the pharmacies, identify barriers and facilitators, and know the opinion of the professionals involved in the colorectal cancer screening program in Catalonia (Spain). Methods Cross-sectional study of the pharmacies that participated in the first round of the program during the first and second trimester of 2010 in Barcelona. A validated questionnaire was used to analyse several functional aspects in the implementation process. Qualitative aspects about the opinion of the pharmacist were studied. A descriptive and bivariate analysis was performed. Results All the pharmacies involved in the program (n = 74) participated in the study. The majority of the sample population was composed of women (70.3%), mean age 44.9 years, and most of them (74%) had attended a specific training session. Pharmacists considered their participation in the program to be an added value to their professional role and a way to increase consumer’s confidence on this kind of services. The average time to provide the service was estimated to be less than 10 minutes per consumer. Only three (4.1%) pharmacists considered that the program involved a lot of extra work in the daily activities of the pharmacy. The level of satisfaction of the pharmacists was very high. Conclusions Community pharmacies can be a successful alternative and great resource to implement a population cancer screening program. This functional model can improve the accessibility and participation rates on target population. The level of motivation of the community pharmacist, the specific training program and the perception to give a better care for their patients can be an enabler.
Dermatophyte surveillance in cats in three animal shelters in Ontario, Canada
Authors: Mozes Rachael , Pearl David L , Rousseau Joyce , Niel Lee , Weese J Scott 
Published: November 2015

Objectives The aim of the study was to determine the prevalence of dermatophyte shedding in cats admitted to three Ontario animal shelters from February to May 2013. Methods Four hundred cats were sampled within 48 h of admission, using a standard toothbrush sampling technique. Dermatophyte culture was performed. Results Dermatophytes were not identified in any of the 400 cats (0–0.9% one-sided exact 97.5% confidence interval). Conclusions and relevance These results imply that dermatophyte shedding is rare in cats admitted to Ontario animal shelters. Consequently, identification of infected animals, particularly multiple animals, represents an unusual occurrence that may justify prompt and intensive control measures.
Diagnostic performance of brain MRI in pharmacovigilance of natalizumab-treated MS patients
Authors: Wattjes Mike P , Wijburg Martijn T , Vennegoor Anke , Witte Birgit I , Roosendaal Stefan D , Sanchez Esther , Liu Yaou , Martins Jarnalo Carine O , Richert Nancy D , Uitdehaag Bernard MJ , Barkhof Frederik , Killestein Joep 
Published: November 2015

Background: In natalizumab-treated multiple sclerosis (MS) patients, magnetic resonance imaging (MRI) is considered as a sensitive tool in detecting both MS disease activity and progressive multifocal leukoencephalopathy (PML). Objective: To investigate the performance of neuroradiologists using brain MRI in detecting new MS lesions and asymptomatic PML lesions and in differentiating between MS and PML lesions in natalizumab-treated MS patients. The secondary aim was to investigate interrater variability. Methods: In this retrospective diagnostic study, four blinded neuroradiologists assessed reference and follow-up brain MRI scans of 48 natalizumab-treated MS patients with new asymptomatic PML lesions ( n = 21) or new MS lesions ( n = 20) or no new lesions ( n = 7). Sensitivity and specificity for detection of new lesions in general (MS and PML lesions), MS and PML lesion differentiation, and PML detection were determined. Interrater agreement was calculated. Results: Overall sensitivity and specificity for the detection of new lesions, regardless of the nature of the lesions, were 77.4% and 89.3%, respectively; for PML-MS lesion differentiation, 74.2% and 84.7%, respectively; and for asymptomatic PML lesion detection, 59.5% and 91.7%, respectively. Interrater agreement for the tested categories was fair to moderate. Conclusion: The diagnostic performance of trained neuroradiologists using brain MRI in pharmacovigilance of natalizumab-treated MS patients is moderately good. Interrater agreement among trained readers is fair to moderate.
High-resolution T1-relaxation time mapping displays subtle, clinically relevant, gray matter damage in long-standing multiple sclerosis
Authors: Steenwijk Martijn D , Vrenken Hugo , Jonkman Laura E , Daams Marita , Geurts Jeroen JG , Barkhof Frederik , Pouwels Petra JW 
Published: November 2015

Background: Gray matter (GM) pathology has high clinical relevance in multiple sclerosis (MS), but conventional magnetic resonance imaging (MRI) is insufficiently sensitive to visualize the rather subtle damage. Objective: To investigate whether high spatial resolution T1-relaxation time (T1-RT) measurements can detect changes in the normal-appearing GM of patients with long-standing MS and whether these changes are associated with physical and cognitive impairment. Methods: High spatial resolution (1.05 × 1.05 × 1.2 mm3) T1-RT measurements were performed at 3 T in 156 long-standing MS patients and 54 healthy controls. T1-RT histogram parameters in several regions were analyzed to investigate group differences. Stepwise linear regression analyses were used to assess the relation of T1-RT with physical and cognitive impairment. Results: In both thalamus and cortex, T1-RT histogram skewness was higher in patients than controls. In the cortex, this was driven by the frontal and temporal lobes. No differences were found in other GM histogram parameters. Cortical skewness, thalamus volume, and average white matter (WM) lesion T1-RT emerged as the strongest predictors for cognitive performance (adjusted R2 = 0.39). Conclusion: Subtle GM damage was present in the cortex and thalamus of MS patients, as indicated by increased T1-RT skewness. Increased cortical skewness emerged as an independent predictor of cognitive dysfunction.
A comparative analysis of Patient-Reported Expanded Disability Status Scale tools
Authors: Collins Christian DE , Ivry Ben , Bowen James D , Cheng Eric M , Dobson Ruth , Goodin Douglas S , Lechner-Scott Jeannette , Kappos Ludwig , Galea Ian 
Published: November 2015

Background: Patient-Reported Expanded Disability Status Scale (PREDSS) tools are an attractive alternative to the Expanded Disability Status Scale (EDSS) during long term or geographically challenging studies, or in pressured clinical service environments. Objectives: Because the studies reporting these tools have used different metrics to compare the PREDSS and EDSS, we undertook an individual patient data level analysis of all available tools. Methods: Spearman’s rho and the Bland–Altman method were used to assess correlation and agreement respectively. Results: A systematic search for validated PREDSS tools covering the full EDSS range identified eight such tools. Individual patient data were available for five PREDSS tools. Excellent correlation was observed between EDSS and PREDSS with all tools. A higher level of agreement was observed with increasing levels of disability. In all tools, the 95% limits of agreement were greater than the minimum EDSS difference considered to be clinically significant. However, the intra-class coefficient was greater than that reported for EDSS raters of mixed seniority. The visual functional system was identified as the most significant predictor of the PREDSS–EDSS difference. Conclusion: This analysis will (1) enable researchers and service providers to make an informed choice of PREDSS tool, depending on their individual requirements, and (2) facilitate improvement of current PREDSS tools.
Transient Receptor Potential Ankyrin 1 that is Induced in Dorsal Root Ganglion Neurons Contributes to Acute Cold Hypersensitivity after Oxaliplatin Administration
Authors: Yamamoto Ken , Chiba Noriko , Chiba Terumasa , Kambe Toshie , Abe Kenji , Kawakami Kazuyoshi , Utsunomiya Iku , Taguchi Kyoji 
Published: November 2015

Background Peripheral cold neuropathic pain is a serious side effect of oxaliplatin treatment. However, the mechanism of oxaliplatin-induced cold hyperalgesia is unknown. In the present study, we investigated the effects of oxaliplatin on transient receptor potential ankyrin 1 (TRPA1) in dorsal root ganglion (DRG) neurons of rats. Results Behavioral assessment using the acetone spray test showed that 3 and 6 mg/kg oxaliplatin (i.p.) induced acute cold hypersensitivity after 1, 2, 4, and 7 days. Real-time PCR showed that oxaliplatin (6 mg/kg) significantly increased TRPA1 mRNA expression in DRGs at days 1, 2, and 4. Western blotting revealed that oxaliplatin significantly increased TRPA1 protein expression in DRGs at days 2, 4, and 7. Moreover, in situ hybridization histochemistry revealed that most TRPA1 mRNA-labeled neurons in the DRGs were small in size. Oxaliplatin significantly increased co-localization of TRPA1 expression and isolectin B4 binding in DRG neurons. Oxaliplatin induced a significant increase in the percent of TRPA1 mRNA-positive small neurons in DRGs at days 1, 2, and 4. In addition, we found that intrathecal administration of TRPA1 antisense, but not TRPA1 mismatched oligodeoxynucleotides, knocked down TRPA1 expression and decreased oxaliplatin-induced cold hyperalgesia. Double labeling showed that p-p38 mitogen-activated protein kinase (MAPK) was co-expressed in TRPA1 mRNA-labeled neurons at day 2 after oxaliplatin administration. Intrathecal administration of the p38 MAPK inhibitor, SB203580, significantly decreased oxaliplatin-induced acute cold hypersensitivity. Conclusions Together, these results demonstrate that TRPA1 expression via activation of p38 MAPK in DRG neurons, at least in part, contributes to the development of oxaliplatin-induced acute cold hyperalgesia.
The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice
Authors: Bermudez-Silva Francisco J. , Romero-Zerbo Silvana Y. , Haissaguerre Magalie , Ruz-Maldonado Inmaculada , Lhamyani Said , El Bekay Rajaa , Tabarin Antoine , Marsicano Giovanni , Cota Daniela 
Published: November 2015

ABSTRACT
The endocannabinoid system (ECS) is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the β-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1) signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1) receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS) at 0.1 µM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6) within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight), which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic β-cell diseases.