bluuebunny/crossref_metadata_2025_split huggingface dataset:
Walker, Aisha & White, Goodith (2013) Technology enhanced language learningOxford University Press (Oxford) isbn 978‐0‐19‐442368‐7 208 pp £22 https://elt.oup.com/catalogue/items/global/teacher_development/oxford_handbooks_for_language_teachers/9780194423687?cc=global&selLanguage=en&mode=hub
Authors: Oddone Cristina 
Published: February 2014

SummaryWalker and White's book provides very interesting insights into the use of new information technology (IT) in language learning contexts. Not only does it show tools and ways of integrating them into teaching in practice—it also contributes to teachers’ understanding of the theoretical underpinnings and issues involved in using new information technology with language learners. The book is not an end in itself as it aims to give language teachers the means to become familiar with relevant IT and therefore to be able to keep up with the new resource types that seem to appear almost every day. Does the content of this book seem likely to be relevant to you? If so, I recommend you buy your own copy.Cristina Oddone
Milestones in understanding platelet production: a historical overview
Authors: Kuter David J. 
Published: February 2014

SummaryThe discovery of thrombopoietin (TPO, also termed THPO) in 1994 was a major achievement in understanding the regulation of platelet production. In prior decades, physiological studies had demonstrated that platelets were produced from bone marrow megakaryocytes and that the megakaryocytes responded to thrombocytopenia by increasing their number, size and DNA ploidy. In 1958, it was proposed that a ‘thrombopoietin’ must exist that regulated this interaction between the circulating platelet mass and the bone marrow megakaryocytes. After over three decades of effort, TPO was finally purified by five independent laboratories. TPO stimulated megakaryocyte colony‐forming cell growth and increased the number, size and ploidy of megakaryocytes. When the genes for TPO or TPO receptor were eliminated in mice, megakaryocytes grew and platelets were made, but at 15% of their normal number. A first generation of recombinant human (rh) TPO molecules [rhTPO and pegylated recombinant human megakaryocyte growth and development factor (PEG‐rhMGDF)] rapidly entered clinical trials in 1995 and increased platelet counts in humans undergoing non‐myeloablative chemotherapy but not in those undergoing stem cell transplantation. Antibodies developed against PEG‐rhMGDF and development of these recombinant thrombopoietins ended. A second generation of TPO receptor agonists (romiplostim and eltrombopag) was then developed. Neither of these TPO receptor agonists demonstrated any significant untoward effects and both are now licensed in many countries for the treatment of immune thrombocytopenia. This review describes the significant experiments that have surrounded the discovery of TPO and its clinical development.
Social Media in Union Communications: An International Study with UNI Global Union Affiliates
Authors: Panagiotopoulos Panagiotis , Barnett Julie 
Published: February 2014

AbstractThis article assesses the use of social media in union communications based on an international survey with 149 unions affiliated with UNI Global Union. High expectations of union modernization, leadership and pressures from members are likely to drive the agenda of social media within unions. However, the actual use of different channels is based on organizational variables such as membership base and participation in communities of practice. Beliefs about the anticipated benefits and risks of social media were not found to be influential in these early assessments. Implications for union communication strategies are discussed.
Exploring the self‐concept of adults with mild learning disabilities
Authors: Pestana Claudio 
Published: February 2014

Accessible Summary

This study tried to find out more about what people with mild learning disabilities think of themselves.

Eight adults with mild learning disabilities were interviewed individually.

Participants said that they were friendly, helpful, supportive, nice looking, artistic, knowledgeable, independent, capable and religious.

Some participants also said that they were anxious, impatient, slow, not normal and were not very mobile.

This study shows that more can be done to help people with learning disabilities think more positively about themselves.

SummaryThis qualitative study aimed to add to the research on the self‐concept of adults with mild learning disabilities and to generate a deeper understanding of their self‐perceptions rather than draw generalised quantitative conclusions. Eight adults diagnosed with mild learning disabilities receiving support from a supported living project were interviewed individually using a semi‐structured interview. The interviews were recorded and transcribed verbatim. The data collected were qualitatively analysed using interpretative phenomenological analysis. The findings revealed that the participants described themselves with mostly positive and some negative attributes in the different self‐concept domains.
Pharmacogenetic diversification by alternative translation initiation: background channels to the fore: Commentary on Kisselbach et al., Br J Pharmacol 171: 5182–5194
Authors: Abbott G W 
Published: February 2014

Linked ArticleThis article is a Commentary on Kisselbach J, Seyler C, Schweizer PA, Gerstberger R, Becker R, Katus HA and Thomas D (2014). Modulation of K2P2.1 and K2P10.1 K+ channel sensitivity to carvedilol by alternative mRNA translation initiation. Br J Pharmacol 171: 5182–5194. doi: 10.1111/bph.12596
The μ‐opioid receptor: an electrophysiologist's perspective from the sharp end
Authors: Henderson Graeme 
Published: February 2014

Morphine, the prototypical opioid analgesic drug, produces its behavioural effects primarily through activation of μ‐opioid receptors expressed in neurones of the central and peripheral nervous systems. This perspective provides a historical view of how, over the past 40 years, the use of electrophysiological recording techniques has helped to reveal the molecular mechanisms by which acute and chronic activation of μ‐opioid receptors by morphine and other opioid drugs modify neuronal function.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Analgesic efficacy of opioids in chronic pain: recent meta‐analyses
Authors: Reinecke H , Weber C , Lange K , Simon M , Stein C , Sorgatz H 
Published: February 2014

Opioids are regularly administered in acute and cancer pain. In chronic non‐cancer pain (CNCP), however, their use is controversial. Previous meta‐analyses and randomized controlled trials (RCTs) lack methodological homogeneity and comparable data. Here we analysed the maximum analgesic efficacies of opioids and non‐opioids compared with placebo, and of physiotherapy and psychotherapy compared with active or waiting‐list controls. We screened 3647 citations and included RCTs if treatment duration was at least 3 weeks, data were sufficient for meta‐analysis, and criteria for high quality were met. Only 46 studies (10 742 patients) met the criteria. Weighted and standardized mean differences (WMD, SMD) between pain intensities were pooled to conduct separate meta‐analyses for each treatment category. At the end of treatment the WMD for pain reduction (100‐point scale) was 12.0 for ‘strong’ opioids, 10.6 for ‘weak’ opioids, 8.4 for non‐opioids (each vs. placebo), 5.5 for psychotherapy and 4.5 for physiotherapy (each vs. active controls). Dropout rates were high in pharmacological studies. The 95% confidence intervals using the outcomes of control groups did not indicate statistical differences between efficacies of the five interventions. Because not enough eligible head‐to‐head trials were available, our analysis is limited to adjusted indirect comparisons. The heterogeneity of pre‐post pain differences in control groups did not allow the definition of a common comparator. In conclusion, although there were statistically significant differences between maximum treatment efficacies, no intervention per se produced clinically important improvements in average pain intensity. Thus, opioids alone are inappropriate and multimodal treatment programmes may be required for CNCP.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Effects of topiramate on ethanol‐cocaine interactions and DNA methyltransferase gene expression in the rat prefrontal cortex
Authors: Echeverry‐Alzate V , Giné E , Bühler K M , Calleja‐Conde J , Olmos P , Gorriti M A , Nadal R , Rodríguez de Fonseca F , López‐Moreno J A 
Published: February 2014

Background and PurposeRecent and ongoing clinical studies have indicated that topiramate (Topamax®) could be effective in treating ethanol or cocaine abuse. However, the effects of topiramate on the co‐administration of ethanol and cocaine remain largely unknown.Experimental ApproachWe studied the effects of topiramate, in Wistar rats, on operant ethanol self‐administration with the co‐administration of cocaine (i.p.). The psychomotor effects of topiramate were examined before ethanol self‐administration and cocaine exposure. Blood samples were collected to analyse ethanol and cocaine metabolism (blood ethanol levels and benzoylecgonine). Quantitative real‐time PCR was used to characterize the gene expression in the prefrontal cortex.Key ResultsTopiramate prevented the cocaine‐induced increased response to ethanol in a dose‐dependent manner without causing any motor impairment by itself. This effect was observed when topiramate was administered before ethanol access, but not when topiramate was administered before the cocaine injection. Topiramate did not block cocaine‐induced psychomotor stimulation. Topiramate reduced blood ethanol levels but did not affect cocaine metabolism. Ethanol increased the gene expression of DNA methyltransferases (Dnmt1 and Dnmt3a), the corepressor Dnmt1‐associated protein 1 (Dmap1), and the RNA methyltransferase Trdmt1. These effects were prevented by topiramate or cocaine. Gene expression of histone deacetylase‐2 and glutamate receptor kainate‐1 were only increased by cocaine treatment. Topiramate and cocaine co‐administration caused an up‐regulation of dopamine (Drd1, Th) and opioid (Oprm1) receptor genes. Topiramate showed a tendency to alter episodic‐like memory.Conclusions and ImplicationsTopiramate is an effective inhibitor of the cocaine‐induced increase in operant ethanol self‐administration.
Mitigation of carbon tetrachloride‐induced hepatic injury by methylene blue, a repurposed drug, is mediated by dual inhibition of GSK3β downstream of PKA
Authors: Wu Hong Min , Lee Chan Gyu , Hwang Se Jin , Kim Sang Geon 
Published: February 2014

Background and PurposeMethylene blue (MB) has recently been considered for new therapeutic applications. In this study, we investigated whether MB has antioxidant and mitochondria‐protecting effects and can prevent the development of toxicant‐induced hepatitis. In addition, we explored the underlying basis of its effects.Experimental ApproachBlood biochemistry and histopathology were assessed in mice injected with CCl4 (0.5 mL·kg−1) following MB administration (3 mg·kg−1·day−1, 3 days). Immunoblottings were performed to measure protein levels. Cell survival, H2O2, and mitochondrial superoxide and membrane permeability transition were determined in HepG2 cells.Key ResultsMB protected cells from oxidative stress induced by arachidonic acid plus iron; it restored GSH content and decreased the production of H2O2. It consistently attenuated mitochondria dysfunction, as indicated by inhibition of superoxide production and mitochondrial permeability transition. MB inhibited glycogen synthase kinase‐3β (GSK3β) and protected the liver against CCl4. Using siRNA, the inhibition of GSK3β was shown to depend on AMPK. MB increased the activation of AMPK in vitro (3–24 h) and in vivo. MB also increased the phosphorylation of liver kinase B1 (LKB1) via cAMP‐dependent PKA. SiRNA knockdown of LKB1 eliminated phosphorylation of AMPK and inhibited MB activation of AMPK. In addition, MB treatment (≤1 h) facilitated PKA‐mediated GSK3β serine phosphorylation independently of AMPK.Conclusions and ImplicationsMB has antioxidant and mitochondria‐protecting effects and protects the liver from toxicants, which results from the dual inhibition of GSK3β by AMPK downstream of PKA‐activated LKB1, and PKA itself. Our findings reveal a novel pharmacological effect of MB and its molecular basis.
Cellular signalling of non‐synonymous single‐nucleotide polymorphisms of the human μ‐opioid receptor (OPRM1)
Authors: Knapman Alisa , Connor Mark 
Published: February 2014

There is significant variability in individual responses to opioid drugs, which is likely to have a significant genetic component. A number of non‐synonymous single‐nucleotide polymorphisms (SNPs) in the coding regions of the μ‐opioid receptor gene (OPRM1) have been postulated to contribute to this variability. Although many studies have investigated the clinical influences of these μ‐opioid receptor variants, the outcomes are reported in the context of thousands of other genes and environmental factors, and we are no closer to being able to predict individual response to opioids based on genotype. Investigation of how μ‐opioid receptor SNPs affect their expression, coupling to second messengers, desensitization and regulation is necessary to understand how subtle changes in receptor structure can impact individual responses to opioids. To date, the few functional studies that have investigated the consequences of SNPs on the signalling profile of the μ‐opioid receptor in vitro have shown that the common N40D variant has altered functional responses to some opioids, while other, rarer, variants display altered signalling or agonist‐dependent regulation. Here, we review the data available on the effects of μ‐opioid receptor polymorphisms on receptor function, expression and regulation in vitro, and discuss the limitations of the studies to date. Whether or not μ‐opioid receptor SNPs contribute to individual variability in opioid responses remains an open question, in large part because we have relatively little good data about how the amino acid changes affect μ‐opioid receptor function.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
PPARβ activation restores the high glucose‐induced impairment of insulin signalling in endothelial cells
Authors: Quintela A M , Jiménez R , Piqueras L , Gómez‐Guzmán M , Haro J , Zarzuelo M J , Cogolludo A , Sanz M J , Toral M , Romero M , Pérez‐Vizcaíno F , Duarte J 
Published: February 2014

Background and PurposePPARβ enhances insulin sensitivity in adipocytes and skeletal muscle cells, but its effects on insulin signalling in endothelial cells are not known. We analysed the effects of the PPARβ/δ (PPARβ) agonists, GW0742 and L165041, on impaired insulin signalling induced by high glucose in HUVECs and aortic and mesenteric arteries from diabetic rats.Experimental ApproachInsulin‐stimulated NO production, Akt‐Ser473 and eNOS‐Ser1177 phosphorylation, and reactive oxygen species (ROS) production were studied in HUVECs incubated in low‐ or high‐glucose medium. Insulin‐stimulated relaxations and protein phosphorylation in vessels from streptozotocin (STZ)‐induced diabetic rats were also analysed.Key ResultsHUVECs incubated in high‐glucose medium showed a significant reduction in insulin‐stimulated production of NO. High glucose also reduced insulin‐induced Akt‐Ser473 and eNOS‐Ser1177 phosphorylation, increased IRS‐1‐Ser636 and ERK1/2‐Thr183‐Tyr185 phosphorylation and increased ROS production. The co‐incubation with the PPARβ agonists GW0742 or L165041 prevented all these effects induced by high glucose. In turn, the effects induced by the agonists were suppressed when HUVEC were also incubated with the PPARβ antagonist GSK0660, the pyruvate dehydrogenase kinase (PDK)4 inhibitor dichloroacetate or after knockdown of both PPARβ and PDK4 with siRNA. The ERK1/2 inhibitor PD98059, ROS scavenger catalase, inhibitor of complex II thenoyltrifluoroacetone or uncoupler of oxidative phosphorylation, carbonyl cyanide m‐chlorophenylhydrazone, also prevented glucose‐induced insulin resistance. In STZ diabetic rats, oral GW0742 also improved insulin signalling and the impaired NO‐mediated vascular relaxation.Conclusion and ImplicationsPPARβ activation in vitro and in vivo restores the endothelial function, preserving the insulin‐Akt‐eNOS pathway impaired by high glucose, at least in part, through PDK4 activation.
Physical predictors, behavioural/emotional attributes and neurochemical determinants of dominant behaviour
Authors: Chichinadze Konstantin , Chichinadze Nodar , Gachechiladze Ledi , Lazarashvili Ann , Nikolaishvili Marina 
Published: February 2014

ABSTRACTSignificant differences in physical and behavioural/emotional/cognitive predictors and attributes, as well as of neurochemical inducers of behaviour, between dominant and subordinate animals are discussed. It is still unknown whether these factors are the causes of differences between dominants and subordinates, or vice versa whether the differences between dominants and subordinates are the origin of differences in these factors. The possibility is discussed that no differences exist among juveniles in the concentrations of neurochemical agents (known in the literature as determinants of dominance) between the brains of future dominants and future subordinates. We describe a study design that makes the assessment of the ‘original’ neurochemical profile of the brain possible.
Array‐comparative genomic hybridization profiling of immunohistochemical subgroups of diffuse large B‐cell lymphoma shows distinct genomic alterations
Authors: Guo Ying , Takeuchi Ichiro , Karnan Sivasundaram , Miyata Tomoko , Ohshima Koichi , Seto Masao 
Published: February 2014

Diffuse large B‐cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic and molecular levels. Subtypes include germinal center B‐cell‐like (GCB) DLBCL and activated B‐cell‐like (ABC) DLBCL, according to microarray analysis, and germinal center type or non‐germinal center type by immunohistochemistry. Although some reports have described genomic aberrations based upon microarray classification system, genomic aberrations based upon immunohistochemical classifications have rarely been reported. The present study aimed to ascertain the relationship between genomic aberrations and subtypes identified by immunohistochemistry, and to study the pathogenetic character of Chinese DLBCL. We conducted immunohistochemistry using antibodies against CD10, BCL6 and MUM1 in 59 samples of DLBCL from Chinese patients, and then performed microarray‐based comparative genomic hybridization for each case. Characteristic genomic differences were found between GCB and non‐GCB DLBCL from the array data. The GCB type was characterized by more gains at 7q (7q22.1, P < 0.05) and losses at 16q (P ≤ 0.05), while the non‐GCB type was characterized by gains at 11q24.3 and 3q13.2 (P < 0.05). We found completely different mutations in BCL6+ and BCL6− non‐GCB type DLBCL, whereby the BCL6− group had a higher number of gains at 1q and a loss at 14q32.13 (P ≤ 0.005), while the BCL6+ group showed a higher number of gains at 14q23.1 (P = 0.15) and losses at 6q (P = 0.07). The BCL6− group had a higher frequency of genomic imbalances compared to the BCL6+ group. In conclusion, the BCL6+ and BCL6− non‐GCB type of DLBCL appear to have different mechanisms of pathogenesis.
High proportions of FOXP3+CD25high T cells in neonates are positively associated with allergic sensitization later in childhood
Authors: Strömbeck A. , Rabe H. , Lundell A.‐C. , Andersson K. , Johansen S. , Adlerberth I. , Wold A. E. , Hesselmar B. , Rudin A. 
Published: February 2014

SummaryBackgroundThe role of FOXP3+ regulatory T cells in the prevention against sensitization and allergy development is controversial.ObjectiveWe followed 65 newborn Swedish children from farming and non‐farming families from birth to 3 years of age and investigated the relation between CD4+ T cell subsets in blood samples and development of sensitization and allergic disease.MethodsThe proportions of FOXP3+CD25high, CTLA‐4+CD25+, CD45RO+, HLA‐DR+, CCR4+ or α4β7+ within the CD4+ T cell population were examined by flow cytometry of blood samples at several time‐points. Mononuclear cells were isolated from blood and stimulated with birch allergen, ovalbumin or the mitogen PHA, and the levels of IL‐1β, IL‐6, TNF, IFN‐γ, IL‐5 and IL‐13 were measured. A clinical evaluation regarding the presence of allergen‐specific IgE and allergy was performed at 18 and 36 months of age.ResultsMultivariate discriminant analysis revealed that children who were sensitized at 18 or 36 months of age had higher proportions of FOXP3+CD25high T cells at birth and at 3 days of life than children who remained non‐sensitized, whereas allergy was unrelated to the neonatal proportions of these cells. The proportions of CTLA‐4+CD25+ T cells were unrelated to both sensitization and allergy. The association between higher proportions of FOXP3+CD25high T cells and sensitization persisted after exclusion of farmer's children. Finally, a farming environment was associated with lower proportions of FOXP3+CD25high T cells in early infancy and to a more prominent T cell memory conversion and cytokine production.Conclusion & Clinical RelevanceOur results indicate that high proportions of FOXP3+CD25high T cells in neonates are not protective against later sensitization or development of allergy.
Inhibition of farnesyl pyrophosphate synthase prevents angiotensin II-induced cardiac fibrosis in vitro
Authors: Li Z , Bi X , Wang M , Zhang J , Song J , Shen X , Han J , Fu G , Ye Y 
Published: February 2014

Summary
Farnesyl pyrophosphate synthase (FPPS)-catalysed isoprenoid intermediates are important for the activation of Ras homologue gene family, member A (RhoA) in angiotensin (Ang) II-induced cardiac fibrosis. This study was designed to investigate the specific role of FPPS in the development of cardiac fibrosis. We demonstrated that FPPS expression was elevated in both in-vivo and in-vitro models of Ang II-mediated cardiac fibrosis. FPPS inhibition by zolendronate and FPPS knock-down by a silencing lentivirus decreased the expression of cardiac fibrosis marker genes, including collagen I, collagen III and transforming growth factor (TGF)-β1. FPPS inhibition was reversed by geranylgeraniol (GGOH) and mimicked by RhoA knock-down with siRhoA. The antagonistic effect of GGOH on the zolendronate-mediated modulation of RhoA activation in Ang II-stimulated cardiac fibroblasts was demonstrated by a pull-down assay. Furthermore, FPPS knock-down also prevented RhoA activation by Ang II in vitro. In conclusion, FPPS and RhoA may be part of a signalling pathway that plays an important role in Ang II-induced cardiac fibrosis in vitro.