bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical genetic strategy for targeting protein kinases based on covalent complementarity
Authors: Garske Adam L. , Peters Ulf , Cortesi Arianna T. , Perez Jenny L. , Shokat Kevan M. 
Published: August 2011

The conserved nature of the ATP-binding site of the > 500 human kinases renders the development of specific inhibitors a challenging task. A widely used chemical genetic strategy to overcome the specificity challenge exploits a large-to-small mutation of the gatekeeper residue (a conserved hydrophobic amino acid) and the use of a bulky inhibitor to achieve specificity via shape complementarity. However, in a number of cases, introduction of a glycine or alanine gatekeeper results in diminished kinase activity and ATP affinity. A new chemical genetic approach based on covalent complementarity between an engineered gatekeeper cysteine and an electrophilic inhibitor was developed to address these challenges. This strategy was evaluated with Src, a proto-oncogenic tyrosine kinase known to lose some enzymatic activity using the shape complementarity chemical genetic strategy. We found that Src with a cysteine gatekeeper recapitulates wild type activity and can be irreversibly inhibited both in vitro and in cells. A cocrystal structure of T338C c-Src with a vinylsulfonamide-derivatized pyrazolopyrimidine inhibitor was solved to elucidate the inhibitor binding mode. A panel of electrophilic inhibitors was analyzed against 307 kinases and MOK (MAPK/MAK/MRK overlapping kinase), one of only two human kinases known to have an endogenous cysteine gatekeeper. This analysis revealed remarkably few off-targets, making these compounds the most selective chemical genetic inhibitors reported to date. Protein engineering studies demonstrated that it is possible to increase inhibitor potency through secondary-site mutations. These results suggest that chemical genetic strategies based on covalent complementarity should be widely applicable to the study of protein kinases.
Howard N. Rose’sThesaurus of Slang(1934)
Authors: Coleman Julie 
Published: August 2011

SummaryThis paper is a re-examination of Howard N. Rose’sThesaurus of Slang(1934): of its purpose, structure, contents, reliability, and sources. Contemporary reviewers were largely unimpressed, and their criticisms are also considered. Despite its undoubtedly poor quality, Rose’s work provides some interesting insights into attitudes towards American English, the power of the word “thesaurus”, and the partiality of the reviewing process.
Evaluating the Potential for Stock Size to Limit Recruitment in Largemouth Bass
Authors: Allen Micheal S. , Rogers Mark W. , Catalano Matthew J. , Gwinn Daniel G. , Walsh Stephen J. 
Published: August 2011

AbstractCompensatory changes in juvenile survival allow fish stocks to maintain relatively constant recruitment across a wide range of stock sizes (and levels of fishing), but few studies have experimentally explored recruitment compensation in fish populations. We evaluated the potential for recruitment compensation in largemouth bass Micropterus salmoides by stocking six 0.4‐ha hatchery ponds with adult densities ranging from 6 to 40 fish over 2 years. Ponds were drained in October each year, and the age‐0 fish densities were used as a measure of recruitment. We found no relationship between stock abundance and recruitment; ponds with low adult densities produced nearly as many recruits as the higher‐density ponds in some cases. Both prey abundance and the growth of age‐0 largemouth bass declined with age‐0 fish density. Recruit abundance was highly variable both within and among the adult density groups, and thus we were unable to identify a clear stock–recruit relationship for largemouth bass. Our results indicate that reducing the number of effective spawners via angling practices would not reduce recruitment over a relatively large range in stock size.
CLASS IN THE SOUTH CAUCASUS
Authors: Roberts Ken , Pollock Gary 
Published: August 2011

ABSTRACT
This paper identifies classes using evidence from surveys taken in 2009 among nationally representative samples of approximately 2000 households from each of the three South Caucasus countries –Armenia, Azerbaijan and Georgia. Information on employment, education and income is used to identify clusters of both individuals and households, in each case a middle class, a working class and a lower class. Using individual classification, the lower classes are the largest classes in each country, which therefore appear to have pyramid-shaped class structures. However, classifying households gives the class structures a diamond shape, with larger working classes than either middle classes or lower classes. The evidence shows that the main differences between classes of households lie in their standards of living, and are driven by differences in income levels. The main differences between classes of individuals are driven primarily by education, which result in differences in attitudes and (to some extent) individual lifestyles. It is argued that in economic and socio-political terms there are as yet just two real classes among actual and potential employees in the South Caucasus –middle classes and lower classes –and that although these classes differ in their standards of living and political dispositions, these are unlikely to become bases for conflict between them.
Laws, causation and dynamics at different levels
Authors: Butterfield Jeremy 
Published: August 2011

I have two main aims. The first is general, and more philosophical (§2). The second is specific, and more closely related to physics (§§3 and 4). The first aim is to state my general views about laws and causation at different ‘levels’. The main task is to understand how the higher levels sustain notions of law and causation that ‘ride free’ of reductions to the lower level or levels. I endeavour to relate my views to those of other symposiasts. The second aim is to give a framework for describing dynamics at different levels, emphasizing how the various levels' dynamics can mesh or fail to mesh. This framework is essentially that of elementary dynamical systems theory. The main idea will be, for simplicity, to work with just two levels, dubbed ‘micro’ and ‘macro’, which are related by coarse-graining. I use this framework to describe, in part, the first four of Ellis' five types of top-down causation.
The ZmASR1 Protein Influences Branched-Chain Amino Acid Biosynthesis and Maintains Kernel Yield in Maize under Water-Limited Conditions
Authors: Virlouvet Laetitia , Jacquemot Marie-Pierre , Gerentes Denise , Corti Hélène , Bouton Sophie , Gilard Françoise , Valot Benoît , Trouverie Jacques , Tcherkez Guillaume , Falque Matthieu , Damerval Catherine , Rogowsky Peter , Perez Pascual , Noctor Graham , Zivy Michel , Coursol Sylvie 
Published: August 2011

Abstract
Abscisic acid-, stress-, and ripening-induced (ASR) proteins were first described about 15 years ago as accumulating to high levels during plant developmental processes and in response to diverse stresses. Currently, the effects of ASRs on water deficit tolerance and the ways in which their physiological and biochemical functions lead to this stress tolerance remain poorly understood. Here, we characterized the ASR gene family from maize (Zea mays), which contains nine paralogous genes, and showed that maize ASR1 (ZmASR1) was encoded by one of the most highly expressed paralogs. Ectopic expression of ZmASR1 had a large overall impact on maize yield that was maintained under water-limited stress conditions in the field. Comparative transcriptomic and proteomic analyses of wild-type and ZmASR1-overexpressing leaves led to the identification of three transcripts and 16 proteins up- or down-regulated by ZmASR1. The majority of them were involved in primary and/or cellular metabolic processes, including branched-chain amino acid (BCAA) biosynthesis. Metabolomic and transcript analyses further indicated that ZmASR1-overexpressing plants showed a decrease in BCAA compounds and changes in BCAA-related gene expression in comparison with wild-type plants. Interestingly, within-group correlation matrix analysis revealed a close link between 13 decreased metabolites in ZmASR1-overexpressing leaves, including two BCAAs. Among these 13 metabolites, six were previously shown to be negatively correlated to biomass, suggesting that ZmASR1-dependent regulation of these 13 metabolites might contribute to regulate leaf growth, resulting in improvement in kernel yield.
Arabidopsis Cys2/His2 Zinc-Finger Proteins AZF1 and AZF2 Negatively Regulate Abscisic Acid-Repressive and Auxin-Inducible Genes under Abiotic Stress Conditions
Authors: Kodaira Ken-Suke , Qin Feng , Tran Lam-Son Phan , Maruyama Kyonoshin , Kidokoro Satoshi , Fujita Yasunari , Shinozaki Kazuo , Yamaguchi-Shinozaki Kazuko 
Published: August 2011

Abstract
In plants, abiotic stresses induce various physiological changes and growth inhibition that result in adaptive responses to these stresses. However, little is known about how such stresses cause plant growth inhibition. Many genes have been reported to be repressed in plants under abiotic stress conditions. ZPT2 (for petunia [Petunia hybrida] zinc-finger protein 2)-related proteins with two Cys2/His2-type zinc-finger motifs and an ethylene-responsive element binding factor-associated amphiphilic repression motif are thought to function as transcriptional repressors. To characterize the roles of this type of transcriptional repressor under abiotic stress conditions, we analyzed the functions of two Arabidopsis (Arabidopsis thaliana) ZPT2-related genes that were induced by osmotic stress and abscisic acid: AZF1 (for Arabidopsis zinc-finger protein 1) and AZF2. The nuclear localization of these two proteins was observed in the roots under control conditions, and the accumulation of AZF2 was clearly detected in the nuclei of leaf cells under stress conditions. Transgenic plants overexpressing AZF1 and AZF2 were generated using stress-responsive promoters or the GVG chemical induction system. The overexpression of these genes caused severe damage to plant growth and viability. Transcriptome analyses of the transgenic plants demonstrated that AZF1 and AZF2 repressed various genes that were down-regulated by osmotic stress and abscisic acid treatment. Moreover, many auxin-responsive genes were found to be commonly down-regulated in the transgenic plants. Gel mobility shift assays revealed that both the AZF1 and AZF2 proteins bound to the promoter regions of these down-regulated genes. These results indicate that AZF1 and AZF2 function as transcriptional repressors involved in the inhibition of plant growth under abiotic stress conditions.
The effects of a single nucleotide polymorphism in SLCO1B1 on the pharmacodynamics of pravastatin
Authors: Martin Nicholas G. , Li Ka Wah , Murray Heather , Putt Wendy , Packard Chris J. , Humphries Steve E. 
Published: August 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The SNP rs4149056 is associated with altered statin pharmacokinetics and increased risk of statin intolerance. LDL‐cholesterol lowering by simvastatin is also affected by rs4149056 but differences between the genotypes are small. Studies of the effect of rs4149056 on pravastatin pharmacodynamics have been inconclusive.WHAT THIS PAPER ADDS• rs4149056 was not associated with an altered lipid or CRP response to 40 mg day−1 pravastatin in more than 600 high risk men from Scotland, suggesting that the rs4149056 genotype does not significantly affect pravastatin efficacy.AIM To determine whether the SNP rs4149056 in SLCO1B1 alters the pharmacodynamics of pravastatin.METHODS rs4149056 was genotyped in 626 pravastatin‐treated participants in the WOSCOPS trial and the response after 1 year of treatment was compared between the different genotypes.RESULTS Pravastatin reduced serum LDL cholesterol by 22.2% in TT homozygotes, by 22.2% in TC heterozygotes and by 17.7% in CC homozygotes (TT + TC vs. CC P value 0.33). There were no significant differences in the response of total cholesterol, LDL, HDL, triglycerides or CRP to pravastatin between the genotypes.CONCLUSION The rs4149056 SNP did not significantly affect the pharmacodynamics of pravastatin.
The impact of foreign caregiving on depression among older people in Taiwan: model testing
Authors: Chiao Chia‐Yi , Schepp Karen G. 
Published: August 2011

chiao c.‐y. & schepp k.g. (2011) The impact of foreign caregiving on depression among older people in Taiwan: model testing. Journal of Advanced Nursing 68(5), 1090–1099.AbstractAim.  This article is a report of a study of predicting the factors that influence depression in the older people in Taiwan.Background.  In 1991, Taiwan opened the labour market to foreign caregivers for the older people who needed long‐term care. With the differences in language, culture and lifestyle between foreign caregivers and older people in Taiwan, it was hypothesized that the older people would not be able to relate to them, and therefore become depressed.Methods.  The data were collected from 116 Taiwanese older people from July to September, 2005. Path analysis using multiple regression analyses was conducted to estimate the direct and indirect effects of caregiving communication, activities of daily living, income and social support on depression among older people in Taiwan. To evaluate the hypotheses for this research, bi‐variate linear regression and multiple regression analyses were used.Results/findings.  The results indicated that the level of activities of daily living (β = −0·201, P = 0·010), care‐giving communication (β = −0·272, P = 0·002) income (β = −0·305, P = 0·000) and social support (β = −0·276, P = 0·002) were the predictors of depression in older people in Taiwan. Social support was a mediating factor for caregiving communication and depression. Furthermore, foreign caregiver care was not correlated with depression among older people in Taiwan.Conclusions.  The findings influence the public awareness of depression in older people, and provide the foundational information to influence the policy makers of Taiwan to evaluate the foreign caregiver policy.
Literature review: using pictographs in discharge instructions for older adults with low‐literacy skills
Authors: Choi Jeungok 
Published: August 2011

Aims.  To evaluate current visual aids used in health education; to explore evidence regarding the use of pictographs (simple line drawings showing explicit health care actions); and to provide suggestions for uses of pictographs in discharge instructions for older adults with low‐literacy skills.Background.  Discharge instructions consist of recommended homecare actions. However, these healthcare actions are provided in text‐based discharge instructions, which are often difficult for patients with low‐literacy skills to follow precisely at home. Various forms of visual aids are currently used to improve health education; however, the appropriateness of these visual aids for educating discharge instructions for older adults with low‐literacy skills is unknown.Design.  A narrative literature review.Methods.  Eligible articles were identified via electronic searches of databases. In total, 44 articles were reviewed and analysed.Results.  Among various visual aids, pictographs using simple line drawings combined with simplified text are the most efficient and effective tool to improve discharge education. Indeed, pictographs are well suited to show a step‐by‐step procedure of complex and lengthy discharge instructions consisting of multiple actions, thus making an entire action sequence easier to learn.Conclusion.  By using pictographs with simplified text, healthcare educators can improve discharge instructions for low‐literate older adults. Further research is needed to develop pictographs representing explicit healthcare actions themselves rather than concepts associated with healthcare actions; and to examine the effects of pictographs on adherence and health outcomes.Relevance to clinical practice.  Healthcare education materials using pictographs provide effective strategies in improving discharge education for low‐literate older adults in acute healthcare settings where nurses have primary responsibility as a first line of healthcare providers. It can also serve as an efficient tool to improve health education for immigrants speaking English as a second language.
A national survey of GP and nurse attitudes and beliefs towards depression after myocardial infarction
Authors: Haws Joanne , Ramjeet Janet , Gray Richard 
Published: August 2011

Aim.  To investigate primary care practitioner’s attitudes to depression after myocardial infarction.Background.  Depression after myocardial infarction affects almost half of all patients and has a considerable negative effect on recovery. Despite the increased prevalence of depression in this population, it is often not recognised or treated.Design.  Survey.Method.  A total of 813 (106 general practitioners and 707 nurses) practitioners responded. Our questionnaire developed for this project by the authors in collaboration with a group of ten cardiovascular nurse specialists contained 27 items that were summated into five subscales.Results.  Primary care practitioners underestimated the prevalence of depression in the post‐myocardial infarction population. General acknowledgement of the negative impact that depression can have was reported by the majority of participants. Diagnosing depression was perceived as complex by both groups but significantly more so by nurses. General practitioners were significantly more positive about their understanding of the signs and symptoms of depression and in using depression‐screening tools. We observed that training seems to have a significant effect on reported practice. Practitioners who reported that they had recent training in the management of depression were significantly more accurate in their estimate of how common depression was in this population.Conclusion.  Depression may be underdiagnosed in this population because primary care practitioners, especially nurses, are not aware of how common the disorder is and lack competence in diagnosis. There is merit in developing and testing a brief training intervention to ensure competence in depression screening and treatment in post‐myocardial infarction patients.Relevance to clinical practice.  Diagnosing depression in post‐myocardial infarction patients is perceived by nurses as complex but training in the management of depression is seen as helping practice.
Improved health or improved decision making? The ethical goals of EBM
Authors: Gupta Mona 
Published: August 2011

AbstractEvidence‐based medicine (EBM) is frequently portrayed as a value‐free approach to knowing what kinds of treatment ‘really work.’ Since practitioners should help patients to improve their health, and EBM tells us which interventions will work, then it follows that wemustpractice EBM, offering only those interventions supported by evidence. The primary goal of EBM, then, is an ethical one – to improve health. More recently, EBM's authors have also committed themselves to ‘shared decision making’ in which evidence plays a role in the clinical encounter, but where patients, motivated by their own values, should have final decision‐making authority. Envisioned this way, strengthening the informed consent process, rather than improved health per se, is viewed as the goal of EBM. In this paper, I will explore this shift in EBM's ethics from the goal of improved health towards the goal of strengthened informed consent. Drawing upon data from a qualitative enquiry of scholars involved in the development of EBM, I will argue that EBM is now committed tobothof these ethical goals. Where they conflict, the aim of the intervention will determine which goal practitioners should pursue. Having increased the ethical complexity of EBM, we are left with the question of whether EBM would still be judged a success if it did not lead to much in the way of improvements in health, but primarily strengthened informed consent. This paper will conclude by arguing that this more nuanced version of EBM's ethics accurately reflects the dynamics of real clinical practice but undermines the original, perceived need for EBM.
Validity and reliability study on traditional Chinese FACT‐C in Chinese patients with colorectal neoplasm
Authors: Wong Carlos K. H. , Lam Cindy L. K. , Law Wai‐Lun , Poon Jensen T. C. , Chan Pierre , Kwong Dora L. W. , Tsang Janice 
Published: August 2011

AbstractObjective  To establish the validity and reliability of traditional Chinese version of the Functional Assessment of Cancer Therapy‐Colorectal (FACT‐C).Methods  A total of 536 subjects self‐administered (n = 331) or interviewer‐administered (n = 205) FACT‐C (version 4), EORTC QLQ‐C30/CR38 and SF‐12v2 instruments for health‐related quality of life assessment. Construct validity was examined by item–scale correlation, scaling success and concurrent validity. Reliability was evaluated by test–retest reliability and internal consistency. Sensitivity was assessed by known‐groups comparisons.Results  The completion rates for FACT‐C were almost perfect (>98%). The FACT‐C demonstrated item‐internal consistency and item discriminant validity through item–scale correlation. Scaling success and concurrent validity were satisfactory to support the construct validity. The five subscales of the FACT‐C showed good internal consistency with Cronbach alpha coefficient and substantial reproducibility, demonstrating good reliability. Sensitivity was supported when there were significant differences in scores related to physical condition between patients who were receiving treatment and those who were not.Conclusion  Traditional Chinese version of the FACT‐C was demonstrated to have satisfactory psychometric properties in terms of applicability, reliability, validity and sensitivity in Chinese patients with colorectal neoplasm. The FACT‐C was valid colorectal‐specific health‐related quality of life tool for the Chinese population.
Development of the vagal innervation of the gut: steering the wandering nerve
Authors: Ratcliffe E. M. , Farrar N. R. , Fox E. A. 
Published: August 2011

AbstractBackground  The vagus nerve is the major neural connection between the gastrointestinal tract and the central nervous system. During fetal development, axons from the cell bodies of the nodose ganglia and the dorsal motor nucleus grow into the gut to find their enteric targets, providing the vagal sensory and motor innervations respectively. Vagal sensory and motor axons innervate selective targets, suggesting a role for guidance cues in the establishment of the normal pattern of enteric vagal innervation.Purpose  This review explores known molecular mechanisms that guide vagal innervation in the gastrointestinal tract. Guidance and growth factors, such as netrin‐1 and its receptor, deleted in colorectal cancer, extracellular matrix molecules, such as laminin‐111, and members of the neurotrophin family of molecules, such as brain‐derived neurotrophic factor have been identified as mediating the guidance of vagal axons to the fetal mouse gut. In addition to increasing our understanding of the development of enteric innervation, studies of vagal development may also reveal clinically relevant insights into the underlying mechanisms of vago‐vagal communication with the gastrointestinal tract.