bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of prenatal stress on expression of p38 MAPK in offspring hippocampus
Authors: Cai Qing , Huang Shuyun , Zhu Zhongliang , Li Hui , Li Qinghong , Jia Ning , Liu Jankang 
Published: June 2008

AbstractThe hippocampus, which has the highest density of GC receptors in the brain, is involved in the regulation of the HPA and the behavioral responses to stress. Overexposure to corticosteroid hormones is harmful to hippocampal neuron integrity. Our purpose is to investigate the effects of prenatal stress (PNS) on expression of p38 mitogen‐activated protein kinase (p38 MAPK) in offspring hippocampal neurons using Western blotting and Immunohistochemistry. The prenatal restraint stress induces significant increase in the expression of p‐p38 MAPK and total p38 MAPK in female offspring hippocampus. The level of p‐p38 MAPK in PNS female offspring rats was significantly increased (126.41 ± 3.937, n = 6) compared with that in the control female offspring rats (101.35 ± 3.468, n = 6, P < 0.01). Immunoblot analysis revealed there was significant difference in the level of total p38 MAPK between the female control and prenatal restraint stress offspring rats (101.70 ± 3.162 vs. 128.111 ± 2.724, respectively, P < 0.01). Immunodensity of p38 MAPK was significantly increased above female control in PNS female offspring hippocampal CA3 and CA4 fields (P < 0.001 vs. control group, CON). The data suggest that exposure of animals to a period of stressful experience during a critical phase could impose lasting effects on the offspring hippocampal neurons cellular signalling of offspring hippocampus.
Ensemble non-negative matrix factorization methods for clustering protein–protein interactions
Authors: Greene Derek , Cagney Gerard , Krogan Nevan , Cunningham Pádraig 
Published: June 2008

Abstract
Motivation: When working with large-scale protein interaction data, an important analysis task is the assignment of pairs of proteins to groups that correspond to higher order assemblies. Previously a common approach to this problem has been to apply standard hierarchical clustering methods to identify such a groups. Here we propose a new algorithm for aggregating a diverse collection of matrix factorizations to produce a more informative clustering, which takes the form of a ‘soft’ hierarchy of clusters.
Results: We apply the proposed Ensemble non-negative matrix factorization (NMF) algorithm to a high-quality assembly of binary protein interactions derived from two proteome-wide studies in yeast. Our experimental evaluation demonstrates that the algorithm lends itself to discovering small localized structures in this data, which correspond to known functional groupings of complexes. In addition, we show that the algorithm also supports the assignment of putative functions for previously uncharacterized proteins, for instance the protein YNR024W, which may be an uncharacterized component of the exosome.
Contact: derek.greene@ucd.ie
Supplementary information: Supplementary data are available at http://mlg.ucd.ie/nmf.
Modeling immune system control of atherogenesis
Authors: Pappalardo Francesco , Musumeci Salvatore , Motta Santo 
Published: June 2008

Abstract
Motivation: Atherosclerosis is a disease that is present in almost all humans, typically beginning in early adolescence. It is a human disease broadly investigated, that is amenable to quantitative analysis. Oxidized low-density lipoproteins (LDLs) and their autoantibodies are involved in the development of atherosclerosis in animal models, but their role in humans is still not clear. Computer models may represent a virtual environment to perform experiments not possible in human volunteers that can provide a useful instrument for monitoring both the evolution of atherosclerotic lesions and to quantify the efficacy of treatments, including vaccines, oriented to reduce the LDLs and their oxidized fraction.
Results: We report the application of an agent-based model to model both the immune response to atherogenesis and the atheromatous plaque progression in a generic artery wall. The level of oxidized LDLs, the immune humoral response with production of autoantibodies, the macrophages activity and the formation of foam cells are in good agreement with available clinical data, including the formation of atheromatous plaques in patients affected by hypercholesterolemia.
Availability: The model is available at http://www.immunogrid.eu/atherogenesis/
Contact: francesco@dmi.unict.it
Sample size for positive and negative predictive value in diagnostic research using case–control designs
Authors: Steinberg David M. , Fine Jason , Chappell Rick 
Published: June 2008

AbstractImportant properties of diagnostic methods are their sensitivity, specificity, and positive and negative predictive values (PPV and NPV). These methods are typically assessed via case–control samples, which include one cohort of cases known to have the disease and a second control cohort of disease-free subjects. Such studies give direct estimates of sensitivity and specificity but only indirect estimates of PPV and NPV, which also depend on the disease prevalence in the tested population. The motivating example arises in assay testing, where usage is contemplated in populations with known prevalences. Further instances include biomarker development, where subjects are selected from a population with known prevalence and assessment of PPV and NPV is crucial, and the assessment of diagnostic imaging procedures for rare diseases, where case–control studies may be the only feasible designs. We develop formulas for optimal allocation of the sample between the case and control cohorts and for computing sample size when the goal of the study is to prove that the test procedure exceeds pre-stated bounds for PPV and/or NPV. Surprisingly, the optimal sampling schemes for many purposes are highly unbalanced, even when information is desired on both PPV and NPV.
Metabolome Analysis of Biosynthetic Mutants Reveals a Diversity of Metabolic Changes and Allows Identification of a Large Number of New Compounds in Arabidopsis
Authors: Böttcher Christoph , von Roepenack-Lahaye Edda , Schmidt Jürgen , Schmotz Constanze , Neumann Steffen , Scheel Dierk , Clemens Stephan 
Published: June 2008

Abstract
Metabolomics is facing a major challenge: the lack of knowledge about metabolites present in a given biological system. Thus, large-scale discovery of metabolites is considered an essential step toward a better understanding of plant metabolism. We show here that the application of a metabolomics approach generating structural information for the analysis of Arabidopsis (Arabidopsis thaliana) mutants allows the efficient cataloging of metabolites. Fifty-six percent of the features that showed significant differences in abundance between seeds of wild-type, transparent testa4, and transparent testa5 plants could be annotated. Seventy-five compounds were structurally characterized, 21 of which could be identified. About 40 compounds had not been known from Arabidopsis before. Also, the high-resolution analysis revealed an unanticipated expansion of metabolic conversions upstream of biosynthetic blocks. Deficiency in chalcone synthase results in the increased seed-specific biosynthesis of a range of phenolic choline esters. Similarly, a lack of chalcone isomerase activity leads to the accumulation of various naringenin chalcone derivatives. Furthermore, our data provide insight into the connection between p-coumaroyl-coenzyme A-dependent pathways. Lack of flavonoid biosynthesis results in elevated synthesis not only of p-coumarate-derived choline esters but also of sinapate-derived metabolites. However, sinapoylcholine is not the only accumulating end product. Instead, we observed specific and sophisticated changes in the complex pattern of sinapate derivatives.
Interactions between theS-Domain Receptor Kinases and AtPUB-ARM E3 Ubiquitin Ligases Suggest a Conserved Signaling Pathway in Arabidopsis
Authors: Samuel Marcus A. , Mudgil Yashwanti , Salt Jennifer N. , Delmas Frédéric , Ramachandran Shaliny , Chilelli Andrea , Goring Daphne R. 
Published: June 2008

AbstractThe Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses.
Channelrhodopsin-1 Initiates Phototaxis and Photophobic Responses inChlamydomonasby Immediate Light-Induced Depolarization
Authors: Berthold Peter , Tsunoda Satoshi P. , Ernst Oliver P. , Mages Wolfgang , Gradmann Dietrich , Hegemann Peter 
Published: June 2008

AbstractChannelrhodopsins (CHR1 and CHR2) are light-gated ion channels acting as sensory photoreceptors in Chlamydomonas reinhardtii. In neuroscience, they are used to trigger action potentials by light in neuronal cells, tissues, or living animals. Here, we demonstrate that Chlamydomonas cells with low CHR2 content exhibit photophobic and phototactic responses that strictly depend on the availability of CHR1. Since CHR1 was described as a H+-channel, the ion specificity of CHR1 was reinvestigated in Xenopus laevis oocytes. Our experiments show that, in addition to H+, CHR1 also conducts Na+, K+, and Ca2+. The kinetic selectivity analysis demonstrates that H+ selectivity is not due to specific translocation but due to selective ion binding. Purified recombinant CHR1 consists of two isoforms with different absorption maxima, CHR1505 and CHR1463, that are in pH-dependent equilibrium. Thus, CHR1 is a photochromic and protochromic sensory photoreceptor that functions as a light-activated cation channel mediating phototactic and photophobic responses via depolarizing currents in a wide range of ionic conditions.
Targeted Degradation of the Cyclin-Dependent Kinase Inhibitor ICK4/KRP6 by RING-Type E3 Ligases Is Essential for Mitotic Cell Cycle Progression duringArabidopsisGametogenesis
Authors: Liu Jingjing , Zhang Yiyue , Qin Genji , Tsuge Tomohiko , Sakaguchi Norihiro , Luo Guo , Sun Kangtai , Shi Dongqiao , Aki Shiori , Zheng Nuoyan , Aoyama Takashi , Oka Atsuhiro , Yang Weicai , Umeda Masaaki , Xie Qi , Gu Hongya , Qu Li-Jia 
Published: June 2008

AbstractFollowing meiosis, plant gametophytes develop through two or three rounds of mitosis. Although the ontogeny of gametophyte development has been defined in Arabidopsis thaliana, the molecular mechanisms regulating mitotic cell cycle progression are not well understood. Here, we report that RING-H2 group F 1a (RHF1a) and RHF2a, two RING-finger E3 ligases, play an important role in Arabidopsis gametogenesis. The rhf1a rhf2a double mutants are defective in the formation of male and female gametophytes due to interphase arrest of the mitotic cell cycle at the microspore stage of pollen development and at female gametophyte stage 1 of embryo sac development. We demonstrate that RHF1a directly interacts with and targets a cyclin-dependent kinase inhibitor ICK4/KRP6 (for Interactors of Cdc2 Kinase 4/Kip-related protein 6) for proteasome-mediated degradation. Inactivation of the two redundant RHF genes leads to the accumulation of ICK4/KRP6, and reduction of ICK4/KRP6 expression largely rescues the gametophytic defects in rhf1a rhf2a double mutants, indicating that ICK4/KRP6 is a substrate of the RHF E3 ligases. Interestingly, in situ hybridization showed that ICK4/KRP6 was predominantly expressed in sporophytes during meiosis. Our findings indicate that RHF1a/2a-mediated degradation of the meiosis-accumulated ICK4/KRP6 is essential to ensure the progression of subsequent mitoses to form gametophytes in Arabidopsis.
Bemused by bibliometrics: using citation analysis to evaluate research quality
Authors: Joint Nicholas 
Published: June 2008

PurposeThe purpose of this paper is to examine the way in which library and information science (LIS) issues have been handled in the formulation of recent UK Higher Education policy concerned with research quality evaluation.Design/methodology/approachA chronological review of decision making about digital rights arrangements for the 2008 Research Assessment Exercise (RAE), and of recent announcements about the new shape of metrics‐based assessment in the Research Excellence Framework, which supersedes the RAE. Against this chronological framework, the likely nature of LIS practitioner reactions to the flow of decision making is suggested.FindingsIt was found that a weak grasp of LIS issues by decision makers undermines the process whereby effective research evaluation models are created. LIS professional opinion should be sampled before key decisions are made.Research limitations/implicationsThis paper makes no sophisticated comments on the complex research issues underlying advanced bibliometric research evaluation models. It does point out that sophisticated and expensive bibliometric consultancies arrive at many conclusions about metrics‐based research assessment that are common knowledge amongst LIS practitioners.Practical implicationsPractical difficulties arise when one announces a decision to move to a new and specific type of research evaluation indicator before one has worked out anything very specific about that indicator.Originality/valueIn this paper, the importance of information management issues to the mainstream issues of government and public administration is underlined. The most valuable conclusion of this paper is that, because LIS issues are now at the heart of democratic decision making, LIS practitioners and professionals should be given some sort of role in advising on such matters.
Legitimacy for large public libraries in the digital age
Authors: Waller Vivienne 
Published: June 2008

PurposeThe purpose of this paper is to critically analyse recent developments in the relationship of large public libraries with digital technologies, suggesting a way of rethinking the future of large public libraries.Design/methodology/approachThis paper bases its critical analysis on a review of the literature and reference to specific cases. Historical quotes preceding sections augment the argument that many of the current concerns about digital technologies are not new issues for libraries.FindingsIssues around library take up of digital technology are continuations of debates that have occurred throughout the history of public libraries about the role of the library. In Australia, library policy makers are focusing on technology and an imagined user in an effort to prove the legitimacy of large public libraries to funding bodies, the library profession and library users. Such attempts seem doomed to fail.Practical implicationsPublic libraries need to be clear about their purpose as publicly funded institutions in the digital age. This requires a renewed understanding of a library's publics and a critical understanding of the nature of services available using digital technologies.Originality/valueThis paper presents an alternative way of thinking about the future of large public libraries, with much of the discussion also relevant to local public libraries.
An insight into the Matthew effect in Mexico
Authors: Licea de Arenas Judith , Arenas Miguel , Márquez Sergio 
Published: June 2008

PurposeThe purpose of this paper is to profile the prizewinners of the most prestigious award in Mexico, the National Prize for Sciences and the Arts and the Emeritus Professorship awarded by the National University of Mexico.Design/methodology/approachThe paper draws upon data retrieved from the Web of Science (1995‐2006).FindingsThe 68 laureates published 1,175 papers and received a total of 13,443 citations. The most productive scientists were in the age group 65‐69, while those over 75 years of age were the least productive as well as the less cited. Most prizewinners have at least 35 years' experience scientists, who have been active as researchers for 30‐39 years, were the most productive and the most cited.Research limitations/implicationsResults presented in this paper could complement other indicators of research performance used to determine the visibility of Mexican science, research institutions and individuals and whether resources and influence should be distributed more equitably. The operationalization of the Matthew effect could be minimized if awards committees were to correlate bibliometrics with the peer review process in order to reward the most creative researchers.Originality/valueThe paper focuses on research performance of Mexican academics.
Small creative industry firms: a development dilemma?
Authors: Chaston Ian 
Published: June 2008

PurposeThe purpose of the paper is to examine whether the standard support service intervention model of providing training programmes to stimulate business growth is an effective economic regeneration model in the case of small creative industry firms.Design/methodology/approachA survey of small creative firms was implemented in the south west UK. The aim of the survey was to gain owner/manager views about participation in training.FindingsThe results reveal the majority of firms are interested in a lifestyle based on fulfilling creative aspirations. Very few respondents exhibit any interest in participating in training schemes aimed at enhancing business performance.Research limitations/implicationsThe limitations of the research are that it only relates to creative industry firms and was restricted to a single geographic area and only generated data from micro‐enterprises. The implications of these findings are discussed in relation to whether regional development agency policies in rural areas should primarily be directed towards supporting industry‐led expansion of existing creative industry small firm clusters.Practical implicationsThe results provide useful guidance in relation to avoiding public sector expenditure on support schemes that are unlikely to stimulate significant economic growth in the small business sector. Additionally a more cost effective approach to stimulating growth in small creative firms outside of metro‐city areas is presentedOriginality/valuePrevious researchers have raised questions about the benefits of offering business training to small firms. This study provides additional knowledge in relation to this issue. More importantly, however, the study offers conclusions about the possible need for support agencies to radically revise their current strategies in relation to stimulating growth and new job creation in the creative industry sector.
Charisma as a cognitive‐affective phenomenon: a follower‐centric approach
Authors: Jayakody J.A.S.K. 
Published: June 2008

PurposeThe intention of this paper is to conceptualize charisma as a multidimensional, cognitive‐affective phenomenon for the reason that the current practice of conceptualization and operationalization of charisma in terms of observable extraordinary behaviour of the leader has diluted “attributed extraordinariness” while disregarding other facets that the theorists assume to be part of charisma.Design/methodology/approachThe existing literature on charisma in many diverse disciplines is appraised in order to enumerate the dimensions of charisma. Accordingly, the paper presents a working definition of charisma and makes suggestions on developing a scale of charisma as a multidimensional, cognitive‐affective phenomenon.FindingsThe paper concludes that charisma is a cognitive‐affective phenomenon and is characterized by “Leader extraordinariness”, “Leader archetypicality” “Leader group prototypicality” (cognitive dimensions), “Reverence with awe” and “Love with enthusiasm” (affective dimensions).Research limitations/implicationsOther than explaining how a scale of charisma could be developed, the paper also explains how the proposed conceptualization opens up new avenues for the exploration of routinization of charisma and follower psychological dynamics.Practical implicationsWhile the paper urges leaders to appeal to followers emotionally and to use the impression management techniques, it urges followers to be vigilant about the “dark side of charisma”.Originality/valueThe present paper can be taken as the first attempt at conceptualizing charisma as a multidimensional, cognitive‐affective phenomenon, though charisma has been long thought to be so. As it takes a follower‐centric approach and incorporates many dimensions of charisma which are presently neglected in operationalizing charisma, the suggested scale of charisma will more validly measure the charisma of leaders than scales presently used.
New directions for the biopharma industry in Canada: modelling and empirical findings
Authors: March‐Chorda Isidre , Yagüe‐Perales Rosa M. 
Published: June 2008

PurposeThe main purpose of this study is to identify features and trends shaping the business models currently prevailing in the Canadian biopharma industry, by disaggregating the business model analysis into four key areas: value creation, investment strategy, business strategy, success factorsDesign/methodology/approachResults arise from an empirical fieldwork of qualitative nature, undertaken by the end of 2004, involving deep interviews to a broad variety of key stakeholders of the biopharma industry in the Quebec region, including biopharma firms, large pharma firms, venture capital funds, research centers and recognized experts from consultancy firms and Universities.FindingsBiopharma firms encounter difficulties to bridge the gap between the research innovation focus to the large scale production focus. The biopharma firms need to announce achievable and promising hits in the near future, mainly by filing patents and also through scientific publications, and making believable their prospects to reach the release phase. Venture capitalists and private investors claim for original, innovative and marketable results, keeping away from just imitative enterprises. The one product firms still largely prevail.Research limitations/implicationsLessons learned through this fieldwork might in the future be complemented with a quantitative survey to biopharma firms in the Quebec region.Practical implicationsWhen funding biopharma firms, private investors claim for original, innovative and marketable results, keeping away from just imitative enterprises. The business model must evolve, and take into account the quick changes in the environment, coming either from the market or from the technologies and research streams.Originality/valueDisaggregating the business model analysis into four key areas will make an original contribution to the limited knowledge about expectations and future prospects of the biopharma industry