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Major Events (major + event)
Selected AbstractsThe effect of a major event on stereotyping: terrorist attacks in Israel and Israeli adolescents' perceptions of Palestinians, Jordanians and ArabsEUROPEAN JOURNAL OF SOCIAL PSYCHOLOGY, Issue 3 2001Daniel Bar-Tal This study examines the effect of a major event (terrorist attacks) on the stereotypic perceptions, attitudes and affects of 119 Israeli adolescents (56 males and 63 females of 5th and 8th grades) toward three target groups: (a) Palestinians, who still have conflictive relations with the Israelis (Palestinian extremists carried out the attacks), (b) Jordanians, who have peaceful relations with the Israelis and (c) Arabs, in general, who are considered a subcategory including Arabs of all nations. The questionnaires were administered to the same adolescents three times: during a relatively peaceful spell in Israeli,Palestinian relations; one day following two terrorist attacks, and three months thereafter. In the last administration adolescents' need for closure was also measured. Adolescents' perceptions, attitudes and affect toward the three target group were differentiated,relating to Palestinians most negatively and to Jordanians most positively. Also, following the terrorist attacks, stereotypic perceptions and attitudes changed in a negative direction, in relation to all the three groups; again with expressed differentiation among the three groups. In the third measurement, some measures remained negative, but some changed to be more positive. Only few effects of age were detected and several significant correlation with need for closure were found. These results indicate that stereotypes and attitudes toward outgroups are context-dependent, influenced by events; thus they serve as ,a seismograph' to the quality of intergroup relations at any given time. Copyright © 2001 John Wiley & Sons, Ltd. [source] Neurodegeneration in an A,-induced model of Alzheimer's disease: the role of Cdk5AGING CELL, Issue 1 2010Joao P. Lopes Summary Cdk5 dysregulation is a major event in the neurodegenerative process of Alzheimer's disease (AD). In vitro studies using differentiated neurons exposed to A, exhibit Cdk5-mediated tau hyperphosphorylation, cell cycle re-entry and neuronal loss. In this study we aimed to determine the role of Cdk5 in neuronal injury occurring in an AD mouse model obtained through the intracerebroventricular (icv) injection of the A,1,40 synthetic peptide. In mice icv-injected with A,, Cdk5 activator p35 is cleaved by calpains, leading to p25 formation and Cdk5 overactivation. Subsequently, there was an increase in tau hyperphosphorylation, as well as decreased levels of synaptic markers. Cell cycle reactivation and a significant neuronal loss were also observed. These neurotoxic events in A,-injected mice were prevented by blocking calpain activation with MDL28170, which was administered intraperitoneally (ip). As MDL prevents p35 cleavage and subsequent Cdk5 overactivation, it is likely that this kinase is involved in tau hyperphosphorylation, cell cycle re-entry, synaptic loss and neuronal death triggered by A,. Altogether, these data demonstrate that Cdk5 plays a pivotal role in tau phosphorylation, cell cycle induction, synaptotoxicity, and apoptotic death in postmitotic neurons exposed to A, peptides in vivo, acting as a link between diverse neurotoxic pathways of AD. [source] Making Meaning: Women's Birth NarrativesJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 4 2004FAAN professor, Lynn Clark Callister RN Birth stories are personal narratives grounded in the pivotal life experience of giving birth. Richly descriptive birth narratives from culturally diverse childbearing women document the importance of listening to the voices of women. Benefits of sharing birth stories include the opportunity for integration of a major event into the framework of a mother's life; the opportunity to share a significant life experience; the opportunity to discuss fears, concerns, "missing pieces" or feelings of inadequacy or disappointment; the opportunity for the woman to gain an understanding of her strengths; and the opportunity to connect with other women. Providing women with the opportunity to share their birth stories is an important nursing intervention. [source] The processing of a Benzo(a)pyrene adduct into a frameshift or a base substitution mutation requires a different set of genes in Escherichia coliMOLECULAR MICROBIOLOGY, Issue 2 2000Nathalie Lenne-Samuel Replication through a single DNA lesion may give rise to a panel of translesion synthesis (TLS) events, which comprise error-free TLS, base substitutions and frameshift mutations. In order to determine the genetic control of the various TLS events induced by a single lesion, we have chosen the major N2-dG adduct of (+)- anti -Benzo(a)pyrene diol epoxide [(+)- anti -BPDE] adduct located within a short run of guanines as a model lesion. Within this sequence context, in addition to the major event, i.e. error-free TLS, the adduct also induces base substitutions (mostly G , T transversions) and ,1 frameshift mutations. The pathway leading to G , T base substitution mutagenesis appears to be SOS independent, suggesting that TLS is most probably performed by the replicative Pol III holoenzyme itself. In contrast, both error-free and frameshift TLS pathways are dependent upon SOS-encoded functions that belong to the pool of inducible DNA polymerases specialized in TLS (translesional DNA polymerases), namely umuDC (Pol V) and dinB (Pol IV). It is likely that, given the diversity of conformations that can be adopted by lesion-containing replication intermediates, cells use one or several translesional DNA polymerases to achieve TLS. [source] Higher-level phylogeny of the Ithomiinae (Lepidoptera: Nymphalidae): classification, patterns of larval hostplant colonization and diversificationCLADISTICS, Issue 4 2006Keith R. Willmott We present a higher-level phylogenetic hypothesis for the diverse neotropical butterfly subfamily Ithomiinae, inferred from one of the largest non-molecular Lepidoptera data sets to date, including 106 species (105 ingroup) and 353 characters (306 informative) from adult and immature stage morphology and ecology. Initial analyses resulted in 1716 most parsimonious trees, which were reduced to a single tree after successive approximations character weighting. The inferred phylogeny was broadly consistent with other past and current work. Although some deeper relationships are uncertain, tribal-level clades were generally strongly supported, with two changes required to existing classification. The tribe Melinaeini is polyphyletic and Athesis + Patricia require a new tribe. Methona should be removed from Mechanitini into the restored tribe Methonini. Dircennini was paraphyletic in analyses of all data but monophyletic based on adult morphology alone, and its status remains to be confirmed. Hypothyris, Episcada, Godyris, Hypoleria and Greta are paraphyletic. A simulation analysis showed that relatively basal branches tended to have higher partitioned Bremer support for immature stage characters. Larval hostplant records were optimized on to a reduced, generic-level phylogeny and indicate that ithomiines moved from Apocynaceae to Solanaceae twice, or that Tithoreini re-colonized Apocynaceae after a basal shift to Solanaceae. Ithomiine clades have specialized on particular plant clades suggesting repeated colonization of novel hostplant niches consistent with adaptive radiation. The shift to Solanum, comprising 70% of neotropical Solanaceae, occurs at the base of a clade containing 89% of all ithomiines, and is interpreted as the major event in the evolution of ithomiine larval hostplant relationships. © The Willi Hennig Society 2006. [source] Sirolimus-induced signaling modifications in Kaposi's sarcoma with resolution in a liver transplant recipientCLINICAL TRANSPLANTATION, Issue 1 2010Cheng-Maw Ho Ho C-M, Huang S-F, Hu R-H, Ho M-C, Wu Y-M, Lee P-H. Sirolimus-induced signaling modifications in Kaposi's sarcoma with resolution in a liver transplant recipient. Clin Transplant 2010: 24: 127,132. © 2009 John Wiley & Sons A/S. Abstract:, Sirolimus is one treatment option in transplant recipients with Kaposi's sarcoma (KS), which involves dysregulation of Akt-mammalian target of rapamycin (mTOR) signaling pathway. Signal modifications after sirolimus therapy in organ recipients with KS are largely unknown and not verified. We reported a case of KS found two yr after liver transplantation in which the immunosuppression was changed from tacrolimus, MMF, and steroid to sirolimus alone. In skin, which was found to have persistent KS after a two-month treatment of sirolimus and was removed completely one yr later, KS was no longer present. The patient went well without graft rejection. Tumor biopsies were performed before, two months, and one yr after the start of sirolimus. Immunohistochemical staining of vascular endothelial growth factor (VEGF), p-Akt, p-mTOR, p-p70 S6 kinase, and Western blot for p-tuberin/ tuberous sclerosis complex (TSC)2 was performed. VEGF was suppressed thoroughly in two-month use of sirolimus. In addition, p-Akt and p-mTOR, which were decreased at two months, could not be detected after one yr of treatment. Moreover, p-p70 S6 kinase, expressed strongly in overlying epidermis initially, was suppressed completely after two months of treatment. However, p-tuberin/TSC2, contrary to suggested theoretically, was not detected through all specimens, implying not to be a significant event. Suppressed expression of VEGF, p-Akt, and p-mTOR was the major event of signaling modification through the long-term use of sirolimus. [source] Transcatheter versus Surgical Closure of Secundum Atrial Septal Defect in Adults: Impact of Age at Intervention.CONGENITAL HEART DISEASE, Issue 3 2007A Concurrent Matched Comparative Study Abstract Objectives., To compare the short- and mid-term outcomes of surgical (SUR) vs. transcatheter closure of secundum atrial septal defect (ASD) using Amplatzer septal occluder (ASO) in adults with a very similar spectrum of the disease; and to identify predictors for the primary end point. Design., Single-center, concurrent comparative study. Surgically treated patients were randomly matched (2:1) by age, sex, date of procedure, ASD size, and hemodynamic profile. Setting., Tertiary referral center. Patients., One hundred sixty-two concurrent patients with ASD submitted to ASO (n = 54) or SUR closure (n = 108) according with their preferences. Main Outcome Measures., Primary end point was a composite index of major events including failure of the procedure, important bleeding, critical arrhythmias, serious infections, embolism, or any major cardiovascular intervention-related complication. Predictors of these major events were investigated. Results., Atrial septal defects were successfully closed in all patients, and there was no mortality. The primary event rate was 13.2% in ASO vs. 25.0% in SUR (P = .001). Multivariate analysis showed that higher rate of events was significantly associated with age >40 years; systemic/pulmonary output ratio <2.1; and systolic pulmonary arterial pressure >50 mm Hg; while in the ASO group the event rate was only associated with the ASD size (>15 cm2/m2; relative risk = 1.75, 95% confidence interval 1.01,8.8). There were no differences in the event-free survival curves in adults with ages <40 years. Conclusions., The efficacy for closure ASD was similar in both groups. The higher morbidity observed in SUR group was observed only in the patients submitted to the procedure with age >40 years. The length of hospital stay was shorter in the ASO group. Surgical closure is a safe and effective treatment, especially in young adults. There is certainly nothing wrong with continuing to do surgery in countries where the resources are limited. [source] Basic fibrobrast growth factor induces the secretion of vascular endothelial growth factor by human aortic smooth muscle cells but not by endothelial cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003F. Belgore Abstract Background, Endothelial cell dysfunction and smooth muscle cell (SMC) proliferation are major events in atherogenesis. Both cells are a source of growth factors that mediate cellular proliferation and chemotaxis. Inappropriate production of, and/or response to, these growth factors (such as vascular endothelial growth factor, VEGF, and basic fibroblast growth factor (bFGF)) may contribute to atherogenesis and therefore to disease progression. Methods, Production of VEGF and its soluble receptor (sFlt-1) by human SMCs and human umbilical endothelial cells (HUVECs) after stimulation with bFGF were examined by ELISA of cell culture media and by Western blotting. Results, Smooth muscle cells produced significantly more VEGF than HUVECs (P < 0·05) after 24 h of culture with bFGF levels , 0·001 µg mL,1. bFGF induced dose-dependent production of VEGF by SMCs, where maximum production was present in 1 µg mL,1 of bFGF. Conversely, the SMCs produced less sFlt-1 than HUVECs (P < 0·05). However, bFGF induced dose-dependent phosphorylation of Flt1 and another VEGF receptor, KDR, in HUVECs but not SMCs. There was no VEGF or sFLT-1 after 6 h of culture in any dose of bFGF in either type of cell. Conclusions, Differences in the production of VEGF and sFlt-1 by SMCs and HUVECs are consistent with the role of these cells in angiogenesis. Induction of VEGF production and expression by bFGF in these cells indicates that this growth factor may participate in angiogenesis indirectly by the induction of VEGF. The production of sFlt-1 by both cell types is in agreement with the notion that sFlt-1 may be involved in the regulation of VEGF activity. Additionally, the ability of bFGF to induce dose-dependent phosphorylation of KDR in HUVECs highlights the important role of bFGF in VEGF-mediated angiogenic processes. [source] On the Mechanism of the Reductive Metallation of Asymmetrically Substituted Silyl ChloridesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 1 2005Martin Oestreich Abstract An investigation of the stereochemical course of the reductive metallation of silyl chlorides with silicon-centred chirality has revealed two major events which are detrimental to stereoselection during silyl anion formation: (1) chloride-induced racemisation of silyl chlorides and (2) nonstereoselective formal dimerisation during metallation providing the corresponding disilane. In control experiments, the stereochemical course of these processes has been independently verified for the reductive metallation of the enantioenriched cyclic silyl chloride (SiS)- 7a (R = H, er , 88:12). A screening of several related derivatives of (SiS)- 7a led to the sterically encumbered silyl chloride (SiR)- 7c (R = iPr, er , 94:6) which displays some unique features. This structural modification prevents racemisation by lithium chloride (T < ,40 °C) as well as dimerisation (T < ,100 °C) thus allowing for the first generation of an asymmetrically substituted silyl anion (SiS)- 8c (er = 74:26) by reductive metallation of a silyl chloride with silicon-centred chirality. Moreover, the enantiospecificity of the preparation of (SiR)- 7c by chlorination [(SiS)- 9c , (SiR)- 7c] and its reduction with aluminium hydrides [(SiR)- 7c , (SiR)- 9c] have been unambiguously determined by X-ray crystallography as retention (,99%) and inversion (,99%), respectively. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] El Niño,southern oscillation events and associated European winter precipitation anomaliesINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 1 2005D. Pozo-Vázquez Abstract The winter precipitation anomalies in the European area have been analysed over the period 1900,98 based on the El Niño,Southern oscillation (ENSO) state. A set of winter and autumn ENSO events is first selected using the Sea-Surface temperature (SST) data of the Niño 3 region, with the constraint that the ENSO event is well developed during the winter and autumn of study, and that it is an extreme event. Cold and warm ENSO events and periods that can be regarded as normal are selected. For the selected winter ENSO events and for the winter following the selected autumn ENSO events, composites of European winter precipitation anomalies have been obtained and compared with each other. A study of the consistency among events of the relationship between ENSO and precipitation anomalies was also carried out. The analysis of the winter precipitation anomalies based on the selected winter ENSO events shows the existence, for the European area and during La Niña events, of a statistically significant precipitation anomaly pattern with positive precipitation anomalies north of the British Isles and in the Scandinavian area and negative anomalies in southern Europe, resembling the precipitation pattern associated with the positive phase of the North Atlantic oscillation (NAO). Particularly, for the southwestern area of the Iberian Peninsula, the negative anomaly reaches 20% of the winter average precipitation. The consistency analysis shows that this precipitation pattern is not the result of a few major events, but rather that it is stable and qualitatively similar to that found during the positive phase of the NAO. A non-linear response to ENSO is found in the eastern Mediterranean area: negative precipitation anomalies are found, having similar amplitude anomalies, both during El Niño and La Niña events. The analysis of the precipitation anomalies for the winter following the selected autumn ENSO events shows very similar results to those found for the previous analysis, thus suggesting the existence of a potential source of seasonal forecasting of European precipitation. An analysis of the sensitivity of the precipitation anomalies to the strength of the ENSO events shows that, when the strength of the ENSO increases, the magnitude of the rainfall anomalies does not change, but the area influenced and the coherence between events do increase slightly. Copyright © 2005 Royal Meteorological Society [source] To go or stay home and watch: exploring the balance between motives and perceived constraints for major events: a case study of the 2008 Beijing Olympic GamesINTERNATIONAL JOURNAL OF TOURISM RESEARCH, Issue 1 2009Daniel C. Funk Abstract The current study offers insight into the role of motivation and constraints on behavioural intentions prior to a mega event. The Psychological Continuum Model framework was used to integrate motivation and leisure constraints theory to examine attraction towards the 2008 Olympic Games. Semi-structured interviews (N = 47) and a questionnaire (N = 235) distributed in Australia and the USA were used to identify and measure three motivational themes: cultural learning, cultural experience and olympic event interest, and three perceived constraints: structural, interpersonal and intrapersonal. Structural Equation Modelling revealed that motives were positively related to behavioural intentions while constraints were negatively related. Analysis further revealed the interaction between motives and perceived constraints led to two different forms of behavioural intentions; intentions to travel and attend the event vs. stay home to watch the event on TV. Policy and marketing implications are discussed that illustrate the benefits of understanding both motives and perceived constraints for tourism travel. Copyright © 2008 John Wiley and Sons, Ltd. [source] Genetic diversity and phylogeographic analysis of Pinus leiophylla: a post-glacial range expansionJOURNAL OF BIOGEOGRAPHY, Issue 9 2009Abril Rodríguez-Banderas Abstract Aim, Mexico is a centre of diversity for species of the genus Pinus, most of which have restricted geographical distributions. An exception is Pinus leiophylla Schiede and Deppe, which is widely distributed throughout most of Mexico's mountainous regions. We attempt to reconstruct the phylogeographic history of this species, in order to determine if its current broad distribution is associated with major events of environmental change that occurred during the Quaternary. Location, Coniferous forests in Sierra Madre Occidental, Eje Volcánico Transversal and Sierra Montañosa del Norte de Oaxaca, Mexico. Methods, A total of 323 individuals of both P. leiophylla var. leiophylla and P. leiophylla var. chihuahuana sampled from 22 populations were screened for variation at six paternally inherited chloroplast DNA microsatellite markers (cpSSR). In addition to haplotypic diversity estimates and neutrality tests, the following clustering methods were employed: principal components analysis (PCA), analysis of molecular variance (AMOVA), spatial analysis of molecular variance (SAMOVA), haplotype network and a technique similar to Croizat's panbiogeographical method of individual and generalized tracks. Results, The combination of mutations at the six microsatellites yielded a total of 92 different haplotypes. The percentage of shared haplotypes between varieties (P. leiophylla var. leiophylla and P. leiophylla var. chihuahuana) was only 2.2%. The average haplotypic diversity for the species was H = 0.760. PCA and SAMOVA indicate the presence of four main genetic clusters. The estimated divergence time between the two most frequent haplotypes was between 75,000 and 110,000 years. Significantly large negative Fs values suggest that most of the sampled populations are currently expanding. Individual and generalized tracks identified three potential zones that may have harboured ancestral populations of P. leiophylla and from which the expansion of this species started, as well as two secondary contact zones between the two varieties. Main conclusions, The results indicate that one of the three potential areas hypothesized to have harboured ancestral populations of P. leiophylla may be related to the origin of P. leiophylla var. chihuahuana, while the other two may be related to the origin of P. leiophylla var. leiophylla. The current broad distribution of P. leiophylla is probably associated with its strong colonization ability. [source] Influence of temperature, friction, and random forces on folding of the B-domain of staphylococcal protein A: All-atom molecular dynamics in implicit solventJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2007Anna Jagielska Abstract The influences of temperature, friction, and random forces on the folding of protein A have been analyzed. A series of all-atom molecular dynamics folding simulations with the Amber ff99 potential and Generalized Born solvation, starting from the fully extended chain, were carried out for temperatures from 300 to 500 K, using (a) the Berendsen thermostat (with no explicit friction or random forces) and (b) Langevin dynamics (with friction and stochastic forces explicitly present in the system). The simulation temperature influences the relative time scale of the major events on the folding pathways of protein A. At lower temperatures, helix 2 folds significantly later than helices 1 and 3. However, with increasing temperature, the folding time of helix 2 approaches the folding times of helices 1 and 3. At lower temperatures, the complete formation of secondary and tertiary structure is significantly separated in time whereas, at higher temperatures, they occur simultaneously. These results suggest that some earlier experimental and theoretical observations of folding events, e.g., the order of helix formation, could depend on the temperature used in those studies. Therefore, the differences in temperature used could be one of the reasons for the discrepancies among published experimental and computational studies of the folding of protein A. Friction and random forces do not change the folding pathway that was observed in the simulations with the Berendsen thermostat, but their explicit presence in the system extends the folding time of protein A. © 2007 Wiley Periodicals, Inc. J Comput Chem 2007 [source] Immediate and Long-Term Outcome of Recanalization of Chronic Total Coronary OcclusionsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 3 2002FEDERICO PISCIONE M.D. Eighty-three consecutive patients with 85 coronary total occlusions undergoing coronary angioplasty were retrospectively studied. Patients were divided into two groups according to the occlusion age that was<30 days (subacute total occlusion [STO]: 25 patients; range 1,30 days) or>30 days (chronic total occlusion [CTO]: 58 patients; range 3,144 months). All procedures were carried out using a hydrophilic guidewire. Clinical success, consisting of crossing the lesion, balloon dilatation, stent deployment without complication, was 96% in STO and 81% in CTO. Multiple stepwise logistic regression analysis identified a family history of coronary artery disease (CAD), left anterior descending and right coronary artery occlusions as independent predictors of a successful procedure. No major events occurred during or immediately after the angioplasty. After a mean follow-up of 24 ± 2 months, no difference was found in survival or freedom from myocardial infarction or target vessel revascularization among the STO and CTO patients. Successful recanalization by using a hydrophilic guidewire was achieved in a high percentage of chronic total occlusions with a low incidence of complications and a satisfactory late clinical outcome. Family history of CAD and occlusion of left anterior descending or right coronary arteries are independent predictors of procedural success. [source] Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of l -carnitineJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Daniela Silva-Adaya Abstract Excitotoxicity and disrupted energy metabolism are major events leading to nerve cell death in neurodegenerative disorders. These cooperative pathways share one common aspect: triggering of oxidative stress by free radical formation. In this work, we evaluated the effects of the antioxidant and energy precursor, levocarnitine (l -CAR), on the oxidative damage and the behavioral, morphological, and neurochemical alterations produced in nerve tissue by the excitotoxin and free radical precursor, quinolinic acid (2,3-pyrindin dicarboxylic acid; QUIN), and the mitochondrial toxin, 3-nitropropionic acid (3-NP). Oxidative damage was assessed by the estimation of reactive oxygen species formation, lipid peroxidation, and mitochondrial dysfunction in synaptosomal fractions. Behavioral, morphological, and neurochemical alterations were evaluated as markers of neurotoxicity in animals systemically administered with l -CAR, chronically injected with 3-NP and/or intrastriatally infused with QUIN. At micromolar concentrations, l -CAR reduced the three markers of oxidative stress stimulated by both toxins alone or in combination. l -CAR also prevented the rotation behavior evoked by QUIN and the hypokinetic pattern induced by 3-NP in rats. Morphological alterations produced by both toxins (increased striatal glial fibrillary acidic protein-immunoreactivity for QUIN and enhanced neuronal damage in different brain regions for 3-NP) were reduced by l -CAR. In addition, l -CAR prevented the synergistic action of 3-NP and QUIN to increase motor asymmetry and depleted striatal GABA levels. Our results suggest that the protective properties of l -CAR in the neurotoxic models tested are mostly mediated by its characteristics as an antioxidant agent. [source] Intracellular membrane trafficking in bone resorbing osteoclastsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 6 2003Mika Mulari Abstract There is ample evidence now that the two major events in bone resorption, namely dissolution of hydroxyapatite and degradation of the organic matrix, are performed by osteoclasts. The resorption cycle involves several specific cellular activities, where intracellular vesicular trafficking plays a crucial role. Although details of these processes started to open up only recently, it is clear that vesicular trafficking is needed in several specific steps of osteoclast functioning. Several plasma membrane domains are formed during the polarization of the resorbing cells. Multinucleated osteoclasts create a tight sealing to the extracellular matrix as a first indicator of their resorption activity. Initial steps of the sealing zone formation are ,v,3 -integrin mediated, but the final molecular interaction(s) between the plasma membrane and mineralized bone matrix is still unknown. A large number of acidic intracellular vesicles then fuse with the bone-facing plasma membrane to form a ruffled border membrane, which is the actual resorbing organelle. The formation of a ruffled border is regulated by a small GTP-binding protein, rab7, which indicates the late endosomal character of the ruffled border membrane. Details of specific membrane transport processes in the osteoclasts, e.g., the formation of the sealing zone and transcytosis of bone degradation products from the resorption lacuna to the functional secretory domain remain to be clarified. It is tempting to speculate that specific features of vesicular trafficking may offer several potential new targets for drug therapy of bone diseases. Microsc. Res. Tech. 61:496,503, 2003. © 2003 Wiley-Liss, Inc. [source] The evolution of the galaxy red sequence in simulated clusters and groupsMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2008A. D. Romeo ABSTRACT N -body/hydrodynamical simulations of the formation and evolution of galaxy groups and clusters in a , cold dark matter (,CDM) cosmology are used in order to follow the building-up of the colour,magnitude relation in two clusters and in 12 groups. We have found that galaxies, starting from the more massive, move to the red sequence (RS) as they get aged over times and eventually set upon a ,dead sequence' (DS) once they have stopped their bulk star formation activity. Fainter galaxies keep having significant star formation out to very recent epochs and lie broader around the RS. Environment plays a role as galaxies in groups and cluster outskirts hold star formation activity longer than the central cluster regions. However, galaxies experiencing infall from the outskirts to the central parts keep star formation on until they settle on to the DS of the core galaxies. Merging contributes to mass assembly until z, 1, after which major events only involve the brightest cluster galaxies. The emerging scenario is that the evolution of the colour,magnitude properties of galaxies within the hierarchical framework is mainly driven by star formation activity during dark matter haloes assembly. Galaxies progressively quenching their star formation settle to a very sharp ,red and dead' sequence, which turns out to be universal, its slope and scatter being almost independent of the redshift (since at least z, 1.5) and environment. Differently from the DS, the operatively defined RS evolves more evidently with z, the epoch when it changes its slope being closely corresponding to that at which the passive galaxies population takes over the star-forming one: this goes from z, 1 in clusters down to 0.4 in normal groups. [source] Parliament and the Problem of China, 1925,7: Priorities, Preoccupations and StereotypesPARLIAMENTARY HISTORY, Issue 3 2010PHOEBE CHOW Though China had never been part of Britain's formal empire, a century of trade and warfare had caused China to cede trading and territorial rights to Britain. But from 1925 to 1927 the rise of the Kuomintang and the anti-imperialistic movement began to threaten British interests in China, alarming policy makers in London. At the same time, the China issue also captured the attention of MPs, who spent long sessions debating British policy towards China. These debates reveal much about MPs' perceptions of China, and can be seen as a microcosm of the British public sphere, encapsulating the multivalent British opinions on the world around them. Discussions of the ,China Situation' became an opportunity to express opinions on most of the important topics of the day , the economy, the General Strike, the Red Scare, disarmament, and the future of empire. A close reading of these debates can tell us much, not only about assumptions MPs held about China and the Chinese people, but also about issues closer to home. Three major events in China grabbed the attention of parliament in the period 1925,7. They were: (1) the May 30th Movement and the subsequent anti-British boycott in 1925; (2) the decision to send troops to Shanghai in January 1927; and (3) the so-called Nanking outrages, when British subjects in China were killed by Nationalist Army troops. What follows is a description and analysis of the debates over these three episodes. [source] Latest news and product developmentsPRESCRIBER, Issue 3 2008Article first published online: 26 FEB 200 Higher risk of CV events in aspirin resistance More than one in four patients may have aspirin resistance, a new metaanalysis shows, and they face a four-to sixfold increased risk of a major cardiovascular event or death compared with aspirin-sensitive patients taking low-dose aspirin (BMJ online: 17 Jan 2008; doi:10. 1136/bmj.39430.529549.BE). The analysis included 20 studies involving a total of 2930 patients with cardiovascular disease. Of these, 28 per cent were defined as having aspirin resistance (according to the various definitions in each study). Compared with aspirin-sensitive patients, the odds ratio of any cardiovascular event or acute coronary syndrome was about 4 and the odds ratio of death was 6. Aspirin-resistant patients did not benefit from other antiplatelet treatment. ADOPT: rosiglitazone fracture risk in women A new analysis of the ADOPT trial (N Engl J Med 2006;355: 2427-43) has found that the risk of fractures during treatment with rosiglitazone (Avandia) is approximately twice as high as with metformin or glibenclamide, but mainly in women (Diabetes Care online: 25 Jan 2008; doi: 10.2337/dc07-2270). The study found a significant difference in risk between the drugs only for women, with a cumulative incidence of 15.1 per cent with rosiglitazone, 7.3 per cent with metformin and 7.7 per cent with glibenclamide after five years. No risk factors were identified although the incidence of fractures was higher among postmenopausal than premenopausal women. New from NICE Infliximab for the treatment of adults with psoriasis. Technology Appraisal Guidance No. 134, Jan 2008 Infliximab (Remicade), a monoclonal antibody against TNF-alpha, should be an option for treating very severe plaque psoriasis in adults, NICE recommends. Using its fast-track single technology appraisal procedure, NICE concluded that infliximab should be considered when standard therapies,methotrexate or ciclosporin (Neoral), or PUVA , have failed or are unsuitable. The criteria for disease severity are defined by the Psoriasis Area Severity Index (PASI) score (,20) and the Dermatology Life Quality Index (DLQI) score (>18). Treatment response is also defined by these measures and infliximab should be continued for longer than 10 weeks only when predefined thresholds are met. Infliximab costs an average of £11 750 annually. In 2006, NICE recommended etanercept (Enbrel) and efalizumab (Raptiva) for patients with severe psoriasis (PASI ,10 and DLQI >10). Commons committee wants tougher targets Most GPs get full QOF points for medicines management even though there is inexplicably large variation in good prescribing practice between PCTs, the Public Accounts Select Committee points out in its latest report, Prescribing Costs in Primary Care. The Committee wants to see tougher QOF targets among several initiatives to reduce prescribing costs. Although most publicity centred on its endorsement of the National Audit Office claim that GPs could save £200 million by prescribing lower-cost drugs, the report contains some more far-reaching proposals. GPs should prescribe generic alternatives within a therapeutic category, so when a brand is not available generically, eg Lipitor, a different drug that is, eg simvastatin, should be used when clinically appropriate. Further, this form of substitution should be rewarded via QOF targets. There should be greater uniformity in the appearance, labelling and packaging of generic and branded equivalents. The Department of Health should consider raising awareness of the value of medicines by printing the cost on packaging, and to reduce the £100 million wasted annually in dumped medicines, it should investigate which drugs aren't used and why patients won't take them. Strategic health authorities should work with the National Prescribing Centre to develop more prescribing indicators with which to measure PCT performance and support PCTs to promulgate best practice. They should also collaborate on promoting joint primary-secondary care formularies and increase the consistency of prescribing, not only between hospital specialists and GPs but also between PCTs. To monitor the influence of the pharmaceutical industry, PCTs should keep a record of gifts and hospitality and publish a register. Questions to ask about mental health treatment The Department of Health has published a booklet designed to raise awareness of medicines management issues affecting people using mental health services and their carers, and professionals in the health and social services. Although one aim of Medicines Management: Everybody's Business is to empower people with mental health problems to ask about their medication, its formal style is better suited to staff who need to improve their person-centred approach to care. It covers what information people should expect and what questions to ask when drug treatment is being considered, what to expect at review and issues to consider when contemplating stopping treatment. Copies can be downloaded at www.dh.gov.uk. Consider statins for all patients with diabetes Treatment with a statin should be considered for all patients with diabetes unless their risk is low, say the authors of a new study (Lancet 2008;371:117-25). Their meta-analysis of 14 randomised trials involving 18 686 people with diabetes and an average follow-up of 4.3 years found that statins reduced vascular events and vascular mortality as much as in nondiabetic populations. The overall benefit was 42 fewer major events per 1000 people treated for five years. This was independent of a history of vascular disease or other baseline characteristics. No evidence for OTC cough medicines There is no evidence that over-the-counter cough medicines for adults and children are effective in relieving acute cough, a new Cochrane review has concluded (Cochrane Database of Systematic Reviews 2008, Issue 1). The review of 17 randomised trials involving 2876 adults and eight involving 616 children reported conflicting findings of uncertain clinical relevance. The trials were heterogeneous and of low quality. Copyright © 2008 Wiley Interface Ltd [source] POINT: A Prescription to Decrease Left Ventricular FunctionPREVENTIVE CARDIOLOGY, Issue 4 2009Myrvin H. Ellestad MD The Courage Trial, published in 2007, has significantly reduced the incidence of treating stable angina with angioplasty. The investigators randomized 2297 patients with documented cardiac ischemia to conservative or invasive therapy and concluded that there was no difference in major events during a follow-up of 2.5 to 7 years and that the urge to open the narrowed artery was unjustified. Over the years it has been well documented by myocardial biopsy that repeated ischemic episodes result in replacement of myocardial cells by fibrous tissue, loss of mitochondria, and deterioration of left ventricular function. Ischemic episodes often occur in the absence of angina so that it is impossible to determine whether the therapy is reducing the magnitude or duration of the process. Also, in their study, 32% of the conservatively treated patients crossed over to invasive. The evidence indicated that conservative treatment may result in a progressive decrease in left ventricular function. [source] MS characterization of apheresis samples from rheumatoid arthritis patients for the improvement of immunoadsorption therapy , a pilot studyPROTEOMICS - CLINICAL APPLICATIONS, Issue 7 2009Mike Kienbaum Abstract Identification of proteins from apheresis samples was performed by both SDS-PAGE and 2-D gel separation of eluted proteins from staphylococcal protein A-based immunoadsorption columns (Prosorba®) followed by MS peptide mass fingerprinting and MS/MS peptide sequencing on a MALDI QIT TOF mass spectrometer. MS/MS peptide sequencing was performed in conjunction with a micro reversed phase HPLC configured with an online MALDI plate-spotting device. Apheresis treatment had been performed in three patients with longstanding therapy refractory rheumatoid arthritis. 2-D gels displayed ca. 500 spots representing proteins that were eluted from the Prosorba® columns. From 54 gels, a total of 1256 protein spots had been picked and yielded in the identification of 56 non-redundant proteins without counting isoforms. Proteins from the eluates belong to five major groups comprising (i) immunoglobulins (IgG, IgA, IgM heavy and light chains; about 40% of the spots), (ii) proteins involved in coagulation, (iii) HDL/LDL-associated proteins, (iv) proteins from the complement system, and (v) acute phase proteins. MS analysis showed that the full-length C3 complement protein had been cleaved upon complement activation, presumably on the column, such that the anaphylatoxin C3a was produced and released during therapy. Our results are consistent with clinical observations on both patient responses to therapy and reported adverse events. For the first time, direct molecular information has become available to support mechanistic reasoning for the principle of function of staphylococcal protein A-based immunoadsorption therapy and for the explanation of adverse events. According to our results, removal and/or modulation of immune complexes together with complement activation can be regarded as the major events that are taking place during Prosorba® therapy. In order to avoid complement activation and induction of an inflammatory cascade, we suggest the prevention of C3a anaphylatoxin-related reactions during immunoadsorption therapy. [source] The patient with cardiovascular disease: Treatment strategies for preventing major eventsCLINICAL CARDIOLOGY, Issue S2 2006Michael Cuffe M.D. Abstract An abundance of clinical data exists to support the ability of pharmacologic interventions to reduce risk for vascular events significantly; however, there remains a gap between this evidence and current clinical practice. Recent data from large-scale, placebo-controlled statin trials demonstrate that these agents dramatically reduce risk for cardiovascular events, even in moderate-risk patients with normal to moderately elevated cholesterol levels. Data from trials of a broad range of antihypertensives reinforce the value of blood pressure (BP) management and indicate that some of these agents may have additional benefits beyond BP reduction. Similarly, meta-analyses of randomized trials confirm that antiplatelet therapy prevents serious cardiovascular events in a wide range of high-risk patients. Each of these interventions alone has been demonstrated to reduce the risk for vascular events by approximately 25 to 30%. A combination approach utilizing intensive risk-reducing therapy with more than one of these agents has the potential to reduce the risk for vascular events by as much as 75%. Combined with nonpharmacologic risk reduction strategies, including exercise, diet, and smoking cessation, an opportunity exists to reduce the incidence of both first and recurrent cardiovascular events dramatically. [source] | |||||||||||||||||||