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Selected AbstractsFunctions of glutamate transporters in cerebellar Purkinje cell synapsesACTA PHYSIOLOGICA, Issue 1 2009Y. Takayasu Abstract Glutamate transporters play a critical role in the maintenance of low extracellular concentrations of glutamate, which prevents the overactivation of post-synaptic glutamate receptors. Four distinct glutamate transporters, GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3 and EAAT4, are distributed in the molecular layer of the cerebellum, especially near glutamatergic synapses in Purkinje cells (PCs). This review summarizes the current knowledge about the differential roles of these transporters at excitatory synapses of PCs. Data come predominantly from electrophysiological experiments in mutant mice that are deficient in each of these transporter genes. GLAST expressed in Bergmann glia contributes to the clearing of the majority of glutamate that floods out of the synaptic cleft immediately after transmitter release from the climbing fibre (CF) and parallel fibre (PF) terminals. It is indispensable to maintain a one-to-one relationship in synaptic transmission at the CF synapses by preventing transcellular glutamate spillover. GLT-1 plays a similar but minor role in the uptake of glutamate as GLAST. Although the loss of neither GLAST nor GLT-1 affects cerebellar morphology, the deletion of both GLAST and GLT-1 genes causes the death of the mutant animal and hinders the folium formation of the cerebellum. EAAT4 removes the low concentrations of glutamate that escape from uptake by glial transporters, preventing the transmitter from spilling over into neighbouring synapses. It also regulates the activation of metabotropic glutamate receptor 1 (mGluR1) in perisynaptic regions at PF synapses, which in turn affects mGluR1-mediated events including slow EPSCs and long-term depression. No change in synaptic function is detected in mice that are deficient in EAAC1. [source] Association of aldose reductase gene Z+2 polymorphism with reduced susceptibility to diabetic nephropathy in Caucasian Type 1 diabetic patientsDIABETIC MEDICINE, Issue 8 2004M. Lajer Abstract Aims The Z,2 allele of the (AC)n polymorphism in the aldose reductase gene (ALR2) confers increased risk of microvascular diabetic complications, whereas the Z+2 allele has been proposed to be a marker of protection. However data are conflicting. Therefore, we investigated whether this polymorphism is associated with diabetic nephropathy and retinopathy in Type 1 diabetes mellitus in a large case,control study and a family-based analysis. Methods A total of 431 Type 1 diabetic patients with diabetic nephropathy and 468 patients with longstanding Type 1 diabetes and persistent normoalbuminuria were genotyped for the case,control study. In addition, 102 case trios and 98 control trios were genotyped for a family-based study. Results Thirteen different alleles were identified. In the case,control study, the Z+2 allele frequency was significantly higher in the normoalbuminuric diabetic than in patients with diabetic nephropathy (0.17 vs. 0.11, P = 0.008), suggesting a protective function of the Z+2 allele. No significant increase in the frequency of the putative risk allele Z,2 was found in patients with diabetic nephropathy vs. controls (0.39 vs. 0.36). No association with diabetic retinopathy was found. Although the results of the transmission of the Z,2 and Z+2 alleles in the independent family-based study were consistent with the association study, the number of informative families was limited and thus differences were not statistically significant. Conclusions The Z+2 allele of the ALR2 promoter polymorphism is associated with a reduced susceptibility to diabetic nephropathy in Danish Type 1 diabetic patients, suggesting a minor role for the polyol pathway in the pathogenesis of diabetic kidney disease. No association of the ALR2 polymorphism with diabetic retinopathy was found. [source] Extreme events controlling erosion and sediment transport in a semi-arid sub-andean valleyEARTH SURFACE PROCESSES AND LANDFORMS, Issue 13 2002R. Coppus Abstract The importance of extreme events in controlling erosion and sediment transport in semi-arid areas has long been appreciated but in practice being by definition rare and episodic they are difficult to study. When they are observed this is frequently in catchments for which little data are available. Another difficulty is that even when catchments are being monitored the instruments that record discharge, sediment load and hillslope sediment fluxes perform inaccurately or unpredictably during extreme weather conditions. This paper describes slope and channel processes that were actually observed by the authors during a (at least) 1 : 30 year 30 minute event with a rainfall intensity of 240 mm h,1 in a second-order tributary of the Rio Camacho near Tarija in southern Bolivia. During the event, it could be observed how different tributary streams and slope sections contributed sediments and flow to the main channel. Evidence for these contributions did not survive the event, which has implications for both modelling and monitoring. Before the onset of the event open erosion plots were functioning on the slopes where rainfall and runoff were being measured. Rainfall experiments were used to obtain infiltration rates. The storm began with a moderate intensity of about 5 cm per hour but increased after 5 minutes to 30 cm per hour and continued for 30 minutes. At this time, the rainfall intensity greatly exceeded the infiltration capacity and water started draining the steep slopes. The ephemeral channel rapidly filled up with runoff. Erosion by hailstones was considerable. Provisionally, the discharge during peak runoff was estimated at 43·7 m3 s,1 (Manning equation). On the basis of sediment loads carried by previous storms, (average concentration of 21 g l,1) the total suspended load discharge during the storm would have been 15 ton ha,1. Within the ephemeral channel, 10 to 50 cm thick layers of coarse sediments were deposited. The collectors of the open erosion plots could not handle the large amounts of runoff and sediment and were completely filled to overflowing. Comparing these data with soil losses during less intense storms it can be concluded that extreme events largely contribute to erosion and sediment transport and that the majority of the rainstorms play only a minor role. The results also show how limited the values of rainfall experiments are in understanding geomorphic events. This makes modelling of erosion and soil losses a difficult and hazardous task. Copyright © 2002 John Wiley & Sons, Ltd. [source] 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP),induced mutagenesis in cultured Big BlueÔ rat mammary epithelial and fibroblast cellsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002Heather M. McDiarmid Abstract Epithelial cells are the primary site of carcinogenesis in most tissues, including the mammary gland. As an alternative to the study of mutation induction in whole tissues in vivo, we have established Big BlueÔ transgenic rat cell lines from the mammary epithelium (BBR/ME) and the mammary stroma (BBR/MFib), to permit a comparison of their mutagenic responses to carcinogens. We previously demonstrated their responsiveness to the alkylating agent N -ethyl- N -nitrosourea (ENU) (McDiarmid H et al. [2001]: Mutat Res 497:39,47). Here, we examined the responses of cultured epithelial and stromal cells to the protein pyrolysis product and mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). Rat hepatic S9 was used as a source of bioactivation enzymes. Mutant induction (cII locus) and clonogenic survival were measured as a function of PhIP concentration. PhIP mutagenicity was observed in the fibroblast cells, but the greater toxicity of PhIP to the epithelial cells prevented a definitive evaluation of mutagenicity. Since PhIP may be detoxified by conjugation with glutathione, we measured glutathione levels and glutathione- S -transferase expression and activities in both cell lines. The epithelial cells had higher glutathione- S -transferase enzyme activity and protein expression than did the fibroblast cell line. Because the epithelial cells were more sensitive to toxicity, glutathione conjugation evidently plays only a minor role in PhIP toxicity and mutagenicity in our cell lines. Environ. Mol. Mutagen. 39:245,253, 2002. © 2002 Wiley-Liss, Inc. [source] The role of alcohol and drugs in homicides in England and WalesADDICTION, Issue 8 2006Jenny Shaw SUMMARY Background The annual number of homicide convictions in England and Wales is increasing. Previous studies have highlighted the aetiological role of alcohol and drugs in homicide. Aims To examine rates of alcohol and drug misuse and dependence in people convicted of homicide; the role of alcohol and drugs in the offence; the social and clinical characteristics of alcohol- and drug-related homicides; and the social and clinical characteristics of patients with dual diagnosis who commit homicide. Methods A national clinical survey based on a 3-year (1996,9) consecutive sample of people convicted of homicide in England and Wales. Information on rates of alcohol and drug misuse/dependence, the role of alcohol and drugs in the offence and social and clinical characteristics of perpetrators were collected from psychiatric reports prepared for the court in homicide convictions. Detailed clinical information was gathered from questionnaires completed by mental health teams for those in contact with mental health services. Results Of the 1594 homicide perpetrators, more than one-third (42%) occurred in people with a history of alcohol misuse or dependence and 40% in people with a history of drug misuse or dependence. Alcohol or drug misuse played a contributory role in two-fifths of homicides. Alcohol played a major role in 52 (6%) and a minor role in 364 (39%) homicides. Drugs played a major role in six (1%) and a minor role in 138 (14%) homicides. Forty-two homicides (17%) were committed by patients with severe mental illness and substance misuse. Alcohol- and drug-related homicides were generally associated with male perpetrators who had a history of violence, personality disorders, mental health service contact and with stranger victims. Conclusions Substance misuse contributes to the majority of homicides in England and Wales. A public health approach to homicide would highlight alcohol and drugs before severe mental illness. [source] Fluctuating Asymmetry, Sexual Selection, and Survivorship in Male Dark-Winged DamselfliesETHOLOGY, Issue 9 2002Michelle L. Beck We examined fluctuating asymmetry and morphology as they relate to reproductive success, territoriality, and relative survivorship in the dark-winged damselfly Calopteryx maculata. Fluctuating asymmetry was not correlated with any aspect of morphology in males, but it did predict mating status in males. Mating males showed significantly lower levels of forewing asymmetry than did non-mating males holding adjacent territories. While fluctuating asymmetry did not relate to survivorship or resource holding ability, body size did. Larger males were able to hold territories longer and lived longer than smaller individuals. We suggest that size is of greater importance in this species with regards to fitness and that fluctuating asymmetry may play a minor role by impacting short-term mating success. [source] Angiotensin-converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in TaiwanEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2008C.-M. Chen Background and purpose:, This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case,control study. Methods:, Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. Results:, Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1,6.5, P = 0.02) was associated with female SDICH. Conclusions:, This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan. [source] Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma modelEXPERIMENTAL DERMATOLOGY, Issue 11 2006Lina Elzaouk Abstract:, Mesenchymal stem cells (MSCs) represent a new tool for delivery of therapeutic agents to tumor cells. In this study, we have evaluated the anti-tumor activity of human MSCs stably transduced with a retroviral vector expressing the cytokine interleukin-12 (IL-12) in a mouse melanoma model. Application of MSC(IL-12) but not control MSCs strongly reduced the formation of lung metastases of B16F10 melanoma cells. The activity of the MSC(IL-12) cells was dependent on the presence of natural killer (NK) cells in this experimental setting. Further, MSC(IL-12) cells elicited a pronounced retardation of tumor growth and led to prolonged survival when injected into established subcutaneous melanoma in a therapeutic regimen. The therapeutic effect of the MSC(IL-12) was in part mediated by CD8+ T cells, while NK cells and CD4+ T cells appeared to play a minor role. The anti-tumor effect of MSC(IL-12) cells was of similar efficiency as observed for application of naked plasmid DNA encoding IL-12. The presented data demonstrate that these two different strategies can induce a similar therapeutic anti-tumor efficacy in the mouse melanoma tumor model. [source] The effect of hfq on global gene expression and virulence in Neisseria gonorrhoeaeFEBS JOURNAL, Issue 19 2009Manuela Dietrich Hfq is an RNA chaperone that functions as a pleiotropic regulator for RNA metabolism in bacteria. In several pathogenic bacteria, Hfq contributes indirectly to virulence by binding to riboregulators that modulate the stability or translation efficiency of RNA transcripts. To characterize the role of Hfq in the pathogenicity of Neisseria gonorrhoeae, we generated an N. gonorrhoeae hfq mutant. Infectivity and global changes in gene expression caused by the hfq mutation in N. gonorrhoeae strain MS11 were analyzed. Transcriptional analysis using a custom-made N. gonorrhoeae microarray revealed that 369 ORFs were differentially regulated in the hfq mutant, MS11hfq, in comparison with the wild-type strain (202 were upregulated, and 167 were downregulated). The loss-of-function mutation in hfq led to pleiotropic phenotypic effects, including an altered bacterial growth rate and reduced adherence to epithelial cells. Twitching motility and microcolony formation were not affected. Hfq also appears to play a minor role in inducing the inflammatory response of infected human epithelial cells. Interleukin-8 production was slightly decreased, and activation of c-Jun N-terminal kinase, a mitogen-activated protein kinase, was reduced in MS11hfq- infected epithelial cells in comparison with wild type-infected cells. However, activation of nuclear factor kappa B, extracellular signal-regulated kinase 1/2 and p38 remained unchanged. The data presented suggest that Hfq plays an important role as a post-transcriptional regulator in N. gonorrhoeae strain MS11 but does not contribute significantly to its virulence in cell culture models. [source] Quantitative modeling of triacylglycerol homeostasis in yeast , metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growthFEBS JOURNAL, Issue 22 2008Jürgen Zanghellini Triacylglycerol metabolism in Saccharomyces cerevisiae was analyzed quantitatively using a systems biological approach. Cellular growth, glucose uptake and ethanol secretion were measured as a function of time and used as input for a dynamic flux-balance model. By combining dynamic mass balances for key metabolites with a detailed steady-state analysis, we trained a model network and simulated the time-dependent degradation of cellular triacylglycerol and its interaction with fatty acid and membrane lipid synthesis. This approach described precisely, both qualitatively and quantitatively, the time evolution of various key metabolites in a consistent and self-contained manner, and the predictions were found to be in excellent agreement with experimental data. We showed that, during pre-logarithmic growth, lipolysis of triacylglycerol allows for the rapid synthesis of membrane lipids, whereas de novo fatty acid synthesis plays only a minor role during this growth phase. Progress in triacylglycerol hydrolysis directly correlates with an increase in cell size, demonstrating the importance of lipolysis for supporting efficient growth initiation. [source] PCR profiling of ammonia-oxidizer communities in acidic soils subjected to nitrogen and sulphur depositionFEMS MICROBIOLOGY ECOLOGY, Issue 2 2007Christoph Stephan Schmidt Abstract Communities of ammonia-oxidizing bacteria (AOB) were characterized in two acidic soil sites experimentally subjected to varying levels of nitrogen and sulphur deposition. The sites were an acidic spruce forest soil in Deepsyke, Southern Scotland, with low background deposition, and a nitrogen-saturated upland grass heath in Pwllpeiran, North Wales. Betaproteobacterial ammonia-oxidizer 16S rRNA and ammonia monooxygenase (amoA) genes were analysed by cloning, sequencing and denaturing gradient gel electrophoresis (DGGE). DGGE profiles of amoA and 16S rRNA gene fragments from Deepsyke soil in 2002 indicated no effect of nitrogen deposition on AOB communities, which contained both Nitrosomonas europaea and Nitrosospira. In 2003, only Nitrosospira could be detected, and no amoA sequences could be retrieved. These results indicate a decrease in the relative abundance of AOB from the year 2002 to 2003 in Deepsyke soil, which may be the result of the exceptionally low rainfall in spring 2003. Nitrosospira -related sequences from Deepsyke soil grouped in all clusters, including cluster 1, which typically contains only sequences from marine environments. In Pwllpeiran soil, 16S rRNA gene libraries were dominated by nonammonia oxidizers and no amoA sequences were detectable. This indicates that autotrophic AOB play only a minor role in these soils even at high nitrogen deposition. [source] Glucose induction pathway regulates meiosis in Saccharomyces cerevisiae in part by controlling turnover of Ime2p meiotic kinaseFEMS YEAST RESEARCH, Issue 5 2008Misa Gray Abstract Several components of the glucose induction pathway, namely the Snf3p glucose sensor and the Rgt1p and Mth1p transcription factors, were shown to be involved in inhibition of sporulation by glucose. The glucose sensors had only a minor role in regulating transcript levels of the two key regulators of meiotic initiation, the Ime1p transcription factor and the Ime2p kinase, but a major role in regulating Ime2p stability. Interestingly, Rgt1p was involved in glucose inhibition of spore formation but not inhibition of Ime2p stability. Thus, the glucose induction pathway may regulate meiosis through both RGT1- dependent and RGT1- independent pathways. [source] Can C4 plants contribute to aquatic food webs of subtropical streams?FRESHWATER BIOLOGY, Issue 6 2003Joanne E. Clapcott Summary 1. Recent stable isotope studies have revealed that C4 plants play a minor role in aquatic food webs, despite their often widespread distribution and production. We compared the breakdown of C3 (Eucalyptus) and C4 (Saccharum and Urochloa) plant litter in a small rain forest stream and used laboratory feeding experiments to determine their potential contribution to the aquatic food web. 2. All species of litter broke down at a fast rate in the stream, although Urochloa was significantly faster than Eucalyptus and Saccharum. This was consistent with the observed higher total organic nitrogen of Urochloa compared with the other two species. 3. The breakdown of Urochloa and Saccharum was, however, not associated with shredding invertebrates, which were poorly represented in leaf packs compared with the native Eucalyptus. The composition of the invertebrate fauna in packs of Urochloa quickly diverged from that of the other two species. 4. Feeding experiments using a common shredding aquatic insect Anisocentropus kirramus showed a distinct preference for Eucalyptus over both C4 species. Anisocentropus was observed to ingest C4 plant litter, particularly in the absence of other choices, and faecal material collected was clearly of C4 origin, as determined by stable isotope analysis. However, the stable carbon isotope values of the larvae did not shift away from their C3 signature in any of the feeding trials. 5. These data suggest that shredders avoid the consumption of C4 plants, in favour of native C3 species that appear to be of lower food quality (based on C : N ratios). Lower rates of consumption and lack of assimilation of C4 carbon also suggest that shredders may have a limited ability to process this material, even in the absence of alternative litter sources. Large scale clearing of forest and vegetation for C4 crops such as sugarcane will undoubtedly have important consequences for stream ecosystem function. [source] Ecotype adaptation and acclimation of leaf traits to rainfall in 29 species of 16-year-old Eucalyptus at two common gardensFUNCTIONAL ECOLOGY, Issue 6 2006C. R. WARREN Summary 1Relationships of leaf traits with rainfall at the place of origin of seed (RPO) are a function of acclimation and adaptation. To disentangle these effects we studied 29 species of 16-year-old Eucalyptus at a productive and an unproductive common garden (mean annual increments of above-ground stem volume = 21 ± 11 and 8 ± 5 m3 ha,1 years,1, respectively). We tested three hypotheses: (i) leaf traits vary between sites, but relationships among them do not; (ii) relationships of leaf traits with RPO do not vary between sites; and (iii) ecotypes originating from low-rainfall areas allocate a small fraction of nitrogen to thylakoid proteins and Rubisco, and have small SLA, small and narrow leaves, and large water-use efficiency (WUE). 2Eleven leaf traits (leaf area, leaf thickness, leaf width/length, specific leaf area, fresh weight/dry weight, N, chlorophyll a/b, carotenoids/chlorophyll, thylakoid N%, Rubisco N%, WUE derived from 13C content) were measured in 1-year-old sun leaves. 3Site had a large effect on not only the absolute values of leaf traits, but also relationships between pairs of traits. There were 20 significant correlations between pairs of traits. Three of the correlations had different slopes between sites, while a further nine had different intercepts. Hence the majority of significant correlations were not independent of site. 4Leaf area and leaf width/length were the only traits related to RPO. There was no evidence that N allocation to Rubisco or thylakoid proteins was related to RPO, or that WUE was greater in ecotypes from dry areas. 5For Eucalyptus, and perhaps other genera, physiological leaf traits may play a minor role in adaptation to water availability. There is large phenotypic plasticity in many leaf traits affecting not only the absolute values of traits, but also relationships among them. [source] Precipitation of lead,zinc ores in the Mississippi Valley-type deposit at Trèves, Cévennes region of southern FranceGEOFLUIDS (ELECTRONIC), Issue 1 2006D. LEACH Abstract The Trèves zinc,lead deposit is one of several Mississippi Valley-type (MVT) deposits in the Cévennes region of southern France. Fluid inclusion studies show that the ore was deposited at temperatures between approximately 80 and 150°C from a brine that derived its salinity mainly from the evaporation of seawater past halite saturation. Lead isotope studies suggest that the metals were extracted from local basement rocks. Sulfur isotope data and studies of organic matter indicate that the reduced sulfur in the ores was derived from the reduction of Mesozoic marine sulfate by thermochemical sulfate reduction or bacterially mediated processes at a different time or place from ore deposition. The large range of ,34S values determined for the minerals in the deposit (12.2,19.2, for barite, 3.8,13.8, for sphalerite and galena, and 8.7 to ,21.2, for pyrite), are best explained by the mixing of fluids containing different sources of sulfur. Geochemical reaction path calculations, based on quantitative fluid inclusion data and constrained by field observations, were used to evaluate possible precipitation mechanisms. The most important precipitation mechanism was probably the mixing of fluids containing different metal and reduced sulfur contents. Cooling, dilution, and changes in pH of the ore fluid probably played a minor role in the precipitation of ores. The optimum results that produced the most metal sulfide deposition with the least amount of fluid was the mixing of a fluid containing low amounts of reduced sulfur with a sulfur-rich, metal poor fluid. In this scenario, large amounts of sphalerite and galena are precipitated, together with smaller quantities of pyrite precipitated and dolomite dissolved. The relative amounts of metal precipitated and dolomite dissolved in this scenario agree with field observations that show only minor dolomite dissolution during ore deposition. The modeling results demonstrate the important control of the reduced sulfur concentration on the Zn and Pb transport capacity of the ore fluid and the volumes of fluid required to form the deposit. The studies of the Trèves ores provide insights into the ore-forming processes of a typical MVT deposit in the Cévennes region. However, the extent to which these processes can be extrapolated to other MVT deposits in the Cévennes region is problematic. Nevertheless, the evidence for the extensive migration of fluids in the basement and sedimentary cover rocks in the Cévennes region suggests that the ore forming processes for the Trèves deposit must be considered equally viable possibilities for the numerous fault-controlled and mineralogically similar MVT deposits in the Cévennes region. [source] Analytical and 3-D numerical modelling of Mt. Etna (Italy) volcano inflationGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 2 2005A. Bonaccorso SUMMARY Since 1993, geodetic data obtained by different techniques (GPS, EDM, SAR, levelling) have detected a consistent inflation of the Mt. Etna volcano. The inflation, culminating with the 1998,2001 strong explosive activity from summit craters and recent 2001 and 2002 flank eruptions, is interpreted in terms of magma ascent and refilling of the volcanic plumbing system and reservoirs. We have modelled the 1993,1997 EDM and GPS data by 3-D pressurized sources to infer the position and dimension of the magma reservoir. We have performed analytical inversions of the observed deformation using both spheroidal and ellipsoidal sources embedded in a homogeneous elastic half-space and by applying different inversion methods. Solutions for these types of sources show evidence of a vertically elongated magma reservoir located 6 km beneath the summit craters. The maximum elevation of topography is comparable to such depth and strong heterogeneities are inferred from seismic tomography; in order to assess their importance, further 3-D numerical models, employing source parameters extracted from analytical models, have been developed using the finite-element technique. The deformation predicted by all the models considered shows a general agreement with the 1993,1997 data, suggesting the primary role of a pressure source, while the complexities of the medium play a minor role under elastic conditions. However, major discrepancies between data and models are located in the SE sector, suggesting that sliding along potential detachment surfaces may contribute to amplify deformation during the inflation. For the first time realistic features of Mt. Etna are studied by a 3-D numerical model characterized by the topography and lateral variations of elastic structure, providing a framework for a deeper insight into the relationships between internal sources and tectonic structures. [source] Distinct roles of protein kinase R and toll-like receptor 3 in the activation of astrocytes by viral stimuliGLIA, Issue 3 2007Pamela A. Carpentier Abstract Impaired immune surveillance and constitutive immunosuppressive properties make the central nervous system (CNS) a particular challenge to immune defense, and require that CNS-resident cells be capable of rapidly recognizing and responding to infection. We have previously shown that astrocytes respond to treatment with a TLR3 ligand, poly I:C, with the upregulation of innate immune functions. In the current study, we examine the activation of innate immune functions of astrocytes by Theiler's murine encephalomyelitis virus (TMEV), a picornavirus, which establishes a persistent infection in the CNS of susceptible strains of mice and leads to the development of an autoimmune demyelinating disease that resembles human multiple sclerosis. Astrocytes infected with TMEV are activated to produce type I interferons, the cytokine IL-6, and chemokines CCL2 and CXCL10. We further examined the mechanisms that are responsible for the activation of astrocytes in response to direct viral infection and treatment with poly I:C. We found that the cytoplasmic dsRNA-activated kinase PKR is important for innate immune responses to TMEV infection, but has no role in their induction by poly I:C delivered extracellularly. In contrast, we found that TLR3 has only a minor role in responses to TMEV infection, but is important for responses to poly I:C. These results highlight the differences between responses induced by direct, nonlytic virus infection and extracellular poly I:C. The activation of astrocytes through these different pathways has implications for the initiation and progression of viral encephalitis and demyelinating diseases such as multiple sclerosis. © 2006 Wiley-Liss, Inc. [source] Calcium signaling in invertebrate glial cellsGLIA, Issue 7 2006Christian Lohr Abstract Calcium signaling studies in invertebrate glial cells have been performed mainly in the nervous systems of the medicinal leech (Hirudo medicinalis) and the sphinx moth Manduca sexta. The main advantages of studing glial cells in invertebrate nervous systems are the large size of invertebrate glial cells and their easy accessibility for optical and electrophysiological recordings. Glial cells in both insects and annelids express voltage-gated calcium channels and, in the case of leech glial cells, calcium-permeable neurotransmitter receptors, which allow calcium influx as one major source for cytosolic calcium transients. Calcium release from intracellular stores can be induced by metabotropic receptor activation in leech glial cells, but appears to play a minor role in calcium signaling. In glial cells of the antennal lobe of Manduca, voltage-gated calcium signaling changes during postembryonic development and is essential for the migration of the glial cells, a key step in axon guidance and in stabilization of the glomerular structures that are characteristic of primary olfactory centers. © 2006 Wiley-Liss, Inc. [source] Physical activity for prevention of osteoporosis in patients with severe haemophilia on long-term prophylaxisHAEMOPHILIA, Issue 3 2010M. KHAWAJI Summary., Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long-term prophylaxis. The study group consisted of 38 patients with severe haemophilia (mean age 30.5 years). All patients received long-term prophylaxis to prevent bleeding. The bone density (BMD g cm,2) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X-ray absorptiometry. Physical activity was assessed using the self-report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density at lumber spine L1-L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects of physical activity and bone density at any other measured sites. With adequate long-term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role. These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis. [source] Interleukin-6 Induction by Helicobacter pylori in Human Macrophages is Dependent on PhagocytosisHELICOBACTER, Issue 3 2006Stefan Odenbreit Abstract Background:, The colonization of the gastric mucosa with Helicobacter pylori is accompanied by elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and IL-8. The aim of our study was to determine the mechanisms of IL-6 stimulation in phagocytes upon H. pylori infection. Materials and Methods:, We investigated the secretion of IL-6 by different professional phagocytes from murine and human origin, including granulocyte- and monocyte-like cells and macrophages derived from human peripheral blood monocytes (PBMCs). The influence of viability, phagocytosis, and the impact of different subcellular fractions of H. pylori bacteria were evaluated. Results:, IL-6 levels induced by H. pylori were low in cell lines derived from murine and human monocytes and in human granulocyte-like cells. By contrast, macrophages derived from human PBMCs were highly responsive to both H. pylori and Escherichia coli. IL-6 induction was blocked by inhibition of actin-dependent processes prior to infection with H. pylori, but not with E. coli or E. coli lipopolysaccharide (LPS). Using cell fractionation, the most activity was found in the H. pylori membrane. H. pylori LPS exhibited a 103 - to 104 -fold lower biologic activity than E. coli LPS, suggesting a minor role for toll-like receptor 4 (TLR4)-mediated signalling from the exterior. Conclusions:, From these data, we conclude that macrophages may be a major source of IL-6 in the gastric mucosa upon H. pylori infection. The IL-6 induction by H. pylori in these cells is a multifactorial process, which requires the uptake and presumably degradation of H. pylori bacteria. [source] Quantitative analysis of anti,hepatitis C virus antibody,secreting B cells in patients with chronic hepatitis C,HEPATOLOGY, Issue 1 2006Takeji Umemura To investigate the quantitative characteristics of humoral immunity in patients with hepatitis C, we established an enzyme-linked immunosorbent spot (ELISpot) assay for detection of anti,hepatitis C virus (HCV)-secreting B cells. Receiver operating characteristic curve analysis demonstrated 100% specificity and 58% to 92% sensitivity for detecting B-cell responses to NS5b, NS3, E2, and core antigens. The median sum of anti-HCV,secreting B cells to all HCV antigens tested was significantly higher in 39 patients with chronic hepatitis C (47.3 spot forming cells [SFCs]/106 peripheral blood mononuclear cells [PBMCs]) than in 9 recovered subjects (15.3 SFCs/106 PBMCs; P = .05) or 11 uninfected controls (5.3 SFCs/106 PBMCs; P < .001); the significant difference (P = .018) in chronic versus recovered patients was in reactivity to nonstructural antigens NS3 and NS5b. Anti-HCV immunoglubulin M (IgM),secreting B cells were also readily detected and persisted decades into HCV infection; there was no difference in IgM-positive cells between chronic and recovered patients. ELISpot reactivity to genotype 1,derived antigens was equivalent in patients of genotypes 1, 2, and 3. There was significant correlation between the numbers of anti-HCV IgG-secreting B cells and serum aminotransferase and to the level of circulating antibody. In conclusion, ELISpot assays can be adapted to study B-cell as well as T-cell responses to HCV. Measurement at the single-cell level suggests that humoral immunity plays a minor role in recovery from HCV infection and that B-cell immunity is strongest in those with persistent infection. (HEPATOLOGY 2005.) [source] Condensation of steam in the presence of air on a single tube and a tube bankINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 4 2003Adrian Briggs Abstract Data are presented for condensation of steam in cross-flow with and without the presence of air on the outside of a single tube and a bank of tubes. The tube bank consisted of ten staggered rows of two and one tubes per row. For pure steam the experimental results for both the single tube and tube bank gave good agreement with single-tube theory when account was taken of the reduction in vapour velocity due to condensation. There was some evidence, however, that condensate inundation may play a minor role in reducing heat-transfer coefficients on the lower tubes in the bank. For the case of condensation from steam,air mixtures, the single-tube data gave good agreement with theory. For condensation from steam,air mixtures on the bank of tubes, the data were significantly under predicted by single-tube theory, possibly because of mixing and re-circulation due to the complex flow pattern around the tubes. Copyright © 2003 John Wiley & Sons, Ltd. [source] The Role of Statistics in the Data Revolution?INTERNATIONAL STATISTICAL REVIEW, Issue 1 2001Jerome H. Friedman Summary The nature of data is rapidly changing. Data sets are becoming increasingly large and complex. Modern methodology for analyzing these new types of data are emerging from the fields of Data Base Managment, Artificial Intelligence, Machine Learning, Pattern Recognition, and Data Visualization. So far Statistics as a field has played a minor role. This paper explores some of the reasons for this, and why statisticians should have an interest in participating in the development of new methods for large and complex data sets. [source] European Integration and Migration Policy: Vertical Policy-making as Venue ShoppingJCMS: JOURNAL OF COMMON MARKET STUDIES, Issue 2 2000Virginie Guiraudon Since the beginning of the 1980s, migration and asylum policy in Europe has increasingly been elaborated in supranational forums and implemented by transnational actors. I argue that a venue-shopping framework is best suited to account for the timing, form and content of European co-operation in this area. The venues less amenable to restrictive migration control policy are national high courts, other ministries and migrant-aid organizations. Building upon pre-existing policy settings and developing new policy frames, governments have circumvented national constraints on migration control by creating transnational co-operation mechanisms dominated by law and order officials, with EU institutions playing a minor role. European transgovernmental working groups have avoided judicial scrutiny, eliminated other national adversaries and enlisted the help of transnational actors such as transit countries and carriers. [source] Burnout and physical and mental health among Swedish healthcare workersJOURNAL OF ADVANCED NURSING, Issue 1 2008Ulla Peterson Abstract Title.,Burnout and physical and mental health among Swedish healthcare workers Aim., This paper is a report of a study to investigate how burnout relates to self-reported physical and mental health, sleep disturbance, memory and lifestyle factors. Background., Previous research on the possible relationship between lifestyle factors and burnout has yielded somewhat inconsistent results. Most of the previous research on possible health implications of burnout has focused on its negative impact on mental health. Exhaustion appears to be the most obvious manifestation of burnout, which also correlates positively with workload and with other stress-related outcomes. Method., A cross-sectional study was conducted, using questionnaires sent to all employees in a Swedish County Council (N = 6118) in 2002. The overall response rate was 65% (n = 3719). A linear discriminant analysis was used to look for different patterns of health indicators and lifestyle factors in four burnout groups (non-burnout, disengaged, exhausted and burnout). Results., Self-reported depression, anxiety, sleep disturbance, memory impairment and neck- and back pain most clearly discriminated burnout and exhausted groups from disengaged and non-burnout groups. Self-reported physical exercise and alcohol consumption played a minor role in discriminating between burnout and non-burnout groups, while physical exercise discriminated the exhausted from the disengaged group. Conclusion., Employees with burnout had most symptoms, compared with those who experienced only exhaustion, disengagement from work or no burnout, and the result underlines the importance of actions taken to prevent and combat burnout. [source] Life history and fitness consequences of ectoparasitesJOURNAL OF ANIMAL ECOLOGY, Issue 2 2004Patrick S. Fitze Summary 1For iteroparous organisms life-history theory predicts a trade-off between current and future reproduction, and therefore the evolution of host responses to current parasite infestation that will maximize lifetime reproductive success. The parasite-induced variation in reproductive success is thus not the net result of parasite infestation alone, but the parasite-mediated outcome of optimal resource allocation among current and future reproductive events. Understanding the importance of parasites for the evolution of host life history therefore requires an experimental investigation of the effects of parasites over the host's life span. Such studies are currently scant. 2We manipulated the load of an ectoparasite, the hen flea (Ceratophyllus gallinae), in the nests of its most common host, the great tit (Parus major), over a period of 4 years and recorded, the components of current and future reproductive success including survival, divorce, breeding dispersal and various reproductive parameters. Finally we assessed, for females only as paternity of males was unknown, the lifetime reproductive success as a close correlate of Darwinian fitness. 3For current reproduction, our experiment demonstrates that parasites reduce current reproductive success via an increase in the probability of nest failure during incubation and the nestling period. In the presence of fleas, clutch size and the number of fledglings were reduced while the incubation and the nestling period were prolonged. Thus parasitism led to an increase in parental effort but nevertheless reduced current reproductive success. 4For future reproduction, the experiment shows that females breeding in infested nests dispersed over longer distances between breeding attempts. The divorce rate following infestation, the probability of breeding locally in the future and residual reproductive success were not affected significantly by ectoparasites. The study thus suggests that hen fleas play a minor role in shaping the trade-off between current and future reproduction. 5Lifetime reproductive success of females, measured as the total number of locally recruiting offspring over the 4 experimental years, was reduced significantly by ectoparasites. The negative effect of parasites arose by a reduction of the number of fledglings per breeding attempt rather than by a reduction of the number of breeding attempts. [source] Spatial and temporal variability in host use by Helicoverpa zea as measured by analyses of stable carbon isotope ratios and gossypol residuesJOURNAL OF APPLIED ECOLOGY, Issue 3 2010Graham Head Summary 1.,A high dose/refuge strategy has been adopted in the USA to manage the risk of Bacillus thuringiensis (Bt) resistance in target pests such as the cotton bollworm (CBW), Helicoverpa zea (Boddie) in transgenic Bt cotton Gossypium hirsutum L. Structured refuges, consisting of non-Bt cotton, have been a mandated part of this strategy to produce non-selected insects that are temporally and spatially synchronous with insects from the Bt crop, diluting Bt resistance alleles through mating. However, the bollworm is highly polyphagous and exploits a large number of crop and weedy hosts concurrently with Bt cotton. 2.,A study was carried out in five major US cotton-producing states during 2002 and 2003 using the ratios of 13C to 12C in bollworm moths to estimate the proportions of the population originating from C3 or C4 plants. A separate study measured gossypol residues in moths from four states in 2005 and 2006, enabling the identification of moths whose natal hosts were cotton rather than other C3 hosts. 3.,C4 hosts served as the principal source of bollworm moths from mid-to-late June to early September, depending on the state. Beginning in late August/early September and lasting 1,4 weeks, the majority of moths exhibited isotopic compositions characteristic of C3 hosts. During this period, however, the minimum percentage of moths that developed as larvae on C4 hosts was typically >25%. By mid-September and through October and November, the majority of the bollworm population exhibited C4 isotopic compositions. 4.,Between late June and early August, cotton-derived bollworm moths (moths with gossypol residues) comprised <1% of moths in all states, and remained below this level throughout the season in North Carolina. In other states, cotton-derived moths increased between early August and early September to peak at an average of 19·1% of all moths. 5.,Synthesis and applications.,Data on 13C/12C ratios and gossypol residues in CBW moths were used to assess the importance of structured non-Bt cotton refuges for the management of Bt resistance risk in H. zea. Weekly estimates of bollworm breeding on cotton, C3 plants other than cotton and C4 plants showed that, throughout the season, the majority of bollworm moths caught in pheromone traps adjacent to cotton fields did not develop as larvae on cotton. This result implies that management practices in cotton such as the use of structured cotton refuges will play a relatively minor role , particularly compared with maize Zea mays L. , in managing potential resistance to Bt cotton in populations of the CBW in the US Cotton Belt. [source] Paddlefish Polyodon spathula juveniles food searching behaviour evoked by natural food odourJOURNAL OF APPLIED ICHTHYOLOGY, Issue 6 2007A. O. Kasumyan Summary Using the behavioural bioassay, food search behaviour was investigated in paddlefish Polyodon spathula juveniles (2.3, 3.0, 5.0, 15.0 and 35.0 cm TL; and 16, 23, 35, 50 and 130 days post-hatch respectively) evoked by Daphnia water extracts. Main characteristics of this behaviour were increased swimming speed, sinking to the lower water layer, short and straight trajectories in the odour cloud and opening of the mouth. These responses were seldom clearly pronounced and had a fairly short time-pattern. Biting and snapping, common in food search by many other species, were never observed. Ability to respond to food odour developed at the beginning of exogenous feeding. Olfactory sensitivity of P. spathula to natural food extract was relatively low, 10,1,10,2 g L,1, 2,3 orders of magnitude lower than in some sturgeons. It was concluded that olfaction plays a minor role in the food search behaviour of paddlefish. [source] Bed articles for nursing care , state of the art in two German hospitalsJOURNAL OF CLINICAL NURSING, Issue 3 2004Thomas Boggatz MA Background., Bed articles are basic instruments for positioning. Research about this topic has concentrated on evidence for better practice. However, little is known about what practitioners really do. Aims and objectives., This study intended to identify the most common bed articles used for positioning in two German hospitals, and to determine the decision-maker for their application and the purposes and criteria for their choice. Methods., Nursing experts from 100 wards were interviewed with the help of a structured questionnaire and based on these data a list of the 10 most frequent devices was compiled. Results., Supporting the body position was the most frequent intervention performed by German nurses, mainly with the help of hydraulic beds, pillows and blankets. Nurses were the main decision-makers for the use of these bed articles. Their choice was mainly based on work experience and patients' desires. Guidelines and literature played a minor role in this process. Relevance to clinical practice., If nurses, despite the medical doctors' role as the main decision-maker in German hospitals, exert significant influence on this aspect of care, they can support their position by evidence-based practice. [source] Effects of resource competition and herbivory on plant performance along a natural productivity gradientJOURNAL OF ECOLOGY, Issue 2 2000René Van Der Wal Summary 1,The effects of resource competition and herbivory on a target species, Triglochin maritima, were studied along a productivity gradient of vegetation biomass in a temperate salt marsh. 2,Transplants were used to measure the impact of grazing, competition and soil fertility over two growing seasons. Three parts of the marsh were selected to represent different successional stages; Triglochin reached local dominance at intermediate biomass of salt-marsh vegetation. At each stage, three competition treatments (full plant competition, root competition only, and no competition) and three grazing treatments (full grazing, no grazing on Triglochin, and no grazing on Triglochin or neighbours) were applied to both seedlings and mature plants. 3,Competition and herbivory reduced biomass and flowering of Triglochin. The impact of grazing was strongest at the stage with the lowest biomass, while both herbivory and competition had a significant impact at the stage with the highest biomass. When plants were protected from direct herbivory, competition operated at all three successional stages. 4,Grazing reduced light competition when vegetation biomass was low or intermediate, but at high biomass there was competition for light even when grazing occurred. Herbivore exclusion increased the effects of plant competition. Except at low biomass, the negative impact of plant competition on Triglochin performance was greater than the positive effect of not being grazed. 5,Grazing played a minor role in seedling survival and establishment which were largely controlled by competitive and facilitative effects. 6,Once established, the persistence of Triglochin will be determined largely by grazing. Intense grazing in the younger marsh and increasing competition for light in the older marsh will restrict the distribution to sites with intermediate biomass. [source] | ||||||||||||||||||||||||||||||||||||||||