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Reduced Sensitivity (reduced + sensitivity)
Selected AbstractsContrasting effects of repeated summer drought on soil carbon efflux in hydric and mesic heathland soilsGLOBAL CHANGE BIOLOGY, Issue 10 2008ALWYN SOWERBY Abstract Current predictions of climate change include altered rainfall patterns throughout Europe, continental USA and areas such as the Amazon. The effect of this on soil carbon efflux remains unclear although several modelling studies have highlighted the potential importance of drought for carbon storage. To test the importance of drought, and more importantly repeated drought year-on-year, we used automated retractable curtains to exclude rain and produce repeated summer drought in three heathlands at varying moisture conditions. This included a hydric system limited by water-excess (in the UK) and two mesic systems with seasonal water limitation in Denmark (DK) and the Netherlands (NL). The experimental rainfall reductions were set to reflect single year droughts observed in the last decade with exclusion of rain for 2,3 months of the year resulting in a 20,26% reduction in annual rainfall and 23,38% reduction in mean soil moisture during the drought period. Unexpectedly, sustained reduction in soil moisture over winter (between drought periods) was also observed at all three sites, along with a reduction in the maximum water-holding capacity attained. Three hypotheses are discussed which may have contributed to this lack of recovery in soil moisture: hydrophobicity of soil organic matter, increased water use by plants and increased cracking of the soil. The responses of soil respiration to this change in soil moisture varied among the sites: decreased rates were observed at the water-limited NL and DK sites whilst they increased at the UK site. Reduced sensitivity of soil respiration to soil temperature was observed at soil moisture contents above 55% at the UK site and below 20% and 13% at the NL and DK sites, respectively. Soil respiration rates recovered to predrought levels in the NL and DK sites during the winter re-wetting period that indicates any change in soil C storage due to changes in soil C efflux may be short lived in these mesic systems. In contrast, in the hydric UK site after 2 years of drought treatment, the persistent reduction in soil moisture throughout the year resulted in a year-round increase in soil respiration flux, a response that accelerated over time to 40% above control levels. These findings suggest that carbon-rich soils with high organic matter content may act as a significant source of CO2 to the atmosphere following repeated summer drought. Nonrecovery of soil moisture and a persistent increase in soil respiration may be the primary mechanism underlying the reported substantial losses of soil carbon from UK organic soils over the last 20 years. These findings indicate that the water status of an ecosystem will be a critical factor to consider in determining the impact of drought on the soil carbon fluxes and storage. [source] A multi-sample design for assessing the comedolytic activity of topical productsINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2004H. Knaggs Synopsis Background:, Facial comedolytic studies allow testing of a maximum of two products. The upper back provides a larger area with a more uniform distribution of microcomedones for comedolytic studies. Objective:, To design a multi-sample method for assessing comedolytic activity of topical products on the back. The effect of season on product discrimination was also explored. Methods:, Three cleansing formulations (products B, C and D), a negative water control and 0.025% Retin-A® cream (positive control) were tested. Seven subjects were recruited in summer and nine in fall. Products were applied for 8 weeks, comedolysis was assessed by visually evaluating cyanoacrylate follicular biopsies taken at baseline and post-treatment. Results:, In all data sets (summer, fall and combined), sites treated with Retin-A® had a significantly lower number of microcomedones as compared to the negative water control. In addition, cleansers B and D showed a significant reduction from baseline in the fall and combined (summer and fall) data, but not in summer data alone indicating different responses to treatment during the year. Conclusions:, The design was sensitive enough to detect differences between cleansing formulations under normal washing conditions. Reduced sensitivity observed during summer suggests hot humid conditions may decrease the comedolytic performance of topical products. Résumé Arrière-plan:, Les études d'agents comédolytiques sur le visage permettent de tester un maximum de deux produits. La partie supérieure du dos offre une plus grande surface couverte d'une distribution plus uniforme de micro-comédons. Objectif:, Mettre au point une méthode multi échantillons permettant d'appréhender l'activité comédolytique de produits appliqués de façon topique sur le dos. L'influence de la saison sur la différenciation des produits a également étéétudiée. Méthode:, Trois formulations lavantes (B, C, D), l'eau en tant que témoin négatif, une crème contenant 0,025% de rétina-A® en tant que témoin positif ont été testées. Sept sujets ont été recrutés en été, neuf l'ont été en automne. Les produits ont été appliqués durant 8 semaines. La comédolyse a étéévaluée par observation visuelle de biopsies folliculaires au cyanoacrylate faite avant et après traitement. Résultat:, Dans chaque groupe de résultats (été, automne et cumulé), les zones traitées avec la rétina-A® possèdent un nombre de micro-comédons statistiquement plus faible, comparé au témoin négatif (l'eau). De plus, les produits de nettoyage B et D ont montré une diminution significative par rapport à la situation avant traitement en automne, ainsi qu'en situation cumulé (automne + été), mais pas en été. Ces résultats indiquent des réponses différentes au traitement durant l'année. Conclusion:, La méthode est assez sensible pour détecter la différence entre des formulations nettoyantes utilisées sous condition normale d'utilisation. La diminution de sensibilité observée en été laisse suggérer que des conditions climatiques chaudes et humides diminuent l'efficacité comédolytique des produits appliqués de façon topique. [source] Refractive group differences in accommodation microfluctuations with changing accommodation stimulusOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 1 2006Mhairi Day Abstract Purpose:, Microfluctuations of accommodation are known to increase in magnitude with increasing accommodation stimulus. Reduced sensitivity to blur in myopic subjects could also lead to increases in the magnitude of the microfluctuations. The aim of this study is to examine the effect of variations in accommodation stimulus upon the microfluctuations in different refractive groups. Methods:, Thirty-six subjects were divided into three groups depending upon their refractive error and age of onset of their myopia; 12 emmetropes (EMMs), 12 early onset myopes (EOMs) and 12 late-onset myopes (LOMs). Steady-state accommodation responses were recorded continuously for 2 min using the Shin-Nippon SRW-5000 autorefractor at a sampling rate of 52 Hz while viewing targets at accommodation stimuli levels of 0, 1, 2, 3 and 4 D in a Badal (+5 D) optical system. Results:, The EMMs and EOMs showed systematic increases in the root mean square (r.m.s.) value of the microfluctuations with increasing accommodation stimulus. In contrast, no systematic variation with accommodation stimulus was found for the LOMs. Power spectrum analysis demonstrated that increases in the size of the microfluctuations were mediated by increases in the power of the low frequency components of the accommodation response. Conclusions:, The magnitude of the microfluctuations in the EMMs and EOMs may be influenced primarily by accommodation response-induced zonular relaxation effects or to changes in the physical properties of the accommodation plant with increasing accommodation response. The LOMs may have an increased baseline neural blur threshold, which appears to modulate the magnitude of the accommodative microfluctuations for low accommodation levels. At higher accommodation demands, the changes in the physical properties of the accommodation plant or the zonular relaxation effects appear to exceed the blur threshold, and the known association between microfluctuations and accommodation stimulus level is restored. [source] Epidemiology of invasive pneumococcal infections in children aged 0,6 years in Denmark: a 19-year nationwide surveillance studyACTA PAEDIATRICA, Issue 2000MS Kaltoft The impact of the new pneumococcal conjugate vaccines on invasive disease burden in Danish children was evaluated by analysing the results from the last 19 years of a nationwide surveillance of invasive pneumococcal infections. During 1981,1999, the Streptococcus Unit at Statens Serum Institut, Copenhagen, received 1123 invasive pneumococcal isolates from children aged 0,6 years. Nearly 72% (71.8%) of the pneumococcal isolates were from children aged <2 y. The median ages of children with pneumococcal meningitis and bacteraemia were 10.2 mo and 15.9 mo, respectively. The incidence of pneumococcal meningitis remained stable during the study period. The mean annual incidence rates of pneumococcal meningitis among children aged <1, <2, and <7 years were 17.4, 12.4, and 4.3 per 100000, respectively, during 1981,1999 (overlapping age groups are used throughout this article to facilitate the comparison of incidence data from different countries or among different studies). The annual incidence of pneumococcal bacteraemia increased from 1981 to 1996, after which a slight fall was noted. During the last six years of the study period, the mean annual incidence rates of bacteraemia were 30.1, 32.5, and 14.0 per 100000 children aged <1, <2, and <7 years. In the 1990s, pneumococcal isolates with reduced sensitivity to penicillin (0,5% each year) and erythromycin (7.4% in 1999) emerged as a cause of invasive infections in children aged 0,6 years in Denmark. During 1981,1999, 10 serotypes (1, 4, 6A, 6B, 7F, 9V, 14, 18C, 19F, 23F) caused 82% of invasive infections in Danish children. Importantly, no significant temporal changes in overall serotype distribution or differences in serotype distributions between girls and boys could be documented during the study period. Conclusion: According to the Kaiser Permanente trial, the 7-, 9-, and 11-valent pneumococcal conjugate vaccines will probably cover around 60%, 70%, and 80%, respectively, of all invasive pneumococcal infections in Danish children aged 0,6 y, corresponding to 12,14 episodes of meningitis and 40,60 episodes of bacteraemia per year. [source] Flow cytometry antibody screening using pooled red cells,CYTOMETRY, Issue 2 2010Dong Il Won Abstract Background: For red cell alloantibody screening, the column agglutination technique (CAT) is used extensively, and flow cytometry (FC) screening has recently been demonstrated to be accurate, rapid, and cost effective. We attempted to determine whether the high sensitivity of FC allows pooling of screening red cells, which is generally not an acceptable technique in CAT. Methods: For FC screening, a commercial two-cell screening panel was utilized for the preparation of individual cells (CSi), as well as pooled cells diluted 1 in 2 (CSp), and 1 in 3 (CS1/3). Another panel was pooled from 120 randomly selected group O donors (RSp). Results: Comparing the endpoint titrations of serial dilutions, CS1/3 was found to be one dilution, on the average, less sensitive than CSi. In 33 CAT-positive patient samples, the sensitivities of CSi and CSp did not differ significantly without polyethylene glycol (PEG) (30/33, 26/33, respectively, P = 0.125), although they did differ significantly with PEG (32/33, 25/33, respectively, P = 0.016). The percentages of reactive cells among the total cells from RSp were roughly proportional to the relevant antigen frequencies of the local donors. Conclusions: A trend toward reduced sensitivity was observed using pooled red cells, even via FC. Pooled cells from randomly selected group O donors may be employed as another method by which the characteristics of known antibodies might be assessed. © 2009 Clinical Cytometry Society [source] PRECLINICAL STUDY: Electroacupuncture treatment reverses morphine-induced physiological changes in dopaminergic neurons within the ventral tegmental areaADDICTION BIOLOGY, Issue 4 2009Ling Hu ABSTRACT Chronic morphine administration decreases the size of dopamine (DA) neurons in the ventral tegmental area (VTA). These transient morphological changes are accompanied by a reduced sensitivity of morphine-induced conditioned place preference (CPP) after chronic exposure to the drug. In this study we examined alterations in the firing rate of DAergic neurons by means of extracellular recording following chronic morphine exposure and applied 100 Hz electroacupuncture (EA) treatment to reverse the reduced firing rate of these neurons. In the first set of experiments we show that in rats, which received chronic morphine treatment for 14 days, a small dose of morphine was not able to induce a CPP response anymore. However, the sensitivity to morphine was reinstated by consecutive EA treatment for 10 days. The electrophysiological response of VTA DA neurons to morphine was markedly reduced in chronic morphine-treated rats compared to saline-treated controls. A substantial recovery of the reactivity of VTA DA neurons to morphine was observed in rats that received 100 Hz EA for 10 days. Our findings suggest that 100 Hz EA is a potential therapy for the treatment of opiate addiction by normalizing the activity of VTA DA neurons. [source] Hepatitis B virus markers in anti-HBc only positive individuals,JOURNAL OF MEDICAL VIROLOGY, Issue 3 2001Bernard Weber Abstract Isolated reactivity to hepatitis B virus (HBV) core antigen (anti-HBc) is observed relatively frequently in immunocompromised individuals, intravenous drug abusers (IVDA), and in the presence of HCV infection. The reason for the lack of HBsAg is not clear. The aim of the present study was to investigate which factors (genetic variability of S gene, low-level HBsAg, and immune complexes may be responsible for the failure of HBsAg detection with commercial HBsAg screening assays. Dilution series of two recombinant HBsAg escape mutants and dilutions of serum samples from chronic HBV carriers with multiple insertions in the a determinant and different HBsAg subtypes were tested with a highly sensitive assay that detects wild-type HBsAg (Elecsys HBsAg, Roche Diagnostics, Penzberg, Germany) and two assays that detect HBV wild-type and escape mutants (Murex HBsAg Version 3, Murex and Enzygnost HBsAg 5.0, Dade Behring, Marburg, Germany). Elecsys HBsAg showed in comparison to Murex HBsAg Version 3 and Enzygnost HBsAg 5.0 a reduced sensitivity for escape mutant detection. On the other hand, the best performance for HBsAg subtype detection was obtained with Elecsys HBsAg. In the second part of the study, a selected panel of isolated anti-HBc reactive (n,=,104) serum samples (AxSYM Core) was submitted to testing by Elecsys HBsAg, Murex HBsAg Version 3, Enzygnost HBsAg 5.0, and HBsAg detection after immune complex dissociation (ICD) and anti-HBs determination with two different assays (AxSYM Ausab and Elecsys Anti-HBs). To assess the specificity of anti-HBc test results, all the samples were tested by a second anti-HBc assay (Elecsys Anti-HBc). Quantitative HBV DNA detection was undertaken with a commercially available HBV PCR assay (Amplicor HBV Monitor). HCV infection was present in 65.4% of anti-HBc only reactive individuals. Five AxSYM Core positive samples were negative by Elecsys Anti-HBc. Overall, 15 (14.4%) AxSYM Ausab negative samples gave positive results with Elecsys Anti-HBs (median value: 21 IU/ml). No low-level HBsAg carrier was detected among the isolated anti-HBc reactive individuals with Elecsys HBsAg. There was no evidence for the presence of immune complexes. Only one sample was repeatedly reactive by the Murex HBsAg, suggesting that the a mutant form of HBsAg was responsible for the isolated anti-HBc reactivity, however neutralisation assay was not interpretable and HBV DNA PCR was negative. Fifteen (14.4%) anti-HBc only positive individuals were HBV DNA carriers with concentrations ranging from 800 to more than >4,000,000 copies of viral DNA/ml. In conclusion, the most probable explanations for isolated anti-HBc reactivity in our study group are a possible interference of HBsAg synthesis by HCV infection (65.4%) and divergence of results of anti-HBs assays (14.4%). There is no evidence for the presence of low-level HBsAg carriers and immune complexes. HBsAg mutants cannot be excluded definitively by the test strategy used in the present evaluation. J. Med. Virol. 64:312,319, 2001. © 2001 Wiley-Liss, Inc. [source] Nociceptive and behavioural sensitisation by protein kinase C, signalling in the CNSJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Kristof Van Kolen Abstract Despite the apparent homology in the protein kinase C (PKC) family, it has become clear that slight structural differences are sufficient to have unique signalling properties for each individual isoform. For PKC, in depth investigation of these aspects revealed unique actions in the CNS and lead to development of specific modulators with clinical perspective. In this review, we describe to which extent PKC, is distinct from other isoforms on the level of tissue expression and protein structure. As this kinase is highly expressed in the brain, we outline three main aspects of PKC, signalling in the CNS. First, its ability to alter the permeability of N-type Ca2+ channels in dorsal root ganglia has been shown to enhance nociception. Secondly, PKC, increases anxiety by diminishing GABAAR-induced inhibitory post-synaptic currents in the prefrontal cortex. Another important aspect of the latter inhibition is the reduced sensitivity of GABAA receptors to ethanol, a mechanism potentially contributing to abuse. A third signalling cascade improves cognitive functions by facilitating cholinergic signalling in the hippocampus. Collectively, these findings point to a physical and behavioural sensitising role for this kinase. [source] NSF binds calcium to regulate its interaction with AMPA receptor subunit GluR2JOURNAL OF NEUROCHEMISTRY, Issue 6 2007Jonathan G. Hanley Abstract N -ethylmaleimide-sensitive fusion protein (NSF) is essential for numerous Ca2+ -triggered vesicle trafficking events. It functions as a molecular chaperone to regulate trafficking protein complexes such as the soluble NSF attachment protein (SNAP) receptor complex and the ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-protein interacting with C-kinase (PICK1) complex. AMPAR trafficking is fundamental to processes of synaptic plasticity, which may underlie learning and memory. Changes in synaptic strength brought about by AMPAR trafficking are triggered by a post-synaptic influx of Ca2+, which may have numerous molecular targets including PICK1. NSF binds AMPAR subunit glutamate receptor subunit 2 (GluR2) and functions to maintain receptors at the synapse. In this study, it was showed that NSF is a Ca2+ -binding protein and that GluR2,NSF interactions are inhibited by the presence of 15 ,mol/L Ca2+. NSF Ca2+ -binding is reciprocally inhibited by the presence of GluR2 C-terminus. Mutant of NSF that binds Ca2+ with reduced affinity and binds GluR2 with reduced sensitivity to Ca2+ was identied. In addition, the interaction of ,SNAP with PICK1 is sensitive to Ca2+. This study demonstrates that the GluR2-NSF-,SNAP-PICK1 complex is regulated directly by Ca2+, allowing for the transduction of Ca2+ signals into concerted alterations in protein,protein interactions to bring about changes in AMPAR trafficking during synaptic plasticity. [source] Opioids in neuropathic painJOURNAL OF NEUROCHEMISTRY, Issue 2003R. Przew Neuropathic pain in human appears not to be opioid-resistant but only reduced sensitivity to systemic opioids is observed in this condition. We studied the contribution of central and peripheral mu-opioid receptors to the antinociception in rats with a spinal nerve ligation-induced neuropathy. Results of the present study indicate that both spinal and peripheral opioid receptors may contribute to the opioid-induced antinociception in the neuropathy. Further, mu-opioid peptide ligands (DAMGO and endomorphins) are more effective than opioid alkaloids in relieving of neuropathic pain. Moreover, reduction of the mu-opioid antinociceptive potency appears to be due to the fact that nerve injury reduced expression of mu-opioid receptors in the spinal ganglia. Identification of the molecular mechanisms involved may be of importance to the understanding of the molecular mechanism of opioid action in neuropathic pain, as well as to the development of better and more effective treatment of neuropathic pain in humans. [source] Hypothalamic-Pituitary-Adrenal Axis Abnormalities in Response to Deletion of 11,-HSD1 is Strain-DependentJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2009R. N. Carter Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity underlie differential vulnerability to neuropsychiatric and metabolic disorders, although the basis of this variation is poorly understood. 11,-Hydroxysteroid dehydrogenase type 1 (11,-HSD1) has previously been shown to influence HPA axis activity. 129/MF1 mice null for 11,-HSD1 (129/MF1 HSD1,/,) have greatly increased adrenal gland size and altered HPA activity, consistent with reduced glucocorticoid negative feedback. On this background, concentrations of plasma corticosterone and adrenocorticotrophic hormone (ACTH) were elevated in unstressed mice, and showed a delayed return to baseline after stress in HSD1-null mice with reduced sensitivity to exogenous glucocorticoid feedback compared to same-background genetic controls. In the present study, we report that the genetic background can dramatically alter this pattern. By contrast to HSD1,/, mice on a 129/MF1 background, HSD1,/, mice congenic on a C57Bl/6J background have normal basal plasma corticosterone and ACTH concentrations and exhibit normal return to baseline of plasma corticosterone and ACTH concentrations after stress. Furthermore, in contrast to 129/MF1 HSD1,/, mice, C57Bl/6J HSD1,/, mice have increased glucocorticoid receptor expression in areas of the brain involved in glucocorticoid negative feedback (hippocampus and paraventricular nucleus), suggesting this may be a compensatory response to normalise feedback control of the HPA axis. In support of this hypothesis, C57Bl/6J HSD1,/, mice show increased sensitivity to dexamethasone-mediated suppression of peak corticosterone. Thus, although 11,-HSD1 appears to contribute to regulation of the HPA axis, the genetic background is crucial in governing the response to (and hence the consequences of) its loss. Similar variations in plasticity may underpin inter-individual differences in vulnerability to disorders associated with HPA axis dysregulation. They also indicate that 11,-HSD1 inhibition does not inevitably activate the HPA axis. [source] Selected Line Difference in the Effects of Ethanol Dependence and Withdrawal on Allopregnanolone Levels and 5,-Reductase Enzyme Activity and ExpressionALCOHOLISM, Issue 12 2009Michelle A. Tanchuck Background:, Allopregnanolone (ALLO) is a progesterone derivative that rapidly potentiates ,-aminobutyric acidA (GABAA) receptor-mediated inhibition and modulates symptoms of ethanol withdrawal. Because clinical and preclinical data indicate that ALLO levels are inversely related to symptoms of withdrawal, the present studies determined whether ethanol dependence and withdrawal differentially altered plasma and cortical ALLO levels in mice selectively bred for differences in ethanol withdrawal severity and determined whether the alterations in ALLO levels corresponded to a concomitant change in activity and expression of the biosynthetic enzyme 5,-reductase. Methods:, Male Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mice were exposed to 72 hours ethanol vapor or air and euthanized at select times following removal from the inhalation chambers. Blood was collected for analysis of ALLO and corticosterone levels by radioimmunoassay. Dissected amygdala, hippocampus, midbrain, and cortex as well as adrenals were examined for 5,-reductase enzyme activity and expression levels. Results:, Plasma ALLO was decreased significantly only in WSP mice, and this corresponded to a decrease in adrenal 5,-reductase expression. Cortical ALLO was decreased up to 54% in WSP mice and up to 46% in WSR mice, with a similar decrease in cortical 5,-reductase activity during withdrawal in the lines. While cortical gene expression was significantly decreased during withdrawal in WSP mice, there was a 4-fold increase in expression in the WSR line during withdrawal. Hippocampal 5,-reductase activity and gene expression was decreased only in dependent WSP mice. Conclusions:, These results suggest that there are line and brain regional differences in the regulation of the neurosteroid biosynthetic enzyme 5,-reductase during ethanol dependence and withdrawal. In conjunction with the finding that WSP mice exhibit reduced sensitivity to ALLO during withdrawal, the present results are consistent with the hypothesis that genetic differences in ethanol withdrawal severity are due, in part, to modulatory effects of GABAergic neurosteroids such as ALLO. [source] In vivo diffusion tensor imaging of the human optic nerve: Pilot study in normal controlsMAGNETIC RESONANCE IN MEDICINE, Issue 2 2006C.A.M. Wheeler-Kingshott Abstract Diffusion tensor imaging (DTI) of the optic nerve (ON) was acquired in normal controls using zonally oblique multislice (ZOOM) DTI, which excites a small field of view (FOV) using a fast sequence with a shortened EPI echo train. This combines the benefit of low sensitivity to motion (due to the single-shot acquisition used), with the additional advantage of reduced sensitivity to magnetic field susceptibility artifacts. Reducing the bright signal from the fat and cerebrospinal fluid (CSF) surrounding the nerve are key requirements for the success of the presented method. Measurements of mean diffusivity (MD) and fractional anisotropy (FA) indices were made in a coronal section of the middle portion of the optic nerve (ON) in the right (rON) and left (lON) ONs. The average values across 10 healthy volunteers were FArON = 0.64 ± 0.09 and FAlON = 0.57 ± 0.10, and MDrON = (1173 ± 227) × 10,6 mm2 s,1 and MDlON = (1266 ± 170) × 10,6 mm2 s,1. Measurements of the principal eigenvalue of the DT and its orthogonal component were also in agreement with those expected from a highly directional structural organization. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] Resistance to carbosulfan in Anopheles gambiae from Ivory Coast, based on reduced sensitivity of acetylcholinesteraseMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2003R. N'Guessan Abstract. Resistance to carbosulfan, a carbamate insecticide, was detected in field populations of the malaria vector mosquito Anopheles gambiae Giles (Diptera: Culicidae) from two ecologically contrasted localities near Bouaké, Ivory Coast: rural M'bé with predominantly M form of An. gambiae susceptible to pyrethroids; suburban Yaokoffikro with predominantly S form of An. gambiae highly resistant to pyrethroids (96% kdr). The discriminating concentration of 0.4% carbosulfan (i.e. double the LC100) was determined from bioassays with the susceptible An. gambiae Kisumu strain. Following exposure to the diagnostic dosage (0.4% carbosulfan for 1 h), mortality rates of female An. gambiae adults (reared from larvae collected from ricefields) were 62% and 29% of those from M'bé and Yaokoffikro, respectively, 24 h post-exposure. Exposure for 3 min to netting impregnated with the operational dosage of carbosulfan 200 mg/m2 gave mortality rates of 88% of those from M'bé and only 12.2% for Yaokoffikro. In each case the control untreated mortality rate was insignificant. Biochemical assays to detect possible resistance mechanism(s) revealed the presence of insensitive AChE in populations of An. gambiae at both localities, more prevalent in the S form at Yaokoffikro than in M form at M'bé, as expected from bioassays results. Our study demonstrates the need to monitor carbamate resistance among populations of the An. gambiae complex in Africa, to determine its spread and anticipate vector control failure if these insecticides are employed. [source] Mutations in the CYP51 gene correlated with changes in sensitivity to sterol 14,-demethylation inhibitors in field isolates of Mycosphaerella graminicolaPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2007Pierre Leroux Abstract In France, as in many other European countries, Mycosphaerella graminicola (Fuckel) Schröter in Cohn (anamorph Septoria tritici), the causal agent of wheat leaf blotch, is controlled by foliar applications of fungicides. With the recent generalization of resistance to strobilurins (QoIs), reliable control is mainly dependent upon inhibitors of sterol 14,-demethylation (DMIs). To date, strains with reduced sensitivity to DMIs are widespread, but disease control using members of this class of sterol biosynthesis inhibitors has not been compromised. In this study, sensitivity assays based on in vitro effects of fungicides towards germ-tube elongation allowed the characterization of seven DMI-resistant phenotypes. In four of them, cross-resistance was not observed between all tested DMIs; this characteristic concerned prochloraz, triflumizole, fluquinconazole and tebuconazole. Moreover, the highest resistant factors to most DMIs were found only in recent isolates; according to their response towards prochloraz, they were classified into two categories. Molecular studies showed that DMI resistance was associated with mutations in the CYP51 gene encoding the sterol 14,-demethylase. Alterations at codons 459, 460 and 461 were related to low resistance levels, whereas, at position 381, a valine instead of an isoleucine, in combination with the previous changes, determined the highest resistance levels to all DMIs except prochloraz. Mutations in codons 316 and 317 were also found in some isolates exhibiting low resistance factors towards most DMIs. Copyright © 2007 Society of Chemical Industry [source] Sensitivity of Uncinula necator to quinoxyfen: evaluation of isolates selected using a discriminatory dose screenPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 6 2006Elizabeth A Green Abstract Quinoxyfen is a protectant fungicide that provides excellent control of many powdery mildew diseases. Prior to the launch of quinoxyfen in vines in 1998, a leaf disc sporulation assay was developed to assess the sensitivity of Uncinula necator (Schw) Burr to quinoxyfen. The distribution of EC50 values from 56 monoconidial U. necator isolates collected from six countries between 1993 and 1996 was found to range from less than 0.03 to 2.6 mg litre,1. Although this range of EC50 values was quite broad, the inability to establish a minimum inhibitory concentration (MIC) for the majority of these isolates, including some of the most sensitive isolates, was unexpected and suggested that the leaf disc sporulation assay may not reflect the true activity of quinoxyfen in the field. In 2002, following the detection of isolates resistant to quinoxyfen in Blumeria graminis Speer f. sp. tritici Marchal, a discriminatory dose screen was developed to test large populations of U. necator for rare individuals with significantly decreased sensitivity to quinoxyfen. The individual isolates selected by this method were tested with the leaf disc sporulation assay. Although a significant proportion were found to have EC50 values within the original distribution, a number of isolates with apparent reduced sensitivity to quinoxyfen were also detected. However, further examination of a subset of these isolates in a more quantitative germination/germ tube elongation inhibition assay suggested that the magnitude of the reduction in sensitivity for some of these isolates was much less than predicted by the sporulation assay. Thus, for an exclusively protectant fungicide such as quinoxyfen, a leaf disc sporulation assay may overestimate the frequency of isolates with significantly reduced sensitivity and the threat of decreased performance due to resistance. Copyright © 2006 Society of Chemical Industry [source] Engineering photosynthetic light capture: impacts on improved solar energy to biomass conversionPLANT BIOTECHNOLOGY JOURNAL, Issue 6 2007Jan H. Mussgnug Summary The main function of the photosynthetic process is to capture solar energy and to store it in the form of chemical ,fuels'. Increasingly, the photosynthetic machinery is being used for the production of biofuels such as bio-ethanol, biodiesel and bio-H2. Fuel production efficiency is directly dependent on the solar photon capture and conversion efficiency of the system. Green algae (e.g. Chlamydomonas reinhardtii) have evolved genetic strategies to assemble large light-harvesting antenna complexes (LHC) to maximize light capture under low-light conditions, with the downside that under high solar irradiance, most of the absorbed photons are wasted as fluorescence and heat to protect against photodamage. This limits the production process efficiency of mass culture. We applied RNAi technology to down-regulate the entire LHC gene family simultaneously to reduce energy losses by fluorescence and heat. The mutant Stm3LR3 had significantly reduced levels of LHCI and LHCII mRNAs and proteins while chlorophyll and pigment synthesis was functional. The grana were markedly less tightly stacked, consistent with the role of LHCII. Stm3LR3 also exhibited reduced levels of fluorescence, a higher photosynthetic quantum yield and a reduced sensitivity to photoinhibition, resulting in an increased efficiency of cell cultivation under elevated light conditions. Collectively, these properties offer three advantages in terms of algal bioreactor efficiency under natural high-light levels: (i) reduced fluorescence and LHC-dependent heat losses and thus increased photosynthetic efficiencies under high-light conditions; (ii) improved light penetration properties; and (iii) potentially reduced risk of oxidative photodamage of PSII. [source] Changes in fungicide sensitivity and relative species abundance in Oculimacula yallundae and O. acuformis populations (eyespot disease of cereals) in Western EuropePLANT PATHOLOGY, Issue 3 2008S. Parnell Changing fungicide sensitivities in populations of Oculimacula yallundae and O. acuformis, the species responsible for cereal eyespot in Western Europe, were determined over a 17 year period between 1984 and 2000. The data were collected by Aventis Crop Science as part of their long-term survey to monitor changes in sensitivity to prochloraz and the methyl benzimidazole carbamate (MBC) fungicides in eyespot populations. The results show evidence for reduced sensitivity to both fungicides over the period of the survey. The decline in MBC sensitivity is in agreement with reports of practical resistance (a detectable loss of disease control in the field) to this fungicide which were widely reported from the mid 1980s onward. Prochloraz sensitivity was more complex, with the emergence of a higher resistance category of isolates in the late 1980s and early 1990s which then decreased in frequency towards the end of the survey. This may be partly explained by the introduction and increased use of cyprodinil in the mid 1990s. Although all trends were similar across Europe, differences were observed between the two eyespot species. A higher frequency of O. yallundae isolates showed decreased sensitivity to MBC, whereas decreased sensitivity to prochloraz was at a higher frequency in O. acuformis populations. The relative abundance of the two eyespot species was influenced by their differential levels of fungicide sensitivity, with the ratio increasing toward the species with the highest level of resistance to the prevailing fungicide. [source] The Influence of Testosterone Combined with a PDE5-inhibitor on Cognitive, Affective, and Physiological Sexual Functioning in Women Suffering from Sexual DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2009Flip Van Der Made MD ABSTRACT Introduction., Women with female sexual dysfunction have a reduced sensitivity to sexual stimuli. Activation of central mechanisms may open a window for phosphodiesterase type 5 inhibitors (PDE5) to be effective; as a consequence, the combination of testosterone and a PDE5 inhibitor will restore sexual function. Aim., To demonstrate that the combination of testosterone and vardenafil will increase the sensitivity for sexual stimuli and will improve the desire and arousal components of the sexual response. Methods., In a double-blind randomly assigned placebo-controlled crossover design, 28 women with desire and/or arousal disorder underwent four different drug treatments on four separate experimental days. A masked version of the emotional Stroop task with sexual and nonsexual words was used to measure sensitivity for sexual content. Neutral and erotic film fragments were used to determine genital,physiological and subjective reactions. Main Outcome Measures., A masked version of the emotional Stroop task, vaginal pulse amplitude. For subjective measurement, responses were collected continuously with a lever and two self-report measures were used. Results., In two subgroups, which were differentiated on the basis of their initial preconscious attentional bias for sexual cues, a different sexual response profile was found. In an initially low-attention group, preconscious attentional bias for sexual cues increased under the testosterone condition. In these women, the combination of testosterone and vardenafil caused an improvement in genital response and subjective indices of sexual functioning. In the group that had initially a high attention for sexual cues, preconscious attentional bias for sexual cues decreased under the condition of testosterone. In these women, the combination of testosterone and vardenafil had no effect on any of the indices of their sexual functioning. Conclusion., In women suffering from low sexual desire,associated with low attention for sexual cues,the combination of testosterone and vardenafil may be a promising new treatment. van der Made F, Bloemers J, Yassem WE, Kleiverda G, Everaerd W, van Ham D, Olivier B, Koppeschaar H, and Tuiten A. The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. J Sex Med 2009;6:777,790. [source] Arabidopsis mitogen-activated protein kinase MPK12 interacts with the MAPK phosphatase IBR5 and regulates auxin signalingTHE PLANT JOURNAL, Issue 6 2009Jin Suk Lee Summary Mitogen-activated protein kinase (MAPK) phosphatases are important negative regulators in the MAPK signaling pathways responsible for many essential processes in plants, including development, stress management and hormonal responses. A mutation in INDOLE-3-BUTYRIC ACID-RESPONSE5 (IBR5), which is predicted to encode a dual-specificity MAPK phosphatase, was previously reported to confer reduced sensitivity to auxin and ABA in Arabidopsis roots. To further characterize IBR5, and to understand how it might help integrate MAPK cascades with hormone signaling, we searched for IBR5-interacting MAPKs. Yeast two-hybrid assays, in vitro binding assays and in vivo protein co-immunoprecipitation studies demonstrated that MPK12 and IBR5 are physically coupled. The C-terminus of MPK12 appears to be essential for its interaction with IBR5, and in vitro dephosphorylation and immunocomplex kinase assays indicated that activated MPK12 is efficiently dephosphorylated and inactivated by IBR5. MPK12 and IBR5 mRNAs are both widely expressed across Arabidopsis tissues, and at the subcellular level each protein is predominantly localized in the nucleus. In transgenic plants with reduced expression of the MPK12 gene, root growth is hypersensitive to exogenous auxins, but shows normal ABA sensitivity. MPK12 suppression in an ibr5 background partially complements the ibr5 auxin-insensitivity phenotype. Our results demonstrate that IBR5 is a bona fide MAPK phosphatase, and suggest that MPK12 is both a physiological substrate of IBR5 and a novel negative regulator of auxin signaling in Arabidopsis. [source] Cellular efflux of auxin catalyzed by the Arabidopsis MDR/PGP transporter AtPGP1THE PLANT JOURNAL, Issue 2 2005Markus Geisler Summary Directional transport of the phytohormone auxin is required for the establishment and maintenance of plant polarity, but the underlying molecular mechanisms have not been fully elucidated. Plant homologs of human multiple drug resistance/P-glycoproteins (MDR/PGPs) have been implicated in auxin transport, as defects in MDR1 (AtPGP19) and AtPGP1 result in reductions of growth and auxin transport in Arabidopsis (atpgp1, atpgp19), maize (brachytic2) and sorghum (dwarf3). Here we examine the localization, activity, substrate specificity and inhibitor sensitivity of AtPGP1. AtPGP1 exhibits non-polar plasma membrane localization at the shoot and root apices, as well as polar localization above the root apex. Protoplasts from Arabidopsis pgp1 leaf mesophyll cells exhibit reduced efflux of natural and synthetic auxins with reduced sensitivity to auxin efflux inhibitors. Expression of AtPGP1 in yeast and in the standard mammalian expression system used to analyze human MDR-type proteins results in enhanced efflux of indole-3-acetic acid (IAA) and the synthetic auxin 1-naphthalene acetic acid (1-NAA), but not the inactive auxin 2-NAA. AtPGP1-mediated efflux is sensitive to auxin efflux and ABC transporter inhibitors. As is seen in planta, AtPGP1 also appears to mediate some efflux of IAA oxidative breakdown products associated with apical sites of high auxin accumulation. However, unlike what is seen in planta, some additional transport of the benzoic acid is observed in yeast and mammalian cells expressing AtPGP1, suggesting that other factors present in plant tissues confer enhanced auxin specificity to PGP-mediated transport. [source] Apoptosis regulators Fau and Bcl-G are down-regulated in prostate cancerTHE PROSTATE, Issue 14 2010Mark R. Pickard Abstract BACKGROUND The molecular control of cell death through apoptosis is compromised in prostate cancer cells, resulting in inappropriate cell survival and resistance to cytotoxic therapy. Reduced expression of the functionally connected apoptosis-regulators and candidate tumor suppressors Fau and Bcl-G has recently been implicated in oncogenesis in other tissues. The present study examines the hypothesis that reduced expression of these genes may be involved in prostate cancer. METHODS Fau and Bcl-G mRNA levels were determined by real time RT-PCR in two independent prostate tissue collections. In experiments in vitro, Fau and Bcl-G levels in prostate cancer cell lines were reduced using RNA interference and the effects on sensitivity to UVC irradiation were determined. RESULTS Fau and Bcl-G mRNA levels were both lower in prostate cancer tissue than in normal prostate and Benign Prostate Hyperplasia. Active down-regulation of Fau and Bcl-G expression in vitro resulted in decreased sensitivity to UVC-induced cytotoxicity. Simultaneous down-regulation of Fau and Bcl-G produced a decrease in sensitivity which was similar to either gene alone. CONCLUSIONS Fau and Bcl-G mRNA levels are both decreased in prostate cancer. In prostate cancer cell lines in vitro such down-regulation results in reduced sensitivity to UVC-induced cytotoxicity, consistent with the putative roles of these genes as candidate prostate tumor suppressors. The absence of an additive effect when Fau and Bcl-G were down-regulated simultaneously is consistent with the two genes acting in the same apoptosis pathway, for example, with the pro-apoptotic effects of Fau being mediated through modulation of Bcl-G. Prostate 70: 1513,1523, 2010. © 2010 Wiley-Liss, Inc. [source] Rho kinase inhibitors reduce neurally evoked contraction of the rat tail artery in vitroBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2005Melanie Yeoh The effects of Rho kinase inhibitors (Y27632, HA-1077) on contractions to electrical stimulation and to application of phenylephrine, clonidine or ,,, -methylene adenosine 5,-triphosphate (,,, -mATP) were investigated in rat tail artery in vitro. In addition, continuous amperometry and intracellular recording were used to monitor the effects of Y27632 on noradrenaline (NA) release and postjunctional electrical activity, respectively. Y27632 (0.5 and 1 ,M) and HA-1077 (5 ,M) reduced neurally evoked contractions. In contrast, the protein kinase C inhibitor, Ro31-8220 (1 ,M), had little effect on neurally evoked contraction. In the absence and the presence of Y27632 (0.5 ,M), the reduction of neurally evoked contraction produced by the , -adrenoceptor antagonists prazosin (10 nM) and idazoxan (0.1 ,M) was similar. The P2-purinoceptor antagonist, suramin (0.1 mM), had no inhibitory effect on neurally evoked contraction in the absence or the presence of Y27632 (1 ,M). In the presence of Y27632, desensitization of P2X-purinoceptors with ,,, -mATP (10 ,M) increased neurally evoked contractions. Y27632 (1 ,M) and H-1077 (5 ,M) reduced sensitivity to phenylephrine and clonidine. In addition, Y27632 reduced contractions to ,,, -mATP (10 ,M). Y27632 (1 ,M) had no effect on the NA-induced oxidation currents or the purinergic excitatory junction potentials and NA-induced slow depolarizations evoked by electrical stimulation. Rho kinase inhibitors reduce sympathetic nerve-mediated contractions of the tail artery. This effect is mediated at a postjunctional site, most likely by inhibition of Rho kinase-mediated ,Ca2+ sensitization' of the contractile apparatus. British Journal of Pharmacology (2005) 146, 854,861. doi:10.1038/sj.bjp.0706377 [source] | ||||||||||||||||||||||