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Various Combinations (various + combination)
Selected AbstractsGating of the expressed T-type Cav3.1 calcium channels is modulated by Ca2+ACTA PHYSIOLOGICA, Issue 4 2006L. Lacinová Abstract Aim:, We have investigated the influence of Ca2+ ions on the basic biophysical properties of T-type calcium channels. Methods:, The Cav3.1 calcium channel was transiently expressed in HEK 293 cells. Current was measured using the whole cell patch clamp technique. Ca2+ or Na+ ions were used as charge carriers. The intracellular Ca2+ was either decreased by the addition of 10 mm ethyleneglycoltetraacetic acid (EGTA) or increased by the addition of 200 ,m Ca2+ into the non-buffered intracellular solution. Various combinations of extra- and intracellular solutions yielded high, intermediate or low intracellular Ca2+ levels. Results:, The amplitude of the calcium current was independent of intracellular Ca2+ concentrations. High levels of intracellular Ca2+ accelerated significantly both the inactivation and the activation time constants of the current. The replacement of extracellular Ca2+ by Na+ as charge carrier did not affect the absolute value of the activation and inactivation time constants, but significantly enhanced the slope factor of the voltage dependence of the inactivation time constant. Slope factors of voltage dependencies of channel activation and inactivation were significantly enhanced. The recovery from inactivation was faster when Ca2+ was a charge carrier. The number of available channels saturated for membrane voltages more negative than ,100 mV for the Ca2+ current, but did not reach steady state even at ,150 mV for the Na+ current. Conclusions:, Ca2+ ions facilitate transitions of Cav3.1 channel from open into closed and inactivated states as well as backwards transition from inactivated into closed state, possibly by interacting with its voltage sensor. [source] The effect of concentrated smoke products on the restoration of highly disturbed mineral sands in southeast VictoriaECOLOGICAL MANAGEMENT & RESTORATION, Issue 2 2003By Terry D. Coates Summary Recent studies have recognized the potential of broad-scale surface application of smoke compounds for enhancing germination from the soil seed-bank in fire-prone vegetation communities. Results suggest that smoke technology may play, in the future, a significant role in the restoration and management of areas supporting indigenous vegetation. An important step in the development of smoke-based restoration tools is the conduct of in situ field trials in a range of geographical locations and environmental conditions. However, most of the published work on the effectiveness of smoke products in promoting seedbank germination has been conducted at sites in southwestern Australia. The present study examines the effect of commercially available smoke-water products on the regeneration of a highly disturbed former mine-site at the Royal Botanic Gardens Cranbourne, in southeastern Victoria. Various combinations of concentrated smoke products and topsoil harvested from a nearby heathy woodland community were applied to exposed, uniform mineral sands to test their effect on seedling density and species richness of regrowth. The trials showed that after 12 months a number of common, herbaceous species including Austrodanthonia setacea, Opercularia varia and Platysace heterophylla were recorded in significantly higher numbers in areas treated with a commercial smoke-water. However, there was no overall improvement in the density of seedlings or the richness of species as a result of the application of the smoke products. Similarly, total seedling density and species richness were not affected by the addition of topsoil, either alone or in combination with smoke products. [source] Extraction of Anthocyanins and Polyphenolics from Blueberry Processing WasteJOURNAL OF FOOD SCIENCE, Issue 7 2004J. Lee ABSTRACT: The effectiveness of temperature, SO2, citric acid, and industrial juice-processing enzymes (n= 9) for producing extracts of blueberries (Vaccinium corymbosum, cv. Rubel) and blueberry skins that are rich in anthocyanins and polyphenolics were evaluated individually and/or in combination. Enzyme treatment had little effect on total monomeric anthocyanins and on total phenolics recovery. Various combinations of heat, SO2, and citric acid yielded extracts with higher concentrations of ACY and TP than the control. The distribution of anthocyanins and polyphenolics in ,Rubel' was also investigated. Anthocyanins existed almost exclusively in the skins, and polyphenolics were mostly in the skins with lesser amounts in flesh and seeds. Skins were also highest in antioxidant activity. All portions contained the same individual anthocyanins but in varying amounts. Cinnamic acid derivatives and flavonol-glycosides were found in the skins and seeds, whereas the flesh contained only cinnamic acids. [source] The enemy of my enemy is still my enemy: competitors add to predator load of a tree-killing bark beetleAGRICULTURAL AND FOREST ENTOMOLOGY, Issue 4 2008Celia K. Boone Abstract 1,The mountain pine beetle Dendroctonus ponderosae is a major tree-killing bark beetle in North America. We evaluated how the subsequent arrival of a competing bark beetle Ips pini influences the arrival of predators and their impact on both species. 2,The predators Temnochila chlorodia and Enoclerus sphegeus were strongly attracted to pheromones of D. ponderosae. By contrast, Enoclerus lecontei was mostly attracted to I. pini pheromones. The host compound myrcene synergized attraction of both D. ponderosae and E. sphegeus to the pheromone of D. ponderosae. However, it inhibited attraction of both I. pini and E. lecontei to I. pini's pheromone. 3,Dendroctonus ponderosae were more attracted to trees than logs treated with its pheromones, whereas I. pini were more attracted to logs than trees treated with its pheromones. Some 78% of T. chlorodia were captured at hosts baited with D. ponderosae pheromones, whereas 83% of E. lecontei were captured at hosts baited with I. pini pheromones. We characterized the sequence of arrival to live trees baited with pheromones of D. ponderosae as: D. ponderosae, T. chlorodia, E. sphegeus, I. pini, E. lecontei. 4,Various combinations of I. pini and predators were added to logs colonized by D. ponderosae in the above sequence of arrival observed in live trees baited with D. ponderosae aggregation pheromones. Ips pini reduced D. ponderosae adult brood production. However, the combination of I. pini and E. lecontei did not raise D. ponderosae brood production above that observed with only I. pini present. Similarly, the combination of I. pini and T. chlorodia did not reduce D. ponderosae brood production below that observed with I. pini alone. By contrast, the combination of I. pini, T. chlorodia and E. lecontei caused more brood loss to D. ponderosae than I. pini alone. 5,Enoclerus lecontei did not reduce brood production by T. chlorodia, whereas T. chlorodia substantially reduced brood production by E. lecontei. 6,Secondary bark beetles that exploit the resource created by primary tree-killing species exert negative effects through both competition and increased predator load. Implications to the population dynamics, ecology and evolution of tree-killing bark beetles are discussed. [source] A Review of the Evidence Comparing the Human Papillomavirus Vaccine Versus Condoms in the Prevention of Human Papillomavirus InfectionsJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 3 2008Shelley Miksis ABSTRACT Objective:, To examine the evidence related to the efficacy of condom use versus the human papillomavirus vaccine in the prevention of human papillomavirus infections. Data sources:, Cochrane, CINHAL, PubMed, and Clinical Evidence. Various combinations of the keywords HPV, vaccine, and condoms were used for the search. Study selection:, Randomized, double-blinded placebo-controlled trials were reviewed for evaluation of the human papillomavirus vaccine. Several longitudinal studies and a meta-analysis were used for review of condom efficacy related to human papillomavirus transmission. Data extraction and synthesis:, Studies evaluating the use of either condoms or the human papillomavirus vaccine and its impact on human papillomavirus transmission rates, detected through either human papillomavirus DNA testing or clinical disease. Conclusions:, The evidence indicates that the greatest degree of protection from specific types of human papillomavirus infection is provided by the vaccine. However, the use of condoms in addition to the human papillomavirus vaccine provides the greatest protection from the untoward effects of human papillomavirus infection and may also provide protection against human papillomavirus types not in the vaccine and other sexually transmitted infections. [source] Identification of gas-producing components in different varieties of Phaseolus vulgaris by in vitro fermentationJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 6 2001M Granito Abstract Phaseolus vulgaris consumption has been limited as part of the occidental diet owing to flatulence production. Raffinose, stachyose and verbascose have been shown to be the main components responsible for flatulence; however, it is thought that soluble fibre could also be involved in this phenomenon. The aim of the present study was to identify the main components of beans influencing flatus. Ten varieties of P vulgaris originating from South America were first analysed for their main nutrient and carbohydrate fractions. Three of the varieties were then fractionated to extract soluble and insoluble fibres. Various combinations of ,-galactosides and soluble and insoluble fibre fractions, in similar proportions to those contained in cooked grains, were used as substrates for in vitro fermentation studies using human faecal inoculum to determine the fermentative capacity of each of the three fractions. Considering the white varieties, total gas production and acidification of the medium were correlated with fermented organic matter from soluble fibre (R2,=,1)) and with ,-galactosides (R2,=,0.75). On the other hand, tannins present in pigmented varieties did not seem to interfere significantly in fermentation of soluble fibre. The total production of gas per gram of mixed fractions of soluble fibre and ,-galactosides in proportions found in cooked grains was lower than that expected from each substrate separately. It can be concluded that soluble fibre and ,-galactosides are good substrates for endogenous colonic flora subjected to in vitro fermentation studies and are thus responsible for flatulence induced by legume consumption. © 2001 Society of Chemical Industry [source] InAsSb/InGaAs quantum nanostructures on InP (100) substrate: observation of 2.35 µm photoluminescencePHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 3 2006F. Doré Abstract A theoretical and experimental study of the electronic properties of InAsSb quantum dots (QDs) grown on InP substrate is presented. Unstrained bulk InAsSb presents a direct gap between 0.1 eV to 0.35 eV, suitable for mid infrared emitters (3,5 µm). However, strain and quantum confinement effects may limit the extension of the emission spectrum of these nanostructures towards longer wavelengths. Various combinations of barrier materials are considered in the simulations. First photoluminescence spectroscopy experiments on molecular beam epitaxy (MBE) grown samples show promising results. Triple stacks of InAs QDs embedded in a GaInAsP alloy lattice matched to InP and grown by the Stranski-Krastanov mode exhibit room temperature (RT) luminescence at about 2 µm. Emission wavelengths as long as 2.35 µm have been observed at RT in a InAsSb/InGaAs/InP structure. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Processability studies of silica-thermoset polymer matrix nanocompositesPOLYMER ENGINEERING & SCIENCE, Issue 2 2008C. Lekakou The aim of this study is to investigate the processability of silica-thermoset polymer matrix nanocomposites in terms of dispersion of silica nanoparticles and their effect on curing. Two thermosetting resins were considered, an epoxy and a polyester resin, with 5% silica, although 1% silica was also used in preliminary studies in the polyester system. Various combinations of mechanical mixing and sonication were investigated for the dispersion of silica nanoparticles under different processing conditions and times in solvent-free and solvent-containing systems. It was found that the best dispersion route involved a solvent-aided dispersion technique. Consequently, different procedures for the solvent removal were investigated. Optical microscopy and SEM were used to characterize the resulting nanocomposites. DSC and rheological DMTA tests demonstrated that the silica nanoparticles shorten the gel time and promote curing in these thermosetting systems. POLYM. ENG. SCI., 2008. © 2007 Society of Plastics Engineers [source] Prognostic factors derived from a prospective database dictate clinical biology of anal cancerCANCER, Issue 17 2010The intergroup trial (RTOG 98-11) Abstract BACKGROUND: Only 4 prospective randomized phase 3 trials have been reported for anal cancer. A prognostic factor analysis for anal cancer from a prospective database has been published from only 1 study (N = 110). To confirm and uncover new prognostic factors, we analyzed the prospective database of intergroup RTOG 98-11. METHODS: Univariate and multivariate analyses of the baseline characteristics for 5-year overall survival (OS) and disease-free survival (DFS) were carried out. Various combinations of tumor diameter and clinically positive nodes (N+) were analyzed to identify subgroups. RESULTS: A total of 644 were assessable and analyzed. Tumor diameter >5 cm was associated with poorer 5-year DFS (P = .0003) and poorer 5-year OS (P = .0031), and N+ was associated with poorer 5-year DFS (P , .0001) and poorer 5-year OS (P = , .0001) in the multivariate analysis. In stratified analyses, N+ had more adverse influence on DFS and OS than did tumor diameter. Patients with >5-cm tumor and N+ had the worst DFS (only 30% at 3 years compared with 74% for the best group; <5 cm primary and N0) and OS (only 48% at 4 years compared with 81% for the best group; <5 cm primary and N0). Men had worse DFS (P = .02) and OS (P = .016). These factors maintained their influence in each treatment arm. CONCLUSIONS: This prospective prognostic factor analysis establishes tumor diameter as an independent prognosticator of poorer 5-year DFS and OS and confirms N+ and male sex as poor prognostic factors. This analysis also uncovers novel subgroups (derived from combining prognostic factors) with incremental worsening of DFS and OS. Cancer 2010. © 2010 American Cancer Society. [source] Mechanism of antibody reduction in cell culture production processesBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2010Yung-Hsiang Kao Abstract We recently observed a significant disulfide reduction problem during the scale-up of a manufacturing process for a therapeutic antibody using a CHO expression system. Under certain conditions, extensive reduction of inter-chain disulfide bonds of an antibody produced by CHO cell culture may occur during the harvest operations and/or the protein A chromatography step, resulting in the observation of antibody fragments (light chain, heavy chain, and various combination of both) in the protein A pools. Although all conditions leading to disulfide reduction have not been completely identified, an excessive amount of mechanical cell lysis generated at the harvest step appears to be an important requirement for antibody reduction (Trexler-Schmidt et al., 2010). We have been able to determine the mechanism by which the antibody is reduced despite the fact that not all requirements for antibody reduction were identified. Here we present data strongly suggesting that the antibody reduction was caused by a thioredoxin system or other reducing enzymes with thioredoxin-like activity. The intracellular reducing enzymes and their substrates/cofactors apparently were released into the harvest cell culture fluid (HCCF) when cells were exposed to mechanical cell shear during harvest operations. Surprisingly, the reducing activity in the HCCF can last for a long period of time, causing the reduction of inter-chain disulfide bonds in an antibody. Our findings provide a basis for designing methods to prevent the antibody reduction during the manufacturing process. Biotechnol. Bioeng. 2010;107:622,632. © 2010 Wiley Periodicals, Inc. [source] The phenomenology of bipolar disorder: what drives the high rate of medical burden and determines long-term prognosis?DEPRESSION AND ANXIETY, Issue 1 2009Isabella Soreca M.D. Abstract Bipolar disorder (BD) has been classically described as one of episodic mood disturbances. New evidence suggests that a chronic course and multisystem involvement is the rule, rather than the exception, and that together with disturbances of circadian rhythms, mood instability, cognitive impairment, a high rate of medical burden is often observed. The current diagnostic approach for BD neither describes the multisystem involvement that the recent literature has highlighted nor points toward potential predictors of long- term outcome. In light of the new evidence that the long-term course of BD is associated with a high prevalence of psychiatric comorbidity and an increased mortality from medical disease, we propose a multidimensional approach that includes several symptom domains, namely affective instability, circadian rhythm dysregulation, and cognitive and executive dysfunction, presenting in various combinations that give shape to each individual presentation, and offers potential indicators of overall long-term prognosis. Depression and Anxiety, 2009. © 2008 Wiley-Liss, Inc. [source] The medical and surgical therapy of pseudofolliculitis barbaeDERMATOLOGIC THERAPY, Issue 2 2004Sharon Bridgeman-Shah ABSTRACT:, Pseudofolliculitis barbae (PFB) is a common, chronic, inflammatory skin disorder seen mainly in individuals with curly hair. This condition is seen most frequently in black men who shave their beards but may also be seen in women of all races who wax or shave the axillary and pubic skin. The etiology of PFB is multifactorial, and heretofore a cure has been considered impossible for those desiring a clean-shaven face. The following article serves to discuss the current medical and surgical therapies available for this condition. Medical treatments for this condition include various combinations of topical antibiotics, corticosteroids, and retinoids. In the surgical arena, laser therapy has revolutionized the treatment of PFB and has enabled cure for the first time for those plagued by this disorder and for whom a beardless face is acceptable. [source] Busulfan-induced central polydactyly, syndactyly and cleft hand or foot: A common mechanism of disruption leads to divergent phenotypesDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2007Takuji Naruse The prevalence of clinical phenotypes that exhibit combinations of central polydactyly, syndactyly, or cleft hand or foot is higher than would be expected for random independent mutations. We have previously demonstrated that maternal ingestion of a chemotherapeutic agent, busulfan, at embryonic day 11 (E11) induces these defects in various combinations in rat embryo limbs. In an effort to determine the mechanism by which busulfan disrupts digital development, we examined cell death by Nile Blue staining and TdT-mediated dUTP nick end labeling (TUNEL) assays; we also carried out whole mount in situ hybridization for fibroblast growth factor-8 (Fgf8), bone morphogenetic protein-4 (Bmp4), and sonic hedgehog (Shh) to examine developmental pathways linked to these defects. In busulfan-treated embryos, diffuse cell death was evident in both ectoderm and mesoderm, peaking at E13. The increased cell death leads to regression of Fgf8 in the apical ectodermal ridge (AER) and Bmp4 and Shh in the underlying mesoderm. The subsequent pattern of interdigital apoptosis and cartilage condensation was variably disrupted. These results suggest that busulfan manifests its teratogenic effects by inducing cell death of both ectoderm and mesoderm, with an associated reduction in tissue and a disruption in the generation of patterning molecules during critical periods of digit specification. [source] Vision in children with hydrocephalusDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2006Susann Andersson MD Hydrocephalus in children has many aetiologies, and can cause multiple ophthalmic and visual disorders. This study sets out to detect and quantify visual and visuoperceptual dysfunction in children who have received surgical treatment for hydrocephalus with and without myelomeningocele, and to relate the results to the associated diagnoses and results from a comparison group. Seventy-five school-aged children (41 males, 34 females) with surgically-treated hydrocephalus and 140 comparison children (76 males, 64 females) matched for age and sex underwent comprehensive ophthalmologic examination. Median age at examination was 9 years and 4 months (range 7y 4mo- 12y 10mo). Visual function deficits were identified in 83% (62/75) of the children with hydrocephalus. Visual impairment (binocular visual acuity <0.3) was found in 15% (11/73; comparison group 0%) but in none with myelomeningocele. Strabismus was found in 69% (51/74; comparison group 4% [5/140], p<0.001), and refractive errors were found in 67% (47/70; comparison group 20% [28/140], p<0.001). Cognitive visual dysfunction was identified in 59% (38/64; comparison group 3% [4/140], p<0.001). These disorders were identified in various combinations and comprised impaired ability to plan movement through depth (e.g. going down a stair), impaired simultaneous perception, impaired perception of movement, impaired orientation, and (least frequently) impaired recognition. In this study, children with hydrocephalus associated with myelomeningocele were least commonly affected. Visual disorders were most frequent in those with epilepsy, cerebral palsy, and/or cognitive disability. [source] Experimental frost weathering of sandstone by various combinations of saltsEARTH SURFACE PROCESSES AND LANDFORMS, Issue 8 2001R. B. G. Williams Abstract Weathering experiments are reported combining frost and a range of salts that occur naturally on rock faces in western and central Europe. Potassium and ammonium alums enhanced frost weathering quite considerably, both singly and in combination, though they were less potent than halite, the destructiveness of which, at sub-zero temperatures, was again confirmed. By contrast, alunogen and gypsum had little or no effect on rates of frost weathering either singly or in combination. Combining halite and gypsum produced breakdown that was intermediate between that of the two salts individually, as did the combination of gypsum and potassium alum. Breakdown in solutions of ammonium alum and gypsum, and in a combination of potassium and ammonium alum with gypsum, caused greater breakdown over 25 cycles of freeze,thaw than was recorded with the salts singly. The results extend the range of salts known to enhance frost weathering, and show that it is difficult to predict the aggressiveness of combinations of salts by experimenting with each salt separately. Copyright © 2001 John Wiley & Sons, Ltd. [source] Coexistence of a sulphate-reducing Desulfovibrio species and the dehalorespiring Desulfitobacterium frappieri TCE1 in defined chemostat cultures grown with various combinations of sulphate and tetrachloroetheneENVIRONMENTAL MICROBIOLOGY, Issue 2 2001Oliver Drzyzga A two-member co-culture consisting of the dehalorespiring Desulfitobacterium frappieri TCE1 and the sulphate-reducing Desulfovibrio sp. strain SULF1 was obtained via anaerobic enrichment from soil contaminated with tetrachloroethene (PCE). In this co-culture, PCE dechlorination to cis -dichloroethene was due to the activity of the dehalorespiring bacterium only. Chemostat experiments with lactate as the primary electron donor for both strains along with varying sulphate and PCE concentrations showed that the sulphate-reducing strain outnumbered the dehalogenating strain at relatively high ratios of sulphate/PCE. Stable co-cultures with both organisms present at similar cell densities were observed when both electron acceptors were supplied in the reservoir medium in nearly equimolar amounts. In the presence of low sulphate/PCE ratios, the Desulfitobacterium sp. became the numerically dominant strain within the chemostat co-culture. Surprisingly, in the absence of sulphate, strain SULF1 did not disappear completely from the co-culture despite the fact that there was no electron acceptor provided with the medium to be used by this sulphate reducer. Therefore, we propose a syntrophic association between the sulphate-reducing and the dehalorespiring bacteria via interspecies hydrogen transfer. The sulphate reducer was able to sustain growth in the chemostat co-culture by fermenting lactate and using the dehalogenating bacterium as a ,biological electron acceptor'. This is the first report describing growth of a sulphate-reducing bacterium in a defined two-member continuous culture by syntrophically coupling the electron and hydrogen transfer to a dehalorespiring bacterium. [source] Topiramate Enhances the Risk of Valproate-associated Side Effects in Three ChildrenEPILEPSIA, Issue 4 2002Elke Longin Summary: ,Purpose: We present three children with severe therapy-refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM). Methods: The clinical symptoms began with apathy in all three children; two of them also had hypothermia. Furthermore all children had elevated blood ammonia levels, one child in combination with increased liver transaminases and one with thrombocytopenia. Results: All children recovered completely after discontinuation of VPA or TPM. Conclusions: TPM seems likely to enhance the risk of side effects usually attributed to VPA and not described in TPM monotherapy. Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM. [source] Effects of hydrogenation parameters on trans isomer formation, selectivity and melting properties of fatEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 3 2008Anar Musavi Abstract Effects of hydrogenation conditions (temperature, hydrogen pressure, stirring rate) on trans fatty acid formation, selectivity and melting behavior of fat were investigated. To this aim, soybean oil was hydrogenated under various conditions and fatty acid composition, trans isomer formation, slip melting point (SMP), solid fat content (SFC) and iodine number (IV) of the samples withdrawn at certain intervals of the reactions were monitored. A constant ratio (0.03%) of Nysosel 222 was used in the various combinations of temperature (150, 165 and 180,°C), stirring speed (500, 750 and 1000,rpm) and hydrogen pressure (1, 2 and 3,bar). Raising the temperature increased the formation of fatty acid isomers, whereas higher stirring rates decreased this formation, while changes in hydrogen pressure had no effect or slightly reduced it, depending on other parameters. Results also indicated that the trans fatty acid ratio increased with IV reduction, reached the highest value when the IV was about 70 and decreased at IV < 70 due to saturation. Selectivity values (S21) at that point ranged between 5.78 and 11.59. Lower temperatures and higher stirring rates decreased not only the trans isomer content but also the S21 values at significant levels. However, same effects were not observed with the changes in hydrogen pressure. It was determined that a high SMP does not necessarily mean a high SFC. Selective conditions produced samples with higher SFC but lower SMP, which is possibly because of higher trans isomer formation as well as lower saturation. [source] Functional screening of traditional antidepressants with primary cortical neuronal networks grown on multielectrode neurochipsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Alexandra Gramowski Abstract We optimized the novel technique of multielectrode neurochip recordings for the rapid and efficient screening of neuroactivity. Changes in the spontaneous activity of cultured networks of primary cortical neurons were quantified to evaluate the action of drugs on the firing dynamics of complex network activity. The multiparametric assessment of electrical activity changes caused by psychoactive herbal extracts from Hypericum, Passiflora and Valeriana, and various combinations thereof revealed a receptor-specific and concentration-dependent inhibition of the firing patterns. The spike and burst rates showed significant substance-dependent effects and significant differences in potency. The effects of specific receptor blockades on the inhibitory responses provided evidence that the herbal extracts act on gamma-amino butyric acid (GABA) and serotonin (5-HT) receptors, which are recognized targets of pharmacological antidepressant treatment. A biphasic effect, serotonergic stimulation of activity at low concentrations that is overridden by GABAergic inhibition at higher concentrations, is apparent with Hypericum alone and the triple combination of the extracts. The more potent neuroactivity of the triple combination compared to Hypericum alone and the additive effect of Passiflora and Valeriana suggest a synergy between constituent herbal extracts. The extracts and their combinations affected the set of derived activity parameters in a concomitant manner suggesting that all three constituent extracts and their combinations have largely similar modes of action. This study also demonstrates the sensitivity, selectivity and robustness of neurochip recordings for high content screening of complex mixtures of neuroactive substances and for providing multiparametric information on neuronal activity changes to assess the therapeutic potential of psychoactive substances. [source] Differentiation-dependent sensitivity to cell death induced in the developing retina by inhibitors of the ubiquitin-proteasome proteolytic pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001D. D. C. Neves Abstract The effects of inhibitors of proteasome function were studied in the retina of developing rats. Explants from the retina of neonatal rats at postnatal day (P) 3 or P6 were incubated with various combinations of the proteasome inhibitor carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132), the protein synthesis inhibitor anisomycin, or the adenylyl cyclase activator forskolin. MG132 induced cell death in a subset of cells within the neuroblastic (proliferative) layer of the retinal tissue. The cells sensitive to degeneration induced by either MG132 or anisomycin, were birthdated by bromodeoxyuridine injections. This showed that the MG132-sensitive population includes both proliferating cells most likely in their last round of cell division, and postmitotic undifferentiated cells, at a slightly earlier stage than the population, sensitive to anisomycin-induced cell death. The results show that sensitivity to cell death induced by proteasome inhibitors defines a window of development in the transition from the cell cycle to the differentiated state in retinal cells. [source] AN EXACT FORM OF THE BREEDER'S EQUATION FOR THE EVOLUTION OF A QUANTITATIVE TRAIT UNDER NATURAL SELECTIONEVOLUTION, Issue 11 2005John S. Heywood Abstract Starting with the Price equation, I show that the total evolutionary change in mean phenotype that occurs in the presence of fitness variation can be partitioned exactly into five components representing logically distinct processes. One component is the linear response to selection, as represented by the breeder's equation of quantitative genetics, but with heritability defined as the linear regression coefficient of mean offspring phenotype on parent phenotype. The other components are identified as constitutive transmission bias, two types of induced transmission bias, and a spurious response to selection caused by a covariance between parental fitness and offspring phenotype that cannot be predicted from parental phenotypes. The partitioning can be accomplished in two ways, one with heritability measured before (in the absence of) selection, and the other with heritability measured after (in the presence of) selection. Measuring heritability after selection, though unconventional, yields a representation for the linear response to selection that is most consistent with Darwinian evolution by natural selection because the response to selection is determined by the reproductive features of the selected group, not of the parent population as a whole. The analysis of an explicitly Mendelian model shows that the relative contributions of the five terms to the total evolutionary change depends on the level of organization (gene, individual, or mated pair) at which the parent population is divided into phenotypes, with each frame of reference providing unique insight. It is shown that all five components of phenotypic evolution will generally have nonzero values as a result of various combinations of the normal features of Mendelian populations, including biparental sex, allelic dominance, inbreeding, epistasis, linkage disequilibrium, and environmental covariances between traits. Additive genetic variance can be a poor predictor of the adaptive response to selection in these models. The narrow-sense heritability s,2A/s,2P should be viewed as an approximation to the offspring-parent linear regression rather than the other way around. [source] Characterization of the sgtR1 and sgtR2 genes and their role in regulating expression of the sprT gene encoding Streptomyces griseus trypsinFEMS MICROBIOLOGY LETTERS, Issue 1 2007Eun A Oh Abstract The sgtR1 and sgtR2 genes encoding putative regulators similar to the Aha1 and ArsR families, respectively, were identified downstream from the sprT gene. To investigate their function, expression vectors containing various combinations of sprT, sgtR1, and sgtR2 were transformed into Streptomyces lividans and Streptomyces griseus. The trypsin activity levels produced by S. lividans harboring pWHM3-TR2 (sprT and sgtR2) or pWHM3-TR1R2 (sprT, sgtR2, and sgtR2) were, respectively, 6.6 or 8.9 times that of S. lividans transformed with pWHM3-T (sprT). In the pWHM3-TR1R2 transformant, the transcription of sprT consistently occurred during the earlier stages of growth and was maintained at a higher level throughout the 6 days of cultivation. Streptomyces griseus IFO13350 harboring pWHM3-TR1R2 also produced trypsin activity 2.1 times that of the pWHM3-T transformant. However, all S. griseus,adpA transformants produced lower SGT activity than the wild-type strain, and none could overcome the deficiency in AdpA transcriptional activator, suggesting that AdpA is an absolute prerequisite for sprT expression. The sprT transcript was detected at a high level only in the wild-type strain, but the sgtR1 and sgtR2 transcript levels were very similar between the S. griseus IFO13350 and ,adpA strains. This clearly demonstrates that the transcription of the sgtR1 and sgtR2 genes is not dependent on AdpA and that they are therefore not members of the AdpA regulon. [source] Genetic data indicate that proteins containing the GGDEF domain possess diguanylate cyclase activityFEMS MICROBIOLOGY LETTERS, Issue 1 2001Nora Ausmees Abstract A conserved domain, called GGDEF (referring to a conserved central sequence pattern), is detected in many procaryotic proteins, often in various combinations with putative sensory-regulatory components. Most sequenced bacterial genomes contain several different GGDEF proteins. The function of this domain has so far not been experimentally shown. Through genetic complementation using genes from three different bacteria encoding proteins with GGDEF domains as the only element in common, we present genetic data indicating (a) that the GGDEF domain is responsible for the diguanylate cyclase activity of these proteins, and (b) that the activity of cellulose synthase in Rhizobium leguminosarum bv. trifolii and Agrobacterium tumefaciens is regulated by cyclic di-GMP as in Acetobacter xylinum. [source] Predicting a State's Foreign Policy: State Preferences between Domestic and International ConstraintsFOREIGN POLICY ANALYSIS, Issue 3 2007Gerry C. Alons In order to understand a state's foreign policy preferences, we need to take both its domestic and international considerations into account. This article aims to contribute to the analysis of foreign policy by exploring the conditions under which states will either give precedence to domestic or international incentives. Two central variables are used to generate predictions on the expected primacy of either level. The first variable is "internal polarity", that is, the degree of concentration of power in the hands of the government relative to society. The second variable is "external polarity", referring to the degree of centralization of power in the international system. It will be argued that various combinations of scores on these variables affect the formation of foreign policy preferences differently. When internal polarity is low and external polarity is high, domestic considerations will be decisive. On the contrary, when internal polarity is high and external polarity is low, international considerations will be decisive. With respect to the other two combinations, process variables such as the degree of domestic mobilization and the sensitivity of the government are expected to gain particular importance in tilting the balance towards either domestic or international considerations. A preliminary test of the theoretical framework is provided by applying it to French and German preference formation on the 1988 CAP-reform and the agricultural aspects of the Uruguay Round of GATT-negotiations between 1990 and 1993. [source] Gender, light and water effects in carbon isotope discrimination, and growth rates in the dioecious tree Ilex aquifoliumFUNCTIONAL ECOLOGY, Issue 5 2000R. Retuerto Abstract 1.,Detailed understanding of the specific physiology of sexes in dioecious species is required to explain patterns in gender dimorphism. Under controlled-environment conditions we tested the hypothesis that sexes of the dioecious tree holly Ilex aquifolium L. (Aquifoliaceae) differed in growth and long-term potential water-use efficiency, as measured by carbon isotope discrimination (,13C), and that these differences were dependent on the environmental context. 2.,Patterns of response in ,13C to the various combinations of light and water were gender-specific. Under more xeric conditions, females maintained significantly higher ,13C than males. 3.,Female plants exhibited significantly greater relative diameter growth rates than male plants. 4.,As expected, ,13C significantly increased with decreasing irradiance, and decreased with increasing limitation in water supply. Light and water effects were not independent, with a more pronounced drought effect in decreasing leaf ,13C under unshaded than under shaded conditions. 5.,Our results suggest that between-sex differences in physiology are context-dependent. Future studies attempting to assess gender dimorphism should take more account of gender-specific interactions with the environment. Gender-specific efficiency in water use could play a decisive role in explaining gender differences in growth and ecological interactions. [source] Pharmacological screening of bryophyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cellsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2009Lucie Krzaczkowski Abstract Antitumor activities of substances from natural sources apart from vascular plants and micro-organisms have been poorly investigated. Here we report on a pharmacological screening of a bryophyte extract library using a phenotypic cell-based assay revealing microtubules, centrosomes and DNA. Among the 219 moss extracts tested, we identified 41 extracts acting on cell division with various combinations of significant effects on interphasic and mitotic cells. Seven extracts were further studied using a cell viability assay, cell cycle analysis and the phenotypic assay. Three distinct pharmacological patterns were identified including two unusual phenotypes. [source] Novel role of nectin: implication in the co-localization of JAM-A and claudin-1 at the same cell,cell adhesion membrane domainGENES TO CELLS, Issue 8 2008Kaori Kuramitsu Tight junctions (TJs) are formed at the apical side of adherens junctions (AJs) in epithelial cells. Major cell adhesion molecules (CAMs) at TJs are JAM and claudin, whereas major CAMs at AJs are nectin and cadherin. We previously showed that nectin initially forms cell,cell adhesion and then recruits cadherin to the nectin-based cell,cell adhesion sites to form AJs, followed by the recruitment of JAM and claudin to the apical side of AJs to form TJs. We investigated the roles of nectin in the formation of TJs by expressing various combinations of CAMs in L fibroblasts with no TJs or AJs. Co-expression of one of the AJ CAMs and one of the TJ CAMs formed two separate cell,cell adhesion membrane domains (CAMDs). Co-expression of nectin-3 and E-cadherin formed the same CAMD, but co-expression of JAM-A and claudin-1 did not form the same CAMD. Co-expression of JAM-A and claudin-1 with nectin-3, but not E-cadherin, made them form the same CAMD, which was separated from the nectin-based CAMD. Nectin-3 required afadin, a nectin- and F-actin-binding protein, for this ability. In conclusion, nectin plays a novel role in the co-localization of JAM and claudin at the same CAMD. [source] Population Synthesis: Comparing the Major Techniques Using a Small, Complete Population of FirmsGEOGRAPHICAL ANALYSIS, Issue 2 2009Justin Ryan Recently, disaggregate modeling efforts that rely on microdata have received wide attention by scholars and practitioners. Synthetic population techniques have been devised and are used as a viable alternative to the collection of microdata that normally are inaccessible because of confidentiality concerns or incomplete because of high acquisition costs. The two most widely discussed synthetic techniques are the synthetic reconstruction method (IPFSR), which makes use of iterative proportional fitting (IPF) techniques, and the combinatorial optimization (CO) method. Both methods are described in this article and then evaluated in terms of their ability to recreate a known population of firms, using limited data extracted from the parent population of the firms. Testing a synthetic population against a known population is seldom done, because obtaining an entire population usually is too difficult. The case presented here uses a small, complete population of firms for the City of Hamilton, Ontario, for the year 1990; firm attributes compiled are number of employees, 3-digit standard industrial classification, and geographic location. Results are summarized for experiments based upon various combinations of sample size and tabulation detail designed to maximize the accuracy of resulting synthetic populations while holding input data costs to a minimum. The output from both methods indicates that increases in sample size and tabulation detail result in higher quality synthetic populations, although the quality of the generated population is more sensitive to increases in tabular detail. Finally, most tests conducted with the created synthetic populations suggest that the CO method is superior to the IPFSR method. Los modelos desagregados basados en micro data han recibido la atención relativamente reciente de los círculos académicos y de aplicación. La colección de dicha data es una tarea difícil por cuestiones de accesibilidad, confidencialidad, datos incompletos o altos costos de adquisición. Por esta razón se han creado indicadores sintéticos como a alternativa a la recolección directa de datos. Los dos indicadores sintéticos mas discutidos/conocidos son el método de Reconstrucción Sintética (Sytnthetic Reconstruction method) (IPFSR) que hace uso de técnicas de Ajuste Proporcional Iterativo (IPF); y el método Optimización Combinatoria (CO). Ambos métodos son descritos en este artículo y luego evaluados en base a su habilidad de recrear una población de empresas ya conocidas o preestablecidas. Contrastar una población sintética versus una población conocida es una operación poco frecuente porque la obtención de una población entera es por lo general bastante difícil. El caso presentado en este estudio utiliza una población pequeña y completa de empresas en la ciudad de Hamilton, Ontario (Canadá) para el año 1990. Las variables recopiladas son el número de empleados, SIC (código estandarizado de clasificación industrial), y ubicación geográfica. Los resultados que se reportan en el presente estudio son producto de varios experimentos basados en varias combinaciones del tamaño de la muestra, y del detalle en la tabulación diseñados, los mismos que fueron diseñados para maximizar la exactitud de las poblaciones sintéticas calculadas y al mismo tiempo minimizar los costos de datos necesarios. Los resultados obtenidos por ambos métodos indica que los incrementos en el tamaño de la muestra y en el detalle de la tabulación resultan en un estimado de poblaciones mejor, aunque este estimado es particularmente sensible a incrementos en el detalle de las tabulaciones. Finalmente, la mayoría de pruebas realizadas con las poblaciones sintéticas generadas para este estudio sugieren que el método CO es superior al método IPFSR. [source] Somatic embryogenesis and multiple-shoot formation from seed-derived shoot apical meristems of rhodesgrass (Chloris gayana Kunth)GRASSLAND SCIENCE, Issue 3 2007Takahiro Gondo Abstract High-frequencies of somatic embryogenesis and multiple-shoot formation were achieved with seed-derived shoot apical meristems of rhodesgrass (Chloris gayana Kunth). Shoot apices as initial explants were isolated from aseptically germinated seedlings, and cultured in vitro. Embryogenic calli and the multiple shoots were induced and maintained on MS basal medium with various combinations of 2,4-dichlorophnoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP), the two most effective treatments being 2.0 mg L,1 2,4-D and 0.1 mg L,1 2,4-D + 2.0 mg L,1 BAP. These embryogenic calli and multiple-shoot formations could be used as alternative regenerable target tissues for genetic transformation using particle bombardment of rhodesgrass. [source] Sequence dependence of cell growth inhibition by EGFR,tyrosine kinase inhibitor ZD1839, docetaxel, and cisplatin in head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2009Carmen M. Klass MD Abstract Background This study was to explore whether the efficacy of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Z, Iressa, gefitinib) plus chemotherapeutic agents docetaxel (D) and cisplatin (P) may benefit from sequencing of the combination. Methods Three head and neck cancer cell lines were used to study the effect of various combinations of and relative sequencing of D, P, and Z in cell growth inhibition. A population pharmacokinetic stimulation study was conducted on Z in silico and used together with the growth inhibition data to derive principles for future in vivo use of this drug combination. Results The inhibitory effects of Z on combinations of D and P were sequence dependent. Treatment simultaneously with DPZ or with DP followed by Z (DP,Z) showed synergistic effects in all 3 cell lines. However, sequencing with Z followed by DP (Z,DP), gave an antagonistic effect, suggesting that D and P should be administered when the effect of Z is low. The induction of apoptosis was also sequence dependent. The in silico pharmacokinetic study suggested the feasibility of deriving a 5-day-on/2-day-off regimen for Z, in which D and P administration commences when levels of Z are low, allowing levels of Z to accumulate sufficiently during the remainder of the cycle. Conclusion These data suggests that it is feasible to design clinical trials with these settings to maximize the efficacy of this combined drug regimen. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||