Important Mechanism (important + mechanism)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Patterns of population genetic diversity in riparian and aquatic plant species along rivers

JOURNAL OF BIOGEOGRAPHY, Issue 9 2010
Olivier Honnay
Abstract Aim, The downstream hydrochoric spread of seeds of aquatic and riparian plant species, without upstream compensation, can be expected to result in downstream accumulation of population genetic diversity. This idea has been termed the ,unidirectional dispersal hypothesis' and is the genetic equivalent of the more generally known ,drift paradox'. Our aim was to test this unidirectional diversity hypothesis, and to present a general synthesis of the patterns of population genetic variation across different riparian and aquatic plant species along rivers. Location, The Meuse River (Belgium) and rivers world-wide. Methods, First, we used amplified fragment length polymorphism markers to compare patterns of within- and between-population genetic diversity among three riparian plant species (Sisymbrium austriacum, Erysimum cheiranthoides and Rorippa sylvestris), typically occurring in different habitats along a gradient perpendicular to the Meuse River. Second, we performed a meta-analysis on studies reporting on the population genetic structure of riparian and aquatic plant species along rivers. Results, Along the Meuse River, we found significant genetic differentiation among populations of all three riparian species, and significant isolation by distance for one of them (R. sylvestris). There was no clear association between the typical habitat of a species and its population genetic structure. None of the three species provided evidence for the unidirectional dispersal hypothesis. The meta-analysis, based on 21 data records, did not support the unidirectional dispersal hypothesis either. Average weighted population genetic differentiation across species was significant. Main conclusions, Important mechanisms of upstream seed dispersal, probably through zoochory, together with higher seed recruitment opportunities in upstream habitats due to density dependence of recruitment, may explain the absence of downstream accumulation of genetic diversity. Also, it seems difficult to find consistent patterns in genetic variation in species from aquatic and riparian habitats. We argue that this is due to the recurrent extinctions and colonizations characteristic of these habitats, resulting in complex genetic patterns. Our results strongly support previous suggestions that stream ecology should consistently embrace metapopulation theory to be able to understand patterns of genetic diversity, as well as species diversity. [source]


COALITIONS AMONG INTELLIGENT AGENTS: A TRACTABLE CASE

COMPUTATIONAL INTELLIGENCE, Issue 1 2006
M. V. Belmonte
Coalition formation is an important mechanism for cooperation in multiagent systems. In this paper we address the problem of coalition formation among self-interested agents in superadditive task-oriented domains. We assume that each agent has some "structure," i.e., that it can be described by the values taken by a set of m nonnegative attributes that represent the resources w each agent is endowed with. By defining the coalitional value as a function V of w, we prove a sufficient condition for the existence of a stable payment configuration,in the sense of the core,in terms of certain properties of V. We apply these ideas to a simple case that can be described by a linear program and show that it is possible to compute for it,in polynomial time,an optimal task allocation and a stable payment configuration. [source]


Development of the Detachment under the Influence of the Supersonic Flow in the Divertor Region

CONTRIBUTIONS TO PLASMA PHYSICS, Issue 1-3 2008
O. Marchuk
Abstract It is demonstrated in the framework of a one-dimensional model for the scrape-off layer that with increasing upstream plasma density and decreasing temperature near divertor target plates a supersonic flow develops in the front of the target. This flow is an important mechanism for the transition from high-recycling regime to a weak detached state and has a significant impact on the plasma parameters, in particular, the pressure and particle flux to the plates, after detachment. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]


Novel agents to override imatinib resistance mechanisms

DRUG DEVELOPMENT RESEARCH, Issue 7 2008
Asumi Yokota
Abstract Chronic myelogenous leukemia (CML) is a disorder of hematopoietic stem cells that results from the Philadelphia chromosome (Ph) created through translocation of human chromosomes 9 and 22. The resulting Bcr-Abl fusion protein has constitutively high tyrosine kinase activity that causes transformation of hematopoietic stem cells. Imatinib mesylate (IM) was developed as a specific Bcr-Abl kinase inhibitor and is efficacious in treating Ph-chromosome-positive (Ph+) leukemias such as CML and Ph+ acute lymphoblastic leukemia (ALL). Within a few years of its introduction to the clinic, IM has dramatically altered the first-line therapy for CML. Although most newly diagnosed CML patients in the chronic phase (CP) achieved durable responses when treated with IM, resistance to IM has become a major problem in patients with advanced-stage disease. The most important mechanism of IM resistance are point mutations within the Abl kinase domain; therefore, there is an urgent need for novel agents that can inhibit mutated Bcr-Abl. In this review, we describe novel Bcr-Abl tyrosine kinase inhibitors, the so-called "Super Gleevec" inhibitors. Drug Dev Res 69:398,406, 2008. © 2008 Wiley-Liss, Inc. [source]


Hydrogenase- and outer membrane c -type cytochrome-facilitated reduction of technetium(VII) by Shewanella oneidensis MR-1

ENVIRONMENTAL MICROBIOLOGY, Issue 1 2008
Matthew J. Marshall
Summary Pertechnetate, 99Tc(VII)O4,, is a highly mobile radionuclide contaminant at US Department of Energy sites that can be enzymatically reduced by a range of anaerobic and facultatively anaerobic microorganisms, including Shewanella oneidensis MR-1, to poorly soluble Tc(IV)O2(s). In other microorganisms, Tc(VII)O4, reduction is generally considered to be catalysed by hydrogenase. Here, we provide evidence that although the NiFe hydrogenase of MR-1 was involved in the H2 -driven reduction of Tc(VII)O4,[presumably through a direct coupling of H2 oxidation and Tc(VII) reduction], the deletion of both hydrogenase genes did not completely eliminate the ability of MR-1 to reduce Tc(VII). With lactate as the electron donor, mutants lacking the outer membrane c -type cytochromes MtrC and OmcA or the proteins required for the maturation of c -type cytochromes were defective in reducing Tc(VII) to nanoparticulate TcO2·nH2O(s) relative to MR-1 or a NiFe hydrogenase mutant. In addition, reduced MtrC and OmcA were oxidized by Tc(VII)O4,, confirming the capacity for direct electron transfer from these OMCs to TcO4,. c -Type cytochrome-catalysed Tc(VII) reduction could be a potentially important mechanism in environments where organic electron donor concentrations are sufficient to allow this reaction to dominate. [source]


Olfactory Communication and Neighbor Recognition in Giant Kangaroo Rats

ETHOLOGY, Issue 2 2001
Heather Gardner Murdock
We hypothesized that olfactory communication facilitates neighbor recognition in the giant kangaroo rat, Dipodomys ingens, and is therefore influential in coordinating social interactions in this solitary, desert rodent. We tested whether (i) D. ingens can discriminate between odors of same- and opposite-sex conspecifics; and (ii) the kangaroo rats exhibit scent preferences based on familiarity. In habituation-discrimination tests, we found that both genders distinguish differences between the scent of individuals of the same- and opposite-sex. In olfactory preference tests, both males and females spent significantly more time investigating the scent of their familiar cagemate than the scent of an unfamiliar conspecific. Giant kangaroo rats may be able to recognize familiar neighbors from olfactory cues, thus supporting a hypothesis of neighbor recognition. Neighbor recognition may be an important mechanism of social interactions in this endangered species. [source]


D-2-Hydroxyglutaric acid inhibits creatine kinase activity from cardiac and skeletal muscle of young rats

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003
C. G. Da Silva
Abstract Background, Tissue accumulation of high amounts of D-2-hydroxyglutaric acid (DGA) is the biochemical hallmark of the inherited neurometabolic disorder D-2-hydroxyglutaric aciduria (DHGA). Patients affected by this disease usually present hypotonia, muscular weakness, hypothrophy and cardiomyopathy, besides severe neurological findings. However, the underlying mechanisms of muscle injury in this disorder are virtually unknown. Materials and methods, In the present study we have evaluated the in vitro role of DGA, at concentrations ranging from 0·25 to 5·0 mm, on total, cytosolic and mitochondrial creatine kinase activities from skeletal and cardiac muscle of 30-day-old Wistar rats. We also tested the effects of various antioxidants on the effects elicited by DGA. Results, We first verified that total creatine kinase (CK) activity from homogenates was significantly inhibited by DGA (22,24% inhibition) in skeletal and cardiac muscle, and that this activity was approximately threefold higher in skeletal muscle than in cardiac muscle. We also observed that CK activities from mitochondrial (Mi-CK) and cytosolic (Cy-CK) preparations from skeletal muscle and cardiac muscle were also inhibited (12,35% inhibition) by DGA at concentrations as low as 0·25 mm, with the effect being more pronounced in cardiac muscle preparations. Finally, we verified that the DGA-inhibitory effect was fully prevented by preincubation of the homogenates with reduced glutathione and cysteine, suggesting that this effect is possibly mediated by modification of essential thiol groups of the enzyme. Furthermore, ,-tocopherol, melatonin and the inhibitor of nitric oxide synthase L-NAME were unable to prevent this effect, indicating that the most common reactive oxygen and nitrogen species were not involved in the inhibition of CK provoked by DGA. Conclusion, Considering the importance of creatine kinase activity for cellular energy homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA might be an important mechanism involved in the myopathy and cardiomyopathy of patients affected by DHGA. [source]


Activation of p53 signalling in acetylsalicylic acid-induced apoptosis in OC2 human oral cancer cells

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003
C.-C. Ho
Abstract Background, Nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid (ASA, aspirin) are well known chemotherapeutic agents of cancers; however, the signalling molecules involved remain unclear. The aim of this study was to investigate the possible existence of a putative p53-dependent pathway underlying the ASA-induced apoptosis in OC2 cells, a human oral cancer cell line. Materials and methods, The methyl tetrazolium (MTT) assay was employed to quantify differences in cell viability. DNA ladder formation on agarose electrophoresis was used as apoptosis assay. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Flow cytometry was used to confirm the effect of ASA on cell cycle. Patterns of changes in expression were scanned and analyzed using the NIH image 1·56 software (NIH, Bethesda, MD, USA). All the data were analyzed by anova. Results, Acetylsalicylic acid reduced cell viability and presence of internucleosomal DNA fragmentation. In the meanwhile, phosphorylation of p53 at serine 15, accumulation of p53 and increased the expression of its downstream target genes, p21 and Bax induced by ASA. The expression of cyclooxygenase-2 was suppressed. Disruption of p53-murine double minute-2 (MDM2) complex formation resulted in increasing the expression of MDM2 60-kDa cleavage fragment. Inhibited the activation of p42/p44 mitogen-activated protein kinase (MAPK) by PD98059, a specific inhibitor of extracellular regulatory kinase (ERK), significantly decreased cell viability and enhanced the expression of p53 induced by ASA. The result of the cell-cycle analysis showed that ASA and PD98059 induced the cell cycle arrested at the G0/G1 phase and resulted in apoptosis. Conclusion, Nonsteroidal anti-inflammatory drug-inhibited cyclooxygenase is not the only or even the most important mechanism of inhibition. Our study presents evidences that activation of p53 signalling involved in apoptosis induced by ASA. Furthermore, the apoptotic effect was enhanced by blocking the activation of p42/p44 MAPK in response to treatment with ASA, thus indicating a negative role for p42/p44 MAPK. [source]


Post-translational and cell type-specific regulation of CXCR4 expression by cytokines

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2003
Hilke Brühl
Abstract We have investigated the regulation and function of the chemokine receptor CXCR4 on neutrophils. CXCR4 is hardly detectable on neutrophils in the peripheral blood. However, overnight culture strongly up-regulates CXCR4 expression on the cell surface. The functional activity of CXCR4 on cultured neutrophils was confirmed by stromal cell-derived factor (SDF)-induced migration and up-regulation of the integrins CD11b and CD11c. CXCR4 surface expression on neutrophils but not on lymphocytes and monocytes is rapidly down-regulated after stimulation with TNF-, and IFN-,, resulting in significantly decreased SDF-induced functional responses of neutrophils. In contrast to surface expression, CXCR4 mRNA expression was several-fold increased in cytokine-stimulated neutrophils, suggesting a post-translational regulation. By confocal microscopy we demonstrate that CXCR4 is internalized after stimulation with TNF-, and IFN-,. The down-modulation of CXCR4 surface expression in response to TNF-, and IFN-, was fully reversible after cytokine removal. Further, CXCR4 down-modulation could be completely blocked by hypertonic sucrose and significantly reduced by chlorpromazine indicating the involvement of clathrin-coated pits. Internalization of CXCR4 by cytokines in a cell type-specific manner is a novel and functionally important mechanism of chemokine receptor regulation. [source]


Recruitment of the Sonic hedgehog signalling cascade in electroconvulsive seizure-mediated regulation of adult rat hippocampal neurogenesis

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005
Sunayana B. Banerjee
Abstract Electroconvulsive seizure (ECS) induces structural remodelling in the adult mammalian brain, including an increase in adult hippocampal neurogenesis. The molecular mechanisms that underlie this increase in the proliferation of adult hippocampal progenitors are at present not well understood. We hypothesized that ECS may recruit the Sonic hedgehog (Shh) pathway to mediate its effects on adult hippocampal neurogenesis, as Shh is known to enhance the proliferation of neuronal progenitors and is expressed in the adult basal forebrain, a region that sends robust projections to the hippocampus. Here we demonstrate that the ECS-induced increase in proliferation of adult hippocampal progenitors was completely blocked in animals treated with cyclopamine, a pharmacological inhibitor of Shh signalling. Our results suggest that both acute and chronic ECS enhance Shh signalling in the adult hippocampus, as we observed a robust upregulation of Patched (Ptc) mRNA, a component of the Shh receptor complex and a downstream transcriptional target of Shh signalling. This increase was rapid and restricted to the dentate gyrus, where the adult hippocampal progenitors reside. In addition, both acute and chronic ECS decreased Smoothened (Smo) mRNA, the other component of the Shh receptor complex, selectively within the dentate gyrus. However, ECS did not appear to influence Shh expression within the basal forebrain, the site from which it has been suggested to be anterogradely transported to the hippocampus. Together, our findings demonstrate that ECS regulates the Shh signalling cascade and indicate that the Shh pathway may be an important mechanism through which ECS enhances adult hippocampal neurogenesis. [source]


Poorly crystalline mineral phases protect organic matter in acid subsoil horizons

EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 6 2005
M. Kleber
Summary Soil minerals are known to influence the biological stability of soil organic matter (SOM). Our study aimed to relate properties of the mineral matrix to its ability to protect organic C against decomposition in acid soils. We used the amount of hydroxyl ions released after exposure to NaF solution to establish a reactivity gradient spanning 12 subsoil horizons collected from 10 different locations. The subsoil horizons represent six soil orders and diverse geological parent materials. Phyllosilicates were characterized by X-ray diffraction and pedogenic oxides by selective dissolution procedures. The organic carbon (C) remaining after chemical removal of an oxidizable fraction of SOM with NaOCl solution was taken to represent a stable organic carbon pool. Stable organic carbon was confirmed as older than bulk organic carbon by a smaller radiocarbon (14C) content after oxidation in all 12 soils. The amount of stable organic C did not depend on clay content or the content of dithionite,citrate-extractable Fe. The combination of oxalate-extractable Fe and Al explained the greatest amount of variation in stable organic C (R2 = 0.78). Our results suggest that in acid soils, organic matter is preferentially protected by interaction with poorly crystalline minerals represented by the oxalate-soluble Fe and Al fraction. This evidence suggests that ligand exchange between mineral surface hydroxyl groups and negatively charged organic functional groups is a quantitatively important mechanism in the stabilization of SOM in acid soils. The results imply a finite stabilization capacity of soil minerals for organic matter, limited by the area density of reactive surface sites. [source]


The effect of organic acids on base cation leaching from the forest floor under six North American tree species

EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 2 2001
F. A. Dijkstra
Summary Organic acidity and its degree of neutralization in the forest floor can have large consequences for base cation leaching under different tree species. We investigated the effect of organic acids on base cation leaching from the forest floor under six common North American tree species. Forest floor samples were analysed for exchangeable cations and forest floor solutions for cations, anions, simple organic acids and acidic properties. Citric and lactic acid were the most common of the acids under all species. Malonic acid was found mainly under Tsuga canadensis (hemlock) and Fagus grandifolia (beech). The organic acids were positively correlated with dissolved organic carbon and contributed significantly to the organic acidity of the solution (up to 26%). Forest floor solutions under Tsuga canadensis contained the most dissolved C and the most weak acidity among the six tree species. Under Tsuga canadensis we also found significant amounts of strong acidity caused by deposition of sulphuric acid from the atmosphere and by strong organic acids. Base cation exchange was the most important mechanism by which acidity was neutralized. Organic acids in solution from Tsuga canadensis, Fagus grandifolia, Acer rubrum (red maple) and Quercus rubra (red oak) were hardly neutralized while much more organic acidity was neutralized for Acer saccharum (sugar maple) and Fraxinus americana (white ash). We conclude that quantity, nature and degree of neutralization of organic acids differ among the different tree species. While the potential for base cation leaching with organic acids from the forest floor is greatest under Tsuga canadensis, actual leaching with organic anions is greatest under Acer saccharum and Fraxinus americana under which the forest floor contains more exchangeable cations than does the strongly acidified forest floor under Tsuga canadensis. [source]


THE ENFORCEMENT OF COOPERATION BY POLICING

EVOLUTION, Issue 7 2010
Claire El Mouden
Policing is regarded as an important mechanism for maintaining cooperation in human and animal social groups. A simple model providing a theoretical overview of the coevolution of policing and cooperation has been analyzed by Frank (1995, 1996b, 2003, 2009), and this suggests that policing will evolve to fully suppress cheating within social groups when relatedness is low. Here, we relax some of the assumptions made by Frank, and investigate the consequences for policing and cooperation. First, we address the implicit assumption that the individual cost of investment into policing is reduced when selfishness dominates. We find that relaxing this assumption leads to policing being favored only at intermediate relatedness. Second, we address the assumption that policing fully recovers the loss of fitness incurred by the group owing to selfishness. We find that relaxing this assumption prohibits the evolution of full policing. Finally, we consider the impact of demography on the coevolution of policing and cooperation, in particular the role for kin competition to disfavor the evolution of policing, using both a heuristic "open" model and a "closed" island model. We find that large groups and increased kin competition disfavor policing, and that policing is maintained more readily than it invades. Policing may be harder to evolve than previously thought. [source]


A TEST OF WORKER POLICING THEORY IN AN ADVANCED EUSOCIAL WASP, VESPULA RUFA

EVOLUTION, Issue 6 2005
T. Wenseleers
Abstract Mutual policing is an important mechanism for maintaining social harmony in group-living organisms. In some ants, bees, and wasps, workers police male eggs laid by other workers in order to maintain the reproductive primacy of the queen. Kin selection theory predicts that multiple mating by the queen is one factor that can selectively favor worker policing. This is because when the queen is mated to multiple males, workers are more closely related to queen's sons than to the sons of other workers. Here we provide an additional test of worker policing theory in Vespinae wasps. We show that the yellowjacket Vespula rufa is characterized by low mating frequency, and that a significant percentage of the males are workers' sons. This supports theoretical predictions for paternities below 2, and contrasts with other Vespula species, in which paternities are higher and few or no adult males are worker produced, probably due to worker policing, which has been shown in one species, Vespula vulgaris. Behavioral observations support the hypothesis that V. rufa has much reduced worker policing compared to other Vespula. In addition, a significant proportion of worker-laid eggs were policed by the queen. [source]


COSTS OF AN INDUCED IMMUNE RESPONSE ON SEXUAL DISPLAY AND LONGEVITY IN FIELD CRICKETS

EVOLUTION, Issue 10 2004
Alain Jacot
Abstract Immune system activation may benefit hosts by generating resistance to parasites. However, natural resources are usually limited, causing a trade-off between the investment in immunity and that in other life-history or sexually selected traits. Despite its importance for the evolution of host defense, state-dependent fitness costs of immunity received little attention under natural conditions. In a field experiment we manipulated the nutritional condition of male field crickets Gryllus campestris and subsequently investigated the effect of an induced immune response through inoculation of bacterial lipopolysaccharides. Immune system activation caused a condition-dependent reduction in body condition, which was proportional to the condition-gain during the preceding food-supplementation period. Independent of nutritional condition, the immune insult induced an enduring reduction in daily calling rate, whereas control-injected males fully regained their baseline level of sexual signaling following a temporary decline. Since daily calling rate affects female mate choice under natural conditions, this suggests a decline in male mating success as a cost of induced immunity. Food supplementation enhanced male life span, whereas the immune insult reduced longevity, independent of nutritional status. Thus, immune system activation ultimately curtails male fitness due to a combined decline in sexual display and life span. Our field study thus indicates a key role for fitness costs of induced immunity in the evolution of host defense. In particular, costs expressed in sexually selected traits might warrant the honest advertisement of male health status, thus representing an important mechanism in parasite-mediated sexual selection. [source]


The thioredoxin-independent isoform of chloroplastic glyceraldehyde-3-phosphate dehydrogenase is selectively regulated by glutathionylation

FEBS JOURNAL, Issue 1 2007
Mirko Zaffagnini
In animal cells, many proteins have been shown to undergo glutathionylation under conditions of oxidative stress. By contrast, very little is known about this post-translational modification in plants. In the present work, we showed, using mass spectrometry, that the recombinant chloroplast A4 -glyceraldehyde-3-phosphate dehydrogenase (A4 -GAPDH) from Arabidopsis thaliana is glutathionylated with either oxidized glutathione or reduced glutathione and H2O2. The formation of a mixed disulfide between glutathione and A4 -GAPDH resulted in the inhibition of enzyme activity. A4 -GAPDH was also inhibited by oxidants such as H2O2. However, the effect of glutathionylation was reversed by reductants, whereas oxidation resulted in irreversible enzyme inactivation. On the other hand, the major isoform of photosynthetic GAPDH of higher plants (i.e. the AnBn -GAPDH isozyme in either A2B2 or A8B8 conformation) was sensitive to oxidants but did not seem to undergo glutathionylation significantly. GAPDH catalysis is based on Cys149 forming a covalent intermediate with the substrate 1,3-bisphosphoglycerate. In the presence of 1,3-bisphosphoglycerate, A4 -GAPDH was fully protected from either oxidation or glutathionylation. Site-directed mutagenesis of Cys153, the only cysteine located in close proximity to the GAPDH active-site Cys149, did not affect enzyme inhibition by glutathionylation or oxidation. Catalytic Cys149 is thus suggested to be the target of both glutathionylation and thiol oxidation. Glutathionylation could be an important mechanism of regulation and protection of chloroplast A4 -GAPDH from irreversible oxidation under stress. [source]


A novel N-terminal hydrophobic motif mediates constitutive degradation of serum- and glucocorticoid-induced kinase-1 by the ubiquitin,proteasome pathway

FEBS JOURNAL, Issue 13 2006
Agata M. Bogusz
Serum- and glucocorticoid-induced protein kinase-1 (SGK-1) plays a critical role in regulation of the epithelial sodium channel, ENaC. SGK-1 also shares significant catalytic domain homology with protein kinase B (PKB/AKT-1) and is a downstream effector of antiapoptotic phosphoinositide 3-kinase signaling. Steady-state levels of an active SGK-1 are tightly regulated by rapid transcriptional activation and post-translational modification including phosphorylation. We show here that endogenous SGK-1 protein is polyubiquitinated and rapidly degraded by the 26S proteasome. In contrast to other rapidly degraded kinases, neither the catalytic activity of SGK-1 nor activation site phosphorylation was required for its ubiquitin modification and degradation. Instead, SGK-1 degradation required a lysine-less six-amino-acid (amino acids 19,24) hydrophobic motif (GMVAIL) within the N-terminal domain. Deletion of amino acids 19,24 significantly increased the half-life of SGK1 and prevented its ubiquitin modification. Interestingly, this minimal region was also required for the association of SGK-1 with the endoplasmic reticulum. Ubiquitin modification and degradation of SGK-1 were increasingly inhibited by the progressive mutation of six N-terminal lysine residues surrounding the GMVAIL motif. Mutation of all six lysines to arginine did not disrupt the subcellular localization of SGK-1 despite a significant decrease in ubiquitination, implying that this modification per se was not required for targeting to the endoplasmic reticulum. These results suggest that constitutive ubiquitin-mediated degradation of SGK-1 is an important mechanism regulating its biological activity. [source]


Patchy distribution of flexible genetic elements in bacterial populations mediates robustness to environmental uncertainty

FEMS MICROBIOLOGY ECOLOGY, Issue 3 2008
Holger Heuer
Abstract The generation and maintenance of genetic variation seems to be a general ecological strategy of bacterial populations. Thereby they gain robustness to irregular environmental change, which is primarily the result of the dynamic evolution of biotic interactions. A benefit of maintaining population heterogeneity is that only a fraction of the population has to bear the cost of not (yet) beneficial deviation. On evolutionary time frames, an added value of the underlying mechanisms is evolvability, i.e. the heritable ability of an evolutionary lineage to generate and maintain genetic variants that are potentially adaptive in the course of evolution. Horizontal gene transfer is an important mechanism that can lead to differences between individuals within bacterial populations. Broad host-range plasmids foster this heterogeneity because they are typically present in only a fraction of the population and provide individual cells with genetic modules newly acquired from other populations or species. We postulate that the benefit of robustness on population level could balance the cost of transfer and replication functions that plasmids impose on their hosts. Consequently, mechanisms that make a subpopulation conducive to specific conjugative plasmids may have evolved, which could explain the persistence of even cryptic plasmids that do not encode any traits. [source]


Intramembrane-sensing histidine kinases: a new family of cell envelope stress sensors in Firmicutes bacteria

FEMS MICROBIOLOGY LETTERS, Issue 2 2006
Thorsten Mascher
Abstract Two-component signal-transducing systems (TCS) consist of a histidine kinase (HK) that senses a specific environmental stimulus, and a cognate response regulator (RR) that mediates the cellular response. Most HK are membrane-anchored proteins harboring two domains: An extracytoplasmic input and a cytoplasmic transmitter (or kinase) domain, separated by transmembrane helices that are crucial for the intramolecular information flow. In contrast to the cytoplasmic domain, the input domain is highly variable, reflecting the plethora of different signals sensed. Intramembrane-sensing HK (IM-HK) are characterized by their short input domain, consisting solely of two putative transmembane helices. They lack an extracytoplasmic domain, indicative for a sensing process at or from within the membrane interface. Most proteins sharing this domain architecture are found in Firmicutes bacteria. Two major groups can be differentiated based on sequence similarity and genomic context: (1) BceS-like IM-HK that are functionally and genetically linked to ABC transporters, and (2) LiaS-like IM-HK, as part of three-component systems. Most IM-HK sense cell envelope stress, and identified target genes are often involved in maintaining cell envelope integrity, mediating antibiotic resistance, or detoxification processes. Therefore, IM-HK seem to constitute an important mechanism of cell envelope stress response in low G+C Gram-positive bacteria. [source]


Seamount volcanism along the Gakkel Ridge, Arctic Ocean

GEOPHYSICAL JOURNAL INTERNATIONAL, Issue 3 2008
James R. Cochran
SUMMARY The Gakkel Ridge in the Arctic Ocean is the slowest spreading portion of the global mid-ocean ridge system. Total spreading rates vary from 12.8 mm yr,1 near Greenland to 6.5 mm yr,1 at the Siberian margin. Melting models predict a dramatic decrease in magma production and resulting crustal thickness at these low spreading rates. At slow spreading ridges, small volcanic seamounts are a dominant morphologic feature of the rift valley floor and an important mechanism in building the oceanic crust. This study quantitatively investigates the extent, nature and distribution of seamount volcanism at the ultraslow Gakkel Ridge, the manner in which it varies along the ridge axis and the relationship of the volcanoes to the larger scale rift morphology. A numerical algorithm is used to identify and characterize isolated volcanic edifices by searching gridded swath-bathymetry data for closed concentric contours protruding above the surrounding seafloor. A maximum likelihood model is used to estimate the total number of seamounts and the characteristic height within different seamount populations. Both the number and size of constructional volcanic features is greatly reduced at the Gakkel Ridge compared with the Mid-Atlantic Ridge (MAR). The density of seamounts (number/area) on the rift valley floor of the Western Volcanic Zone (WVZ) is ,55% that of the MAR. The observed volcanoes are also much smaller, so, the amount of erupted material is greatly reduced compared with the MAR. However, the WVZ is still able to maintain a MAR-like morphology with axial volcanic ridges, volcanoes scattered on the valley floor and rift valley walls consisting of high-angle faults. Seamount density at the Eastern Volcanic Zone (EVZ) is ,45% that of the WVZ (,25% that of the MAR). Seamounts are clustered at the widely spaced magmatic centres characteristic of the EVZ, although some seamounts are found between magmatic centres. These seamounts tend to be located at the edge of the rift valley or on the valley walls rather than on the valley floor. Seamounts in the Sparsely Magmatic Zone (SMZ) are located almost entirely at the 19°E magmatic centre with none observed within a 185 km-long portion of the rift valley floor. The EVZ and SMZ appear to display a mode of crustal accretion, characterized by extreme focusing of melt to the magmatic centres. Magmas erupted between the magmatic centres appear to have ascended along faults. This is very different from what is observed at the WVZ (or the MAR), and there is a threshold transition between the two modes of crustal accretion. At the Gakkel Ridge, the location of the transition appears to be localized by a boundary in mantle composition. [source]


Global-scale patterns of nutrient resorption associated with latitude, temperature and precipitation

GLOBAL ECOLOGY, Issue 1 2009
Z. Y. Yuan
ABSTRACT Aim Nutrient resorption from senescing leaves is an important mechanism of nutrient conservation in plants, but the patterns of nutrient resorption at the global scale are unknown. Because soil nutrients vary along climatic gradients, we hypothesize that nutrient resorption changes with latitude, temperature and precipitation. Location Global. Methods We conducted a meta-analysis on a global data set collected from published literature on nitrogen (N) and phosphorus (P) resorption of woody plants. Results For all data pooled, both N resorption efficiency (NRE) and P resorption efficiency (PRE) were significantly related to latitude, mean annual temperature (MAT) and mean annual precipitation (MAP): NRE increased with latitude but decreased with MAT and MAP. In contrast, PRE decreased with latitude but increased with MAT and MAP. When functional groups (shrub versus tree, coniferous versus broadleaf and evergreen versus deciduous) were examined individually, the patterns of NRE and PRE in relation to latitude, MAT and MAP were generally similar. Main conclusions The relationships between N and P resorption and latitude, MAT and MAP indicate the existence of geographical patterns of plant nutrient conservation strategies in relation to temperature and precipitation at the global scale, particularly for PRE, which can be an indicator for P limitation in the tropics and selective pressure shaping the evolution of plant traits. Our results suggest that, although the magnitude of plant nutrient resorption might be regulated by local factors such as substrate, spatial patterns are also controlled by temperature or precipitation. [source]


The Neurogenic Basis of Migraine

HEADACHE, Issue 9 2008
F. Michael Cutrer MD
There is accumulating evidence of a neurogenic basis of migraine. This evidence arises from both the clinical and experimental domains. Many of the well known clinical features of migraine attacks including the prodrome are not explained by changes in vascular caliber. Despite the fact that ergotamines and triptans are vasoactive does not provide substantive proof that vasoconstriction is their most important mechanism of action. Several effective treatments for migraine, both old and new, do not affect vascular caliber. Experimental evidence from investigation of both the aura and headache phases of migraine clearly supports a neural basis of migraine. All genes thus far conclusively associated with hemiplegic migraine code for neural proteins. [source]


Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites

HEPATOLOGY, Issue 1 2000
María Pérez-Paramo
Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with ,-adrenoceptor blockers, but the impact of this treatment in the factors promoting bacterial translocation has not been investigated. This study was aimed at investigating in cirrhotic rats with ascites the effect of propranolol on intestinal bacterial load, transit, and permeability of the bowel and on the rate of bacterial translocation. Bacterial translocation to mesenteric lymph nodes and intestinal bacterial overgrowth, permeability (urinary excretion of 99mTc-diethylenetriaminepentaacetic acid [99mTc-DTPA]), and transit (geometric center ratio of 51Cr) were assessed in 29 rats with carbon tetrachloride (CCl4 ) cirrhosis and 20 controls. These variables were then measured in 12 placebo- and in 13 propranolol-treated ascitic cirrhotic rats. Bacterial translocation was present in 48% of the cirrhotic rats and in none of the controls. Cirrhotic rats with intestinal bacterial overgrowth had a significantly higher rate of translocation and slower intestinal transit than those without it. Among the 15 rats with overgrowth and a 99mTc-DTPA excretion greater than 10%, 15 had translocation and 2 had bacterial peritonitis. Only 1 of the 14 rats with either intestinal overgrowth or a 99mTc-DTPA excretion greater than 10% presented translocation. Compared with the placebo group, propranolol-treated animals had significantly lower portal pressure, faster intestinal transit, and lower rates of bacterial overgrowth and translocation. In ascitic cirrhotic rats, bacterial translocation results from intestinal overgrowth and severe damage to gut permeability. In this setting, intestinal overgrowth is associated with intestinal hypomotility. Propranolol accelerates the intestinal transit, decreasing the rates of bacterial overgrowth and translocation. [source]


T cell anergy and costimulation

IMMUNOLOGICAL REVIEWS, Issue 1 2003
Leonard J. Appleman
Summary:, T lymphocytes play a key role in immunity by distinguishing self from nonself peptide antigens and regulating both the cellular and humoral arms of the immune system. Acquired, antigen-specific unresponsiveness is an important mechanism by which T cell responses to antigen are regulated in vivo. Clonal anergy is the term that describes T cell unresponsiveness at the cellular level. Anergic T cells do not proliferate or secrete interleukin (IL)-2 in response to appropriate antigenic stimulation. However, anergic T cells express the IL-2 receptor, and anergy can be broken by exogenous IL-2. Anergy can be induced by submitogenic exposure to peptide antigen in the absence of a costimulatory signal provided by soluble cytokines or by interactions between costimulatory receptors on T cells and counter-receptors on antigen-presenting cells. The molecular events that mediate the induction and maintenance of T cell anergy are the focus of this review. The molecular consequences of CD28,B7 interaction are discussed as a model for the costimulatory signal that leads to T cell activation rather than the induction of anergy. [source]


Identification of differentially methylated CpG islands in prostate cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2004
Yasushi Yamada
Abstract Epigenetic change such as DNA methylation is one important mechanism for regulating gene expression as genetic change, such as mutation or loss of heterozygosity. Methylation of cancer-related genes has been shown to play an important role in carcinogenesis and tumor progression. Using methylated CpG island amplification (MCA)/representational difference analysis (RDA), we identified four CpG islands in neurotrophin tyrosine kinase receptor type 2 (NTRK2), Protocadherine Flamingo1 and MFPC (Methylated Fragments in Prostate Cancer) 7 and 8. Bisulfite sequencing revealed that 2 regions of NTRK2 as well as MFPC7 and MFPC8 were aberrantly methylated in prostate cancer cell lines, and COBRA showed that 48 (76.24%), 37 (58.7%) and 14 (22.2%) of 63 prostate cancer tissues were methylated, respectively, for these sites. On the other hand, none of 13 benign prostate samples were methylated, except for 1 (7.7%) with NTRK2. For NTRK2, mRNA expression was negative in prostate cancer cell lines (LNCaP and DU145) but was recovered on a methyltransferase inhibitor (5-Aza-CdR) treatment. The role of NTRK2 within NTRK remains unclear. Our results suggest that these 3 hypermethylated DNA fragments also may be markers of prostate cancer detection. © 2004 Wiley-Liss, Inc. [source]


Water vapour transport associated with tropical,temperate trough systems over southern Africa and the southwest Indian Ocean

INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 5 2004
Martin C. Todd
Abstract Tropical,temperate trough (TTT) systems are the dominant rain-producing synoptic type over southern Africa. They represent an important mechanism of poleward transport of energy and momentum. This paper provides an analysis of water vapour transport in TTT systems. An objective sampling of TTT systems is conducted from analysis of daily satellite rainfall products. During the sampled TTT events, rain bands extend from tropical southern Africa near 10 °S to the midlatitudes of the southwest Indian Ocean. The divergent and non-divergent (streamfunction) components of vertically integrated water vapour flux associated with major TTT events are calculated, from National Centers for Environmental Prediction reanalysis data. During TTT events the streamfunction circulation dominates water vapour transport, although adjustments to the divergent component are relatively more important. The results indicate that TTT events facilitate a substantial water vapour flux from the tropics into the midlatitudes. Water vapour transport to the midlatitudes along the TTT axis is facilitated largely by changes to the streamfunction, associated with a strengthening and eastward displacement of the Indian Ocean high, and the advent of midlatitude transients. It is also shown that TTT systems are major regions of moisture convergence. The high vapour concentrations along the full extent of the TTT rain bands are maintained by the divergent circulation. The structure of these divergent vapour flux anomalies is suggestive of adjustments to the Walker circulation, involving strong anomalous divergence over the maritime continent/west Pacific and a weaker enhancement of the major divergence centre over the tropical Atlantic. Copyright © 2004 Royal Meteorological Society [source]


Performance of statistical downscaling models in GCM validation and regional climate change estimates: application for Swedish precipitation

INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 5 2001
Aristita Busuioc
Abstract This study deals with an analysis of the performance of a general circulation model (GCM) (HadCM2) in reproducing the large-scale circulation mechanisms controlling Swedish precipitation variability, and in estimating regional climate changes owing to increased CO2 concentration by using canonical correlation analysis (CCA). Seasonal precipitation amounts at 33 stations in Sweden over the period 1899,1990 are used. The large-scale circulation is represented by sea level pressure (SLP) over the Atlantic,European region. The link between seasonal Swedish precipitation and large-scale SLP variability is strong in all seasons, but especially in winter and autumn. For these two seasons, the link is a consequence of the North Atlantic Oscillation (NAO) pattern. In winter, another important mechanism is related to a cyclonic/anticyclonic structure centred over southern Scandinavia. In the past century, this connection has remained almost unchanged in time for all seasons except spring. The downscaling model that is built on the basis of this link is skilful in all seasons, but especially so in winter and autumn. This observed link is only partially reproduced by the HadCM2 model, while large-scale SLP variability is fairly well reproduced in all seasons. A concept about optimum statistical downscaling models for climate change purposes is proposed. The idea is related to the capability of the statistical downscaling model to reproduce low frequency variability, rather than having the highest skill in terms of explained variance. By using these downscaling models, it was found that grid point and downscaled climate signals are similar (increasing precipitation) in summer and autumn, while in winter, the amplitudes of the two signals are different. In spring, both signals show a slight increase in the northern and southern parts of Sweden. Copyright © 2001 Royal Meteorological Society [source]


TCRBV3S1 and TCRBV18 gene segment polymorphisms in Brazilian Caucasoid and Black populations

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2002
C. Dresch
Summary The T-cell receptor (TCR) repertoire plays an important role in shaping specific immune responses. Genetic polymorphisms at the TCR locus, in both constant and variable regions, seem to represent an important mechanism for generating inter-individual and inter-population differences. Considering the scarcity of immune parameters characterized for normal human populations, we decided to determine the frequency of two TCRBV polymorphisms (located in the TCRBV3S1 and TCRBV18 gene segments) in two ethnically distinct groups of the general Brazilian population. Both polymorphisms are related to the expression of these segments at the T-cell surface and can consequently modulate the T-cell repertoire, potentially modifying the capacity of a given individual to develop an immune response. These DNA polymorphisms were analysed in material obtained from adult, normal South-American Caucasoid and Black individuals. A total of 139 individuals were analysed for the TCRBV3S1 and 141 for the TCRBV18 gene segment polymorphisms. The data indicated statistically significant differences in allelic frequencies for the two ethnic groups analysed, suggesting that any correlation between TCR usage or T-cell repertoire and development of a given disease should take in account the ethnic origin of the population studied. [source]


Root Distribution of Drought-Resistant Peanut Genotypes in Response to Drought

JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2008
P. Songsri
Abstract The ability of a plant to modify its root distribution to exploit deeper stored soil water may be an important mechanism to avoid drought. This study aimed at assessing root distributions, variations in root length density (RLD) and percentage of root distribution, and the relevance of root traits for yield of drought-resistant peanut genotypes under different available soil water levels. The experiment was conducted in the dry season during the years 2003/04 and 2004/05. Eleven peanut genotypes (ICGV 98300, ICGV 98303, ICGV 98305, ICGV 98308, ICGV 98324, ICGV 98330, ICGV 98348, ICGV 98353, Tainan 9, KK 60-3 and Tifton-8) and three soil moisture levels [field capacity (FC), 2/3 available soil water (AW) and 1/3 AW] were laid out in a split-plot design with four replications. Roots were sampled by a core sampler at 37, 67 and 97 days after sowing (DAS). Root length was determined by a scanner and the WINRHIZO Pro 2004a software. RLD was calculated as the ratio of root length (cm) and soil volume (cm3). Graphical illustration of root distribution was constructed by merging RLD in the first and second soil layers (0,40 cm) as upper roots and pooling RLD at the third, fourth and fifth layers (40,100 cm) as lower roots. Pod yield, biomass and harvest index (HI) were recorded at harvest. A drought tolerance index (DTI) was calculated for each parameter as the ratio of the parameter under stress treatment to that under well-watered conditions. Variations in RLD in 40 to 100 cm layer (RLD40 to 100 cm) were found under well-watered conditions, and the peanut genotypes could be readily identified as high, intermediate and low for this trait. Changes in RLD in the 40 to 100 cm soil layer were found at 2/3 AW and were more evident at 1/3 AW. ICGV 98300, ICGV 98303, ICGV 98305, ICGV 98308 and KK 60-3 were classified as drought responsive as they increased RLD in the deeper subsoil level in response to drought. In general, RLD under drought conditions was not related to biomass production. The ability to maintain the percentage of RLD (DTI for %RLD) was related to pod yield, DTI for pod yield and DTI for HI. ICGV 98300, ICGV 98303, ICGV 98305 exhibited high DTI (RLD40 to 100 cm) which may explain their high pod yield, DTI (PY) and DTI (HI). Based on these observations we classified them as drought-avoiding genotypes. [source]


Withdrawal of Fall-Risk-Increasing Drugs in Older Persons: Effect on Tilt-Table Test Outcomes

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2007
Nathalie Van Der Velde MD
OBJECTIVES: To determine whether outcomes of tilt-table tests improved after withdrawal of fall-risk-increasing drugs (FRIDs). DESIGN: Prospective cohort study. SETTING: Geriatric outpatient clinic. PARTICIPANTS: Two hundred eleven new, consecutive outpatients, recruited from April 2003 until December 2004. MEASUREMENTS: Tilt-table testing was performed on all participants at baseline. Subsequently, FRIDs were withdrawn in all fallers in whom it was safely possible. At a mean follow-up of 6.7 months, tilt-table testing was repeated in 137 participants. Tilt-table testing addressed carotid sinus hypersensitivity (CSH), orthostatic hypotension (OH), and vasovagal collapse (VVC). Odds ratios (ORs) of tilt-table-test normalization according to withdrawal (discontinuation or dose reduction) of FRIDs were calculated using multivariate logistic regression analysis. RESULTS: After adjustment for confounders, the reduction of abnormal test outcomes (ORs) according to overall FRID withdrawal was 0.34 (95% confidence interval (CI)=0.06,1.86) for CSH, 0.35 (95% CI=0.13,0.99) for OH, and 0.27 (95% CI=0.02,3.31) for VVC. For the subgroup of cardiovascular FRIDs, the adjusted OR was 0.13 (95% CI=0.03,0.59) for CSH, 0.44 (95% CI=0.18,1.0) for OH, and 0.21 (95% CI=0.03,1.51) for VVC. CONCLUSION: OH improved significantly after withdrawal of FRIDs. Subgroup analysis of cardiovascular FRID withdrawal showed a significant reduction in OH and CSH. These results imply that FRID withdrawal can cause substantial improvement in cardiovascular homeostasis. Derangement of cardiovascular homeostasis may be an important mechanism by which FRID use results in falls. [source]