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Key Mechanism (key + mechanism)
Selected AbstractsCollagen Remodeling After 585-nm Pulsed Dye Laser Irradiation: An Ultrasonographic AnalysisDERMATOLOGIC SURGERY, Issue 10 2003Brent R. Moody MD Background and Objectives. Nonablative dermal remodeling is an evolving technology that has generated great interest among both laser surgeons and patients. Evidence indicates that dermal collagen formation is the key mechanism of action for the nonablative techniques. We studied, with ultrasound, new collagen formation after nonablative laser irradiation. Methods. Ten patients with facial rhytids underwent a single treatment with a 585-nm pulsed dye laser. The patients were all female, ranging in age from 47 to 67, and were Fitzpatrick skin types I,III. Laser parameters were as follows: an energy fluence of 2.4 to 3.0 J/cm2, a pulse duration of 350 ,sec, and a spot size of 5 mm with no overlap. Ultrasonographic assessments of dermal collagen were taken at baseline and at 30 and 90 days after treatment. Results. Ultrasonography demonstrated an increase in dermal collagen after a single treatment with the 585-nm pulsed dye laser. The greatest degree of neocollagenesis occurred periocularly. Conclusion. A single treatment with a 585-nm pulsed dye laser appears to increase dermal collagen. This increase in dermal collagen can be assessed with noninvasive cutaneous ultrasound. [source] Intraspecific diversity and dominant genotypes resist plant invasionsECOLOGY LETTERS, Issue 1 2008Gregory M. Crutsinger Abstract Numerous studies have asked whether communities with many species deter invasions more so than do species-poor communities or whether dominant species deter invasion by colonizing species. However, little is known about whether high intraspecific diversity can deter biological invasions or whether particular genotypes might deter invasions. In this study, we present experimental evidence that intraspecific diversity and particular genotypes of tall goldenrod, Solidago altissima, can act as a barrier to colonization by new species. We found that biomass of colonizing species was negatively correlated with genotypic diversity, and particular genotypes affected the richness, cover, and biomass of colonizing species. Stem density of S. altissima increased with genotypic diversity and varied among genotypes, suggesting that stem density is a key mechanism in limiting colonization dynamics in this system. Our results indicate that the loss of intraspecific diversity within a dominant plant species can increase susceptibility to plant invasions. [source] Aqueous films limit bacterial cell motility and colony expansion on partially saturated rough surfacesENVIRONMENTAL MICROBIOLOGY, Issue 5 2010Gang Wang Summary Bacterial motility is a key mechanism for survival in a patchy environment and is important for ecosystem biodiversity maintenance. Quantitative description of bacterial motility in soils is hindered by inherent heterogeneity, pore-space complexity and dynamics of microhydrological conditions. Unsaturated conditions result in fragmented aquatic habitats often too small to support full bacterial immersion thereby forcing strong interactions with mineral and air interfaces that significantly restrict motility. A new hybrid model was developed to study hydration effects on bacterial motility. Simulation results using literature parameter values illustrate sensitivity of colony expansion rates to hydration conditions and are in general agreement with measured values. Under matric potentials greater than ,0.5 kPa (wet), bacterial colonies grew fast at colony expansion rates exceeding 421 ± 94 µm h,1; rates dropped significantly to 31 ± 10 µm h,1 at ,2 kPa; as expected, no significant colony expansion was observed at ,5 kPa because of the dominance of capillary pinning forces in the submicrometric water film. Quantification of hydration-related constraints on bacterial motion provides insights into optimal conditions for bacterial dispersion and spatial ranges of resource accessibility important for bioremediation and biogeochemical cycles. Results define surprisingly narrow range of hydration conditions where motility confers ecological advantage on natural surfaces. [source] Hormetic effects of gamma radiation on the stress axis of natural populations of meadow voles (Microtus pennsylvanicus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2005Rudy Boonstra Abstract We tested the hypothesis that low doses of gamma radiation have beneficial, hormetic effects on the stress axis (the hypothalamic-pituitary-adrenocortical axis) of free-ranging meadow vole populations (Microtus pennsylvanicus). Voles were exposed to chronic gamma radiation from a 137Cs field irradiator. In isolated populations, voles received one of three treatments over a four-year period: Controls (0.19,0.42 ,Gy/h , levels that were 2,5X above background levels [0.1 ,Gy/h] and live-trapped in all years , 1982,1985), low doses (22.6 ,Gy/h , 50,200X background, live-trapped from November 1982,April 1985), or high doses (3,840 ,Gy/h , 40,000X background, live-trapped from November 1983,April 1985). Voles exposed to a low dose had levels of free and total corticosterone that were significantly higher than those in the control or high-dose groups. Differences in response to radiation between the sexes were apparent for maximum corticosterone-binding capacity, with females exposed to low doses having higher binding capacity than control or high-dose females, whereas males exposed to low doses had lower binding capacity than control or high-dose males. Low-dose voles had higher counts of neutrophils than either the controls or high-dose voles; hematocrit was greater in the controls than in irradiated voles. These results indicate that voles display a hormetic response to radiation, wherein low doses of an otherwise harmful agent produce a beneficial effect. The stimulation of the stress axis resulting in the increased secretion of glucocorticoids, which may protect against the excessive actions of the immune and inflammatory responses, may be a key mechanism producing this effect. [source] AN EXAMINATION OF THE CONTENT OF COMMUNITY FINANCIAL REPORTS IN QUEENSLAND LOCAL GOVERNMENT AUTHORITIESFINANCIAL ACCOUNTABILITY & MANAGEMENT, Issue 4 2008Trevor Stanley Annual reports, including general purpose financial statements, have been adopted as a key mechanism by which public sector entities discharge their accountability. However, there is concern about the complexity of public sector general purpose financial statements and consequently their effectiveness as an accountability mechanism. In Australia, the Queensland government has moved to address this issue in local government authorities by introducing a Community Financial Report as a means of simplifying the financial statements. A feature of this initiative was the lack of prescription given to local government authorities in the preparation of this report. This paper examines the form and content included in Community Financial Reports and also uses a disclosure index to determine the level of disclosure in the reports. The results of this research show that the form and content of the Community Financial Reports varied considerably. There was no definitive style, with each report being unique. The disclosure index revealed low levels of disclosure by local government authorities in the first year of the report as well as a lack of analysis of the Statements of Financial Performance, Position and Cash Flows. As well, there was a significant difference in the disclosures made by rural local government authorities compared with urban local government authorities. The results of this research will be of interest to local government authorities and local government regulators as they aim to provide useful, understandable information for stakeholders. [source] CREATIVE INDUSTRIES IN THE NETHERLANDS: STRUCTURE, DEVELOPMENT, INNOVATIVENESS AND EFFECTS ON URBAN GROWTHGEOGRAFISKA ANNALER SERIES B: HUMAN GEOGRAPHY, Issue 2 2008Erik Stam ABSTRACT. Creativity is central in stimulating economic growth in cities, regions and advanced capitalist economies in general. There is, of course, no one-to-one relation of the number of firms in creative industries to economic growth. Innovation is a key mechanism explaining the relationship of creative industries with economic performance. Based on an empirical study in the Netherlands we explore the effect of creative industries on innovation, and ultimately on employment growth in cities. In the Netherlands the three specific domains of creative industries - arts, media and publishing, and creative business services - make up 9 per cent of the business population. Drawing on survey data we find that firms in creative industries are indeed relatively innovative. Yet substantial differences are found across the three domains: firms in the arts domain are clearly less innovative, most likely due to a different (less market-oriented) dominant ideology. In addition, firms in creative industries located in urban areas are more innovative than their rural counterparts. We go on to analyse how the concentration of creative industries across cities is connected with employment growth. With the exception of the metropolitan city of Amsterdam, we find no measurable spill-over effect from creative industries. The presence of the creative class (in all kinds of industries other than creative ones) appears to be a much stronger driver of employment growth than creative industries. [source] Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection,HEPATOLOGY, Issue 1 2010Nabora Soledad Reyes de Mochel Oxidative stress has been identified as a key mechanism of hepatitis C virus (HCV),induced pathogenesis. Studies have suggested that HCV increases the generation of hydroxyl radical and peroxynitrite close to the cell nucleus, inflicting DNA damage, but the source of reactive oxygen species (ROS) remains incompletely characterized. We hypothesized that HCV increases the generation of superoxide and hydrogen peroxide close to the hepatocyte nucleus and that this source of ROS is reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase 4 (Nox4). Huh7 human hepatoma cells and telomerase-reconstituted primary human hepatocytes, transfected or infected with virus-producing HCV strains of genotypes 2a and 1b, were examined for messenger RNA (mRNA), protein, and subcellular localization of Nox proteins along with the human liver. We found that genotype 2a HCV induced persistent elevations of Nox1 and Nox4 mRNA and proteins in Huh7 cells. HCV genotype 1b likewise elevated the levels of Nox1 and Nox4 in telomerase-reconstituted primary human hepatocytes. Furthermore, Nox1 and Nox4 proteins were increased in HCV-infected human liver versus uninfected liver samples. Unlike Nox1, Nox4 was prominent in the nuclear compartment of these cells as well as the human liver, particularly in the presence of HCV. HCV-induced ROS and nuclear nitrotyrosine could be decreased with small interfering RNAs to Nox1 and Nox4. Finally, HCV increased the level of transforming growth factor beta 1 (TGF,1). TGF,1 could elevate Nox4 expression in the presence of infectious HCV, and HCV increased Nox4 at least in part through TGF,1. Conclusion: HCV induced a persistent elevation of Nox1 and Nox4 and increased nuclear localization of Nox4 in hepatocytes in vitro and in the human liver. Hepatocyte Nox proteins are likely to act as a persistent, endogenous source of ROS during HCV-induced pathogenesis. Hepatology 2010 [source] Imagining the Future: Children, Education and Intergenerational Transmission of Poverty in Urban BangladeshIDS BULLETIN, Issue 1 2009Naila Kabeer Failure to invest in children's education is widely recognised as a key mechanism for the intergenerational transmission of poverty. At the same time, rising levels of education among different socioeconomic groups in countries like Bangladesh suggest that poverty on its own is not an adequate explanation for this failure. This article uses survey data on low-income households in urban Bangladesh to explore what differentiates parents who have managed to send their children to school from those who have not. One factor is education: parents with no education are more likely to have children of school-going age who are not at school. Different aspects of household vulnerability, as captured by asset deficits, reliance on casual labour and female headship, also play an important role in determining whether children go to school or not. In addition, the article argues that contextual factors have an important influence on how parents imagine their children's future and how children themselves regard education. The hazards of daily life in slum environments, the limited range of job opportunities available and the absence of decent educational facilities all serve to undermine parental commitment and children's motivation with regard to education. The article suggests that the state and civil society should collaborate to promote educational and livelihood interventions which are responsive to the needs of the more vulnerable sections of the poor and to reshape how parents and children envisage the future. [source] Prostacyclin inhibits endothelial cell XIAP ubiquitination and degradationJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Jun-Yang Liou To understand the role of prostacyclin (PGI2) in protecting endothelial cells from apoptosis, we evaluated the effects of carbaprostacyclin (cPGI2) on H2O2 -induced human umbilical vein endothelial cell (HUVEC) apoptosis. cPGI2 suppressed H2O2 -induced annexin V-positive cells in a concentration- and time-dependent manner. Pre-treatment of HUVEC with 50 µM cPGI2 for 4 h produced the maximal anti-apoptotic effect. Authentic PGI2 generated by adenoviral transfer of PGI2 synthetic genes exerted a similar protective effect. cPGI2 inhibited Smac/DIABLO release from mitochondria, caspase 3 activation, focal adhesion protein degradation, and cell detachment. cPGI2 selectively protected X-linked inhibitor of apoptosis protein (X-linked IAP, XIAP) from H2O2 -induced ubiquitination, and preserved XIAP protein levels. PD-98059 but not H-89 abrogated the protective action of cPGI2. cPGI2 increased ERK phosphorylation which was blocked by PD-98059. HUVEC stably transfected with dominant negative Ras abrogated XIAP preservation by cPGI2 while constitutive active Ras increased ERK phosphorylation and protected XIAP from degradation. Our results demonstrate for the first time that PGI2 inhibits XIAP ubiquitination and degradation via the Ras/MEK-1/ERK signaling pathway. Preservation of XIAP proteins represents a key mechanism by which PGI2 protects endothelial cells from oxidant-induced apoptosis. J. Cell. Physiol. 212:840,848, 2007. © 2007 Wiley-Liss, Inc. [source] Size-dependence of growth and mortality influence the shade tolerance of trees in a lowland temperate rain forestJOURNAL OF ECOLOGY, Issue 4 2009Georges Kunstler Summary 1A trade-off between growth in high-light and survival in low-light of species is often proposed as a key mechanism underpinning the dynamics of trees in forest communities. Yet, growth and survival are known to depend on plant size and few studies have analysed how this trade-off can vary between juvenile life stages and the potential consequences of the trade-off for the differences in regeneration rate between species in mixed forests. 2We quantified growth and mortality for two different juvenile life stages , seedlings and saplings , of seven tree species common in temperate rain forests in New Zealand using data from field studies. We found strong evidence that the ranking of species for survival in shade and growth in full light was affected by size. There was a trade-off between seedling survival in low light and sapling height growth in high light, but no trade-offs were observed when considering other combinations of life stages (seedling growth vs. seedling survival, seedling growth vs. sapling survival, or sapling growth vs. sapling survival). 3We ran simulations with an individual-based forest dynamics model , SORTIE/NZ , to explore how the trade-off drives the differences in tree species regeneration success in gaps vs. under closed forest conditions. These simulations indicate that because species' ranks in shade tolerance varied with life stage, regeneration success was not predicted from knowledge of tree performance at a single life stage. For instance, high-light sapling growth was a strong determinant of regeneration success in forest gaps, but seedling growth was also influential. Under closed forest, regeneration success was primarily limited by low-light mortality at the seedling stage, but seedling growth and sapling survival were also influential. 4Synthesis. Growth-survival trade-offs can be strongly affected by the size of the individual analysed, resulting in completely different rankings of the shade tolerance of species across different juvenile life stages. Performance of both seedlings and saplings influenced regeneration success, highlighting the need to consider growth-survival trade-offs and the shade-tolerance strategies of tree species over a large range of juvenile sizes. [source] Changing the pathogenetic roadmap of liver fibrosis?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7pt1 2008Where did it start; where will it go? Abstract The pathophysiology of liver injury has attracted the interest of experimentalists and clinicians over many centuries. With the discovery of liver-specific pericytes , formerly called fat-storing cells, Ito-cells, lipocytes, and currently designated as hepatic stellate cells (HSC) , the insight into the cellular and molecular pathobiology of liver fibrosis has evolved and the pivotal role of HSC as a precursor cell-type for extracellular matrix,producing myofibroblasts has been established. Although activation and transdifferentiation of HSC to myofibroblasts is still regarded as the pathogenetic key mechanism of fibrogenesis, recent studies point to a prominent heterogeneity of the origin of myofibroblasts. Currently, the generation of matrix-synthesizing fibroblasts by epithelial,mesenchymal transition, by influx of bone marrow,derived fibrocytes into damaged liver tissue, and by differentiation of circulating monocytes to fibroblasts after homing in the injured liver are discussed as important complementary mechanisms to enlarge the pool of (myo-)fibroblasts in the fibrosing liver. Among the molecular mediators, transforming growth factor-beta (TGF-,) plays a central role, which is controlled by the bone-morphogenetic protein (BMP)-7, an important antagonist of TGF-, action. The newly discovered pathways supplement the linear concept of HSC activation to myofibroblasts, point to fibrosis as a systemic response involving extrahepatic organs and reactions, add further evidence to a more or less uniform concept of organ fibrosis in general (e.g. liver, lung, kidney), and offer innovative approaches for the development of non-invasive biomarkers and antifibrotic trials. [source] Differential effects of the mitochondrial uncoupling agent, 2,4-dinitrophenol, or the nitroxide antioxidant, Tempol, on synaptic or nonsynaptic mitochondria after spinal cord injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2009Samir P. Patel Abstract We recently documented the progressive nature of mitochondrial dysfunction over 24 hr after contusion spinal cord injury (SCI), but the underlying mechanism has not been elucidated. We investigated the effects of targeting two distinct possible mechanisms of mitochondrial dysfunction by using the mitochondrial uncoupler 2,4-dinitrophenol (2,4-DNP) or the nitroxide antioxidant Tempol after contusion SCI in rats. A novel aspect of this study was that all assessments were made in both synaptosomal (neuronal)- and nonsynaptosomal (glial and neuronal soma)-derived mitochondria 24 hr after injury. Mitochondrial uncouplers target Ca2+ cycling and subsequent reactive oxygen species production in mitochondria after injury. When 2,4-DNP was injected 15 and 30 min after injury, mitochondrial function was preserved in both populations compared with vehicle-treated rats, whereas 1 hr postinjury treatment was ineffective. Conversely, targeting peroxynitrite with Tempol failed to maintain normal bioenergetics in synaptic mitochondria, but was effective in nonsynaptic mitochondria when administered 15 min after injury. When administered at 15 and 30 min after injury, increased hydroxynonenal, 3-NT, and protein carbonyl levels were significantly reduced by 2,4-DNP, whereas Tempol only reduced 3-NT and protein carbonyls after SCI. Despite such antioxidant effects, only 2,4-DNP was effective in preventing mitochondrial dysfunction, indicating that mitochondrial Ca2+ overload may be the key mechanism involved in acute mitochondrial damage after SCI. Collectively, our observations demonstrate the significant role that mitochondrial dysfunction plays in SCI neuropathology. Moreover, they indicate that combinatorial therapeutic approaches targeting different populations of mitochondria holds great potential in fostering neuroprotection after acute SCI. © 2008 Wiley-Liss, Inc. [source] Quantifying effects of particulate properties on powder flow properties using a ring shear testerJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2008Hao Hou Abstract Effects of particle size, morphology, particle density, and surface silicification, on powder flow properties were investigated using a ring shear tester. Flow properties were quantified by flow function (FF), that is, unconfined yield strength, fc, as a function of major principal stress. A total of 11 powders from three series of microcrystalline cellulose (MCC): Avicel (regular MCC, elongated particles), Prosolv (silicified MCC, elongated particles), and Celphere (spherical MCC), were studied. Particle size distribution in each type of MCC was systematically different. Within each series, smaller particles always led to poorer powder flow properties. The slope of FF line was correlated to degree of powder consolidation by external stress. A key mechanism of the detrimental effect of particle size reduction on flow properties was the larger powder specific surface area. Flow properties of Celphere were significantly better than Avicel of comparable particles size, suggesting spherical morphology promoted better powder flow properties. Flow properties of powders different in densities but similar in particle size, shape, and surface properties were similar. When corrected for density effect, higher particle density corresponded to better flow behavior. Surface silicification significantly improved flow properties of finer MCC, but did not improve those of coarser. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4030,4039, 2008 [source] The vitamin D slant on allergyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2006Matthias Wjst Oral vitamin D supplementation has been introduced into modern medicine to prevent rickets without the knowledge that this may have profound immunological consequences. The main vitamin D metabolite calcitriol suppresses dendritic cell maturation and consecutive Th1 cell development, which has independently described as a key mechanism of allergy development. Animal studies and epidemiological surveys now provide a first link of early vitamin D supplementation and later allergy where several vitamin D regulated genes seem to be involved. A randomized clinical trial of vitamin D supplementation could be a further step to follow up the vitamin hypothesis. [source] Efficacy of ultraviolet A1 phototherapy on the expression of bcl-2 in atopic dermatitis and cutaneous T-cell lymphoma in vivo: a comparison studyPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2002F. Breuckmann Background/Purpose: Atopic dermatitis (AD) is characterized immunohistochemically by a high number of skin infiltrating T-helper cells (CD4 + ). In most cases cutaneous T-cell lymphoma (CTCL) is characterized by a malignant proliferation of CD4 + T-helper lymphocytes. The purpose of our study was to evaluate the extent of anti-apoptotic effects in patients suffering from AD or CTCL, respectively, which may contribute to the prolonged inflammation. Furthermore, we investigated whether medium-dose ultraviolet A1 (UVA1) phototherapy is able to modulate the expression of bcl-2 within the dermal inflammatory infiltrate. Methods: In order to enumerate bcl-2+ cells pre- and post-therapeutic punch skin biopsies of ten patients with AD and five patients with CTCL were stained immunohistochemically for features of apoptosis using a monoclonal antibody detecting bcl-2. Results: Both AD and CTCL sections revealed a high percentage of bcl-2+ cells within the dermal perivascular infiltrate before therapy. After the successful treatment using medium-dose UVA1 phototherapy this percentage could be decreased significantly. Conclusion: Both T-cell-derived skin diseases exhibit an increased pre-therapeutic number of bcl-2+ cells. After medium-dose UVA1 phototherapy the substantial improvement of the skin condition was linked to a significant decrease of the dermal bcl-2+ cell count. Moreover, we could demonstrate a remarkable correlation referring to the decrease and staining pattern of bcl-2 between these two groups as well as within each group. Because the bcl-2 protein is known to act as an apoptosis inhibitor, its pre-therapeutic increase may provide the persistent cutaneous inflammatory reaction in T-cell-derived skin diseases. Additionally, the post-therapeutic reduction of bcl-2+ cells might represent a key mechanism of medium-dose UVA1 phototherapy. [source] Demyelination Induces the Decline of the Myelinated Fiber Length in Aged Rat White MatterTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2009Chen Li Abstract To determine the exact reason for the age-related decline of the myelinated fiber length in white matter, we performed this study. In middle-aged rats, there was age-related loss of the unmyelinated fibers with large diameters. The demyelination of the myelinated fibers with small diameters in middle-aged rat white matter might make the age-related decrease of the unmyelinated fibers with small diameters in the white matter unnoticeable. However, in old-aged female rats, the unmyelinated fibers with large and small diameters significantly degenerated together and that the unmyelinated fibers formed from the demyelination of the myelinated fibers could not replenish the age-related loss of the unmyelinated fibers in the white matter. In conclusion, this study suggested that demyelination of myelinated fibers with small diameters in aged white matter might be the key mechanism of the significant decline of the myelinated fiber length in aged white matter. Anat Rec, 292:528,535, 2009. © 2009 Wiley-Liss, Inc. [source] Effective Practice in Probation: An Example of ,Advanced Liberal' Responsibilisation?THE HOWARD JOURNAL OF CRIMINAL JUSTICE, Issue 1 2002Hazel Kemshall This article argues that the dominant emphasis upon effective practice in probation work, particularly the emergence of effective programmes can be understood as an example of a key mechanism of social control in advanced liberal societies. Utilising Rose's concept of ,responsibilisation' the article examines the role of effective programmes in the emerging social policy agenda of citizen re-moralisation, responsibilisation and inclusion exemplified in late modern advanced liberal welfare states. The article concludes that the embracement of effective programmes has reconstituted the probation service as a key agency in the social control and exclusion of those citizens deemed ,intransigent' or ,irresponsible', thus assisting in the demarcation of those who can play a full role in the welfare society from those who cannot. [source] Saliva of the graminivorous Theropithecus gelada lacks proline-rich proteins and tannin-binding capacityAMERICAN JOURNAL OF PRIMATOLOGY, Issue 8 2009Marcus Mau Abstract Gelada baboons are the sole survivors of the genus Theropithecus and the only known graminivorous primates. They developed special adaptations to their diet such as high-crowned teeth for processing hard and abrasive feed. The fine-tuning of salivary protein composition might be another key mechanism that is used by species for adapting to the environment and competing with rivals for exploiting new ecological niches. In order to test whether gelada (graminivorous) and hamadryas baboons (omnivorous) differ in their salivary protein composition, we compared whole saliva samples of captive Theropithecus gelada and Papio hamadryas using gel electrophoresis and tannin-binding assay. We hypothesized that the amount of proline-rich salivary proteins with tannin-binding capacity is higher in baboons consuming a feed with high dicot/monocot rations. Dicots produce tannins as a chemical defense system, discouraging animals from eating them. In contrast to dicots, monocots do not synthesize tannins. The presence of tannin-binding proteins in saliva should effectively inactivate the dicot tannin-based defense mechanism and increase the dietary breadth and/or the capability to switch between monocots and dicot leaves. The lack of such tannin-binding proteins in saliva would indicate a narrow dietary spectrum more restricted to monocots. We found T. gelada to completely lack proline-rich proteins (PRPs) and tannin-binding capacity similar to a great variety of other grazing mammals. In contrast, P. hamadryas does possess PRPs with tannin-binding activity. The findings support a growing body of evidence suggesting a high-level specialization of T. gelada to grass diets. However, it remains unclear, whether loss of salivary tannin-binding capacity drove the gelada into its narrow feeding niche, or whether this loss is the result of a long process of increased specialization. Thus, from an ecological point of view, T. gelada appears to be more vulnerable to environmental changes than other baboon species owing to its narrow dietary traits. Am. J. Primatol. 71:663,669, 2009. © 2009 Wiley-Liss, Inc. [source] Alloimmune Activation Enhances Innate Tissue Inflammation/Injury in a Mouse Model of Liver Ischemia/Reperfusion InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010X. Shen The deleterious sensitization to donor MHC Ags represents one of the most challenging problems in clinical organ transplantation. Although the role of effector/memory T cells in the rejection cascade has been extensively studied, it remains unknown whether and how these ,Ag-specific' cells influence host innate immunity, such as tissue inflammation associated with ischemia and reperfusion injury (IRI). In this study, we analyzed how allogeneic skin transplant (Tx) affected the sequel of host's own liver damage induced by partial warm ischemia and reperfusion. Our data clearly showed that allo-Tx recipients had increased inflammatory response against IR insult in their native livers, as evidenced by significantly more severe hepatocelluar damage, compared with syngeneic Tx recipient controls, and determined by serum ALT levels, liver histology (Suzuki's score) and intrahepatic proinflammatory gene inductions (TNF-,, IL-1, and CXCL10). The CD4 T cells, but neither CD8 nor NK cells, mediated the detrimental effect of allo-Ag sensitization in liver IRI. Furthermore, CD154, but not IFN-,, was the key mechanism in allo-Tx recipients to facilitate IR-triggered liver damage. These results provide new evidence that alloreactive CD4 T cells are capable of enhancing innate tissue inflammation and organ injury via an Ag-nonspecific CD154-dependent but IFN-, independent mechanism. [source] Sensitivity of moist convection to environmental humidityTHE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 604 2004S. H. Derbyshire Abstract As part of the EUROCS (EUROpean Cloud Systems study) project, cloud-resolving model (CRM) simulations and parallel single-column model (SCM) tests of the sensitivity of moist atmospheric convection to midtropospheric humidity are presented. This sensitivity is broadly supported by observations and some previous model studies, but is still poorly quantified. Mixing between clouds and environment is a key mechanism, central to many of the fundamental differences between convection schemes. Here, we define an idealized quasi-steady ,testbed', in which the large-scale environment is assumed to adjust the local mean profiles on a timescale of one hour. We then test sensitivity to the target profiles at heights above 2 km. Two independent CRMs agree reasonably well in their response to the different background profiles and both show strong deep precipitating convection in the more moist cases, but only shallow convection in the driest case. The CRM results also appear to be numerically robust. All the SCMs, most of which are one-dimensional versions of global climate models (GCMs), show sensitivity to humidity but differ in various ways from the CRMs. Some of the SCMs are improved in the light of these comparisons, with GCM improvements documented elsewhere. © Crown copyright, 2004. [source] Anti-thrombin Therapy During Warm Ischemia and Cold Preservation Prevents Chronic Kidney Graft Fibrosis in a DCD ModelAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010F. Favreau Ischemia reperfusion injury (IRI) is pivotal for renal fibrosis development via peritubular capillaries injury. Coagulation represents a key mechanism involved in this process. Melagatran® (M), a thrombin inhibitor, was evaluated in an autotransplanted kidney model, using Large White pigs. To mimic deceased after cardiac death donor conditions, kidneys underwent warm ischemia (WI) for 60 min before cold preservation for 24 h in University of Wisconsin solution. Treatment with M before WI and/or in the preservation solution drastically improved survival at 3 months, reduced renal dysfunction related to a critical reduction in interstitial fibrosis, measured by Sirius Red staining. Tissue analysis revealed reduced expression of transforming growth factor-, (TGF-,) and activation level of its effectors phospho-Smad3, Smad4 and connective tissue growth factor (CTGF) after M treatment. Fibrinolysis activation was also observed, evidenced by downregulation of PAI-1 protein and gene expression. In addition, M reduced S100A4 expression and vimentin staining, which are markers for epithelial mesenchymal transition, a major pathway to chronic kidney fibrosis. Finally, expression of oxidative stress markers Nox2 and iNOS was reduced. We conclude that inhibition of thrombin is an effective therapy against IRI that reduces chronic graft fibrosis, with a significantly positive effect on survival. [source] Glutamate receptors on myelinated spinal cord axons: I. GluR6 kainate receptors,ANNALS OF NEUROLOGY, Issue 2 2009Mohamed Ouardouz PhD Objective The deleterious effects of glutamate excitotoxicity are well described for central nervous system gray matter. Although overactivation of glutamate receptors also contributes to axonal injury, the mechanisms are poorly understood. Our goal was to elucidate the mechanisms of kainate receptor,dependent axonal Ca2+ deregulation. Methods Dorsal column axons were loaded with a Ca2+ indicator and imaged in vitro using confocal laser-scanning microscopy. Results Activation of glutamate receptor 6 (GluR6) kainate receptors promoted a substantial increase in axonal [Ca2+]. This Ca2+ accumulation was due not only to influx from the extracellular space, but a significant component originated from ryanodine-dependent intracellular stores, which, in turn, depended on activation of L-type Ca2+ channels: ryanodine, nimodipine, or nifedipine blocked the agonist-induced Ca2+ increase. Also, GluR6 stimulation induced intraaxonal production of nitric oxide (NO), which greatly enhanced the Ca2+ response: quenching of NO with intraaxonal (but not extracellular) scavengers, or inhibition of neuronal NO synthase with intraaxonal N,-nitro-L-arginine methyl ester, blocked the Ca2+ increase. Loading axons with a peptide that mimics the C-terminal PDZ binding sequence of GluR6, thus interfering with the coupling of GluR6 to downstream effectors, greatly reduced the agonist-induced axonal Ca2+ increase. Immunohistochemistry showed GluR6/7 clusters on the axolemma colocalized with neuronal NO synthase and Cav1.2. Interpretation Myelinated spinal axons express functional GluR6-containing kainate receptors, forming part of novel signaling complexes reminiscent of postsynaptic membranes of glutamatergic synapses. The ability of such axonal "nanocomplexes" to release toxic amounts of Ca2+ may represent a key mechanism of axonal degeneration in disorders such as multiple sclerosis where abnormal accumulation of glutamate and NO are known to occur. Ann Neurol 2009 [source] Susceptibility of four field populations of the diamondback moth Plutella xylostella L. (Lepidoptera: Yponomeutidae) to six insecticides in the Sydney region, New South Wales, AustraliaAUSTRALIAN JOURNAL OF ENTOMOLOGY, Issue 4 2008Vincent Y Eziah Abstract Concerns about the failure of insecticides to control the diamondback moth (DBM) Plutella xylostella in the Sydney region of New South Wales, Australia, necessitated the current investigation to establish the susceptibility of four field populations of the DBM to six insecticides. These include two each of organophosphates (OPs), and synthetic pyrethroid insecticides as well as two new products with different modes of action, spinosad and indoxacarb, currently recommended for DBM control in the region. Topical application of the insecticides to the third-instar larvae showed high resistance to pyrethroids (permethrin and esfenvalerate) of 35.0- to 490.0-fold. Resistance to the OPs (methamidophos and chlorpyrifos) and indoxacarb ranged from 12.1- to 36.2-fold and from 11.4- to 34.6-fold, respectively. However, the field populations were susceptible to spinosad (resistance factors only two- to threefold compared with the susceptible strain). A 2 h pre-treatment of the esfenvalerate-resistant strain with the synergists piperonyl butoxide and diethyl maleate increased the toxicity of esfenvalerate by 30.0- and 1.9-fold, respectively, suggesting the involvement of esterases and/or monooxygenases as the key mechanism(s) of insecticide resistance with glutathione S-transferases playing a minor role. [source] Epigenetic aberrations and therapeutic implications in gliomasCANCER SCIENCE, Issue 6 2010Atsushi Natsume Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing , a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia. (Cancer Sci 2010) [source] G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus -induced suppression of TNF production in macrophagesCELLULAR MICROBIOLOGY, Issue 12 2006Sung O. Kim Summary Lactobacillus rhamnosus is a human commensal with known immunomodulatory properties. To date the mechanism of these immunomodulatory effects is not well understood. To unravel the immunomodulatory signalling mechanism, we investigated the effects of two strains of L. rhamnosus, L. rhamnosus GG and GR-1, in modulating production of tumour necrosis factor-, (TNF) in human monocytic cell line THP-1 and mouse macrophages. Live L. rhamnosus GG and GR-1 or their spent culture supernatant induced minuscule amounts of TNF production but large quantities of granulocyte-colony stimulating factor (G-CSF) in macrophages compared with those induced by pathogenic Escherichia coli GR-12 and Enterococcus faecalis. By using neutralizing antibodies and G-CSF receptor knockout mice, we demonstrated that G-CSF secreted from L. rhamnosus GG- and GR-1-exposed macrophages suppressed TNF production induced by E. coli - or lipopolysaccharide-activated macrophages through a paracrine route. The suppression of TNF production by G-CSF was mediated through activation of STAT3 and subsequent inhibition of c-Jun-N-terminal kinases (JNKs). The inhibition of JNK activation required STAT3,-mediated de novo protein synthesis. This demonstrates a novel role of G-CSF in L. rhamnosus -triggered anti-inflammatory effects and its mechanism in the suppression of TNF production in macrophages. [source] A sympathetic view of the sympathetic nervous system and human blood pressure regulationEXPERIMENTAL PHYSIOLOGY, Issue 6 2008Michael J. Joyner New ideas about the relative importance of the autonomic nervous system (and especially its sympathetic arm) in long-term blood pressure regulation are emerging. It is well known that mean arterial blood pressure is normally regulated in a fairly narrow range at rest and that blood pressure is also able to rise and fall ,appropriately' to meet the demands of various forms of mental, emotional and physical stress. By contrast, blood pressure varies widely when the autonomic nervous system is absent or when key mechanisms that govern it are destroyed. However, 24 h mean arterial pressure is still surprisingly normal under these conditions. Thus, the dominant idea has been that the kidney is the main long-term regulator of blood pressure and the autonomic nervous system is important in short-term regulation. However, this ,renocentric' scheme can be challenged by observations in humans showing that there is a high degree of individual variability in elements of the autonomic nervous system. Along these lines, the level of sympathetic outflow, the adrenergic responsiveness of blood vessels and individual haemodynamic patterns appear to exist in a complex, but appropriate, balance in normotension. Furthermore, evidence from animals and humans has now clearly shown that the sympathetic nervous system can play an important role in longer term blood pressure regulation in both normotension and hypertension. Finally, humans with high baseline sympathetic traffic might be at increased risk for hypertension if the ,balance' among factors deteriorates or is lost. In this context, the goal of this review is to encourage a comprehensive rethinking of the complexities related to long-term blood pressure regulation in humans and promote finer appreciation of physiological relationships among the autonomic nervous system, vascular function, ageing, metabolism and blood pressure. [source] Modulation of Activation-Induced Cytidine Deaminase by Curcumin in Helicobacter pylori -Infected Gastric Epithelial CellsHELICOBACTER, Issue 6 2009Syed Faisal Haider Zaidi Abstract Background:, Anomalous expression of activation-induced cytidine deaminase (AID) in Helicobacter pylori -infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)-,B activation by H. pylori and hence, inhibition of NF-,B pathway can downregulate the expression of AID. Curcumin, a spice-derived polyphenol, is known for its anti-inflammatory activity via NF-,B inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF-,B inhibitory activity in H. pylori -infected gastric epithelial cells. Materials and Methods:, MKN-28 or MKN-45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co-culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme-linked immunosorbent assay was performed to evaluate the anti-adhesion activity of curcumin. Real-time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF-,B, inhibitors of NF-,B (I,B), and I,B kinase (IKK) complex regulation with or without curcumin. Results:, The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (,10 ,mol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF-,B activation inhibitor (SN-50) and proteasome inhibitor (MG-132) also downregulated the mRNA expression of AID. Moreover, curcumin (,10 ,mol/L) has suppressed H. pylori -induced NF-,B activation via inhibition of IKK activation and I,B degradation. Conclusion:, Nonbactericidal concentrations of curcumin downregulated H. pylori -induced AID expression in gastric epithelial cells, probably via the inhibition of NF-,B pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori -related gastric carcinogenesis. [source] Foreign subsidiary perspectives on the mechanisms of global HRM integrationHUMAN RESOURCE MANAGEMENT JOURNAL, Issue 2 2008Adam Smale Often in connection with the integration-responsiveness dilemma, research on HRM in multinational corporations (MNCs) speaks more to explaining the appearance of HRM practices in foreign subsidiaries than to the mechanisms through which such practices are globally integrated. Accordingly, and adopting a subsidiary perspective, the present study has two main aims. The first is to identify the key mechanisms of global HRM integration, how they are used and by whom, and the second is to investigate the factors that explain their usage. The study uses qualitative data from 40 personal interviews conducted with general managers and the most senior HR personnel across 20 Finnish-owned subsidiaries in China. Based on the contingency view of organisations, explanations for mechanism usage are attributed to certain internal characteristics of the subsidiaries and to the Chinese institutional environment. [source] Central and peripheral autoantigen presentation in immune toleranceIMMUNOLOGY, Issue 2 2004Alberto Pugliese Summary Recent studies in both humans and experimental rodent models provide new insight into key mechanisms regulating tolerance to self-molecules. These recent advances are bringing about a paradigm shift in our views about tolerance to self-molecules with tissue-restricted expression. There is, indeed, mounting evidence that selected antigen-presenting cells (APCs) have the ability to synthesize and express self-molecules, and that such expression is critical for self-tolerance. Insulin is a key hormone produced exclusively by pancreatic ,-cells and a critical autoantigen in type 1 diabetes. It provides an excellent example of a molecule with tissue-restricted expression that is expressed ectopically by APCs. The fact that APCs expressing insulin have been demonstrated in both thymus and peripheral lymphoid tissues suggests that they may play a role in insulin presentation in both the central and peripheral immune system. Experimental mice, in which insulin expression was altered, provide functional data that help to dissect the role of insulin presentation by APCs of the immune system. This review addresses recent literature and emerging concepts about the expression of self-molecules in the thymus and peripheral lymphoid tissues and its relation to self-tolerance. [source] Meshfree simulation of failure modes in thin cylinders subjected to combined loads of internal pressure and localized heatINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 8 2008Dong Qian Abstract This paper focuses on the non-linear responses in thin cylindrical structures subjected to combined mechanical and thermal loads. The coupling effects of mechanical deformation and temperature in the material are considered through the development of a thermo-elasto-viscoplastic constitutive model at finite strain. A meshfree Galerkin approach is used to discretize the weak forms of the energy and momentum equations. Due to the different time scales involved in thermal conduction and failure development, an explicit,implicit time integration scheme is developed to link the time scale differences between the two key mechanisms. We apply the developed approach to the analysis of the failure of cylindrical shell subjected to both heat sources and internal pressure. The numerical results show four different failure modes: dynamic fragmentation, single crack with branch, thermally induced cracks and cracks due to the combined effects of pressure and temperature. These results illustrate the important roles of thermal and mechanical loads with different time scales. Copyright © 2008 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||