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One Possible Mechanism (one + possible_mechanism)
Selected AbstractsThe withdrawal of antimicrobial treatment as a mechanism for defeating resistant microorganismsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2008David J. Stokes Abstract Antimicrobial resistance is a major concern in health care and farming settings throughout the world. The level of antimicrobial resistance continues to increase and the requirement for a novel and possibly dramatic change in therapy choices is required. One possible mechanism for overcoming resistance is the actual removal of antimicrobial treatment from the therapeutic armoury. This review examines the potential for success of a policy advocating the reduction of antimicrobial use and additionally the withdrawal of such treatments. Evidence from agriculture suggests that the removal of certain drugs from animal husbandry can result in concomitant falls in certain drug resistances in human patients. [source] Simulated geomagnetic reversals and preferred virtual geomagnetic pole pathsGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 3 2004C. Kutzner SUMMARY The question of whether virtual geomagnetic poles (VGPs) recorded during reversals and excursions show a longitudinal preference is a controversial one amongst palaeomagnetists. One possible mechanism for such VGP clustering is the heterogeneity of heat flux at the core,mantle boundary (CMB). We use 3-D convection-driven numerical dynamo models with imposed non-uniform CMB heat flow that show stochastic reversals of the dipole field. We calculate transitional VGPs for a large number of token sites at the Earth's surface. In a model with a simple heat flux variation given by a Y22 harmonic, the VGP density maps for individual reversals differ substantially from each other, but the VGPs have a tendency to fall around a longitude of high heat flow. The mean VGP density for many reversals and excursions shows a statistically significant correlation with the heat flow. In a model with an imposed heat flux pattern derived from seismic tomography we find maxima of the mean VGP density at American and East Asian longitudes, roughly consistent with the VGP paths seen in several palaeomagnetic studies. We find that low-latitude regions of high heat flow are centres of magnetic activity where intense magnetic flux bundles are generated. They contribute to the equatorial dipole component and bias its orientation in longitude. During reversals the equatorial dipole part is not necessarily dominant at the Earth's surface, but is strong enough to explain the longitudinal preference of VGPs as seen from different sites. [source] A case-control study of the association of the polymorphisms and haplotypes of DNA ligase I with lung and upper-aerodigestive-tract cancersINTERNATIONAL JOURNAL OF CANCER, Issue 7 2008Yuan-Chin Amy Lee Abstract Tobacco smoking is a major risk factor for lung and upper-aerodigestive-tract (UADT) cancers. One possible mechanism for the associations may be through DNA damage pathways. DNA Ligase I (LIG1) is a DNA repair gene involved in both the nucleotide excision repair (NER) and the base excision repair (BER) pathways. We examined the association of 4 LIG1 polymorphisms with lung and UADT cancers, and their potential interactions with smoking in a population-based case-control study in Los Angeles County. We performed genotyping using the SNPlex method from Applied Biosystems. Logistic regression analyses of 551 lung cancer cases, 489 UADT cancer cases and 948 controls showed the expected associations of tobacco smoking with lung and UADT cancers and new associations between the LIG1 haplotypes and these cancers. For lung cancer, when compared to the most common haplotype (rs20581-rs20580-rs20579-rs439132 = T-C-C-A), the adjusted odds ratio (OR) is 1.2 (95% confidence limits (CL) = 0.95, 1.5) for the CACA haplotype, 1.4 (1.0, 1.9) for the CATA haplotype and 1.8 (1.1, 2.8) for the CCCG haplotype, after controlling for age, gender, race/ethnicity, education and tobacco smoking. We observed weaker associations between the LIG1 haplotypes and UADT cancers. Our findings suggest the LIG1 haplotypes may affect the risk of lung and UADT cancers. © 2007 Wiley-Liss, Inc. [source] Recombinant human platelet-derived growth factor BB (rhPDGF-BB) and beta-tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2009Loay Al-Zube Abstract Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 µg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p,<,0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1074,1081, 2009 [source] Increased Fibronectin Expression in Lung in the Setting of Chronic Alcohol AbuseALCOHOLISM, Issue 4 2007Ellen L. Burnham Rationale: The incidence and severity of the acute respiratory distress syndrome (ARDS) is increased in individuals who abuse alcohol. One possible mechanism by which alcohol increases susceptibility to acute lung injury is through alterations in alveolar macrophage function and induction of tissue remodeling activity. Our objective was to determine whether alcohol abuse, independent of other comorbidities, alters fibronectin and metalloproteinase gene expression in alveolar macrophages and in epithelial lining fluid (ELF) of the lung. Methods: Otherwise healthy subjects with alcohol abuse (n=21) and smoking-matched controls (n=17) underwent bronchoalveolar lavage. Alveolar macrophage fibronectin and matrix metalloproteinase (MMP) mRNA expression were measured via reverse transcription-polymerase chain reaction. The supernatant from cultured alveolar macrophages and lung ELF were tested for their ability to induce fibronectin and MMP-9 gene transcription in cell-based assays. Results: Alveolar macrophages from subjects with alcohol abuse demonstrated increased fibronectin mRNA expression (p<0.001), and their ELF also elicited more fibronectin gene transcription in lung fibroblasts compared with controls (p<0.001). In contrast, alveolar macrophages from subjects with alcohol abuse had decreased MMP-9 and MMP-2 mRNA expression (p<0.03 and p<0.005, respectively). Similarly, the supernatant (p<0.001) and ELF (p<0.01) from these subjects induced less MMP-9 gene transcription in THP-1 cells. Discussion: Alcohol abuse is associated with increased fibronectin mRNA expression in alveolar macrophages and increased fibronectin-inducing activity in the ELF. This appears to be a specific effect as other tissue remodeling genes, such as MMPs, were not equally affected. These findings suggest activation of tissue remodeling that may contribute to the increased susceptibility for the ARDS observed in alcoholism. [source] Clumpy shocks and the clump mass functionMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2006Paul C. Clark ABSTRACT One possible mechanism for the formation of molecular clouds is large-scale colliding flows. In this paper, we examine whether clumpy, colliding, flows could be responsible for the clump mass functions that have been observed in several regions of embedded star formation, which have been shown to be described by a Salpeter-type slope. The flows presented here, which comprise a population of initially identical clumps, are modelled using smoothed particle hydrodynamics (SPH) and calculations are performed with and without the inclusion of self-gravity. When the shock region is at its densest, we find that the clump mass spectrum is always well modelled by a Salpeter-type slope. This is true regardless of whether the self-gravity is included in the simulations or not, and for our choice of filling factors for the clumpy flows (10, 20 and 40 per cent), and Mach number (5, 10 and 20). In the non-self-gravitating simulations, this slope is retained at lower Mach numbers as the simulations progress past the densest phase. In the simulations which include self-gravity, we find that low Mach number runs yield a flatter mass function after the densest phase. This is simply a result of increased coagulation due to gravitational collapse of the flows. In the high Mach number runs the Salpeter slope is always lost. The self-gravitating calculations also show that the subgroup of gravitationally bound clumps in which star formation occurs, always contain the most massive clumps in the population. Typically these clumps have a mass of order of the Jeans mass of the initial clumps. The mass function of these bound star-forming clumps is not at all similar to the Salpeter-type mass function observed for stars in the field. We conclude that the clump mass function may not only have nothing to do with gravity, but also nothing to do with the star formation process and the resulting mass distribution of stars. This raises doubt over the claims that the clump mass function is the origin of the stellar initial mass function (IMF), for regions such as , Oph, Serpens and the Orion B cloud. [source] Transforming growth factor- ,3 (Tgf- ,3) down-regulates Tgf- , receptor type I (T,r-I) during rescue of cranial sutures from osseous obliterationORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 1 2002LA Opperman Abstract Appropriate biochemical regulation of intramembranous bone growth from sutures is necessary to achieve correct craniofacial morphology. Failure to form sutures (agenesis) or to maintain sutures in their unossified state (craniosynostosis) can result in severe facial dysmorphology. Several factors such as Twist, Msx2, fibroblast growth factors (Fgfs), bone morphogenetic proteins (Bmps) and transforming growth factors- , (Tgf- ,s) regulate suture patency, likely by interacting with one another. Tgf- ,2 and Tgf- ,3 use the same cell surface receptors, yet have opposite effects on suture patency, cellular proliferation and apoptosis within the suture. One possible mechanism by which Tgf- ,3 rescues sutures from obliteration is by regulating the ability of suture cells to respond to Tgf- ,2. As Tgf- ,3 does not regulate protein levels of Tgf- ,2 in sutures, Tgf- ,3 could regulate tissue responsiveness to Tgf- ,2 by regulating Tgf- ,2 access to receptors. Tgf- ,3 is a more potent competitor than Tgf- ,2 for cell surface receptors, so it is proposed that Tgf- ,3 binds to and down-regulates Tgf- , receptor type I (T,r-I) expression by suture cells. This down-regulation would limit the ability of cells to respond to all Tgf- ,s, including Tgf- ,2. To test this hypothesis, an in vitro culture model was used in which fetal rat sutures either remain patent or are induced to fuse when cultured in the presence or absence of dura mater, respectively. Tgf- ,3 was added to cultured calvaria and changes in the number of receptor positive cells within the suture were established. Data were compared with that seen in control sutures and in normal sutures in vivo. It was found that the numbers of cells expressing T,r-I within the suture matrix increased over time in sutures remaining patent. Osteoblastic cells lining the bone fronts on either side of sutures were T,r-I positive during early morphogenesis, but these numbers declined as sutures fused, both in vivo and in vitro. Addition of Tgf- ,3 to calvaria in culture decreased the number of T,r-I expressing cells in both fusing and non-fusing sutures, with dramatic decreases in the numbers of osteoblasts expressing T,r-I. [source] Elucidation of the gating of the GIRK channel using a spectroscopic approachTHE JOURNAL OF PHYSIOLOGY, Issue 22 2009Adi Raveh The traditional view of G protein-coupled receptor (GPCR)-mediated signalling puts the players in this signalling cascade, namely the GPCR, the G protein and its effector, as individual components in space, where the signalling specificity is obtained mainly by the interaction of the GPCR and the G, subunits of the G protein. A question is then raised as to how fidelity in receptor signalling is achieved, given that many systems use the same components of the G protein signalling machinery. One possible mechanism for obtaining the specific flow of the downstream signals, from the activated G protein to its specific effector target, in a timely manner, is compartmentalization, a spatial arrangement of the complex in a rather restricted space. Here we review our recent findings related to these issues, using the G protein-coupled potassium channel (GIRK) as a model effector and fluorescence-based approaches to reveal how the signalling complex is arranged and how the G protein exerts its action to activate the GIRK channel in intact cells. [source] | |||||||||||||