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Of Mechanisms (of + mechanism)
Kinds of Of Mechanisms Selected AbstractsThe Polyhydroxy Acid Gluconolactone Protects Against Ultraviolet Radiation in an In Vitro Model of Cutaneous PhotoagingDERMATOLOGIC SURGERY, Issue 2 2004Eric F. Bernstein MD Background. Ultraviolet (UV) radiation damages skin through a variety of mechanisms, including the generation of free radicals. Gluconolactone is a polyhydroxy acid (PHA) that is capable of chelating metals and may also function by scavenging free radicals, thereby protecting skin from some of the damaging effects of UV radiation. Objective. This study measured the ability of gluconolactone to protect against UV radiation,induced damage. Methods. The ability of gluconolactone to prevent UV radiation,induced elastin promoter activation was determined in vitro using a transgenic model of cutaneous photoaging. Gluconolactone was also evaluated to determine its ability to promote the formation of sunburn cells in human skin after exposure to UV radiation. Results. Gluconolactone provided up to 50% protection against UV radiation, as measured in our in vitro system, and did not significantly increase sunburn cells in human skin. Conclusions. These results demonstrate the ability of the PHA gluconolactone to protect against UV radiation,induced elastin promoter activation. In addition, in vivo studies demonstrated that gluconolactone treatment does not result in a significant increase in sunburn cells. Further investigation of this and other PHAs is necessary to identify their potential role in preventing and repairing cutaneous photodamage. [source] From meiosis to postmeiotic events: Homologous recombination is obligatory but flexibleFEBS JOURNAL, Issue 3 2010Lóránt Székvölgyi Sexual reproduction depends on the success of faithful chromosome transmission during meiosis to yield viable gametes. Central to meiosis is the process of recombination between paternal and maternal chromosomes, which boosts the genetic diversity of progeny and ensures normal homologous chromosome segregation. Imperfections in meiotic recombination are the source of de novo germline mutations, abnormal gametes, and infertility. Thus, not surprisingly, cells have developed a variety of mechanisms and tight controls to ensure sufficient and well-distributed recombination events within their genomes, the details of which remain to be fully elucidated. Local and genome-wide studies of normal and genetically engineered cells have uncovered a remarkable stochasticity in the number and positioning of recombination events per chromosome and per cell, which reveals an impressive level of flexibility. In this minireview, we summarize our contemporary understanding of meiotic recombination and its control mechanisms, and address the seemingly paradoxical and poorly understood diversity of recombination sites. Flexibility in the distribution of meiotic recombination events within genomes may reside in regulation at the chromatin level, with histone modifications playing a recently recognized role. [source] Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytesIUBMB LIFE, Issue 3 2007Seung-Soon Im Abstract The gene expression of glucose transporter type 4 isoform (GLUT4) is known to be controlled by metabolic, nutritional, or hormonal status. Understanding the molecular mechanisms governing GLUT4 gene expression is critical, because glucose disposal in the body depends on the activities of GLUT4 in the muscle and adipocytes. The GLUT4 activities are regulated by a variety of mechanisms. One of them is transcriptional regulation. GLUT4 gene expression is regulated by a variety of transcriptional factors in muscle and adipose tissue. These data are accumulating regarding the transcriptional factors regulating GLUT4 gene expression. These include MyoD, MEF2A, GEF, TNF-,, TR-1,, KLF15, SREBP-1c, C/EBP-,, O/E-1, free fatty acids, PAPR,, LXR,, NF-1, etc. These factors are involved in the positive or negative regulation of GLUT4 gene expression. In addition, there is a complex interplay between these factors in transactivating GLUT4 promoter activity. Understanding the mechanisms controlling GLUT4 gene transcription in these tissues will greatly promote the potential therapeutic drug development for obesity and T2DM. IUBMB Life, 59: 134-145, 2007 [source] Sp1 and krüppel-like factor family of transcription factors in cell growth regulation and cancerJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2001Adrian R. Black The Sp/KLF family contains at least twenty identified members which include Sp1-4 and numerous krüppel-like factors. Members of the family bind with varying affinities to sequences designated as ,Sp1 sites' (e.g., GC-boxes, CACCC-boxes, and basic transcription elements). Family members have different transcriptional properties and can modulate each other's activity by a variety of mechanisms. Since cells can express multiple family members, Sp/KLF factors are likely to make up a transcriptional network through which gene expression can be fine-tuned. ,Sp1 site'-dependent transcription can be growth-regulated, and the activity, expression, and/or post-translational modification of multiple family members is altered with cell growth. Furthermore, Sp/KLF factors are involved in many growth-related signal transduction pathways and their overexpression can have positive or negative effects on proliferation. In addition to growth control, Sp/KLF factors have been implicated in apoptosis and angiogenesis; thus, the family is involved in several aspects of tumorigenesis. Consistent with a role in cancer, Sp/KLF factors interact with oncogenes and tumor suppressors, they can be oncogenic themselves, and altered expression of family members has been detected in tumors. Effects of changes in Sp/KLF factors are context-dependent and can appear contradictory. Since these factors act within a network, this diversity of effects may arise from differences in the expression profile of family members in various cells. Thus, it is likely that the properties of the overall network of Sp/KLF factors play a determining role in regulation of cell growth and tumor progression. © 2001 Wiley-Liss, Inc. [source] Systemic medications: clinical significance in periodonticsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2002Sebastian G. Ciancio Abstract Systemic medications are of value as adjuncts to periodontal therapy. These medications can be divided into two major categories: antibiotics and agents for host modulation. Antibiotics have been shown to be valuable adjuncts in specialized types of periodontal disease, such as localized and generalized aggressive periodontitis, and of possible value in severe chronic periodontitis. Antibiotics have been studied individually, in combination and in sequential therapy. Host modulators include Periostat, non-steroidal anti-inflammatory agents, alendronate (Fosamax), hormone replacement therapy and anti-arthritic medications. These agents produce their beneficial effects by a variety of mechanisms of action, including inhibition of matrix metalloproteinases, inhibition of prostaglandin production, stimulation of osteoblasts, inhibition of osteoclasts, and other anti-inflammatory mechanisms of action. [source] Chemokine receptors and neurotrophic factors: Potential therapy against aids dementia?JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2008Italo Mocchetti Abstract Chemokine receptors, in particular, CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV-1) infection of immunocompetent cells and the apoptosis of these cells. However, the virus does not infect neurons. Yet through a variety of mechanisms, HIV promotes glial cell activation, synaptodendritic alterations, and neuronal loss that ultimately lead to motor and cognitive impairment. Chemokines and chemokine receptors are abundant in the adult central nervous system and play a role in neuronal apoptosis evoked by HIV proteins. Thus, reducing the availability of chemokine receptors may prevent the neuronal degeneration seen in HIV-positive patients. In this article, we present and discuss a recent experimental approach aimed at testing effective neuroprotective therapies against HIV-mediated neuronal degeneration. © 2007 Wiley-Liss, Inc. [source] Antibiotics: Has the magic gone?JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 5 2007Yogesh Chander Abstract The emergence of antibiotic resistant bacteria has diminished the efficacy of several antibiotics that were used to treat infectious diseases in humans and animals. In recent years, the problem of antibiotic resistance has become more apparent as increasing numbers of bacteria have acquired resistance to multiple antibiotics. Antibiotics inhibit bacterial growth through a variety of mechanisms including inhibition of cell wall or protein synthesis, interference with DNA (or RNA) replication, and disruption of metabolic pathways or cell membrane. Bacteria develop resistance through genetic mutations or by acquiring resistant genes involved in the production of antibiotic degrading enzymes, overproduction of target molecules, efflux pumps to drain out antibiotics, and/or altered cell wall permeability to survive adverse physiological conditions. Published literature suggests that sub-therapeutic feeding of food animals for growth promotion along with casual use of antibiotics in household products such as soaps and creams is contributing to increased antimicrobial resistance in the environment. If steps are not taken to minimize selective pressure on bacteria, the effectiveness of antibiotics (hailed as ,magic bullets') may be marginalized. Important steps in the judicious use of antibiotics on the farm are: (1) education of farmers on the pitfalls of using antibiotics sub-therapeutically in the production of food animals; (2) development of animal production practices that reduce dependence on antibiotics; and (3) development of manure disposal practices that minimize the spread of residual antibiotics and antibiotic resistant bacteria into the environment. In addition, educating the general public on the use and misuse of antibiotics in daily life is also important if there is to be any significant impact on reducing the environmental spread of antibiotic resistance. Copyright © 2006 Society of Chemical Industry [source] Platelet activation in type 2 diabetes mellitusJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2004P. Ferroni Summary., The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, pro-thrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. [source] Parent age differentially influences offspring size over the course of development in Laysan albatrossJOURNAL OF ZOOLOGY, Issue 1 2008D. C. Dearborn Abstract Offspring growth and survival are predicted to be higher for older parents, due to a variety of mechanisms, such as increased breeding experience or greater investment favored by low residual reproductive value. Yet the extent to which parent age affects offspring viability is likely to vary between different aspects of growth and survival, perhaps being most pronounced at the most stressful stages of reproduction. We studied the link between parent age and nestling growth and survival in the Laysan albatross, a long-lived seabird with a mean first breeding age of 8 years. Offspring of older parents were more likely to survive to fledging. Among those that did fledge, nestlings of older parents grew more rapidly. However, parent age did not influence the eventual asymptotic size that nestlings reached before fledging: fast-growing nestlings of older parents reached 90% of asymptotic size roughly 1 week sooner, but slow-growing nestlings of younger parents eventually caught up in size before fledging. Older parents bred c. 2 days earlier than younger parents, but hatch date did not explain observed variation in offspring success. The extent to which parent age accounted for variation in size of individual nestlings was not constant but peaked near the midpoint of development. This could reflect a time period when demands on parents reveal age-based differences in parental quality. Overall, growth and survival of offspring increased with parent age in this species, even though the late age of first breeding potentially provides a 7-year period for birds to hone their foraging skills or for selection to eliminate low-quality individuals. [source] End-Anchored Polymers: Compression by Different Mechanisms and Interpenetration of Apposing LayersMACROMOLECULAR THEORY AND SIMULATIONS, Issue 2 2005Mark D. Whitmore Abstract Summary: This paper presents a systematic study of the compression of end-anchored polymer layers by a variety of mechanisms. We treat layers in both good and , solvents, and in the range of polymer densities that is normally encountered in experiments. Our primary technique is numerical self-consistent field (NSCF) theory. We compare the NSCF results for the different mechanisms with each other, and with those of the analytic SCF theory. For each mechanism, we calculate the density profiles, layer thicknesses, and free energies, all as functions of the degree of polymerization and surface coverage. The free energy and the deformation of each layer depend on the compression mechanism, and they can be very different from the ASCF theory. For example, the energy of compression can be as much as three times greater than the analytical SCF (ASCF) prediction, and it does not reduce to simple, universal functions of the reduced distance between the surfaces. The overall physical picture simplifies if the free energy is expressed in terms of the layer deformation, rather than the reduced surface separation. We also examine and quantify the interpenetration of layers, discuss why ASCF theory applies better to some compression mechanisms than others, and end with comments on the difficulties in extracting quantitative information from surface-forces experiments. Comparisons of forces of compression in a good solvent for the three different systems, as functions of D/nb. The lower three curves are for ,*,=,3, and the upper three are for ,*,=,23. [source] Identification of proteins to predict the molecular basis for the observed gender susceptibility in a rat model of alcoholic steatohepatitis by 2-D gel proteomicsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 20 2008Atrayee Banerjee Abstract Females are reported to be highly susceptible to alcoholic steatohepatitis (ASH) compared to the males. Although a variety of mechanisms have been proposed to explain this higher sensitivity of females, the precise mechanism is not well understood. The objective of this study was to identify changes in global protein expression in liver tissues of male and female rats with pathologically evident ASH by 2-DE (dimensional electrophoresis). ASH was induced in the SD (Sprague-Dawley) rats by feeding ethanol (EtOH) containing Lieber-DeCarli diet for 6,wk followed by a single injection of lipopolysaccharide (LPS, 10,mg/kg, i.p.). Higher liver injury in females in the ASH group as compared to the males was confirmed by HE stained liver sections. As identified by 2-DE, 22 protein-spots were differentially expressed in the females in the ASH group as compared to the males. Following identification of these proteins by MALDI-MS, they were mainly categorized into metabolism and oxidative stress-related proteins. The expression pattern of a few of these oxidative stress-related proteins like Ferritin Heavy chain (Ferritin-H chain), ER stress protein 60 (ER 60) and Heat-shock protein-60 (HSP 60) were verified by Western blotting. To conclude, the current study has identified a set of proteins that highlights potential novel mechanisms associated with higher liver injury noted in the female rat ASH model. [source] The nature of market visioning for technology-based radical innovationTHE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 4 2001Gina Colarelli O'Connor The ability to link advanced technologies to market opportunities is a crucial aspect of radical innovation. When markets do not yet exist, it is difficult to persevere, given organizational pressures for immediate profit. To study this problem, eleven radical innovation projects are examined in nine large, mature organizations in a real-time field setting. The sample is augmented by interviews of four additional individuals who have repeated experiences in linking advanced technologies to markets. From results that are qualitative in nature, four themes emerge. First, vision is built and sustained through a variety of mechanisms that may operate in combination or serially. Second, there are a number of roles that individuals play in creating and evangelizing a vision through an organization. Third, there exist a few tools and methods for aiding in developing visions that are not dependent strictly on individual initiative, but these are not systematically employed by organizations. Finally, visions undergo a process of validation and internal acceptance that may depend heavily on reaching out beyond the familiar customer/market set of the firm. Building on these themes, we derive two sets of insights. The first identifies three different ways that visions might develop. We did not discover a singular process across firms or even within a single firm by which visions develop. Second, we identify three elements that occur when a vision is formulated and utilized in organizations: Motivation, Insight and Elaboration. Thus a vision does not arise through a single creative leap, but develops over time and requires focus, discipline, energy, and the involvement of many people. Awareness of this conceptual underpinning of visioning may help managers understand how to encourage this activity and help sustain long-term growth and renewal in their organizations. [source] Glycoside hydrolases: Catalytic base/nucleophile diversityBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010Thu V. Vuong Abstract Recent studies have shown that a number of glycoside hydrolase families do not follow the classical catalytic mechanisms, as they lack a typical catalytic base/nucleophile. A variety of mechanisms are used to replace this function, including substrate-assisted catalysis, a network of several residues, and the use of non-carboxylate residues or exogenous nucleophiles. Removal of the catalytic base/nucleophile by mutation can have a profound impact on substrate specificity, producing enzymes with completely new functions. Biotechnol. Bioeng. 2010;107: 195,205. © 2010 Wiley Periodicals, Inc. [source] Nitrite, NO and hypoxic vasodilationBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2009Jason D Allen The ability to deliver oxygen and other nutrients to working tissues at a rate acutely matched to demand is the quintessential function of the cardiovascular system. Thus, an understanding of the biochemical mechanisms involved in hypoxic vasodilation remains a major goal in vascular biology. Nitric oxide, its metabolites, and oxidation status are recognized as playing important roles in this process. Previous work examining how nitrite can be converted to bioactive nitric oxide (NO) under hypoxic conditions has focused on the role of the red blood cell and haemoglobin. In a recent issue of the British Journal of Pharmacology, Pinder et al. demonstrate that plasma nitrite, in the absence of haemoglobin, is capable of increasing the maximal dilation of rabbit aortic rings under hypoxic conditions. Furthermore, they demonstrate that this relaxation can occur with or without the endothelium. This observation, even if it is only a small proportion of the relaxant activity of nitrite, highlights how NO metabolites may be involved in a variety of mechanisms of vessel control. [source] ROLE OF MACROPHAGES IN COMPLICATIONS OF TYPE 2 DIABETESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007GH TeschArticle first published online: 15 AUG 200 SUMMARY 1Macrophage accumulation is a feature of Type 2 diabetes and is associated with the development of diabetic complications (nephropathy, atherosclerosis, neuropathy and retinopathy). The present article reviews the current evidence that macrophages contribute to the complications of Type 2 diabetes. 2Macrophage-depletion studies in rodent models have demonstrated a causal role for macrophages in the development of diabetic complications. 3Components of the diabetic milieu (high glucose, advanced glycation end-products and oxidized low-density lipoprotein) promote macrophage accumulation (via induction of chemokines and adhesion molecules) and macrophage activation within diabetic tissues. 4Macrophages mediate diabetic injury through a variety of mechanisms, including production of reactive oxygen species, cytokines and proteases, which result in tissue damage leading to sclerosis. 5A number of existing and experimental therapies can indirectly reduce macrophage-mediated injury in diabetic complications. The present article discusses the use of these therapies, given alone and in combination, in suppressing macrophage accumulation and activity. 6In conclusion, current evidence supports a critical role for macrophages in the evolution of diabetic complications. Present therapies are limited in slowing the progression of macrophage-mediated injury. Novel strategies that are more specific at targeting macrophages may provide better protection against the development of Type 2 diabetic complications. [source] | ||||||||||||||||