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Selected AbstractsMechanotransduction of bovine articular cartilage superficial zone protein by transforming growth factor , signalingARTHRITIS & RHEUMATISM, Issue 11 2007Corey P. Neu Objective Mechanical signals are key determinants in tissue morphogenesis, maintenance, and restoration strategies in regenerative medicine, although molecular mechanisms of mechanotransduction remain to be elucidated. This study was undertaken to investigate the mechanotransduction process of expression of superficial zone protein (SZP), a critical joint lubricant. Methods Regional expression of SZP was first quantified in cartilage obtained from the femoral condyles of immature bovines, using immunoblotting, and visualized by immunohistochemistry. Contact pressure mapping in whole joints was accomplished using pressure-sensitive film and a load application system for joint testing. Friction measurements on cartilage plugs were acquired under boundary lubrication conditions using a pin-on-disk tribometer modified for reciprocating sliding. Direct mechanical stimulation by shear loading of articular cartilage explants was performed with and without inhibition of transforming growth factor , (TGF,) signaling, and SZP content in media was quantified by enzyme-linked immunosorbent assay. Results An unexpected pattern of SZP localization in knee cartilage was initially identified, with anterior regions exhibiting high levels of SZP expression. Regional SZP patterns were regulated by mechanical signals and correlated with tribological behavior. Direct relationships were demonstrated between high levels of SZP expression, maximum contact pressures, and low friction coefficients. Levels of SZP expression and accumulation were increased by applying shear stress, depending on location within the knee, and were decreased to control levels with the use of a specific inhibitor of TGF, receptor type I kinase and subsequent phospho-Smad2/3 activity. Conclusion These findings indicate a new role for TGF, signaling in the mechanism of cellular mechanotransduction that is especially significant for joint lubrication. [source] THE SOCIAL ECOLOGY OF VIOLENCE AGAINST WOMEN,CRIMINOLOGY, Issue 2 2004JANET L. LAURITSEN Despite more than three decades of research on the topic of violence against women, the relative contribution of individual, family and community factors to victimization risk remains unknown. We use self-report data from the Area-Identified National Crime Victimization Survey to study the correlates of stranger, nonstranger and intimate,partner violence against women. Regardless of victim-offender relationship, we find that the risk for victimization is highest among young, single women with children, particularly those who have lived in the current home for relatively shorter periods. Area family and age composition appear to have stronger direct relationships with women's violence than poverty or racial composition measures. We also find there to be more similarities than differences in the individual, family, and community correlates of stranger, nonstranger and intimate partner violence. We discuss these findings as part of the growing body of multilevel literature on violence and on violence against women. [source] Enhanced glycogenesis is involved in cellular senescence via GSK3/GS modulationAGING CELL, Issue 6 2008Yong-Hak Seo Summary Glycogen biogenesis and its response to physiological stimuli have often been implicated in age-related diseases. However, their direct relationships to cell senescence and aging have not been clearly elucidated. Here, we report the central involvement of enhanced glycogenesis in cellular senescence. Glycogen accumulation, glycogen synthase (GS) activation, and glycogen synthase kinase 3 (GSK3) inactivation commonly occurred in diverse cellular senescence models, including the liver tissues of aging F344 rats. Subcytotoxic concentrations of GSK3 inhibitors (SB415286 and LiCl) were sufficient to induce cellular senescence with increased glycogenesis. Interestingly, the SB415286-induced glycogenesis was irreversible, as were increased levels of reactive oxygen species and gain of senescence phenotypes. Blocking GSK3 activity using siRNA or dominant negative mutant (GSK3,-K85A) also effectively induced senescence phenotypes, and GS knock-down significantly attenuated the stress-induced senescence phenotypes. Taken together, these results clearly demonstrate that augmented glycogenesis is not only common, but is also directly linked to cellular senescence and aging, suggesting GSK3 and GS as novel modulators of senescence, and providing new insight into the metabolic backgrounds of aging and aging-related pathogenesis. [source] SUPPLY MANAGEMENT, SUPPLY FLEXIBILITY AND PERFORMANCE OUTCOMES: AN EMPIRICAL INVESTIGATION OF MANUFACTURING FIRMSJOURNAL OF SUPPLY CHAIN MANAGEMENT, Issue 3 2010YING LIAO Increasingly, the global market environment is becoming more turbulent, complex and uncertain. Literature has explored the importance of supply management and its direct impact on performance. However, the nature of strategic supply management and its impact on supply flexibility needs further clarification in the context of the use of supplier resources and supplier network coordination. This research presents a model of supply management, supply flexibility and supply chain performance. In this study, we examine the relationships between supply management and supply flexibility, and extend the concept of supply flexibility in terms of supplier flexibility and supply network flexibility on relevant supply chain performance measures. Data for the study were collected from 201 manufacturing firms, and the measurement scales of supply flexibility were tested and validated using structural equation modeling. The results indicate strong, positive and direct relationships between supply management practices and supply flexibility, and between supply flexibility and supply chain performance. Concluding theoretical and managerial implications are discussed. [source] Relationship of serum cholesterol levels to atopy in the US populationALLERGY, Issue 7 2010M. B. Fessler To cite this article: Fessler MB, Jaramillo R, Crockett PW, Zeldin DC. Relationship of serum cholesterol levels to atopy in the US population. Allergy 2010; 65: 859,864. Abstract Background:, Cholesterol promotes Th2 immunity and allergic inflammation in rodents; whether this occurs in humans is unclear. Reports of both direct and inverse associations between serum cholesterol and atopy in different populations suggest that race and/or other demographic variables may modify these relationships. Aims of the study:, To determine the relationships between levels of three serum cholesterol measures [total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and non-HDL-C] and atopy in a sample representative of the US population. Methods:, Cross-sectional study of 6854 participants aged ,6 years from the 2005,2006 National Health and Nutrition Examination Survey. Results:, In the overall population, adjusted odds ratios (AORs) per two-standard deviation increase in TC and non-HDL-C for biochemical atopy (defined as ,1 allergen-specific IgE to 19 allergens) were 1.17 [95% confidence interval (CI), 1.00,1.38] and 1.19 (95% CI, 1.03,1.39), respectively. Interactions by race were noted for the two relationships (interaction P = 0.004 and P = 0.009, respectively) with non-Hispanic Whites (NHWs) having direct relationships [TC: AOR 1.27 (95% CI, 1.03,1.57); non-HDL-C: AOR 1.27 (95% CI, 1.03,1.56)] and non-Hispanic Blacks (NHBs) inverse relationships [TC: AOR 0.77 (95% CI, 0.62,0.95); non-HDL-C: AOR 0.86 (95% CI, 0.69,1.08)]. The adjusted HDL-C,atopy relationship was nonsignificant for NHWs and inverse for NHBs [AOR 0.77 (95% CI, 0.61,0.96)]. Relationships were independent of body mass index and serum C-reactive protein and unmodified by corticosteroid or statin usage. Results were similar using current hay fever/allergy as the atopy outcome. Conclusions:, There are marked inter-racial differences in the relationship between serum cholesterol and atopy in the US population. [source] PL1 Subepithelial bullous diseases , topic overviewORAL DISEASES, Issue 2006M Mravak-Stipeti Subepithelial bullous diseases comprise the group of mucocutaneous autoimmune blistering diseases characterized by subepithelial separation and the deposition of immunoglobulin and complement against several antigens along the basement membrane zone (BMZ). This result in spectrum of diseases that affect skin, oral mucosa, and other mucosal membranes and include bullous pemphigoid (BP), mucous membrane (cicatricial) pemphigoid (MMP), linear IgA disease (LAD), and chronic bullous dermatosis of childhood (CBDC). The most common clinical features are oral erosions, desquamative gingivitis and conjunctival fibrosis, as well as skin lesions, predominantly in older female population. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. In addition to the clinical presentation and a subepithelial vesicle or bullae on routine histologic analysis, the diagnosis is based on direct and indirect immunofluorescence studies. The nature of the disease is determined by the target antigens in the epithelium and BMZ such as antigen 180 (BP180), antigen 230 (BP230), laminin 5, and beta 4 integrin. Circulating IgG and IgA antibodies bind to different epitopes of BP180. The use of salt-split skin substrate enables differentiation between epidermal and dermal 'binders'. Since the antigen and the antibody titer appear to have direct relationships with the disease severity, and a combination of clinical finding and antibody titer provides valuable prognostic data, these investigations should be carried out routinely. Clinicians should recognize clinical spectrum of SBD, the histopathologic and immunopathologic characteristics, the differential diagnosis, the treatment, and the natural history of the disease. Involvement of oral medicine specialists, dermatologists, ophthalmologists, otolaryngologists and gastroenterologists contribute to early diagnosis and will aid in providing SBD patients with the highest quality of care. [source] Habitual throwing and swimming correspond with upper limb diaphyseal strength and shape in modern human athletesAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2009Colin N. Shaw Abstract Variation in upper limb long bone cross-sectional properties may reflect a phenotypically plastic response to habitual loading patterns. Structural differences between limb bones have often been used to infer past behavior from hominin remains; however, few studies have examined direct relationships between behavioral differences and bone structure in humans. To help address this, cross-sectional images (50% length) of the humeri and ulnae of university varsity-level swimmers, cricketers, and controls were captured using peripheral quantitative computed tomography. High levels of humeral robusticity were found in the dominant arms of cricketers, and bilaterally among swimmers, whereas the most gracile humeri were found in both arms of controls, and the nondominant arms of cricketers. In addition, the dominant humeri of cricketers were more circular than controls. The highest levels of ulnar robusticity were also found in the dominant arm of cricketers, and bilaterally amongst swimmers. Bilateral asymmetry in humeral rigidity among cricketers was greater than swimmers and controls, while asymmetry for ulnar rigidity was greater in cricketers than controls. The results suggest that more mechanically loaded upper limb elements,,unilaterally or bilaterally,,are strengthened relative to less mechanically loaded elements, and that differences in mechanical loading may have a more significant effect on proximal compared to distal limb segments. The more circular humerus in the dominant arm in cricketers may be an adaptation to torsional strain associated with throwing activities. The reported correspondence between habitual activity patterns and upper limb diaphyseal properties may inform future behavioral interpretations involving hominin skeletal remains. Am J Phys Anthropol 2009. © 2009 Wiley-Liss, Inc. [source] A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophyACTA PAEDIATRICA, Issue 5 2009Eva Arkblad Abstract Aims: To describe the occurrence of spinal muscular atrophy (SMA) in childhood; to evaluate if any of the genes in the SMA region on chromosome 5q13 correlates with disease severity; to make genotype,phenotype correlations; to evaluate the variability of different disease alleles in carriers and the sensitivity of multiplex ligation-dependent probe amplification (MLPA) for detecting carriers. Methods: In a population-based study from Western Sweden MLPA was used to determine the copy-numbers of several genes in the SMA region (SMN1, SMN2, BIRC1, GTF2H2 and SERF1A) in SMA-patients and their parents. Results: We estimated the incidence of SMN1-related SMA in childhood at 1 in 11 800 live births and confirmed the relationship between the number of SMN2 copies and the severity of disease. No other direct relationships were found. All but one of the analysed parents were confirmed as carriers by MLPA analysis. A total of at least 30 different disease alleles were identified and no specific disease allele represented more than 15% of the total. Conclusion: The childhood incidence of SMA in the Swedish population is around 1 in 12 000 live births and it is unlikely that there is any founder effect involved in SMA in western Sweden. [source] |