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Independent Activities (independent + activity)
Selected AbstractsDLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanismsMOLECULAR CARCINOGENESIS, Issue 5 2008Kevin D. Healy Abstract Expression of the tumor suppressor deleted in liver cancer-1 (DLC-1) is lost in non-small cell lung (NSCLC) and other human carcinomas, and ectopic DLC-1 expression dramatically reduces proliferation and tumorigenicity. DLC-1 is a multi-domain protein that includes a Rho GTPase activating protein (RhoGAP) domain which has been hypothesized to be the basis of its tumor suppressive actions. To address the importance of the RhoGAP function of DLC-1 in tumor suppression, we performed biochemical and biological studies evaluating DLC-1 in NSCLC. Full-length DLC-1 exhibited strong GAP activity for RhoA as well as RhoB and RhoC, but only very limited activity for Cdc42 in vitro. In contrast, the isolated RhoGAP domain showed 5- to 20-fold enhanced activity for RhoA, RhoB, RhoC, and Cdc42. DLC-1 protein expression was absent in six of nine NSCLC cell lines. Restoration of DLC-1 expression in DLC-1-deficient NSCLC cell lines reduced RhoA activity, and experiments with a RhoA biosensor demonstrated that DLC-1 dramatically reduces RhoA activity at the leading edge of cellular protrusions. Furthermore, DLC-1 expression in NSCLC cell lines impaired both anchorage-dependent and -independent growth, as well as invasion in vitro. Surprisingly, we found that the anti-tumor activity of DLC-1 was due to both RhoGAP-dependent and -independent activities. Unlike the rat homologue p122RhoGAP, DLC-1 was not capable of activating the phospholipid hydrolysis activity of phospholipase C-,1. Combined, these studies provide information on the mechanism of DLC-1 function and regulation, and further support the role of DLC-1 tumor suppression in NSCLC. © 2007 Wiley-Liss, Inc. [source] The Effects of Pain and Depression on Physical Functioning in Elderly Residents of a Continuing Care Retirement CommunityPAIN MEDICINE, Issue 4 2000Jana M. Mossey PhD Objective., Explore the relationships between pain, depression, and functional disability in elderly persons. Design.,A cross-sectional, observational study of 228 independently living retirement community residents. Methods., Self-report measures of pain (adaptation of McGill Pain Questionnaire), depression (Geriatric Depression Scale [GDS]) and physical functioning (Physical performance difficulties, activities of daily living [ADL], independent activities of daily living [IADL], and 3-meter walking speed) were employed. Outcome Measures.,Physical functioning variables were dichotomized. Individuals in the lowest quartiles of functional performance and of walking speed were contrasted to all others; for ADL and IADL, those needing some help were compared with those independent in activities. Results., Pain and depression levels were strongly related to physical performance; depression levels were related to ADL and walking speed. In multivariate analyses, an interaction effect was observed where the effects of pain were a function of level of depression. Individuals reporting activity-limiting pain and slightly elevated depressive symptom levels, sub-threshold depression, or major depression were significantly more likely (AOR 7.8; 95% CI, 3.07,20.03) than non-depressed persons to be in the lowest quartile of self-reported physical performance. Conclusions., While both pain and depression level affect physical performance, depressive symptoms rather than pain appear the more influential factor. When seeing elderly patients, identifying, evaluating, and treating both pain complaints and depressive symptoms and disorders may reduce functional impairment. [source] Bidirectional synaptic plasticity as a consequence of interdependent Ca2+ -controlled phosphorylation and dephosphorylation pathwaysEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Pablo D'Alcantara Abstract Postsynaptic Ca2+ signals of different amplitudes and durations are able to induce either long-lasting potentiation (LPT) or depression (LTD). The bidirectional character of synaptic plasticity may result at least in part from an increased or decreased responsiveness of the glutamatergic ,-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPA-R) due to the modification of conductance and/or channel number, and controlled by the balance between the activities of phosphorylation and dephosphorylation pathways. AMPA-R depression can be induced by a long-lived Ca2+ signal of moderate amplitude favouring the activation of the dephosphorylation pathway, whereas a shorter but higher Ca2+ signal would induce AMPA-R potentiation resulting from the preferential activation of the phosphorylation pathway. Within the framework of a model involving calcium/calmodulin-dependent protein kinase II (CaMKII), calcineurin (PP2B) and type 1 protein phosphatase (PP1), we aimed at delineating the conditions allowing a biphasic U-shaped relationship between AMPA-R and Ca2+ signal amplitude, and thus bidirectional plasticity. Our theoretical analysis shows that such a property may be observed if the phosphorylation pathway: (i) displays higher cooperativity in its Ca2+ -dependence than the dephosphorylation pathway; (ii) displays a basal Ca2+ -independent activity; or (iii) is directly inhibited by the dephosphorylation pathway. Because the experimentally observed inactivation of CaMKII by PP1 accounts for this latter characteristic, we aimed at verifying whether a realistic model using reported parameters values can simulate the induction of either LTP or LTD, depending on the time and amplitude characteristics of the Ca2+ signal. Our simulations demonstrate that the experimentally observed bidirectional nature of Ca2+ -dependent synaptic plasticity could be the consequence of the PP1-mediated inactivation of CaMKII. [source] A Nursing Home in Arab-Israeli Society: Targeting Utilization in a Changing Social and Economic EnvironmentJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2005Khalid Suleiman MD This article is a case study of the first 10 years of operation (1992,2002) of the Dabouriya Home for the Aged, the first publicly funded culturally adapted nursing home for Israeli citizens of Arab descent. Although 44% of Arab Israelis and 26% of Jewish Israelis aged 65 and older are disabled, in 1999, 4.3% of the Jewish population but only 0.7% of the Arab-Israeli population aged 65 or older lived in long-term care institutions; disabled Arab-Israeli elderly were mainly cared for by families. As Arab-Israeli society modernizes and traditional caregiving is reduced, alternatives must be found for this growing, disabled population. Medical and administrative records of 404 people admitted consecutively to a 136-bed facility over 10 years were analyzed. Two distinct segments of the needy population were served: people with independent activity of daily living (ADL) function but little or no family to provide help with intermediate ADLs and those dependent in ADLs and with health problems, especially dementia. Economic, demographic, and social changes in Arab-Israeli society may mean that traditional caregivers will not be able to adequately care for this highly disabled population. Administrators of the public health system in Israel should be aware of the underutilization of publicly funded long-term care by disabled Arab Israelis and the lack of care alternatives for the population that does use nursing homes, because there may be severe consequences in terms of caregiver burden and social stress when disabled elderly people remain in unsuitable environments. [source] | ||||||||||