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101.
Ramón C. Hermida Diana E. Ayala Artemio Mojón Michael H. Smolensky José R. Fernández 《Chronobiology international》2013,30(11):1515-1527
ABSTRACTThe cost-effectiveness of ambulatory blood pressure (BP) monitoring (ABPM) versus traditional office BP measurement (OBPM) for the diagnosis and management of hypertension has been evaluated only by few studies and based solely on the reduction of medical care expenses through avoiding treatment of isolated-office hypertension. Data from the 21963 participants in the Hygia Project, a multicenter outcomes study that incorporates into routine primary care periodic, at least yearly, 48 h ABPM evaluation, were utilized to assess the cost-effectiveness – relative to vascular pathology expenditures countrywide in Spain – of ABPM versus OBPM. The actual reported Spanish healthcare expenditure for vascular pathology in 2015 – aggregate costs of medical examinations, outpatient and inpatient care, therapeutic interventions, plus non-healthcare services (productivity losses due to morbidity/mortality and informal family/friends-provided care) – was used to compare yearly costs when diagnostic and treatment decisions for hypertension are based on the OBPM versus the ABPM-model. Our economic analysis is based on the more realistic and feasible approach of restricting ABPM solely to high-risk individuals of age ≥60 years and/or with diabetes, chronic kidney disease, and/or previous cardiovascular event, who in the Hygia Project accounted for >90% of all documented events. The projected net benefit countrywide in favor of the proposed ABPM-model is ~5294M€/year, i.e., 360.33€/year (95%CI [347.52–374.85]) per ABPM-evaluated person. This highly conservative economic analysis indicates ABPM is a much more cost-effective strategy than repeated OBPM not only for accurate diagnosis and management of true hypertension but marked reduction of expenditures on elevated BP-associated vascular pathology. 相似文献
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104.
Tracy M. Crotty Tomoyuki Nakano Diana M. Stafforini Matthew K. Topham 《The Journal of biological chemistry》2013,288(3):1439-1447
Discovering proteins that modulate Akt signaling has become a critical task, given the oncogenic role of Akt in a wide variety of cancers. We have discovered a novel diacylglycerol signaling pathway that promotes dephosphorylation of Akt. This pathway is regulated by diacylglycerol kinase δ (DGKδ). In DGKδ-deficient cells, we found reduced Akt phosphorylation downstream of three receptor tyrosine kinases. Phosphorylation upstream of Akt was not affected. Our data indicate that PKCα, which is excessively active in DGKδ-deficient cells, promotes dephosphorylation of Akt through pleckstrin homology domain leucine-rich repeats protein phosphatase (PHLPP) 2. Depletion of either PKCα or PHLPP2 rescued Akt phosphorylation in DGKδ-deficient cells. In contrast, depletion of PHLPP1, another Akt phosphatase, failed to rescue Akt phosphorylation. Other PHLPP substrates were not affected by DGKδ deficiency, suggesting mechanisms allowing specific modulation of Akt dephosphorylation. We found that β-arrestin 1 acted as a scaffold for PHLPP2 and Akt1, providing a mechanism for specificity. Because of its ability to reduce Akt phosphorylation, we tested whether depletion of DGKδ could attenuate tumorigenic properties of cultured cells and found that DGKδ deficiency reduced cell proliferation and migration and enhanced apoptosis. We have, thus, discovered a novel pathway in which diacylglycerol signaling negatively regulates Akt activity. Our collective data indicate that DGKδ is a pertinent cancer target, and our studies could lay the groundwork for development of novel cancer therapeutics. 相似文献
105.
Bridget E. Hawkins Shashirekha Krishnamurthy Diana L. Castillo-Carranza Urmi Sengupta Donald S. Prough George R. Jackson Douglas S. DeWitt Rakez Kayed 《The Journal of biological chemistry》2013,288(23):17042-17050
Traumatic brain injury (TBI) is a serious problem that affects millions of people in the United States alone. Multiple concussions or even a single moderate to severe TBI can also predispose individuals to develop a pathologically distinct form of tauopathy-related dementia at an early age. No effective treatments are currently available for TBI or TBI-related dementia; moreover, only recently has insight been gained regarding the mechanisms behind their connection. Here, we used antibodies to detect oligomeric and phosphorylated Tau proteins in a non-transgenic rodent model of parasagittal fluid percussion injury. Oligomeric and phosphorylated Tau proteins were detected 4 and 24 h and 2 weeks post-TBI in injured, but not sham control rats. These findings suggest that diagnostic tools and therapeutics that target only toxic forms of Tau may provide earlier detection and safe, more effective treatments for tauopathies associated with repetitive neurotrauma. 相似文献
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Microalgae contain lipid bodies (LBs) composed of triacylglycerols, which can be converted to biodiesel. Here we demonstrate a method to study the accumulation patterns of LBs in different microalgae strains and culture conditions utilizing laser scanning confocal microscopy (LSCM) with BODIPY 505/515 (4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene) staining, in parallel with Nile Red (9-diethylamino-5H-benzo-a-phenoxazine-5-one) fluorescence analysis of intracellular lipids in microplates. Phaeodactylum tricornutum and Tetraselmis suecica were selected as model organisms and monitored throughout the growth phases in standard and nitrogen-deficient growth conditions. Utilizing image quantification techniques, the number and morphology of LBs suggest that P. tricornutum accumulates lipids by merging with existing LBs, while T. suecica synthesizes new LBs. We observed that T. suecica accumulates a higher number of LBs and total volume of lipids per cell, while P. tricornutum accumulates only 1–2 LBs with a larger volume per LB. LSCM analysis complements Nile Red (NR) methods because LSCM provides three-dimensional images of lipid accumulation at a cellular level, while NR analysis can quickly monitor the total levels of intracellular lipids for phenotypic screening. Using NR analysis, we have observed that the optimal harvest date for P. tricornutum and T. suecica in standard cultivation conditions is 24 and 42 days, respectively. Comparison with nitrogen-deficient growth conditions is utilized as a model to confirm that LSCM and NR analysis can be used to study lipid storage and productivity for diverse growth conditions and various strains of microalgae. 相似文献
108.
Diana Alvarez-Prada 《Studies on Neotropical Fauna and Environment》2013,48(2):80-95
The Wattled Curassow (Crax globulosa, Cracidae, Aves) is a large bird living in the Western Amazon basin and a critically endangered species in the Colombian and in the Peruvian Amazon. We carried out the first population genetics analysis of this species employing six nuclear microsatellite markers and sequences of the mtND2 gene. The main results are as follows. (1) The levels of gene diversity were high for the overall population as well as for each of the three islands for both microsatellites and mtDNA. (2) A small amount of genetic differentiation among populations was found with both types of markers (FST = 0.027 for microsatellites and NST = 0.17 for mitochondrial sequences). (3) Using microsatellites, the Geneclass 2.0 software detected a low correct assignment of individuals to their respective populations. The Structure software only detected one gene pool for the entire area studied. These results are relevant for conservation efforts of this critically endangered species. 相似文献
109.
Diana Lima 《Ethnos》2013,78(3):372-399
This article analyses how social subjects from low-income communities in a historically peripheral country like Brazil access and process the economic ideas now prevalent in the contemporary world by examining the rationalizations involved in the adherence to the individualist message of prosperity theology. Based on the classical Weberian premise of a relation between religious ethics and economic ethos (Weber, Max. 1987. A Ética Protestante e o Espírito do Capitalismo. São Paulo: Livraria Pioneira Editora), I analyse the commitment of faith made with the Universal Church of the Kingdom of God by members of a network of worshippers formed by around 20 men aged between 18 and 45 years with low levels of schooling, living in favelas of Rio de Janeiro, in order to comprehend how the principles of neoliberal cosmology, adopted as central elements of Brazilian economic policy since the 1990s, have been incorporated by people from the poorest sectors of urban Brazil. 相似文献
110.
Mario Venza Maria Visalli Teresa Catalano Cinzia Fortunato Rosaria Oteri Diana Teti Isabella Venza 《Biochemical and biophysical research communications》2013
Aberrant promoter methylation and resultant silencing of TRAIL decoy receptors were reported in a variety of cancers, but to date little is known about the relevance of this epigenetic modification in melanoma. In this study, we examined the methylation and the expression status of TRAIL receptor genes in cutaneous and uveal melanoma cell lines and specimens and their interaction with DNA methyltransferases (DNMTs) DNMT1, DNMT3a, and DNMT3b. DR4 and DR5 methylation was not frequent in cutaneous melanoma but on the contrary it was very frequent in uveal melanoma. No correlation between methylation status of DR4 and DR5 and gene expression was found. DcR1 and DcR2 were hypermethylated with very high frequency in both cutaneous and uveal melanoma. The concordance between methylation and loss of gene expression ranged from 91% to 97%. Here we showed that DNMT1 was crucial for DcR2 hypermethylation and that DNMT1 and DNMT3a coregulate the methylation status of DcR1. Our work also revealed the critical relevance of DcR1 and DcR2 expression in cell growth and apoptosis either in cutaneous or uveal melanoma. In conclusion, the results presented here claim for a relevant impact of aberrant methylation of decoy receptors in melanoma and allow to understand how the silencing of DcR1 and DcR2 is related to melanomagenesis. 相似文献