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101.
Rositch AF Hudgens MG Backes DM Moses S Agot K Nyagaya E Snijders PJ Meijer CJ Bailey RC Smith JS 《The Journal of infectious diseases》2012,206(5):669-677
Background.Little is known about type-specific associations between prevalent human papillomavirus (HPV) infections and risk of acquiring other HPV types in men. Data on natural clustering of HPV types are needed as a prevaccine distribution to which postvaccine data can be compared. Methods.Using data from a randomized controlled trial of male circumcision in Kisumu, Kenya, adjusted mean survival ratios were estimated for acquisition of any-HPV, high-risk (HR) HPV, and individual HR-HPV types among men uninfected as compared to those infected with vaccine-relevant HPV types 16, 18, 31, 45, 6, or 11 at baseline. Results.Among 1097 human immunodeficiency virus-negative, uncircumcised men, 2303 incident HPV infections were detected over 2534 person-years of follow-up. Although acquisition of individual HR-HPV types varied by baseline HPV type, there was no clear evidence of shorter times to acquisition among men without vaccine-relevant HPV-16, -18, -31, -45, -6, or -11 infections at baseline, as compared to men who did have these infections at baseline. Conclusions.These prospective data on combinations of HPV infections over time do not suggest the potential for postvaccination HPV type replacement. Future surveillance studies are needed to definitely determine whether elimination of HPV types by vaccination will alter the HPV type distribution in the population. 相似文献
102.
103.
Sehgal N Gupta A Valli RK Joshi SD Mills JT Hamel E Khanna P Jain SC Thakur SS Ravindranath V 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(9):3510-3515
A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Aβ and a decrease in brain Aβ monomer after 7 d, indicating increased transport of Aβ from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Aβ-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Aβ levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Aβ. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Aβ, indicating that increase in liver LRP and sLRP occurring independent of Aβ concentration could result in clearance of Aβ. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models. 相似文献
104.
Yashina S Gubin S Maksimovich S Yashina A Gakhova E Gilichinsky D 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(10):4008-4013
Whole, fertile plants of Silene stenophylla Ledeb. (Caryophyllaceae) have been uniquely regenerated from maternal, immature fruit tissue of Late Pleistocene age using in vitro tissue culture and clonal micropropagation. The fruits were excavated in northeastern Siberia from fossil squirrel burrows buried at a depth of 38 m in undisturbed and never thawed Late Pleistocene permafrost sediments with a temperature of -7 °C. Accelerator mass spectrometry (AMS) radiocarbon dating showed fruits to be 31,800 ± 300 y old. The total γ-radiation dose accumulated by the fruits during this time was calculated as 0.07 kGy; this is the maximal reported dose after which tissues remain viable and seeds still germinate. Regenerated plants were brought to flowering and fruiting and they set viable seeds. At present, plants of S. stenophylla are the most ancient, viable, multicellular, living organisms. Morphophysiological studies comparing regenerated and extant plants obtained from modern seeds of the same species in the same region revealed that they were distinct phenotypes of S. stenophylla. The first generation cultivated from seeds obtained from regenerated plants progressed through all developmental stages and had the same morphological features as parent plants. The investigation showed high cryoresistance of plant placental tissue in permafrost. This natural cryopreservation of plant tissue over many thousands of years demonstrates a role for permafrost as a depository for an ancient gene pool, i.e., preexisting life, which hypothetically has long since vanished from the earth's surface, a potential source of ancient germplasm, and a laboratory for the study of rates of microevolution. 相似文献
105.
106.
van Greevenbroek MM Jacobs M van der Kallen CJ Blaak EE Jansen EH Schalkwijk CG Feskens EJ Stehouwer CD 《International journal of cardiology》2012,154(2):158-162
Background
Complement C3 is an emerging risk factor for coronary heart disease (CHD) and is particularly increased in the metabolic syndrome. A direct effect of smoking on structure and function of complement C3 has been suggested.Hypothesis
Smoking behavior may affect the cardiovascular risk that is associated with plasma complement C3.Methods
The association between plasma C3 and CHD was studied in the CODAM (Cohort on Diabetes and Atherosclerosis Maastricht) study population (n = 562, 61% male) with examination of effect modification by smoking.Results
The overall prevalence of CHD was 23.3%. Higher plasma C3 levels were associated with a higher CHD prevalence, and there was a significant interaction with heavy smoking (p = 0.01). In never & light smokers, the univariate OR for CHD per 1 s.d. (0.33 g/L) increase in C3 was 1.09 [95% confidence interval (CI) 0.85-1.41] (p = 0.505) whereas in heavy smokers it was 2.05 [1.43-2.93] (p < 0.001). The association in the group of heavy smokers remained significant (OR 2.38 [1.54-3.68], p < 0.001) after adjustment for traditional risk factors for cardiovascular disease and also after further adjustment for other cardiometabolic risk factors, i.e. the metabolic syndrome, CRP and insulin resistance (HOMA2IR) (OR C3 between 2.16 and 2.29, all p ≤ 0.001).Conclusion
Human plasma complement C3 is associated with prevalent CHD, but only in heavy smokers, and this association is independent of important metabolic cardiovascular risk factors. 相似文献107.
Kim TK Wang J Janjetovic Z Chen J Tuckey RC Nguyen MN Tang EK Miller D Li W Slominski AT 《Molecular and cellular endocrinology》2012,361(1-2):143-152
To define the interaction of novel secosteroids produced by the action of cytochrome P450scc with vitamin D receptor (VDR), we used a human melanoma line overexpressing VDR fused with enhanced green fluorescent protein (EGFP) and tested the ligand induced translocation of VDR from the cytoplasm to the nucleus. Hydroxyderivatives of vitamin D(3) with a full length (D(3)) side chain and hydroxy-secosteroids with a shortened side chain (pD) stimulated VDR translocation and inhibited proliferation, however, with different potencies. In general the D(3) were more potent than pD analogues. Molecular modeling of the binding of the secosteroids to the VDR genomic binding pocket (G-pocket) correlated well with the experimental data for VDR translocation. In contrast, docking scores for the non-genomic binding site of the VDR were poor. In conclusion, both the length of the side chain and the number and position of hydroxyl groups affect the activation of VDR by novel secosteroids. 相似文献
108.
Danya M. Lavin Linda Zhang Stacia Furtado Richard A. Hopkins Edith Mathiowitz 《Acta biomaterialia》2013,9(1):4569-4578
Wet spun microfibers have great potential for the design of multifunctional controlled release scaffolds. Understanding aspects of drug delivery and mechanical strength, specific to protein molecular weight, may aid in the optimization and development of wet spun fiber platforms. This study investigated the intrinsic material properties and release kinetics of poly(l-lactic acid) (PLLA) and poly(lactic-co-glycolic acid) (PLGA) wet spun microfibers encapsulating proteins with varying molecular weights. A cryogenic emulsion technique developed in our laboratory was used to encapsulate insulin (5.8 kDa), lysozyme (14.3 kDa) and bovine serum albumin (BSA, 66.0 kDa) within wet spun microfibers (~100 μm). Protein loading was found to significantly influence mechanical strength and drug release kinetics of PLGA and PLLA microfibers in a molecular-weight-dependent manner. BSA encapsulation resulted in the most significant decrease in strength and ductility for both PLGA and PLLA microfibers. Interestingly, BSA-loaded PLGA microfibers had a twofold increase (8 ± 2 MPa to 16 ± 1 MPa) in tensile strength and a fourfold increase (3 ± 1% to 12 ± 6%) in elongation until failure in comparison to PLLA microfibers. PLGA and PLLA microfibers exhibited prolonged protein release up to 63 days in vitro. Further analysis with the Korsmeyer–Peppas kinetic model determined that the mechanism of protein release was dependent on Fickian diffusion. These results emphasize the critical role protein molecular weight has on the properties of wet spun filaments, highlighting the importance of designing small molecular analogues to replace growth factors with large molecular weights. 相似文献
109.
Francisco Javier Guzmán-de la Garza Juan Manuel Ibarra-Hernández Paula Cordero-Pérez Pablo Villegas-Quintero Claudia Ivette Villarreal-Ovalle Liliana Torres-González Norma Edith Oliva-Sosa Gabriela Alarcón-Galván Nancy Esthela Fernández-Garza Linda Elsa Mu?oz-Espinosa Carlos Rodrigo Cámara-Lemarroy José Gerardo Carrillo-Arriaga 《Clinics (S?o Paulo, Brazil)》2013,68(7):1034-1038