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11.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献12.
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14.
I. A. Boldyrev I. V. Grechishnikova Yu. B. Pavlova Jul. G. Molotkovsky 《Russian Journal of Bioorganic Chemistry》2004,30(1):71-74
A new fluorescent probe, a 3-perylenoyl derivative of the lipophilized antitumor drug merphalan (sarcolysine), was synthesized. The probe is suitable for studying intracellular traffic and metabolism of merphalan and its derivatives. The perylenoyl fluorescence is partially quenched by the merphalan chromophore, which broadens the probe potentialities. 相似文献
15.
A. V. Semakov A. A. Blinkov G. P. Gaenko A. G. Vostrova J. G. Molotkovsky 《Russian Journal of Bioorganic Chemistry》2013,39(3):299-305
A series of N 1-acyl derivatives of 5-fluorouracil (5-FU) bearing the residues of palmitic, p-myristoylaminobenzoic, p-oleoylaminobenzoic, and adamantane-1-carboxylic acids have been synthesized. The relative hydrolysis rates for the derivatives under physiological conditions (pH 7.2 and 37°C) have been determined, and it has been shown that the resistance of these compounds to hydrolysis increases as the steric accessibility of the amide group at residue N 1 of 5-FU decreases. The derivatives easily incorporate into the lipid bilayer; their liposomal preparations show a marked cytostatic activity on human breast lymphoma cells (LD50 ~1 μM) and are of interest as potential antitumor preparations. In addition, a fluorescent analogue of the above derivatives, 1-[8-(3-perylenyl)octanoyl]-5-fluorouracil, has been synthesized, which is intended for studying the behavior of 5-FU derivatives in cells and tissues by instrumental methods. 相似文献
16.
A Emami-Khoyi DA Hartley RH Cruickshank LJ Boren JG Ross 《New Zealand journal of zoology.》2016,43(4):322-335
New Zealand fur seals are one of many pinniped species that survived the commercial sealing of the eighteenth and nineteenth centuries in dangerously low numbers. After the enforcement of a series of protection measures in the early twentieth century, New Zealand fur seals began to recover from the brink of extinction. We examined the New Zealand fur seal populations of Banks Peninsula, South Island, New Zealand using the mitochondrial DNA control region. We identified a panmictic population structure around Banks Peninsula. The most abundant haplotype in the area showed a slight significant aggregated structure. The Horseshoe Bay colony showed the least number of shared haplotypes with other colonies, suggesting a different origin of re-colonisation of this specific colony. The effective population size of the New Zealand fur seal population at Banks Peninsula was estimated at approximately 2500 individuals. The exponential population growth rate parameter for the area was 35, which corresponds to an expanding population. In general, samples from adjacent colonies shared 4.4 haplotypes while samples collected from colonies separated by between five and eight bays shared 1.9 haplotypes. The genetic data support the spill-over dynamics of colony expansion already suggested for this species. Approximate Bayesian computations analysis suggests re-colonisation of the area from two main clades identified across New Zealand with a most likely admixture coefficient of 0.41 to form the Banks Peninsula population. Approximate Bayesian computations analysis estimated a founder population size of approximately 372 breeding individuals for the area, which then rapidly increased in size with successive waves of external recruitment. The population of fur seals in the area is probably in the late phase of maturity in the colony expansion dynamic. 相似文献
17.
Purification and characterization of Dolichos lablab lectin 总被引:1,自引:0,他引:1
The mannose/glucose-binding Dolichos lablab lectin (designated DLL) has
been purified from seeds of Dolichos lablab (hyacinth bean) to
electrophoretic homogeneity by affinity chromatography on an ovalbumin-
Sepharose 4B column. The purified lectin gave a single symmetric protein
peak with an apparent molecular mass of 67 kDa on gel filtration
chromatography, and five bands ranging from 10 kDa to 22 kDa upon SDS-PAGE.
N-Terminal sequence analysis of these bands revealed subunit heterogeneity
due to posttranslational proteolytic truncation at different sites mostly
at the carboxyl terminus. The carbohydrate binding properties of the
purified lectin were investigated by three different approaches:
hemagglutination inhibition assay, quantitative precipitation inhibition
assay, and ELISA. On the basis of these studies, it is concluded that the
Dolichos lablab lectin has neither an extended carbohydrate combining site,
nor a hydrophobic binding site adjacent to it. The carbohydrate combining
site of DLL appears to most effectively accommodate a nonreducing terminal
alpha-d-mannosyl unit, and to be complementary to the C-3, C-4, and C-6
equatorial hydroxyl groups of alpha-d-mannopyranosyl and
alpha-d-glucopyranosyl residues. DLL strongly precipitates murine IgM but
not IgG, and the recent finding that this lectin interacts specifically
with NIH 3T3 fibroblasts transfected with the Flt3 tyrosine kinase receptor
and preserves human cord blood stem cells and progenitors in a quiescent
state for prolonged periods in culture, make this lectin a valuable tool in
biomedical research.
相似文献
18.
I M Molotkovskaya N A Zelenova G V Lutsenko A M Sapozhnikov I I Mikhalyov J G Molotkovsky 《Membrane & cell biology》1999,12(6):783-791
Gangliosides have been shown to inhibit proliferation of the interleukin-4 (IL-4) responsive cell line CT.4R. Kinetic analysis has revealed that ganglioside GT1b is a competitive inhibitor of proliferation, while GM and GM3 show a mixed pattern of inhibition, i.e., exhibit more than one inhibition type. Contribution of the competitive cell inhibition for GM1 and GM3 depends on serum factors added: the higher is the percentage of FCS, the larger is the contribution of competitive inhibition. The pattern of proliferation inhibition shown for GT1b does not depend on the FCS content. We have also studied the interaction of the recombinant IL-4 with fluorescent (anthrylvinyl-labelled) gangliosides GM1 and GM3 and lactosylceramide incorporated into liposomes. Dissociation constants of the IL-4-ganglioside complexes have been determined; lactosylceramide does not interact with rIL-4. The K(d) values for the lymphokine complexes with gangliosides support the conclusion based on the kinetic analysis that IL-4 has a higher affinity for GM3 (K(d) = 5 nM) than for GM1 (K(d) = 0.28 microM). 相似文献
19.
20.
Svetlana I. Galkina Julia M. Romanova Vladimir I. Stadnichuk Julian G. Molotkovsky Galina F. Sud'ina & Thomas Klein 《FEMS immunology and medical microbiology》2009,56(2):162-171
Nitric oxide (NO) plays an important role in host defense against bacterial infections such as salmonellosis. NO and 4-bromophenacyl bromide (BPB) induce the formation of long tubulovesicular extensions (TVE, cytonemes, membrane tethers) from human neutrophils. These TVE serve as cellular sensory and adhesive organelles. In the present study, we demonstrated that in the presence of the NO donor, diethylamine NONOate or BPB human neutrophils bound and aggregated Salmonella enterica serovar Typhimurium bacteria extracellularly by TVE. In contrast, inhibition of NO-synthase activity by N ω -nitro- l -arginine methyl ester stimulated neutrophil phagocytosis (ingestion) of bacteria. Neutrophil TVE consisted of membrane-covered cytoplasm as was shown by the fluorescent cytoplasmic dye 2',7'-bis(2carboxyethyl)-5,(6)-carboxyfluorescein, and the fluorescent lipid, BODIPY-labeled sulfatide. Disruption and shedding of TVE were accompanied by the appearance of specific invaginations (porosomes) on neutrophil cell bodies. These invaginations corresponded to the variations in diameter of TVE (160–240 nm). We hypothesized that TVE represented protrusions of neutrophil exocytotic trafficking through special structures on the neutrophil surface. In conclusion, we propose a novel mechanism by which NO-induced TVE formation enables neutrophils to bind and aggregate bacteria at a distance. 相似文献