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1.
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2.
Yan Lu Shulin/SL Li Shiguo/SG Zhu Yabin/YB Gong Jun/J Shi Ling/ L Xu 《Biological procedures online》2017,19(1):2
DNA/RNA methylation plays an important role in lung cancer initiation and progression. Liquid biopsy makes use of cells, nucleotides and proteins released from tumor cells into body fluids to help with cancer diagnosis and prognosis. Methylation of circulating tumor DNA (ctDNA) has gained increasing attention as biomarkers for lung cancer. Here we briefly introduce the biological basis and detection method of ctDNA methylation, and review various applications of methylated DNA in body fluids in lung cancer screening, diagnosis, prognosis, monitoring and treatment prediction. We also discuss the emerging role of RNA methylation as biomarkers for cancer. 相似文献
3.
Out of Africa and back again: nested cladistic analysis of human Y chromosome variation 总被引:18,自引:3,他引:15
Hammer MF; Karafet T; Rasanayagam A; Wood ET; Altheide TK; Jenkins T; Griffiths RC; Templeton AR; Zegura SL 《Molecular biology and evolution》1998,15(4):427-441
We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
individuals from Africa, Asia, Europe, Oceania, and the New World.
Phylogenetic analyses of these nine sites resulted in a tree for 10
distinct Y haplotypes with a coalescence time of approximately 150,000
years. The 10 haplotypes were unevenly distributed among human populations:
5 were restricted to a particular continent, 2 were shared between Africa
and Europe, 1 was present only in the Old World, and 2 were found in all
geographic regions surveyed. The ancestral haplotype was limited to African
populations. Random permutation procedures revealed statistically
significant patterns of geographical structuring of this paternal genetic
variation. The results of a nested cladistic analysis indicated that these
geographical associations arose through a combination of processes,
including restricted, recurrent gene flow (isolation by distance) and range
expansions. We inferred that one of the oldest events in the nested
cladistic analysis was a range expansion out of Africa which resulted in
the complete replacement of Y chromosomes throughout the Old World, a
finding consistent with many versions of the Out of Africa Replacement
Model. A second and more recent range expansion brought Asian Y chromosomes
back to Africa without replacing the indigenous African male gene pool.
Thus, the previously observed high levels of Y chromosomal genetic
diversity in Africa may be due in part to bidirectional population
movements. Finally, a comparison of our results with those from nested
cladistic analyses of human mtDNA and beta-globin data revealed different
patterns of inferences for males and females concerning the relative roles
of population history (range expansions) and population structure
(recurrent gene flow), thereby adding a new sex-specific component to
models of human evolution.
相似文献
4.
5.
Lateralized behaviour occurs in diverse animals, but relatively few studies examine the phenomenon in invertebrates. Here we report a population-level left turn bias in the giant water bug Belostoma flumineum Say (Heteroptera: Belostomatidae) in an underwater T-maze. Individuals made significantly more left turns than right turns, including when they were naïve and first introduced to the maze. Water bugs also showed significantly longer runs of consecutive left turns than right turns (i.e. LLLLL). The length of these runs, however, did not increase with experience in the maze, suggesting that the effect is not the result of learning. There were also no differences in turning bias between male and female water bugs. The proximate mechanism(s) underlying the left turn bias is unknown, but directional cues in the environment were eliminated by rotating the maze 180° between experiments, suggesting the mechanism(s) is endogenous. To our knowledge this is the first study of lateralized behaviour in the Heteroptera or in a swimming invertebrate animal. 相似文献
6.
Palevitch O Kight K Abraham E Wray S Zohar Y Gothilf Y 《Cell and tissue research》2007,327(2):313-322
The ontogeny of two gonadotropin-releasing-hormone (GnRH) systems, salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), was
investigated in zebrafish (Danio rerio). In situ hybridization (ISH) first detected sGnRH mRNA-expressing cells at 1 day post-fertilization (pf) anterior to the
developing olfactory organs. Subsequently, cells were seen along the ventral olfactory organs and the olfactory bulbs, reaching
the terminal nerve (TN) ganglion at 5–6 days pf. Some cells were detected passing posteriorly through the ventral telencephalon
(10–25 days pf), and by 25–30 days pf, sGnRH cells were found in the hypothalamic/preoptic area. Continuous documentation
in live zebrafish was achieved by a promoter-reporter expression system. The expression of enhanced green fluorescent protein
(EGFP) driven by the sGnRH promoter allowed the earlier detection of cells and projections and the migration of sGnRH neurons.
This expression system revealed that long leading processes, presumably axons, preceded the migration of the sGnRH neuron
somata. cGnRH-II mRNA expressing cells were initially detected (1 day pf) by ISH analysis at lateral aspects of the midbrain
and later on (starting at 5 days pf) at the midline of the midbrain tegmentum. Detection of red fluorescent protein (DsRed)
driven by the cGnRH-II promoter confirmed the midbrain expression domain and identified specific hindbrain and forebrain cGnRH-II-cells
that were not identified by ISH. The forebrain DsRed-expressing cells seemed to emerge from the same site as the sGnRH-EGFP-expressing
cells, as revealed by co-injection of both constructs. These studies indicate that zebrafish TN and hypothalamic sGnRH cell
populations share a common embryonic origin and migratory path, and that midbrain cGnRH-II cells originate within the midbrain.
This study was supported by the US-Israel Bi-national Agricultural Research and Development (BARD) Foundation (grant 3428-03). 相似文献
7.
R A Dunham A C Ramboux P L Duncan M Hayat T T Chen C M Lin K Kight I Gonzalez-Villasenor D A Powers 《Molecular Marine Biology and Biotechnology》1992,1(4-5):380-389
We examined expression and inheritance of salmonid growth hormone genes RSVLTR-rtGH1 cDNA and RSVLTR-csGH cDNA, transferred to channel catfish (Ictalurus punctatus) by microinjection. One to 9 copies of the foreign DNA were inserted in either head-to-tail tandem array at single insertion sites or single copies at multiple insertion sites. All P1 transgenic catfish evaluated produced salmonid growth hormone regardless of the construct. Five P1 x P1 matings were accomplished. The spawning rate and fertility of these P1 transgenics in artificial spawning conditions were comparable to those of normal channel catfish. In two of three years, 100% spawning and 100% hatch were obtained. Percent transgenic progeny observed in the five matings were 20, 52, 7, 47, and 0%, which was lower (P < 0.001, chi 2) than the 75% inheritance expected assuming the P1 brood stock had at least one copy of the foreign gene integrated and were not mosaics in the germ line. At least 7 of 10 P1 were mosaics, and a minimum of 2 of 10 P1 did not possess the salmonid growth hormone genes in their germ line. P1 transgenics grew at the same rate as their nontransgenic full siblings, which is not surprising because the P1 were mosaics. F1 transgenic progeny in two families possessing RSVLTR-csGH cDNA grew 26% faster, to 40 to 50 gm, than their nontransgenic full siblings when evaluated communally. One F1 progeny group produced by RSVLTR-rtGH1 cDNA x RSVLTR-csGH cDNA mating and one F1 progeny group (parents either RSVLTR-rtGH1 cDNA or RSVLTR-csGH cDNA) grew at the same rate as normal full siblings when grown communally to 25 gm and 60 mg, respectively. In families where F1 progeny grew faster than controls, the range in body weight and coefficient of variation for the transgenic full siblings were less than those for controls. In families where F1 progeny grew at the same rate as controls, range in body weight and coefficient of variation were similar for transgenic and normal individuals. The percent deformities observed in P1 transgenics (13.6%) was higher (P < 0.05) than in microinjected P1 nontransgenics (5.1%). Percent deformities in transgenics and control F1 channel catfish was not different (p > 0.05; 0.5 and 2.8%, respectively). 相似文献
8.
Hardies SC; Martin SL; Voliva CF; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1986,3(2):109-125
9.
Summary Microsomal and soluble fractions of Pleurotus pulmonarius exhibited a reduced carbon monoxide difference spectrum with P450 maxima at 448nm and 450–452nm respectively. Substrate induced Type I spectra were observed on addition of benzo(a)pyrene to both fractions. Benzo(a)pyrene hydroxylation was measured using the aryl hydrocarbon hydroxylase assay and was observed to be P450 dependent as indicated by carbon monoxide inhibition together with the substrate binding characteristics. The activity of the fractions were observed to give Km of 200mM and 660mM and Vmax of 1.25 nmol/min/nmol P450 and 0.57 nmol/min/nmol P450 for the microsomal and cytosolic fractions respectively. 相似文献
10.
Naomi J. Marty Dakshinamurthy Rajalingam Alicia D. Kight Nathaniel E. Lewis Daniel Fologea Thallapuranam Krishnaswamy Suresh Kumar Ralph L. Henry Robyn L. Goforth 《The Journal of biological chemistry》2009,284(22):14891-14903
The chloroplast signal recognition particle (cpSRP) and its receptor
(cpFtsY) function in thylakoid biogenesis to target integral membrane proteins
to thylakoids. Unlike cytosolic SRP receptors in eukaryotes, cpFtsY partitions
between thylakoid membranes and the soluble stroma. Based on sequence
alignments, a membrane-binding motif identified in Escherichia coli
FtsY appears to be conserved in cpFtsY, yet whether the proposed motif is
responsible for the membrane-binding function of cpFtsY has yet to be shown
experimentally. Our studies show that a small N-terminal region in cpFtsY
stabilizes a membrane interaction critical to cpFtsY function in
cpSRP-dependent protein targeting. This membrane-binding motif is both
necessary and sufficient to direct cpFtsY and fused passenger proteins to
thylakoids. Our results demonstrate that the cpFtsY membrane-binding motif may
be functionally replaced by the corresponding region from E. coli,
confirming that the membrane-binding motif is conserved among organellar and
prokaryotic homologs. Furthermore, the capacity of cpFtsY for lipid binding
correlates with liposome-induced GTP hydrolysis stimulation. Mutations that
debilitate the membrane-binding motif in cpFtsY result in higher rates of GTP
hydrolysis, suggesting that negative regulation is provided by the intact
membrane-binding region in the absence of a bilayer. Furthermore, NMR and CD
structural studies of the N-terminal region and the analogous region in the
E. coli SRP receptor revealed a conformational change in secondary
structure that takes place upon lipid binding. These studies suggest that the
cpFtsY membrane-binding motif plays a critical role in the intramolecular
communication that regulates cpSRP receptor functions at the membrane.Proper compartmentalization of proteins relies on the ability of protein
localization pathways to transport proteins efficiently from their sites of
synthesis to their sites of function. The signal recognition particle
(SRP)2 and its
receptor function in every kingdom of life to target proteins to the
endoplasmic reticulum (eukaryotes), cytoplasmic membrane (prokaryotes), and
thylakoid membrane (chloroplasts)
(1). The targeting function of
SRP relies on a conserved 54-kDa SRP subunit (SRP54; Ffh in Escherichia
coli and cpSRP54 in chloroplasts) as well as a conserved SRP receptor
(SRα; FtsY in E. coli and cpFtsY in chloroplasts). For
cytosolic SRPs (SRP54 and Ffh), interactions with a substrate signal sequence
and an SRP RNA moiety are prerequisite for interaction with the SRP receptor
(SRα and FtsY) (2). GTP
binding and hydrolysis by both SRP54 and SRα coordinate substrate
release from SRP to the translocon and release of SRP from SRα. In
chloroplasts, cpFtsY functions along with a unique SRP (cpSRP) to
post-translationally target nuclear encoded proteins to thylakoid membranes
(3). Light-harvesting
chlorophyll a/b-binding proteins (LHCPs) imported into the
chloroplast stroma are bound by cpSRP to form a soluble targeting complex,
which directs the LHCP substrate to the thylakoid membrane translocon Alb3
(Albino3) in a GTP- and cpFtsY-dependent manner
(14,
36). Although many general
steps of SRP protein targeting seem largely conserved across evolutionary
boundaries, the nature and dynamics of the receptor appear to have
diverged.In eukaryotic systems, SRα is peripherally bound to the membrane
through association with the integral membrane subunit SRβ. In contrast,
no chloroplast or bacterial homolog of SRβ has been identified. cpFtsY
and E. coli FtsY (EcFtsY) are found partitioned between the membrane
and the stroma or cytosol, respectively. The membrane-binding capacity of
EcFtsY serves to stimulate GTPase activity and appears critical in that only
membrane-associated EcFtsY supports the release of nascent chains from SRP to
the translocon (4,
5). However, the partitioning
activity is not strictly required because EcFtsY tethered to the membrane is
functional in vivo
(37). Given the conserved
nature of partitioning among bacterial and chloroplast SRP receptors,
partitioning may play an, as of yet, unidentified role in protein targeting by
SRP. Nevertheless, differences in lipid composition between bacterial and
thylakoid membranes make it interesting to speculate that there are
mechanistic differences in membrane partitioning.Like many prokaryotic FtsY homologs (e.g. Thermus aquaticus),
cpFtsY lacks the N-terminal acidic domain (A domain) implicated in EcFtsY
membrane binding (6). Although
the highly conserved FtsY GTPase domain (NG domain) of EcFtsY
(EcFtsYNG) fails to support protein targeting, the addition of the
last A domain residue, Phe-196 of a conserved double-Phe motif
(EcFtsYNG+1), restores protein targeting in vivo
(7). In vitro studies
also show that EcFtsYNG+1 retains the capacity to bind membranes
and support integration of SRP-dependent substrates, although at significantly
reduced levels compared with full-length EcFtsY
(8). A resolved structure of
EcFtsYNG+1 suggests that the amphipathic nature of the region
containing Phe-196 plays a critical role in membrane association
(9). Furthermore, it has been
demonstrated that liposomes stimulate GTP hydrolysis rates of SRP with
EcFtsYNG+1, but not with EcFtsYNG, supporting the idea
that the A domain in its entirety is not strictly required.For cpFtsY, the necessity and functional role(s) of partitioning between a
thylakoid-bound and a soluble phase, as well as the role of N-terminal
residues in these functions, remain unknown. In addition, both the
conformational state of membrane-bound cpFtsY and EcFtsY and the mechanism
responsible for controlling membrane partitioning and altered GTPase activity
remain unclear. Because of the gain of function exhibited by
EcFtsYNG+1 and the conserved nature of the surrounding motif
(9), it seems likely that this
conserved region is necessary to support membrane binding and corresponding
functions not only in EcFtsY but also in FtsY homologs.To examine the functional role of the N-terminal region of cpFtsY, we have
utilized deletion and point mutants in assays that reconstitute cpFtsY
activities, including the cpSRP-dependent integration of LHCP. Together, our
data indicate that the conserved lipid-binding motif identified in bacterial
FtsY homologs is present in cpFtsY and is both necessary and sufficient for
thylakoid binding and critical for LHCP targeting. 相似文献