Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study

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.     

Effect of temperature on invertase, invertase inhibitor, and sugars in potato tubers

The accumulation of reducing sugars in potato tubers exposed to low temperatures occurs with concomitant formation of the enzyme invertase. During the initial period of cold treatment when reducing sugars increase rapidly, invertase formation proceeds until the level of enzyme exceeds that of an endogenous macromolecular invertase inhibitor, resulting in a basal invertase activity. As the rate of sugar accumulation decreases and the sugar level becomes nearly constant, total invertase decreases, the basal activity disappears, and a low excess of inhibitor develops. On transfer of cold-stored tubers to warmer temperatures, sugars and invertase decrease sharply and a large excess of inhibitor develops. These changes in sugars, invertase and inhibitor occur reversibly when the tubers are subjected to alternating temperatures.     

Mitochondrial DNA structure and colony expansion dynamics of New Zealand fur seals (Arctocephalus forsteri) around Banks Peninsula

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.     

The structure, catalytic mechanism and regulation of adenylyl cyclase

The recent structure determinations of the mammalian effector enzyme adenylyl cyclase reveal the structure of its catalytic core, provide new insights into its catalytic mechanism and suggest how diverse signaling molecules regulate its activity.     

Nucleotide variation at the hypervariable esterase 6 isozyme locus of Drosophila simulans

Esterase 6 (Est-6/EST6) is polymorphic in both Drosophila melanogaster and D. simulans for two common allozyme forms, as well as for several other less common variants. Parallel latitudinal clines in the frequencies of the common EST6-F and EST6-S allozymes in these species have previously been interpreted in terms of a shared amino acid polymorphism that distinguishes the two variants and is subject to selection. Here we compare the sequences of four D. simulans Est-6 isolates and show that overall estimates of nucleotide heterozygosity in both coding and 5' flanking regions are more than threefold higher than those obtained previously for this gene in D. melanogaster. Nevertheless, the ratio of replacement to exon silent-site polymorphism in D. simulans is less than the ratio of replacement to silent divergence between D. simulans and D. melanogaster, which could be the result of increased efficiency of selection against replacement polymorphisms in D. simulans or to divergent selection between the two species. We also find that the amino acid polymorphisms separating EST6- F and EST6-S in D. simulans are not the same as those that separate these allozymes in D. melanogaster, implying that the shared clines do not reflect shared molecular targets for selection. All comparisons within and between the two species reveal a remarkable paucity of variation in a stretch of nearly 400 bp immediately 5' of the gene, indicative of strong selective constraint to retain essential aspects of Est-6 promoter function.      

Reserve selection in the Succulent Karoo,South Africa: coping with high compositional turnover

The Succulent Karoo biome is home to the world's richest succulent flora. It has approximately 1954 endemic plant species, and is the only semi-arid region to qualify as a hotspot of global significance. Despite its importance, only 2% of the biome is currently protected. Based on its flora, the biome can be divided into 12 bioregions, reflecting its high compositional turnover in relation to environmental and geographical gradients. Only three of these bioregions (the Gariep Centre, the Namaqualand Rocky Hills and the Tanqua Karoo) contain National Parks, and three contain large (over 10000 ha) provincial reserves (the Gariep Centre, the Namaqualand Rocky Hills and the Little Karoo). The current reserve system does little to conserve biodiversity, with only one reserve significantly conserving Red Data Book (RDB) plant diversity. Using a RDB plant species database of 3874 records at a quarter degree scale (QDS = 15×15), we used hotspot analyses and iterative reserve selection algorithms to identify possible locations for future reserves. The hotspot analysis and iterative analyses yielded similar results for the top 11 QDS, mainly due to very high local endemism. Also because of the local endemism and the high species turnover within the biome, the real-world iterative algorithm (starting with the seven already reserved QDS) selected a very large total number of QDS (59% of the total in the biome) to conserve all RDB species. As a possible alternative to conservation planning based on QDS, we also assessed priorities at the scale of bioregions, but showed that representation at this geographic level misses important areas defined at a finer scale. We suggest that if the objective is to maximise the retention of RDB species in the landscape (to pre-empt extinction by scheduling the allocation of limited conservation resources), at least the top 5% of QDS (n=11) selected by the iterative procedure, and identified as the core conservation sequence by analysis of endemicity and threat, should be given priority for reservation. Less extensive and, in some cases, less formal conservation action can be applied to QDS later in the sequence, based on species-specific monitoring and action plans. Of the 11 core areas, four fall in a node centred on the Vanrhynsdorp Centre, two fall in a node centred on the Kamiesberg, and the remaining five are isolated. With existing reserves, the core areas capture 50% of the RDB flora in 8% of the biome.     

Characterization of SPACR, a sialoprotein associated with cones and rods present in the interphotoreceptor matrix of the human retina: immunological and lectin binding analysis

Rod and cone photoreceptors project from the outer retinal surface into a carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM glycoconjugates are distributed around rods and cones. Wheat germ agglutinin (WGA) strongly decorates the rod matrix domains and weakly decorates the cone matrix domains. This study characterizes the major WGA-binding glycoprotein in the human IPM, which we refer to as SPACR (sialoprotein associated with cones and rods). SPACR, which has a molecular weight of 147 kDa, was isolated and purified from the IPM by lectin affinity chromatography. A polyclonal antibody to SPACR was prepared that colocalizes in tissue preparations with WGA-binding domains in the IPM. Sequential digestion of SPACR with N- and O- glycosidases results in a systematic increase in electrophorectic mobility, indicating the presence of both N- and O-linked glycoconjugates. Complete deglycosylation results in a reduction in the relative molecular mass of SPACR by about 30%. Analysis of lectin binding allowed us to identify some of the structural characteristics of SPACR glycoconjugates. Treatment with neuraminidase exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA), specific for alpha2-6 linked sialic acid, does not, indicating that the dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate, NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR suggests that this glycoprotein may contribute substantially to the polyanionic nature of the IPM. The carbohydrate chains present on SPACR could also provide sites for extensive crosslinking and participate in the formation of the ordered IPM lattice that surrounds the elongate photoreceptors projecting from the outer retinal surface.      

Measuring the difference made by conservation initiatives: protected areas and their environmental and social impacts

Success in conservation depends on our ability to reduce human pressures in areas that harbour biological diversity and ecosystem services. Legally protecting some of these areas through the creation of protected areas is a key component of conservation efforts globally. To develop effective protected area networks, practitioners need credible, scientific evidence about the degree to which protected areas affect environmental and social outcomes, and how these effects vary with context. Such evidence has been lacking, but the situation is changing as conservation scientists adopt more sophisticated research designs for evaluating protected areas'' past impacts and for predicting their future impacts. Complementing these scientific advances, conservation funders and practitioners are paying increasing attention to evaluating their investments with more scientifically rigorous evaluation designs. This theme issue highlights recent advances in the science of protected area evaluations and explores the challenges to developing a more credible evidence base that can help societies achieve their goals of protecting nature while enhancing human welfare.