Birth Weight in Relation to Leisure Time Physical Activity in Adolescence and Adulthood: Meta-Analysis of Results from 13 Nordic Cohorts

Background

Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk.

Methods/Principal Findings

We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26–3.75 kg), the birth weight categories of 1.26–1.75, 1.76–2.25, 2.26–2.75, and 4.76–5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking.

Conclusions/Significance

The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk.     

FGF‐8b induces growth and rich vascularization in an orthotopic PC‐3 model of prostate cancer

Fibroblast growth factor 8 (FGF‐8) is expressed at an increased level in a high proportion of prostate cancers and it is associated with a poor prognosis of the disease. Our aim was to study the effects of FGF‐8b on proliferation of PC‐3 prostate cancer cells and growth of PC‐3 tumors, and to identify FGF‐8b‐associated molecular targets. Expression of ectopic FGF‐8b in PC‐3 cells caused a 1.5‐fold increase in cell proliferation in vitro and a four‐ to fivefold increase in the size of subcutaneous and orthotopic prostate tumors in nude mice. Tumors expressing FGF‐8b showed a characteristic morphology with a very rich network of capillaries. This was associated with increased spread of the cancer cells to the lungs as measured by RT‐qPCR of FGF‐8b mRNA. Microarray analyses revealed significantly altered, up‐ and downregulated, genes in PC‐3 cell cultures (169 genes) and in orthotopic PC‐3 tumors (61 genes). IPA network analysis of the upregulated genes showed the strongest association with development, cell proliferation (CRIP1, SHC1), angiogenesis (CCL2, DDAH2), bone metastasis (SPP1), cell‐to‐cell signaling and energy production, and the downregulated genes associated with differentiation (DKK‐1, VDR) and cell death (CYCS). The changes in gene expression were confirmed by RT‐qPCR. In conclusion, our results demonstrate that FGF‐8b increases the growth and angiogenesis of orthotopic prostate tumors. The associated gene expression signature suggests potential mediators for FGF‐8b actions on prostate cancer progression and metastasis. J. Cell. Biochem. 107: 769–784, 2009. © 2009 Wiley‐Liss, Inc.     

Crystal Structure of Liganded Rat Peroxisomal Multifunctional Enzyme Type 1: A FLEXIBLE MOLECULE WITH TWO INTERCONNECTED ACTIVE SITES*

The crystal structure of the full-length rat peroxisomal multifunctional enzyme, type 1 (rpMFE1), has been determined at 2.8 Å resolution. This enzyme has three catalytic activities and two active sites. The N-terminal part has the crotonase fold, which builds the active site for the Δ³,Δ²-enoyl-CoA isomerase and the Δ²-enoyl-CoA hydratase-1 catalytic activities, and the C-terminal part has the (3S)-hydroxyacyl-CoA dehydrogenase fold and makes the (3S)-hydroxyacyl-CoA dehydrogenase active site. rpMFE1 is a multidomain protein having five domains (A–E). The crystal structure of full-length rpMFE1 shows a flexible arrangement of the A-domain with respect to the B–E-domains. Because of a hinge region near the end of the A-domain, two different positions of the A-domain were observed for the two protein molecules (A and B) of the asymmetric unit. In the most closed conformation, the mode of binding of CoA is stabilized by domains A and B (helix-10), as seen in other crotonase fold members. Domain B, although functionally belonging to the N-terminal part, is found tightly associated with the C-terminal part, i.e. fixed to the E-domain. The two active sites of rpMFE1 are ∼40 Å apart, separated by a tunnel, characterized by an excess of positively charged side chains. Comparison of the structures of rpMFE1 with the monofunctional crotonase and (3S)-hydroxyacyl-CoA dehydrogenase superfamily enzymes, as well as with the bacterial α₂β₂-fatty acid oxidation multienzyme complex, reveals that this tunnel could be important for substrate channeling, as observed earlier on the basis of the kinetics of rpMFE1 purified from rat liver.     

Structural studies of MFE-1: the 1.9 A crystal structure of the dehydrogenase part of rat peroxisomal MFE-1

The 1.9 A structure of the C-terminal dehydrogenase part of the rat peroxisomal monomeric multifunctional enzyme type 1 (MFE-1) has been determined. In this construct (residues 260-722 and referred to as MFE1-DH) the N-terminal hydratase part of MFE-1 has been deleted. The structure of MFE1-DH shows that it consists of an N-terminal helix, followed by a Rossmann-fold domain (domain C), followed by two tightly associated helical domains (domains D and E), which have similar topology. The structure of MFE1-DH is compared with the two known homologous structures: human mitochondrial 3-hydroxyacyl-CoA dehydrogenase (HAD; sequence identity is 33%) (which is dimeric and monofunctional) and with the dimeric multifunctional alpha-chain (alphaFOM; sequence identity is 28%) of the bacterial fatty acid beta-oxidation alpha2beta2-multienzyme complex. Like MFE-1, alphaFOM has an N-terminal hydratase part and a C-terminal dehydrogenase part, and the structure comparisons show that the N-terminal helix of MFE1-DH corresponds to the alphaFOM linker helix, located between its hydratase and dehydrogenase part. It is also shown that this helix corresponds to the C-terminal helix-10 of the hydratase/isomerase superfamily, suggesting that functionally it belongs to the N-terminal hydratase part of MFE-1.     

Fourier transform infrared study of fully hydrated dimyristoylphosphatidylglycerol. Effects of Na+ on the sn-1' and sn-3' headgroup stereoisomers

Molecular packing and the thermotropic phase behavior of fully hydrated ammonium salts of 1,2-dimyristoyl-sn-glycero-3-phosphatidyl-sn-1'-glycerol (1'-DMPG) and the corresponding 3' stereoisomer (3'-DMPG) as well as the effects of 300 mM NaCl on these lipids were studied by Fourier transform infrared (FTIR) spectroscopy. The ammonium salts of both stereoisomer show similar thermotropic phase behavior and have an order-disorder phase transition at approximately 21 degrees C. While complexing with Na+, however, an incubation of liposomes at +6 degrees C for 3 days results in significant structural differences between liposomes of 1'-DMPG and 3'-DMPG. In the presence of 300 mM NaCl the infrared spectra for 3'-DMPG reveal the appearance of a more solidified lipid nominated here as the highly crystalline phase with a transition into the liquid-crystalline state at a significantly higher temperature (approximately at 33 degrees C) than that for 1'-DMPG (approximately at 23 degrees C). Crystal field splitting resulting from interchain vibrational coupling is observed in the CH2 scissoring mode of the 3'-DMPG(Na+) complex in the highly crystalline phase (T less than 33 degrees C); i.e., the acyl chains are packed in a rigid orthorhombic- or monoclinic-like crystal lattice. At temperatures above the transition at 33 degrees C the acyl chains of 3'-DMPG(Na+) give rise to infrared spectra indicative of hexagonal packing. The latter type of hydrocarbon chain packing is also found for the ammonium salts of 1'-DMPG and 3'-DMPG without Na+ as well as for 1'-DMPG with Na+. In addition, the binding of Na+ to 3'-DMPG causes narrowing of the bands associated with the interfacial and polar headgroup regions of 3'-DMPG and thus reveals reduced motional freedom. This demonstrates that Na+ binds tightly to 3'-DMPG, leading to the immobilization of the entire phospholipid polar headgroup. Such effects by Na+ are not observed for 1'-DMPG.     

Integrity of the pericellular fibronectin matrix of fibroblasts is independent of sulfated glycosaminoglycans.

The pericellular matrix fibers of cultured human fibroblasts contain fibronectin, other glycoproteins, and heparan and chondroitin sulfate proteoglycans. In the present study, cell-free pericellular matrices were isolated from metabolically labeled fibroblast cultures. The isolated matrices were digested with heparinase from Flavobacterium heparinum, and then analyzed for sulfated glycosaminoglycans (GAGs). Nitrous acid degradation was used to distinguish the N-sulfated GAGs (heparan sulfate) from chondroitin sulfate. Fibronectin and the other major matrix polypeptides were studied using gel electrophoresis, enzyme immunoassay and immunofluorescence. Upon heparinase digestion, greater than 95% of sulfated GAGs were degraded in the matrix without detectable release of fibronectin or other matrix polypeptides or alteration of the fibrillar matrix structure. We conclude that in fibroblast cultures the integrity of the fibrillar matrix is independent of sulfated GAGs. Together with earlier observations, this suggests that filamentous polymerization of fibronectin forms the backbone of early connective tissue matrix.     

Comparison of Acridine Orange, Acriflavine, and Bisbenzimide Stains for Enumeration of Bacteria in Clear and Humic Waters

In highly humic water, acridine orange precipitated with dissolved humic matter, resulting in such bright background fluorescence that no bacteria could be seen. With bisbenzimide staining, a similar precipitate was nonfluorescent but obscured many cells. An acriflavine staining method proved useful and reproducible both in clear and in humic waters. Fading of fluorescence was not a problem, and stained samples could be stored after preparation. The fluorescence of cells stained with acriflavine was weaker than that with acridine orange, making counting extremely small cells slightly more difficult with the former stain.     

On the importance of dissolved organic matter in the nutrition of zooplankton in some lake waters

Summary A steady state, radiotracer technique was used to study the original source of the carbon in zooplankton. The experiments were started in filtered lake water with added inorganic radiocarbon. At the beginning of the experiments, a proportionally insignificant volume of unfiltered water was introduced into the culture, together with some ovigerous zooplankton individuals. Since the radioactivity: carbon ratio in the dissolved inorganic carbon was kept constant, a similar ratio would be expected to develop in the autotrophic phytoplankton. The same ratio would then be expected to develop in the zooplankton, if its sole carbon source was autotrophic phytoplankton.According to the results of this approach dissolved organic matter seems to be an important food resource for zooplankton, particularly in highly humic lakes. This conclusion was confirmed by the finding that zooplankton from these lakes was able to grow and reproduce in experiments started with filtered lake water and conducted in complete darkness.The development of algae was followed over the course of one experiment in highly humic water. The same micro-flagellates reproduced equally well in both light and darkness, which indicates the importance of heterotrophic metabolism in their nutrition. Although there are no direct observations about the food of zooplankton in our experiments, it appears likely that heterotrophic flagellates play an important role as a food of zooplankton in humic waters.The importance of dissolved organic matter in the nutrition of aquatic organisms would seem to be much greater than has generally been recognized. Consequently the prevailing concepts of the structure and functioning of planktonic ecosystem should be thoroughly re-evaluated.