Matrix gla protein in xenopus laevis: molecular cloning, tissue distribution, and evolutionary considerations

Matrix Gla protein (MGP) belongs to the family of vitamin K-dependent, Gla-containing proteins and in higher vertebrates, is found in the extracellular matrix of mineralized tissues and soft tissues. MGP synthesis is highly regulated at the transcription and posttranscription levels and is now known to be involved in the regulation of extracellular matrix calcification and maintenance of cartilage and soft tissue integrity during growth and development. However, its mode of action at the molecular level remains unknown. Because there is a large degree of conservation between amino,acid sequences of shark and human MGP, the function of MGP probably has been conserved throughout evolution. Given the complexity of the mammalian system, the study of MGP in a lower vertebrate might be advantageous to relate the onset of MGP expression with specific events during development. Toward this goal, MGP was purified from Xenopus long bones and its N-terminal amino acid sequence was determined and used to clone the Xenopus MGP complementary DNA (cDNA) by a mixture of reverse-transcription (RT)- and 5'- rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR). MGP messenger RNA (mRNA) was present in all tissues analyzed although predominantly expressed in Xenopus bone and heart and its presence was detected early in development at the onset of chondrocranium development and long before the appearance of the first calcified structures and metamorphosis. These results show that in this system, as in mammals, MGP may be required to delay or prevent mineralization of cartilage and soft tissues during the early stages of development and indicate that Xenopus is an adequate model organism to further study MGP function during growth and development.NATO/CRG940751/SA5.2.05, Praxis XXI/BIA 469/94, (NIH; grant AR 25921) (Praxis XXI/BPD/18816) (Praxis XXI/BICJ-2985

Ketocarotenoid production in tomato triggers metabolic reprogramming and cellular adaptation: The quest for homeostasis

Plants are sessile and therefore have developed an extraordinary capacity to adapt to external signals. Here, the focus is on the plasticity of the plant cell to respond to new intracellular cues. Ketocarotenoids are high-value natural red pigments with potent antioxidant activity. In the present study, system-level analyses have revealed that the heterologous biosynthesis of ketocarotenoids in tomato initiated a series of cellular and metabolic mechanisms to cope with the formation of metabolites that are non-endogenous to the plant. The broad multilevel changes were linked to, among others, (i) the remodelling of the plastidial membrane, where the synthesis and storage of ketocarotenoids occurs; (ii) the recruiting of core metabolic pathways for the generation of metabolite precursors and energy; and (iii) redox control. The involvement of the metabolites as regulators of cellular processes shown here reinforces their pivotal role suggested in the remodelled ‘central dogma’ concept. Furthermore, the role of metabolic reprogramming to ensure cellular homeostasis is propose

Field-study science classrooms as positive and enjoyable learning environments

We investigated differences between field-study classrooms and traditional science classrooms in terms of the learning environment and students’ attitudes to science, as well as the differential effectiveness of field-study classrooms for students differing in sex and English proficiency. A modified version of selected scales from the What Is Happening In this Class? questionnaire was used to assess the learning environment, whereas students’ attitudes were assessed with a shortened version of a scale from the Test of Science Related Attitudes. A sample of 765 grade 5 students from 17 schools responded to the learning environment and attitude scales in terms of both their traditional science classrooms and classrooms at a field-study centre in Florida. Large effect sizes supported the effectiveness of the field-studies classroom in terms of both the learning environment and student attitudes. Relative to the home school science class, the field-study class was considerably more effective for students with limited English proficiency than for native English speakers

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

Matrix gla protein in turbot (Scophthalmus maximus): gene expression analysis and identification of sites of protein accumulation

Matrix Gla protein (Mgp) is a secreted vitamin K-dependent extracellular matrix protein and a physiological inhibitor of calcification whose gene structure, amino acid sequence and tissue distribution have been conserved throughout evolution. In the present work, the turbot (Scophthalmus maximus) mgp cDNA was cloned and the sequence of the deduced protein compared to that of other vertebrates. As expected, it was closer to teleosts than to other vertebrate groups but there was a strict conservation of amino-acids thought to be important for protein function. Analysis of mgp gene expression indicated branchial arches as the site with higher levels of expression, followed by heart, vertebra and kidney. These results were confirmed by in situ hybridization with a strong mgp expression in branchial arch chondrocytes. Mgp was found to accumulate in gills where it appeared to be restricted to chondrocytes from branchial filaments, while in vertebrae it was localized in vertebral end plates, in growth zones, in vertebral arches and spines and in notochord cells. In the soft tissues analysed, Mgp was mainly detected in kidney and heart, consistent with previous data and providing further evidence for a role of Mgp as a calcification inhibitor and a modulator of the mineralization process. Our studies provide evidence that turbot, an important new species for aquaculture, is also a useful model to study function and expression of Mgp

Association of Osteocalcin and Abdominal Aortic Calcification in Older Women: The Study of Osteoporotic Fractures

Osteocalcin (OC) is produced by osteoblasts and vascular smooth muscle cells. In animal models, serum OC levels are strongly correlated with vascular calcium content, however, the association of OC with vascular calcification in humans is uncertain. The Study of Osteoporotic Fractures (SOF) enrolled community-living women, age ≥65 years. The present study included a subsample of 363 randomly selected SOF participants. Serum total OC was measured by ELISA, and abdominal aortic calcification (AAC) was evaluated on lateral lumbar radiographs. We examined the cross-sectional association between serum OC and AAC. The mean serum OC level was 24 ± 11 ng/ml and AAC was present in 188 subjects (52%). We observed no association of OC and AAC in either unadjusted or adjusted analyses. For example, each standard deviation higher OC level was associated with an odds ratio (OR) for AAC prevalence (AAC score >0) near unity (OR = 1.06; 95% CI, 0.82–1.36) in models adjusted for CVD risk factors. Further adjustment for intact parathyroid hormone, bone-specific alkaline phosphatase, 25-hydroxyvitamin D, and hip and spine bone mineral density did not materially change the results (OR = 1.22; 95% CI, 0.86–1.75). Similarly, higher OC levels were not associated with severity of AAC (P = 0.87). In conclusion, among community-living older women, serum OC is not associated with AAC. These findings suggest that serum OC levels may more closely reflect bone formation than vascular calcification in humans

Static and Dynamic Properties of a Viscous Silica Melt Molecular Dynamics Computer Simulations

We present the results of a large scale molecular dynamics computer simulation in which we investigated the static and dynamic properties of a silica melt in the temperature range in which the viscosity of the system changes from O(10^-2) Poise to O(10^2) Poise. We show that even at temperatures as high as 4000 K the structure of this system is very similar to the random tetrahedral network found in silica at lower temperatures. The temperature dependence of the concentration of the defects in this network shows an Arrhenius law. From the partial structure factors we calculate the neutron scattering function and find that it agrees very well with experimental neutron scattering data. At low temperatures the temperature dependence of the diffusion constants $D$ shows an Arrhenius law with activation energies which are in very good agreement with the experimental values. With increasing temperature we find that this dependence shows a cross-over to one which can be described well by a power-law, D\propto (T-T_c)^gamma. The critical temperature T_c is 3330 K and the exponent gamma is close to 2.1. Since we find a similar cross-over in the viscosity we have evidence that the relaxation dynamics of the system changes from a flow-like motion of the particles, as described by the ideal version of mode-coupling theory, to a hopping like motion. We show that such a change of the transport mechanism is also observed in the product of the diffusion constant and the life time of a Si-O bond, or the space and time dependence of the van Hove correlation functions.Comment: 30 pages of Latex, 14 figure

Slow-blue nuclear hypervariables in PanSTARRS-1

We discuss 76 large amplitude transients (Δm > 1.5) occurring in the nuclei of galaxies, nearly all with no previously known active galactic nucleus (AGN). They have been discovered as part of the Pan-STARRS1 (PS1) 3π survey, by comparison with Sloan Digital Sky Survey (SDSS) photometry a decade earlier, and then monitored with the Liverpool Telescope, and studied spectroscopically with the William Herschel Telescope (WHT). Based on colours, light-curve shape, and spectra, these transients fall into four groups. A few are misclassified stars or objects of unknown type. Some are red/fast transients and are known or likely nuclear supernovae. A few are either radio sources or erratic variables and so likely blazars. However the majority (∼66 per cent) are blue and evolve slowly, on a time-scale of years. Spectroscopy shows them to be AGN at z ∼ 0.3 − 1.4, which must have brightened since the SDSS photometry by around an order of magnitude. It is likely that these objects were in fact AGN a decade ago, but too weak to be recognized by SDSS; they could then be classed as ‘hypervariable’ AGN. By searching the SDSS Stripe 82 quasar database, we find 15 similar objects. We discuss several possible explanations for these slow-blue hypervariables – (i) unusually luminous tidal disruption events; (ii) extinction events; (iii) changes in accretion state; and (iv) large amplitude microlensing by stars in foreground galaxies. A mixture of explanations (iii) and (iv) seems most likely. Both hold promise of considerable new insight into the AGN phenomenon

Network Archaeology: Uncovering Ancient Networks from Present-day Interactions

Often questions arise about old or extinct networks. What proteins interacted in a long-extinct ancestor species of yeast? Who were the central players in the Last.fm social network 3 years ago? Our ability to answer such questions has been limited by the unavailability of past versions of networks. To overcome these limitations, we propose several algorithms for reconstructing a network's history of growth given only the network as it exists today and a generative model by which the network is believed to have evolved. Our likelihood-based method finds a probable previous state of the network by reversing the forward growth model. This approach retains node identities so that the history of individual nodes can be tracked. We apply these algorithms to uncover older, non-extant biological and social networks believed to have grown via several models, including duplication-mutation with complementarity, forest fire, and preferential attachment. Through experiments on both synthetic and real-world data, we find that our algorithms can estimate node arrival times, identify anchor nodes from which new nodes copy links, and can reveal significant features of networks that have long since disappeared.Comment: 16 pages, 10 figure