Skeletal muscle and the maintenance of vitamin d status

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Vitamin D, unlike the micronutrients, vitamins A, E, and K, is largely obtained not from food, but by the action of solar ultraviolet (UV) light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Since no defined storage organ or tissue has been found for vitamin D, it has been assumed that an adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D), which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into the blood. This uptake and release of 25(OH)D by muscle accounts for the very long half-life of this metabolite in the circulation. Since 25(OH)D concentration in the blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain an adequate vitamin D status in winter

The effect of parathyroid hormone on the uptake and retention of 25-hydroxyvitamin D in skeletal muscle cells

© 2017 Elsevier Ltd Data from our studies, and those of others, support the proposal that there is a role for skeletal muscle in the maintenance of vitamin D status. We demonstrated that skeletal muscle is able to internalise extracellular vitamin D binding protein, which then binds to actin in the cytoplasm, to provide high affinity binding sites which accumulate 25-hydroxyvitamin D3 (25(OH)D3) [1]. This study investigated the concentration- and time-dependent effects of parathyroid hormone (PTH) on the capacity of muscle cells to take up and release 3H-25(OH)D3. Uptake and retention studies for 3H-25(OH)D3 were carried out with C2C12 cells differentiated into myotubes and with primary mouse muscle fibers as described [1]. The presence of PTH receptors on mouse muscle fibers was demonstrated by immunohistochemistry and PTH receptors were detected in differentiated myotubes, but not myoblasts, and on muscle fibers by Western blot. Addition of low concentrations of vitamin D binding protein to the incubation media did not alter uptake of 25(OH)D3. Pre-incubation of C2 myotubes or primary mouse muscle fibers with PTH (0.1 to 100 pM) for 3 h resulted in a concentration-dependent decrease in 25(OH)D3 uptake after 4 or 16 h. These effects were significant at 0.1 or 1 pM PTH (p \u3c 0.001) and plateaued at 10 pM, with 25(OH)D3 uptake reduced by over 60% (p \u3c 0.001) in both cell types. In C2 myotubes, retention of 25(OH)D3 was decreased after addition of PTH (0.1 to 100 pM) in a concentration-dependent manner by up to 80% (p \u3c 0.001) compared to non-PTH treated-C2 myotubes. These data show that muscle uptake and retention of 25(OH)D3 are modulated by PTH, a physiological regulator of mineral homeostasis, but the cell culture model may not be a comprehensive reflection of vitamin D homeostatic mechanisms in whole animals

Aspects of four-jet production in polarized proton-proton collisions

We examine the intrinsic spin-dependence of the dominant $gg \rightarrow gggg$ subprocess contribution to four-jet production in polarized proton-proton collisions using helicity amplitude techniques. We find that the partonic level, longitudinal spin-spin asymmetry, $\hat{a}_{LL}$, is intrinsically large in the kinematic regions probed in experiments detecting four isolated jets. Such events may provide another qualitative or semi-quantitative test of the spin-structure of QCD in planned polarized $pp$ collisions at RHIC.Comment: 9 pages, LaTeX, 2 uuencoded postscript files attache

Gliese 581g as a scaled-up version of Earth: atmospheric circulation simulations

We use three-dimensional simulations to study the atmospheric circulation on the first Earth-sized exoplanet discovered in the habitable zone of an M star. We treat Gliese 581g as a scaled-up version of Earth by considering increased values for the exoplanetary radius and surface gravity, while retaining terrestrial values for parameters which are unconstrained by current observations. We examine the long-term, global temperature and wind maps near the surface of the exoplanet --- the climate. The specific locations for habitability on Gliese 581g depend on whether the exoplanet is tidally-locked and how fast radiative cooling occurs on a global scale. Independent of whether the existence of Gliese 581g is confirmed, our study highlights the use of general circulation models to quantify the atmospheric circulation on potentially habitable, Earth-sized exoplanets, which will be the prime targets of exoplanet discovery and characterization campaigns in the next decade.Comment: Accepted by MNRAS. 15 pages, 13 figures. Sample movies of simulations are available at http://www.phys.ethz.ch/~kheng/fms

The effect of minor and major mergers on the evolution of low excitation radio galaxies

We use deep, μ r lesssim 28 mag arcsec−2, r-band imaging from the Dark Energy Camera Legacy Survey to search for past, or ongoing, merger activity in a sample of 282 low-excitation radio galaxies (LERGs) at z 4σ excess of major mergers in the LERGs with M * lesssim 1011 M⊙, with 10 ± 1.5% of these active galactic nuclei involved in such large-scale interactions compared to 3.2 ± 0.4% of control galaxies. This excess of major mergers in LERGs decreases with increasing stellar mass, vanishing by M * > 1011.3 M⊙. These observations show that minor mergers do not fuel LERGs, and are consistent with typical LERGs being powered by accretion of matter from their halo. Where LERGs are associated with major mergers, these objects may evolve into more efficiently accreting active galactic nuclei as the merger progresses and more gas falls on to the central engine

Tau accumulation in autosomal dominant Alzheimer’s disease: a longitudinal [18F]flortaucipir study

Cortical tau accumulation is a key pathological event that partly defines Alzheimer’s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging

Discovery of a Modified Tetrapolar Sexual Cycle in Cryptococcus amylolentus and the Evolution of MAT in the Cryptococcus Species Complex

Sexual reproduction in fungi is governed by a specialized genomic region called the mating-type locus (MAT). The human fungal pathogenic and basidiomycetous yeast Cryptococcus neoformans has evolved a bipolar mating system (a, α) in which the MAT locus is unusually large (>100 kb) and encodes >20 genes including homeodomain (HD) and pheromone/receptor (P/R) genes. To understand how this unique bipolar mating system evolved, we investigated MAT in the closely related species Tsuchiyaea wingfieldii and Cryptococcus amylolentus and discovered two physically unlinked loci encoding the HD and P/R genes. Interestingly, the HD (B) locus sex-specific region is restricted (∼2 kb) and encodes two linked and divergently oriented homeodomain genes in contrast to the solo HD genes (SXI1α, SXI2a) of C. neoformans and Cryptococcus gattii. The P/R (A) locus contains the pheromone and pheromone receptor genes but has expanded considerably compared to other outgroup species (Cryptococcus heveanensis) and is linked to many of the genes also found in the MAT locus of the pathogenic Cryptococcus species. Our discovery of a heterothallic sexual cycle for C. amylolentus allowed us to establish the biological roles of the sex-determining regions. Matings between two strains of opposite mating-types (A1B1×A2B2) produced dikaryotic hyphae with fused clamp connections, basidia, and basidiospores. Genotyping progeny using markers linked and unlinked to MAT revealed that meiosis and uniparental mitochondrial inheritance occur during the sexual cycle of C. amylolentus. The sexual cycle is tetrapolar and produces fertile progeny of four mating-types (A1B1, A1B2, A2B1, and A2B2), but a high proportion of progeny are infertile, and fertility is biased towards one parental mating-type (A1B1). Our studies reveal insights into the plasticity and transitions in both mechanisms of sex determination (bipolar versus tetrapolar) and sexual reproduction (outcrossing versus inbreeding) with implications for similar evolutionary transitions and processes in fungi, plants, and animals

Variable Evolved Stars and YSOs Discovered in the Large Magellanic Cloud using the SAGE Survey

We present initial results and source lists of variable sources in the Large Magellanic Cloud (LMC) for which we detect thermal infrared variability from the SAGE (Surveying the Agents of a Galaxy's Evolution) survey, which had 2 epochs of photometry separated by three months. The SAGE survey mapped a 7 degree by 7 degree region of the LMC using the IRAC and the MIPS instruments on board Spitzer. Variable sources are identified using a combination of the IRAC 3.6, 4.5, 5.8, 8.0 \micron bands and the MIPS 24 \micron bands. An error-weighted flux difference between the two epochs is used to assess the variability. Of the ~ 3 million sources detected at both epochs we find ~ 2,000 variable sources for which we provide electronic catalogs. Most of the variable sources can be classified as asymptotic giant branch (AGB) stars. A large fraction (> 66%) of the extreme AGB stars are variable and only smaller fractions of carbon-rich (6.1%) and oxygen-rich (2.0%) stars are detected as variable. We also detect a population of variable young stellar object candidates.Comment: Accepted for publication in A

The mass-loss return from evolved stars to the Large Magellanic Cloud III. Dust properties for carbon-rich asymptotic giant branch stars

We present a 2Dust model for the dust shell around a LMC long-period variable (LPV) previously studied as part of the OGLE survey. OGLE LMC LPV 28579 (SAGE J051306.40-690946.3) is a carbon-rich asymptotic giant branch (AGB) star for which we have photometry and spectra from the Spitzer SAGE and SAGE-Spec programs along with UBVIJHK_s photometry. By modeling this source, we obtain a baseline set of dust properties to be used in the construction of a grid of models for carbon stars. We reproduce its spectral energy distribution using a mixture of AmC and SiC (15% by mass). The grain sizes are distributed according to the KMH model. The best-fit model has an optical depth of 0.28 for the shell at the peak of the SiC feature, with R_in~1430 R_sun or 4.4 R_star. The temperature at this inner radius is 1310 K. Assuming an expansion velocity of 10 km s^-1, we obtain a dust mass-loss rate of 2.5x10^-9 M_sun yr-1. We calculate a 15% variation in this rate by testing the fit sensitivity against variation in input parameters. We also present a simple model for the molecular gas in the extended atmosphere that could give rise to the 13.7 \mu m feature seen in the spectrum. We find that a combination of CO and C_2H_2 gas at an excitation temperature of about 1000 K and column densities of 3x10^21 cm^-2 and 10^19 cm^-2 respectively are able to reproduce the observations. Given that the excitation temperature is close to T_dust(R_in), most of the molecular contribution probably arises from the inner shell region. The luminosity corresponding to the first epoch of SAGE observations is 6580 L_sun. For an effective temperature of about 3000 K, this implies a stellar mass of 1.5-2 M_sun and an age of 1-2.5 Gyr. For a gas:dust ratio of 200, we obtain a gas mass-loss rate of 5.0x10^-7 M_sun yr^-1, consistent with the gas mass-loss rates estimated from the period, color and 8 \mu m flux of the source.Comment: 14 pages, 5 figures, accepted for publication in Astronomy & Astrophysic