Pre-analytical factors affecting whole blood and plasma glucose concentrations in loggerhead sea turtles (Caretta caretta)

Blood glucose is vital for many physiological pathways and can be quantified by clinical chemistry analyzers and in-house point-of-care (POC) devices. Pre-analytical and analytical factors can influence blood glucose measurements. This project aimed to investigate pre-analytical factors on whole blood and plasma glucose measurements in loggerhead sea turtles (Caretta caretta) by evaluating the effects of storage (refrigeration) up to 48h after sampling and of packed cell volume (PCV) on whole blood glucose analysis by POC glucometer (time series n = 13); and by evaluating the effects of storage (room temperature and refrigeration) on plasma glucose concentrations using a dry slide chemistry analyzer (DCA) at various conditions: immediate processing and delayed plasma separation from erythrocytes at 24h and 48h (time series n = 14). The POC glucometer had overall strong agreement with the DCA (CCC = 0.76, r = 0.84, Cb = 0.90), but consistently overestimated glucose concentrations (mean difference: +0.4 mmol/L). The POC glucometer results decreased significantly over time, resulting in a substantial decline within the first 2h (0.41±0.47 mmol/L; 8±9%) that could potentially alter clinical decisions, thereby highlighting the need for immediate analysis using this method. The effects of PCV on glucose could not be assessed, as the statistical significance was associated with one outlier. Storage method significantly affected plasma glucose measurements using DCA, with room temperature samples resulting in rapid decreases of 3.57±0.89 mmol/L (77±9%) over the first 48h, while refrigerated samples provided consistent plasma glucose results over the same time period (decrease of 0.26±0.23 mmol/L; 6±5%). The results from this study provide new insights into optimal blood sample handling and processing for glucose analysis in sea turtles, show the suitability of the POC glucometer as a rapid diagnostic test, and confirm the reliability of plasma glucose measurements using refrigeration. These findings emphasize the need to consider pre-/analytical factors when interpreting blood glucose results from loggerhead sea turtles

Supernovae from rotating stars

The present paper discusses the main physical effects produced by stellar rotation on presupernovae, as well as observations which confirm these effects and their consequences for presupernova models. Rotation critically influences the mass of the exploding cores, the mass and chemical composition of the envelopes and the types of supernovae, as well as the properties of the remnants and the chemical yields. In the formation of gamma-ray bursts, rotation and the properties of rotating stars appear as the key factor. In binaries, the interaction between axial rotation and tidal effects often leads to interesting and unexpected results. Rotation plays a key role in shaping the evolution and nucleosynthesis in massive stars with very low metallicities (metallicity below about the Small Magellanic Cloud metallicity down to Population III stars). At solar and higher metallicities, the effects of rotation compete with those of stellar winds. In close binaries, the synchronisation process can lock the star at a high rotation rate despite strong mass loss and thus both effects, rotation and stellar winds, have a strong impact. In conclusion, rotation is a key physical ingredient of the stellar models and of presupernova stages, and the evolution both of single stars and close binaries. Moreover, important effects are expected along the whole cosmic history.Comment: 36 pages, 15 figures, published in Handbook of Supernovae, A.W. Alsabti and P. Murdin (eds), Springe

Observational Manifestations of the First Protogalaxies in the 21 cm Line

The absorption properties of the first low-mass protogalaxies (mini-halos) forming at high redshifts in the 21-cm line of atomic hydrogen are considered. The absorption properties of these protogalaxies are shown to depend strongly on both their mass and evolutionary status. The optical depths in the line reach $\sim$0.1-0.2 for small impact parameters of the line of sight. When a protogalaxy being compressed, the influence of gas accretion can be seen manifested in a non-monotonic frequency dependence of the optical depth. The absorption characteristics in the 21-cm line are determined by the thermal and dynamical evolution of the gas in protogalaxies. Since the theoretical line width in the observer's reference frame is 1-6 kHz and the expected separation between lines 8.4 kHz, the lines from low mass protogalaxies can be resolved using ongoing and future low frequency interferometers.Comment: 12 pages, 5 figure

A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome

BACKGROUNDWolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene sodium, may be beneficial.METHODSBased on results from preclinical studies on dantrolene sodium and ongoing longitudinal studies, we assembled what we believe is the first-ever clinical trial in pediatric and adult Wolfram syndrome patients with an open-label phase Ib/IIa trial design. The primary objective was to assess the safety and tolerability of dantrolene sodium in adult and pediatric Wolfram syndrome patients. Secondary objectives were to evaluate the efficacy of dantrolene sodium on residual pancreatic β cell functions, visual acuity, quality-of-life measures related to vision, and neurological functions.RESULTSDantrolene sodium was well tolerated by Wolfram syndrome patients. Overall, β cell functions were not significantly improved, but there was a significant correlation between baseline β cell functions and change in β cell responsiveness (R2, P = 0.004) after 6-month dantrolene therapy. Visual acuity and neurological functions were not improved by 6-month dantrolene sodium. Markers of inflammatory cytokines and oxidative stress, such as IFN-γ, IL-1β, TNF-α, and isoprostane, were elevated in subjects.CONCLUSIONThis study justifies further investigation into using dantrolene sodium and other small molecules targeting the ER for treatment of Wolfram syndrome.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02829268FUNDINGNIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK112921, DK113487, DK020579), NIH/National Center for Advancing Translational Sciences (NCATS) (TR002065, TR000448), NIH training grant (F30DK111070), Silberman Fund, Ellie White Foundation, Snow Foundation, Unravel Wolfram Syndrome Fund, Stowe Fund, Eye Hope Foundation, Feiock Fund, Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NIH/NCATS, Bursky Center for Human Immunology & Immunotherapy Programs

Exploring the Universe with Metal-Poor Stars

The early chemical evolution of the Galaxy and the Universe is vital to our understanding of a host of astrophysical phenomena. Since the most metal-poor Galactic stars (with metallicities down to [Fe/H]\sim-5.5) are relics from the high-redshift Universe, they probe the chemical and dynamical conditions of the Milky Way and the origin and evolution of the elements through nucleosynthesis. They also provide constraints on the nature of the first stars, their associated supernovae and initial mass function, and early star and galaxy formation. The Milky Way's dwarf satellites contain a large fraction (~30%) of the known most metal-poor stars that have chemical abundances that closely resemble those of equivalent halo stars. This suggests that chemical evolution may be universal, at least at early times, and that it is driven by massive, energetic SNe. Some of these surviving, ultra-faint systems may show the signature of just one such PopIII star; they may even be surviving first galaxies. Early analogs of the surviving dwarfs may thus have played an important role in the assembly of the old Galactic halo whose formation can now be studied with stellar chemistry. Following the cosmic evolution of small halos in simulations of structure formation enables tracing the cosmological origin of the most metal-poor stars in the halo and dwarf galaxies. Together with future observations and additional modeling, many of these issues, including the reionization history of the Milky Way, may be constrained this way. The chapter concludes with an outlook about upcoming observational challenges and ways forward is to use metal-poor stars to constrain theoretical studies.Comment: 34 pages, 11 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin

First Stars. II. Evolution with mass loss

The first stars are assumed to be predominantly massive. Although, due to the low initial abundances of heavy elements the line-driven stellar winds are supposed to be inefficient in the first stars, these stars may loose a significant amount of their initial mass by other mechanisms. In this work, we study the evolution with a prescribed mass loss rate of very massive, galactic and pregalactic, Population III stars, with initial metallicities $Z=10^{-6}$ and $Z=10^{-9}$, respectively, and initial masses 100, 120, 150, 200, and 250$\,M_{\odot}$ during the hydrogen and helium burning phases. The evolution of these stars depends on their initial mass, metallicity and the mass loss rate. Low metallicity stars are hotter, compact and luminous, and they are shifted to the blue upper part in the Hertzprung-Russell diagram. With mass loss these stars provide an efficient mixing of nucleosynthetic products, and depending on the He-core mass their final fate could be either pair-instability supernovae or energetic hypernovae. These stars contributed to the reionization of the universe and its enrichment with heavy elements, which influences the subsequent star formation properties.Comment: Accepted for publication in Astrophysics & Space Science. 15 pages, 18 figure

Does prior acute exercise affect postexercise substrate oxidation in response to a high carbohydrate meal?

<p>Abstract</p> <p>Background</p> <p>Consumption of a mixed meal increases postprandial carbohydrate utilization and decreases fat oxidation. On the other hand, acute endurance exercise increases fat oxidation and decreases carbohydrate utilization during the post-exercise recovery period. It is possible that the resulting post-exercise increase in circulating nonesterified fatty acids could attenuate the ability of ingested carbohydrate to inhibit lipid oxidation. The purpose of this study was to determine whether prior exercise attenuates the usual meal-induced decline in lipid oxidation.</p> <p>Methods</p> <p>Six healthy, physically active young subjects (x age = 26.3 years, 4 males, 2 females) completed three treatments in random order after a ~10 h fast: (a) Exercise/Carbohydrate (Ex/CHO) – subjects completed a bout of exercise at 70% VO_2peak(targeted net energy cost of 400 kcals), followed by consumption of a carbohydrate-rich meal; (b) Exercise/Placebo (Ex/Placebo) – subjects completed an identical bout of exercise followed by consumption of a placebo; and (c) No Exercise/Carbohydrate (NoEx/CHO) – subjects sat quietly rather than exercising and then consumed the carbohydrate-rich meal. Blood samples were obtained before and during the postprandial period to determine plasma glucose, insulin, and non-esterified fatty acids (NEFA). Respiratory gas exchange measures were used to estimate rates of fat and carbohydrate oxidation.</p> <p>Results</p> <p>Plasma NEFA were approximately two-fold higher immediately following the two exercise conditions compared to the no-exercise condition, while meal consumption significantly increased insulin and glucose in both Ex/CHO and NoEx/CHO. NEFA concentrations fell rapidly during the 2-h postprandial period, but remained higher compared to the NoEx/CHO treatment. Carbohydrate oxidation increased rapidly and fat oxidation decreased in response to the meal, with no differences in the rates of carbohydrate and fat oxidation during recovery between the Ex/CHO and NoEx/CHO conditions.</p> <p>Conclusion</p> <p>The plasma NEFA concentration is increased during the post exercise period, which is associated with elevated fat oxidation when no meal is consumed. However, when a mixed meal is consumed immediately following exercise, the initially elevated plasma NEFA concentration decreases rapidly, and postexercise fat oxidation during this 2-h postexercise, postprandial period is no higher than that of the 2-h postprandial period without prior exercise.</p

21-cm cosmology

Imaging the Universe during the first hundreds of millions of years remains one of the exciting challenges facing modern cosmology. Observations of the redshifted 21 cm line of atomic hydrogen offer the potential of opening a new window into this epoch. This would transform our understanding of the formation of the first stars and galaxies and of the thermal history of the Universe. A new generation of radio telescopes is being constructed for this purpose with the first results starting to trickle in. In this review, we detail the physics that governs the 21 cm signal and describe what might be learnt from upcoming observations. We also generalize our discussion to intensity mapping of other atomic and molecular lines.Comment: 64 pages, 20 figures, submitted to Reports on Progress in Physics, comments welcom

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Molecular identification of 1-Cys peroxiredoxin and anthocyanidin/flavonol 3-O-galactosyltransferase from proanthocyanidin-rich young fruits of persimmon (Diospyros kaki Thunb.)

Fruits of persimmon (Diospyros kaki Thunb.) accumulate large amounts of proanthocyanidins (PAs) in the early stages of development. Astringent (A)-type fruits remain rich in soluble PAs even after they reach full-mature stage, whereas non-astringent (NA)-type fruits lose these compounds before full maturation. As a first step to elucidate the mechanism of PA accumulation in this non-model species, we used suppression subtractive hybridization to identify transcripts accumulating differently in young fruits of A- and NA-type. Interestingly, only a few clones involved in PA biosynthesis were identified in A–NA libraries. Represented by multiple clones were those encoding a novel 1-Cys peroxiredoxin and a new member of family 1 glycosyltransferases. Quantitative RT-PCR analyses confirmed correlation of the amount of PAs and accumulation of transcripts encoding these proteins in young persimmon fruits. Furthermore, the new family 1 glycosyltransferase was produced in Escherichia coli and shown to efficiently catalyze galactosylation at 3-hydroxyl groups of several anthocyanidins and flavonols. These findings suggest a complex mechanism of PA accumulation in persimmon fruits