The role of non-gray model atmospheres in the evolution of low mass metal poor stars

Gray model atmospheres are generally considered a reasonable approximation to make upon stars of mass greater than about 0.6 M-circle dot. Here we show that non-gray atmospheres can significantly affect evolutionary models, with masses up to 0.9 M-circle dot. The effect of including a non-gray atmosphere is strongest in the pre-main and post-main Sequence. This may have implications for the ages of the oldest globular clusters

Recent advances in the chemical synthesis of sugar-nucleotides

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Synthesis and Isolation of Diastereomeric Anomeric Sulfoxides from a d-Mannuronate Thioglycoside Building Block

Methyl [S-phenyl 4-O-acetyl-2,3-di-O-benzyl-1-thio-α-d-mannopyranoside (R/S)S-oxide] uronate was synthesised from a thioglycoside mannosyl uronate donor in a 98% yield. By using one equivalent of meta-chloroperbenzoic acid (m-CPBA) as the sulphur oxidant, a smooth conversion to the diastereomeric sulfoxide products was achieved. The product was fully characterized by 1H, 13C and 2D NMR alongside MS analysis

The Effect of the Electron Donor H⁺₃ on the Pre-Main-Sequence and Main-Sequence Evolution of Low-Mass, Zero-Metallicity Stars

H₃⁺ has been shown (1991 work of Lenzuni and coworkers) to be the dominant positive ion in a zero-metallicity gas at low temperature and intermediate to high density. It therefore affects both the number of free electrons and the opacity of the gas. The most recent H₃⁺ partition function (1995 work of Neale & Tennyson) is an order of magnitude larger at 4000 K than all previous partition functions, implying that H₃⁺ is a more important electron donor than previously thought. Here we present new Rosseland mean opacities for a hydrogen-helium gas of 1000 K ≤ T ≤ 9000 K and -14 ≤ log₁₀ [ρ (g cm⁻³)] ≤ -2. In the calculation of these opacities, we have made use of the latest collision-induced absorption data as well as the most recent H₃⁺ partition function and line opacity data. It is shown that these updated and new sources of opacity give rise to a Rosseland mean opacity for a hydrogen-helium gas that is, in general, greater than that calculated in earlier works. The new opacity data are then used to model the evolution of low-mass (0.15-0.8 M_{☉}), zero-metallicity stars, from pre-main-sequence collapse to main-sequence turnoff. To investigate the effect of H₃⁺ on the evolution of low-mass, zero-metallicity stars, we repeat our calculations neglecting H₃⁺ as a source of electrons and line opacity. We find that H₃⁺ can have an effect on the structure and evolution of stars of mass ~0.5 M_{☉} or less. A gray atmosphere is used for the calculation, which is sufficient to demonstrate that H₃⁺ affects the evolution of very low mass stars to a greater degree than previously believed

Making the longest sugars: a chemical synthesis of heparin-related [4](n) oligosaccharides from 16-mer to 40-mer

The chemical synthesis of long oligosaccharides remains a major challenge. In particular, the synthesis of glycosaminoglycan (GAG) oligosaccharides belonging to the heparin and heparan sulfate (H/HS) family has been a high profile target, particularly with respect to the longer heparanome. Herein we describe a synthesis of the longest heparin-related oligosaccharide to date and concurrently provide an entry to the longest synthetic oligosaccharides of any type yet reported. Specifically, the iterative construction of a series of [4]n-mer heparin-backbone oligosaccharides ranging from 16-mer through to the 40-mer in length is described. This demonstrates for the first time the viability of generating long sequence heparanoids by chemical synthesis, via practical solution-phase synthesis. Pure-Shift HSQC NMR provides a dramatic improvement in anomeric signal resolution, allowing full resolution of all 12 anomeric protons and extrapolation to support anomeric integrity of the longer species. A chemically pure 6-O-desfulfated GlcNS-IdoAS icosasaccharide (20-mer) represents the longest pure synthetic heparin-like oligosaccharide

ITPK1 mediates the lipid-independent synthesis of inositol phosphates controlled by metabolism

Inositol phosphates (IPs) comprise a network of phosphorylated molecules that play multiple signaling roles in eukaryotes. IPs synthesis is believed to originate with IP_{3} generated from PIP_{2} by phospholipase C (PLC). Here, we report that in mammalian cells PLC-generated IPs are rapidly recycled to inositol, and uncover the enzymology behind an alternative “soluble” route to synthesis of IPs. Inositol tetrakisphosphate 1-kinase 1 (ITPK1)—found in Asgard archaea, social amoeba, plants, and animals—phosphorylates I(3)P_{1} originating from glucose-6-phosphate, and I(1)P_{1} generated from sphingolipids, to enable synthesis of IP_{6}. We also found using PAGE mass assay that metabolic blockage by phosphate starvation surprisingly increased IP_{6} levels in a ITPK1-dependent manner, establishing a route to IP_{6} controlled by cellular metabolic status, that is not detectable by traditional [{3}^H]-inositol labeling. The presence of ITPK1 in archaeal clades thought to define eukaryogenesis indicates that IPs had functional roles before the appearance of the eukaryote

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

Alginate is a biocompatible and industrially relevant polysaccharide that derives many of its important properties from the charged carboxylate groups within its polyuronic acid backbone. The design and inclusion of isosteric replacements for these carboxylates would underpin provision of new oligo-/polysaccharide materials with alternate physicochemical properties. Presented herein is our synthesis of mannuronic acid building blocks, appropriately modified at the carboxylate C6 position with a bioisosteric tetrazole. Thioglycosides containing a protected C6-tetrazole are accessed from a C6-nitrile, through dipolar cycloaddition using NaN3 with n-Bu2SnO. We also demonstrate access to orthogonally C4-protected donors, suitable for iterative oligosaccharide synthesis. The development of these building blocks is showcased to access anomeric 3-aminopropyl- and 1-phosphate free sugars containing this non-native motif.</jats:p

Advances in biocatalytic and chemoenzymatic synthesis of nucleoside analogues.

INTRODUCTION: Nucleoside analogues represent a cornerstone of achievement in drug discovery, rising to prominence particularly in the fields of antiviral and anticancer discovery over the last 60 years. Traditionally accessed using chemical synthesis, a paradigm shift to include the use of biocatalytic synthesis is now apparent. AREAS COVERED: Herein the authors discuss the recent advances using this technology to access nucleoside analogues. Two key aspects are covered, the first surrounding methodology concepts, effectively using enzymes to access diverse nucleoside analogue space and also for producing key building blocks. The second focuses on the use of biocatalytic cascades for de novo syntheses of nucleoside analogue drugs. Finally, recent advances in technologies for effecting enzymatic nucleoside synthesis are considered, chiefly immobilisation and flow. EXPERT OPINION: Enzymatic synthesis of nucleoside analogues is maturing but has yet to usurp chemical synthesis as a first-hand synthesis technology, with scalability and substrate modification primary issues. Moving forward, tandem approaches that harness expertise across molecular microbiology and chemical synthesis will be vital to unlocking the potential of nucleoside analogues

Recent advances in the enzymatic synthesis of sugar-nucleotides using nucleotidylyltransferases and glycosyltransferases

Sugar-nucleotides are imperative to carbohydrate metabolism and glycoconjugate biosynthesis. Enzymatic methods to access these key materials offer a powerful alternative to traditional chemical synthesis routes. Herein we review recent advances in the enzymatic pyrophosphorylation of glycosyl 1-phosphates for the provision of both native and modified sugar-nucleotides

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis.

The recently completed European trial of interferon beta-1b (IFN beta -1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T-1-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFN beta -1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFN<beta>-1b (placebo 2.6%, IFN beta -1b, 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFN beta. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFN beta -treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease