Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality

Corrigendum: Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis

Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis (Nature Communications (2015) 6 (6046) DOI:10.1038/ncomms7046

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

6C-butylglucoses from glucuronolactone: Suppression of silyl migration during borohydride reduction of lactols by cerium (III) chloride: Inhibition of phosphoglucomutase

The synthesis of the epimeric 6C-butylglucoses from D-glucuronolactone is reported. The sodium borohydride reduction of two fully protected lactols is highly stereoselective but is accompanied by migration of a silyl protecting group; in the presence of cerium(III) chloride, there is little change in the stereoselectivity but the migration of the silyl group is suppressed. 6R-6C-Methylglucose and 6R-6C-butlylglucose are both better inhibitors of phosphoglucomutase than their 6S epimers

6R-, and 6S, -6C-methylglucose from D-glucuronolactone: Efficient synthesis of a seven carbon fucose analogue: Inhibition of some enzymes of primary metabolism

Syntheses of the two epimeric 6C-methylglucoses from D-glucuronolactone rely on a non-stereoselective reduction of an intermediate lactol. A highly stereoselective reduction of a silylated lactol, which is accompanied by a silyl migration, gives easy access to 6S-6C-methylglucose - a seven carbon fucose analogue - in five steps from glucuronolactone in an overall yield of 40%. An azido analogue of 6R-6C-methylglucose is also reported, Such compounds may provide new materials for the selective inhibition of various enzymes of primary metabolism including glucokinase, glucose-6-phosphatase, and phosphoglucomutase. X-ray crystal structures of (1S,3R,4S,5S,7R,8R)-3-methyl-7,8-O-isopropylidene-3,4,7,8-tetr ahydroxy-2,6 -dioxabicyclo[3,3,0]-octane and 7-deoxy-1,2-5,6-di-O-isopropylidene-L-glycero-α-D-gluco-hepto furanose are reported