The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of ...human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. ...The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.
Wormald et al discuss the available techniques for determining the conformation and dynamics of oligosaccharides and glycoproteins and how the complementary data from NMR spectroscopy, X-ray ...crystallography and molecular modeling can be used to address these problems.
We identified 25 children (10 girls and 15 boys) who had been treated with single bone intramedullary fixation for diaphyseal fractures of both forearm bones. Their mean age was 10.75 years (4.6 to ...15.9). All had a good functional outcome. We conclude that in selected children, single bone intramedullary nailing is a suitable method of treatment for diaphyseal fractures of both bones of the forearm.
Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we ...present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.
Two synthetic O-GlcNAc-bearing peptides that elicit H-2D super(b)-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, ...we present the crystal structures of the H-2D super(b) glycopeptide complexes to 2.85 Angstrom resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.
We report the results of imaging with labelled white cells in 52 patients before the revision of 54 cemented joint prostheses at which the diagnosis of infection was made from biopsies. Twenty-five ...hips were imaged with 111In-oxine-labelled cells; 20 hips and 11 knees were imaged with 99mTc-hexamethylpropylene-amineoxime-labelled cells. Of these, 13 hips and five knees proved to be infected. The scans taken together had an accuracy of 82%, a sensitivity of 44% and a specificity of 100%. Indium scans gave 37% sensitivity, 99mTc labelling 50% sensitivity. Infected arthroplasties with positive scans had presented significantly earlier than those with negative scans, the time after the original insertion being 1.1 years for the true-positive scans and 6.1 years for the false-negative scans. The value of labelled white-cell scans in the detection of infection in failed joint replacements is dependent on the activity of the infection. There is reduced sensitivity to the more insidious infections which affect arthroplasties and aspiration under controlled conditions remains an important investigation.
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