Andrew Lynch

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We show that the two-component signal transduction system of Escherichia coli, CpxA-CpxR, controls the expression of genes encoding cell envelope proteins involved in protein folding and degradation. These findings are based on three lines of evidence. First, activation of the Cpx pathway induces 5- to 10-fold the synthesis of DsbA, required for disulfide(More)
The Eph receptor VAB-1 is required in neurons for epidermal morphogenesis during C. elegans embryogenesis. Two models were proposed for the non-autonomous role of VAB-1: neuronal VAB-1 might signal directly to epidermis, or VAB-1 signaling between neurons might be required for epidermal development. We show that the ephrin VAB-2 (also known as EFN-1) is a(More)
ArcA protein bearing an amino-terminal, oligohistidine extension has been purified, and its DNA binding activity has been characterized with or without prior incubation with carbamoyl phosphate. Electrophoretic mobility shift assays and DNase I protection assays indicate that where the phosphorylated form of the ArcA protein (ArcA-P) is expected to act as a(More)
INTRODUCTION The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric(More)
The ArcB and ArcA proteins constitute a two-component signal transduction system that plays a broad role in transcriptional regulation. Under anoxic or environmentally reducing conditions, the sensor kinase (ArcB) is stimulated to autophosphorylate at the expense of ATP and subsequently transphosphorylates the response regulator (ArcA). ArcB is a complex,(More)
All cellular organisms use specialized RNA polymerases called "primases" to synthesize RNA primers for the initiation of DNA replication. The high-resolution crystal structure of a primase, comprising the catalytic core of the Escherichia coli DnaG protein, was determined. The core structure contains an active-site architecture that is unrelated to other(More)
RNA polymerase (RNAP) is the central enzyme of gene expression. Despite availability of crystal structures, details of its nucleotide addition cycle remain obscure. We describe bacterial RNAP inhibitors (the CBR703 series) whose properties illuminate this mechanism. These compounds inhibit known catalytic activities of RNAP (nucleotide addition,(More)
The cysB gene of Klebsiella aerogenes has been cloned, sequenced and shown to complement the cysteine auxotrophic phenotype of Escherichia coli cysB mutants. The K. aerogenes cysB gene is predicted to encode a protein of 324 amino acid residues that shares approx. 95% sequence similarity with the Salmonella typhimurium and E. coli CysB proteins.(More)
CONTEXT Dyspnea is a disabling distressing symptom that is common in advanced disease affecting millions of people worldwide. Current palliative strategies are partially effective in managing this symptom; facial cooling has been shown to reduce the sensation of breathlessness when induced in volunteers but has not been formally investigated in dyspnea(More)
BACKGROUND In highly sensitized patients (HSP) awaiting renal transplantation, accurate delineation of acceptable human leukocyte antigen (HLA) mismatches (AMM) aids identification of suitable crossmatch negative donors. Comparison of differences in polymorphic triplet amino acid sequences in antibody accessible regions of HLA may predict immunogenicity. We(More)