S Selvanayagam | PubMed Health

PubMed2006

Iterative ACORN as a high throughput tool in structural genomics.

High throughput macromolecular structure determination is very essential in structural genomics as the available number of sequence information far exceeds the number of available 3D structures. ACORN, a freely available resource in the CCP4 suite of programs is a comprehensive and efficient program for phasing in the determination of protein structures, when atomic resolution data are available. ACORN with the automatic model-building program ARP/wARP and refinement program REFMAC is a suitable combination for the high throughput structural genomics. ACORN can also be run with secondary structural elements like helices and sheets as inputs with high resolution data. In situations, where ACORN phasing is not sufficient for building the protein model, the fragments (incomplete model/dummy atoms) can again be used as a starting input. Iterative ACORN is proved to work efficiently in the subsequent model building stages in congerin (PDB-ID: lis3) and catalase (PDB-ID: 1gwe) for which models are available.

Animals↗

PubMed2004

The use of ACORN in solving a 39.5 kDa macromolecule with 1.9 A resolution laboratory source data.

Data from the alkaline cellulase apo form were collected at a resolution of 1.9 A using an in-house X-ray source (Cu K alpha). By using different fragments of helices from the model solved by macromolecular crystallographic means, the direct-methods program ACORN was used to arrive at the complete model. Attempts have been made to use various percentages of input phasing information from these helices. The minimum input phasing required in feeding the fragments was about 14% of the whole structure. The phases obtained from ACORN were of superb quality, allowing automated model building to be carried out using ARP/wARP. Minimal manual model building was required and the structure determination was completed using the maximum-likelihood refinement program REFMAC. The whole process, starting from the running of ACORN and ending with the refined model, took nearly 15 h of CPU time using a Pentium III PC.

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PubMed2000

The epidemiology of melioidosis in Australia and Papua New Guinea.

Melioidosis was first described in Australia in an outbreak in sheep in 1949 in north Queensland (22 degrees S). Human melioidosis was first described from Townsville (19 degrees S) in 1950. Melioidosis is hyperendemic in the Top End of the Northern Territory (NT) and as in parts of northeastern Thailand it is the commonest cause of fatal community-acquired septicemic pneumonia. In the 9 years since 1989 the prospective NT melioidosis study at Royal Darwin Hospital (12 degrees S) has documented 206 culture confirmed cases of melioidosis, with an average annual incidence of 16.5/100,000. Melioidosis is also seen in the north of Western Australia and north Queensland, including the Torres Strait Islands, but is uncommon in adjacent Papua New Guinea. Serological studies suggest that infection is rare in the Port Moresby region, but there is emerging evidence of melioidosis from Western Province. The NT study has documented inoculating events in 52 (25%) of cases, with an incubation period of 1-21 days (mean 9 days); 84% of cases had acute disease from presumed recent acquisition and 13% had chronic disease (sick, > 2 months). In 4% there was evidence of possible reactivation from a latent focus; 28 of 153 (18%) males had prostatic abscesses. The overall mortality was 21% (43 cases), with a mortality rate in septicemic cases (95) of 39% and in non-septicemic cases (103) of 4%. Pneumonia was the commonest presentation in both groups and, in addition, eight patients (two deaths) presented with melioidosis encephalomyelitis. Melioidosis clusters in temperate Australia are attributed to animals imported from the north. Molecular typing of Burkholderia pseudomallei isolates from temperate southwest Western Australia showed clonality over 25 years. In this outbreak and in studies from the NT, some soil isolates are molecularly identical to epidemiologically related animal and human isolates. Molecular typing has implicated the water supply in two clonal outbreaks in remote aboriginal communities in northern Australia. Further prospective collaborative studies are required to evaluate whether there are truly regional differences in clinical features of melioidosis and to better understand how B. pseudomallei is acquired from the environment.

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