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Biomedical subjects

Steven Jones

Publications and source records attributed to Steven Jones.

44 records · Page 3Linked to original sources

Mass spectrometric characterization of proteins from the SARS virus: a preliminary report.

A new coronavirus has been implicated as the causative agent of severe acute respiratory syndrome (SARS). We have used convalescent sera from several SARS patients to detect proteins in the culture supernatants from cells exposed to lavage another SARS patient. The most prominent protein in the supernatant was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a approximately 46-kDa species. This was found to be a novel nucleocapsid protein that matched almost exactly one predicted by an open reading frame in the recently published nucleotide sequence of the same virus isolate (>96% coverage). A second viral protein corresponding to the predicted approximately 139-kDa spike glycoprotein has also been examined by MALDI-TOF MS (42% coverage). After peptide N-glycosidase F digestion, 12 glycosylation sites in this protein were confirmed. The sugars attached to four of the sites were also identified. These results suggest that the nucleocapsid protein is a major immunogen that may be useful for early diagnostics, and that the spike glycoprotein may present a particularly attractive target for prophylactic intervention in combating SARS.

Amino Acid Sequence↗

The Genome sequence of the SARS-associated coronavirus.

We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.

3' Untranslated Regions↗

Ebola virus: from discovery to vaccine.

Ebola virus, being highly pathogenic for humans and non-human primates and the subject of former weapons programmes, is now one of the most feared pathogens worldwide. In addition, the lack of pre- and post-exposure interventions makes the development of rapid diagnostics, new antiviral agents and protective vaccines a priority for many nations. Further insight into the ecology, immunology and pathogenesis of Ebola virus will promote the delivery of these urgently required tools.

Animals↗

Emerging and re-emerging infectious diseases.

In human history, numerous infectious diseases have emerged and re-emerged. Aside from many others, the so-called 'exotic' agents in particular are a threat to our public health systems due to limited experience in case management and lack of appropriate resources. Many of these agents are zoonotic in origin and transmitted from animals to man either directly or via vectors. The reservoirs are often infected subclinically or asymptomatically and the distribution of the diseases basically reflects the range and the population dynamics of their reservoir hosts. As examples, emergence/re-emergence is discussed here for diseases caused by filoviruses, hantaviruses, paramyxoviruses, flaviviruses and Yersinia pestis. In addition, bioterrorism is addressed as one factor which has now to be considered in infectious disease emergence/re-emergence. Preparedness for known and unknown infectious diseases will be a top priority for our public health systems in the beginning of the millennium.

Animals↗

A physical map of the mouse genome.

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.

Animals↗

Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation.

Hereditary hemochromatosis (HH) is classically associated with a Cys282Tyr (C282Y) mutation of the HFE gene. Non-C282Y HH is a heterogeneous group accounting for 15% of HH in Northern Europe. Pathogenic mutations of the transferrin receptor 2 (TfR2) gene have been identified in 4 Italian pedigrees with the latter syndrome. The goal of this study was to perform a mutational analysis of the TfR2 and HFE genes in a cohort of non-C282Y iron overload patients of mixed ethnic backgrounds. Several sequence variants were identified within the TfR2 gene, including a homozygous missense change in exon 17, c2069 A-->C, which changes a glutamine to a proline residue at position 690. This putative mutation was found in a severely affected Portuguese man and 2 family members with the same genotype. In summary, pathologic TfR2 mutations are present outside of Italy, accounting for a small proportion of non-C282Y HH.

Canada↗