Biomedical subjects

Ian Small

Publications and source records attributed to Ian Small.

17 recordsLinked to original sources

PubMed2006

SUBA: the Arabidopsis Subcellular Database.

Knowledge of protein localisation contributes towards our understanding of protein function and of biological inter-relationships. A variety of experimental methods are currently being used to produce localisation data that need to be made accessible in an integrated manner. Chimeric fluorescent fusion proteins have been used to define subcellular localisations with at least 1100 related experiments completed in Arabidopsis. More recently, many studies have employed mass spectrometry to undertake proteomic surveys of subcellular components in Arabidopsis yielding localisation information for approximately 2600 proteins. Further protein localisation information may be obtained from other literature references to analysis of locations (AmiGO: approximately 900 proteins), location information from Swiss-Prot annotations (approximately 2000 proteins); and location inferred from gene descriptions (approximately 2700 proteins). Additionally, an increasing volume of available software provides location prediction information for proteins based on amino acid sequence. We have undertaken to bring these various data sources together to build SUBA, a SUBcellular location database for Arabidopsis proteins. The localisation data in SUBA encompasses 10 distinct subcellular locations, >6743 non-redundant proteins and represents the proteins encoded in the transcripts responsible for 51% of Arabidopsis expressed sequence tags. The SUBA database provides a powerful means by which to assess protein subcellular localisation in Arabidopsis (http://www.suba.bcs.uwa.edu.au).

Arabidopsis Proteins↗

PubMed2006

Recent surprises in protein targeting to mitochondria and plastids.

The functions of mitochondria and chloroplasts rely on thousands of proteins, mostly imported from the cytosol through specialized import channels. Neither the detailed import mechanisms nor the identities of all targeted proteins are known. Recent surprises include unexpected results concerning import receptors, unexpectedly frequent dual-targeting of proteins, and the discovery of novel routes of protein trafficking. Such findings make it more difficult to predict which proteins really are targeted to organelles. By combining experimental and bioinformatics data, we estimate the size of the mitochondrial and plastid proteomes to be approximately 2000 and 2700 proteins, respectively. Advances in cell and organelle fractionation coupled with modern proteomics techniques are probably the best route to understanding organellar protein composition.

Mitochondria↗

PubMed2005

GeneFarm, structural and functional annotation of Arabidopsis gene and protein families by a network of experts.

Genomic projects heavily depend on genome annotations and are limited by the current deficiencies in the published predictions of gene structure and function. It follows that, improved annotation will allow better data mining of genomes, and more secure planning and design of experiments. The purpose of the GeneFarm project is to obtain homogeneous, reliable, documented and traceable annotations for Arabidopsis nuclear genes and gene products, and to enter them into an added-value database. This re-annotation project is being performed exhaustively on every member of each gene family. Performing a family-wide annotation makes the task easier and more efficient than a gene-by-gene approach since many features obtained for one gene can be extrapolated to some or all the other genes of a family. A complete annotation procedure based on the most efficient prediction tools available is being used by 16 partner laboratories, each contributing annotated families from its field of expertise. A database, named GeneFarm, and an associated user-friendly interface to query the annotations have been developed. More than 3000 genes distributed over 300 families have been annotated and are available at http://genoplante-info.infobiogen.fr/Genefarm/. Furthermore, collaboration with the Swiss Institute of Bioinformatics is underway to integrate the GeneFarm data into the protein knowledgebase Swiss-Prot.

Arabidopsis↗

PubMed2005

Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic.

Recent cross species transmission of avian influenza has highlighted the threat of pandemic influenza. Oseltamivir (Tamiflu) has been shown to be effective in the treatment and prevention of epidemic influenza infection in adults, adolescents and children (> or = 1 year). Although oseltamivir has not been approved for prophylactic use in children, it has been shown to be effective. Oseltamivir is also active against avian influenza virus strains. Evidence suggests that lower doses or shorter durations of treatment/chemoprophylaxis other than those approved may not be effective and may contribute to emergence of viral resistance. Safety data from dose ranging studies show that 5 day courses of 150 mg twice daily for treatment and 6 week courses of 75 mg twice daily for prophylaxis were as well tolerated as the approved dose regimens. The use of oseltamivir in a pandemic is influenced by the goals of the pandemic plan developed by the responsible Government and Health Authority. To optimize use of antiviral medications, processes will be needed to collect, collate and report outcome data from treated patients and/or from use for chemoprophylaxis of pandemic influenza during the first-wave outbreaks. If oseltamivir is included in a national or regional pandemic plan, stockpiling of the material, either in the form of capsules or the bulk active pharmaceutical ingredient will be necessary. In the absence of a stockpile, there is no guarantee that an adequate supply of oseltamivir will be available.

Acetamides↗

PubMed2004

Genome-wide analysis of Arabidopsis pentatricopeptide repeat proteins reveals their essential role in organelle biogenesis.

The complete sequence of the Arabidopsis thaliana genome revealed thousands of previously unsuspected genes, many of which cannot be ascribed even putative functions. One of the largest and most enigmatic gene families discovered in this way is characterized by tandem arrays of pentatricopeptide repeats (PPRs). We describe a detailed bioinformatic analysis of 441 members of the Arabidopsis PPR family plus genomic and genetic data on the expression (microarray data), localization (green fluorescent protein and red fluorescent protein fusions), and general function (insertion mutants and RNA binding assays) of many family members. The basic picture that arises from these studies is that PPR proteins play constitutive, often essential roles in mitochondria and chloroplasts, probably via binding to organellar transcripts. These results confirm, but massively extend, the very sparse observations previously obtained from detailed characterization of individual mutants in other organisms.

Amino Acid Motifs↗

PubMed2004

Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis.

We determined the efficacy of postexposure prophylaxis (PEP) and treatment of ill index cases with oseltamivir, in an attempt to prevent influenza transmission in households, in a study conducted in 277 households with 298 index cases (62% with laboratory-confirmed influenza) and 812 contacts aged > or =1 year. Contacts were randomized by household to receive treatment (5 days; n=402), if illness developed, or PEP for 10 days (n=410), and the number of households with at least 1 contact developing laboratory-confirmed influenza was measured. PEP provided a protective efficacy of 58.5% (95% confidence interval [CI], 15.6%-79.6%; P=.0114) for households against proven influenza and 68.0% (95% CI, 34.9%-84.2%; P=.0017) for individual contacts, compared with treatment of index cases alone. No oseltamivir-resistant variants were detected in treated index cases or contacts. PEP of household contacts of those with influenza reduces the secondary spread of influenza in families when the initial household case is treated.

Acetamides↗

PubMed2004

Predotar: A tool for rapidly screening proteomes for N-terminal targeting sequences.

Probably more than 25% of the proteins encoded by the nuclear genomes of multicellular eukaryotes are targeted to membrane-bound compartments by N-terminal targeting signals. The major signals are those for the endoplasmic reticulum, the mitochondria, and in plants, plastids. The most abundant of these targeted proteins are well-known and well-studied, but a large proportion remain unknown, including most of those involved in regulation of organellar gene expression or regulation of biochemical pathways. The discovery and characterization of these proteins by biochemical means will be long and difficult. An alternative method is to identify candidate organellar proteins via their characteristic N-terminal targeting sequences. We have developed a neural network-based approach (Predotar--Prediction of Organelle Targeting sequences) for identifying genes encoding these proteins amongst eukaryotic genome sequences. The power of this approach for identifying and annotating novel gene families has been illustrated by the discovery of the pentatricopeptide repeat family.

Arabidopsis Proteins↗

PubMed2004

Versatile gene-specific sequence tags for Arabidopsis functional genomics: transcript profiling and reverse genetics applications.

Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics.

Arabidopsis↗

PubMed2004

Multidrug-resistant tuberculosis in central Asia.

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB.

Adolescent↗

PubMed2003

Discrete mutations in the presequence of potato formate dehydrogenase inhibit the in vivo targeting of GFP fusions into mitochondria.

Most mitochondrial proteins are encoded by the nucleus, translated in the cytosol, and imported. Mitochondrial precursors generally contain their targeting information in a cleavable N-terminal presequence, which is rich in hydroxylated and positively charged residues and can form amphiphilic alpha-helices. We report the in vivo targeting of green fluorescent protein (GFP) by the FDH presequence, as well as several truncated or mutated variants. Some of these mutations modify the amphiphilicity of the predicted alpha-helix. The removal of the first two residues abolishes import and some single amino acid mutations strongly inhibit import. Such strong effects on import had not been observed in similar studies on other plant mitochondrial presequences, suggesting that the FDH presequence is a particularly good model for functional studies.

Amino Acid Sequence↗

PubMed2003

Impacts of an environmental disaster on psychosocial health and well-being in Karakalpakstan.

The people of Karakalpakstan, along with those of the entire Aral Sea region, are facing a multitude of health problems corresponding to the drying of the Aral Sea and accompanying ecological consequences. In case studies of other environmental disasters, research has shown that environmental exposures may impact not only the physiological but also the psychosocial health of individuals. This research aims to determine the contribution of the environmental disaster to the psychosocial health of people living in Karakalpakstan, a semi-autonomous Republic in Uzbekistan. An interview survey was carried out by Médecins Sans Frontières, with the assistance of the McMaster Institute of Environment and Health, local Universities and local health care workers, on a random sample of 1118 individuals aged 18 years and older in three communities in Karakalpakstan in May/June 1999. The communities were chosen according to distance from the former seashore, urban/rural characteristics and ethnic composition. The survey included questions about perceived general health, the General Health Questionnaire, the somatic symptom checklist of the Symptom Check List-90, questions about perceptions of the environmental disaster, social support as well as socio-demographic and socio-economic characteristics. Findings show that 41% of all respondents reported environmental concern while 48% reported levels of somatic symptoms (SCL-90) associated with emotional distress, above the normalized cut-point. Significant differences in levels of emotional distress were reported between men and women as well as between ethnic groups. Environmental problems are commonly perceived to be the cause of somatic symptoms and are significantly related to self-rated health status.

Adolescent↗

PubMed2003

The Aral Sea disaster and self-rated health.

This study examined the effect of psychosocial factors and environmental perceptions on self-rated health in the environmentally devastated Aral Sea area of Karakalpakstan. Self-rated health was assessed using a questionnaire on 881 randomly selected individuals from three communities. Communities were chosen based on relative differences with regards to economic and ethnic characteristics, and distance from the sea coast. Consistent with mortality rates in the area, the prevalence of 'poor' self-rated health was high. Factors negatively associated with self-rated health include psychosocial impacts and reported environmental concern, as well as community of residence and age. These results demonstrate that the population has a poor perception of their own health, a significant finding given that self-rated health is a strong predictor of morbidity and mortality. It is also clear that psychosocial health is strongly associated with health perceptions. Thus, to improve the overall health of this population, health remediation measures must address physical as well as psychosocial health problems.

Adult↗

PubMed2003

European consortia building integrated resources for Arabidopsis functional genomics.

European laboratories specializing in functional genomics technologies collaborate in several consortia to build resources that facilitate gene function discovery in Arabidopsis thaliana. These resources include CATMA (a repertoire of gene-specific sequence tags), CAGE (a compendium of transcript profiles), AGRIKOLA (which consists of plasmids and mutant lines for gene silencing), ORFEUS (a collection of open reading frames) and SAP (a collection of promoter regions).

Arabidopsis↗

PubMed2003

Identification of the fertility restoration locus, Rfo, in radish, as a member of the pentatricopeptide-repeat protein family.

Ogura cytoplasmic male sterility (CMS) in radish (Raphanus sativus) is caused by an aberrant mitochondrial gene, Orf138, that prevents the production of functional pollen without affecting female fertility. Rfo, a nuclear gene that restores male fertility, alters the expression of Orf138 at the post-transcriptional level. The Ogura CMS/Rfo two-component system is a useful model for investigating nuclear-cytoplasmic interactions, as well as the physiological basis of fertility restoration. Using a combination of positional cloning and microsynteny analysis of Arabidopsis thaliana and radish, we genetically and physically delimited the Rfo locus to a 15-kb DNA segment. Analysis of this segment shows that Rfo is a member of the pentatricopeptide repeat (PPR) family. In Arabidopsis, this family contains more than 450 members of unknown function, although most of them are predicted to be targeted to mitochondria and chloroplasts and are thought to have roles in organellar gene expression.

Amino Acid Sequence↗

PubMed2003

Safe water for the Aral Sea Area: could it get any worse?

The environmental adversities around the Aral Sea in Central Asia have been the subject of recent research. Attempts at sustainable provision of palatable drinking water in low chemical and microbial contaminants for the 4 million people in the two countries around the Aral littoral have been largely unsuccessful. In the last few years, severe drought has further depleted the amount of available water. This shortage has negatively impacted on agriculture, and accentuated the out migration of people. An appeal is made to assist the local population in this arid area to cope with the acute and chronic deterioration of water security.

Agriculture↗

PubMed2003

Assessment of dietary exposure to some persistent organic pollutants in the Republic of Karakalpakstan of Uzbekistan.

A 1999 study heightened long-standing concerns over persistent organic pollutant contamination in the Aral Sea area, detecting elevated levels in breast milk and cord blood of women in Karakalpakstan (western Uzbekistan). These findings prompted a collaborative research study aimed at linking such human findings with evidence of food chain contamination in the area. An international team carried out analyses of organochlorine and organophosphate pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) on samples of 12 foods commonly produced and consumed in Karakalpakstan. Analysis consistently detected long-lasting organochlorine pesticides and their metabolites in all foods of animal origin and in some vegetables such as onions and carrots--two low-cost components of many traditional dishes. Levels of PCBs were relatively low in all samples except fish. Analyses revealed high levels of PCDDs and PCDFs (together often termed "dioxins") in sheep fat, dairy cream, eggs, and edible cottonseed oil, among other foodstuffs. These findings indicate that food traditionally grown, sold, and consumed in Karakalpakstan is a major route of human exposure to several persistent toxic contaminants, including the most toxic of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Intake estimations demonstrate that consumption of even small amounts of locally grown food may expose consumers to dioxin levels that considerably exceed the monthly tolerable dioxin intake levels set by the World Health Organization. Data presented in this study allow a first assessment of the risk associated with the consumption of certain food products in Karakalpakstan and highlight a critical public health situation.

Dioxins↗

PubMed2002

The gene encoding Arabidopsis thaliana mitochondrial ribosomal protein S13 is a recent duplication of the gene encoding plastid S13.

A gene encoding mitochondrial S13 is generally present in the mitochondrial genome of higher plants, but is lacking from the Arabidopsis thaliana mitochondrial genome. Previous research has failed to identify a nuclear gene capable of encoding a mitochondrial S13 protein or the protein itself. Doubts have even been raised as to whether a mitochondrial S13 exists in Arabidopsis. Here, we show that the nuclear gene encoding the plastid S13 has been partially duplicated in A. thaliana, such that the copy has lost the exon encoding the plastid transit peptide and acquired a sequence capable of encoding a mitochondrial targeting sequence. The two S13 sequences were fused to green fluorescent protein and shown to be targeted to plastids and mitochondria respectively.

Amino Acid Sequence↗