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Owen White

Publications and source records attributed to Owen White.

At least 19 recordsLinked to original sources
PubMed2006

TIGRFAMs and Genome Properties: tools for the assignment of molecular function and biological process in prokaryotic genomes.

TIGRFAMs is a collection of protein family definitions built to aid in high-throughput annotation of specific protein functions. Each family is based on a hidden Markov model (HMM), where both cutoff scores and membership in the seed alignment are chosen so that the HMMs can classify numerous proteins according to their specific molecular functions. Most TIGRFAMs models describe 'equivalog' families, where both orthology and lateral gene transfer may be part of the evolutionary history, but where a single molecular function has been conserved. The Genome Properties system contains a queriable set of metabolic reconstructions, genome metrics and extractions of information from the scientific literature. Its genome-by-genome assertions of whether or not specific structures, pathways or systems are present provide high-level conceptual descriptions of genomic content. These assertions enable comparative genomics, provide a meaningful biological context to aid in manual annotation, support assignments of Gene Ontology (GO) biological process terms and help validate HMM-based predictions of protein function. The Genome Properties system is particularly useful as a generator of phylogenetic profiles, through which new protein family functions may be discovered. The TIGRFAMs and Genome Properties systems can be accessed at http://www.tigr.org/TIGRFAMs and http://www.tigr.org/Genome_Properties.

Archaeal Proteins↗
PubMed2006

Ophthalmoplegia in tiger snake envenomation.

Herein, we present the case of a 67-year-old grazier who was bitten by a tiger snake and developed coagulopathy and respiratory distress. The patient required intubation and ventilation in intensive care. There was delayed detection of snake envenomation and administration of antivenom. On extubation several days later, gross external ocular paresis was noted. Clinical testing indicated that the ocular pathology was secondary to neurotoxin-mediated presynaptic blockade. The paresis was partially resolved by the time of discharge one week later. The present case report discusses the possible mechanisms for the delayed development of ophthalmoplegia.

Aged↗
PubMed2006

Comparative genomics of emerging human ehrlichiosis agents.

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.

Animals↗
PubMed2006

Saccadic trajectory in Huntington's disease.

Trajectories of saccadic eye movements can be modulated by the presence of a competing visual distractor. It is proposed that the superior colliculus (SC) controls the initial deviation through competitive lateral interactions. Given the ramifications of connections between basal ganglia (BG) thalamo-cortical circuitry and the SC, it was anticipated that this modulation would be differentially effected in those with Huntington's disease, which in its early stages is primarily a disorder of the BG. Horizontal deviation was determined for exogenously driven and endogenously driven vertical saccades in the presence of peripheral distractors. For neurologically healthy participants, the initial trajectories of both saccade types curved away from distractor locations, as predicted. However, for HD participants exogenous saccades consistently deviated leftwards, irrespective of distractor location. Endogenous saccades also revealed anomalous horizontal deviation, with significant leftward deviation evident for saccades directed upward and significant rightward deviation for saccades directed downward. Further, both groups generated a comparable proportion of erroneous responses to distractor stimuli, but only neurologically healthy participants demonstrated a response time advantage for compatible target/distractor presentation. These results suggest anomalous regulation of distractor-related activity in HD.

Adult↗
PubMed2006

The role of the basal ganglia in the control of automatic visuospatial attention.

Cognitive impairments in patients with basal ganglia dysfunction are primarily revealed where performance relies on internal, voluntary control processes. Evidence suggests that this also extends to impaired control of more automatic processes, including visuospatial attention. The present study used a non-predictive peripheral cueing paradigm to compare and contrast visuospatial deficits in patients with Parkinson's disease (PD) with those previously revealed in patients with Huntington's disease (HD) (Fielding et al., 2006a). Compared to age-matched controls, both PD and HD patients exhibited increased distractibility or poor fixation, however only PD patients responded erroneously to cue stimuli more frequently than control subjects. All subjects demonstrated initial facilitation for valid versus invalid cues following the shorter stimulus-onset asynchronies (SOAs) and a performance decrement at the longer SOAs (inhibition of return), although there was a clear differentiation between these groups for immediate SOAs. Unlike both control and PD subjects, where IOR manifested between 350 and 1000 msec, IOR was evident as early as 150 msec for HD patients. Further, for PD patients, spatially valid cues resulted in hyper-reflexivity following 150 msec SOAs, with saccadic latencies shorter than those generated in response to un-cued targets. Thus contrasting deficits were revealed in PD and HD, emphasizing the important contribution of the basal ganglia in the control of more automatic behaviors

Aged↗
PubMed2005

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus.

Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.

Allergens↗
PubMed2005

Temporal variation in the control of goal-directed visuospatial attention in basal ganglia disorders.

A predictive central-cueing paradigm was used to compare visuospatial deficits in patients with Parkinson's (PD) and Huntington's diseases (HD), employing directionally valid and invalid visual cues over a range of stimulus onset asynchronies (SOA) to elicit a saccadic response. Compared to age-matched control groups, both PD and HD patients responded erroneously to cue stimuli more frequently, increasing significantly over longer SOAs. Both valid and invalid cues resulted in elevated latencies compared to un-cued visually guided saccades, the associated 'cost' of invalid cueing significantly greater than that for valid cueing, over all SOAs. Unlike control subjects, PD and HD patients demonstrated temporal variation with cue presentation. For PD patients, latencies following directionally invalid cues were significantly longer for intermediate SOAs, suggesting difficulty overcoming a build-up of inhibitory activity over time. No validity effect was found at 1000 ms. For HD patients, latencies for validly cued saccades with 150 ms SOAs were shorter than latencies for no-cue trials, representing a 'benefit' of valid cueing. For 500 ms SOAs latencies were comparably elevated following directionally valid and invalid cues, and for 1000 ms SOAs neither cue condition resulted in increased latencies. These findings reflect the consequence of disruption to the balance of activity over the basal ganglia facilitatory and inhibitory pathways. Imbalance in PD resulted in difficulty sustaining goal-directed behaviour, and in HD, difficulty gating inappropriate behaviour.

Adult↗
PubMed2005

Analysis of the transcriptome of the protozoan Theileria parva using MPSS reveals that the majority of genes are transcriptionally active in the schizont stage.

Massively parallel signature sequencing (MPSS) was used to analyze the transcriptome of the intracellular protozoan Theileria parva. In total 1,095,000, 20 bp sequences representing 4371 different signatures were generated from T.parva schizonts. Reproducible signatures were identified within 73% of potentially detectable predicted genes and 83% had signatures in at least one MPSS cycle. A predicted leader peptide was detected on 405 expressed genes. The quantitative range of signatures was 4-52,256 transcripts per million (t.p.m.). Rare transcripts (<50 t.p.m.) were detected from 36% of genes. Sequence signatures approximated a lognormal distribution, as in microarray. Transcripts were widely distributed throughout the genome, although only 47% of 138 telomere-associated open reading frames exhibited signatures. Antisense signatures comprised 13.8% of the total, comparable with Plasmodium. Eighty five predicted genes with antisense signatures lacked a sense signature. Antisense transcripts were independently amplified from schizont cDNA and verified by sequencing. The MPSS transcripts per million for seven genes encoding schizont antigens recognized by bovine CD8 T cells varied 1000-fold. There was concordance between transcription and protein expression for heat shock proteins that were very highly expressed according to MPSS and proteomics. The data suggests a low level of baseline transcription from the majority of protein-coding genes.

Animals↗
PubMed2005

Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.

Amino Acid Sequence↗
PubMed2005

Accelerated time-course of inhibition of return in Huntington's disease.

A non-predictive peripheral cueing paradigm was used to evaluate visuospatial attentional deficits in symptomatic HD patients, employing spatially valid and invalid visual cues over a range of stimulus onset asynchronies (SOA) to elicit a saccadic response. Although both patients and controls demonstrated initial facilitation for valid versus invalid cues following the shortest SOA, and a performance decrement (inhibition of return), at the longest SOA, a clear differentiation between these groups was found for the intermediate SOAs. Unlike controls, where IOR manifested between 350 and 1000 ms, IOR was evident as early as 150 ms for HD patients. Further, the benefit of valid cueing correlated significantly with the level of impairment. Although patients exhibited poor fixation, principally attributable to saccadic intrusions, they were capable of appropriately suppressing a purely stimulus-driven response to the cue. A similar proportion of erroneous saccades to the cue were generated by both groups prior to stimulus onset, also correlating significantly with level of impairment. These results are discussed with respect to neural processes implicated in spatial cueing and within the context of reduced inhibitory activity of the BG in HD.

Adult↗
PubMed2005

Sequence, annotation, and analysis of synteny between rice chromosome 3 and diverged grass species.

Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.

Arabidopsis↗
PubMed2005

Comparative genomics of trypanosomatid parasitic protozoa.

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.

Animals↗
PubMed2005

The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.

Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.

Animals↗
PubMed2005

The genome of the African trypanosome Trypanosoma brucei.

African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

Amino Acids↗
PubMed2005

Complete reannotation of the Arabidopsis genome: methods, tools, protocols and the final release.

BACKGROUND: Since the initial publication of its complete genome sequence, Arabidopsis thaliana has become more important than ever as a model for plant research. However, the initial genome annotation was submitted by multiple centers using inconsistent methods, making the data difficult to use for many applications. RESULTS: Over the course of three years, TIGR has completed its effort to standardize the structural and functional annotation of the Arabidopsis genome. Using both manual and automated methods, Arabidopsis gene structures were refined and gene products were renamed and assigned to Gene Ontology categories. We present an overview of the methods employed, tools developed, and protocols followed, summarizing the contents of each data release with special emphasis on our final annotation release (version 5). CONCLUSION: Over the entire period, several thousand new genes and pseudogenes were added to the annotation. Approximately one third of the originally annotated gene models were significantly refined yielding improved gene structure annotations, and every protein-coding gene was manually inspected and classified using Gene Ontology terms.

Alternative Splicing↗
PubMed2005

No sequence dependent modulation of the Simon effect in Parkinson's disease.

This study sought to evaluate impaired response tendencies and modulation of automatic processes in Parkinson's disease (PD), utilising a saccadic Simon task with stimulus-response (S-R) compatibility determined on the basis of cue shape. The appearance of either a circle or a square in one of two boxes presented peripherally required the generation of a leftward or rightward horizontal saccade, respectively. These goal-directed responses were considered behaviourally relevant to an examination of visuospatial performance. Although response times are typically faster when stimulus and response are spatially compatible than when they are not, sequence-dependent modulation of this effect results in large differences between S-R compatible and S-R incompatible trials when stimulus and response are spatially compatible in the preceding trial, and reduced or absent differences when stimulus and response are spatially incompatible in the preceding trial. Unlike control subjects, PD patients demonstrated significantly shorter saccadic latencies overall, compared to a baseline condition involving endogenously-driven saccades. Patients also responded erroneously to cue stimuli with greater frequency. Analyses of both saccadic latency and errors to cue demonstrated a Simon effect (relatively faster response for S-R compatible trials), irrespective of the preceding trial. This suggests impaired modulation of the Simon effect in PD, consistent with predictions of inhibitory dysfunction, or impaired episodic memory. These results demonstrate the pivotal role of the basal ganglia in the regulation of context-dependent neural activity.

Adult↗
PubMed2005

Whole-genome sequence analysis of Pseudomonas syringae pv. phaseolicola 1448A reveals divergence among pathovars in genes involved in virulence and transposition.

Pseudomonas syringae pv. phaseolicola, a gram-negative bacterial plant pathogen, is the causal agent of halo blight of bean. In this study, we report on the genome sequence of P. syringae pv. phaseolicola isolate 1448A, which encodes 5,353 open reading frames (ORFs) on one circular chromosome (5,928,787 bp) and two plasmids (131,950 bp and 51,711 bp). Comparative analyses with a phylogenetically divergent pathovar, P. syringae pv. tomato DC3000, revealed a strong degree of conservation at the gene and genome levels. In total, 4,133 ORFs were identified as putative orthologs in these two pathovars using a reciprocal best-hit method, with 3,941 ORFs present in conserved, syntenic blocks. Although these two pathovars are highly similar at the physiological level, they have distinct host ranges; 1448A causes disease in beans, and DC3000 is pathogenic on tomato and Arabidopsis. Examination of the complement of ORFs encoding virulence, fitness, and survival factors revealed a substantial, but not complete, overlap between these two pathovars. Another distinguishing feature between the two pathovars is their distinctive sets of transposable elements. With access to a fifth complete pseudomonad genome sequence, we were able to identify 3,567 ORFs that likely comprise the core Pseudomonas genome and 365 ORFs that are P. syringae specific.

Bacterial Proteins↗