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John Holt

Publications and source records attributed to John Holt.

8 recordsLinked to original sources
PubMed2004

Structural studies of arthrin: monoubiquitinated actin.

Here, we report on the structure and in situ location of arthrin (monoubiquitinated actin). Labelling of insect muscle thin filaments with a ubiquitin antibody reveals that every seventh subunit along the filament long-pitch helices is ubiquitinated. A three-dimensional reconstruction of frozen-hydrated arthrin filaments was produced. This was based on a novel algorithm that divides filament images into short segments that are used for single-particle image processing. Difference maps with an actin filament reconstruction locate ubiquitin at the side of actin sub-domain 1 opposite where myosin binds. Consistent with the reconstructions, peptide mapping places the ubiquitin linkage on lysine 118 in actin. Molecular modelling was used to generate arthrin monomers from ubiquitin and actin crystal structures. Filament models constructed from these monomers were compared with the arthrin reconstruction. The reconstruction suggests ubiquitin attached to Lys118 adopts one or a few conformers, stabilized by a small interface with actin. The function of actin ubiquitination is not known, but may involve regulation of muscle contractile activity.

Actins↗
PubMed2004

Investigation of clusters of giardiasis using GIS and a spatial scan statistic.

BACKGROUND: Giardia lamblia is the most frequently identified human intestinal parasite in Canada with prevalence estimates of 4-10%. However, infection rates vary by geographical area and localized 'pockets' of high or low infection rates are thought to exist. Water-borne transmission is one of the major routes of infection. Sources of contamination of drinking water include humans, domestic and wild animals. A previous study in southern Ontario, Canada, indicated a bivariate association between giardiasis rates and livestock density and/or manure use on agricultural land; however these variables were not significant when the variable 'rural' was added to the model. In that study, urban areas were defined as those with a minimum of 1,000 persons and a population density of at least 400 persons per Km2; all other areas were considered rural. This paper investigates the presence of local giardiasis clusters and considers the extent to which livestock density and manure application on agricultural land might explain the 'rural' effect. A spatial scan statistic was used to identify spatial clusters and geographical correlation analysis was used to explore associations of giardiasis rates with manure application on agricultural land and livestock density. RESULTS: Significant (P < 0.05) high rate spatial clusters were identified in a number of areas. Results also showed significant (P < 0.05) associations between giardiasis rates and both livestock density and manure application on agricultural land. However, the associations were observed in only two regions. CONCLUSIONS: There is evidence that giardiasis clusters in space in southern Ontario. However, there is no strong evidence to suggest that either livestock density or manure application on agricultural land plays an important role in the epidemiology of giardiasis in the study area. Therefore these factors do not seem to explain the higher rates of giardiasis reported in rural areas. The spatial scan statistics methodology used in this study has an important potential use in disease surveillance for confirming or refuting cluster alarms.

Journal Article↗
PubMed2003

Geographical and temporal distribution of human giardiasis in Ontario, Canada.

BACKGROUND: Giardia is the most frequently identified intestinal parasite in North America. Although information on geographical distribution of giardiasis is critical in identifying communities at high risk, little has been done in this area. Therefore, the objective of this study was to investigate the geographical and temporal distribution of human giardiasis in Ontario in order to identify possible high risk areas and seasons. Two spatial scales of analyses and two disease measures were used with a view to identifying the best of each in assessing geographical patterns of giardiasis in Ontario. Global Moran's I and Moran Local Indicators of Spatial Associations were used to test for evidence of global and local spatial clustering, respectively. RESULTS: There were seasonal patterns with summer peaks and a significant (P < 0.001) decreasing temporal trend. Significant (P < 0.05) global spatial clustering of high rates was observed at the Census Sub-division spatial scale but not at the Census Division scale. The Census Sub-division scale was a better scale of analyses but required spatial empirical Bayesian smoothing of the rates. A number of areas with significant local clustering of giardiasis rates were identified. CONCLUSIONS: The study identified spatial and temporal patterns in giardiasis distribution. This information is important in guiding decisions on disease control strategies. The study also showed that there is benefit in performing spatial analyses at more than one spatial scale to assess geographical patterns in disease distribution and that smoothing of disease rates for mapping in small areas enhances visualization of spatial patterns.

Journal Article↗
PubMed2002

Collaboration among sex offender treatment providers and probation and parole officers: the beliefs and behaviors of treatment providers.

New and emerging collaborative responses to sex offender management are challenging traditional notions about how treatment providers and probation and parole officers (POs) deliver services to this difficult population. Typically, sex offender treatment professionals provide community-based services to offenders who are supervised by POs. Yet, no comprehensive survey has investigated how treatment providers and POs collaborate and view their relationships with each other. This national random survey examined the beliefs and behaviors of community-based adult sex-offender treatment providers concerning various types of provider and PO interactions and collaborative models. Overall, treatment providers reported that they value frequent and substantive communication with POs concerning mutual clients. There was, however, considerable diversity in practice and opinion among providers with regard to POs leading, coleading, and observing sex offender treatment groups. Treatment providers' opinions about various clinical, ethical, and legal issues evident in these collaborative approaches are examined.

Adult↗
PubMed2001

The inhibition of cAMP-dependent protein kinase by full-length hepatitis C virus NS3/4A complex is due to ATP hydrolysis.

Hepatitis C virus (HCV) is an important cause of chronic liver disease, but the molecular mechanisms of viral pathogenesis remain to be established. The HCV non-structural protein NS3 complexes with NS4A and has three enzymatic activities: a proteinase and a helicase/NTPase. Recently, catalytically inactive NS3 fragments containing an arginine-rich motif have been reported to interact with, and inhibit, the catalytic subunit of cAMP-dependent protein kinase (PKA C-subunit). Here we demonstrate that full-length, catalytically active NS3/4A, purified from recombinant baculovirus-infected insect cells, is also able to inhibit PKA C-subunit in vitro. This inhibition was abrogated by mutation of either the arginine-rich motif or the conserved helicase motif II, both of which also abolished NTPase activity. As PKA C-subunit inhibition was also enhanced by poly(U) (an activator of NS3 NTPase activity), we hypothesized that PKA C-subunit inhibition could be due to NS3/4A-mediated ATP hydrolysis. This was confirmed by experiments in which a constant ATP concentration was maintained by addition of an ATP regeneration system--under these conditions PKA C-subunit inhibition was not observed. Interestingly, the mutations also abrogated the ability of wild-type NS3/4A to inhibit the PKA-regulated transcription factor CREB in transiently transfected hepatoma cells. Our data are thus not consistent with the previously proposed model in which the arginine-rich motif of NS3 was suggested to act as a pseudosubstrate inhibitor of PKA C-subunit. However, in vivo effects of NS3/4A suggest that ATPase activity may play a role in viral pathology in the infected liver.

Adenosine Triphosphate↗
PubMedDate not supplied

The status of drinking water in Ontario, Canada (1992-1999).

OBJECTIVE: This study was conducted to investigate the characteristics of public water works (PWW) in southern Ontario with respect to their water sources and treatment regimes. METHODS: Data from 481 PWW covering the period 1992-1999 were collected and cartographic manipulations as well as descriptive analyses of the PWW attributes were performed. Tests of associations between different PWW attributes were done using Fisher's Exact test and Cochran-Mantel-Haenszel statistics. RESULTS: Water sources for the PWW included surface water (SW) (21% lakes; 13% rivers), ground water (GW) (64%) and mixed sources (2%). Most (81%) of the population was supplied with SW. Filtration was performed by 84% and 8% of the PWW using SW and GW, respectively. Similarly, disinfection was performed by 99% and 91% of the PWW using SW and GW respectively. There was no significant difference in treatment regimes between PWW in urban and those in rural areas but treatment regime was a function of water source. Overall, most PWW (87.8%) met the minimum treatment requirements of the then Ontario Drinking Water Objectives (ODWO). DISCUSSION: The study shows that most PWW complied with the minimum treatment requirements of the then ODWO. The minimum treatment required by the ODWO was disinfection for GW and both disinfection and filtration for SW. The non-compliant PWW will need to comply for continued provision of safe drinking water. Suffice it to say that both watershed protection and improved water treatment will be imperative for the continued provision of safe drinking water and control of waterborne diseases.

Databases, Factual↗
PubMedDate not supplied

New vet school.

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Animals↗