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Biomedical subjects

Peter Watson

Publications and source records attributed to Peter Watson.

At least 19 recordsLinked to original sources
PubMed2006

Toxin entry and trafficking in mammalian cells.

There is a vast number of bacterial and plant toxins that affect cytosolic targets in mammalian cells, and whether the purpose of the toxin is to act as a defence mechanism against predators, or to cause deliberate cell death in order to form an environment more suitable for bacterial growth, each of these toxins must cross a lipid membrane barrier in order to exert their effect. This review looks at the methods employed by bacterial and plant toxins in order to reach their target. We examine the trafficking methods involved in toxin transport throughout the cell, highlighting the proteins necessary for the toxins movement, and noting how many of the toxins hijack the cells own trafficking and protein processing machinery in order to reach their goals. Studying the trafficking of toxins has led to a greater understanding of retrograde transport, a process which has key relevance to the correct intracellular delivery of pharmacological agents.

Animals↗
PubMed2006

Sec16 defines endoplasmic reticulum exit sites and is required for secretory cargo export in mammalian cells.

The selective export of proteins and lipids from the endoplasmic reticulum (ER) is mediated by the coat protein complex II (COPII) that assembles onto the ER membrane. In higher eukaryotes, COPII proteins assemble at discrete sites on the membrane known as ER exit sites (ERES). Here, we identify Sec16 as the protein that defines ERES in mammalian cells. Sec16 localizes to ERES independent of Sec23/24 and Sec13/31. Overexpression, and to a lesser extent, small interfering RNA depletion of Sec16, both inhibit ER-to-Golgi transport suggesting that Sec16 is required in stoichiometric amounts. Sar1 activity is required to maintain the localization of Sec16 at discrete locations on the ER membrane, probably through preventing its dissociation. Our data suggest that Sar1-GTP-dependent assembly of Sec16 on the ER membrane forms an organized scaffold defining an ERES.

Cell Line↗
PubMed2006

Perceived access to community facilities, social motivation, and physical activity among New Zealand youth.

The current study describes motivations for physical activity and relationships between recreational facilities and physical activity among a nationally representative sample of New Zealand youth. Our findings suggest that physical activity interventions should address both the social (opportunities for social engagement) and physical (access to recreational facilities) environments of adolescents.

Adolescent↗
PubMed2006

Microtubule plus-end loading of p150(Glued) is mediated by EB1 and CLIP-170 but is not required for intracellular membrane traffic in mammalian cells.

Microtubule dynamics and function are regulated, at least in part, by a family of proteins that localize to microtubule plus-ends, and include EB1, CLIP-170 and the dynactin component p150(Glued). Plus-end pools of these proteins, notably dynactin, have been invoked in a number of ;search-and-capture' mechanisms, including the attachment of microtubules to kinetochores during mitosis and to endomembranes prior to the initiation of intracellular transport. Here we show that, in mammalian cells, EB1 is required for the plus-end localization of CLIP-170, and that this is in turn required to localize p150(Glued) to plus-ends. Specific depletion of CLIP-170 results in defects in microtubule dynamics, cell polarization in response to scratch wounding and a loss of p150(Glued) from plus ends. By contrast, removal of p150(Glued) from plus-ends by depletion of either EB1 or CLIP-170 caused no defects in the localization of intracellular organelles, the dynamics of ER-to-Golgi transport, the efficiency of transferrin uptake or the motility of early endosomes or lysosomes. In addition to labelling microtubule plus-ends, we show that GFP-p150(Glued) becomes incorporated into the dynactin complex and labels small, highly dynamic, punctate structures that move along microtubules. A subset of these structures colocalizes with ER-Golgi transport intermediates. Together, these data show that the function of CLIP-170 and p150(Glued) in membrane trafficking is not associated with their plus-end localization.

Biological Transport↗
PubMed2006

The relationship of neuronal activity within the sensori-motor region of the subthalamic nucleus to speech.

Microelectrode recordings of human sensori-motor subthalamic neuronal activity during spoken sentence and syllable-repetition tasks provided an opportunity to evaluate the relationship between changes in neuronal activities and specific aspects of these vocal behaviors. Observed patterns of neuronal activity included a build up of activity in anticipation of the start of the utterance, a marked reduction in activity associated with the start of the utterance, and a burst of activity during the course of the sentence between the noun phrase and the verb phrase. Overall, changes of neuronal activity were more robust for the sentence repetition task. These data suggest that the basal ganglia play a role in generating meaningful speech utterances, which may parallel its role in complex sequential limb movements. It is possible that the basal ganglia play a role in generating the syntactical structure of language.

Aged↗
PubMed2006

Contraceptive use by Maori youth in New Zealand: associated risk and protective factors.

AIMS: To identify risk and protective factors associated with consistent contraception use by sexually active Maori youth. METHODS: Secondary analysis was undertaken utilising Youth2000, an anonymous nationally representative secondary school health and wellbeing survey, undertaken in 2001. We describe the self-reported sexual health and contraceptive use behaviours of Maori students. A multiple logistic regression model was utilised to identify risk and protective factors associated with consistent contraception use by sexually active Maori students. RESULTS: Half of the Maori students have had sexual intercourse (54% males; 48% females) and a third are currently sexually active (33% males; 34% females). Most Maori youth who have ever had sex use condoms for contraception (82%) and most sexually active Maori youth reported consistent use of contraception (71% males; 70% females). Maori youth who use contraception consistently are more likely to report getting enough time with a parent (OR 1.50; 95% CI 1.05-2.14; p=0.03) and less likely to report weekly marijuana use (OR 0.53; 95% CI 0.37-0.76; p=0.0006). CONCLUSIONS: Consistent use of condoms is a common self-reported contraceptive practice by many young Maori. However this behaviour is not universal, and in view of the significant sexual and reproductive health disparities that exist for Maori youth, sexual and reproductive health programs should examine a broader strategy of promoting protective factors such as strengthening youth-parent relationships and reducing risk factors, such as minimising substance misuse. Together with existing efforts in education, whanau (family), and community based programs, these strategies may support healthier sexual health outcomes for Maori youth.

Adolescent↗
PubMed2006

Do patients benefit from participating in medical decision making? Longitudinal follow-up of women with breast cancer.

This study sought to examine the relationships between decisional role (preferred and assumed) at time of surgical treatment (baseline), congruence between assumed role at baseline and preferred role 3 years later (follow-up), and quality of life at follow-up. Two hundred and five women diagnosed with breast cancer completed the decisional role preference scale at baseline and follow-up, and the EORTC QLQ-C30 at follow-up. A statistically significant number of women had decisional role regret, with most of these women preferring greater involvement in treatment planning than was afforded them. Women who indicated at baseline that they were actively involved in choosing their surgical treatment had significantly higher overall quality of life at follow-up than women who indicated passive involvement. These actively involved women had significantly higher physical and social functioning and significantly less fatigue than women who assumed a passive role. Quality of life was significantly related to reports of experienced involvement in treatment decision making, but not to reports of preferred involvement, or congruence between preferred and experienced involvement.

Aged↗
PubMed2006

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease.

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.

Adult↗
PubMed2006

Acne, anxiety, depression and suicide in teenagers: a cross-sectional survey of New Zealand secondary school students.

AIM: To examine the associations between acne and depressive symptoms, anxiety and suicidal behaviours. METHODS: This was a secondary analysis of a cross-sectional survey -'Youth2000' (New Zealand national survey of youth health). A total of 9567 secondary school students aged 12-18 years participated in the survey. The main outcome measures were self-reported acne, depressive symptoms (Reynolds Adolescent Depression Scale > 77), anxiety (Anxiety Disorder Index from Multidimensional Anxiety Scale for Children) and self-reported suicide attempts. RESULTS: 'Problem acne' was associated with an increased probability of depressive symptoms, odds ratio 2.04 (95% confidence interval 1.70-2.45); anxiety, odds ratio 2.3 (1.74-3.00); and suicide attempts, odds ratio 1.83 (1.51-2.22) in a logistic model that included age, gender, ethnicity, school decile and socio-economic status. The association of acne with suicide attempts remained after controlling for depressive symptoms and anxiety, odds ratio 1.50 (1.21-1.86). CONCLUSION: Young people presenting with acne are at increased risk of depression, anxiety and suicide attempts. Attention should be paid to their mental health, and the importance of asking directly regarding suicide is emphasised.

Acne Vulgaris↗
PubMed2005

Melanin in the trabecular meshwork is associated with age, POAG but not Latanoprost treatment. A masked morphometric study.

We wished to conduct a light and electron microscopic investigation of pigmentation within the trabecular meshwork of normals and primary open angle glaucoma (POAG) patients. In particular we wished to get a precise determination of whether there was a relationship between pigmentation and age. In addition we wanted to know if there was a difference between normals and POAGs and whether trabecular meshwork hyperpigmentation was associated with topical latanoprost medication. A total of 25 sham trabeculectomies conducted on post mortem donor eyes provided the age-matched normals and there were 62 trabeculectomy specimens from POAG patients. These were masked and the meshwork subjected to qualitative and quantitative morphological investigation. Light and electron microscopy confirmed that most of the trabecular meshwork melanin was phagocytosed and within meshwork cells. The granules were measured and found to be of the large iris epithelial type. Light microscopic morphometric analysis showed that the number of meshwork cell profiles that contained melanin increased both in normals and POAGs with age. However there was nearly three times more pigmented meshwork cells in the POAGs than the normals. The POAGs were divided into three groups of (1) minimal or no medication prior to surgery, (2) maximal medical therapy and (3) maximum medical therapy including latanoprost (12 specimens). All groups were significantly greater that the normals but of the three it was the maximal medical therapy group (without latanoprost) that had the highest pigmentation. We concluded that pigmentation of the meshwork is age-related and it is elevated in POAG by mechanisms unknown. The melanin accumulation seems to be partly due to the disease process, partly as a consequence of chronic antiglaucoma medication but interestingly not due to latanoprost even in patients where there is iris darkening (four specimens).

Administration, Topical↗
PubMed2005

Social reasoning, emotion and empathy in frontotemporal dementia.

INTRODUCTION: Social cognition is crucial for human interaction, and is markedly impaired in the frontal variant of frontotemporal dementia (fvFTD). The relationship of various aspects of social functioning, however, remains controversial in this group. METHODS: Patients with fvFTD (n = 18), and matched controls (n = 13), were tested using tasks designed to assess their Theory of Mind (ToM), moral reasoning, emotion recognition and executive function. Caregivers documented changes in empathy compared to premorbid functioning. RESULTS: We found marked impairments in the abilities of fvFTD patients, relative to controls, in ability to mentalise (ToM), which was evident on a cartoon test, but not on a story-based ToM task. Knowledge of social rules was intact, but moral reasoning was defective, and was due, in part, to an inability to rate the seriousness of moral and conventional transgressions appropriately. Executive function was impaired in this group, and compromised aspects of moral reasoning, but ToM performance was independent of this. Emotion recognition was globally impaired in fvFTD, but was particularly so for anger and disgust which may partly explain the difficulty these patients have with identifying social violations. Empathy, as rated by carers, was also shown to be abnormal. CONCLUSION: It appears that social reasoning is disrupted in a number of ways in fvFTD, and the findings provide a basis for the understanding and further study of abnormal behaviour in this disease. The results are discussed in light of neuroimaging findings in studies of social cognition and the locus of pathology in fvFTD.

Adult↗
PubMed2005

ER-to-Golgi transport: form and formation of vesicular and tubular carriers.

The transport of proteins and lipids between the endoplasmic reticulum and Golgi apparatus is initiated by the collection of secretory cargo from within the lumen of the endoplasmic reticulum. Subsequently, transport carriers are formed that bud from this membrane and are transported to, and subsequently merge with, the Golgi. The principle driving force behind the budding process is the multi-subunit coat protein complex, COPII. A considerable amount of information is now available regarding the molecular mechanisms by which COPII components operate together to drive cargo selection and transport carrier formation. In contrast, the precise nature of the transport carriers formed is still a matter of considerable debate. Vesicular and tubular carriers have been characterized that are, or in other cases are not, coated with the COPII complex. Here, we seek to integrate much of the data surrounding this topic and try to understand the mechanisms by which vesicular and/or tubular carriers might be generated.

Animals↗
PubMed2005

Intracellular trafficking pathways and drug delivery: fluorescence imaging of living and fixed cells.

Cellular processes depend on the fidelity of intracellular membrane traffic. Lipids, proteins, receptor ligands and solute molecules are trafficked to distinct compartments within the cell through both the biosynthetic and endocytic pathways. An appreciation of these pathways is vital for a complete understanding of intracellular drug delivery. Recent advances in fluorescence imaging have facilitated the analysis of these pathways in great detail. It is now possible to gain insight into the real-time dynamics of cellular components and macromolecular pharmacological agents as they are delivered into and traffic within single cells. Here, we discuss the analysis of intracellular drug delivery from the perspective of fluorescence imaging of both living and fixed cells. This review aims to cover trafficking pathways, markers for subcellular compartments, fluorescent labels for intracellular structures and pharmacological agents and relevant recent developments in imaging technology. In particular, we shall focus on the application of live cell imaging to the study of endocytic drug delivery.

Bacterial Toxins↗
PubMed2005

The role of microtubules in transport between the endoplasmic reticulum and Golgi apparatus in mammalian cells.

The organization of intracellular compartments and the transfer of components between them are central to the correct functioning of mammalian cells. Proteins and lipids are transferred between compartments by the formation, movement and subsequent specific fusion of transport intermediates. These vesicles and membrane clusters must be coupled to the cytoskeleton and to motor proteins that drive motility. Anterograde ER (endoplasmic reticulum)-to-Golgi transport, and the converse step of retrograde traffic from the Golgi to the ER, are now known to involve coupling of membranes to the microtubule cytoskeleton. Here we shall discuss our current understanding of the mechanisms that link membrane traffic in the early secretory pathway to the microtubule cytoskeleton in mammalian cells. Recent data have also provided molecular detail of functional co-ordination of motor proteins to specify directionality, as well as mechanisms for regulating motor activity by protein phosphorylation.

Animals↗
PubMed2005

A randomized control trial to evaluate a paging system for people with traumatic brain injury.

Although memory problems following acquired brain damage are common, some people are able to compensate for these problems through external aids. It was recently demonstrated that a paging system could reduce the everyday memory and planning problems for people with non-progressive brain injury. The 143 patients who participated in the study comprised several diagnostic groups. This paper reports on the sub-group of people with TBI (n=63). This sub-group was part of the larger sample of 143 already published in the 2001 study. A randomized control cross-over design randomly allocated people to group A (pager first) or group B (waiting list first). Each participant chose their own tasks for which they needed reminders. During a 2 week baseline, successful task achievement was documented. Group A achieved 47.14% of tasks and group B 47.88%. People in group A then received a pager for 7 weeks. During the last 2 weeks of this 7 week period, task achievement was documented again. Group A now achieved 71.80% of tasks and group B (on the waiting list) achieved 49.05% (no different from baseline). Group A then returned their pagers and group B received pagers. During the last 2 weeks of this stage participants were monitored once more. At this point, people in group A had dropped back slightly but were still statistically significantly better than during the baseline (67.23%). Group B, meanwhile, were now achieving 73.62% of tasks. This was statistically significantly better than baseline and significantly better than group A, now in the post-pager phase. It is concluded that this paging system significantly reduces the everyday memory and planning problems of people with TBI.

Activities of Daily Living↗