Biomedical subjects

Michael J Smith

Publications and source records attributed to Michael J Smith.

7 recordsLinked to original sources

PubMed2004

Complete mitochondrial genome DNA sequence for two ophiuroids and a holothuroid: the utility of protein gene sequence and gene maps in the analyses of deep deuterostome phylogeny.

The complete mitochondrial genome sequences have been determined for the holothuroid Cucumaria miniata and two ophiuroid species Ophiopholis aculeata and Ophiura lütkeni. In addition, the nucleotide sequence of the mitochondrial protein-coding genes for the asteroid Pisaster ochraceus has been completed. Maximum-likelihood and LogDet distance analyses of concatenated protein-coding sequences produced a series of trees that did not conclusively support generally accepted models of echinoderm phylogeny. The ophiuroid data consistently demonstrated accelerated nucleotide divergence rates and lack of stationarity. This confounds the phylogenetic analyses. Molecular investigations using individual protein-coding gene alignments demonstrated that the cytochrome b gene exhibits the least deviation in rate and stationarity and generated some trees consistent with proposed echinoderm phylogenies. Phylogenies based on echinoderm mitochondrial gene rearrangements also proved problematic because of extensive variation in gene order between and within classes. A comparison of the two distinctive ophiuroid mitochondrial gene orders supports the hypothesis that O. lütkeni has a more derived mitochondrial gene order versus O. aculeata. The variation in the echinoderm mitochondrial gene maps reinforces the limitations of the application of mitochondrial gene rearrangements as a global phylogenetic tool.

Animals↗

PubMed2003

Age-associated changes in the monoaminergic innervation of rat lumbosacral spinal cord.

The effects of ageing on the innervation patterns of lumbosacral spinal nuclei involved in controlling lower urinary tract functions, including micturition, were studied using immunohistochemistry for serotonin (5-HT) and tyrosine hydroxylase (TH) in male Wistar rats of 3 and 24 months. Quantitative image analysis revealed significant age-associated declines in the innervation of most regions including the intermediolateral cell nucleus, sacral parasympathetic nucleus, dorsal grey commissure and in the ventral horn including the dorsolateral nucleus which in the rat is one of the component nuclei homologous to Onuf's nucleus in man. Notable exceptions to this generalised decline were observed in the 5-HT innervation of the sacral parasympathetic nucleus, which was maintained, and in the region of the dorsolateral motor nucleus where TH-like immunoreactivity did not significantly decline. These results suggest that the changes in micturition characteristics observed in aged rats may in part be a consequence of the alterations in, and decline of, aminergic inputs to both autonomic and somatic spinal nuclei associated with bladder function.

Aging↗

PubMed2003

Do ergonomics improvements increase computer workers' productivity?: an intervention study in a call centre.

This paper examines whether improving physical ergonomics working conditions affects worker productivity in a call centre with computer-intensive work. A field study was conducted at a catalogue retail service organization to explore the impact of ergonomics improvements on worker production. There were three levels of ergonomics interventions, each adding incrementally to the previous one. The first level was ergonomics training for all computer users accompanied by workstation ergonomics analysis leading to specific customized adjustments to better fit each worker (Group C). The second level added specific workstation accessories to improve the worker fit if the ergonomics analysis indicated a need for them (Group B). The third level met Group B requirements plus an improved chair (Group A). Productivity data was gathered from 72 volunteer participants who received ergonomics improvements to their workstations and 370 control subjects working in the same departments. Daily company records of production outputs for each worker were taken before ergonomics intervention (baseline) and 12 months after ergonomics intervention. Productivity improvement from baseline to 12 months post-intervention was examined across all ergonomics conditions combined, and also compared to the control group. The findings showed that worker performance increased for 50% of the ergonomics improvement participants and decreased for 50%. Overall, there was a 4.87% output increase for the ergonomics improvement group as compared to a 3.46% output decrease for the control group. The level of productivity increase varied by the type of the ergonomics improvements with Group C showing the best improvement (9.43%). Even though the average production improved, caution must be used in interpreting the findings since the ergonomics interventions were not successful for one-half of the participants.

Computers↗

PubMed2003

Repeat motifs of tau bind to the insides of microtubules in the absence of taxol.

The tau family of microtubule-associated proteins has a microtubule-binding domain which includes three or four conserved sequence repeats. Pelleting assays show that when tubulin and tau are co- assembled into microtubules, the presence of taxol reduces the amount of tau incorporated. In the absence of taxol, strong binding sites for tau are filled by one repeat motif per tubulin dimer; additional tau molecules bind more weakly. We have labelled a repeat motif with nanogold and used three-dimensional electron cryomicroscopy to compare images of microtubules assembled with labelled or unlabelled tau. With kinesin motor domains bound to the microtubule outer surface to distinguish between alpha- and beta-tubulin, we show that the gold label lies on the inner surface close to the taxol binding site on beta-tubulin. Loops within the repeat motifs of tau have sequence similarity to an extended loop which occupies a site in alpha-tubulin equivalent to the taxol-binding pocket in beta-tubulin. We propose that loops in bound tau stabilize microtubules in a similar way to taxol, although with lower affinity so that assembly is reversible.

Amino Acid Sequence↗

PubMed2002

Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein.

The identification of mutations in the Tau gene in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has made it possible to express human tau protein with pathogenic mutations in transgenic animals. Here we report on the production and characterization of a line of mice transgenic for the 383 aa isoform of human tau with the P301S mutation. At 5-6 months of age, homozygous animals from this line developed a neurological phenotype dominated by a severe paraparesis. According to light microscopy, many nerve cells in brain and spinal cord were strongly immunoreactive for hyperphosphorylated tau. According to electron microscopy, abundant filaments made of hyperphosphorylated tau protein were present. The majority of filaments resembled the half-twisted ribbons described previously in cases of FTDP-17, with a minority of filaments resembling the paired helical filaments of Alzheimer's disease. Sarkosyl-insoluble tau from brains and spinal cords of transgenic mice ran as a hyperphosphorylated 64 kDa band, the same apparent molecular mass as that of the 383 aa tau isoform in the human tauopathies. Perchloric acid-soluble tau was also phosphorylated at many sites, with the notable exception of serine 214. In the spinal cord, neurodegeneration was present, as indicated by a 49% reduction in the number of motor neurons. No evidence for apoptosis was obtained, despite the extensive colocalization of hyperphosphorylated tau protein with activated MAP kinase family members. The latter may be involved in the hyperphosphorylation of tau.

Amino Acid Substitution↗

PubMed2002

A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease.

Mutations in the tau gene cause familial frontotemporal dementia and parkinsonism linked to chromosome 17. In this article, we describe a novel missense mutation, S320F, in the tau gene in a family with presenile dementia. To our knowledge, it is the first mutation to be described in exon 11 of tau. The proband died at age 53 years, after a disease duration of 15 years, and autopsy revealed a neuropathological picture similar to Pick's disease. Recombinant tau protein with the S320F mutation showed a greatly reduced ability to promote microtubule assembly.

Adult↗

PubMed2002

Naturopathy.

Naturopathic medicine is an eclectic form of primary health care that encompasses many complementary modalities in the treatment and prevention of disease. Treatment protocols are integrative in nature, combining the most suitable therapies to address the individual patient's needs. Although naturopathic physicians often are referred to as general practitioners of complementary medicine, practitioners share a common philosophical belief in the profession's founding principles. Naturopathic physicians have started to contribute to research and incorporate modern scientific methods into clinical practice, which has served to develop and validate the profession further. In contrast to many other forms of complementary medicine, naturopathic medicine is regulated partially by law. Legislation of naturopathic medicine has worked well in jurisdictions where it is legislated and has led to uniform standards of education and practice. In addition, regulation has helped with integration and naturopathic cooperation with all other branches of medical science. Within licensed jurisdictions, patients receiving naturopathic care can expect the practitioner to be held to high standards, established by state or provincial law. As alternative therapies become more integrated in nature, conventional medicine will face new challenges. Licensed naturopathic physicians are trained sufficiently to play an active role in this new primary health care team. Although the exact role has yet to be determined, the eclectic approach taken by naturopathic physicians may be of benefit in this evolutionary process.

Education, Medical, Undergraduate↗