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Biomedical subjects

K Snell

Publications and source records attributed to K Snell.

At least 19 recordsLinked to original sources
PubMed1999

Inclusive instruction and learning for deaf students in postsecondary education.

This article explores how students who are deaf and their instructors experience mainstream college classes. Both quantitative and qualitative procedures were used to examine student access to information and their sense of belonging and engagement in learning. Instructors were asked to discuss their approach to teaching and any instructional modifications made to address the needs of deaf learners. Results indicate that deaf students viewed classroom communication and engagement in a similar manner as their hearing peers. Deaf students were more concerned about the pace of instruction and did not feel as much a part of the 'university family' as did their hearing peers. Faculty generally indicated that they made few if any modifications for deaf students and saw support service faculty as responsible for the success or failure of these students. We discuss results of these and additional findings with regard to barriers to equal access and strategies for overcoming these barriers.

Journal Article↗
PubMed1998

The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy.

BACKGROUND: Serine hydroxymethyltransferase (SHMT) is a ubiquitous enzyme found in all prokaryotes and eukaryotes. As an enzyme of the thymidylate synthase metabolic cycle, SHMT catalyses the retro-aldol cleavage of serine to glycine, with the resulting hydroxymethyl group being transferred to tetrahydrofolate to form 5, 10-methylene-tetrahydrofolate. The latter is the major source of one-carbon units in metabolism. Elevated SHMT activity has been shown to be coupled to the increased demand for DNA synthesis in rapidly proliferating cells, particularly tumour cells. Consequently, the central role of SHMT in nucleotide biosynthesis makes it an attractive target for cancer chemotherapy. RESULTS: We have solved the crystal structure of human cytosolic SHMT by multiple isomorphous replacement to 2.65 A resolution. The monomer has a fold typical for alpha class pyridoxal 5'-phosphate (PLP) dependent enzymes. The tetramer association is best described as a 'dimer of dimers' where residues from both subunits of one 'tight' dimer contribute to the active site. CONCLUSIONS: The crystal structure shows the evolutionary relationship between SHMT and other alpha class PLP-dependent enzymes, as the fold is highly conserved. Many of the results of site-directed mutagenesis studies can easily be rationalised or re-interpreted in light of the structure presented here. For example, His 151 is not the catalytic base, contrary to the findings of others. A mechanism for the cleavage of serine to glycine and formaldehyde is proposed.

Binding Sites↗
PubMed1998

Purification, crystallization and preliminary X-ray analysis of human recombinant cytosolic serine hydroxymethyltransferase.

As an enzyme of the thymidylate synthase cycle, serine hydroxymethyltransferase (SHMT) has a key role in nucleotide biosynthesis. Elevated activities of SHMT have been correlated with the increased demand for nucleotide biosynthesis in tumors of human and rodent origin, making this enzyme a novel target for cancer chemotherapy. Here the purification and crystallization of recombinant human cytosolic SHMT are reported. Crystals belong to space group P6222 or P6422 with cell parameters a = b = 155.0, c = 235.5 A and diffract to at least 3.0 A resolution.

Crystallization↗
PubMed1996

Characterisation of a human serine hydroxymethyltransferase pseudogene and its localisation to 1p32.3-33.

The conversion of serine and tetrahydrofolate to glycine and 5,10 methylene tetrahydrofolate by serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) is the major route for the provision of one-carbon units for biosynthetic reactions. SHMT cDNAs have been cloned from both rabbit and man, and a human mitochondrial SHMT gene sequence has recently been reported. We have isolated phage clones containing human genomic sequences homologous to cytosolic SHMT and have found these to contain a processed pseudogene (SHMT-ps1) with a 90% identity to cloned SHMT cDNAs. SHMT-ps1 contains 2335 nt that are homologous to SHMT but it has an additional leader sequence of 203 nt of unknown origin. The complete SHMT-ps1 sequence of 2538 nt is bounded by two 16 nt direct repeats that are characteristic of retroelement insertion sites. Two phage clones containing SHMT-ps1 have been mapped by fluorescence in situ hybridisation to 1p32.3-33. In addition, an SHMT CDNA clone hybridized to the same region and to 17p11.2-12. The latter is consistent with a previous localisation of the gene for cytosolic SHMT.

Base Sequence↗
PubMed1995

Translational control of mammalian serine hydroxymethyltransferase expression.

We have investigated the role of an open reading frame upstream of and overlapping that coding for rabbit cytosolic serine hydroxymethyltransferase in the post-transcriptional regulation of enzyme expression. Elimination of the AUG codon initiating translation of the upstream open reading frame by site-directed mutagenesis (to an AUC codon) was assessed by a transfection assay in COS-1 cells. The mutation relieves translational repression with a 100-fold increase in expressed serine hydroxymethyltransferase activity compared to control-transfected cells and in the absence of any increase in the level of serine hydroxymethyltransferase mRNA. The upstream open reading frame may play a regulatory role in changing levels of expression of serine hydroxymethyltransferase through a translational control mechanism.

Amino Acid Sequence↗
PubMed1993

Hepatic handling of an oral glucose load in suckling and weaned rats.

Changes in the net balance of glucose and lactate across the intestine and liver have been studied in 15-day-old suckling and 25-day-old weaned rats over 60 min following an oral glucose load. The intestinal balance of suckling rats showed a net release of glucose that accounted for 80% of the oral load. By contrast, weaned animals showed a nil glucose balance. The hepatic balance of suckling rats switched rapidly from glucose output to glucose uptake following the oral glucose load, and this was associated with a net glycogen deposition. In weaned animals there was a net glucose release by the liver. The liver of 15-day-old suckling rats is able to extract glucose from the blood when circulating levels are raised under physiological circumstances, as well as the ability to synthesize glycogen.

Administration, Oral↗
PubMed1992

Effects of lactation on the regulation of hepatic metabolism in the rat and sheep: adrenergic receptors and cyclic AMP responses.

The number and coupling efficiency of beta-adrenoceptors in liver membranes and intact hepatocytes of lactating and non-lactating female rats were compared to assess whether or not alterations in this signalling system could contribute towards the changed pattern of hepatic metabolism during lactation. In view of the different adaptations of hepatic metabolism to lactation in ruminants, the adrenergic receptor profile of sheep liver membranes was also determined. Post-receptor responses at two stages 'down-stream' of cyclic AMP generation were also evaluated in rat hepatocytes in response to the beta-adrenergic agonist isoprenaline. No changes in the number of affinity of hepatic beta-adrenoceptors were found in sheep or rats when lactating and non-lactating individuals were compared. Sheep liver was found to have a much greater concentration of beta-adrenoceptors than rat liver, and a much higher ratio of beta:alpha 1. The sensitivity and responsiveness of cyclic AMP generation in response to isoprenaline were similar in hepatocytes prepared from lactating and non-lactating rats, although the response to saturating concentrations of glucagon was diminished in hepatocytes from lactating rats. The activity ratio of cyclic AMP-dependent protein kinase (PK-A) also reacted similarly (in respect of both responsiveness and sensitivity) to isoprenaline in these two groups of hepatocytes. Contrastingly, the sensitivity of rat hepatocyte phosphorylase activity to beta-adrenergic stimulation was greatly diminished during lactation.

Adenylyl Cyclases↗