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K Franks

Publications and source records attributed to K Franks.

13 recordsLinked to original sources
PubMed2006

Statistical modeling of biomedical corpora: mining the Caenorhabditis Genetic Center Bibliography for genes related to life span.

BACKGROUND: The statistical modeling of biomedical corpora could yield integrated, coarse-to-fine views of biological phenomena that complement discoveries made from analysis of molecular sequence and profiling data. Here, the potential of such modeling is demonstrated by examining the 5,225 free-text items in the Caenorhabditis Genetic Center (CGC) Bibliography using techniques from statistical information retrieval. Items in the CGC biomedical text corpus were modeled using the Latent Dirichlet Allocation (LDA) model. LDA is a hierarchical Bayesian model which represents a document as a random mixture over latent topics; each topic is characterized by a distribution over words. RESULTS: An LDA model estimated from CGC items had better predictive performance than two standard models (unigram and mixture of unigrams) trained using the same data. To illustrate the practical utility of LDA models of biomedical corpora, a trained CGC LDA model was used for a retrospective study of nematode genes known to be associated with life span modification. Corpus-, document-, and word-level LDA parameters were combined with terms from the Gene Ontology to enhance the explanatory value of the CGC LDA model, and to suggest additional candidates for age-related genes. A novel, pairwise document similarity measure based on the posterior distribution on the topic simplex was formulated and used to search the CGC database for "homologs" of a "query" document discussing the life span-modifying clk-2 gene. Inspection of these document homologs enabled and facilitated the production of hypotheses about the function and role of clk-2. CONCLUSION: Like other graphical models for genetic, genomic and other types of biological data, LDA provides a method for extracting unanticipated insights and generating predictions amenable to subsequent experimental validation.

Animals↗
PubMed2002

The effect of MgO on the solubility behavior and cell proliferation in a quaternary soluble phosphate based glass system.

This paper presents a systematic study of the MgO-CaO-Na(2)O-P(2)O(5) glass system, which has great potential to be used as temporary hard and soft tissue implant materials. An overall study of solubility behavior of ternary and quaternary-based phosphate glass system have been carried out in order to understand the out-leaching progress of different ions and to determine their effect on cell proliferation. Originally, soluble phosphate based glasses within the ternary glass system of Na(2)O-CaO-P(2)O(5) have been developed to create a simple baseline system. This paper, however, presents the development of this system by introducing magnesium oxide as a partial calcium oxide substitute and solubility behaviors as well as cell studies have been carried out to check the effect on magnesium ions. Glasses have been prepared via standard glass melting techniques and their solubility behavior has been tested in distilled water via simple weight loss, pH and ion measurements. The way the glasses dissolve is an inverse exponential behavior which is mirrored by the calcium ion release. Other ions show a less exponential behavior. The MTT test has been used to check preliminary in vitro studies on a human MG63 cell line and the result indicates that cell proliferation is increased for glasses with minimal CaO substitution.

Journal Article↗
PubMed2001

Investigation of thermal parameters and crytallisation in a ternary CaO-Na2O-P2O5-based glass system.

This paper presents the results of a study of the thermal properties of a range of phosphate-based glasses in the system CaO-Na2O-P2O5. The glasses had a fixed P2O5 content of 45 mol% and the CaO:Na2O ratio was varied. The glasses were produced and ground and their thermal properties measured using a Setaram differential thermal analyser (DTA). Initial data showed that for the high Na2O containing glass, NaPO3 forms and a second unidentified phase that is probably calcium rich. In the middle compositional region, multiple phases precipitated out and were identified as NaPO3 and Na4Ca(PO3)6. For the high CaO content glasses, Na4Ca(PO3)6 was the only phase formed. Further studies were carried out to examine whether the phases were bulk or surface nucleating, by grinding the samples to different particle sizes. From this data, it is evident that the NaPO3 forms via a bulk nucleation mechanism and that Na4Ca(PO3)6 forms via surface nucleation. The factors controlling this precipitation process are discussed and ionic radius as a controlling factor is hypothesised.

Calcium Compounds↗
PubMed2001

Investigation of the solubility and ion release in the glass system K2O-Na2O-CaO-P2O5.

Glasses from the quaternary glass system K2O-Na2O-CaO-P2O5 were produced by standard glass forming techniques. The compositions were limited by fixing the P2O5 at 45 mol%, fixing the CaO content at either 20, 24 or 28 mol%. The K2O and Na2O made up the residual varying from 0 to 25 mol% K2O. General trends showed that with increasing CaO content, the glasses showed a decrease in solubility as expected. For a single system of fixed CaO content, with increasing K2O content, there was an increase in solubility. This was seen at all three CaO contents. All the glasses showed an initial increase in pH followed by a gradual decrease with time and this was accounted for by the initial release of Na+ ions into solution. For the ion release curves, for all fixed CaO contents, the glass with 0 mol% K2O showed the lowest Ca2+ release. This was accounted for as being due to the low solubility compared to the K2O containing glasses. The Na+ release appeared anomalous, as it was higher than all the K2O containing glasses. Even though the glasses with 0 mol% K2O showed the lowest solubility, the amount of Na+ contained in the glass was high, hence the high levels of release.

Glass↗
PubMed2000

Development of soluble glasses for biomedical use Part II: the biological response of human osteoblast cell lines to phosphate-based soluble glasses.

Soluble glasses are considered to be of potential clinical value in orthopaedic and dental surgery. However, the biological response to these materials is not well understood. To determine the effects of these glasses, two human osteoblast cell lines, MG63 and HOS (TE85), were incubated in vitro in the presence of increasing concentrations of extracts of the glasses. The effects of the extracts on cell growth was measured using the MTT assay and an ELISA assay was used to measure the expression of bone sialoprotein (BSP), osteonectin (ON) and fibronectin (FN), antigens which play a fundamental part in the integrity and function of hard connective tissue. The results showed that the proliferation of the cells was adversely affected only by the more soluble glasses, which also down-regulated the expression of the bone-associated proteins. In contrast, the extract of the glass with the lowest dissolution rate, which contains relatively elevated levels of Ca2+, was found to enhance bone cell growth and antigen expression. These findings suggest that the compositions of these glasses at least partly determine the response of cells and thus, that the glasses could be modified to elicit a more optimal biological response and clinical efficacy.

Journal Article↗
PubMed2000

Development of soluble glasses for biomedical use Part I: in vitro solubility measurement.

In this study soluble glasses have been developed for biomedical applications containing P2O5 as a network former and CaO and Na2O as modifiers. This study shows that as expected, the glasses have an inverse exponential relationship between solubility and CaO content. Furthermore, there is evidence for compositional related non-linearity in the dissolution of the glasses with time. This is thought to be due to either layer formation on the glass surface hindering ion diffusion, ion exchange process or change of ionic strength of the solution. Bioactivity of these glasses is indicated by the formation of a brushite precipitate, a precursor to apatite formation. Further evidence for bioactivity is also presented in the second part of this paper.

Journal Article↗
PubMed1992

Paramagnetic probes attached to a light chain on the myosin head are highly disordered in active muscle fibers.

We have measured the orientation of a region of the myosin head, close to the junction with the rod, during active force generation. Paramagnetic probes were attached specifically to a reactive cysteine (Cys 125) of purified myosin light chain 2 (LC2) and exchanged into myosin heads in glycerinated rabbit psoas muscle. Electron paramagnetic resonance spectroscopy was used to monitor the orientation of the probes. Previous work has shown that the LC2 bound spin probes are significantly ordered in rigor and muscle in the presence of adenosine diphosphate (ADP). In contrast, there is a nearly random angular distribution in relaxed muscle. We show here that during the generation of isometric tension, all of the LC2 bound spin probes (98 +/- 1.6%) show an angular distribution similar to that of relaxed muscle. These findings contrast with results obtained from probes attached to Cys 707 on the cross-bridge, located close to the actin binding site, where, during active force generation, a proportion of the spin probes were ordered as in rigor, whereas the remaining probes were disordered as in relaxation. To test the hypothesis that this ordered component is due to modification of Cys 707, we measured the spectra obtained from probes attached to LC2 in fibers modified at Cys 707. The modification of Cys 707 did not produce an ordered component in these spectra. The absence of an ordered component at the LC2 site limits the populations of some states in active fibers. An actin/myosin/ADP state is thought to be the major force-producing state. Our present results show that the populations of states with ordered probes on LC2 are < 2% in active fibers; thus, the major force-producing state is different from the one obtained by addition of ADP to rigor fibers.

Adenosine Triphosphate↗
PubMed1991

Orientation of spin-labeled light chain-2 exchanged onto myosin cross-bridges in glycerinated muscle fibers.

Electron paramagnetic resonance (EPR) spectroscopy has been used to study the angular distribution of a spin label attached to rabbit skeletal muscle myosin light chain 2. A cysteine reactive spin label, 3-(5-fluoro-2,4-dinitroanilino)-2,2,5,5- tetramethyl-1-pyrrolidinyloxy (FDNA-SL) was bound to purified LC2. The labeled LC2 was exchanged into glycerinated muscle fibers and into myosin and its subfragments. Analysis of the spectra of labeled fibers in rigor showed that the probe was oriented with respect to the fiber axis, but that it was also undergoing restricted rotations. The motion of the probe could be modeled assuming rapid rotational diffusion (rotational correlation time faster than 5 ns) within a "cone" whose full width was 70 degrees. Very different spectra of rigor fibers were obtained with the fiber oriented parallel and perpendicular to the magnetic field, showing that the centroid of each cone had the same orientation for all myosin heads, making an angle of approximately 74 degrees to the fiber axis. Binding of light chains or labeled myosin subfragment-1 to ion exchange heads immobilized the probes, showing that most of the motion of the probe arose from protein mobility and not from mobility of the probe relative to the protein. Relaxed labeled fibers produced EPR spectra with a highly disordered angular distribution, consistent with myosin heads being detached from the thin filament and undergoing large angular motions. Addition of pyrophosphate, ADP, or an ATP analogue (AMPPNP), in low ionic strength buffer where these ligands do not dissociate cross-bridges from actin, failed to perturb the rigor spectrum. Applying static strains as high as 0.16 N/mm2 to the labeled rigor fibers also failed to change the orientation of the spin label. Labeled light chain was exchanged into myosin subfragment-1 (S1) and the labeled S1 was diffused into fibers. EPR spectra of these fibers had a component similar to that seen in the spectra of fibers into which labeled LC2 had been exchanged directly. However, the fraction of disordered probes was greater than seen in fibers. In summary, the above data indicate that the region of the myosin head proximal to the thick filament is ordered in rigor, and disordered in relaxation.

Actins↗
PubMed1988

The inhibition of rabbit skeletal muscle contraction by hydrogen ions and phosphate.

1. The effects of phosphate and protons on the mechanics and energetics of muscle contraction have been investigated using glycerinated rabbit psoas muscle. 2. Fibres were fully activated by addition of Ca2+ (pCa 4-5) at 10 degrees C. The velocities of contraction were measured in isotonic load clamps, and the velocities of unloaded fibres were measured by applying a series of step changes in fibre length. Fibre ATPase activity was monitored using an enzyme system to couple ADP production to reduced nicotinamide-adenine dinucleotide (NADH) and measuring the depletion of NADH by optical density. 3. At pH 7.0 and 3 mM-phosphate, isometric tension (P0) was 13.2 +/- 0.9 N/cm (mean +/- S.E.M., n = 10 observations), the maximum contraction velocity (Vmax) was 1.63 +/- 0.05 lengths/s (n = 5) and the ATPase activity was 1.27 +/- 0.12 s-1 myosin head-1 (n = 35). Increasing phosphate from 3 to 20 mM at pH 7.0 does not affect Vmax, causes a small decrease in the ATPase activity (15-20%) and decreases P0 by approximately 20%. Changing pH from 7 to 6 at 3 mM-phosphate decreases P0 by 45% and both Vmax and ATPase activity by 25-30%. The effects of changing both pH and phosphate were approximately additive for all parameters measured. The inhibition of these parameters by low pH and high concentration of phosphate was reversible. 4. The force-velocity relation was fitted by the Hill equation using a non-linear least-squares method. The value of the parameter which describes the curvature, a/P0, was 0.20. The curvature of the force-velocity relation was not changed by addition of phosphate or by changes in pH. 5. These data provide information on both the kinetics of the actomyosin interaction and on the process of muscle fatigue. The data are consistent with models of cross-bridge kinetics in which phosphate is released within the powerstroke in a step involving a rapid equilibrium between states. The inhibition by protons is more complex, and may involve less specific effects on protein structure. 6. During moderate fatigue of living skeletal muscle, MgATP concentration is known to remain approximately constant at 4 mM, phosphate to increase from 3 to 20 mM, and protons from 0.1 to 1 microM. The data suggest that much of the inhibition of P0 observed during moderate fatigue can be explained by the increased levels of phosphate and protons, and that much of the inhibition of fibre Vmax and ATPase activity can be explained by the increase in protons.

Adenosine Triphosphatases↗
PubMed1984

Myosin phosphorylation decreases the ATPase activity of cardiac myofibrils.

Our previous work showed that myosin phosphorylation decreased the ATPase activity of skeletal muscle myofibrils that were lightly fixed with glutaraldehyde. The fixation process prevented sarcomere shortening and destruction of the ordered filament array upon the addition of ATP. We have now extended these results to myofibrils prepared from hearts of rabbits, dogs and rats. Myofibrils were phosphorylated by incubation with myosin light chain kinase, calmodulin and either ATP-gamma s or ATP, for 15 minutes at 25 degrees C. The extent of myosin light chain phosphorylation was 50% to 80%. The ATPase activity of unphosphorylated myofibrils was not altered by reaction with 0.01% glutaraldehyde for 5 minutes at 0 degrees C, and the ATPase activity of unfixed myofibrils was not changed by phosphorylation. However, phosphorylation decreased the ATPase activity of fixed myofibrils by 50%. The effect on myocardial myofibrillar ATPase activity of phosphorylation was similar in the three animal species. These results suggest that in both skeletal and cardiac muscle, myosin phosphorylation decreases the rate of cross-bridge cycling resulting in decreased energy expenditure. It also appears that the effect of myosin light chain phosphorylation on ATPase activity requires an ordered myofilament structure.

Adenosine Triphosphatases↗