James McFarlane

The hormone leptin, which is thought to be primarily produced by adipose tissue, is a polypeptide that was initially characterized by its ability to regulate food intake and energy metabolism. Leptin appears to signal the status of body energy stores to the brain, resulting in the regulation of food intake and whole-body energy expenditure. Subsequently, it was recognized as a cytokine with a wide range of peripheral actions and is involved in the regulation of a number of physiological systems including reproduction. In the fed state, leptin circulates in the plasma in proportion to body adiposity in all species studied to date. However other factors such as sex, age, body mass index (BMI), sex steroids and pregnancy may also affect leptin levels in plasma. In pregnant mice and humans, the placenta is also a major site of leptin expression. Leptin circulates in biological fluids both as free protein and in a form that is bound to the soluble isoform of its receptor or other binding...

The sorption of carbon tetrachloride, ethylene dibromide, and trichloroethylene in two silty clay loam soils and aluminium (Al(3+)) or calcium (Ca(2+)) saturated montmorillonite clay was studied. When the adsorbents were exposed to environmental levels of these chemicals (10 to 1000 ppb in water) the amounts of each of the chemicals sorbed were 6% or less of that available except for a 17% sorption of trichloroethylene by Al-saturated clay. In the case of the Ca-saturated clay, there was no apparent sorption of carbon tetrachloride or trichloroethylene. When soil sorption was normalized based on the soil organic carbon content (K oc) a correlation was found between the K oc, water solubility, and octanol/water partitioning coefficients of the chemicals. However, carbon tetrachloride did not behave according to with the predicted relationships.

Catalytic reactions are limited in their turnover by certain steps in the cycle. We present a free, open-source, web-based interface to generate visualizations of the rate constants of various steps in the cycle. Population of a web form using known data will generate a highly customizable graphic for annotation by the user to represent their chemistry.

Epigenetic regulation of gene expression is in part controlled by post-translational modifications on histone proteins. Histone methylation is a key epigenetic mark that controls gene transcription and repression. There are five human polycomb paralog proteins (Cbx2/4/6/7/8) which use their chromodomains to recognize trimethylated lysine 27 on Histone 3 (H3K27me3). Recognition of the methyllysine side chain is achieved through multiple cation-pi interactions within an ‘aromatic cage’ motif. Despite high structural similarity within the chromodomains of this protein family, they each have unique functional roles and are linked to different cancers. Selective inhibition of different CBX proteins is highly desirable for both fundamental studies and potential therapeutic applications. We will report on a series of peptidic inhibitors that selectively target certain polycomb paralogs. We have identified peptidic scaffolds with sub-micromolar potency, and will report examples that are pan...

The work in this submission presents a molecular simulation technique that is able to overcome induced-fit binding issues with a uniquely challenging binding site. This method differs from commercially available methods in that we use a combined software approach that allows users to patch together inexpensive and academically available programs. Our method also differs fundamentally in how the potential energy of the interaction is explored and lends itself to the success in modeling our test system. As an added benefit, our test system is CBX8, an epigenetic reader protein and speculative target for chemotherapy. The method was not only successful in matching crystal structure data, but uncovered a number of induced-fit structural features of the binding motif that are useful in the design of potential inhibitors for this protein.

This retrospective cohort study compared the diagnostic utility (sensitivity, specificity and negative predictive value (NPV)) of the age-times-10 adjusted d-dimer cut-off used in combination with the original and simplified Well's pulmonary embolism (PE) scores and the original and simplified revised Geneva scores to identify patients in whom PE is classified as unlikely according to each score. The PE risk scores performed similarly with high sensitivity (97.6, 97.1, 96.9 and 97.1% respectively) and NPV (99.3, 99.3, 99.2 and 99.2% respectively). Each missed only one PE. The age-times-10 age-adjusted d-dimer assay cut-off performed similarly with each of the clinical risk scores tested with high sensitivity and NPV.

The importance of natural biotype differences affecting insect pest status and consequent pest management is indicated and discussed, including the occurrence of such differences in association with resistance to pesticides. Data on observed differences, especially those affecting the capacity to damage stored grain, are presented for Rhyzopertha dominica, Prostephanus truncatus, Sitophilus oryzae and Tribolium castaneum. Simple tests to discriminate between biotypes, in this capacity and in some other characteristics, are briefly described. It is proposed that such tests should be included where pest management improvements are a research objective, and that their potential usefulness in field situations, where the information obtained may be especially relevant, should be more widely considered.

ABSTRACT Bone morphogenetic proteins (BMPs) regulation of ovarian function has been investigated in several animal models, demonstrating their role in primordial germ cell formation, primordial-to-primary follicle recruitment, follicle development, steroidogenesis and ovulation. However, the mechanism by which BMPs regulate individual processes of ovarian function is not well understood. The aim of this study was to investigate the effect of the BMP receptor mutation in Booroola sheep on primordial follicle formation and rate of recruitment in comparison to that in normal merino sheep in vivo. Whole ovaries from Booroola and merino sheep at birth, 1.5 years and 5 years of age were obtained by bilateral ovariectomy and processed for the quantification of primordial and primary follicles using computerised stereological methods(Stereo Investigator Software Version 7, MicroBrightField, Inc.)and JMP 6 statistical package (SAS Institute Inc, 2005). Regardless of animal strain, the overall absolute number of primordial and primary follicles per ovary of newborn sheep was considerably higher than in the 1.5 and 5-year old ewes. Log transformed data analyses revealed that the total number of primordial follicles in newborn Booroola sheep was significantly (P=0.0065) lower than in merino of the same age. At 1.5 years a trend showing a considerable reversal in the number of primordial follicles was observed in Booroola ewes, which then significantly (p<0.0036)increased at 5 years of age. The rate of primordial follicle recruitment was substantially lower in Booroola ewes compared with that in merino, as reflected by the difference in the absolute number of primordial follicles remaining at 1.5 and 5 years of age. Immediately after birth, the mean total number of primordial follicles in Booroola strain was only 36% of that present in the merino strain. This ratio became 207% and 367% at 1.5 and5 years, respectively. The ratios of primordial follicle consumption in Booroola ewes were 51% and 66% up to the age of 1.5 and 5years respectively compared to 92% and 97% of primordial follicles have been used in merino ewes. On the other hand, the mean numbers of primary follicles per ovary in newborn animals was similar in both sheep strains. However, at 1.5 years, Booroola ewes possess more primary follicles than merino, and the absolute number of primary follicles present at 1.5 years was equal to26% of the number present at birth, compared with only 8% of primary follicles present in merino ewes. At 5 years of age the primary follicles were not counted in either animal strain. These findings suggest that attenuation of the intra ovarian signalling pathway of BMPs may in fact be a successful means of rationalizing follicle consumption, preventing unnecessary loss of follicles from the initial follicle pool, hence increasing reproductive age and fertility.

The aim of this pilot study was to attempt to define a set of equations from histological observations of tissue affected with coeliac disease (CD) to predict Marsh score. Tissue from 15 patients with untreated CD, 6 patients with treated CD and 9 healthy control patients were stained using the standard H&E, Giemsa's staining for tissue sections and Alcian Blue protocols. A number of histological measures were then taken from each section and the data was used to ultimately design a set of linear predictive algorithms to calculate Marsh score. Using MANOVA and discriminant analysis, two linear functions were defined which could accurately predict the Marsh score of patients 62.5% (full Marsh score) to 79.2% (simplified Marsh score) of the time. This pilot study has shown that a set of objective histological measures can be used to define algorithms to predict Marsh score in CD patients and also monitor treatment compliance and progression.

We did not discover the phenomenon so described; it had been evident in various ways to various people for perhaps a century; it is now, I suppose, apparent to most. Or at least most now see that in the nineteenth century, Western Man moved across a rubicon which, if as ...

The small physical size of self assembled quantum dots gives rise to pronounced Coulomb interactions within the dots. By studying different excitons in the same quantum dot we show that the Coulomb interactions significantly alter the radiative recombination lifetime. The lifetime changes are larger upon charging from the neutral exciton to the positively charged exciton than from charging from the neutral exciton to the negatively charged exciton. This is attributed to a frozen electron wavefunction and a non-frozen hole wavefunction, leading to a non-perturbative hole-hole Coulomb interaction. Theoretical calculations based on a path integral quantum Monte-Carlo approach show good agreement between experiment and theory.

The influence of transpiration rate on the uptake and translocation of two industrial waste compounds, phenol and nitrobenzene, and one pesticide, 5-bromo-3-sec-butyl-6-methyluracil (bromacil), was examined. Carbon-14 moieties of each compound were provided separately in hydroponic solution to mature soybean plants maintained under three humidity conditions. The uptake of each compound was determined by monitoring the removal of ¹⁴C from the

Initial studies on inhibin, activin and follistatin focussed on their role as regulators of adult gonadal function via feedback regulation of anterior pituitary hormones and via intragonadal control of steroid hormones. The discovery of isoforms of follistatin which are either secreted or retained on the cell surface and which bind activin and, to a lesser extent, inhibin adds a further dimension to the regulation of these peptides. More recently, the cloning of inhibin and activin, and the observation of their close homology to the transforming growth factor-beta family of peptides, has led to an interest in their possible role as growth and differentiation factors. Activin, inhibin and follistatin are expressed in embryonic and fetal tissues, as well as in the placenta. However, although activin is a potent regulator of growth and differentiation in a number of cell types, their role in embryonic and fetal development has yet to be established. High concentrations of inhibin have been observed in the fetal gonads, particularly the testes, and in the fetal adrenals of a number of species and a sex difference in fetal plasma concentrations has also been observed. Although the stimulus for high concentrations of inhibin in the fetus is not know, they are associated with decreased testicular testosterone and a decrease in the concentration of circulating follicle-stimulating hormone (FSH); this suggests that, as in the adult, inhibin may be involved in the regulation of fetal testicular androgen and pituitary FSH secretion during late gestation. The recent reports of elevated concentrations of inhibin and, particularly, activin in amniotic fluid during late gestation and its ability to stimulate the production of prostaglandin E2 by fetal membranes provides yet another potential role for this hormone in the regulation of events leading to parturition.

... two back-to-back development cycles have resulted in the recent availability of the low cost ($25K ... commenced development of a navigator which will use bottom contour maps for navigation in much ... sensor platform For a ROV system operated in a vertical position relative to the ...

Studies have shown that follistatin may be involved in the regulation of ovarian development, pregnancy and parturition. The aim of the present study was to measure follistatin levels in maternal plasma and foetal fluids during pregnancy and parturition in sheep. Using a previously described follistatin radioimmunoassay, we found that follistatin in foetal plasma and allantoic fluid was higher in the female than in the male at days 50-75 of gestation. Follistatin concentrations in maternal plasma declined from -9 to -3h before the completion of lamb delivery, and increased from 21 to 39 h after parturition. These results suggest that follistatin may play a role in femaleness development, and that follistatin may be involved in the mechanism of normal parturition and in regulation of the tissue repair after parturition.

In the last decade, an increasing number of Americans use the web to access information and services. Government agencies have responded to their citizens' need by providing a substantial array of online services through websites to reach a wider spectrum of the population. However, in recent years, focus on the web has shifted from online services to information exchange and

Stick-slip friction in hydraulic actuators is a problem for accuracy and repeatability. Friction compensation has been approached through various control techniques. This work presents an alternative solution, namely, friction avoidance. By rotating the piston and rod the Stribeck region of the friction-velocity curve is avoided and the axial friction opposing the piston movement is linearized, making control more accurate and