Cyclic changes in the testis of the brook stickleback Eucalia inconstans (Kirtland)

The cyclic changes in the testis of the five-spined stickleback Eucalia inconstans (Kirtland) were studied histologically. Specimens were trapped between July 1965 and July 1967 in a shallow pond near London, Ontario. A three-dimensional microscopic study showed a main vas deferens and a system of primary, secondary and tertiary tubules. The testis cycle was divided into seven arbitrary stages. Spawning takes place from mid-April to mid-July. This is followed by the division of primary spermatogonia which are located along the walls of the tubules, producing cysts of spermatogonia enclosed in connective tissue which is surrounded by a thin epithelium. Both primary and secondary spermatocytes develop within these cysts. Breakdown of the cysts occurs with the development of spermatids and spermiogenesis occurs while spermatids are free in the tubules. Over-wintering of mature sperm takes place. Development of mature sperm from primary spermatogonia takes about 156 days. Germinal epithelium is absent but primary germ cells are believed to be those cells occupying the spaces between the tubules of the testis. No tissue which might be implicated in hormone production was observed. Phagocytic invasion of the testis has been studied. Massive infiltration by phagocytes is believed to be responsible for the sudden increase in testis weight observed during spawning. These cells ingest sperm nuclei and groups of them have been observed in the lumen of the tubules and the vas deferens, probably on their way out of the body.     

The effect of lower-limb anatomy on knee loads during seated cycling.

Overuse knee joint injuries are the primary injuries to cyclists. Overuse injuries have been intuitively linked to the anatomic structure of the foot because external loads are applied to the foot in cycling. Thus, the structure and function of the foot should dictate in part how the loads are transmitted to the knee joint. Therefore, it was hypothesized that patterns in knee loads are related to the anatomic structure of the foot. To test this hypothesis, peak knee loads (dependent variables) were related to anatomical variables (independent variables) through statistical analyses. This required first the detailed evaluation (i.e. measurement) of the anatomical structure of the foot and leg for 23 subjects. Next, three-dimensional knee joint loads were determined for a standardized riding condition. The results of the statistical analyses indicated that a group of cyclists with the most extreme inversion of the forefoot relative to the transverse plane developed significantly greater average posterior knee force and extensive knee moment. In addition, a number of anatomical variables significantly accounted for the variability in peak values of the posterior force, the extensive moment, the varus/valgus moment and the external axial moment. Based on these results, the hypothesis is accepted.     

How do the macrocyclic lactones kill filarial nematode larvae?

The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system.     

THE GENETIC BASIS OF MALE POTENCY IN VOLVOX CARTERI F. NAGARIENSIS (CHLOROPHYCEAE)1,2

Sexual males of Volvox carteri Stein f. nagariensis Iyengar secrete a hormone which induces sexual rather than asexual development in the next generation. Male recombinants from the original strains isolated from Japan showed an increase in potency of up to 100 times that of the original male clone, with later descendants showing potencies ranging from 100 times to 1/1000 the potency of this male. Potency is defined as the extent to which the hormone produced in 1 ml of medium by one parental spheroid containing 16 male spheroids can be diluted and retain its capacity to induce sexual differentiation. This is recorded as the percent of female response in the tube of limiting dilution, asexual females of the normal female strain being used as assay inoculum in a 1 in 10 dilution series of samples of male fluid containing the sexual hormone. Investigation of the genetic basis for potency in this species included selection of high and low potency male clones and crossing with sib females or backcrossing with original female. Results of the various crosses are interpreted as multigenic system not linked with sex, with more than one genotypic class per dilution level and with more than one genotypic class per apparent phenotypic class. Possible genic interactions are described in their relevance to the biosynthesis of a glycoprotein molecule, the sexual hormone having been characterized as a glycoprotein by Starr and Jaenicke (18).     

In silico screening for identification of fatty acid synthase inhibitors and evaluation of their antiproliferative activity using human cancer cell lines

Abstract

De novo lipogenesis (DNL) by upregulation of fatty acid synthase (FASN) is an important metabolic alteration of cancer cells. FASN is over-expressed in several cancers and is often associated with a high risk of recurrence and poor prognosis. Differential expression of FASN in cancer cells and their normal counterparts leads to the impression that FASN can be an attractive druggable target in cancer therapy. Present study focuses on identification of inhibitors against FASN ketoacyl synthase (KS) domain from Asinex Biodesign compound database using in silico tools. Virtual screening resulted in the identification of two hit compounds BDD27845077 and BDD27845082 with a common core structure. Molecular Docking studies showed that BDD27845077 and BDD27845082 bind at the substrate entry channel of KS domain with GScore –12.03?kcal/mol and –12.29?kcal/mol respectively. Molecular dynamics (MD) simulation of the protein-ligand complexes shows the binding stability of ligands with FASN-KS. In vitro validation of BDD27845082 demonstrated that the compound possesses antiproliferative activity in a panel of human cancer cell lines including MDA-MB-231 (breast cancer), HCT-116 (colon cancer) and HeLa (cervical cancer) with maximum sensitivity against HCT-116 (IC 50?=?25?µM). The study put forward two lead compounds against FASN with favorable pharmacokinetic profile as indicated by virtual screening tools for the development of cancer chemotherapeutics.     

Experience with a hospital-based weight reduction program

A pilot project “Nutritional Service for Weight Reduction”, utilizing allied health personnel, was organized by the Departments of Medicine and Dietetics at the Calgary General Hospital. Body measurements and biochemical tests were required at the beginning and end of the 12-week program. Meetings were held at which the subjects submitted their weekly food record, received counselling by nutritionists, and attended lectures on physiology, metabolism of food, nutrition and the importance of exercise. Thirty-one subjects completed the program. All lost weight, the total for the group being 197 kg. At the first follow-up meeting, 17 subjects showed further weight loss, three maintained their weight and 11 regained some weight.