Huntington's disease in a Sudanese family from Khartoum

Typical Huntington's disease (HD) was studied in a 40-year-old Sudanese man from Khartoum. He had 51 CAG repeats in the Huntington's gene. It is suspected that his mother and his 16-year-old son (both deceased) were also affected. Up to now, there had only been anecdotal evidence of HD in the Sudanese.     

Analysis of several key active site residues of ricin A chain by mutagenesis and X-ray crystallography.

Active site residues of ricin A chain were analyzed by site-directed mutagenesis and X-ray diffraction to help assess their roles in the mechanism of action of this toxic N-glycosidase enzyme. Arg180 is thought, from X-ray studies, to protonate the adenine substrate at N3; this facilitates bond cleavage and is crucial to the mechanisms of action. The residue was converted to Gln and initial rate data measured. Km for the mutant is not significantly affected, increasing only 2-fold. The kcat, however, is decreased approximately 1000-fold. This is consistent with a simple interpretation that Arg180 is involved more in transition state stabilization than in substrate binding. Tyrosines 80 and 123 are known from X-ray models to stack on either side of the substrate adenine ring. When they were each converted to serine overall activity was reduced 160- and 70-fold respectively against ribosomes from Artemia salina. These effects are each approximately 10 times greater than when the residues were previously converted to phenylalanines. Sufficient protein for the Tyr80 to Phe mutant was obtained to carry out an X-ray analysis. Together with mutagenesis data, the structure suggests that the invariance of the two active site Tyr residues is largely caused by structural stability.     

Lipids of Angiostrongylus cantonensis (Nematoda: Metastrongyloidea): a comparison between young adults and gravid worms

1. All major classes of lipids were found in the young adults in brain (22 days post-infection) and gravid Angiostrongylus cantonensis in lung of rats (34 days post-infection) comprising approximately 60% of phospholipids, 30% of neutral lipids and the rest, glycolipids. 2. The relative composition of phospholipids were quite similar between worms from the two different habitats, with phosphatidylcholine predominating. The glycolipid profiles were also similar. 3. More neutral lipids in the worms from brain existed as cholesterol and cholesterol esters than those from the lung. More than 20% of the fatty acids in these lipids of the brain were found as C10-C14 acids while oleic acid was the main component in the lung worm.     

Ability of progesterone to reverse anti-androgen (hydroxyflutamide)-induced interference with the preovulatory LH surge and ovulation in PMSG-primed immature rats

In Exp. 1, PMSG was injected to 26-day-old prepubertal rats to induce ovulations. On Day 2 (2 days later, the equivalent of the day of pro-oestrus) they received at 08:00 h 5 mg hydroxyflutamide or vehicle and at 12:00 h 2 mg progesterone or testosterone or vehicle. Animals were killed at 18:00 h on Day 2 or at 09:00 h on Day 3. Progesterone but not testosterone restored the preovulatory LH surge and ovulation in hydroxyflutamide-treated rats. In Exp. 2, 2 mg progesterone or testosterone were injected between 10:30 and 11:00 h on Day 2, to advance the pro-oestrous LH surge and ovulation in PMSG-primed prepubertal rats. Injection of hydroxyflutamide abolished the ability of progesterone to advance the LH surge or ovulation. Testosterone did not induce the advancement of LH surge or ovulation. In Exp. 3, ovariectomized prepubertal rats implanted with oestradiol-17 beta showed significantly (P less than 0.01) elevated serum LH concentrations at 18:00 h over those observed at 10:00 h. Progesterone injection to these animals further elevated the serum LH concentrations at 18:00 h, in a dose-dependent manner, with maximal values resulting from 1 mg progesterone. Hydroxyflutamide treatment significantly (P less than 0.003) reduced the serum LH values in rats receiving 0-1 mg progesterone but 2 mg progesterone were able to overcome this inhibition. It is concluded that progesterone but not testosterone can reverse the effects of hydroxyflutamide on the preovulatory LH surge and ovulation. It appears that hydroxyflutamide may interfere with progesterone action in induction of the LH surge, suggesting a hitherto undescribed anti-progestagenic action of hydroxyflutamide.     

Cell Therapy as a Way to Correct Impaired Neurogenesis in the Adult Brain in a Model of Alzheimer’s Disease

Journal of Evolutionary Biochemistry and Physiology - This work is based on the hypothesis of an impairment in neurogenesis during aging, which may be one of the causes of neurodegenerative...