Inactivation of a testis-specific Lis1 transcript in mice prevents spermatid differentiation and causes male infertility

Lis1 protein is the non-catalytic component of platelet-activating factor acetylhydrolase 1b (PAF-AH 1B) and associated with microtubular structures. Hemizygous mutations of the LIS1 gene cause type I lissencephaly, a brain abnormality with developmental defects of neuronal migration. Lis1 is also expressed in testis, but its function there has not been determined. We have generated a mouse mutant (LIS1GT/GT) by gene trap integration leading to selective disruption of a Lis1 splicing variant in testis. Homozygous mutant males are infertile with no other apparent phenotype. We demonstrate that Lis1 is predominantly expressed in spermatids, and spermiogenesis is blocked when Lis1 is absent. Mutant spermatids fail to form correct acrosomes and nuclei appear distorted in size and shape. The tissue architecture in mutant testis appears severely disturbed displaying collapsed seminiferous tubules, mislocated germ cells, and increased apoptosis. These results provide evidence for an essential and hitherto uncharacterized role of the Lis1 protein in spermatogenesis, particularly in the differentiation of spermatids into spermatozoa.     

Studies on the agglutinating activity of pancreatic extracts and its relevance to function

Summary Agglutination of washed rabbit erythrocytes caused by pancreatic acinar cell extract was inhibited by glucose, maltose and cellobiose. Process of elimination and purification divulged that the acinar cell enzyme -amylase was responsible for attributing the agglutinin activity. Assay of enzyme and agglutinin activity data of different fractions of re-purified -amylase eluted from HPLC column showed that both the activity resides in the same fraction which suggests that the enzyme binds to the glucosyl residues of the rabbit erythrocytes via the carbohydrate binding/catalytic sites. Similar properties of other glycosidases were also noted.     

Adrenomedullary hormonal stimulation and hyperglycemia following intermale aggression in the bandicoot rat

The aim of the present investigation is to evaluate adrenomedullary hormones and blood glucose responses to intermale aggression in the bandicoot rat. Aggression elicited a rise in adrenaline and noradrenaline content of the adrenal gland and in blood glucose level in the subordinate rats. No significant change was marked in the dominant rats after aggression. It is suggested that during aggression the subordinate rats suffered from psychosomatic stress that resulted in hyperactivity of the adrenal medulla and consequently hyperglycemia.     

Effect of DDVP (insecticide) on citric acid fermentation in Aspergillus niger

The effect of the insecticide 2,2-dichlorovinyldimethylphosphate (DDVP) on citric acid fermentation in Aspergillus niger was studied. The appearance of citric acid in the culture medium was increasingly delayed with increasing concentration of the insecticide, and at concentrations at or above 80 μg/ml medium, citric acid production was first observed after 192 h incubation, compared with 96 h in the control flasks. The timing of the maximum rate of citric acid formation was also similarly delayed. DDVP also resulted in a delay in the utilization of inorganic phosphate by the cultures.     

Enzymatic conversion of bilirubin monoglucuronide to diglucuronide by rat liver plasma membranes.

Formation of bilirubin monoglucuronide from unconjugated bilirubin requires a microsomal enzyme, UDP-glucuronate glucuronyltransferase (EC 2.4.1.17). Conversion of bilirubin monoglucuronide to bilirubin diglucuronide, the major bilirubin conjugate in bile, was studied in subcellular fractions of rat liver. The highest specific activity for bilirubin diglucuronide formation occurred in a fraction highly enriched in plasma membranes. Studies of reaction stoichiometry and utilization of UDP-D-[14C]glucuronic acid revealed that conversion of bilirubin monoglucuronide to bilirubin diglucuronide is not catalyzed by UDP-glucuronyltransferase, and results from transglucuronidation of bilirubin monoglucuronide, with formation of bilirubin diglucuronide and unconjugated bilirubin. When unconjugated bilirubin was infused intravenously into rats at rates exceeding the maximal hepatic excretory capacity, bilirubin monoglucuronide accumulated in serum and bilirubin diglucuronide was found exclusively in bile as the predominant bilirubin metabolite. These results suggest that formation of bilirubin diglucuronide occurs at the surface membrane of the liver cell. Conversion of bilirubin monoglucuronide to bilirubin diglucuronide may play a role in the transport of bilirubin glucuronides from liver to bile.     

Differentials of fertility between polygynous and monogamous marriages in rural Bangladesh

This paper discusses polygynous marriages in rural Bangladesh, using marital status and birth registration data from the Demographic Surveillance System (DSS) of the International Center for Diarrheal Disease Research, for the period 1975-79. Of all the marriages recorded during this period about 5% were polygynous. To identify the women polygynously married, 1974 census data of the DSS area were used. The difference in age at marriage between the polygynous groom and his subsequent wife was 15 years on average. The socioeconomic indicators studied were education, occupation and area of dwelling space. In general, these indicators between women in monogamous marriages were significantly higher than between the women in polygynous unions. During the period 1976-79, 863 polygynous marriages were recorded (4.9% of all marriages in the study area). Polygynous marriages were found to be less frequent among men with 2ndary and higher levels of education. The highest proportion of polygynous marriages occurred among husbands with no schooling or Koranic education. The general fertility rate of women in monogamous marriages was significantly higher than for women in polygynous marriages, overall and in all age groups except 20-24. During the period 1975-79, the mean number of liveborn children for monogamous women was higher than that of polygynous women.     

Oxidation of N-Nitrosoalkylamines by Human Cytochrome P450 2A6: SEQUENTIAL OXIDATION TO ALDEHYDES AND CARBOXYLIC ACIDS AND ANALYSIS OF REACTION STEPS*

Cytochrome P450 (P450) 2A6 activates nitrosamines, including N,N-dimethylnitrosamine (DMN) and N,N-diethylnitrosamine (DEN), to alkyl diazohydroxides (which are DNA-alkylating agents) and also aldehydes (HCHO from DMN and CH₃CHO from DEN). The N-dealkylation of DMN had a high intrinsic kinetic deuterium isotope effect (^Dk_app ∼ 10), which was highly expressed in a variety of competitive and non-competitive experiments. The ^Dk_app for DEN was ∼3 and not expressed in non-competitive experiments. DMN and DEN were also oxidized to HCO₂H and CH₃CO₂H, respectively. In neither case was a lag observed, which was unexpected considering the k_cat and K_m parameters measured for oxidation of DMN and DEN to the aldehydes and for oxidation of the aldehydes to the carboxylic acids. Spectral analysis did not indicate strong affinity of the aldehydes for P450 2A6, but pulse-chase experiments showed only limited exchange with added (unlabeled) aldehydes in the oxidations of DMN and DEN to carboxylic acids. Substoichiometric kinetic bursts were observed in the pre-steady-state oxidations of DMN and DEN to aldehydes. A minimal kinetic model was developed that was consistent with all of the observed phenomena and involves a conformational change of P450 2A6 following substrate binding, equilibrium of the P450-substrate complex with a non-productive form, and oxidation of the aldehydes to carboxylic acids in a process that avoids relaxation of the conformation following the first oxidation (i.e. of DMN or DEN to an aldehyde).     

Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents

A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC²), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis.