Relationship of cloacal gland with testes, testosterone and fertility in different lines of male Japanese quail

An attempt has been made to investigate the relationship of cloacal gland with testes, testosterone and fertility in different lines of Japanese quail (Coturnix coturnix japonica). For this study, three lines of healthy adult male Japanese quails (<12 weeks) viz., heavy body weight (HB), white breasted (WB), and white egg shell (WES) were taken. They were housed in individual cages under uniform husbandry conditions and were provided with normal quail breeder ration and water ad libitum, with 14 h light/day. The experimental birds were selected from each of these three lines and categorized into different groups (15 birds/group) based on the increasing order of the area of cloacal gland. At the end of this experiment (24 weeks) the data indicated that size of the cloacal gland was directly proportional to foam discharge, foam weight, testicular weight, fertility and testosterone concentration in plasma. From this study it may be concluded that area of cloacal gland in Japanese quail is positively correlated with testicular weight, level of testosterone in plasma and fertility. Visual examination of cloacal gland and cloacal foam may provide a valuable non-invasive tool for predicting the fertilizing ability of individual male bird.     

Effect of Oxygen on the Induction of Tryptophan Hydroxylase by Adrenergic Agents in Organ Cultures of Rat Pineal Glands

Rat pineal glands, cultured under 95% air and 5% CO2, lost 50% of their tryptophan hydroxylase activity within 5 h. This loss was accelerated by the addition of cycloheximide or puromycin to the medium. Activity was, however, largely maintained in 95% O2 and 5% CO2. Under these conditions, L-noradrenaline (100 microM), L-isoproterenol (10 microM), and dibutyryl cyclic AMP (1 mM) induced enzyme activity. They failed to do so when 95% air and 5% CO2 was used. Noradrenaline induced serotonin N-acetyltransferase activity with either atmosphere.     

A new pyrimidine-specific ribonuclease from bovine seminal plasma that is active on both single and double-stranded polyribonucleotides and that can distinguish between Mg2+-containing and Mg2+-depleted naturally occurring RNAs

The purification to homogeneity of a new ribonuclease, named RNAase SPL, from bovine seminal plasma is described. This nuclease, like the bovine pancreatic RNAase A, is pyrimidine specific. Its activity on single-stranded synthetic polyribonucleotides such as poly(rU) is significantly higher than that of RNAase A. However, unlike RNAase A, RNAase SPL is highly active on a double-stranded RNA such as poly[r(A · U)], and shows extremely limited activity on naturally occurring RNAs, such as Escherichia coli RNA, prepared with Mg²⁺ present throughout the isolation procedure. Under conditions of limiting hydrolysis in which RNAase A degrades 60 to 90% of total E. coli RNA to acid-soluble material and the remaining to material having a molecular weight lower than that of transfer RNA, RNAase SPL does not yield any acid-soluble products: it does not appear to degrade tRNA or 5 S RNA, and causes only a small number of nicks in the remaining RNAs to yield a limiting digest containing products with molecular weights ranging between 10,000 and 150,000. Absence of Mg²⁺ during the isolation procedure, or heat denaturation of the RNA makes it as susceptible to RNAase SPL as it is to RNAase A.The above and other related observations reported here support the view that there are Mg²⁺-dependent structural features, besides single and doublestrandedness, in naturally occurring RNAs, that can be distinguished by using the two nucleases RNAase SPL and RNAase A.     

DIURNAL RHYTHM AND TURNOVER OF TRYPTOPHAN HYDROXYLASE IN THE PINEAL GLAND OF THE RAT

Tryptophan hydroxylase in the pineal gland of the rat was found to undergo a diurnal rhythm in activity with an elevated activity at night. The rhythm was abolished in constant light. Cycloheximide (15 mg/kg, i.p.), administered both at night and during the day, caused a rapid decay in activity suggesting that tryptophan hydroxylase was subject to a rapid turnover in vivo. The primary site of control appeared to be at the level of translation since actinomycin D had no effect. Some relevant properties of the enzyme were studied. Thiol-containing compounds were shown to substantially protect pineal tryptophan hydroxylase from inactivation at 0°C but provided little protection at higher temperatures. The inactivation process appeared to be independent of oxygen. The activity of the enzyme, lost after ageing at 0°C. could be recovered by incubation with dithiothreitol under anaerobic conditions. Fresh enzyme, or enzyme inactivated at 37°C could not be activated by this process. A re-examination of the action of p-chlorophenylalanine (PCPA) on pineal tryptophan hydroxylase revealed that an irreversible inactivation occurred within 6h (25% of initial activity) followed by a recovery within 24 h. The rapid turnover of the enzyme is the probable reason for the failure of previous studies to observe an irreversible inhibition of this enzyme by PCPA.     

Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity. The current study was aimed to develop antitumor phramacophore, BP-1C as JAK2 specific inhibitor against lung neoplastic progression. The study validates and identifies the molecular targets of BP-1C induced cell death. Cell based screening against multiple cancer cell lines identified, lung adenocarcinoma as its specific target through promotion of apoptosis. The BP-1C is able to induce, specific hall marks of apoptosis and there by conferring anti-neoplastic activity. Validation of its molecular mechanism, identified, BP-1C specifically targets JAK2^Tyr1007/1008 phosphorylation, and inhibits its downstream STAT3^Tyr705 signalling pathway to induce cell death. As a consequence, modulation in Akt/Src survival signal and altered expression of interwoven apoptotic genes were evident. The results were reproducible in an in-vivo LLC tumor model and in-ovo xenograft studies. The computational approaches viz, drug finger printing confers, BP-1C as novel class JAK2 inhibitor and molecular simulations studies assures its efficiency in binding with JAK2. Overall, BP-1C is a novel JAK2 inhibitor with experimental evidence and could be effectively developed into a promising drug for lung cancer treatment.

Graphical abstract

     

Effect of Novel Amino Acids and Dipeptides Substituted 3-Morpholino Arecoline Derivatives as Muscarinic Receptor 1 Agonists in Alzheimer’s Dementia Models

A series of novel, potent and selective muscarinic receptor 1 agonists (M1 receptor agonists) that employ a key N-substituted morpholine arecoline moiety has been synthesized as part of research effort for the therapy of Alzheimer’s diseases. The ester group of arecoline (which is reported as mucarinic agonist) has been replaced by N-substituted morpholine ring. The structure activity relationship reveals that the increase in lipophilic carbon chain on the nitrogen atom of the morpholine ring increases the affinity of M1 receptor. In the present study, we are reporting N-amino acid substituted 9(a–k) and dipeptides substituted 10(a–j) and 11(a–j) morpholino arecoline derivatives, along with their in vitro muscarinic binding studies by using [³H]QNB and also in vivo evaluation of memory and learning in male Wistar rats (passive avoidance test plus maze studies) as M1 receptor agonist. Some molecules from the dipeptide series (10b, 10c and 10j) showed potent M1 receptor agonist activity. Other derivatives also showed considerable M1 receptor binding affinity.     

Seminalplasmin

The importance of seminal plasma in fertilization was appreciated as early as 1677 and would thus hardly seem a source for the search of antibacterial agents. The observation that seminal plasma had the ability to inhibit the growth of microorganisms in 1940 led to a systematic search for molecules possessing antimicrobial activity in addition to factors that might have a role in reproductive physiology. Extensive investigations led to the discovery in bovine seminal fluid of a 47-residue peptide, possessing potent antimicrobial activity as well as calcium transport modulatory properties in bovine sperm. We describe in this article the two, apparently unrelated, biological activities of this peptide.     

Microradioisotopic assay for indoleamine N-methyltransferase and analysis of products by liquid chromatography

A rapid method for the separation of tryptamine, 5-hydroxytryptamine, and their N-methylated derivatives is described. The method involves liquid chromatography using a cation exchange column with the eluant monitored either by ultraviolet or fluorescence spectroscopy. The latter technique permits the detection of picogram quantities of indoleamines. Using normal-phase liquid chromatography a complete separation of tryptamine, its N-methylated derivatives, and their β-carboline analogs was also achieved. A radioisotopic assay with the potential to detect indoleamine N-methyltransferase activity in milligram quantities of rabbit lung tissue was developed. The radioisotopically labeled products formed from a number of substrates in such assays were characterized by liquid chromatography.