Hemiorchidectomy leads to dramatic and immediate alterations in pituitary follicle-stimulating hormone secretion and the functional activity of the remaining testis in the adult male bonnet monkey (Macaca radiata)

The aim of the present study was to examine the effect of hemiorchidectomy (HO) on serum FSH, LH, testosterone (T), and inhibin (INH) concentrations as well as on the testicular volume (TV) and on changes in the kinetics of germ cell turnovers in the remaining testis of adult male bonnet monkeys. Blood samples collected at 2200 h at various times before and after HO and testicular biopsies obtained at different periods were subjected to hormone analysis and DNA flow cytometry. Though serum T levels were lowered (p < 0.05) at 12 h after HO, T levels rapidly returned to intact control concentrations by Day 5. While serum LH remained unaltered, serum FSH increased markedly within 2 days of HO and remained significantly (p < 0.05) elevated over the next 90 days. Though serum INH showed a significant decrease (p < 0.05) by 15 min of HO, it returned to approximately 80% of intact levels within one week. The TV of the remaining testis showed maximal increment by Day 30 (p < 0.05) of HO. DNA flow cytometric analysis 24 days after HO showed increases (p < 0.05) in spermatogonia (2C) and primary spermatocytes (4C). These cell types by Day 45 had transformed to round (1C) and elongate (HC) (by 38%, p < 0.001) spermatids. Overall spermatogenesis (conversion of 2C to 1C and HC) showed significant enhancement at Days 110 and 175, suggesting that the spurt in spermatogenic activity is not confined to a single spermatogenic cycle

Enhanced susceptibility of follicle-stimulating-hormone-deprived infertile bonnet monkey (Macaca radiata) spermatozoa to dithiothreitol-induced DNA decondensation in situ

Immunoneutralization of endogenous follicle-stimulating hormone (FSH) of adult male monkeys leads to oligospermia and infertility despite unchanged testosterone levels. The inability of these monkeys to impregnate despite repeated exposures to cycling females appeared to be due to abnormal alterations in the kinetics of germ cell transformations and deficient spermiogenesis. Here we investigated the stability of sperm chromatin in oFSH-immunized monkeys as a marker for spermiogenesis. The susceptibility of spermatozoa to in vitro decondensation induced by dithiothreitol (DTT, 0.05-50 mM) was studied by measuring the nuclear fluorescence of DTT-treated, ethidium bromide (EB)-stained sperm using flow cytometry. Changes in sperm morphology and binding of thiol-specific 14C-iodoacetamide (14C-IA) were also monitored under the same conditions. Sperm from the immunized monkeys decondensed at a lower concentration of DTT, bound more EB, and decondensed more extensively than those from control animals. The difference was apparent in sperm from all regions of the epididymis. Immunized monkey sperm also bound significantly more 14C-IA at all concentrations of DTT. Overall, the effective concentration of DTT required to elicit 50% of maximal decondensation (ED50) of epididymal and ejaculated sperm was significantly lower for the immunized monkeys than even the caput sperm of controls. These results suggest that FSH deprivation in monkeys results in production of sperm with limited potential for disulfide formation and reduced chromatin stability

Long-term contraceptive efficacy of vaccine of ovine follicle-stimulating hormone in male bonnet monkeys (Macaca radiata)

A group of ten healthy fertile adult male bonnet monkeys were actively immunized using procedures acceptable for human use with pure follicle-stimulating hormone (oFSH) isolated from sheep pituitaries. The vaccine elicited an immunogenic response in all ten monkeys; the antibody-binding capacity, determined by Scatchard analysis, varied from 3 to 18 μg oFSH ml-1, the binding affinity ranging from 0.13 to 2.0 × 1010mol-1. A substantial population of antibodies against oFSH crossreacted with 125I-labelled human (h) FSH, used here as a representative ligand of primate FSH. The bioneutralization activity of the antisera assessed by a specific bioassay in vitro, when the antibody titre was high, was 6.9 ± 0.18 μg hFSH ml-1. Immunization for 4.7-5.7 years did not affect the health and libido of the animals. Concentration of testosterone in serum remained normal throughout the study, but, within 150 days of immunization, there was a marked decrease (75-100%) in the number of spermatozoa in seminal ejaculates. Oligospermic status interspersed with azoospermia was maintained by periodic boosting. The fertility of these animals was monitored between 6 months and 2 years after primary immunization. All the ten animals proved infertile in repeated mating experiments with females of proven fertility. After stopping booster injections, nine of ten animals regained fertility, but the time taken for this depended upon the rate of decline of antibody titres. Re-boosting these monkeys with 100 μg oFSH after confirming that recovery had occurred revealed prompt increases in antibody titres followed once again by onset of oligo-azoospermia and infertility, underscoring the specificity of immunization effect. The immunized monkeys, apart from being acutely oligospermic, ejaculated spermatozoa that were markedly deficient in key acrosomal enzymes, such as acrosin and hyaluronidase, and motility as well as in their ability to penetrate a gel in vitro, suggesting that the infertility observed was due to gross reductions in the numbers of spermatozoa that could effectively interact with the oocyte and cause successful fertilization

(3E,5E)-1-Benzyl-3,5-bis­(2-fluoro­benzyl­idene)piperidin-4-one

The inversion-related mol­ecules of the title compound, C26H21F2NO, associate into closed dimeric subunits via co-operative C—H⋯π inter­actions. Two non-classical C—H⋯O and one C—H⋯N intra­molecular hydrogen bonds are also found in the crystal structure. The piperidin-4-one ring adopts a sofa conforamtion with the 1-benzyl group in the equatorial position, and the equiplanar fluoro­phenyl substituents in the 3- and 5-positions stretched out on either side. The 1-benzyl group is disposed towards the substituent in the 6th position of the piperidin-4-one ring. The 3,5-diene units possess E configurations

(3E,5E)-3,5-Bis(4-allyl­oxybenzyl­idene)-1-benzyl­piperidin-4-one

In the title compound C32H31NO3, the all­yloxy groups on either side of the piperidin-4-one ring are conformationally disordered. The contribution of major and minor components of the allyloxy group at the 3rd position of the ring are 0.576 (4) and 0.424 (4), respectively, and those at the 5th position are 0.885 (3) and 0.115 (3), respectively. The six-membered piperidin-4-one ring adopts a sofa conformation with the benzyl group occupying an equatorial position and the olefinic double bonds possessing an E configuration. Flanking phenyl substituents are stretched out on either side of the six-membered ring. π–π inter­actions with a centroid–centroid distance of 3.885 (1) Å give rise to mol­ecular dimers and short C—H⋯π contacts lead to chains along the c axis

(3E,5E)-1-Benzyl-3,5-dibenzyl­idenepiperidin-4-one

In the title compound, C26H23NO, C—H⋯O hydrogen bonds generate a ribbon structure along the a axis. These ribbons further assemble into a one-dimensional sheet parallel to the ac plane via C—H⋯π inter­actions. The piperidin-4-one ring adopts a sofa conformation with the 1-benzyl group in the equatorial position, and the 3- and 5-phenyl substituents stretched out on either side. The benzyl­idene units adopt E configurations and the 1-benzyl group is disposed towards the 3- substituent of the piperidin-4-one ring

Bioinformatics Based: in Silico Docking Analysis of Polyherbal Formulation for The Management of Parkinson’s Disease (Nadukku Vatham)

Background: The discipline of Siddha medicine, particularly herbal formulations, can benefit greatly from the use of molecular docking because it enables the molecular interactions of the formulation’s lead molecules with receptors to be understood, as well as the inference of the formulation's basic biochemical targets.  Aim: The goal of this study is to carry out an In-silico computational analysis of the phytochemicals found in Kuruver Kudineer (KK), a traditional Siddha remedy that is used for managing behavioral deficit in Parkinsons disease.  Methodology: The ligand structures were developed and optimized using Auto Dock Tools (Morris, Goodsell et al., 1998). Using Auto dock Vina, the compounds were all docked. The function of the target protein Monoamine Oxidase -A (PDB 2Z5X), which is involved in the breakdown of the neurotransmitters by MAO-A, will be inhibited by the creation of a hydrogen bond between phytocomponents and the target's core amino acids (Tyr 69, Ile 335, Tyr 407, and Tyr 444). In order to control the dopamine level, phytocomponents that inhibit the target enzyme MAO-A may be used as potential targets. Results: The compounds present in Kuruver Kudineer (KK) like Gingerenone-A, Betulinic acid, Zingiberene, Rutin, Geniposide and β-sitosterol showed maximum interactions with MAO –A when compared to that of Clorgyline. According to the outcomes of the computational investigation, the bio-active substances present in the Siddha formulation Kuruver Kudineer (KK) have significant affinity to the target MAO-A (PDB 2Z5X). Conclusions: From the results of the present study, it was concluded that the MAO – A reveal significant effect to managing the behavioral deficit and thereby considered an excellent drug choice for the clinical management of Parkinson’s disease (Nadukku vatham

The DLV System for Knowledge Representation and Reasoning

This paper presents the DLV system, which is widely considered the state-of-the-art implementation of disjunctive logic programming, and addresses several aspects. As for problem solving, we provide a formal definition of its kernel language, function-free disjunctive logic programs (also known as disjunctive datalog), extended by weak constraints, which are a powerful tool to express optimization problems. We then illustrate the usage of DLV as a tool for knowledge representation and reasoning, describing a new declarative programming methodology which allows one to encode complex problems (up to $\Delta^P_3$-complete problems) in a declarative fashion. On the foundational side, we provide a detailed analysis of the computational complexity of the language of DLV, and by deriving new complexity results we chart a complete picture of the complexity of this language and important fragments thereof. Furthermore, we illustrate the general architecture of the DLV system which has been influenced by these results. As for applications, we overview application front-ends which have been developed on top of DLV to solve specific knowledge representation tasks, and we briefly describe the main international projects investigating the potential of the system for industrial exploitation. Finally, we report about thorough experimentation and benchmarking, which has been carried out to assess the efficiency of the system. The experimental results confirm the solidity of DLV and highlight its potential for emerging application areas like knowledge management and information integration.Comment: 56 pages, 9 figures, 6 table

Distribution of lipids in the grain of wheat (cv Hereward) determined by lipidomic analysis of milling and pearling fractions

Lipidomic analyses of milling and pearling fractions from wheat grain were carried out to determine differences in composition which could relate to the spatial distribution of lipids in the grain. Free fatty acids and triacylglycerols were major components in all fractions, but the relative contents of polar lipids varied, particularly lysophosphatidyl choline and digalactosyldiglyceride, which were enriched in flour fractions. By contrast, minor phospholipids were enriched in bran and offal fractions. The most abundant fatty acids in the analysed acyl lipids were C16:0 and C18:2 and their combinations, including C36:4 and C34:2. Phospholipids and galactolipids have been reported to have beneficial properties for bread making, while free fatty acids and triacylglycerols are considered detrimental. The subtle differences in the compositions of fractions determined in the present study could therefore underpin the production of flour fractions with optimised compositions for different end uses