Synthesis of sulfonamide,amide and amine hybrid pharmacophore,an entry of new class of carbonic anhydrase II inhibitors and evaluation of chemo-informatics and binding analysis

Selective inhibition of carbonic anhydrase (CA) enzyme is an active area of research for medicinal chemists. In the current account, a hybrid pharmacophore approach was employed to design sulfonamide, amide and amine containing new series of potent carbonic anhydrase II inhibitors. The aromatic fragment associated with pharmacophore was altered suitably in order to find effective inhibitors of CA-II. All the derivatives 4a-4m showed better inhibition compared to the standard acetazolamide. In particular, compound 4l exhibited significant inhibition with IC₅₀ value of 0.01796 ± 0.00036 µM. The chemo-informatics analysis justified that all the designed compounds possess <10 HBA and <5 HBD. The ligands-protein binding analyses showed that 4l confined in the active binding pocket with three hydrogen bonds observed with His63, Asn66 and Thr197 residues.     

Analysis of growth during phototropic curvature of cress hypocotyls

Abstract. Growth rates throughout an organ curving phototropically under continuous, unilateral while light were monitored by lime-lapse photography of cress hypocotyls marked into 1 mm sections by two rows of ion-exchange beads. Curvature resulted from an integrated sequence of changes in growth rate on each side of the organ, but the actual patterns of change and, therefore rales of curvature, differed within even this one species, depending upon the immediate pretreatment of the seedlings. Transference of seedlings from darkness to unilateral irradiation gave immediate growth inhibition on both sides of the organ. Curvature resulted from differential recovery of growth rate, being seen first on the shaded side, most prominently in the apical regions; only 2h after initial exposure to light did growth recover on the lit (lower) side. On the other hand, transfer of seedlings from omnilateral to unilateral irradiation of the same intensity resulted in simultaneous growth inhibition on the irradiated side and stimulated growth on the shaded side: this growth stimulation of the shaded side was greater than occurred in totally darkened control plants.     

A Generalization of the GMANOVA-Model

It is shown that in some experimental designs the MANOVA- and the GMANOVA-model are too restrictive either to yield all hypothesis tests of interest or to reflect all known features of the design. An extension of these models is derived by relating the response vectors with the unknown model parameters by linear equations which may be completely different for each of the p components of the response vector and for each of the n independent vectors. For situations, in which a Wishart-distributed estimator for the underlying common covariance matrix is attainable, a test for any s-dimensional linear hypothesis on the model parameters is derived.     

Analysis of Profiles Based on Ordinal Classification Functions and Rank Tests

In this article a test for the comparison of K groups of independent profiles is suggested. It is based on rank tests, in which the criterion is obtained by using a suitably chosen ordinal classification function. This function represents a specific view on the profiles. The test, which is easy to use, can be regarded as a generalisation of other well known tests and can be applied within a variety of situations. The relationships to other procedures for the analysis of profiles are described. Some properties are discussed.     

Tests for Trends in Incidence Rate Ratios

Breslow (1984) described an efficient score test for trend in incidence density rate ratios for cohort studies under a conditional Poisson or binomial model employing maximum likelihood estimation of the rate parameters. In this communication, an alternative derivation of this statistic that is based on an unconditional approach is provided, along with an examination of associated goodness-of-fit tests and methods of confidence interval estimation. The procedures are illustrated by a cohort study of ischemic heart disease mortality following industrial exposure to carbon disulfide.     

Measuring sexual selection on females in sex‐role‐reversed Mormon crickets (Anabrus simplex,Orthoptera: Tettigoniidae)

Although many studies examine the form of sexual selection in males, studies characterizing this selection in females remain sparse. Sexual selection on females is predicted for sex‐role‐reversed Mormon crickets, Anabrus simplex, where males are choosy of mates and nutrient‐deprived females compete for matings and nutritious nuptial gifts. We used selection analyses to describe the strength and form of sexual selection on female morphology. There was no positive linear sexual selection on the female body size traits predicted to be associated with male preferences and female competition. Instead, we detected selection for decreasing head width and mandible length, with stabilizing selection as the dominant form of nonlinear selection. Additionally, we tested the validity of a commonly used instantaneous measure of mating success by comparing selection results with those determined using cumulative mating rate. The two fitness measures yielded similar patterns of selection, supporting the common sampling method comparing mated and unmated fractions.     

Expression patterns and association analysis of the porcine DHX58 gene

RIG-1 signalling is responsible for the detection of cytoplasmic viral RNA molecules. DEXH (Asp-Glu-X-His) box polypeptide 58 (encoded by DHX58) is a negative regulator of the RIG-1 signalling pathway. In human, the DHX58 gene can be upregulated and can inhibit the RIG-1 signalling pathway during viral infection. In this study, porcine DHX58 gene expression patterns were studied. According to our results, the porcine DHX58 gene was upregulated not only by the stimulation of Poly I:C but also by the stimulation of 1ipopolysaccharides (LPS). One polymorphism (g.4919G>C), detected in the ninth intron, was significantly associated with some blood parameters including the red cell distribution width of 1-day-old pigs and white blood cell counts, lymphocyte absolute counts, and platelet distribution width of 17-day-old pigs (P < 0.05). Moreover, the individuals with the genotype GG have a significantly higher mean white blood cell count than individuals with genotype CC or GC (P < 0.05). Our study indicates that DHX58 is an important gene that is associated with the immune response in swine.     

Floristic variation,chorological types and diversity: do they correspond at broad and local scales?

Abstract. The relationships between biogeographical patterns and local‐scale patterns based on microscale features, such as topoclimate, are well known in plant biogeography. Here we present a method of determining this correspondence using constrained ordination and correlations. We examined compositional gradients at two different scales, biogeographical chorotypes, and diversity. Compositional data (124 taxa × 113 plots) were sampled at four regularly spaced sites in south‐eastern Spain. Longitude (LONGI) was used as a spatial variable representing an east–west climate gradient, together with a radiation index (RADIN), elevation, and a disturbance indicator. All factors correlated with the compositional gradients, but the local‐topoclimate factor (RADIN) and the broad‐scale factor (LONGI) were most important. These two, spatially independent factors were both correlated with the two first ordination axes, and therefore should relate to the same general trend in species‐turnover. There was a significant Spearman's rank correlation between the species order along these two gradients. This is interpreted as an ecological self‐similar pattern, i.e. coenoclines repeating at different scales. A consistent order of species along local‐ and broad‐scale coenoclines may indicate that similar operational factors act at several scales, here related to moisture and temperature. The distribution of Mediterraneo–Macaronesian, Mediterraneo–Saharo–Arabian and Ibero–Maghribian species confirmed the correspondence between the broad‐ and local‐scale gradients. The former group decreases in number with increasing aridity along both gradients, whereas the two latter groups increase. A discordant pattern was found with south‐eastern Iberian endemics, but this may be explained by several of them being edaphic (saxicolous) specialists. There is a significant decrease in species richness with high radiation, but the expected increase along the longitudinal gradient from west (dry) to east (moist) was not statistically significant. This may be due to the correspondence between high richness and disturbance, both occurring in the middle of the broad‐scale gradient.     

Chromatographic separation of extruded iron-sulfur cores from the apoproteins of Clostridium pasteurianum and spinach ferredoxins in aqueous Triton X-100/urea

Iron-sulfur core extrusions from spinach [( 2Fe-2S]) and Clostridium pasteurianum (2[4Fe-4S]) ferredoxins in aqueous Triton X-100/urea containing excess benzenethiol yield quantitatively [FenSn(SPh)4]2- with n = 2 and n = 4, respectively. The iron-sulfur cluster can be separated from the corresponding apoprotein by rapid passage of the extrusion mixture over a small anaerobic column of Whatman DE-52 anion-exchange cellulose. Essentially quantitative recovery of [FenSn (SPh)4]2- is achieved in the eluate. The apoprotein remaining on the column can be eluted with 0.5 M NaCl. Most of the residual Triton X-100 and benzenethiol can be removed by passage of the apoprotein eluate over a small column of Bio-Beads SM-2, a hydrophobic polystyrene adsorbent. Apoprotein recovery is comparable to that obtained by other chromatographic methods. At least with spinach ferredoxin, the apoprotein prepared in this fashion can be reconstituted. The procedures developed in this work are potentially most applicable to selective removal of [2Fe-2S] and [4Fe-4S] centers from a multicenter enzyme without irreversible denaturation.     

Preparing nuclei from cells in monolayer cultures suitable for counting and for following synchronized cells through the cell cycle

A procedure is described for preparing nuclei from cells in monolayer culture so that they may be counted using an electronic particle counter. It takes only 10 to 15 min, and consists of swelling the cells in hypotonic buffer and then lysing them with the quaternary ammonium salt, ethylhexadecyldimethylammonium bromide. The cells are completely lysed, yielding a suspension of clean single nuclei which is stable, free of debris, and easily counted. The method was developed for a cell line of epithelial origin (MCF-7), which is often difficult to trypsinize to single cells. It works equally well at all cell densities up to and beyond confluence, and has been used with a variety of cells in culture, including 3T3 cells, bovine macrophages, rat mammary epithelial cells, mouse mammary tumor cell lines, and human fibroblasts. The size of the nuclei produced by this procedure is related to their DNA content, and the method is thus suitable for following cultures of synchronized cells through the cell cycle, and for performing differential counts of cells with substantial differences in DNA content.