Diazaspirocyclic compounds as selective ligands for the α4β2 nicotinic acetylcholine receptor

Diazaspirocyclic ligands have been synthesized in four steps as selective α4β2 nicotinic acetylcholine receptor antagonists. Structural assignment of 1-(pyridin-3-yl)-2-spiropyrrolidino-3,2'-1-azabiclo[2.2.1]heptane 2, was confirmed using a combination of NMR experiments on a key intermediate, spirolactam 9. All three target compounds synthesized in this diazaspirocyclic series exhibited high affinity (K(i)<35 nM) at the human α4β2 nAChR subtype, and very low affinity for the human α7, α3β4 (ganglion) and α1β1γδ (muscle) subtypes (K(i)>500 nM).     

On Testing for Equicorrelation in Random Coefficient Models

Recently BHATTI (1993) considered an efficient estimation of random coefficient model based on survey data. The main objective of this paper is to construct one sided test for testing equicorrelation coefficient in presence of random coefficients using optimal testing procedure. The test statistic is a ratio of quadratic forms in normal variables which is most powerful and point optimal invariant.     

Ethnobotanical study and conservation status of trees in the district Sargodha,Punjab, Pakistan

Sargodha district is one of the least studied regions of Pakistan regarding its ethnobotanical values. This paper is the first report related to the documentation and conservation status of the tree species in the Sargodha district, and their folk ethnobotanical uses. An interview base survey was conducted in the study area in 2010-2013. The ethnobotanical data revealed the use of 100 tree species (6 gymnosperms, 94 angiosperms) belonging to 77 genera (6 gymnosperms, 71 angiosperms) and 39 families (4 gymnosperms, 35 angiosperms), with the Fabaceae ranking first with 19 tree species, followed by the Moraceae (12 species). Tree species like Aegle marmelos, Butea monosperma, Diospyrus malabarica, Gmelina arborea, Kigelia africana, Manilkara hexandra, Manilkara zapota, Mimusops elengi, Nyctanthes arbor-tristis, Putranjiva roxburghii, Terminalia arjuna and Terminalia bellerica are not only unique in their medicinal value but also interesting because of their unusual occurrence here. Thevetia peruviana, Cassia fistula, Celtis australis, Delonix regia, Diospyrus malabarica, Grevillea robusta, Haplophragma adenophylum, Jacaranda mimosifolia, Lagerstroemia speciosa, Plumeria rubra, Pterospermum acerifolium, Roystonea regia, Taxodium distichum and Tectona grandis are included among the worth looking ornamental tree species. Capparis decidua, Dalbergia sissoo, Tamarix aphylla, Tamarix dioica, Prosopis cineraria and Ziziphus mauritiana are the most commonly used timber species. Other common ethnobotanical utilization of these trees includes either sheltering or fuel or agricultural uses. Lack of awareness about the potential uses of these species, and particularly ignorance of the concerned authorities, have led to a decline in the population of this precious tree flora. Documentation of this tree flora, and as-sociated indigenous knowledge, can be used as a basis for developing management plans for conservation and sustainable use of this flora in the study area. A well-organized management is critical to restore and conserve this endangered natural resource in the District Sargodha, Pakistan. The immense medicinal and timber value of these tree species make it necessary to promote their conservation to simultaneously alleviate the poverty and improve the socio-economic status of the study area.     

Environmental variation,vegetation distribution,carbon dynamics and water/energy exchange at high latitudes

Abstract. The responses of high latitude ecosystems to global change involve complex interactions among environmental variables, vegetation distribution, carbon dynamics, and water and energy exchange. These responses may have important consequences for the earth system. In this study, we evaluated how vegetation distribution, carbon stocks and turnover, and water and energy exchange are related to environmental variation spanned by the network of the IGBP high latitude transects. While the most notable feature of the high latitude transects is that they generally span temperature gradients from southern to northern latitudes, there are substantial differences in temperature among the transects. Also, along each transect temperature co‐varies with precipitation and photosynthetically active radiation, which are also variable among the transects. Both climate and disturbance interact to influence latitudinal patterns of vegetation and soil carbon storage among the transects, and vegetation distribution appears to interact with climate to determine exchanges of heat and moisture in high latitudes. Despite limitations imposed by the data we assembled, the analyses in this study have taken an important step toward clarifying the complexity of interactions among environmental variables, vegetation distribution, carbon stocks and turnover, and water and energy exchange in high latitude regions. This study reveals the need to conduct coordinated global change studies in high latitudes to further elucidate how interactions among climate, disturbance, and vegetation distribution influence carbon dynamics and water and energy exchange in high latitudes.     

Single-Nucleotide Polymorphism Alleles in the Insulin Receptor Gene Are Associated with Typical Migraine

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.     

Production and characterization of anti-peptide monoclonal antibodies with specificity for staphylococcal enterotoxins A and B

A synthetic peptide containing selected epitopes from staphylococcal enterotoxin A (SEA) and enterotoxin B (SEB) was used to produce monoclonal antibodies (Mabs) to respective enterotoxins in a single fusion procedure. The peptide inhibited the reaction of polyclonal anti-SEA or anti-SEB antisera with their homologous enterotoxin, thus showing that the chosen epitopes are part of the antibody-inducing enterotoxin sequences. Two Mabs, Mab-A and Mab-B, reacted with both the peptide and with either SEA or SEB. Used in a double antibody sandwich ELISA, the Mabs were able to quantitate the native SEA or SEB toxins at nanogram levels.     

Induction of carbofuran oxidation to 4-hydroxycarbofuran by Pseudomonas sp. 50432

Pseudomonas sp. 50432 biotransformed a highly toxic pesticide, carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) to 7-phenol (2,3-dihydro-2,2-dimethyl-7-hydroxy benzofuran) and several unknown metabolites. One of the unknown metabolites identified by gas chromatography/mass spectroscopy was 4-hydroxycarbofuran (2,3-dihydro-2,2-dimethyl-4-hydroxybenzofuran-7-yl methylcarbamate). It had a mass (237) similar to 3-hydroxycarbofuran and 5-hydroxycarbofuran but different fragmentation patterns. This is the first report in which an inducible oxidative enzyme, hydroxylase, mediated the conversion of carbofuran to 4-hydroxycarbofuran. A second constitutively synthesized enzyme hyrolase transformed carbofuran to 7-phenol.