2,3-Ethylene- and 2,3-trimethylene-bridged analogues of the group III metabotropic glutamate receptor ligand 2-amino-4-phosphonobutanoic acid

The racemic trans- and cis-isomers of 1-amino-2-phosphonomethyl-cyclobutanecarboxylic acid (5 and 6) and 1-amino-2-phosphonomethyl-cyclopentanecarboxylic acid (7 and 8) were synthesized as extensions of the mGluR4 agonists trans- and cis-1-amino-2-phosphonomethyl-cyclopropanecarboxylic acid (3 and 4). Although the methylene bridge in 3 and 4 allows for retention of affinity toward the mGluR4 receptor, increasing the bridging unit to the ethylene group as in 5 and 6 or to the trimethylene group as in 7 and 8 introduces sufficient steric hindrance to eliminate affinity for the mGluR4 receptor.     

Anti-malarial activity of Baylis-Hillman adducts from substituted 2-chloronicotinaldehydes

New Baylis–Hillman adducts are synthesized based on substituted 2-chloronicotinaldehydes and screened for their in vitro anti-malarial activity against chloroquine sensitive and chloroquine resistant Plasmodium falciparum. Out of the six new compounds synthesized and screened, 2b, 2c and 2d compounds showed substantial anti-malarial activity.     

Isolation and characterization of phenanthrene-degrading <Emphasis Type="Italic">Sphingomonas paucimobilis</Emphasis> strain ZX4

Phenanthrene-degrading bacterium strain ZX4 was isolated from an oil-contaminated soil, and identified as Sphingomonas paucimobilis based on 16S rDNA sequence, cellular fatty acid composition, mol% G + C and Biolog-GN tests. Besides phenanthrene, strain ZX4 could also utilize naphthalene, fluorene and other aromatic compounds. The growth on salicylic acid and catechol showed that the strain degraded phenanthrene via salicylate pathway, while the assay of catechol 2, 3-dioxygenase revealed catechol could be metabolized through meta-cleavage pathway. Three genes, including two of meta-cleavage operon genes and one of GST encoding gene were obtained. The order of genes arrangement was similar to S-type meta-pathway operons. The phylogenetic trees based on 16S rDNA sequence and meta-pathway gene both revealed that strain ZX4 is clustered with strains from genus Sphingomonas.     

Ventral migration of early-born neurons requires Dcc and is essential for the projections of primary afferents in the spinal cord

Neuronal migration and lamina-specific primary afferent projections are crucial for establishing spinal cord circuits, but the underlying mechanisms are poorly understood. Here, we report that in mice lacking Dcc (deleted in colorectal cancer), some early-born neurons could not migrate ventrally in the spinal cord. Conversely, forced expression of Dcc caused ventral migration and prevented dorsolateral migration of late-born spinal neurons. In the superficial layer of the spinal cord of Dcc-/- mutants, mislocalized neurons are followed by proprioceptive afferents, while their presence repels nociceptive afferents through Sema3a. Thus, our study has shown that Dcc is a key molecule required for ventral migration of early-born neurons, and that appropriate neuronal migration is a prerequisite for, and coupled to, normal projections of primary afferents in the developing spinal cord.     

A novel method of estimation of lipophilicity using distance-based topological indices: dominating role of equalized electronegativity

Attempt is made to propose yet another method of estimating lipophilicity of a heterogeneous set of 223 compounds. The method is based on the use of equalized electronegativity along with topological indices. It was observed that excellent results are obtained in multiparametric regression upon introduction of indicator parameters. The results are discussed critically on the basis various statistical parameters.     

Cytokine-induced stable neuronal differentiation of human bone marrow mesenchymal stem cells in a serum/feeder cell-free condition

The characteristics and multilineage differentiation potential of bone marrow mesenchymal stem cells (BM MSC) remain controversial. This study aimed to characterize human BM MSC isolated by plastic adherent or antibody selection and their neuronal differentiation potential using growth factors or chemical inducing agents. MSC were found to express low levels of neuronal markers: neurofilament-M, beta tubulin III, and neuron specific enolase. Under a serum- and feeder cell-free condition, basic fibroblast growth factor, epidermal growth factor, and platelet-derived growth factor induced neuronal morphology in MSC. In addition to the above markers, these cells expressed neurotransmitters or associated proteins: gamma-aminobutyric acid, tyrosine hydroxylase and serotonin. These changes were maintained for up to 3 months in all bone marrow specimens (N = 6). In contrast, butylated hydroxyanisole and dimethylsulfoxide were unable to induce sustained neuronal differentiation. Our results show that MSC isolated by two different procedures produced identical lineage differentiation with defined growth factors in a serum- and feeder cell-free condition.     

Effects of elevated CO<Subscript>2</Subscript> and nitrogen on wheat growth and photosynthesis

The effects of nitrogen [75 and 150 kg (N) ha⁻¹] and elevated CO₂ on growth, photosynthetic rate, contents of soluble leaf proteins and activities of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and nitrate reductase (NR) were studied on wheat (Triticum aestivum L. cv. HD-2285) grown in open top chambers under either ambient (AC) or elevated (EC) CO₂ concentration (350 ± 50, 600 ± 50 μmol mol⁻¹) and analyzed at 40, 60 and 90 d after sowing. Plants grown under EC showed greater photosynthetic rate and were taller and attained greater leaf area along with higher total plant dry mass at all growth stages than those grown under AC. Total soluble and Rubisco protein contents decreased under EC but the activation of Rubisco was higher at EC with higher N supply. Nitrogen increased the NR activity whereas EC reduced it. Thus, EC causes increased growth and P_N ability per unit uptake of N in wheat plants, even if N is limiting.     

Towards precise classification of cancers based on robust gene functional expression profiles

Background

Despite the continuous production of genome sequence for a number of organisms, reliable, comprehensive, and cost effective gene prediction remains problematic. This is particularly true for genomes for which there is not a large collection of known gene sequences, such as the recently published chicken genome. We used the chicken sequence to test comparative and homology-based gene-finding methods followed by experimental validation as an effective genome annotation method.

Results

We performed experimental evaluation by RT-PCR of three different computational gene finders, Ensembl, SGP2 and TWINSCAN, applied to the chicken genome. A Venn diagram was computed and each component of it was evaluated. The results showed that de novo comparative methods can identify up to about 700 chicken genes with no previous evidence of expression, and can correctly extend about 40% of homology-based predictions at the 5' end.

Conclusions

De novo comparative gene prediction followed by experimental verification is effective at enhancing the annotation of the newly sequenced genomes provided by standard homology-based methods.     

Genome wide survey of G protein-coupled receptors in <Emphasis Type="Italic">Tetraodon nigroviridis</Emphasis>

Background  

The G-protein-coupled receptors (GPCRs) constitute one of the largest and most ancient superfamilies of membrane proteins. They play a central role in physiological processes affecting almost all aspects of the life cycle of an organism. Availability of the complete sets of putative members of a family from diverse species provides the basis for cross genome comparative studies.