Synthesis and evaluation of thiomannosides,potent and orally active FimH inhibitors

FimH is a type I fimbrial lectin located at the tip of type-1 pili of Gram-negative uropathogenic Escherichia coli (UPEC) guiding its ability to adhere and infect urothelial cells. Accordingly, blocking FimH with small molecule inhibitor is considered as a promising new therapeutic alternative to treat urinary tract infections caused by UPEC. Herein, we report that compounds having the S-glycosidic bond (thiomannosides) had improved metabolic stability and plasma exposures when dosed orally. Especially compound 5h showed the potential to inhibit biofilm formation and also to disrupt the preformed biofilm. And compound 5h showed prophylactic effect in UTI model in mice.     

Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1.

Autosomal dominant cerebellar ataxia is a group of clinically and genetically heterogeneous disorders. We carried out genomewide linkage analysis in 15 families with autosomal dominant pure cerebellar ataxia (ADPCA). Evidence for linkage to chromosome 19p markers was found in nine families, and combined multipoint analysis refined the candidate region to a 13.3-cM interval in 19p13.1-p13.2. The remaining six families were excluded for this region. Analysis of CAG-repeat expansion in the alpha1A-voltage-dependent calcium channel (CACNL1A4) gene lying in 19p13.1, recently identified among 8 small American kindreds with ADPCA (spinocerebellar ataxia type 6 [SCA6]), revealed that 8 of the 15 families studied had similar, very small expansion in this gene: all affected individuals had larger alleles (range of CAG repeats 21-25), compared with alleles observed in neurologically normal Japanese (range 5-20 repeats). Inverse correlation between the CAG-repeat number and the age at onset was found in affected individuals with expansion. The number of CAG repeats in expanded chromosomes was completely stable within each family, which was consistent with the fact that anticipation was not statistically proved in the SCA6 families that we studied. We conclude that more than half of Japanese cases of ADPCA map to 19p13.1-p13.2 and are strongly associated with the mild CAG expansion in the SCA6/CACNL1A4 gene.     

Malcofaunal Diversity of Chilika Lake,Odisha, India

Investigation during the period of 3 years from 2007 to 2010 on the malacofauna of Chilika lake revealed the occurrence of 126 molluscan taxa belonging to 56 families, 18 orders of three classes in the bottom sediment. Of these 61 species belonged to Bivalvia, 64 species belonged to Gastropoda and one species belonged to Polyplacophora. Maximum Bivalvia and Gastropoda taxa were found in the outer channel region of the lake. The dominating species were Crassostrea cuttackensis, Saccostrea cucullata, Brachidontes undulatus, Meretrix meretrix among bivalves and Cerethideopsilla cingulata, Bullia vittata, Nassarious stolatus, Indothias lacera, Natica tigrina, Turritella attenuata were from the gastropods. Occurrence of a large number of marine taxa is most probably associated with the opening of new lagoon during 1st August 2008.     

Regulation of mRNAs for Three Enzymes in the Glial Cell Model C6 Cell Line

In the glial cell line C6, regulation of actinomycin D (Act-D)-sensitive translatable polysomal mRNAs of three key enzymes--glycerol phosphate dehydrogenase (GPDH; EC 1.1.1.8) and glutamine synthetase (GS) by glucocorticoids and lactate dehydrogenase (LDH; EC 1.1.1.27) by catecholamines--is described. Though the first two enzymes are hydrocortisone (HC)-inducible, the nature of their response to the hyperacetylating agent sodium butyrate is dramatically different. Furthermore the appearance of GPDH translatable poly(A)+ RNA in HC-induced cells is inhibited by the presence of cycloheximide (CHX), whereas the induction of GS is unaffected by CHX. These observations necessitate further probing into an existing model system to explain the varied mechanisms of induction of these two enzymes by a single inducer. In combination with the third enzyme whose induction by catecholamines is glial specific, we believe that the C6 cell represents the most appropriate cell line for molecular neurobiologists to study the mechanisms of hormone action in glia.     

Genetic structure of island and mainland populations of a Neotropical bumble bee species

As a consequence of founder effects, small population size and demographic constraints, island populations are often characterized by low genetic diversity and high inbreeding. The effects of inbreeding are more pronounced in haplo-diploid insects like bees than in similar diploid species, because their method of sex determination requires heterozygosity at a sex locus. Inbreeding leads to homozygosity at the sex locus and the production of non-viable diploid males. This means that island populations of bees are particularly prone to extinction. Here we determine the levels of diversity and isolation between islands and mainland populations of the bumble bee Bombus morio in southeast Brazil. We analyzed 659 individuals from 24 populations, sequencing two mitochondrial genes (COI and Cytb) and genotyping all individuals at 14 microsatellite loci. Surprisingly, genetic diversity was high and genetic isolation was low in all populations except Teodoro Sampaio (mainland) and Ilha da Vitória (island). Genetic diversity is not significantly correlated with island area, but is lower in populations that are more distant from the mainland. Except perhaps for Ilha da Vitória, we suggest that the island populations are unlikely to go extinct due to genetic factors. Finally, based on its genetic distance from all other populations, we identify a putative new subspecies in the Teodoro Sampaio region.     

dEMBF: A Comprehensive Database of Enzymes of Microalgal Biofuel Feedstock

Microalgae have attracted wide attention as one of the most versatile renewable feedstocks for production of biofuel. To develop genetically engineered high lipid yielding algal strains, a thorough understanding of the lipid biosynthetic pathway and the underpinning enzymes is essential. In this work, we have systematically mined the genomes of fifteen diverse algal species belonging to Chlorophyta, Heterokontophyta, Rhodophyta, and Haptophyta, to identify and annotate the putative enzymes of lipid metabolic pathway. Consequently, we have also developed a database, dEMBF (Database of Enzymes of Microalgal Biofuel Feedstock), which catalogues the complete list of identified enzymes along with their computed annotation details including length, hydrophobicity, amino acid composition, subcellular location, gene ontology, KEGG pathway, orthologous group, Pfam domain, intron-exon organization, transmembrane topology, and secondary/tertiary structural data. Furthermore, to facilitate functional and evolutionary study of these enzymes, a collection of built-in applications for BLAST search, motif identification, sequence and phylogenetic analysis have been seamlessly integrated into the database. dEMBF is the first database that brings together all enzymes responsible for lipid synthesis from available algal genomes, and provides an integrative platform for enzyme inquiry and analysis. This database will be extremely useful for algal biofuel research. It can be accessed at http://bbprof.immt.res.in/embf.