Steroidal saponins from Dioscorea floribunda: Structures of floribundasaponins A and B

Two steroidal saponins, floribundasaponins A and B isolated from the yams of Dioscorea floribunda, have been characterized as pennogenin-3-O-β-d-glucopyranoside and pennogenin-3-O-α-l-rhamnopyranosyl(1→4)-β-d-glucopyranoside.     

Precise Mapping of the Homothallism Genes HML and HMR in SACCHAROMYCES CEREVISIAE

The HML and HMR loci carry unexpressed copies of MATa and MATα information, and a replica of that information is transposed to MAT during mating-type interchange in Saccharomyces yeasts. A negative control mechanism keeps silent the information located at the HML and HMR loci. We mapped these loci by constructing strains in which these loci are expressed. In these strains, the mating type of the segregants is dependent upon the allele at HML and HMR. This novel approach is independent of their switching function. HML is located on the left arm of chromosome III distal to his4 by about 26.8 centimorgans (cM). HMR maps on the right arm of the same chromosome distal to thr4 by about 39.8 cM and proximal to MAL2 by about 1.0 cM. The results allow the exact placement of these loci and are in accord with the observations made by Harashima and Oshima (1976).     

The possible mode of action of prostaglandins: X. Antagonism between prostaglandin F2a and prolactin or human chorionic gonadotropin : A comparative study

A comparative assessment of the efficacy of prolactin or HCG in reversing the luteolytic property of a single dose (2.0 mg/kg) of PGF₂a was conducted in pregnant (day 10) rats. It was found that prolactin maintained pregnancy in 90% of the test animals. HCG though found to maintain pregnancy in 70% of the PGF₂a-treated pregnants, the fetal survival rate was, however, recorded to be 62% against the control value of 98%. Conversely, prolactin replacement maintained the fetal survival rate as high as 93.4%. Moreover, the growth of the fetuses, placentae and corpus luteum in the pregnants having prolactin in conjunction with PGF₂a was also found to be greater compared to the animals which h ad a combined regimen of PGF₂a and HCG, but identical to controls. On the other hand, similar combined regimen when applied to hysterectomized pregnant rats, it was observed that though the vaginal diestrus was maintained by the prolactin or HCG in the presence of PGF₂a, the prolactin regimen was found to be superb compared to HCG in the maintenance of luteal weight and functional activity. It was concluded that the antifertility effect of PGF₂a in the rat is primarily the consequence of luteolysis and prolactin seems to be a much more appropriate hormonal replacement compared to HCG, a long-acting LH, in antagonizing the luteolytic property of PGF₂a.     

Integrated analysis of numerous heterogeneous gene expression profiles for detecting robust disease-specific biomarkers and proposing drug targets

Genome-wide expression profiling has revolutionized biomedical research; vast amounts of expression data from numerous studies of many diseases are now available. Making the best use of this resource in order to better understand disease processes and treatment remains an open challenge. In particular, disease biomarkers detected in case–control studies suffer from low reliability and are only weakly reproducible. Here, we present a systematic integrative analysis methodology to overcome these shortcomings. We assembled and manually curated more than 14 000 expression profiles spanning 48 diseases and 18 expression platforms. We show that when studying a particular disease, judicious utilization of profiles from other diseases and information on disease hierarchy improves classification quality, avoids overoptimistic evaluation of that quality, and enhances disease-specific biomarker discovery. This approach yielded specific biomarkers for 24 of the analyzed diseases. We demonstrate how to combine these biomarkers with large-scale interaction, mutation and drug target data, forming a highly valuable disease summary that suggests novel directions in disease understanding and drug repurposing. Our analysis also estimates the number of samples required to reach a desired level of biomarker stability. This methodology can greatly improve the exploitation of the mountain of expression profiles for better disease analysis.     

Purification and Production of Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Bioactive Peptides Derived from Fermented Goat Milk

International Journal of Peptide Research and Therapeutics - In the study, five different Lactobacillus cultures i.e. L. rhamnosus (NK2) (KR080695), L. casei (NK9) (KR732325), L. fermentum (M5)...     

Cloning and functional characterization of endo-β-1,4-glucanase gene from metagenomic library of vermicompost

In the vermicomposting of paper mill sludge, the activity of earthworms is very dependent on dietetic polysaccharides including cellulose as energy sources. Most of these polymers are degraded by the host microbiota and considered potentially important source for cellulolytic enzymes. In the present study, a metagenomic library was constructed from vermicompost (VC) prepared with paper mill sludge and dairy sludge (fresh sludge, FS) and functionally screened for cellulolytic activities. Eighteen cellulase expressing clones were isolated from about 89,000 fosmid clones libraries. A short fragment library was constructed from the most active positive clone (cMGL504) and one open reading frame (ORF) of 1,092 bp encoding an endo-β-1,4-glucanase was indentified which showed 88% similarity with Cellvibrio mixtus cellulase A gene. The endo-β-1,4-glucanase cmgl504 gene was overexpressed in Escherichia coli. The purified recombinant cmgl504 cellulase displayed activities at a broad range of temperature (25–55°C) and pH (5.5–8.5). The enzyme degraded carboxymethyl cellulose (CMC) with 15.4 U, while having low activity against avicel. No detectable activity was found for xylan and laminarin. The enzyme activity was stimulated by potassium chloride. The deduced protein and three-dimensional structure of metagenome-derived cellulase cmgl504 possessed all features, including general architecture, signature motifs, and N-terminal signal peptide, followed by the catalytic domain of cellulase belonging to glycosyl hydrolase family 5 (GHF5). The cellulases cloned in this work may play important roles in the degradation of celluloses in vermicomposting process and could be exploited for industrial application in future.     

Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model

The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins.