Carcinoembryonic antigens (CD66) on epithelial cells and neutrophils are receptors for Opa proteins of pathogenic neisseriae

Opa protein-expressing pathogenic neisseriae interact with CD66a-transfected COS (African green monkey kidney) and CHO (Chinese hamster ovary) cells. CD66a (BGP) is a member of carcinoembryonic antigen (CEA, CD66) family. The interactions occur at the N-terminal domain of CD66a, a region that is highly conserved between members of the CEA subgroup of the CD66 family. In this study, we have investigated the roles of CD66 expressed on human epithelial cells and polymorphonuclear phagocytes (PMNs) in adhesion mediated via Opa proteins. Using human colonic (HT29) and lung (A549) epithelial cell lines known to express CD66 molecules, we show that these receptors are used by meningococci. A monoclonal antibody, YTH71.3, against the N-terminal domain of CD66, but not 3B10 directed against domains, A1/B1, inhibited meningococcal adhesion to host cells. When acapsulate bacteria expressing Opa proteins were used, large numbers of bacteria adhered to HT29 and A549 cells. In addition, both CD66a-transfected CHO cells and human epithelial cells were invaded by Opa-expressing meningococci, suggesting that epithelial cell invasion may occur via Opa–CD66 interactions. In previous studies we have shown that serogroup A strain C751 expresses three Opa proteins, all of which mediate non-opsonic interactions with neutrophils. We have examined the mechanisms of these interactions using antibodies and soluble chimeric receptors. The results indicate that the nature of their interactions with purified CD66a molecules and with CD66 on neutrophils is alike and that these interactions occur at the N-terminal domain of CD66. Thus, the Opa family of neisserial ligands may interact with several members of the CD66 family via their largely conserved N-terminal domains.     

Hypoaminoacidemia caused by imipramine but not by clenbuterol is dissociable from hyperglycemia and hyperinsulinemia

The effects of the tricyclic antidepressant imipramine (20 mg/kg) and the beta-adrenoceptor agonist clenbuterol (0.5 mg/kg) on the serum concentrations of tyrosine, tryptophan, glucose and insulin were compared 30 min after intraperitoneal injection. The drugs had nearly identical effects on serum tyrosine, which was reduced to 73% of control by both drugs, and on tryptophan, which was reduced to 72% by imipramine and to 66% by clenbuterol. In contrast, whereas clenbuterol raised serum glucose to 174% and insulin to 379% of control, imipramine had no significant effects on either glucose or insulin. The results clearly demonstrate that the effects of imipramine on blood amino acid levels are dissociable from effects on glucose and insulin. We conclude, therefore, that hypoaminoacidemia caused by imipramine is not mediated by stimulating insulin release.     

Evidence for a simple Cl conductance pathway in nutrient membrane of frog stomach

A decrease in nutrient Cl⁻ results in an increased negativity of the nutrient relative to the secretory side. The possibility emerged that Cl⁻ transport could be attributed to a neutral mechanism involving Cl⁻ in the nutrient membrane coupled to a simple Cl⁻ conductance pathway in the secretory membrane. The decrease in PD (potential difference) with a decrease in nutrient Cl⁻ could arise from a decrease in cellular Cl⁻ so that the ratio of Cl⁻ in cell to Cl⁻ in secretory solution was decreased. Experiments were designed to determine whether there was a need to assume a simple Cl⁻ conductance pathway. A 10-fold decrease in Cl⁻ gave in HCO₃⁻-containing nutrient solutions a PD decrease of 20 mV, in HCO₃⁻-free nutrient solutions, a PD decrease of 13.5 mV, and in HCO₃⁻-free and Na⁺-free solutions, a PD decrease of 6.7 mV. The decrease of 6.7 mV could not be attributed to a neutral Cl⁻HCO₃⁻ exchanger or a NaCl symport. Also there was no evidence for a KCl symport from changes in Cl⁻ in presence and absence of K⁺. It followed that the decrease of 6.7 mV provided evidence for a simple Cl⁻ conductance pathway in the nutrient membrane.     

Association of TNF-α polymorphisms (−857, −863 and −1031), TNF-α serum level and lipid profile with acne vulgaris

BackgroundAcne is an inflammatory condition principally affected by genetic and dietary factors. Investigation into functional polymorphisms of TNF-α gene and their association with acne vulgaris will be helpful in exploring genetic influence on skin immune mediated inflammatory events. In the present study, we analyzed association of TNF-α gene polymorphisms, its expression levels and lipid profiles in a large cohort of acne patients and controls.MethodsWe used PCR-RFLP to study association of TNF-α polymorphisms at −857C/T, −863C/A and −1031 T/C sites with acne vulgaris. Lipid profiles were measured using enzymatic end-point method. The serum levels of TNF-α and apolipoprotein a were measured using ELISA. NIH, LDlink was used to investigate patterns of linkage disequilibrium across south Asian reference genome (Punjabi from Lahore Pakistan).ResultsWe found that TNF-α −863 polymorphism is strongly associated with acne in overall population as well as in gender and severity based groups of acne patients. Polymorphisms at −863 and −1031 position were in linkage disequilibrium. Importantly, TNF-α serum level was significantly increased in acne patients with severe disease symptoms. Furthermore, levels of total cholesterol (TC) and triglycerides (TG) were significantly increased, whereas high density lipoprotein cholesterol (HDL-C) level was significantly decreased in acne patients. The levels of apolipoprotein a varied widely in studied populations and no significant difference was found in the analyzed groups.ConclusionIn conclusion, we found that TNF-α expression increases in acne patients affected by TNF-α polymorphisms, and that the lipid profile is specifically disrupted in acne patients.     

Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome

MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs.     

Enhancement of antitumor effect of paclitaxel in combination with immunomodulatory Withania somnifera on benzo(a)pyrene induced experimental lung cancer

The current experimental work deals with the immunomodulatory studies on the extract of Withania somnifera (L.) Dunal root powder against benzo(a)pyrene induced lung cancer in male Swiss albino mice. In our previous study, we reported the antioxidant and anticarcinogenic effect of W. somnifera (L.) Dunal along with paclitaxel. Immune dysfunction has been found to be associated with cancer and chemotherapy. Benzo(a)pyrene induced cancer animals were treated with 400mg/kg bodyweight of W. somnifera (L.) Dunal extract for 30 days significantly alters the levels of immunocompetent cells, immune complexes and immunoglobulins. Based on the data, the carcinogen as well as the paclitaxel affects the immune system, the toxic side effects on the immune system is more reversible and more controllable by W. somnifera (L.) Dunal. These results concluded the immunomodulatory activity of W. somnifera (L.) Dunal extract, which is a known immunomodulator in indigenous medicine.     

The acyl-homoserine lactone-type quorum-sensing system modulates cell motility and virulence of Erwinia chrysanthemi pv. zeae

Erwinia chrysanthemi pv. zeae is one of the Erwinia chrysanthemi pathovars that infects on both dicotyledons and monocotyledons. However, little is known about the molecular basis and regulatory mechanisms of its virulence. By using a transposon mutagenesis approach, we cloned the genes coding for an E. chrysanthemi pv. zeae synthase of acyl-homoserine lactone (AHL) quorum-sensing signals (expI_Ecz) and a cognate response regulator (expR_Ecz). Chromatography analysis showed that expI_Ecz encoded production of the AHL signal N-(3-oxo-hexanoyl)-homoserine lactone (OHHL). Null mutation of expI_Ecz in the E. chrysanthemi pv. zeae strain EC1 abolished AHL production, increased bacterial swimming and swarming motility, disabled formation of multicell aggregates, and attenuated virulence of the pathogen on potato tubers. The mutation also marginally reduced the inhibitory activity of E. chrysanthemi pv. zeae on rice seed germination. The mutant phenotypes were rescued by either exogenous addition of AHL signal or in trans expression of expI_Ecz. These data demonstrate that the AHL-type QS signal plays an essential role in modulation of E. chrysanthemi pv. zeae cell motility and the ability to form multicell aggregates and is involved in regulation of bacterial virulence.     

Import and processing of heart mitochondrial cyclophilin D.

Cyclophilins are a family of cyclosporin-A-binding proteins which catalyse rotation about prolyl peptide bonds. A mitochondrial isoform in mammalian cells, cyclophilin D, is a component of the permeability transition pore that is formed by the adenine nucleotide translocase and the voltage-dependent anion channel at contact sites between the inner and outer membrane. This study investigated the submitochondrial location of cyclophilin D by following the fate of radiolabelled protein following import. Precursor [(35)S]cyclophilin D was expressed in vitro from a PCR-generated cDNA. The precursor was imported by rat heart mitochondria and processed in a single step to a 21-kDa protein that was identical (SDS/PAGE) to an in vitro expressed mature protein and a cyclophilin D purified from rat heart mitochondria. No further modification of the mature protein could be demonstrated. Fractionation of mitochondria following import established that cyclophilin D locates only to the matrix. It is concluded that cyclophilin D binding to the permeability transition pore must occur at the inner face of the mitochondrial inner membrane.     

The diversity of Rhizobia, Sinorhizobia and novel non-Rhizobial Paenibacillus nodulating wild herbaceous legumes

The objective of the present study was to isolate and characterize nodulating bacteria associated with wild legumes. For this purpose, we recovered twenty isolates from root nodules of five wild legume species: Melilotus alles, Melilotus officinalis, Trifolium pratense, Trifolium repens and Medicago sp. Most of the isolates were morphologically analogous with only few exceptions in colony shape, appearance and incubation time. All isolates were Gram negative except T.P2-4. Random amplification of polymorphic DNA showed genetic variation among isolates. The 16S rRNA sequence analysis revealed these isolates as Rhizobium, Sinorhizobium and Paenibacillus. Each of these was also screened for nod D and nod F genes with marked variation at these loci; however, the nucleotide sequence analysis confirmed the presence of nod genes. The assignment of strains to their hosts revealed a unique symbiotic association of Paenibacillus sp. nodulating T .pratense which is being reported here for the first time.     

MAPS Database: Medicinal plant Activities,Phytochemical and Structural Database

Drug development from natural sources is an important and fast developing area. Natural sources (plants) have been used to cure a range of diseases for Thousands of years. Different online medicinal plant databases provide information about classifications, activities, phytochemicals and structure of phytochemicals in different formats. These databases do not cover all aspects of medicinal plants. MAPS (Medicinal plant Activities, Phytochemicals & structural database) has been constructed with uniqueness that it combines all information in one web resource and additionally provides test targets on which particular plant found to be effective with reference to the original paper as well. MAPS database is user friendly information resource, including the data of > 500 medicinal plants. This database includes phytochemical constituents, their structure in mol format, different activities possessed by the medicinal plant with the targets reported in literature.

Availability

http://www.mapsdatabase.com