Type 2 diabetes mellitus: phylogenetic motifs for predicting protein functional sites

Diabetes mellitus, commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood. Keeping this view, we demonstrate the phylogenetic motifs (PMs) identification in type 2 diabetes mellitus very likely corresponding to protein functional sites. In this article, we have identified PMs for all the candidate genes for type 2 diabetes mellitus. Glycine 310 remains conserved for glucokinase and potassium channel KCNJ11. Isoleucine 137 was conserved for insulin receptor and regulatory subunit of a phosphorylating enzyme. Whereas residues valine, leucine, methionine were highly conserved for insulin receptor.Occurrence of proline was very high for calpain 10 gene and glucose transporter.     

Regulation of the Heparan Sulfate Proteoglycan, Perlecan, by Injury and Interleukin-1α

Perlecan is a specific proteoglycan that binds to amyloid precursor protein and beta-amyloid peptide, is present within amyloid deposits, and has been implicated in plaque formation. Because plaque formation is associated with local inflammation, we hypothesized that the mechanisms involved in brain inflammatory responses could influence perlecan biosynthesis. To test this hypothesis, we first studied perlecan regulation in mice after inflammation induced by a brain stab wound. Perlecan mRNA and immunoreactivity were both increased 3 days after injury. Interleukin-1alpha (IL-1alpha) is a cytokine induced after injury and plays an important role in inflammation. As such, IL-1alpha may be one of the factors participating in regulating perlecan synthesis. We thus studied perlecan regulation by IL-1alpha, in vivo. Regulation of perlecan mRNA by this cytokine was area-specific, showing up-regulation in hippocampus, whereas in striatum, perlecan mRNA was unchanged. To support this differential regulation of perlecan mRNA by IL-1alpha, basic fibroblast growth factor (bFGF), a growth factor also present in plaques, was studied in parallel. bFGF mRNA did not show any regional difference, being up-regulated in both hippocampus and striatum in vivo. In vitro, both astrocyte and microglia were immunoreactive for perlecan. Moreover, perlecan mRNA was increased in hippocampal glial cultures after IL-1alpha but not in striatal glia. These results show an increase in perlecan biosynthesis after injury and suggest a specific regulation of perlecan mRNA by IL-1alpha, which depends on brain area. Such regulation may have important implications in the understanding of regional brain variations in amyloid plaque formation.     

Motility and chemotactic response of Pseudomonas fluorescens toward chemoattractants present in the exudate of Macrophomina phaseolina

Pseudomonas fluorescens strains (LAM1-hydrophilic) and (LAM2-hydrophobic) showed positive chemotaxis towards attractants (sugars, amino acids, polyols and organic acids) present in the exudate of Macrophomina phaseolina (a soilborne plant pathogenic fungus). The varied response of motility traits such as speed, rate of change in direction (RCDI) and net to gross displacement ratio (NGDR) was observed for different chemoattractants. Swimming speed of the strains was highest in 10-fold diluted exudate or 100–1000 μM strength of different attractants, but further dilutions significantly decreased the swimming speed (P = 0.05). Chemotactic response of P. fluorescens was positively correlated with swimming speed (P = 0.05; r = 0.76). Relative to control, the RCDI values decreased 1.5-fold in amino acids or sugars, and 1.2-fold in polyols or organic acids. With increase in swimming speed, the NGDR of both strains also increased, but the RCDI decreased. Both hydrophilic and hydrophobic strains did not show significant differences in their motility traits. The results demonstrate that M. phaseolina exudate contains chemical attractants that serve as signal for flagellar motility of P. fluorescens. Motile P. fluorescens strains thus may consume fungal exudate as nutrients, and thus spores could offer a niche for these bacteria in soil.     

Role of salicylic acid in systemic resistance induced by Pseudomonas fluorescens against Fusarium oxysporum f. sp. ciceri in chickpea

Selected isolates of Pseudomonas fluorescens (Pf1-94, Pf4-92, Pf12-94, Pf151-94 and Pf179-94) and chemical resistance inducers (salicylic acid, acetylsalicylic acid, DL-norvaline, indole-3-carbinol and lichenan) were examined for growth promotion and induced systemic resistance against Fusarium wilt of chickpea. A marked increase in shoot and root length was observed in P. fluorescens treated plants. The isolates of P. fluorescens systemically induced resistance against Fusarium wilt of chickpea caused by Fusarium. oxysporum f.sp. ciceri (FocRs1), and significantly (P = 0.05) reduced the wilt disease by 26-50% as compared to control. Varied degree of protection against Fusarium wilt was recorded with chemical inducers. The reduction in disease was more pronounced when chemical inducers were applied with P. fluorescens. Among chemical inducers, SA showed the highest protection of chickpea seedlings against wilting. Fifty two- to 64% reduction of wilting was observed in soil treated with isolate Pf4-92 along with chemical inducers. A significant (P = 0.05; r = -0.946) negative correlation was observed in concentration of salicylic acid and mycelial growth of FocRs1 and at a concentration of 2000 microg ml(-1) mycelial growth was completely arrested. Exogenously supplied SA also stimulated systemic resistance against wilt and reduced the disease severity by 23% and 43% in the plants treated with 40 and 80 microg ml(-1) of SA through root application. All the isolates of P. fluorescens produced SA in synthetic medium and in root tissues. HPLC analysis indicated that Pf4-92 produced comparatively more SA than the other isolates. 1700 to 2000 nanog SA g(-1) fresh root was detected from the application site of root after one day of bacterization whereas, the amount of SA at distant site ranged between 400-500 nanog. After three days of bacterization the SA level decreased and was found more or less equal at both the detection sites.     

The nicotine‐mediated decline in l‐dopa‐induced dyskinesias is associated with a decrease in striatal dopamine release

l ‐dopa‐induced dyskinesias (LIDs) are a side effect of Parkinson's disease therapy that is thought to arise, at least in part, because of excessive dopaminergic activity. Thus, drugs that regulate dopaminergic tone may provide an approach to manage LIDs. Our previous studies showed that nicotine treatment reduced LIDs in Parkinsonian animal models. This study investigates whether nicotine may exert its beneficial effects by modulating pre‐synaptic dopaminergic function. Rats were unilaterally lesioned by injection of 6‐hydroxydopamine (6‐OHDA) (2 × 3 ug per site) into the medial forebrain bundle to yield moderate Parkinsonism. They were then implanted with minipumps containing vehicle or nicotine (2.0 mg/kg/d) and rendered dyskinetic with l ‐dopa (8 mg/kg plus 15 mg/kg benserazide). Lesioning alone decreased the striatal dopamine transporter, nicotinic receptor (nAChR) levels, and nAChR‐mediated ³H‐dopamine release, consistent with previous results. Nicotine administration reduced l ‐dopa‐induced abnormal involuntary movements throughout the course of the study (4 months). Nicotine treatment led to declines in the striatal dopamine transporter, α6β2* nAChRs and various components of α6β2* and α4β2* nAChR‐mediated release. l ‐dopa treatment had no effect. These data suggest that nicotine may improve LIDs in Parkinsonian animal models by dampening striatal dopaminergic activity.     

Detection of Prunus necrotic ring spot virus in plum,cherry and almond by serological and molecular techniques from India

Stone fruits are cultivated in the temperate and sub-temperate regions of India. During surveys in stone fruit growing areas, viral symptoms were observed in almond, cherry and plum. These samples were brought to the laboratory for further detection at serological and molecular levels to check the presence of virus. In the present study, incidence of PNRSV is reported on plum (Prunus domestica), almond (Prunus dulcis) and cherry (Prunus avium) using serological and molecular techniques. Coat protein gene of PNRSV was amplified from almond, cherry and plum. This is the first molecular evidence of PNRSV on these stone fruits reported from India.     

Multivalent human blood group ABH and Lewis glycotopes are key recognition factors for a lFuc>Man binding lectin from phytopathogenic Ralstonia solanacearum

Ralstonia solanacearum lectin (RSL), that might be involved in phytopathogenicity, has been defined as lFuc?Man specific. However, the effects of polyvalency of glycotopes and mammalian structural units on binding have not been established. In this study, recognition factors of RSL were comprehensively examined with natural multivalent glycotopes and monomeric ligands using enzyme linked lectin-sorbent and inhibition assays. Among the glycans tested, RSL reacted strongly with multivalent blood group A_h (GalNAcα1–3[Fucα1–2]Gal) and H (Fucα1–2Gal) active glycotopes, followed by B_h (Galα1–3[Fucα1–2]Gal), Le^a (Galβ1–3[Fucα1–4]GlcNAc) and Le^b (Fucα1–2Galβ1–3[Fucα1–4]GlcNAc) active glycotopes. But weak or negligible binding was observed for blood group precursors having Galβ1–3/4GlcNAcβ1- (I_β/II_β) residues or Galβ1–3GalNAcα1- (T_α), GalNAcα1-Ser/Thr (Tn) bearing glycoproteins. These results indicate that the density and degree of exposure of multivalent ligands of α1–2 linked lFuc to Gal at the non-reducing end is the most critical factor for binding. An inhibition study with monomeric ligands revealed that the combining site of RSL should be of a groove type to fit trisaccharide binding with highest complementarity to blood group H trisaccharide (H_L; Fucα1–2Galβ1–4Glc). The outstandingly broad RSL saccharide-binding profile might be related to the unusually wide spectrum of plants that suffer from R. solanacearum pathogenicity and provide ideas for protective antiadhesion strategies.