Partial regeneration of β-cells in the islets of Langerhans by Nymphayol a sterol isolated from Nymphaea stellata (Willd.) flowers

Reduction of the β-cell mass is critical in the pathogenesis of diabetes mellitus. The discovery of agents which induce regeneration of pancreatic β-cells would be useful to develop new therapeutic approaches to treat diabetes. The present study was aimed at identifying a new agent for the control of diabetes through regeneration of pancreatic β cells and insulin secretory potential. Nymphaea stellata flower chloroform extract (NSFCExt) showed significant plasma glucose lowering effect. Further NSFCExt was utilized to isolate and identify the lead compound based on bioassay guided fractionation; we found Nymphayol (25,26-dinorcholest-5-en-3β-ol) a new crystal [space group P2₁ (No. 4), a = 9.618(5), b = 7.518(5), c = 37.491(5)]. It was purified by repeat column. The structure was determined on the basis of X-ray crystallography and spectral data. Oral administration of Nymphayol for 45 days significantly (p < 0.05) lowered the blood glucose level and more importantly it effectively increased the insulin content in diabetic rats. In addition, Nymphayol increased the number of β cell mass enormously. Islet-like cell clusters in the islets of Langerhans were clearly observed based on histochemical and immunohistochemical study.     

The discovery and structure–activity relationships of 2-(piperidin-3-yl)-1H-benzimidazoles as selective,CNS penetrating H1-antihistamines for insomnia

A series of 2-(3-aminopiperidine)-benzimidazoles were identified as selective H₁-antihistamines for evaluation as potential sedative hypnotics. Representative compounds showed improved hERG selectivity over a previously identified 2-aminobenzimidazole series. While hERG activity could be modulated via manipulation of the benzimidazole N1 substituent, this approach led to a reduction in CNS exposure for the more selective compounds. One example, 9q, retained a suitable selectivity profile with CNS exposure equivalent to known centrally active H₁-antihistamines.     

Spectrum of 32P-induced mutants of Caenorbabditis elegans

Mutants of the free living nematode C. elegans were isolated by using ³²P as a mutagen. It is shown that most of these mutants arise from ³²P suicide. A comparison of EMS-induced and ³²P-induced autosomal recesive mutations shows that there are no large regions of C. elegans genome which are protected from chemical mutagenic action of EMS.     

Cold stress induced high molecular weight membrane polypeptides are responsible for cold tolerance in Rhizobium DDSS69

Cold stress induces a lag phase in the growth cycle of Rhizobium DDSS69. Two cold sensitive mutants of DDSS69 were generated through Tn5 tagged mutagenesis. These mutants do not grow below 15 degrees C but show a growth curve comparable with the wild type grown at 5 degrees C. There is a rapid induction of two high molecular weight membrane polypeptides of 135 and 119 kDa within 15 min of exposure to 5 degrees C in DDSS69. PAGE membrane protein profiles of stressed and non-stressed cells reveal differential regulation of genes. At 15 degrees C both mutants lack the high molecular weight polypeptides, suggesting a role in alleviation of cold stress.     

Evaluation of Markers of Oxidative Stress,Antioxidant Function and Astrocytic Proliferation in the Striatum and Frontal Cortex of Parkinson’s Disease Brains

Dopaminergic neurons die in Parkinson’s disease (PD) due to oxidative stress and mitochondrial dysfunction in the substantia nigra (SN). We evaluated if oxidative stress occurs in other brain regions like the caudate nucleus (CD), putamen (Put) and frontal cortex (FC) in human postmortem PD brains (n = 6). While protein oxidation was elevated only in CD (P < 0.05), lipid peroxidation was increased only in FC (P < 0.05) and protein nitration was unchanged in PD compared to controls. Interestingly, mitochondrial complex I (CI) activity was unaffected in PD compared to controls. There was a 3–5 fold increase in the total glutathione (GSH) levels in the three regions (P < 0.01 in FC and CD; P < 0.05 in Put) but activities of antioxidant enzymes catalase, superoxide dismutase, glutathione reductase and glutathione-s-tranferase were not increased. Total GSH levels were elevated in these areas because of decreased activity of gamma glutamyl transpeptidase (γ-GT) (P < 0.05) activity suggesting a decreased breakdown of GSH. There was an increase in expression of glial fibrillary acidic protein (GFAP) (P < 0.001 in FC; P < 0.05 in CD) and glutathione peroxidase (P < 0.05 in CD and Put) activity due to proliferation of astrocytes. We suggest that increased GSH and astrocytic proliferation protects non-SN brain regions from oxidative and mitochondrial damage in PD.     

The immunoglobulin super family protein RIG-3 prevents synaptic potentiation and regulates Wnt signaling

Cell surface Ig superfamily proteins (IgSF) have been implicated in several aspects of neuron development and function. Here, we describe the function of a?Caenorhabditis elegans IgSF protein, RIG-3. Mutants lacking RIG-3 have an exaggerated paralytic response to a cholinesterase inhibitor, aldicarb. Although RIG-3 is expressed in motor neurons, heightened drug responsiveness was caused by an aldicarb-induced increase in muscle ACR-16 acetylcholine receptor (AChR) abundance, and a corresponding potentiation of postsynaptic responses at neuromuscular junctions. Mutants lacking RIG-3 also had defects in the anteroposterior polarity of the ALM mechanosensory neurons. The effects of RIG-3 on synaptic transmission and ALM polarity were both mediated by changes in Wnt signaling, and in particular by inhibiting CAM-1, a Ror-type receptor tyrosine kinase that binds Wnt ligands. These results identify RIG-3 as a regulator of Wnt signaling, and suggest that RIG-3 has an anti-plasticity function that prevents activity-induced changes in postsynaptic receptor fields.     

Konjac mosaic virus Naturally Infecting Three Aroid Plant Species in Andhra Pradesh,India

The genomes of three potyvirus isolates from, respectively, naturally infected Colocasia esculenta, Caladium spp. and Dieffenbachia spp. in Andhra Pradesh, India, were amplified by RT‐PCR using degenerate potyvirus primers. Sequence analysis of RT‐PCR amplicons (1599 nucleotides) showed maximum identity of 97% with the KoMV‐Zan isolate of Konjac mosaic virus (KoMV) from Taiwan (A/C AF332872). The three isolates had a maximum identity of 99.4%. The length of coat protein (CP) gene of three isolates was 846 nucleotides encoding 282 amino acids with a deduced size of 32.25 kDa. The CP gene of the isolates had, respectively, 78.1–95.7% and 88.2–96.4% identity at nucleotide and amino acid levels with KoMV isolates. The CP gene of the three isolates had 93.1–100% (nucleotide) and 98.2–100% (amino acid) identity. The 3′‐UTR of the three isolates showed maximum identity of 91.1–100% identity between and with other KoMV isolates. In the CP amino acid–based phylogenetic analyses, the isolates branched as a distinct cluster along with known KoMV isolates. The three potyvirus isolates associated with mosaic, chlorotic feathery mottling, chlorotic spots, leaf deformation and chlorotic ring spots on three aroids were identified as isolates of KoMV for the first time from Andhra Pradesh, India.     

Synthesis and X-ray crystallographic investigation of N-(3-deoxy-3-acetamido-��-D-glycopyranosyl)alkanamides as analogs of N-glycoprotein linkage region

As part of our ongoing program aimed at understanding the structural significance of GlcNAcβAsn linkage conserved in all eukaryotic N-glycoproteins, the present study reports on the synthesis and X-ray crystal structures of N-(3-deoxy-3-acetamido-β-D-glycopyranosyl)acetamide (Glc3NAcβNHAc) and the corresponding propionamide (Glc3NAcβNHPr). Comparative analysis of these structures with those of the corresponding GlcNAc (C2 acetamido) compounds showed that the bifurcated anti-parallel pattern involving N-H…O and C-H…O hydrogen bonds, the hallmark feature of the N-glycoprotein models, GlcNAcβNHAc and GlcNAcβAsn, is absent in both the C3 acetamido analogs. The extended (anti) conformation of the amido aglycon moiety as defined by χ(2) seen in the case of C2 acetamido derivative, GlcNAcβNHPr, turns into gauche for the C3 acetamido analog (Glc3NAcβNHPr). This observation is consistent with the earlier work on the critical role of the C2-NHAc group of GlcNAcβAsn in controlling χ(2) at the linkage region of N-glycoproteins.