Investigations on unconventional hydrogen bonds in RNA binding proteins: the role of CH...O=C interactions

We have investigated the roles played by C-H...O=C interactions in RNA binding proteins. There was an average of 78 CH...O=C interactions per protein and also there was an average of one significant CH...O=C interactions for every 6 residues in the 59 RNA binding proteins studied. Main chain-Main chain (MM) CH...O=C interactions are the predominant type of interactions in RNA binding proteins. The donor atom contribution to CH...O=C interactions was mainly from aliphatic residues. The acceptor atom contribution for MM CH...O=C interactions was mainly from Val, Phe, Leu, Ile, Arg and Ala. The secondary structure preference analysis of CH...O=C interacting residues showed that, Arg, Gln, Glu and Tyr preferred to be in helix, while Ala, Asp, Cys, Gly, Ile, Leu, Lys, Met, Phe, Trp and Val preferred to be in strand conformation. Most of the CH...O=C interacting polar amino acid residues were solvent exposed while, majority of the CH...O=C interacting non polar residues were excluded from the solvent. Long and medium-range CH...O=C interactions are the predominant type of interactions in RNA binding proteins. More than 50% of CH...O=C interacting residues had a higher conservation score. Significant percentage of CH...O=C interacting residues had one or more stabilization centers. Sixty-six percent of the theoretically predicted stabilizing residues were also involved in CH...O=C interactions and hence these residues may also contribute additional stability to RNA binding proteins.     

Preliminary studies on antihyperglycemic effect of aqueous extract of Brassica nigra (L.) Koch in streptozotocin induced diabetic rats

In the streptozotocin induced diabetic rats treated separately with aqueous, ethanol, acetone and chloroform extracts of the seeds of B. nigra, the increase in serum glucose value between 0 and 1 hr of glucose tolerance test (GTT) was the least (29 mg/dl) in aqueous extract treated animals while it was 54, 44 and 44 mg/dl with chloroform, acetone and ethanol extracts respectively. In further studies carried out with aqueous extract, the effective dose was found to be 200 mg/kg body weight in GTT. Administration of 200 mg/kg body weight of aqueous extract to diabetic animals daily once for one month brought down fasting serum glucose (FSG) levels while in the untreated group FSG remained at a higher value. In the treated animals the increase in glycosylated hemoglobin (HbA1c) and serum lipids was much less when compared with the levels in untreated diabetic controls. These findings suggest that further studies with the aqueous extract of B. nigra seeds on its antidiabetic activity would be useful.     

Plant mitochondrial recombination surveillance requires unusual RecA and MutS homologs

For >20 years, the enigmatic behavior of plant mitochondrial genomes has been well described but not well understood. Chimeric genes appear, and occasionally are differentially replicated or expressed, with significant effects on plant phenotype, most notably on male fertility, yet the mechanisms of DNA replication, chimera formation, and recombination have remained elusive. Using mutations in two important genes of mitochondrial DNA metabolism, we have observed reproducible asymmetric recombination events occurring at specific locations in the mitochondrial genome. Based on these experiments and existing models of double-strand break repair, we propose a model for plant mitochondrial DNA replication, chimeric gene formation, and the illegitimate recombination events that lead to stoichiometric changes. We also address the physiological and developmental effects of aberrant events in mitochondrial genome maintenance, showing that mitochondrial genome rearrangements, when controlled, influence plant reproduction, but when uncontrolled, lead to aberrant growth phenotypes and dramatic reduction of the cell cycle.     

Madeline 2.0 PDE: a new program for local and web-based pedigree drawing

The Madeline 2.0 Pedigree Drawing Engine (PDE) is a pedigree drawing program for use in linkage and family-based association studies. The program is designed to handle large and complex pedigrees with an emphasis on readability and aesthetics. For complex pedigrees, we use a hybrid algorithm in which consanguinous loops are drawn as cyclic graphs whenever possible, but we resort to acyclic graphs when matings can no longer be connected without line crossings. A similar hybrid approach is used to avoid line crossings for matings between distant descendants of different founding groups. Written in object-oriented C++ and released under the GNU General Public License (GPL), Madeline 2.0 PDE reads input files specified on the command line and generates pedigree drawings without user interaction. Pedigree output in scalable vector graphics (SVG) format can be viewed in browsers with native SVG rendering support or in vector graphics editors. We provide an easy-to-use public web service, which is experimental and still under development. Availability: http://kellogg.umich.edu/madeline.     

tSNP-based identification of allelic loss of gene expression in a patient with a balanced chromosomal rearrangement

Identification of genes affected by disease-associated rare chromosomal rearrangements has led to the cloning of several disease genes. Here we have used a simple approach involving allele-specific RT-PCR-based detection of gene expression to identify a gene affected by a balanced autosome;autosome translocation. We identified a transcribed SNP (tSNP), c.68G-->A, present in a novel untranslated exon of the CLDN14 gene in a male patient with mental retardation who had a balanced t(13;21) chromosomal translocation. We determined an allelic loss of expression of the CLDN14 gene isoform at the 21q22.1 chromosomal breakpoint. Although additional work is necessary to explore a possible function of the novel CLDN14 isoform in brain development and function and the potential pathogenic consequences of its disruption in this patient, the result clearly demonstrates the utility of a tSNP-based detection of allelic loss of gene expression in studies involving chromosomal rearrangements.     

Antidiabetic potential of Citrus sinensis and Punica granatum peel extracts in alloxan treated male mice

An investigation on the effects of four different concentrations of peel extract from Citrus sinensis (CS) or Punica granatum (PG) in male mice revealed the maximum glucose lowering and antiperoxidative activities at 25 mg/kg of CS and 200 mg/kg of PG. In a separate experiment their potential was evaluated with respect to the regulation of alloxan induced diabetes mellitus. While a single dose of alloxan (120 mg/kg) increased the serum levels of glucose and alpha-amylase activity, rate of water consumption and lipid peroxidation (LPO) in hepatic, cardiac and renal tissues with a parallel decrease in serum insulin level, administration of 25 mg/kg of CS or 200 mg/kg of PG was found to normalize all the adverse changes induced by alloxan, revealing the antidiabetic and anti peroxidative potential of test fruit peel extracts. Subsequent phytochemical analysis indicated that the high content of total polyphenols in the test peels might be related to the antidiabetic and antiperoxidative effects of the test peels.     

Antidiabetic and antioxidative effects of Annona squamosa leaves are possibly mediated through quercetin-3-O-glucoside

Present investigation was made to reveal the involvement of a quercetin in the antidiabetic and antiperoxidative effects of Annona squamosa leaf extract. Quercetin-3-O-glucoside (characterized by UV, IR, MS and NMR analyses) was isolated from Annona squamosa leaves and examined for its potential to regulate alloxan-induced hyperglycemia and lipid peroxidation (LPO) in rats. While in alloxan treated animals, an increase in the concentration of serum glucose with a parallel decrease in insulin level was observed, administration of 15 mg/kg/day of isolated quercetin-3-O-glucoside for 10 consecutive days to the hyperglycemic animals reversed these effects and simultaneously inhibited the activity of hepatic glucose-6-phosphatase. It further decreased the hepatic and renal LPO with a concomitant increase in the activities of antioxidative enzymes, such as catalase (CAT) and superoxide dismutase (SOD) and in glutathione (GSH) content, indicating its safe and antiperoxidative effects. These findings suggest the potential of quercetin-3-O-glucoside in the amelioration of diabetes mellitus and tissue lipid peroxidation. It also appears that the antidiabetic effects of A. squamosa leaf extract is possibly mediated through the insulin stimulating and/or free radical scavenging properties of its active constituent, quercetin-3-O-glucoside.     

"Pseudosarcoma" in a pregnant woman

Background

As a result of improvements in diagnostic accuracy, the primary source of the tumour is identified in more than 99% of cases presenting with a malignancy. Whilst the axial skeleton is a common site of metastases, the sternum is rarely affected, especially by isolated metastases.

Case presentation

We report a case of a 68 year old male who was referred to the surgical outpatient clinic with a six month history of sternal pain. The patient was known to have essential thrombocythaemia, which had recently transformed into acute myeloid leukaemia but a sternal biospy showed mucinous adenocarcinoma. He had not localising symptoms and full evaluation failed to localise the primary tumour.

Conclusion

Solitary sternal metastases are rare and when found an underlying neoplasm is usually identified allowing targeted treatment. If however, there is no symptomatic tumour, the metastasis should simply be treated symptomatically.