Syntheses of 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-d-glucopyranose (n-acetylmaltosamine) and 2-acetamido-2-deoxy-4-O-β-d-glucopyranosyl-α-d-glucopyranose

Condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-benzyl-1-O-(N-methyl)acetimidoyl-β-D-glucopyranose gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-α-D-glucopyranoside which was catalytically hydrogenolysed to crystalline 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-D-glucopyranose (N-acetylmaltosamine). In an alternative route, the aforementioned imidate was condensed with 2-acetamido-3-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose, and the resulting disaccharide was catalytically hydrogenolysed, acetylated, and acetolysed to give 2-acetamido-1,3,6-tri-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-α-D-glucopyranose Deacetylation gave N-acetylmaltosamine. The synthesis of 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranose involved condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in the presence of mercuric bromide, followed by deacetylation and catalytic hydrogenolysis of the condensation product.     

Spectral index for assessment of differential protein expression in shotgun proteomics

Detecting differentially expressed proteins is a key goal of proteomics. We describe a label-free method, the spectral index, for analyzing relative protein abundance in large-scale data sets derived from biological samples by shotgun proteomics. The spectral index is comprised of two biochemically plausible features: relative protein abundance (assessed by spectral counts) and the number of samples within a group with detectable peptides. We combined the spectral index with permutation analysis to establish confidence intervals for assessing differential protein expression in bronchoalveolar lavage fluid from cystic fibrosis and control subjects. Significant differences in protein abundance determined by the spectral index agreed well with independent biochemical measurements. When used to analyze simulated data sets, the spectral index outperformed four other statistical tests (Student's t-test, G-test, Bayesian t-test, and Significance Analysis of Microarrays) by correctly identifying the largest number of differentially expressed proteins. Correspondence analysis and functional annotation analysis indicated that the spectral index improves the identification of enriched proteins corresponding to clinical phenotypes. The spectral index is easily implemented and statistically robust, and its results are readily interpreted graphically. Therefore, it should be useful for biomarker discovery and comparisons of protein expression between normal and disease states.     

The effects of organic amendments on mineral element uptake and fruit quality of raspberries

The organic produce industry is gaining popularity with consumers because of the perception for healthier foods and the environmental benefits of this agricultural practice. Common amendments in organic agriculture include compost and compost tea, the latter being a relatively new product in North America. The main objective of this study was to assess the effectiveness of ruminant and municipal solid waste compost and compost teas made from these composts on selected soil, leaf and fruit parameters of raspberries. Generally, foliar compost tea application was as effective as compost addition in raspberry production. Concentrations of K in leaf and fruits were significantly lower (p?=?0.05) in compost tea treated raspberries. Furthermore, the compost tea increased leaf Na compared to compost amendments which suggested that raspberries preferentially take up Na via foliar applications compared to root Na applications. The yield, total antioxidant capacity of fruit, and vitamin C content of fruit were not affected by treatment but differed greatly among years. Precipitation also varied greatly among years as did soil nutrient concentrations and may have influenced yield, total antioxidant capacity, and vitamin C content.     

An interesting diagnosis for a presacral mass: case report

A presacral mass can present a diagnostic dilemma for the surgical oncologist. Differential diagnoses include congenital causes such as teratoma or chordoma, neurological causes such as neurilemoma or neurofibroma or other malignancies such as lymphoma or sarcoma. Diagnosis usually requires imaging such as CT and MRI and tissue biopsy. We present an unusual cause of a presacral mass being extramedullary haematopoiesis, found incidentally in a 71 year old female. Extramedullary haematopoiesis is defined as the production of myeloid and erythroid elements outside of the bone-marrow. This diagnosis is extremely rare in the presacral area especially in a patient with no haematological abnormalities. A review of the literature is presented.     

Continuous Quinacrine Treatment Results in the Formation of Drug-Resistant Prions

Quinacrine is a potent antiprion compound in cell culture models of prion disease but has failed to show efficacy in animal bioassays and human clinical trials. Previous studies demonstrated that quinacrine inefficiently penetrates the blood-brain barrier (BBB), which could contribute to its lack of efficacy in vivo. As quinacrine is known to be a substrate for P-glycoprotein multi-drug resistance (MDR) transporters, we circumvented its poor BBB permeability by utilizing MDR^0/0 mice that are deficient in mdr1a and mdr1b genes. Mice treated with 40 mg/kg/day of quinacrine accumulated up to 100 µM of quinacrine in their brains without acute toxicity. PrP^Sc levels in the brains of prion-inoculated MDR^0/0 mice diminished upon the initiation of quinacrine treatment. However, this reduction was transient and PrP^Sc levels recovered despite the continuous administration of quinacrine. Treatment with quinacrine did not prolong the survival times of prion-inoculated, wild-type or MDR^0/0 mice compared to untreated mice. A similar phenomenon was observed in cultured differentiated prion-infected neuroblastoma cells: PrP^Sc levels initially decreased after quinacrine treatment then rapidly recovered after 3 d of continuous treatment. Biochemical characterization of PrP^Sc that persisted in the brains of quinacrine-treated mice had a lower conformational stability and different immunoaffinities compared to that found in the brains of untreated controls. These physical properties were not maintained upon passage in MDR^0/0 mice. From these data, we propose that quinacrine eliminates a specific subset of PrP^Sc conformers, resulting in the survival of drug-resistant prion conformations. Transient accumulation of this drug-resistant prion population provides a possible explanation for the lack of in vivo efficacy of quinacrine and other antiprion drugs.     

Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents

Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies.     

Differences and similarities between mesenchymal stem cell and endothelial progenitor cell immunoregulatory properties against T cells

Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders. Although both cell populations have been already studied and used for their regenerative potentials, recently their special immunoregulatory features have brought much more attention. Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response, particularly T cell proliferation, activation, and cytokine production. This makes them suitable choices for allogeneic stem cell transplantation. Nevertheless, these two cells do not have equal immunoregulatory activities. Many elements including their extraction sources, age/passage, expression of different markers, secretion of bioactive mediators, and some others could change the efficiency of their immunosuppressive function. However, to our knowledge, no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells. This review aims to specifically compare the immunoregulatory effect of these two populations including their Tcell suppression, deactivation, cytokine production, and regulatory T cells induction capacities. Moreover, it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties.     

Characterization of a putative filovirus vaccine: Virus-like particles

Filoviruses are hemorrhagic fever viruses endemic to parts of Africa and the Philippines. Infection carries with it a mortality rate of up to 90% and currently there are no effective vaccines or therapeutics available to combat infection. However, the filovirus virus-like particles (VLP), which are currently under development, have been shown to be a promising vaccine candidate. They provide protection from infection in the mouse, guinea pig, and nonhuman primate models of infection, eliciting high anti-glycoprotein antibody titers and T cell responses to viral proteins. In this review, we will highlight the development of the filovirus VLP and describe the current understanding of VLP immunogenicity and correlates of protection.