Refuse derived bio-organics and immobilized soybean peroxidase for green chemical technology

A silica monolith was prepared from commercial silica powder dispersed in water containing polymeric water soluble bio-organics (SBOs) isolated from composted urban vegetable wastes. The monolith and the pristine powder were characterized for their morphology and reactivity for immobilizing soybean peroxidase (SBP). Compared to the pristine powder, the monolith exhibited lower specific surface area (about 30% less), total pore volume and pore size (of about 200 Å of width), and bond less SBP under the same experimental conditions. The immobilized SBP products were tested for their catalytic activity in the reaction of hydrogen peroxide, 3-(dimethylamino)benzoic acid (DMAB) and 3-methyl-2-benzothiazolinone hydrazone (MBTH), by comparison with the same reaction performed with native SBP in solution. The reaction performed in the presence of immobilized SBP was slower than that catalyzed by native SBP in solution. However, in spite of its lower SBP content, monolith immobilized SBP (M-SBP) was found kinetically more active than the powder immobilized SBP (P-SBP). Also, M-SBP allowed to achieve the same reagents conversion as native SBP (95% of reagent conversion), although in longer time, whereas the maximum reagent conversion achieved with P-SBP was much lower (75% of reagent conversion). The M-SBP was more easily recovered from the reaction medium and found more stable than P-SBP upon repeated catalyst recycling (after 20 cycles 75–80% of the initial activity was retained by both immobilized samples, slightly higher in the case of M-SBP).     

C. elegans Expressing Human β2-Microglobulin: A Novel Model for Studying the Relationship between the Molecular Assembly and the Toxic Phenotype

Availability of living organisms to mimic key step of amyloidogenesis of human protein has become an indispensable tool for our translation approach aiming at filling the deep gap existing between the biophysical and biochemical data obtained in vitro and the pathological features observed in patients. Human β₂-microglobulin (β₂-m) causes systemic amyloidosis in haemodialysed patients. The structure, misfolding propensity, kinetics of fibrillogenesis and cytotoxicity of this protein, in vitro, have been studied more extensively than for any other globular protein. However, no suitable animal model for β₂-m amyloidosis has been so far reported. We have now established and characterized three new transgenic C. elegans strains expressing wild type human β₂-m and two highly amyloidogenic isoforms: P32G variant and the truncated form ΔN6 lacking of the 6 N-terminal residues. The expression of human β₂-m affects the larval growth of C. elegans and the severity of the damage correlates with the intrinsic propensity to self-aggregate that has been reported in previous in vitro studies. We have no evidence of the formation of amyloid deposits in the body-wall muscles of worms. However, we discovered a strict correlation between the pathological phenotype and the presence of oligomeric species recognized by the A11 antibody. The strains expressing human β₂-m exhibit a locomotory defect quantified with the body bends assay. Here we show that tetracyclines can correct this abnormality confirming that these compounds are able to protect a living organism from the proteotoxicity of human β₂-m.     

Incoming pathogens team up with harmless 'resident' bacteria

Microbial diseases occur as a result of multifarious host-pathogen interactions. However, invading pathogens encounter a large number of different harmless and beneficial bacterial species, which colonize and reside in the host. Surprisingly, there has been little study of the possible interactions between incoming pathogens and the resident bacterial community. Recent studies have revealed that resident bacteria assist different types of incoming pathogens via a wide variety of mechanisms including cell-cell signaling, metabolic interactions, evasion of the immune response and a resident-to-pathogen switch. This calls for serious consideration of pathogen-microbe interactions in the host with respect to disease severity and progression.     

Study of the collateral capacity of the circle of Willis of patients with severe carotid artery stenosis by 3D computational modeling

This numerical study aims to investigate the capacity of the circle of Wills (CoW) to provide collateral blood supply for patients with unilateral carotid arterial stenosis. The basic 3D geometry of the CoW was reconstructed based on a magnetic resonance angiogram of a normal human subject. A total of 52 computational fluid dynamics simulations were performed for four geometry configurations of the CoW with an artificially inserted axisymmetric stenosis of different luminal area reductions in an internal carotid artery (ICA) under a variety of boundary conditions. The CoW geometric configurations included (a) a normal CoW with all communicating arteries; (b) as model (a) but with enlarged communicating arterial diameters; (c) as (a) but with the ipsilateral posterior communicating artery missing, and (d) as (c) but with enlarged communicating arteries. It is found that the blood perfusion pressure drop between the ipsilateral ICA and the middle cerebral artery (MCA) only becomes significant when the degree of stenosis is greater than 86%. The cerebral autoregulation range varied significantly between the different CoW configurations for the severe stenosis cases. Without causing the flow rates to decrease at the efferent arterial ends, the mean perfusion pressure in the ipsilateral ICA can drop from 100 to 73, 67, 92 and 84mmHg for the CoW models (a)-(d) with 96% luminal area reduction stenosis, respectively. The additional pathways are able to raise the ipsilateral MCA pressure significantly without reducing the total flow perfusion. Cerebral autoregulation effects were not directly included in the study. Therefore, the findings in the study should be interpreted with cautions when comes to the biological and clinical significance.     

Ghrelin induces proliferation in human aortic endothelial cells via ERK1/2 and PI3K/Akt activation

The direct ghrelin (Ghr) involvement in cardiovascular (CV) system homeostasis has been suggested by the expression of its receptor in CV tissues and by evidence that ghrelin mediates CV activities in animals and in humans. Moreover, low Ghr plasma levels have been reported in pathological conditions characterized by high cardiovascular risk. In the present study, we investigated Ghr effect on proliferation of human aortic endothelial cell (HAEC) and involved transduction pathways. Our results indicate that ghrelin elicited proliferation in a dose-dependent manner (EC(50) about of 5nmol/L) in cultured HAEC, and that this effect was inhibited by the receptor antagonist (D-Lys3)-GHRP-6. Western blot experiments documented an activation of external receptor activated kinases (ERK1/2) and Akt in a dose-dependent fashion, as well as involvement of the cAMP pathway in ERK1/2 phosphorylation. Experiments conducted with appropriate pharmacological inhibitors to investigate Ghr-induced HAEC proliferation confirmed the involvement of ERK1/2 and I3P/Akt pathways, as well as the role of AMP cyclase/PKA pathway in ERK1/2 phosphorylation. Our results indicate that Ghr promotes HAEC proliferation, and thus may be a protective factor against vascular damage. The low ghrelin serum levels reported in insulin-resistant states may not be able to effectively counteract endothelial cell injury.     

Temporin A is effective in MRSA-infected wounds through bactericidal activity and acceleration of wound repair in a murine model

We investigated the effect of topical temporin A in the management of methicillin-resistant strain of Staphylococcus aureus (MRSA)-infected experimental surgical wounds in mice. The wound, cut through the panniculus carnosus of BALB/c mice, was inoculated with 5x10(7) colony-forming units of MRSA. Mice were treated with Allevyn, temporin A-soaked Allevyn, Allevyn and daily intraperitoneal teicoplanin (7mg/kg), temporin A-soaked Allevyn and daily intraperitoneal teicoplanin. Main outcome measurements were: quantitative bacterial culture, histological examination with assessment of micro-vessel density and of vascular endothelial growth factor (VEGF) expression in tissue sections, and VEGF plasma levels alike. Treatment with temporin-A associated with teicoplanin injection significantly reduced bacterial load to 0.85 x 10(1)+/-0.1 x 10(1)CFU/ml. Histological examination showed that infected mice receiving temporin A-soaked Allevyn (with or without teicoplanin) had a higher degree of granulation tissue formation and collagen deposition compared to the other treated groups. A significant increase in serum VEGF expression was observed in mice receiving temporin A topically and temporin A topically associated with intraperitoneal teicoplanin. In conclusion our results demonstrated that temporin A is effective in the management of infected wounds, by a significant bacterial growth inhibition and acceleration of wound repair process.     

Forecasting airborne pollen concentrations: Development of local models

People's sensitivity to allergies may representone of the most important health factors of thenext century to which attention must be paid inorder to reduce the incidence of social costsand improve the quality of life.Taking into consideration the earnest requestsof the medical-scientific communityEmilia-Romagna ARPA (Regional Agency for thePrevention of the Environment) moved theattention from the monitoring to a short andmedium term prediction of the concentration ofallergenic pollens in the air in order toachieve a more effective therapeutic action.Our main objectives are to improve seasonalforecasts and to interpret anomalous years.A neural network model for grass pollenforecasting has been implemented. Inputvariables were meteorological situations, i.e.,daily temperature (max., min. and average) andrainfall, in addition to combinations ofindividual variables and their thresholds. Theoutput was daily pollen concentration.The model was able to understand and predictanomalous years. We demonstrate that therelationships between pollen concentrations andmeteorological situations are independent fromsite. This means that such models canunderstand the differences in differentareas.     

Lack of CD27-CD45RA-V gamma 9V delta 2+ T cell effectors in immunocompromised hosts and during active pulmonary tuberculosis.

In humans, the circulating pool of mycobacteria-reactive Vgamma9Vdelta2+ T cells is expanded with age and may contribute to Mycobacterium tuberculosis immunosurveillance. We observed that two subsets of Vgamma9Vdelta2+ T cells could be identified on the basis of CD27 expression in immunocompetent adults, showing that functionally differentiated gammadelta T cells have lost CD27 expression. In contrast, the CD27-CD45RA-Vgamma9Vdelta2+ T cell subset of effector cells was absent in cord blood cells from healthy newborns and lacking in the peripheral blood from HIV-infected patients. Moreover, circulating Vgamma9Vdelta2+ T cell effectors were significantly reduced in patients with acute pulmonary tuberculosis, resulting in a reduced frequency of IFN-gamma-producing cells after stimulation with nonpeptidic mycobacterial ligands. These observations indicate that monitoring and boosting gammadelta T cell effectors could be clinically relevant both in immunocompromised hosts and during active tuberculosis disease.     

Polymorphism and mapping of the IGF1 gene,and absence of association with stature among African Pygmies

Summary Probes detecting restriction fragment length polymorphisms (RFLPs) in the insulinlike growth factor (IGF1) gene were isolated and allele frequencies in different human populations determined. No difference was detected between the distribution of IGF1 alleles in Pygmies versus non-Pygmy black Africans, despite the proposal that a defect in the IGF1 gene might be responsible for Pygmy short stature. This was supported by the absence of a correlation of IGF1 genotype with height in the C.A.R. Pygmies. Polymerase chain reaction (PCR) and direct sequencing failed to demonstrate an alteration in the region upstream the IGF1 start site in Pygmies. Linkage analysis demonstrated that IGF1 is tightly linked to the phenylalanine hydroxylase gene on chromosome 12q22–24.1.