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211.
212.
Mitigation measures for pandemic influenza in Italy: an individual based model considering different scenarios 总被引:1,自引:0,他引:1
Ciofi degli Atti ML Merler S Rizzo C Ajelli M Massari M Manfredi P Furlanello C Scalia Tomba G Iannelli M 《PloS one》2008,3(3):e1790
Background
Individual-based models can provide the most reliable estimates of the spread of infectious diseases. In the present study, we evaluated the diffusion of pandemic influenza in Italy and the impact of various control measures, coupling a global SEIR model for importation of cases with an individual based model (IBM) describing the Italian epidemic.Methodology/Principal Findings
We co-located the Italian population (57 million inhabitants) to households, schools and workplaces and we assigned travel destinations to match the 2001 census data. We considered different R0 values (1.4; 1.7; 2), evaluating the impact of control measures (vaccination, antiviral prophylaxis -AVP-, international air travel restrictions and increased social distancing). The administration of two vaccine doses was considered, assuming that first dose would be administered 1-6 months after the first world case, and different values for vaccine effectiveness (VE). With no interventions, importation would occur 37–77 days after the first world case. Air travel restrictions would delay the importation of the pandemic by 7–37 days. With an R0 of 1.4 or 1.7, the use of combined measures would reduce clinical attack rates (AR) from 21–31% to 0.3–4%. Assuming an R0 of 2, the AR would decrease from 38% to 8%, yet only if vaccination were started within 2 months of the first world case, in combination with a 90% reduction in international air traffic, closure of schools/workplaces for 4 weeks and AVP of household and school/work close contacts of clinical cases. Varying VE would not substantially affect the results.Conclusions
This IBM, which is based on country-specific demographic data, could be suitable for the real-time evaluation of measures to be undertaken in the event of the emergence of a new pandemic influenza virus. All preventive measures considered should be implemented to mitigate the pandemic. 相似文献213.
Notari S Strammiello R Capellari S Giese A Cescatti M Grassi J Ghetti B Langeveld JP Zou WQ Gambetti P Kretzschmar HA Parchi P 《The Journal of biological chemistry》2008,283(45):30557-30565
In prion disease, the abnormal conformer of the cellular prion protein, PrP(Sc), deposits in fibrillar protein aggregates in brain and other organs. Limited exposure of PrP(Sc) to proteolytic digestion in vitro generates a core fragment of 19-21 kDa, named PrP27-30, which is also found in vivo. Recent evidence indicates that abnormal truncated fragments other than PrP27-30 may form in prion disease either in vivo or in vitro. We characterized a novel protease-resistant PrP fragment migrating 2-3 kDa faster than PrP27-30 in Creutzfeldt-Jakob disease (CJD) brains. The fragment has a size of about 18.5 kDa when associated with PrP27-30 type 1 (21 kDa) and of 17 kDa when associated with type 2 (19 kDa). Molecular mass and epitope mapping showed that the two fragments share the primary N-terminal sequence with PrP27-30 types 1 and 2, respectively, but lack a few amino acids at the very end of C terminus together with the glycosylphosphatidylinositol anchor. The amounts of the 18.5- or 17-kDa fragments and the previously described 13-kDa PrP(Sc) C-terminal fragment relatively to the PrP27-30 signal significantly differed among CJD subtypes. Furthermore, protease digestion of PrP(Sc) or PrP27-30 in partially denaturing conditions generated an additional truncated fragment of about 16 kDa only in typical sporadic CJD (i.e. MM1). These results show that the physicochemical heterogeneity of PrP(Sc) in CJD extends to abnormal truncated forms of the protein. The findings support the notion of distinct structural "conformers" of PrP(Sc) and indicate that the characterization of truncated PrP(Sc) forms may further improve molecular typing in CJD. 相似文献
214.
Coexistence of predominantly nonculturable rhizobia with diverse, endophytic bacterial taxa within nodules of wild legumes 总被引:1,自引:0,他引:1
Muresu R Polone E Sulas L Baldan B Tondello A Delogu G Cappuccinelli P Alberghini S Benhizia Y Benhizia H Benguedouar A Mori B Calamassi R Dazzo FB Squartini A 《FEMS microbiology ecology》2008,63(3):383-400
A previous analysis showed that Gammaproteobacteria could be the sole recoverable bacteria from surface-sterilized nodules of three wild species of Hedysarum. In this study we extended the analysis to eight Mediterranean native, uninoculated legumes never previously investigated regarding their root-nodule microsymbionts. The structural organization of the nodules was studied by light and electron microscopy, and their bacterial occupants were assessed by combined cultural and molecular approaches. On examination of 100 field-collected nodules, culturable isolates of rhizobia were hardly ever found, whereas over 24 other bacterial taxa were isolated from nodules. None of these nonrhizobial isolates could nodulate the original host when reinoculated in gnotobiotic culture. Despite the inability to culture rhizobial endosymbionts from within the nodules using standard culture media, a direct 16S rRNA gene PCR analysis revealed that most of these nodules contained rhizobia as the predominant population. The presence of nodular endophytes colocalized with rhizobia was verified by immunofluorescence microscopy of nodule sections using an Enterobacter-specific antibody. Hypotheses to explain the nonculturability of rhizobia are presented, and pertinent literature on legume endophytes is discussed. 相似文献
215.
Pica-Mattoccia L Orsini T Basso A Festucci A Liberti P Guidi A Marcatto-Maggi AL Nobre-Santana S Troiani AR Cioli D Valle C 《Experimental parasitology》2008,119(3):332-335
The schistosomicidal activity of praziquantel (PZQ) is accompanied by a large influx of calcium into the worms, suggesting that this phenomenon could be the source of the observed muscular contraction, surface disruption and eventual death of the parasite. We have incubated live adult schistosomes in a medium containing radioactive calcium and we were able to confirm that PZQ does indeed stimulate calcium entry into the parasite. An even higher calcium uptake, however, occurred in schistosomes exposed to PZQ after pre-incubation with cytochalasin D, a condition that suppresses PZQ schistosomicidal effects and allows the complete survival of the parasites. The calcium blockers nicardipine and nifedipine also failed to prevent the calcium influx induced by PZQ. Similarly, a large calcium influx occurred in 28-day-old worms exposed to PZQ, in spite of the fact that these immature worms are largely insensitive to the schistosomicidal effects of the drug. Schistosomes incubated overnight with radioactive calcium and PZQ and then returned to normal medium, retained a calcium content higher than worms pre-incubated with cytochalasin D, but the difference could be a consequence—rather than a cause—of schistosomicidal effects. These results suggest that calcium accumulation by itself, at least as measured in whole parasites maintained in vitro, may not represent an exhaustive explanation for the schistosomicidal effects of PZQ. 相似文献
216.
Ricchiuto P Rocco AG Gianazza E Corrada D Beringhelli T Eberini I 《Journal of molecular recognition : JMR》2008,21(5):348-354
Chicken liver bile acid binding protein (cL-BABP) crystallizes with water molecules in its binding site. To obtain insights on the role of internal water, we performed two 100 ns molecular dynamics (MD) simulations in explicit solvent for cL-BABP, as apo form and as a complex with two molecules of cholic acid, and analyzed in detail the dynamics properties of all water molecules. The diffusion coefficients of the more persistent internal water molecules are significantly different from the bulk, but similar between the two protein forms. A different number of molecules and a different organization are observed for apo- and holo-cL-BABP. Most water molecules identified in the binding site of the apo-crystal diffuse to the bulk during the simulation. In contrast, almost all the internal waters of the holo-crystal maintain the same interactions with internal sidechains and ligands, which suggests they have a relevant role in protein-ligand molecular recognition. Only in the presence of these water molecules we were able to reproduce, by a classical molecular docking approach, the structure of the complex cL-BABP::cholic acid with a low ligand root mean square deviation (RMSD) with respect to its reference positioning. Literature data reported a conserved pattern of hydrogen bonds between a single water molecule and three amino acid residues of the binding site in a series of crystallized FABP. In cL-BABP, the interactions between this conserved water molecule and the three residues are present in the crystal of both apo- and holo-cL-BABP but are lost immediately after the start of molecular dynamics. Copyright (c) 2008 John Wiley & Sons, Ltd. 相似文献
217.
Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis 总被引:1,自引:0,他引:1
Grattagliano I Palmieri VO Portincasa P Moschetta A Palasciano G 《The Journal of nutritional biochemistry》2008,19(8):491-504
Although the biochemical steps linking insulin resistance with the metabolic syndrome have not been completely clarified, mounting experimental and clinical evidence indicate oxidative stress as an attractive candidate for a central pathogenic role since it potentially explains the appearance of all risk factors and supports the clinical manifestations. In fact, metabolic syndrome patients exhibit activation of biochemical pathways leading to increased delivery of reactive oxygen species, decreased antioxidant protection and increased lipid peroxidation. The described associations between increased abdominal fat storage, liver steatosis and systemic oxidative stress, the diminished concentration of nitric oxide derivatives and antioxidant vitamins and the endothelial oxidative damages observed in subjects with the metabolic syndrome definitively support oxidative stress as the common second-level event in a unifying pathogenic view. Moreover, it has been observed that oxidative stress regulates the expression of genes governing lipid and glucose metabolism through activation or inhibition of intracellular sensors. Diet constituents can modulate redox reactions and the oxidative stress extent, thus also acting on nuclear gene expression. As a consequence of the food-gene interaction, metabolic syndrome patients may express different disease features and extents according to the different pathways activated by oxidative stress-modulated effectors. This view could also explain family differences and interethnic variations in determining risk factor appearance. This review mechanistically focused on oxidative stress events leading to individual disease factor appearance in metabolic syndrome patients and their setting for a more helpful clinical approach. 相似文献
218.
RecG interacts directly with SSB: implications for stalled replication fork regression 总被引:1,自引:1,他引:0
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RecG and RuvAB are proposed to act at stalled DNA replication forks to facilitate replication restart. To define the roles of these proteins in fork regression, we used a combination of assays to determine whether RecG, RuvAB or both are capable of acting at a stalled fork. The results show that RecG binds to the C-terminus of single-stranded DNA binding protein (SSB) forming a stoichiometric complex of 2 RecG monomers per SSB tetramer. This binding occurs in solution and to SSB protein bound to single stranded DNA (ssDNA). The result of this binding is stabilization of the interaction of RecG with ssDNA. In contrast, RuvAB does not bind to SSB. Side-by-side analysis of the catalytic efficiency of the ATPase activity of each enzyme revealed that (−)scDNA and ssDNA are potent stimulators of the ATPase activity of RecG but not for RuvAB, whereas relaxed circular DNA is a poor cofactor for RecG but an excellent one for RuvAB. Collectively, these data suggest that the timing of repair protein access to the DNA at stalled forks is determined by the nature of the DNA available at the fork. We propose that RecG acts first, with RuvAB acting either after RecG or in a separate pathway following protein-independent fork regression. 相似文献
219.
Perrino E Cappelletti G Tazzari V Giavini E Del Soldato P Sparatore A 《Bioorganic & medicinal chemistry letters》2008,18(6):1893-1897
One dithiolthione and two new methanethiosulfonate derivatives of valproic acid (VPA) were synthesized and tested in vitro as histone deacetylase (HDAC) inhibitors. The new molecules, as well as their sulfurated moieties, exhibited a much stronger inhibition of HDAC enzymatic and antiproliferative activities and histone hyperacetylation than VPA. ACS 2 is the most interesting compound among the new VPA derivatives and its sulfurated moiety, 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione, also known to be a metabolite of anethole trithione, seems to contribute significantly to its activity. This is the first time that HDAC inhibitory activity is described for dithiolethiones and thiosulfonates. 相似文献
220.
Piero Genovesi 《Biological invasions》2005,7(1):127-133
Eradication of alien species is a key conservation tool to mitigate the impacts caused by biologic invasions. The aim of the
present paper is to review the eradications successfully completed in Europe and to discuss the main limits to a wider application
of this management option in the region. On the basis of the available literature – including conference proceedings, national
reports to the Bern Convention, etc. – a total of 37 eradication programmes have been recorded. Thirty-three eradications
were carried out on islands and four on the mainland. The rat (Rattus spp.) has been the most common target (n = 25, 67%), followed by the rabbit (n = 4). In many cases, these eradications determined a significant recovery of native biodiversity. Differently to other regions
of the world, no eradications of alien invertebrates and marine organisms have been recorded; regarding invasive alien plants,
it appears that only some very localized removals have been completed so far in Europe. The limited number of eradications
carried out in Europe so far is probably due to the limited awareness of the public and the decision makers, the inadequacy
of the legal framework, and the scarcity of resources. Synthetic guidelines for improving the ability of European states to
respond to aliens incursions are presented.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献