Interaction of Pseudomonas Bacteriophage 2 with the Slime Polysaccharide and Lipopolysaccharide of Pseudomonas aeruginosa Strain BI

Purified slime polysaccharide B and lipopolysaccharide of Pseudomonas aeruginosa strain BI were shown to possess receptor-like properties in inactivating Pseudomonas phage 2, whereas lipoprotein and glycopeptide fractions were devoid of activity. On a weight basis, slime polysaccharide B was more effective than lipopolysaccharide in inactivating phage. The specificity of the reaction with slime polysaccharide B was indicated by the fact that slime polysaccharide A of P. aeruginosa strain EI failed to inactivate phage 2. Electron micrographs showed phage 2 in typical, tail-first position of attachment on intact cells of strain BI, slime polysaccharide B, and lipopolysaccharide. Tail fibers were discernible during phage attachment.     

Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²–3×10⁻¹⁰), with heterogeneity detected only at the PSMB9/TAP1 locus (I² = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻⁴). A seven–SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²⁸). This model paralleled the known East–West gradient in disease risk. Moreover, the prediction of a South–North axis was confirmed by registry data showing that the prevalence of IgAN–attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.     

Aging and sex influence the permeability of the blood-brain barrier in the rat

The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging- and sex-related alterations in the permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.     

Tag loss is a minor limiting factor in sea turtle tagging programs relying on distant tag returns: the case of Mediterranean loggerhead sea turtles

As in many other species, tagging has been routinely conducted for decades in over a hundred sea turtle capture-mark-recapture (CMR) programs worldwide. Tag loss is a key limiting factor because it violates the main assumption in CMR models; however, very few estimates of tag loss exist, and we provide here a review. No published estimations of tag loss are available for the Mediterranean, in spite of intensive tagging since the 1980s. This study aims to provide an estimation of tag loss in loggerhead turtles tagged in the Mediterranean. We modeled 64 tag returns out of ca. 2200 loggerhead turtles tagged at Mediterranean foraging grounds, with mark-recapture intervals up to 11.5 years, in order to estimate a daily tag loss probability of the most used tag applied to the most common turtle species in the region. Five models were evaluated through maximum likelihood estimation. The model with the best fit described a tag loss initially high and then decreasing to a lower asymptote, which is probably due to some defective tag applications. The resulting tag loss (0.15 in the first year and 0.31 after 5 years) was comparable or even lower than those from other areas and/or species and predictions indicate that double tagging can make a turtle identifiable for a long period. Hence, in our tagging program and probably in similar ones as well, tag loss appears to be the less important of the factors affecting tag returns, and efforts in other directions are more likely to improve CMR results.     

The tissue banking in cancer and stem cell research

The Sapio Award was established in 1999 by the Sapio Group along with several Italian universities and research centers to recognize Italian scientists who have made a major contribution to the discovery or development of novel technologies in the fields of biotechnology, social and health services, nonotechnology and biosecurity in agricultural production and scientific distribution. The 2006 edition of the award meeting centered around the issues of tissue banks and biorepositories and translational medicine. The organizing committee divided this edition into a pre-meeting held in Milan on October 18, 2006 and a master meeting on October 19, 2006, held at the ISS in Rome. A summary of these meetings is given.     

Speciation of phytate ion in aqueous solution. Protonation constants and copper(II) interactions in NaNO3aq at different ionic strengths

The acid base behavior of phytate has been studied (at t=25 degrees C by potentiometry, ISE-H+ glass electrode) in NaNO3aq at different ionic strengths (0.1 < or = I/mol L(-1) < or = 1.0). The interactions with copper(II) were investigated in the same experimental conditions in different metal to ligand (Phy) ratios (1:1 < or = Cu2+ :Phy < or = 4:1), by using both ISE-H+ and ISE-Cu2+ electrodes. Phytate acid base behavior in sodium nitrate is very similar to that in sodium chloride, previously investigated. In the experimental conditions adopted, the formation of three CuiHjPhy(12-2i-j)- species is observed: the mononuclear CuH4Phy6- and CuH5Phy5-, and the dinuclear Cu2H5Phy3-. Analysis of complex formation constants at different ionic strengths reveals that both ISE-H+ and ISE-Cu2+ electrodes gave, within the experimental error, analogous values. Dependence of complex formation constants on ionic strength was modeled by EDH (Extended Debye-Hückel) and SIT (Specific ion Interaction Theory) equations. The sequestering ability of phytate toward copper(II) has been evaluated by the calculation of pL50 (the total ligand concentration, as -log CL, able to bind 50% of metal cation), an empirical parameter already proposed for an objective "quantification" of this ability. A thorough analysis of literature data on phytate-copper(II) complexes has been performed.     

Differences in Variation of Human Immunodeficiency Virus Type 1 Sequences from Henan and Shanghai Regions of China

Illegally paid blood donation was a risk factor for HIV acquisition exclusively in Henan and Hubei Provinces of China,and not in Shanghai.Nucleotide sequences in the gag and env genes of HIV-1 were compared between isolates from Henan and Shanghai regions of China to test whether an expected higher degree of a common source of infections from this unique blood donation transmission risk would be evident as decreased variation among Henan isolates in an exploratory cross-sectional analysis.Among 38 isolates studied,23 of 23(100%)from Henan and 8 of 15(54%)from Shanghai were subtype B.In addition,fewer sequence differences were found in gp41 of subtype B isolates from Henan than from Shanghai isolates.Further studies with additional controls are therefore warranted to confirm the role of the degree of a common source of infections in differences in HIV variation across populations.     

Glycerophosphoinositol-4-phosphate enhances SDF-1alpha-stimulated T-cell chemotaxis through PTK-dependent activation of Vav

Glycerophosphoinositols (GPIs) are water-soluble phosphoinosite metabolites produced by all cell types, whose levels increase in response to a variety of extracellular stimuli, and are particularly high in Ras-transformed cells. GPIs are released to the extracellular space, wherefrom they can be taken up by other cells through a specific transporter. Exogenous GPIs affect a plethora of cellular functions. Among these compounds the most active is GroPIns4P, which affects cAMP levels and PKA-dependent functions through the inhibition of heterotrimeric Gs proteins. GroPIns4P has also recently been found to promote actin cytoskeleton reorganization by inducing Rho and Rac activation through an as yet unidentified mechanism. Here we have assessed the potential effects of GroPIns4P on T-cells. We found that GroPIns4P enhances CXCR4-dependent chemotaxis. This activity results from the capacity of GroPIns4P to activate the Rho GTPase exchange factor, Vav, through an Lck-dependent pathway which also results in activation of the stress kinases JNK and p38. GroPIns4P was also found to activate with a delayed kinetics the Lck-dependent activation of ZAP-70, Shc and Erk1/2. The activities of GroPIns4P were found to be dependent on its capacity to inhibit cAMP production and PKA activation. Collectively, the data provide the first evidence of a role of glycerophosphoinositols as modulators of T-cell signaling and establish a mechanistic basis for the effects of this phosphoinositide derivative on F-actin dynamics.