CpG drives human transitional B cells to terminal differentiation and production of natural antibodies

The receptor TLR9, recognizing unmethylated bacterial DNA (CpG), is expressed by B cells and plays a role in the maintenance of serological memory. Little is known about the response of B cells stimulated with CpG alone, without additional cytokines. In this study, we show for the first time the phenotypic modification, changes in gene expression, and functional events downstream to TLR9 stimulation in human B cell subsets. In addition, we demonstrate that upon CpG stimulation, IgM memory B cells differentiate into plasma cells producing IgM Abs directed against the capsular polysaccharides of Streptococcus pneumoniae. This novel finding proves that IgM memory is the B cell compartment responsible for the defense against encapsulated bacteria. We also show that cord blood transitional B cells, corresponding to new bone marrow emigrants, respond to CpG. Upon TLR9 engagement, they de novo express AID and Blimp-1, genes necessary for hypersomatic mutation, class-switch recombination, and plasma cell differentiation and produce Abs with anti-pneumococcal specificity. Transitional B cells, isolated from cord blood, have not been exposed to pneumococcus in vivo. In addition, it is known that Ag binding through the BCR causes apoptotic cell death at this stage of development. Therefore, the ability of transitional B cells to sense bacterial DNA through TLR9 represents a tool to rapidly build up the repertoire of natural Abs necessary for our first-line defense at birth.     

The intervention of antioxidant therapy on platelet adhesion and immunomodulation in experimental physical stress

During effort overstress the reactive oxygen species act chiefly on unsaturated lipids, inducing the formation of certain peroxidation products. We have investigated malondialdehide (MDA), platelet adhesion index, and immunological activation parameters during effort overstress and administration of vitamins E and C. Biochemical measurements were performed on erythrocytes and heart homogenate. In the vitamin E supplemented group, the platelet adhesion index was constantly correlated with the MDA level (p < 0.001). There is a protecting effect concerning the oxidative stress in animals pretreated with vitamin E and C, which is expressed through the diminution of the MDA quantity both in the erythrocyte and in the heart. The physical effort required by swimming led to a decrease in the NBT test values and in the activity of the serum complement. The steady administration of vitamin E in the effort overstress, due to its antioxidant properties, causes the progressive decrease in peroxidation and platelet adhesion.     

Functional and postural lateral preferences in humans: interrelations and life-span age differences

This study aimed to provide data on lateral preferences among older subjects, to analyze age differences, and to determine interrelations between lateral preferences. Four functional preferences (handedness, footedness, eyedness, earedness) and three postural lateral preferences (hand-clasping, arm-folding, leg-crossing) were assessed in 628 Germans (252 men, 376 women) aged between 19 and 90 years. Sex differences, age differences, and associations between lateralities were analyzed applying chi-square tests. Logistic regression analyses considering age, sex, and interactions between variables were applied to analyze combined effects on laterality measures. Right-sided preference for handedness, footedness, eyedness, earedness, and leg-crossing characterized 86.8%, 77.1%, 70.9%, 67.8%, and 56.6%, respectively, of subjects, while a left-sided preference for hand-clasping and arm-folding characterized 56.4% and 60.2%, respectively, of all participants. Results are within the range of other populations. Only footedness differed between the sexes: there were more left-footed men. Older cohorts showed a rightward shift in handedness, eyedness, earedness, and leg-crossing, the opposite for arm-folding. No age-related differences exist in footedness or hand-clasping. Logistic regression models indicate no interaction between age and sex for each laterality measure. The four functional lateralities are significantly interrelated. All also are positively associated with leg-crossing. Conversely, the postural lateralities generally are not correlated, although leg-crossing and arm-folding are, inversely. The observed relationships among lateralities support the hypothesis that handedness, footedness, leg-crossing, and earedness might be aspects of a larger phenotype that is independent of hand-clasping and arm-folding.     

Synthesis, physicochemical properties, and preliminary biological characterizations of a novel amphoteric agmatine-based poly(amidoamine) with RGD-like repeating units

A linear, amphoteric poly(amidoamine) nicknamed AGMA1, based on 4-aminobutylguanidine, or agmatine, was successfully prepared by Michael-type polyaddition of monoprotonated agmatine and 2,2-bis(acrylamido)acetic acid (BAC). Copolymers between AGMA1 and the biocompatible poly(amidoamine) ISA23 (deriving from the polyaddition of 2-methylpiperazine with BAC) were also prepared. Acid-base titrations gave for AGMA1 three acid dissociation constants, with pKa values of 2.25, 7.45, and >or=12.1, corresponding to a strong acid, a medium-weak base, and a strong base, respectively. The charge distribution profiles show that this polymer is prevailingly cationic at all physiological pH values, the positive net average charge per unit varying from about 0.5 at pH 7.4 to about 1.0 at pH 5, with an isoelectric point at pH approximately 10. Zeta-potential measurements confirmed this. Despite that, AGMA1 is nontoxic and nonhemolytic in vitro within all pH ranges tested (4-7.5). This is in contrast with the previously observed behavior of amphoteric PAAs, for instance ISA23, that are weakly hemolytic at pH 7.4 but highly hemolytic at pH 5/5.5. The lack of hemolytic activity of AGMA1 even at acidic pH values seems typical of the agmatine-BAC sequences and may be ascribed to their RGD-like structure. In fact, AGMA1-ISA23 copolymers behave in a way increasingly similar to that of ISA23; that is, they become hemolytic at low pH values as their ISA23 content increases.