1,721,043 research outputs found
Franco Colombo, Livio Dorigo, Walter Macovaz, Franca Maselli Scotti, Claudia Pecile, Roland Marino, Vido Vivoda: Civiltà contadina in Istria. Trieste, Circolo di cultura istro-veneta \u27Istria\u27, 2005
Franco Colombo, Livio Dorigo, Walter Macovaz, Franca Maselli Scotti, Claudia Pecile, Roland Marino, Vido Vivoda: Civilta contadina in Istria. Trieste, Circolo di cultura istro-veneta \u27Istria\u27, 200
A HIGHLY STABLE, PROTEASE-RESISTANT E. COLI ASPARAGINASE
An invention which can help the treatment of Acute Lymphoblastic Leukaemia
Structural basis of affinity maturation of the TEPC15/Vkappa 45.1 anti-2-phenyl-5-oxazolone antibodies.
Affinity maturation is a process that leads to the emergence of more efficient antibodies following initial antigen encounter and represents a key strategy of the adaptive immunity of vertebrate organisms. Earlier and detailed sequence studies of the antibody response to a model antigen, the hapten 2-phenyl-5-oxazolone (phOx), define three different classes of antibodies. Class I antibodies use the V(H)Ox1/V(kappa)Ox1 gene pair and dominate the early stages of the anti-phOx response, class II antibodies use the V(kappa)Ox1 gene but a different V(H) segment and are common in the intermediate stages, and class III antibodies use the TEPC15/V(kappa)45.1 genes and play the greatest role in the late stages. Only the crystal structure of one anti-phOx antibody, the class II NQ10/12.5 Fab fragment, has been described. Here we report the crystal structures of the scFv form of the low and high affinity anti-phOx class III antibodies NQ10/1.12 and NQ16/113.8 complexed with the hapten. The two antibodies differ by nine amino acid substitutions, all located in the V(H) domain. Analysis of the two structures shows that affinity maturation results from an increase in surface complementarity, as a consequence of a finely tuned and highly concerted process chaperoned by the somatic mutations, and implies a more efficient hapten-induced fit in the mature antibody. The data also demonstrate that class III antibodies respond in a completely different way to the architectural problem of binding phOx compared to the class II antibody NQ10/12.5
Real Time Cell Analysis of Model Target Cell Lines Exposed to Purified Lipoprotein (a)
Lipoprotein (a) [Lp(a)] is a novel independent cardiovascular risk factor and it includes, beyond
apoB100, apolipoprotein (a), whose molecular weight is dependent on the number of genetically
encoded kringle IV type 2 repeats and inversely related with Lp(a) plasma concentration. Risk
thresholds for molecular weights have been proposed, but there is not a full consensus and the
role of the different isoforms in pathogenesis has not yet been clarified. The aim of the present
work is to explore the biological effect of low and high molecular weight Lp(a) isoforms on cultured
cells. Real-time impedance analysis has been performed on model cell lines of atherogenesis and
Lp(a) metabolism (THP-1, HUVEC, HASMC and HepG2) using affinity purified Lp(a) with 22 (low
number) and 31 (high number) kringle IV type 2 repeats, respectively. Normalized Cell Index data
show that all the cell lines tested are modified by Lp(a), though with a variable intensity. Low and
high molecular weight Lp(a) isoforms at similar concentrations can exert opposite modifications onthe impedance kinetics of different cell lines. These data suggest that purified Lp(a) can modify the
behaviour of adherent cell lines, an effect which can be detected as impedance variation and which
is influenced by its specific isoform
Structural Basis of Affinity Maturation of Antibodies in the 2-Phenyl-5-Oxazolone System
Structural Basis of Affinity Maturation of Antibodies in the 2-Phenyl-5-Oxazolone System
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