Restriction of AID activity and somatic hypermutation by PARP-1

Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has been identified to date. Here we show that poly(ADP-ribose) polymerase-1 (PARP-1) is a key factor restricting AID activity during somatic hypermutation. Poly(ADP-ribose) (PAR) chains formed at DNA breaks trigger AID-PAR association, thus preventing excessive DNA damage induction at sites of AID action. Accordingly, AID activity and somatic hypermutation at the Ig variable region is decreased by PARP-1 activity. In addition, PARP-1 regulates DNA lesion processing by affecting strand biased A:T mutagenesis. Our study establishes a novel function of the ancestral genome maintenance factor PARP-1 as a critical local feedback regulator of both AID activity and DNA repair during Ig gene diversification

Freeze-drying method as a new approach to the synthesis of polyurea aerogels from isocyanate and water

Polyurea (PUA) aerogels were prepared as the polycondensation product of triisocyanate and water. PUA aerogels were formed through supercritical drying (SC) and, for comparison, by freeze-drying (FD). The effect of isocyanate concentration, catalyst concentration, and drying method on properties like density, specific surface area, pore volume, compressive strength, and morphology was investigated. The properties of aerogels strongly depend on the concentration of the isocyanate in the parent solution and, to a lesser extent, on catalyst concentration. For example, aerogels with higher isocyanate concentration exhibited a higher surface area and modulus. Depending on the formulation, the materials had a density between 0.128 and 0.220 g/cm3, surface area between 140 and 210 m2/g, pore volume between 0.593 and 1.500 cm3/g, compressive modulus between 6.5 and 25 MPa, and thermal conductivity between about 0.028 and 0.033 W/m K. Most importantly, the drying method did not strongly affect the properties of the materials. These were within ~15% for SC and FD. The results indicate that freeze-drying can be successfully used to fabricate aerogels in a cost-effective way. Open image

Density and shrinkage as guiding criteria for the optimization of the thermal conductivity of poly(urethane)-class aerogels

We investigated the effect of gelation solvent, monomer type, and monomer concentration on the physical properties of freeze-dried poly(urethane)-poly(isocyanurate) (PUR-PIR) aerogels, with particular emphasis on their thermal conductivity. It was found that the gelation solvent considerably affects aerogel morphology and physical properties. Aerogels with the lowest thermal conductivity were obtained using a mixture of tetrahydrofuran (THF) and acetonitrile, in a 50% volume ratio. The influence on thermal conductivity of polyol and isocyanate structure and of their concentration was also investigated. Rigid precursors, phloroglucinol (POL), and an aromatic polyisocyanate based on toluene diisocyanate (Desmodur RC) yielded the lowest thermal conductivity. Our results were compared with recent work reporting on parameters that could be used as predictors of thermal conductivity and other physical properties of organic aerogels. None of these parameters were found to be satisfactory predictors of aerogel properties. For example, no systematic correlation between solvent solubility parameters and aerogel properties was observed. We also examined the role of the K-index. This index, defined as the ratio between porosity and contact angle, was shown recently to be a good predictor of the properties of polyurea aerogels. While the thermal conductivity scaled with the K-index, the scaling was different for each of the isocyanate monomers considered in our experiments. Thermal conductivity, instead, scaled well with the product of density and shrinkage of aerogels, independent of monomer type. The reasons of this dependence on shrinkage and density are discussed, and the use of these parameters to guide experimentation on other systems is discussed. Physical properties such as static and dynamic compression modulus and thermal stability of the most promising formulations were also examined