Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.

The P-N bond hydrolysis of the 4-methoxyphenyl-ammonium ethylamido-phosphonodithioato ligand during its complexation to NiII leads to the first example of phosphonodithioato nickel(II) complex having a cis configuration; this complex is stabilised in the solid state by an extensive and intricate network of hydrogen bondings involving the released ethylenediamine and a water molecule.

In this paper we present the experimental results obtained from phenyl acetate hydrolysis in a microwave-irradiated environment and in water solutions containing catalytic acetate ions. The kinetics of the reaction were studied in an irradiated environment where radiation, at a frequency of 2.45 GHz, was given to the reacting system at a power of 0.500 ± 0.025 W. The energy absorbed by the reacting system was measured using a directional coupler, which can separate the radiation directed to the reactor from any reflected one. The system was irradiated with a power greater than that required to run the reaction; however, any energy in excess of that absorbed by the reaction was quite easily taken up by a thermostatic system. In this way the reaction system could run without any thermal effect due to radiation. The temperature was set at 25 °C and was kept constant during the reaction by using carbon tetrachloride as the thermostating fluid. The results obtained show that the kinetics of the reaction studied were greatly enhanced with respect to those of the reaction running in a nonirradiated environment. The kinetic constant at zero concentration of the catalytic species rises from 1.92 × 10-4 h-1 in a nonirradiated environment to the value 27.58 × 10-4 h-1 found here. The observed kinetic constant retains the same value for all of the studied catalytic acetate ion concentrations. This fact suggests that microwave radiation produces something like a catalytic effect which can replace that given by acetate ions in nonirradiated environments.

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