Characterization of Metal and Trace Element Contents of Particulate Matter (PM10) Emitted by Vehicles Running on Brazilian FuelsHydrated Ethanol and Gasoline with 22% of Anhydrous Ethanol

Emission of fine particles by mobile sources has been a matter of great concern due to its potential risk both to human health and the environment. Although there is no evidence that one sole component may be responsible for the adverse health outcomes, it is postulated that the metal particle content is one of the most important factors, mainly in relation to oxidative stress. Data concerning the amount and type of metal particles emitted by automotive vehicles using Brazilian fuels are limited. The aim of this study was to identify inhalable particles (PM10) and their trace metal content in two light-duty vehicles where one was fueled with ethanol while the other was fueled with gasoline mixed with 22% of anhydrous ethanol (gasohol); these engines were tested on a chassis dynamometer. The elementary composition of the samples was evaluated by the particle-induced x-ray emission technique. The experiment showed that total emission factors ranged from 2.5 to 11.8 mg/km in the gasohol vehicle, and from 1.2 to 3 mg/km in the ethanol vehicle. The majority of particles emitted were in the fine fraction (PM2.5), in which Al, Si, Ca, and Fe corresponded to 80% of the total weight. PM10 emissions from the ethanol vehicle were about threefold lower than those of gasohol. The elevated amount of fine particulate matter is an aggravating factor, considering that these particles, and consequently associated metals, readily penetrate deeply into the respiratory tract, producing damage to lungs and other tissues.

Craniometaphyseal Dysplasia With Severe Craniofacial Involvement Shows Homozygosity at 6q21-22.1 Locus

Craniotubular dysplasias (CTD) are a heterogeneous group of genetic disorders of skeletal development, whose clinical and etiological classification is still much debated. One of the most common form is the autosomal dominant craniometaphyseal dysplasia (CMD) which is associated with mutation in the ANKH gene. In the literature a few families are reported with CMD phenotype that suggest an autosomal recessive (AR) pattern of inheritance. A candidate locus at 6q21-22 has been mapped in a large inbred Brazilian family, but the gene of the recessive form is still unknown. Our data on a female patient with CMD phenotype, born from healthy first degree cousins and displaying homozygosity for polymorphic markers at the 6q21-22 locus, further support the existence of an AR CMD, expanding its clinical spectrum to a more severe phenotype. (C) 2011 Wiley-Liss, Inc.

Novel OTOF mutations in Brazilian patients with auditory neuropathy

The OTOF gene encoding otoferlin is associated with auditory neuropathy (AN), a type of non-syndromic deafness. We investigated the contribution of OTOF mutations to AN and to non-syndromic recessive deafness in Brazil. A test for the Q829X mutation was carried out on a sample of 342 unrelated individuals with non-syndromic hearing loss, but none presented this mutation. We selected 48 cases suggestive of autosomal recessive inheritance, plus four familial and seven isolated cases of AN, for genotyping of five microsatellite markers linked to the OTOF gene. The haplotype analysis showed compatibility with linkage in 11 families (including the four families with AN). Samples of the 11 probands from these families and from seven isolated cases of AN were selected for an exon-by-exon screening for mutations in the OTOF gene. Ten different pathogenic variants were detected, among which six are novel. Among the 52 pedigrees with autosomal recessive inheritance (including four familial cases of AN), mutations were identified in 4 (7.7%). Among the 11 probands with AN, seven had at least one pathogenic mutation in the OTOF gene. Mutations in the OTOF gene are frequent causes of AN in Brazil and our results confirm that they are spread worldwide. Journal of Human Genetics (2009) 54, 382-385; doi: 10.1038/jhg.2009.45; published online 22 May 2009

Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism

Interleukin-22 (IL-22) is a member of the interleukin-10 cytokine family, which is involved in anti-microbial defenses, tissue damage protection and repair, and acute phase responses. Its signaling mechanism involves the sequential binding of IL-22 to interleukin-22 receptor 1 (IL-22R1), and of this dimer to interleukin-10 receptor 2 (IL-10R2) extracellular domain. We report a 1.9 A crystal structure of the IL-22/IL-22R1 complex, revealing crucial interacting residues at the IL-22/IL-22R1 interface. Functional importance of key residues was confirmed by site-directed mutagenesis and functional studies. Based on the X-ray structure of the binary complex, we discuss a molecular basis of the IL-22/IL-22R1 recognition by IL-10R2.

Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22

Interleukin-22 (IL-22) plays an important role in the regulation of immune and inflammatory responses in mammals. The IL-22 binding protein (IL-22BP), a soluble receptor that specifically binds IL-22, prevents the IL-22/interleukin-22 receptor 1 (IL-22R1)/interleukin-10 receptor 2 (IL-10R2) complex assembly and blocks IL-22 biological activity. Here we present the crystal structure of the IL-22/IL-22BP complex at 2.75 angstrom resolution. The structure reveals IL-22BP residues critical for IL-22 binding, which were confirmed by site-directed mutagenesis and functional studies. Comparison of IL-22/IL-22BP and IL-22/IL-22R1 crystal structures shows that both receptors display an overlapping IL-22 binding surface, which is consistent with the inhibitory role played by IL-22 binding protein.

Selective Sulfenylative Desulfonylation or Decarbalkoxylation of -Sulfonyl Malonates with DABCO or Bu3N: Reactivity and Conformational Analysis

The study on reactivity of several -substituted -sulfonyl malonates toward 1,4-diazabicyclo[2.2.2]octane (DABCO) and Bu3N is described. The reactivity with DABCO revealed the possible competition between decarbalkoxylation and unexpected desulfonylation, depending on the -substituent, because of sterical hindrance around the electrophilic centers (SO2 and CO2R). The derivatives with crowded -substituents suffer selective desulfonylation, and a novel and efficient desulfonylation method can be proposed. The dependence of the reactivity of -sulfonyl malonates on the sterical hindrance around the electrophilic centers is confirmed by conformational analysis (Macromodel/MM2* and Mopac/MP3). The carbanionic mechanism is proved because the corresponding protonated, deuterated, and sulfenylated products were obtained by addition of the corresponding electrophilic agents. Bu3N showed itself to be a novel selective decarbalkoxylation agent for any -substituted -sulfonyl malonate.