RESUMO
In bacteria, the transcription of virulence genes is usually controlled by a cell density-dependent process known as "quorum sensing" (QS). QS relies on small diffusible signaling molecules that cross the bacterial cell wall and activate target transcription factors after a threshold concentration has been reached. Besides two hierarchical QS circuits based on N-acylhomoserine lactones, the human opportunistic pathogen Pseudomonas aeruginosa integrates a signaling system that depends on 2-heptyl-3-hydroxy-4-quinolone, termed "Pseudomonas quinolone signal" (PQS). PQS is produced from genes encoded in the pqs operon, which in addition to the biosynthetic enzymes PqsA-D contains a fifth gene, pqsE, that is not required for production of PQS but whose disruption leads to loss of signal transduction in several but not all pqs operon-dependent processes. PqsE was hence termed "PQS response protein", but its exact mechanism of action is unknown. We have determined the crystal structure of recombinant PqsE and show that it possesses a metallo-beta-lactamase fold with an Fe(II)Fe(III) center in the active site. A copurified ligand was assigned as benzoate and may indicate that PqsE exerts its regulatory effect by converting a chorismate-derived molecule. Further, PqsE was found to slowly hydrolyze phosphodiesters including single- and double-stranded DNA as well as mRNA and also the thioester S-(4-nitrobenzoyl)mercaptoethane. Higher activity was observed after incubation with Co(2+) and, to lesser entent, Mn(2+), suggesting that the Fe(II)Fe(III) center of recombinant PqsE may be an artifact of heterologous expression. A crystal complex of the E182A mutant with bis-pNPP was obtained and suggests a catalytic mechanism for hydrolysis.
Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Hidrolases/metabolismo , Pseudomonas aeruginosa/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas de Bactérias/genética , Calorimetria , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Regulação Bacteriana da Expressão Gênica/genética , Regulação Bacteriana da Expressão Gênica/fisiologia , Hidrolases/genética , Cinética , Modelos Genéticos , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Estrutura Secundária de Proteína , Pseudomonas aeruginosa/genética , Quinolonas/metabolismo , Percepção de Quorum/fisiologia , Proteínas Recombinantes/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismoRESUMO
The genetic relationships between economic traits and genetic markers were studied in 147 goats including Chaidamu goat (CS), Chaidamu Cashmere goat (CRS) and Liaoning Cashmere goat (LRS) in Qinghai province, China. CRS was the population of CSxLRS crossbred. The results showed as follows: the selection reaction of these blood protein polymorphisic loci were great, such as EsD, LAP and P(A-3); and EsD2-2, LAPBB and PA-32-2 were the superior marker genotypes on body weight ,Cashmere yield and Cashmere fineness respectively by Least Square method. The interaction between marker genotypes at double loci was found frequently, and their ratio between interaction variance component and genetic variance was higher. With the method of marker assisted prediction( MAP), some interaction effect could be used effectively in the crossbreed population. On the aspect of random amplified polymorphic DNA (RAPD), the number of the superior RAPD marker bands were 11 on body weight trait, 9 and 6 RAPD marker bands on Cashmere yield and Cashmere fineness. For multi-goal traits, CY0818/A0 type and OPW19/C1 type were superior RAPD markers of body weight and Cashmere yield, CY0818/G1 type was superior one of body weight and Cashmere fineness.
Assuntos
Cruzamento/economia , Marcadores Genéticos , Cabras/genética , Característica Quantitativa Herdável , Seleção Genética , Animais , Peso Corporal/genética , China , Genótipo , Cabras/classificação , Leucil Aminopeptidase/genética , Pré-Albumina/genética , Tioléster Hidrolases/genética , Lã/economiaRESUMO
We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualité Sociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.