Genes encoding 2-deoxy-D-ribose-5-phosphate aldolase (DERA) homologues from two hyperthermophiles, the archaeon Pyrobaculum aerophilum and the bacterium Thermotoga maritima, were expressed individually in Escherichia coli, after which the structures and activities of the enzymes produced were characterized and compared with those of E. coli DERA. To our surprise, the two hyperthermophilic DERAs showed much greater catalysis of sequential aldol condensation using three acetaldehydes as substrates than the E. coli enzyme, even at a low temperature (25°C), although both enzymes showed much less 2-deoxy-D-ribose-5-phosphate synthetic activity. Both the enzymes were highly resistant to high concentrations of acetaldehyde and retained about 50% of their initial activities after a 20-h exposure to 300 mM acetaldehyde at 25°C, whereas the E. coli DERA was almost completely inactivated after a 2-h exposure under the same conditions. The structure of the P. aerophilum DERA was determined by X-ray crystallography to a resolution of 2.0 Å. The main chain coordinate of the P. aerophilum enzyme monomer was quite similar to those of the T. maritima and E. coli enzymes, whose crystal structures have already been solved. However, the quaternary structure of the hyperthermophilic enzymes was totally different from that of the E. coli DERA. The areas of the subunit-subunit interface in the dimer of the hyperthermophilic enzymes are much larger than that of the E. coli enzyme. This promotes the formation of the unique dimeric structure and strengthens the hydrophobic intersubunit interactions. These structural features are considered responsible for the extremely high stability of the hyperthermophilic DERAs.Using acetaldehyde and D-glyceraldehyde-3-phosphate as substrates, 2-deoxy-D-ribose-5-phosphate aldolase (DERA; EC 4.1.2.4) catalyzes a reversible aldol reaction that generates 2-deoxy-D-ribose-5-phosphate (DRP) (1,17). DERA is unique in that it catalyzes the aldol reaction between two aldehydes, which serve as both the aldol donor and the acceptor components. In addition, DERA is the only aldolase known to accept three aldehydes in a sequential and stereoselective manner during an aldol condensation reaction, which makes it a particularly interesting potential biocatalyst for synthetic organic chemistry. Gijsen and Wong (6) were the first to observe Escherichia coli DERA (DERA Eco ) catalyze a double aldol condensation of three acetaldehyde molecules (Fig. 1): the reaction started with a stereospecific addition of acetaldehyde to a substituted acetaldehyde to form 3-hydroxy-4-substituted butylaldehyde, which in turn reacted with a third acetaldehyde. After the second condensation, the product (compound 1) largely cyclized to form stable 2,4,6-trideoxy-D-erythro-hexapyranoside, which is a useful chiral synthon of hydroxymethylglutaryl-coenzyme A reductase inhibitors. This has prompted investigation of the feasibility of applying DERA Eco for the synthesis of cholesterol-lowering agents (5-7, 23). The practical application of th...
P561T heterozygous missense mutation in the growth hormone receptor (GHR) is a candidate genetic polymorphism (single-nucleotide polymorphism) for human mandibular growth. The purpose of this study was to assess whether this mutation affects mandibular growth during early childhood. The difference in mandibular growth between P561T heterozygous and wild-type individuals was analysed by cephalometric measurements during childhood. The subjects included 33 children with mandibular protrusion (aged 3-12 years, 16 males and 17 females) and 27 normal children (aged 3-13 years, 14 males and 13 females). Genomic DNA extracted from buccal epithelial cells was genotyped for the P561T heterozygous mutation with a molecular analysis (polymerase chain reaction--restriction fragment length polymorphism method). Two of the patients with normal occlusion and five with mandibular protrusion were heterozygous for the mutation. Chi-square analysis showed that the frequency of this mutation did not differ statistically between the normal and mandibular protrusion subjects. Multilevel model analysis of the 101 cephalograms showed that the mutation reduced the linear measurements of the mandible. These findings suggest that P561T heterozygous mutation affects mandibular growth during early childhood, and this mutation in the GHR gene is hypothesized to function as an inhibitory factor in the process of mandibular growth.
This study offers an analysis of the elderly (over 65 years of age) among a general community population in terms of the percentages of: (i) persons with recurring thoughts of death and/or of committing suicide, and (ii) people who have consulted others, including medical professionals, with regard to these problems. Among 433 elderly over the age of 65 in one community in a town in Aomori Prefecture, 358 agreed to participate in the project. Forty-four participants (12.3%) responded that they had either 'thoughts of death' or 'thoughts of suicide', and these thoughts had continued for more than 2 weeks in 12 participants (3.4%). Only 15 of the 44 suicidal elderly responded that they had consulted someone about their problems. Although there are many elderly people exhibiting a subclinical depressive state with recurring thoughts of death or thoughts of suicide, the number of people who consult family members, professionals, or others is very low. This suggests the importance of community networking through educational activities so that people can more readily talk to and support one another.
This study aims to evaluate outcomes of a community-based program to prevent suicide among the elderly ( ≥ 65 years old) using a quasi-experimental design with two neighboring references. During 1999During -2004, the program including depression screening and group activity was conducted by the public health nurses in the Minami district (population 1685) of Nagawa town, rural Japan. Prepost changes in the risk of completing suicide were estimated by the incidence rate ratios (IRR). The risk for Minami's elderly females was reduced by 74% (age-adjusted IRR, 0.26; 90% CI, 0.07-0.98) more than the historical trend, while there was no change in the risk of Minami's males and nor in the male or female references. The local intervention using public health nursing would be effective against suicide for elderly females without diffusing to the surroundings.
Patients with acquired cystic disease of the kidney (ACDK) were followed longitudinally over an average of 21.7 +/- 5.4 years to determine the natural history of the disease; that is, how big the kidneys become, when the kidney size reaches a plateau, and when the size regresses. Twenty-seven male and 20 female patients with chronic glomerulonephritis treated at our hospital were investigated. CT scans were performed once a year and kidney volume was measured. Two different quadratic curves with a node of 5.2 years for males and 2.5 years for females after the start of hemodialysis were fitted to log-transformed kidney volume to the duration of hemodialysis using a linear mixed model. The maximum kidney volume in male patients was obtained 21.1 years after the start of hemodialysis using this model. Peak values of kidney volume were demonstrated in 19 of 26 cases during the observation period. The median peak value (interquartile range) of bilateral kidney volumes was 274 (165-849) mL/1.73 m(2) occurring 19.1 +/- 4.5 years after the start of dialysis. In one male patient who had undergone nephrectomy due to renal cell carcinoma and in two of the remaining 26 male patients, the maximum kidney volume of 782 (residual kidney), 1151, and 1129 mL regressed to 428, 616, and 847 mL (reduction rate: 45.3, 46.5, and 25.0%) at 20.6, 25.4, and 23.1 years after the start of hemodialysis, respectively. Kidney enlargement due to ACDK reached a plateau after 21.1 years of hemodialysis in the male patients. Partial regression of severe ACDK may occur naturally after long-term hemodialysis without renal transplantation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.