The two steps of group II intron self-splicing are mechanistically distinguishable

The two transesterification reactions catalyzed by self-splicing group II introns take place in either two active sites or two conformations of a single active site involving rearrangements of the positions of the reacting groups. We have investigated the effects on the rates of the chemical steps of the two reactions due to sulfur substitution of nonbridging oxygens at both the 5' and 3' splice sites as well as the deoxyribose substitution of the ribose 2' hydroxyl group at the 5' splice site. The data suggest that the two active sites differ in their interactions with several of these groups. Specifically, sulfur substitution of the pro-Sp nonbridging oxygen at the 5' splice site reduces the chemical rate of the step one branching reaction by at least 250-fold, whereas substitution of the pro-Sp oxygen at the 3' splice site has only a 4.5-fold effect on the chemical rate of step two. Previous work demonstrated that the Rp phosphorothioate substitutions at both the 5' and 3' splice sites reduced the rate of both steps of splicing to an undetectable level. These results suggest that either two distinct active sites catalyze the two steps or that more significant alterations must be made in a single bifunctional active site to accommodate the two different reactions.     

An epidemiological profile of elderly suicides in Hong Kong

Suicide rates in Hong Kong increased with age, and the highest suicide rate occurred among the oldest age groups. Hong Kong has one of the highest elderly suicide rates in the world. The elderly suicide rate was four to five times above the average. Furthermore, gender differences were observed among different marital status groups. For example, single males had a much higher rate than single females and married males had a higher rate than their widowed counterparts. The suicide rate for an economically inactive person was six times higher than for an active one. Jumping has become increasingly common and seems to substitute for other methods of suicide. Winter months and the Chinese New Year period had the lowest suicide occurrence. Some explanations are given.     

Effect of radiographic positioning on interpretation of cubital joint congruity in dogs

OBJECTIVE: To ascertain effects of x-ray beam centering and limb position on apparent congruity of a normal cubital joint (elbow). ANIMALS: 6 skeletally mature male Treeing Walker Coonhounds without physical, radiographic, or gross evidence of elbow abnormalities. PROCEDURE: Relative movement among humerus, radius, and ulna and measured joint space width on mediolateral and craniocaudal radiographic views was compared, using various x-ray beam centering and limb positions. RESULTS: Highest agreement and greatest certainty on subjective determination of congruity was for the flexed 90 degrees mediolateral radiographic view with the x-ray beam centered on the elbow. Distortion artifact of the proximal ulnar measurements was significant when the x-ray beam was centered on the midpoint of the radius. On the mediolateral view, the humeroradial joint space became significantly wide when the elbow was flexed. On the craniocaudal view, maximal humeroradial joint space width was obtained when the x-ray beam bisected the angle of the joint or was angled +30 degrees toward the humerus. CONCLUSIONS: Artifact distortion of joint width affected objective and subjective assessment of elbow congruity when the limb was placed in extreme flexion or extension or when the x-ray beam was not centered over the area of interest. Optimal visualization of the humeroradial joint space on the craniocaudal view was achieved when the x-ray beam bisected the angle of the elbow or was slightly angled toward the humerus. CLINICAL RELEVANCE: Elbow congruity was best assessed on the flexed 90 degrees lateral radiographic view with the x-ray beam centered on the joint.     

Effect of local standards on the implementation of national guidelines for asthma: primary care agreement with national asthma guidelines

In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18%, respectively, at 3 mg kg(-1) i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT(1B/1D) agonist antimigraine drugs.     

The complex pathology of trinucleotide repeats

The expansion of trinucleotide repeat sequences has now been shown to be the underlying cause of at least ten human disorders. Unifying features among these diseases include the unstable behavior of the triplet repeat during germline transmission when the length of the repeat exceeds a critical value. However, the trinucleotide repeat disorders can be divided into two distinct groups. Type I disorders involve the expansion of CAG repeats, which encode an expanded polyglutamine, inserted into the open-reading frame of a gene that is usually quite broadly expressed. Recently, mouse models for type I disorders have been developed and the basis of pathology is under study, both in these models and through biochemical and cell biological approaches. The type II disorders involve repeat expansions in noncoding regions of genes. The mechanisms by which these repeat expansions lead to pathology may be quite diverse.     

Modification of αAI2O3 Platelet/ZrO2 Matrix Interface by Epitaxial Growth of β-AI2O3 on the α-AI2O3

An epitaxial β-alumina crystal growth method was used to modify α-AI₂O₃ platelet surfaces before inclusion as a reinforcing phase in partially stabilized zirconia (3Y-TZP). The as-grown surface phase was Na-β"-AI₂O₃. This was converted to Ca-β"-AI₂O₃ by ion exchange, as the latter is more temperature-stable at composite sintering temperatures. The conditions of formation, thermal stability, and chemical compatibility of these interfacial phases were examined. α-AI₂O₃ platelets with Ca-β"-AI₂O₃ film were incorporated into 3Y-TZP. The β"-AI₂O₃/ZrO₂ interface was found to promote platelet debonding and pullout, thus enhancing the α-AI₂O₃ platelet/crack interactions during the fracture process.