Detailed active site configuration of a new crystal form of methanol dehydrogenase from Methylophilus W3A1 at 1.9 A resolution

The three-dimensional structure of a new crystal form of methanol dehydrogenase from Methylophilus W3A1 has been obtained in the presence of substrate using data recorded at a synchrotron. The structure of this approximately 140 kDa heterotetramer, refined at 1. 9 A resolution, reveals the detailed configuration of its redox cofactor, pyrroloquinoline quinone (PQQ). C4, one of the oxygen-bearing atoms of this orthoquinone is in a planar configuration while C5, which bears the other quinone oxygen, is tetrahedral, suggesting that the PQQ is in the semiquinone redox state. The substrate binding site has been identified close to PQQ and to the side chain of Asp297, the putative active site base. The proximity of the hydroxyl of methanol to C5 of PQQ compared to the greater separation of the substrate methyl group from C5 supports the addition-elimination reaction mechanism involving a hemiketal intermediate.     

Fossils, molecules and embryos: new perspectives on the Cambrian explosion

The Cambrian explosion is named for the geologically sudden appearance of numerous metazoan body plans (many of living phyla) between about 530 and 520 million years ago, only 1.7% of the duration of the fossil record of animals. Earlier indications of metazoans are found in the Neoproterozic; minute trails suggesting bilaterian activity date from about 600 million years ago. Larger and more elaborate fossil burrows appear near 543 million years ago, the beginning of the Cambrian Period. Evidence of metazoan activity in both trace and body fossils then increased during the 13 million years leading to the explosion. All living phyla may have originated by the end of the explosion. Molecular divergences among lineages leading to phyla record speciation events that have been earlier than the origins of the new body plans, which can arise many tens of millions of years after an initial branching. Various attempts to date those branchings by using molecular clocks have disagreed widely. While the timing of the evolution of the developmental systems of living metazoan body plans is still uncertain, the distribution of Hox and other developmental control genes among metazoans indicates that an extensive patterning system was in place prior to the Cambrian. However, it is likely that much genomic repatterning occurred during the Early Cambrian, involving both key control genes and regulators within their downstream cascades, as novel body plans evolved.     

The founding of the Psychological Laboratory, University College London: "Dear Galton…Yours truly, J Sully."

The events leading up to the founding of the Psychological Laboratory at University College London are examined in the light of correspondence from James Sully to Francis Galton. The correspondence reveals the dependence of Sully on Galton for detailed advice at every stage of the process, possible reasons for which are discussed. It also provides sufficient clues to enable identification of a hitherto anonymous donor. Although Galton may have inspired and advised on the initial setting up of the laboratory, his influence on its work did not become apparent until after his death. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal cocaine exposure on embryonic expression of sonic hedgehog

PURPOSE: To estimate the impact of visual impairment in older Australians on the use of community support services. METHODS: In the Blue Mountains Eye Study, 3654 people aged 49 or older were examined- 82.4% of eligible residents in an area west of Sydney, Australia. Presenting and best-corrected visual acuities were measured using a LogMAR chart. Subjects were categorized as having visual impairment if their better eye read 40 or fewer letters (20/40 or worse). Interview data included marital and other socioeconomic status measures, living status (alone or with spouse or other person), use of community support services, reliance on regular help from nonspouse family members or friends, and perceived ability to go out alone. RESULTS: After adjusting for age, gender, education, living status, walking disability, and health-related factors, for each one-line (five-letter) decrease in best-corrected visual acuity, there was a corresponding increase in reliance on community support services (odds ratio [OR], 1.17; 95% confidence interval, [CI] 1.07-1.28) or combined community and family support (OR 1.22; 95% CI, 1.12-1.32). Visually impaired persons were three times as likely to use regular support services provided by the municipality (OR 3.1; 95% CI, 1.8-5.1). A similar increased reliance on regular help from community, nonspouse family members, or friends was found. Visually impaired persons were also much more likely to state that they thought they were unable to go out alone (OR 6.2; 95% CI, 2.6-14.3). The findings were similar when presenting visual acuity was used to define visual impairment or after subjects with walking disabilities were excluded. Visual impairment seemed to have a greater effect on use of community support services in women than in men. CONCLUSIONS: After adjustment was made for confounding factors, visual impairment was found to affect significantly and negatively the independence of elderly people, particularly older women. Presenting visual acuity closely approximated best-corrected visual acuity in its impact on the use of community support services.     

Influence of neutron irradiation on Eudragit coated tablets: validation of neutron activation II

Enteric coated dexchlorpheniramine maleate (DCPA) tablets and pellets with varying coating thickness were subjected to several in vitro tests after irradiation by thermal neutrons in a flux of 1. 1 x 10(13) n cm-2 s-1 for 2, 4 or 15 min. The appearance of the tablet formulation changed extensively after exposure of the tablets to pile radiation. The irradiation caused the film to loosen from the surface of the core, indicating the generation of gases during the irradiation process. Already after irradiating the tablets for 2 min the disintegration and dissolution behaviour were significantly changed. The extent of tablet damage increased with increasing time of exposure and increasing thickness of the coating. Compared with the tablet formulation, the cores could resist a larger amount of irradiation since dissolution behaviour of the cores was only affected after 15 min of irradiation. This indicates that the irradiation procedure initially affects the coating of the formulation. Although the dissolution behaviour of the pellet formulations changed significantly after the irradiation procedure, the changes were too small to be attributed exclusively to radiation damage.     

Results of transition zone biopsy in black and white men with suspected prostate cancer

OBJECTIVES: To determine whether biopsy-detectable transition zone tumors are more common in black than in white men with suspected Stage T1c and T2 prostate cancer. METHODS: We performed a prospective study of transition zone prostate biopsy (TZ biopsy) in 1 78 black and 261 white men who had not undergone previous prostate biopsy and in 61 black and 65 white men who had undergone one benign sextant peripheral zone prostate biopsy (PZ biopsy). RESULTS: The mean age of the 239 black and 326 white study patients was 68.6+/-7.4 and 67.2+/-7.2 years, respectively (P = 0.02), the mean prostate-specific antigen (PSA) was 8.4+/-7.4 and 6.4+/-5.4 ng/mL, respectively (P = 0.003), and the mean PSA density was 0.20+/-0.23 and 0.16+/-0.16 ng/mL/mL, respectively (P = 0.006). Overall, cancer was diagnosed by TZ biopsy only in 7 black men (3%) and in no white men (0%) (P = 0.003). However, cancer detection with a TZ biopsy only was not significantly different in the black and white men when controlled for age, PSA, or PSA density (P>0.90). A TZ biopsy only detected cancer in 1% of patients who had not undergone prior PZ biopsy and in 2% of patients who had undergone prior PZ biopsy. Of the seven cancers detected with TZ biopsy, six (86%) had a Gleason score of 2 to 6. CONCLUSIONS: Prostate cancer detection with a TZ biopsy only is not common and when controlled for confounding variables is the same in black and white men. The preferential use of TZ biopsies in black men is not warranted, and the low diagnostic yield argues against routine use of the biopsy technique in men of either race.