Supersites within superfolds. Binding site similarity in the absence of homology

A method is presented to assess the significance of binding site similarities within superimposed protein three-dimensional (3D) structures and applied to all similar structures in the Protein Data Bank. For similarities between 3D structures lacking significant sequence similarity, the important distinction was made between remote homology (an ancient common ancestor) and analogy (likely convergence to a folding motif) according to the structural classification of proteins (SCOP) database. Supersites were defined as structural locations on groups of analogous proteins (i.e. superfolds) showing a statistically significant tendency to bind substrates despite little evidence of a common ancestor for the proteins considered. We identify three potentially new superfolds containing supersites: ferredoxin-like folds, four-helical bundles and double-stranded beta helices. In addition, the method quantifies binding site similarities within homologous proteins and previously identified supersites such as that found in the beta/alpha (TIM) barrels. For the nine superfolds, the accuracy of predictions of binding site locations is assessed. Implications for protein evolution, and the prediction of protein function either through fold recognition or tertiary structure comparison, are discussed.     

Crystal structure at 1.95 A resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition

The anti-breast tumour antibody SM3 has a high selectivity in reacting specifically with carcinoma-associated mucin. SM3 recognises the core repeating motif (Pro-Asp-Thr-Arg-Pro) of aberrantly glycosylated epithelial mucin MUC1, and has potential as a therapeutic and diagnostic tool. Here we report the crystal structure of the Fab fragment of SM3 in complex with a 13-residue MUC1 peptide antigen (Thr1P-Ser2P-Ala3P-Pro4P-Asp5P-Thr6P -Arg7P-Pro8P-Ala9P-Pro10P-Gly11P- Ser12P-Thr13P). The SM3-MUC1 peptide structure was solved by molecular replacement, and the current model is refined at 1.95 A resolution with an R-factor of 21.3% and R-free 28.3%. The MUC1 peptide is bound both by non-polar interactions and hydrogen bonds in an elongated groove in the antibody-combining site through interactions with Complimentarity Determining Regions (CDRs), three of the light chain (L1, L2, L3) and two of the heavy chain (H1 and H3). The conformation of the peptide is mainly extended with no discernable standard secondary structure. There is a single non-proline cis-peptide bond in H3 (Val95H-Gly96H-Gln97H-Phe98H-Ala101H-Ty r102H) between Gly96H and Gln97H, which appears to play a role in SM3-peptide antigen interactions, and represents the first such example within an antibody hypervariable loop. The SM3-MUC1 peptide structure has implications for rational therapeutic and diagnostic antibody engineering.     

Pre-emptive glycopyrrolate 0.2 mg and bradycardia during gynaecological laparoscopy with mivacurium

In a prospective, randomized, double-blind, placebo-controlled trial, the effect of pre-emptive glycopyrrolate 0.2 mg given intravenously on the incidence of bradycardia in patients undergoing elective gynaecological laparoscopy with mivacurium neuromuscular blockade was investigated. Seven out of 32 (21.6%) control patients developed bradycardia (heart rate < 50 min-1), compared with 3 of 31 (9.6%) patients receiving glycopyrrolate (P = 0.4). Glycopyrrolate 0.2 mg, given immediately before induction in gynaecological laparoscopy with mivacurium, did not significantly reduce the incidence of intraoperative bradycardia.     

There are no public-policy implicatons: A reply to Rushton and Jensen (2005).

J. P. Rushton and A. R. Jensen (see record 2005-03637-001) purport to show public-policy implications arising from their analysis of alleged genetic bases for group mean differences in IQ. This article argues that none of these implications in fact follow from any of the data they present. The risk in work such as this is that public-policy implications may come to be ideologically driven rather than data driven, and to drive the research rather than be driven by the data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Marine macrofouling: a review of control technology in the context of an on-line experiment in the turbine condenser water box of Al-Jubail Phase-1 power/MSF plants

The problem of macrofouling has serious implications in the performance of desalination and power plants. Intake structures, screens, seawater piping systems and heat-exchanger tubes are the sites worst affected in the plants, causing an overall decline in plant efficiency at great economic cost. The last half century has witnessed significant advancements in the development ofmacrofouling control technologies. Materials of inherent antifouling properties are widely used in the construction sector. Control technologies available include antifouling paints and coatings, injection of biocides, marine bio-active compounds, materials of inherent antifouling properties, heat treatment, pulse-power devices, UV and nuclear radiation, scrubbing devices, biological control, etc. A literature search carried out during the last few years has yielded about 450 references. This paper presents, in a very concise manner, state-of-the- art macrofouling control technologies pertinent to desalination and power plants in the Kingdom. The paper also discusses the issues of biofouling control in the Al-Jubail plants based on the results of an on-line macrofouling experiment conducted in one of the turbine condensers of Al-Jubail phase-I MSF/power plants.     

The publication and citation output of German Faculties of Economics and Social Sciences - a comparison of faculties and disciplines based upon SSCI data

Summary The purpose of this study is to quantify and compare the publication and citation output of the biggest faculties of economics and social sciences in Germany. Various publication and citation measures based upon Social Science Citation Index (SSCI) data are used to explore the comparative strengths and weaknesses of ten academic fields at the named faculties. To reflect the varying size of the fields and faculties, output measures as well as productivity measures are explicitly considered. From a bibliometric perspective empirical results demonstrate that various measures are necessary to adequately identify the comparative strengths and weaknesses of entire faculties and of selected disciplines within faculties.     

Racing toward the finish line.

Replies to published comments on our original article (R. L. Sternberg, E. L. Grigorenko, and K. K. Kidd, see record 2005-00117-006). G. Carey (see record 2006-01690-008) cited in his response to our article a study by Tang et al. (2005) showing that "of 3,636 subjects of varying race/ethnicity, only 5 (0.14%) showed genetic cluster membership different from their self-identified race/ethnicity" (p. 268). At Carey's invitation, we are glad to provide a counterresponse. Correspondence between self-identification and biological characteristics does not form a suitable basis for assigning people to "races." Moreover, it appears that Carey's (2006) response to our article can be explained, at least partially, by his incomplete understanding of the data, analyses, and results presented in Tang et al. (2005). With regard to D. I. Templer's (see record 2006-01690-009) response, we do not give much credence to the M. Snyderman and S. Rothman (1988) survey. If the survey were done in 1908, probably there would have been even more emphasis on genes. If scientists in earlier times were surveyed on the causes of fire, they might well all have agreed that phlogiston was responsible. In another era, they would have agreed that the Sun revolves around the Earth. Implicit theories are useful ways of ascertaining popular folk beliefs, including those of scientists, but they are not scientifically definitive. As to Rushton's (1995) findings, we are not clear on what conclusion is to be drawn from the correlations--that people with larger cranial capacities are more likely to move away from the equator, that moving away from the equator produces greater cranial capacity, or that both larger cranial capacity and distance from the equator are dependent on some unknown third variable. Finally, in response to C. L. McLafferty (see record 2006-01690-010), we agree that the dichotomization of nature and nurture is a somewhat artificial analytical division that has been at times misused. Whereas we might not fully accept the revised classification proposed by McLafferty, we agree that the nature-nurture division has outlived its value. Nor is there a simple continuum between fully nature and fully nurture--the relevance of variation in nurture depends on the mean and range of variation in nature, and vice versa (Lewontin, 1974). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Embodied and Operational Energy Consumption in the City

This study shows how estimates of energy consumption can be extracted from existing data sets and efficiently related to characteristics of the real property making up the discrete areas of the city. The study suggests that embodied energy consumption may be more significant than previously thought and suggests how estimates of embodied and operational energy may be used as a development control tool in the planning system.