Pi (antitrypsin) typing methods. A comparison of acid starch-gel electrophoresis and isoelectric focusing

The Pi typing methods acid starch-gel electrophoresis (ASGE) and isoelectric focusing (IEF) have been compared by three reference laboratories: 564 samples of phenotypes Pi M, MS and MZ were tested in each of the three laboratories with a 96% agreement on initial typing. The discrepancies are recorded and reasons for disagreement discussed. IEF is a reliable method for Pi typing and gives results comparable to those obtained by ASGE.     

Polyketide biosynthesis: understanding and exploiting modularity

Polyketide-based pharmaceuticals are some of our most important medicines. They are constructed in micro-organisms (typically bacteria and fungi) by gigantic enzyme catalysts called polyketide synthases (PKSs). The organization of PKSs into molecular assembly lines makes them particularly appealing targets for genetic engineering because, in principle, an alteration in the enzyme organization might translate into a predictable change in polyketide structure. Excitingly, this has been shown repeatedly to work in practice, but the efficiency of the engineered PKSs is frequently too low to be useful for large-scale drug synthesis. To reach this goal, researchers need a deeper understanding of the structure and function of these proteins, which are among the most complex in nature. This review highlights some recent experiments which are providing key information about the molecular organization, mechanism and orchestration of these magnificent catalysts, and opening up fresh prospects of truly combinatorial biosynthesis of novel polyketides as leads in drug discovery.     

Mutation in the Arabidopsis PASTICCINO1 gene, which encodes a new FK506-binding protein-like protein, has a dramatic effect on plant development

The pasticcino (pas) mutants of Arabidopsis thaliana are a new class of plant developmental mutants; members of this class show ectopic cell proliferation in cotyledons, extra layers of cells in the hypocotyl, and an abnormal apical meristem. This phenotype is correlated with both cell division and cell elongation defects. There are three complementation groups of pas mutants (pas1, pas2, and pas3, with, respectively 2, 1, and 4 alleles). Here we describe in more detail the pas1-1 allele, which was obtained by insertional mutagenesis. The PAS1 gene has been cloned and characterized; it encodes an immunophilin-like protein similar to the p59 FK506-binding protein (FKBP52). PAS1 is characterized by an FKBP-like domain and three tetratricopeptide repeat units. Although the presence of immunophilins in plants has already been demonstrated, the pas1-1 mutant represents the first inactivation of an FKBP-like gene in plants. PAS1 expression is altered in pas1 mutants and in the pas2 and pas3 mutants. The expression of the PAS1 gene is increased in the presence of cytokinins, a class of phytohormones originally discovered because of their ability to stimulate cell division. These results are of particular relevance as they show for the first time that an FKBP-like protein plays an important role in the control of plant development.     

Results of cemented metal-backed acetabular components: a 10-year-average follow-up study

We have developed a computer program for the rapid assessment of the primary structure differences between a protein of unknown sequence and a homologous known protein. Both proteins are reduced, alkylated, and digested with the same hydrolytic agent. The unfractionated peptide mixtures are submitted to automatic sequence analysis. Based on the knowledge of the reference sequence, the program utilizes the analysis data to identify all the potential peptides present in the two mixtures, determining their primary structure, homology degree, and molecular weight calculated both as integer MH+ and average mass variables. These fingerprints allow the user to easily identify the structural differences between the two proteins and clarify possible doubts by a mass spectrometric analysis of the two mixtures. In order to verify the utility of the program, we provide an application example using the already reported data of two homologous proteins.     

Esterified estrogens with and without methyltestosterone decrease arterial LDL metabolism in cynomolgus monkeys

OBJECTIVES: To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. MATERIALS AND METHODS: Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). RESULTS: Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. CONCLUSION: Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.     

Computer vision for interactive computer graphics

Vision can be a powerful interface device for computers because of its potential for sensing body position, head orientation, direction of gaze, pointing commands, and gestures. Such unencumbered interaction can make computers easier to use. We describe vision algorithms for interactive graphics and present vision-controlled graphics applications using these algorithms. Some applications employ an artificial retina chip for image detection or preprocessing     

Gallop: The Benefits of Wide-Area Computing for Parallel Processing

Internet computing has emerged, as an attractive paradigm for many applications that require access to distributed resources such as telemedicine, collaboratories, and transaction systems. For applications that require high performance, the Internet is assumed to be inappropriate. However, it is possible to obtain high performance for parallel scientific applications in an Internet environment. A wide-area scheduling system called Gallop has been developed to exploit opportunities for high performance using remote Internet resources for these applications. This paper describes the Gallop architecture and scheduling model, and performance results obtained for three parallel applications. The initial results indicate that wide-area parallel processing can lead to better performance even with Internet technology, but that current Internet bandwidth is a major bottleneck for file and binary transfer. This overhead limits the class of suitable applications to those that are large-grained or that will be run multiple times to amortize the transfer cost.     

A hemispheric division of labor aids mental rotation.

In the present study, we investigated whether a hemispheric division of labor is most advantageous to performance when lateralized inputs place unequal resource demands on the left and right cerebral hemispheres. In each trial, participants decided whether 2 rotated letters, presented either in the same visual field (within-field trials) or in opposite visual fields (across-field trials), were both of normal orientation, or whether one was normal and the other was mirror-reversed. To discriminate a letter's orientation, one must rotate the letter to the upright position. Therefore, we manipulated whether the two letters imposed similar or dissimilar demands on cognitive resources by varying the number of degrees that each letter needed to be rotated to reach the upright position. As predicted, in 2 experiments we found that the across-field advantage increased as the number of degrees each letter needed to be rotated became more dissimilar. These findings support a current model of hemispheric interactions, which posits that an unequal hemispheric distribution of cognitive load allows the cerebral hemispheres to take the lead for different aspects of cognitive processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Photoaffinity labeling of the human erythrocyte nucleoside transporter by N6-(p-Azidobenzyl)adenosine and nitrobenzylthioinosine. Evidence that the transporter is a band 4.5 polypeptide

N6-(p-Azidobenzyl)adenosine (ABA) and nitrobenzylthioinosine (NBMPR) were employed as covalent probes of the nucleoside transport mechanism in human erythrocytes. NBMPR, a potent inhibitor of nucleoside transport, binds tightly (KD 0.3-1 nM) to specific sites on nucleoside transporter elements. ABA, a less potent inhibitor of uridine influx, competitively inhibited NBMPR binding (Ki 15 nM). [3H]ABA was bound tightly (KD 13.4 nM) but reversibly to sites on erythrocytes which appeared to be those which bind NBMPR. ABA binding was inhibited by uridine and adenosine. Irradiation with UV light caused site-bound [3H]ABA on erythrocyte membranes to become covalently bound and, similarly, photoactivation resulted in covalent attachment of membrane-bound [3H]NBMPR. In the presence of dithiothreitol, a free radical scavenger, photoactivation of the site-bound 3H-ligand on membranes depleted of extrinsic membrane proteins resulted in selective incorporation of 3H into band 4.5 of the membrane polypeptides which were resolved on sodium dodecyl sulfate-polyacrylamide gel electropherograms. This result, when considered with previous findings, indicates that the NBMPR-binding component of the nucleoside transport mechanism (or the entire mechanism, if the NBMPR site is an integral part) is a band 4.5 polypeptide.