Topological side-chain classification of beta-turns: Ideal motifs for peptidomimetic development

beta-turns are important topological motifs for biological recognition of proteins and peptides. Organic molecules that sample the side chain positions of beta-turns have shown broad binding capacity to multiple different receptors, for example benzodiazepines. beta-turns have traditionally been classified into various types based on the backbone dihedral angles (phi 2, psi 2, phi 3 and psi 3). Indeed, 57-68% of beta-turns are currently classified into 8 different backbone families (Type I, Type II, Type I', Type II', Type VIII, Type VIa1, Type VIa2 and Type VIb and Type IV which represents unclassified beta-turns). Although this classification of beta-turns has been useful, the resulting beta-turn types are not ideal for the design of beta-turn mimetics as they do not reflect topological features of the recognition elements, the side chains. To overcome this, we have extracted beta-turns from a data set of non-homologous and high-resolution protein crystal structures. The side chain positions, as defined by C-alpha-C-beta vectors, of these turns have been clustered using the kth nearest neighbor clustering and filtered nearest centroid sorting algorithms. Nine clusters were obtained that cluster 90% of the data, and the average intra-cluster RMSD of the four C-alpha-C-beta vectors is 0.36. The nine clusters therefore represent the topology of the side chain scaffold architecture of the vast majority of beta-turns. The mean structures of the nine clusters are useful for the development of beta-turn mimetics and as biological descriptors for focusing combinatorial chemistry towards biologically relevant topological space.

Contact angle effects on microdroplet deformation using CFD

In this paper we use computational fluid dynamics (CFD) to study the effect of contact angle on droplet shape as it moves through a contraction. A new non-dimensional number is proposed in order to predict situations where the deformed droplet will form a slug in the contraction and thus have the opportunity to interact with the channel wall. It is proposed that droplet flow into a contraction is a useful method to ensure that a droplet will wet a channel surface without a trapped lubrication film, and thus help ensure that a slug will remain attached to the wall downstream of the contraction. We demonstrate that when a droplet is larger than a contraction, capillary and Reynolds numbers, and fluid properties may not be sufficient to fully describe the droplet dynamics through a contraction. We show that, with everything else constant, droplet shape and breakup can be controlled simply by changing the wetting properties of the channel wall. CFD simulations with contact angles ranging from 30 degrees to 150 degrees show that lower contact angles can induce droplet breakup while higher contact angles can form slugs with contact angle dependent shape. Crown Copyright (c) 2005 Published by Elsevier Inc. All rights reserved.

RAFT-mediated emulsion polymerization of styrene using a non-ionic surfactant

We report the successful RAFT-mediated emulsion polymerization of styrene using a non-ionic surfactant (Brij98), the highly reactive 1-phenylethyl phenyldithioacetate (PEPDTA) RAFT agent, and water-soluble initiator ammonium persulfate (APS). The molar ratio of RAFT agent to APS was identical in all experiments. Most of the monomer was contained within the micelles, analogous to microemulsion or miniemulsion systems but without the need of shear, sonication, cosurfactant, or a hydrophobe. The number-average molecular weight increased with conversion and the polydispersity index was below 1.2. This ideal 'living' behavior was only found when molecular weights of 9000 and below were targeted. It was postulated that the rapid transportation of RAFT agent from the monomer swollen micelles to the growing particles was fast on the polymerization timescale, and most if not all the RAFT agent is consumed within the first 10% conversion. In addition, it was postulated that the high nucleation rate from the high rate of exit ( of the R radical from the RAFT agent) and high entry rate from water-phase radicals ( high APS concentration) reduced the effects of 'superswelling' and therefore a similar molar ratio of RAFT agent to monomer was maintained in all growing particles. The high polydispersity indexes found when targeting molecular weights greater than 9000 were postulated to be due to the lower nucleation rate from the lower weight fractions of both APS and RAFT agent. In these cases, 'superswelling' played a dominant role leading to a heterogeneous distribution of RAFT to monomer ratios among the particles nucleated at different times.

Relationship of body condition score and blood urea and ammonia to pregnancy in Italian Mediterranean buffaloes

The relationship of body condition score ( BCS) and blood urea and ammonia to pregnancy outcome was examined in Italian Mediterranean Buffalo cows mated by AI. The study was conducted on 150 buffaloes at 145 +/- 83 days in milk that were fed a diet comprising 14.8% crude protein, 0.9 milk forage units . kg(-1) dry matter and a non- structural carbohydrate/ crude protein ratio of 2.14. The stage of the oestrous cycle was synchronised by the Ovsynch- TAI programme and blood urea and ammonia levels were assessed on the day of AI. Energy corrected milk ( ECM) production and BCS were recorded bi- weekly. The pregnancy risk was 46.7% and was slightly lower in buffaloes with BCS < 6.0 and BCS > 7.5. There were no significant differences in ECM, urea and ammonia between pregnant and non- pregnant buffaloes. However, pregnancy outcome was higher ( P = 0.02) in buffaloes with blood urea < 6.83 mmol . L-1. The likelihood of pregnancy for buffaloes with low urea blood level was 2.6 greater than for high urea level and exposure to a high urea level lowered the probability of pregnancy by about 0.25. The findings indicate that buffaloes are similar to cattle and increased blood levels of urea are associated with reduced fertility when animals are mated by AI.

Scaling and non-scaling of muscle activity, kinematics, and dynamics in sit-ups with different degrees of difficulty

The purpose of this study was to investigate how the CNS adjusts motor patterns for variants of a complex axial movement-the situp. Adjustments were induced by changing the support surface contact and mass distribution of the body. Healthy adults performed straight-legged sit-ups, 3 s in duration, with support added to or removed from the lumbar trunk, or with mass added to the head or to the legs. Each of these interventions either increased or decreased the difficulty of the task. The study addressed the extent to which changes in sit-up difficulty are compensated by scaling of muscle activity, kinematics, and dynamics versus the extent to which they are compensated by changing discretely the motor pattern. The analysis of muscle activity, kinematics, and dynamics focused on the first 30-40% of the sit-up-the trunk flexion phase-since this is the most critical part of the movement. Our results demonstrate that, in some respects, sit-up kinematics and dynamics scaled with difficulty, but in other respects, they did not. Muscle activity also scaled, in many respects, but in more difficult sit-ups, abdominal flexor activity decreased instead of increased. Non-scaling changes in these parameters suggest that complex movements, such as the sit-up, may require discrete changes in motor pattern in order to deal with large loads, which challenge the available leverage. (C) 2005 Elsevier Ltd. All rights reserved.

Type III secretion contact-dependent model for the intracellular development of Chlamydia

The medically significant genus Chlamydia is a class of obligate intracellular bacterial pathogens that replicate within vacuoles in host eukaryotic cells termed inclusions. Chlamydia's developmental cycle involves two forms; an infectious extracellular form, known as an elementary body (EB), and a non-infectious form, known as the reticulate body (RB), that replicates inside the vacuoles of the host cells. The RB surface is covered in projections that are in intimate contact with the inclusion membrane. Late in the developmental cycle, these reticulate bodies differentiate into the elementary body form. In this paper, we present a hypothesis for the modulation of these developmental events involving the contact-dependent type III secretion (TTS) system. TTS surface projections mediate intimate contact between the RB and the inclusion membrane. Below a certain number of projections, detachment of the RB provides a signal for late differentiation of RB into EB. We use data and develop a mathematical model investigating this hypothesis. If the hypothesis proves to be accurate, then we have shown that increasing the number of inclusions per host cell will increase the number of infectious progeny EB until some optimal number of inclusions. For more inclusions than this optimum, the infectious yield is reduced because of spatial restrictions. We also predict that a reduction in the number of projections on the surface of the RB (and as early as possible during development) will significantly reduce the burst size of infectious EB particles. Many of the results predicted by the model can be tested experimentally and may lead to the identification of potential targets for drug design. © Society for Mathematical Biology 2006.

Non-major-histocompatibility-complex genetics of ankylosing spondylitis

There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-I gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-IA. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.

Chemical deterrence of a marine cyanobacterium against sympatric and non-sympatric consumers

This study investigates the influence of mesograzer prior exposure to toxic metabolites on palatability of the marine cyanobacterium, Lyngbya majuscula. We examined the palatability of L. majuscula crude extract obtained from a bloom in Moreton Bay, South East Queensland, Australia, containing lyngbyatoxin-a (LTA) and debromoaplysiatoxin (DAT), to two groups: (1) mesograzers of L. majuscula from Guam where LTA and DAT production is rare; and (2) macro- and mesograzers found feeding on L. majuscula blooms in Moreton Bay where LTA and DAT are often prevalent secondary metabolites. Pair-wise feeding assays using artificial diets consisting of Ulva clathrata suspended in agar (control) or coated with Moreton Bay L. majuscula crude extracts (treatment) were used to determine palatability to a variety of consumers. In Guam, the amphipods, Parhyale hawaiensis and Cymadusa imbroglio; the majid crab Menaethius monoceros; and the urchin Echinometra mathaei were significantly deterred by the Moreton Bay crude extract. The sea hares, Stylocheilus striatus, from Guam were stimulated to feed by treatment food whereas S. striatus collected from Moreton Bay showed no discrimination between food types. In Moreton Bay, the cephalaspidean Diniatys dentifer and wild caught rabbitfish Siganus fuscescens were significantly deterred by the crude extract. However, captive-bred S. fuscescens with no known experience with L. majuscula did not clearly discriminate between food choices. Lyngbya majuscula crude extract deters feeding by most mesograzers regardless of prior contact or association with blooms.