The CATH Hierarchy Revisited-Structural Divergence in Domain Superfamilies and the Continuity of Fold Space

This paper explores the structural continuum in CATH and the extent to which superfamilies adopt distinct folds. Although most superfamilies are structurally conserved, in some of the most highly populated superfamilies (4% of all superfamilies) there is considerable structural divergence. While relatives share a similar fold in the evolutionary conserved core, diverse elaborations to this core can result in significant differences in the global structures. Applying similar protocols to examine the extent to which structural overlaps occur between different fold groups, it appears this effect is confined to just a few architectures and is largely due to small, recurring super-secondary motifs (e.g., alpha beta-motifs, alpha-hairpins). Although 24% of superfamilies overlap with superfamilies having different folds, only 14% of nonredundant structures in CATH are involved in overlaps. Nevertheless, the existence of these overlaps suggests that, in some regions of structure space, the fold universe should be seen as more continuous.

Focusing in on structural genomics : the University of Queensland structural biology pipeline

The flood of new genomic sequence information together with technological innovations in protein structure determination have led to worldwide structural genomics (SG) initiatives. The goals of SG initiatives are to accelerate the process of protein structure determination, to fill in protein fold space and to provide information about the function of uncharacterized proteins. In the long-term, these outcomes are likely to impact on medical biotechnology and drug discovery, leading to a better understanding of disease as well as the development of new therapeutics. Here we describe the high throughput pipeline established at the University of Queensland in Australia. In this focused pipeline, the targets for structure determination are proteins that are expressed in mouse macrophage cells and that are inferred to have a role in innate immunity. The aim is to characterize the molecular structure and the biochemical and cellular function of these targets by using a parallel processing pipeline. The pipeline is designed to work with tens to hundreds of target gene products and comprises target selection, cloning, expression, purification, crystallization and structure determination. The structures from this pipeline will provide insights into the function of previously uncharacterized macrophage proteins and could lead to the validation of new drug targets for chronic obstructive pulmonary disease and arthritis.

Aspects of the biology of the abalone Haliotis laevigata and Haliotis scalaris

The abalone Haliotis laevigata Donovan is commercially exploited in southern Australia; Haliotis scalaris Leach is a smaller, noncommercial species. This thesis describes the early life history of both species and other aspects of the fishery biology of H. Iaevigata required for fishery management. Both abalone species recruit onto a crustose coralline substratum variously from spring to winter. After settlement the growth rate of both species Is linear for a number of years (1 .7mm/month for H. Iaevigata and 1.1mm/month for H. scalaris) . Crustose coralline algae are the main food during the first year of life but thereafter the diet switches largely to drift algae and seagrass. Survival of newly-settled cohorts differed between years and between species. Overall, it appeared to be density Independent at low densities but density-dependent at high densities, Recruitment strength (measured at 2-1/2 - 3 years of age) and natural mortality of adults in a closed population was measured over 17 years at West I. There were sequences of strong and weak recruitments, but no relationship with presumed spawning stock size was apparent. Adult natural mortality rates ranged from 0.02 to 0.86 and were strongly density dependent. Stingrays were a major, and octopuses a minor, cause of mortality. The fecundity of H. Iaevigata was investigated at a number of sites and was adequately described by linear regressions of fecundity on total weight. Fecundity ratios and growth rate differed between sites and fecundity appears subject to phenotyplc and genotypic variation. The short and long term movement of H. laevigata was also examined, !n short term studies sexually mature Individuals aggregate during the spawning season but disperse randomly at other times of the year. In the longer term the amount of movement depends on availability of crevice space and size. Movement is also directional and, at one site, was toward that of the approaching swell. A method is described for estimating density of abalone by using a free-range search technique and adjusting for individual variation in power and efficiency of different divers and in differing degrees of habitat heterogeneity. The method is useful for estimating recruitment strength and density of abalone in surveys of abalone stocks.

Disorder and the body of drugs : addiction, consumption, control, and city space

Different cultures and the specific culture manifested within them are intrinsically linked to addiction in a complex fashion which has a long history. For important thinkers, such as Nietzsche, addiction actually embodies human culture, rendering addiction and culture inseparable. This is clearly seen within the Western world’s addiction to the consumption of material goods and the damage that results.

Utopia has often become dystopia. Not only is an understanding of addiction key to understanding culture but to an understanding of the very act thinking itself and the way of being in the world. Addiction raises key philosophical questions, such as: do people really have a choice in their behavior, and what governs them; is it free will or predetermination? Is it biology or environment is it the external world or the internal that drives addiction, or a complex combination of both?

In a contemporary context the media frenzy around celebrity addiction continually fuels public debate in this area, and this book deepens the understanding of addiction within this contentious context. This book addresses a key concern over how addiction became the norm, and it seeks to understand its dominance comprehensively. How did it come to pass that not being an addict was a transgressive act and way of being?

While there has been a great deal of debate about addiction utilizing the discourse of individual and often competing disciplines such as biology and psychology, little attention has been paid to the cultural aspects of addiction. The innovative approach taken by this book is to offer insights into this complex area through a contemporary methodology that covers diverse interrelated areas. Drawing on different disciplines, offering deeper insights, from the analysis of music lyrics to empirical social science and anthropological work in AA groups in Mexico and the portrayal of the “addiction’ to therapy in film and television, amongst other areas, this book addresses the need for a more comprehensive approach.

Academic analysis is also given to the discourse on celebrity culture and addiction. A contemporary fusion of the humanities and the social sciences is the best way forward to tackle this subject and move the debate on. The focus of this study is an innovative interdisciplinary and intercultural approach to addiction, from the social sciences to the humanities, including cultural studies, film and media studies, and literary studies. Areas that have been overlooked, such as lost women’s writings, are examined, in addition to comics, popular film and television, and the work of AA groups.

This edited collection is the first study to provide such a comprehensive analysis of the cultures of addiction. Traversing cultures across the globe, including Asia, Central America, as well as Europe and America, this book opens up the debate in addiction studies and cultural studies. The important insights the book delivers helps to answer questions such as: In what way can Deleuze further the understanding of addiction through the analysis of rock lyrics? How does anthropology improve the understanding of AA groups? How can cultural studies deepen knowledge on the “addiction” to therapy? These are just some of the vast array of areas this book covers. Other areas include the condemnation of “addiction” to comic reading through an historical examination, violence in popular culture, and lost women’s writing on addiction. No other book has such depth and contemporary breadth.

Cultures of Addiction is an important book for those taking cultural studies courses across a range of interrelated disciplines, including English and literary studies, history, American studies, and film and media studies. This will be invaluable to library collections in these fields and beyond in the social sciences, and specifically in addiction studies and psychology.

(Jason Lee, Editor)

Basic ingredients for mathematical modeling of tumor growth in vitro: Cooperative effects and search for space

Based on the literature data from HT-29 cell monolayers, we develop a model for its growth, analogous to an epidemic model, mixing local and global interactions. First, we propose and solve a deterministic equation for the progress of these colonies. Thus, we add a stochastic (local) interaction and simulate the evolution of an Eden-like aggregate by using dynamical Monte Carlo methods. The growth curves of both deterministic and stochastic models are in excellent agreement with the experimental observations. The waiting times distributions, generated via our stochastic model, allowed us to analyze the role of mesoscopic events. We obtain log-normal distributions in the initial stages of the growth and Gaussians at long times. We interpret these outcomes in the light of cellular division events: in the early stages, the phenomena are dependent each other in a multiplicative geometric-based process, and they are independent at long times. We conclude that the main ingredients for a good minimalist model of tumor growth, at mesoscopic level, are intrinsic cooperative mechanisms and competitive search for space. © 2013 Elsevier Ltd.

Using occupancy models to investigate space partitioning between two sympatric large predators, the jaguar and puma in central Brazil

Coexistence of sympatric species is mediated by resource partitioning. Pumas occur sympatrically with jaguars throughout most of the jaguar's range but few studies have investigated space partitioning between both species. Here, camera trapping and occupancy models accounting for imperfect detection were employed in a Bayesian framework to investigate space partitioning between the jaguar and puma in Emas National Park (ENP), central Brazil. Jaguars were estimated to occupy 54.1% and pumas 39.3% of the sample sites. Jaguar occupancy was negatively correlated with distance to water and positively correlated with the amount of dense habitat surrounding the camera trap. Puma occupancy only showed a weak negative correlation with distance to water and with jaguar presence. Both species were less often present at the same site than expected under independent distributions. Jaguars had a significantly higher detection probability at cameras on roads than at off-road locations. For pumas, detection was similar on and off-road. Results indicate that both differences in habitat use and active avoidance shape space partitioning between jaguars and pumas in ENP. Considering its size, the jaguar is likely the competitively dominant of the two species. Owing to its habitat preferences, suitable jaguar habitat outside the park is probably sparse. Consequently, the jaguar population is likely largely confined to the park, while the puma population is known to extend into ENP's surroundings. (C) 2011 Deutsche Gesellschaft fur Saugetierkunde. Published by Elsevier GmbH. All rights reserved.

Ecological distribution of semi-demersal fishes in space and time on the shelf of Antalya Gulf

In this study we provide a baseline data on semidemersal fish assemblages and biology in a heterogeneous and yet less studied portion of the shelf of Antalya Gulf. The distribution of fish abundance in three transects subjected to different fisheries regulations (fishery vs non fishery areas), and including depths of 10, 25, 75, 125, 200 m, was studied between May 2014 and February 2015 in representative months of winter, spring, summer and autumn seasons. A total of 76 fish species belonging to 40 families was collected and semidemersal species distribution was analyzed in comparison with the whole community. Spatial distribution of fish was driven mainly by depth and two main assemblages were observed: shallow waters (10-25; 75 m) and deep waters (125-200 m). Significant differences among transects were found for the whole community but not for the semidemersal species. Analysis showed that this was due to a strong relation of these species with local environmental characteristics rather than to a different fishing pressure over transects. Firstly all species distribute according to the bathymetrical gradient and secondly to the bottom type structure. Semidemersal species were then found more related to zooplankton and suspended matter availability. The main morphological characteristics, sex and size distribution of the target semidemersal species Spicara smaris (Linnaeus, 1758), Saurida undosquamis (Richardson, 1848), Pagellus acarne (Risso, 1827) were also investigated.

Screening the Structural Space of Bicyclo-DNA: Synthesis and Properties of Bicyclo-DNA Functionalized at C(6’)

The synthesis of a novel bicyclo-thymidine nucleoside bearing an ester functionality at C(6') (bc(alpha-alk)-nucleosides) is reported. This nucleoside was incorporated into oligodeoxynucleotides via solid phase phosphoramidite chemistry, and the ester moiety was post-synthetically converted to an amide or a carboxy group, or was left unchanged. Thermal melting data (T-m) with complementary DNA and RNA were collected and compared to natural DNA and to bc- and bc(ox)-DNA. It was found that single incorporations of bc(alpha-alk)-nucleosides in DNA duplexes were destabilizing by 0.5 to 2.5 degrees C/mod, whereas two consecutive bc(alpha-alk)-residues were less destabilizing, and in some cases even stabilizing by 0.5 degrees C/mod. In duplexes with complementary RNA, isolated bc(alpha-alk)-residues destabilized the duplex by -1.0 to -4.0 degrees C/mod, depending on the chemical nature of the substituent, whereas two consecutive modifications were only destabilizing by 0.3-1.0 degrees C/mod. The pairing selectivity was similar to that of unmodified or bc-DNA.

Is virtuality close enough to reality? A comparison of the effectiveness of simulations with traditional laboratory activities in a high school biology class

Some schools do not have ideal access to laboratory space and supplies. Computer simulations of laboratory activities can be a cost-effective way of presenting experiences to students, but are those simulations as effective at supplementing content concepts? This study compared the use of traditional lab activities illustrating the principles of cell respiration and photosynthesis in an introductory high school biology class with virtual simulations of the same activities. Additionally student results were analyzed to assess if student conceptual understanding was affected by the complexity of the simulation. Although all student groups posted average gain increases between the pre and post-tests coupled with positive effect sizes, students who completed the wet lab version of the activity consistently outperformed the students who completed the virtual simulation of the same activity. There was no significant difference between the use of more or less complex simulations. Students also tended to rate the wet lab experience higher on a motivation and interest inventory.

MQN-Mapplet: Visualization of Chemical Space with Interactive Maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13

The MQN-mapplet is a Java application giving access to the structure of small molecules in large databases via color-coded maps of their chemical space. These maps are projections from a 42-dimensional property space defined by 42 integer value descriptors called molecular quantum numbers (MQN), which count different categories of atoms, bonds, polar groups, and topological features and categorize molecules by size, rigidity, and polarity. Despite its simplicity, MQN-space is relevant to biological activities. The MQN-mapplet allows localization of any molecule on the color-coded images, visualization of the molecules, and identification of analogs as neighbors on the MQN-map or in the original 42-dimensional MQN-space. No query molecule is necessary to start the exploration, which may be particularly attractive for nonchemists. To our knowledge, this type of interactive exploration tool is unprecedented for very large databases such as PubChem and GDB-13 (almost one billion molecules). The application is freely available for download at www.gdb.unibe.ch.