(Table 1) Concentrations of neutral and phenolic organohalogen compounds in adipose tissue, blood, brain and liver of polar bears (Ursus maritimus) from East Greenland

The tissue-specific composition of sum classes of brominated and chlorinated contaminants and metabolic/degradation byproducts was determined in adult male and female polar bears from East Greenland. Significantly (p < 0.05) higher concentrations of SUM-PCBs, various other organochlorines such as SUM-CHL, p,p'-DDE, SUM-CBz, SUM-HCHs, octachlorostyrene (OCS),SUM-mirex, dieldrin, the flame retardants SUM-PBDEs, and total-(R)-hexabromocyclododecane (HBCD), SUM-methylsulfonyl (MeSO2)-PCBs and 3-MeSO2-p,p'-DDE, were found in the adipose and liver tissues relative to whole blood and brain. In contrast, SUM-hydroxyl (OH)-PCB, 4-OH-heptachlorostyrene and SUM-OH-PBDE concentrations were significantly highest (p < 0.05) in whole blood, whereas the highest concentrations of SUM-OH-PBBs were found in the adipose tissue. Based on the total concentrations of all organohalogens in all three tissues and blood, the combined body burden was estimated to be 1.34 ± 0.12 g, where >91% of this amount was accounted for by the adipose tissue alone, followed by the liver, whole blood, and brain. These results show that factors such as protein association and lipid solubility appear to be differentially influencing the toxicokinetics, in terms of tissue composition/localization and burden, of organohalogen classes with respect to chemical structure and properties such as the type of halogenation (e.g., chlorination or bromination), and the presence or absence of additional phenyl group substituents (e.g., MeO and OH groups). The tissue- and blood-specific accumulation (or retention) among organohalogen classes indicates that exposure and any potential contaminant-mediated effects in these polar bears are likely tissue or blood specific.

Issues Affecting the Movement of Rural Labour in Myanmar: Rakhine Case Study

This paper presents issues affecting the movement of rural labour in Myanmar, by examining the background, purpose and earned income of labourers migrating to fishing villages in southern Rakhine. A broad range of socioeconomic classes, from poor to rich, farmers to fishermen, is migrating from broader areas to specific labour-intensive fishing subsectors, such as anchovy fishing. These labourers are a mixed group of people whose motives lie either in supplementing their household income or accumulating capital for further expansion of their economic activities. The concentration of migrating labourers with different objectives in this particular unstable, unskilled employment opportunity suggests an insufficiently developed domestic labour market in rural Myanmar. There is a pressing need to create stable labour-intensive industries to meet this demand.

Analytical properties of horizontal visibility graphs in the Feigenbaum scenario

Time series are proficiently converted into graphs via the horizontal visibility (HV) algorithm, which prompts interest in its capability for capturing the nature of different classes of series in a network context. We have recently shown [B. Luque et al., PLoS ONE 6, 9 (2011)] that dynamical systems can be studied from a novel perspective via the use of this method. Specifically, the period-doubling and band-splitting attractor cascades that characterize unimodal maps transform into families of graphs that turn out to be independent of map nonlinearity or other particulars. Here, we provide an in depth description of the HV treatment of the Feigenbaum scenario, together with analytical derivations that relate to the degree distributions, mean distances, clustering coefficients, etc., associated to the bifurcation cascades and their accumulation points. We describe how the resultant families of graphs can be framed into a renormalization group scheme in which fixed-point graphs reveal their scaling properties. These fixed points are then re-derived from an entropy optimization process defined for the graph sets, confirming a suggested connection between renormalization group and entropy optimization. Finally, we provide analytical and numerical results for the graph entropy and show that it emulates the Lyapunov exponent of the map independently of its sign.

Meromorphic continuation of functions and arbitrary distribution of interpolation points

We characterize the region of meromorphic continuation of an analytic function ff in terms of the geometric rate of convergence on a compact set of sequences of multi-point rational interpolants of ff. The rational approximants have a bounded number of poles and the distribution of interpolation points is arbitrary.

YUCCA8 and YUCCA9 overexpression reveals a link between auxin signaling and lignification through the induction of ethylene biosynthesis.

Auxin is associated with the regulation of virtually every aspect of plant growth and development. Many previous genetic and biochemical studies revealed that, among the proposed routes for the production of auxin, the so-called indole-3-pyruvic acid (IPA) pathway is the main source for indole-3-acetic acid (IAA) in plants. The IPA pathway involves the action of 2 classes of enzymes, tryptophan-pyruvate aminotransferases (TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1(TAA1)/TRYPTOPHAN AMINOTRANSFERASE RELATED (TAR)) and flavin monooxygenases (YUCCA). Both enzyme classes appear to be encoded by small gene families in Arabidopsis consisting of 5 and 11 members, respectively. We recently showed that it is possible to induce transcript accumulation of 2 YUCCA genes, YUC8 and YUC9, by methyl jasmonate treatment. Both gene products were demonstrated to contribute to auxin biosynthesis in planta.1 Here we report that the overexpression of YUC8 as well as YUC9 led to strong lignification of plant aerial tissues. Furthermore, new evidence indicates that this abnormally strong secondary growth is linked to increased levels of ethylene production.

Sight distance studies on roads: influence of digital elevation models and roadside elements

Sight distance plays an important role in road traffic safety. Two types of Digital Elevation Models (DEMs) are utilized for the estimation of available sight distance in roads: Digital Terrain Models (DTMs) and Digital Surface Models (DSMs). DTMs, which represent the bare ground surface, are commonly used to determine available sight distance at the design stage. Additionally, the use of DSMs provides further information about elements by the roadsides such as trees, buildings, walls or even traffic signals which may reduce available sight distance. This document analyses the influence of three classes of DEMs in available sight distance estimation. For this purpose, diverse roads within the Region of Madrid (Spain) have been studied using software based on geographic information systems. The study evidences the influence of using each DEM in the outcome as well as the pros and cons of using each model.

Leslie Martin, Colin St. John Wilson y James Stirling : revisión de la modernidad en la arquitectura británica = Leslie Martin, Colin St. John Wilson and James Stirling : review of modernity in British architecture

La búsqueda de nuevas formas de modernidad se convirtió en la cuestión principal de la obras desarrolladas por Leslie Martin, Colin St. John Wilson y James Stirling entre los años 1955 y 1970. Enmarcadas dentro de la sensibilidad surgida en la posguerra británica, su profundo sentido crítico supone una renovada interpretación de alguno fundamentos del Movimiento Moderno así como la reflexión sobre la modificación y el uso de formas que tienen sus raíces en la tradición cultural. Esta investigación se estructura en cuatro temas ampliamente debatidos y que han articulado parte de la revisión moderna a lo largo de la segunda mitad del siglo XX: » la abstracción y el realismo » la revisión de la idea funcionalista » la reconsideración de los arquetipos formales » la relación entre forma y contexto urbano se muestran como base crítica para las obras seleccionadas. La tendencia hacia el realismo surgió como respuesta a la voluntad de universalidad (y objetividad) que representó el lenguaje abstracto, del mismo modo que la revisión de la idea funcionalista pretendió superar la consideración de la obra arquitectónica como producto racional de su función y tecnología. La reconsideración de los arquetipos de la tradición, a su vez, muestra una preocupación por el significado de las formas culturales del pasado, una cuestión igualmente decisiva en la renovada atención a la estructura de la ciudad histórica. Estos temas evidencian un interés por ampliar la arquitectura moderna sin que el reconocimiento de las formas del pasado suponga un distanciamiento respecto al futuro. La idea de revisión, asimismo, se convierte en estrategia a la hora de encontrar nuevas respuestas. Si algunos de los principios del Movimiento Moderno surgen como reacción al clasicismo Beaux Arts que le precedió, las propuestas analizadas muestran la validez operativa de este enfoque para crear obras de una intensa modernidad. Su interés, por lo tanto, no solo radica en su consideración como objetos de estudio que amplían nuestro conocimiento de un período determinado, sino como tradición reciente que sirve de base crítica para la práctica actual. ABSTRACT The search of new forms of modernity became the main theme of the works developed by Leslie Martin, Colin St. John Wilson and James Stirling between 1955 and 1970. Belonging to the sensitivity emerged in postwar Britain, their deep critical sense encourages a renewed interpretation of some principles of Modern Movement and a reflection about the modification or the use of forms that are rooted in cultural tradition. This research is divided into four themes widely discussed and which has articulated part of modern review along the second half of the twentieth century: » Abstraction and realism » Review of Functionalism » The reconsideration of the formal archetypes » The relationship between form and urban context are shown as critical base for the selected works. The trend toward realism arose in response to the will of universality (and objectivity) that represented the abstract language, just as the review of Functionalism aimed to overcome the consideration of architecture's work as rational product of its function and technology. The reconsideration of traditional archetypes, in turn, shows a concern for the meaning of the cultural forms, a matter equally decisive in the renewed attention to the structure of the historical city. These themes evidence an interest to extend modern architecture, without thereby the recognition of the past forms imply a distancing regarding the future. The idea of review also becomes strategy in finding new answers. If some principles of the Modern Movement arose in reaction to Beaux-Arts classicism which preceded it, the analyzed proposals show the operational validity of this approach to create works of a strong modernity. Their interest, therefore, lies not only in its consideration as study cases that broaden our knowledge of a certain period, but as a recent tradition which serves as a critic basis for the current practice.

NMR determination of the major solution conformation of a peptoid pentamer with chiral side chains

Polymers of N-substituted glycines (“peptoids”) containing chiral centers at the α position of their side chains can form stable structures in solution. We studied a prototypical peptoid, consisting of five para-substituted (S)-N-(1-phenylethyl)glycine residues, by NMR spectroscopy. Multiple configurational isomers were observed, but because of extensive signal overlap, only the major isomer containing all cis-amide bonds was examined in detail. The NMR data for this molecule, in conjunction with previous CD spectroscopic results, indicate that the major species in methanol is a right-handed helix with cis-amide bonds. The periodicity of the helix is three residues per turn, with a pitch of ≈6 Å. This conformation is similar to that anticipated by computational studies of a chiral peptoid octamer. The helical repeat orients the amide bond chromophores in a manner consistent with the intensity of the CD signal exhibited by this molecule. Many other chiral polypeptoids have similar CD spectra, suggesting that a whole family of peptoids containing chiral side chains is capable of adopting this secondary structure motif. Taken together, our experimental and theoretical studies of the structural properties of chiral peptoids lay the groundwork for the rational design of more complex polypeptoid molecules, with a variety of applications, ranging from nanostructures to nonviral gene delivery systems.

Enhanced immunogenicity of HIV-1 vaccine construct by modification of the native peptide sequence

Viral proteins are not naturally selected for high affinity major histocompatibility complex (MHC) binding sequences; indeed, if there is any selection, it is likely to be negative in nature. Thus, one should be able to increase viral peptide binding to MHC in the rational design of synthetic peptide vaccines. The T1 helper peptide from the HIV-1 envelope protein was made more immunogenic for inducing T cell proliferation to the native sequence by replacing a residue that exerts an adverse influence on peptide binding to an MHC class II molecule. Mice immunized with vaccine constructs combining the more potent Th helper (Th) epitope with a cytotoxic T lymphocyte (CTL) determinant developed greatly enhanced CTL responses. Use of class II MHC-congenic mice confirmed that the enhancement of CTL response was due to class II-restricted help. Thus, enhanced T cell help is key for optimal induction of CTL, and, by modification of the native immunogen to increase binding to MHC, it is possible to develop second generation vaccine constructs that enhance both Th cell activation and CTL induction.

Systematic derivation of partition functions for ligand binding to two-dimensional lattices

The Ising problem consists in finding the analytical solution of the partition function of a lattice once the interaction geometry among its elements is specified. No general analytical solution is available for this problem, except for the one-dimensional case. Using site-specific thermodynamics, it is shown that the partition function for ligand binding to a two-dimensional lattice can be obtained from those of one-dimensional lattices with known solution. The complexity of the lattice is reduced recursively by application of a contact transformation that involves a relatively small number of steps. The transformation implemented in a computer code solves the partition function of the lattice by operating on the connectivity matrix of the graph associated with it. This provides a powerful new approach to the Ising problem, and enables a systematic analysis of two-dimensional lattices that model many biologically relevant phenomena. Application of this approach to finite two-dimensional lattices with positive cooperativity indicates that the binding capacity per site diverges as Na (N = number of sites in the lattice) and experiences a phase-transition-like discontinuity in the thermodynamic limit N → ∞. The zeroes of the partition function tend to distribute on a slightly distorted unit circle in complex plane and approach the positive real axis already for a 5×5 square lattice. When the lattice has negative cooperativity, its properties mimic those of a system composed of two classes of independent sites with the apparent population of low-affinity binding sites increasing with the size of the lattice, thereby accounting for a phenomenon encountered in many ligand-receptor interactions.

The protein kinases of Caenorhabditis elegans: A model for signal transduction in multicellular organisms

Caenorhabditis elegans should soon be the first multicellular organism whose complete genomic sequence has been determined. This achievement provides a unique opportunity for a comprehensive assessment of the signal transduction molecules required for the existence of a multicellular animal. Although the worm C. elegans may not much resemble humans, the molecules that regulate signal transduction in these two organisms prove to be quite similar. We focus here on the content and diversity of protein kinases present in worms, together with an assessment of other classes of proteins that regulate protein phosphorylation. By systematic analysis of the 19,099 predicted C. elegans proteins, and thorough analysis of the finished and unfinished genomic sequences, we have identified 411 full length protein kinases and 21 partial kinase fragments. We also describe 82 additional proteins that are predicted to be structurally similar to conventional protein kinases even though they share minimal primary sequence identity. Finally, the richness of phosphorylation-dependent signaling pathways in worms is further supported with the identification of 185 protein phosphatases and 128 phosphoprotein-binding domains (SH2, PTB, STYX, SBF, 14-3-3, FHA, and WW) in the worm genome.

A transient expansion of the native state precedes aggregation of recombinant human interferon-γ

Aggregation of proteins, even under conditions favoring the native state, is a ubiquitous problem in biotechnology and biomedical engineering. Providing a mechanistic basis for the pathways that lead to aggregation should allow development of rational approaches for its prevention. We have chosen recombinant human interferon-γ (rhIFN-γ) as a model protein for a mechanistic study of aggregation. In the presence of 0.9 M guanidinium hydrochloride, rhIFN-γ aggregates with first order kinetics, a process that is inhibited by addition of sucrose. We describe a pathway that accounts for both the observed first-order aggregation of rhIFN-γ and the effect of sucrose. In this pathway, aggregation proceeds through a transient expansion of the native state. Sucrose shifts the equilibrium within the ensemble of rhIFN-γ native conformations to favor the most compact native species over more expanded ones, thus stabilizing rhIFN-γ against aggregation. This phenomenon is attributed to the preferential exclusion of sucrose from the protein surface. In addition, kinetic analysis combined with solution thermodynamics shows that only a small (9%) expansion surface area is needed to form the transient native state that precedes aggregation. The approaches used here link thermodynamics and aggregation kinetics to provide a powerful tool for understanding both the pathway of protein aggregation and the rational use of excipients to inhibit the process.

Unexpected crucial role of residue 225 in serine proteases

Residue 225 in serine proteases of the chymotrypsin family is Pro or Tyr in more than 95% of nearly 300 available sequences. Proteases with Y225 (like some blood coagulation and complement factors) are almost exclusively found in vertebrates, whereas proteases with P225 (like degradative enzymes) are present from bacteria to human. Saturation mutagenesis of Y225 in thrombin shows that residue 225 affects ligand recognition up to 60,000-fold. With the exception of Tyr and Phe, all residues are associated with comparable or greatly reduced catalytic activity relative to Pro. The crystal structures of three mutants that differ widely in catalytic activity (Y225F, Y225P, and Y225I) show that although residue 225 makes no contact with substrate, it drastically influences the shape of the water channel around the primary specificity site. The activity profiles obtained for thrombin also suggest that the conversion of Pro to Tyr or Phe documented in the vertebrates occurred through Ser and was driven by a significant gain (up to 50-fold) in catalytic activity. In fact, Ser and Phe are documented in 4% of serine proteases, which together with Pro and Tyr account for almost the entire distribution of residues at position 225. The unexpected crucial role of residue 225 in serine proteases explains the evolutionary selection of residues at this position and shows that the structural determinants of protease activity and specificity are more complex than currently believed. These findings have broad implications in the rational design of enzymes with enhanced catalytic properties.

Mechanism of Ca2+-dependent nuclear accumulation of calmodulin

The intracellular Ca2+ receptor calmodulin (CaM) coordinates responses to extracellular stimuli by modulating the activities of its various binding proteins. Recent reports suggest that, in addition to its familiar functions in the cytoplasm, CaM may be directly involved in rapid signaling between cytoplasm and nucleus. Here we show that Ca2+-dependent nuclear accumulation of CaM can be reconstituted in permeabilized cells. Accumulation was blocked by M13, a CaM antagonist peptide, but did not require cytosolic factors or an ATP regenerating system. Ca2+-dependent influx of CaM into nuclei was not blocked by inhibitors of nuclear localization signal-mediated nuclear import in either permeabilized or intact cells. Fluorescence recovery after photobleaching studies of CaM in intact cells showed that influx is a first-order process with a rate constant similar to that of a freely diffusible control molecule (20-kDa dextran). Studies of CaM efflux from preloaded nuclei in permeablized cells revealed the existence of three classes of nuclear binding sites that are distinguished by their Ca2+-dependence and affinity. At high [Ca2+], efflux was enhanced by addition of a high affinity CaM-binding protein outside the nucleus. These data suggest that CaM diffuses freely through nuclear pores and that CaM-binding proteins in the nucleus act as a sink for Ca2+-CaM, resulting in accumulation of CaM in the nucleus on elevation of intracellular free Ca2+.