The trans-membrane protein p25 forms highly specialized domains that regulate membrane composition and dynamics

Trans-membrane proteins of the p24 family are abundant, oligomeric proteins predominantly found in cis-Golgi membranes. They are not easily studied in vivo and their functions are controversial. We found that p25 can be targeted to the plasma membrane after inactivation of its canonical KKXX motif (KK to SS, p25SS), and that p25SS causes the co-transport of other p24 proteins beyond the Golgi complex, indicating that wild-type p25 plays a crucial role in retaining p24 proteins in cis-Golgi membranes. We then made use of these observations to study the intrinsic properties of these proteins, when present in a different membrane context. At the cell surface, the p25SS mutant segregates away from both the transferrin receptor and markers of lipid rafts, which are enriched in cholesterol and glycosphingolipids. This suggests that p25SS localizes to, or contributes to form, specialized membrane domains, presumably corresponding to oligomers of p25SS and other p24 proteins. Once at the cell surface, p25SS is endocytosed, together with other p24 proteins, and eventually accumulates in late endosomes, where it remains confined to well-defined membrane regions visible by electron microscopy. We find that this p25SS accumulation causes a concomitant accumulation of cholesterol in late endosomes, and an inhibition of their motility - two processes that are functionally linked. Yet, the p25SS-rich regions themselves seem to-exclude not only Lamp1 but also accumulated cholesterol. One may envision that p25SS accumulation, by excluding cholesterol from oligomers, eventually overloads neighboring late endosomal membranes with cholesterol beyond their capacity (see Discussion). In any case, our data show that p25 and presumably other p24 proteins are endowed with the intrinsic capacity to form highly specialized domains that control membrane composition and dynamics. We propose that p25 and other p24 proteins control the fidelity of membrane transport by maintaining cholesterol-poor membranes in the Golgi complex.

Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds

Linkage disequilibrium (LD) mapping is commonly used as a fine mapping tool in human genome mapping and has been used with some success for initial disease gene isolation in certain isolated inbred human populations. An understanding of the population history of domestic dog breeds suggests that LID mapping could be routinely utilized in this species for initial genome-wide scans. Such an approach offers significant advantages over traditional linkage analysis. Here, we demonstrate, using canine copper toxicosis in the Bedlington terrier as the model, that LID mapping could be reasonably expected to be a useful strategy in low-resolution, genome-wide scans in pure-bred dogs. Significant LID was demonstrated over distances up to 33.3 cM. It is very unlikely, for a number of reasons discussed, that this result could be extrapolated to the rest of the genome. It is, however, consistent with the expectation given the population structure of canine breeds and, in this breed at least, with the hypothesis that it may be possible to utilize LID in a genome-wide scan. In this study, LD mapping confirmed the location of the copper toxicosis in Bedlington terrier gene (CT-BT) and was able to do so in a population that was refractory to traditional linkage analysis.

Epitope map for a growth hormone receptor agonist monoclonal antibody, MAb 263

Monoclonal antibody (MAb) 263 is a widely used monoclonal antibody that recognizes the extracellular domain (ECD) of the GH receptor. It has been shown to act as a GH agonist both in vitro and in vivo, and we report here that it must be divalent to exert its effect on the full-length receptor. To understand the mechanism of its agonist action, we have determined the precise epitope for this antibody using a novel random PCR mutagenesis approach together with expression screening in yeast. A library of 5200 clones of rabbit GH receptor ECD mutants were screened both with MAb 263 and with an anticarboxy-tag antibody to verify complete ECD expression. Sequencing for clones that expressed complete ECD but were not MAb 263 positive identified 20 epitope residues distributed in a discontinuous manner throughout the ECD. The major part of the epitope, as revealed after mapping onto the crystal structure model of the ECD molecule, was located on the side and upper portion of domain 1, particularly within the D - E strand disulfide loop 79 - 96. Molecular dynamics docking of an antibody of the same isotype as MAb 263 was used to dock the bivalent antibody to the 1528-Angstrom(2) epitope and to visualize the likely consequences of MAb binding. The minimized model enables the antibody to grasp two receptors in a pincer-like movement from opposite sides, facilitating alignment of the receptor dimerization domains in a manner similar to, but not identical with, GH.

Mapping the royal road and other hierarchical functions

In this paper we present a technique for visualising hierarchical and symmetric, multimodal fitness functions that have been investigated in the evolutionary computation literature. The focus of this technique is on landscapes in moderate-dimensional, binary spaces (i.e., fitness functions defined over {0, 1}(n), for n less than or equal to 16). The visualisation approach involves an unfolding of the hyperspace into a two-dimensional graph, whose layout represents the topology of the space using a recursive relationship, and whose shading defines the shape of the cost surface defined on the space. Using this technique we present case-study explorations of three fitness functions: royal road, hierarchical-if-and-only-if (H-IFF), and hierarchically decomposable functions (HDF). The visualisation approach provides an insight into the properties of these functions, particularly with respect to the size and shape of the basins of attraction around each of the local optima.

Mapping the Obama administration's response to the Arab Spring

When the Arab Spring broke out, the United States was in a quandary over how to handle the crisis in its attempt to balance its moral obligations and ideals without undercutting its strategic interests and those of its close allies. Flaws in US diplomatic approach have contributed to one of the most serious foreign policy crisis for a US administration to date with consequential upheaval and erosion of the US-built balance of power. The reactions and policy responses of the Obama administration highlight the difficulties in grasping with the new reality in the Middle East and in enunciating a policy platform that could combine American interests and values.

The decentralized social networking systems towards mobilizing actions of citizenship and solidarity against cancer

The goal of the present study is mapping the nature of possible contributions of participatory online platforms in citizen actions that may contribute in the fight against cancer and its associated consequences. These platforms are usually associated with entertainment: in that sense, we intent to test their validity in other domains such as health, as well as contribute to an expanded perception of their potential by their users. The research is based on the analysis of online solidarity networks, namely the ones residing on Facebook, Orkut and the blogosphere, that citizens have been gradually resorting to. The research is also based on the development of newer and more efficient solutions that provide the individual (directly or indirectly affected by issues of oncology) with the means to overcome feelings of impotence and fatality. In this article, we aim at summarizing the processes of usage of these decentralized, freer participatory platforms by citizens and institutions, while attempting to unravel existing hype and stigma; we also provide a first survey of the importance and the role of institutions in this kind of endeavor; lastly, we present a prototype, developed in the context of the present study, that is specifically dedicated to addressing oncology through social media. This prototype is already available online at www.talkingaboutcancer.org, however, still under development and testing. The main objective of this platform is to allow every citizen to freely build their network of contacts and information, according to their own individual and/ or collective needs and desires.

Piezoresistive sensors for force mapping of hip-prostheses

The success of artificial prosthetic replacements depends on the fixation of the artificial prosthetic component after being implanted in the thighbone. The materials for fixation are subject to mechanical stresses, which originate permanent deformations, incipient cracks and even fatigue fractures. This work shows the possibility of monitoring the mechanical stress over time in prosthesis. In this way, highly sensitive silicon thin-film piezoresistive sensors were developed attached to prosthesis and their results compared with commercial strain gauge sensors. Mechanical stress-strain experiments were performed in compressive mode, during 10,000 cycles. Experimental data was acquired at mechanical vibration frequencies of 0.5 Hz, 1 Hz and 5 Hz, and sent to a computer by means of a wireless link. The results show that there is a decrease in sensitivity of the thin-film silicon piezoresistive sensors when they are attached to the prosthesis, but this decrease does not compromise its monitoring performance. The sensitivity, compared to that of commercial strain gauges, is much larger due to their higher gauge factors (-23.5), when compared to the GFs of commercial sensors (2).

Mapping Culture and Compromised Art in the Era of Globalization

This work presents an analysis of the cultural and artistic field, positively compromised with social and political questions. The authors start with the categorization of the idea of culture and move to vindication art movements. These movements, which followed the first vanguards and worked from the compromise with “otherness”, are at the origin of the contemporary denomination of political art. In this context, the authors approach the origins of activist art, referring to issues of gender, multiculturalism, globalization, and poverty. The different forms of presenting content are also an object of analysis: from art tradition to the contamination of daily life, from local to global, from street contact to digital.

Teaching drawing: an interdisciplinary pedagogical experience in a graphic design course

Various authors have written about the importance of drawing in design methodology. Their general conclusion points drawing as an essential tool for design research, as it allows investigation of several alternative solutions in design process (Cross, 2007). The recent profound changes in design nature (Norman, 2011), justify a discussion on the purpose of drawing in design courses. As a consequence of this new reality, the educational institutions face the challenge of the definition of their curricular structures and teaching methodologies. Among others, concepts such as collaboration and multidisciplinary design approaches have been discussed as strategies for design education (Heller and Talarico, 2011, pp. 82-85). In this context, and using our teaching activity experience in Drawing and Design areas, the authors discuss:  how can drawing methods be included in the current design teaching?  can drawing be considered as an interdisciplinary approach?  what contributions can these methodologies provide to the educational/learning process? Based on these concerns, we developed an interdisciplinary project in the Graphic Design Course with two curricular units: Drawing 1 and Aesthetic and Design Theory 1. In this article the authors present the aims and process developed, and discuss the outcomes of this pedagogical experience.

Exploring the interdisciplinary process in design education

The work presented herein follows an ongoing research that aims to analyze methodological practices to be applied in Design Education. A reflection about methodological strategies in Design Education and the function of drawing in Design represents the beginning of this study. Then, we developed an interdisciplinary pedagogical experience with the Graphic Design 1st grade students from our institution (IPCA). In the current academic year, 2013/2014, we continue to evolve this project, introducing changes in the initial proposal. Major alterations focused on the aspects that could be strengthened in terms of interdisciplinarity. In this article, the authors describe those changes and discuss the outcomes of the novel proposal. As we have already reported, this investigation follows a reflection about working methods to be adopted in Design Education. This is in accordance with other previously published works that purpose the enlargement of Design into new knowledge fields such as Experience or Service Design, changing not only the role of the graphic designer, but also the skills required to be a professional designer (Alain Findelli, 2001), (Brian Lawson, 2006), (Ciampa-Brewer, 2010). Furthermore, concepts such as cooperation or multidisciplinary design, amongst others, have been frequently debated as design teaching strategies (Heller and Talarico, 2011, pp. 82-85). These educational approaches also have an impact on our research. The analysis of all these authors’ contributions together with a reflection on our teaching practice allowed us to propose an improved interdisciplinary intervention.

Geostatistical Mapping of Outfall Plume Dispersion Data gathered with an autonomous underwater vehicle

The main purpose of this study was to examine the applicability of geostatistical modeling to obtain valuable information for assessing the environmental impact of sewage outfall discharges. The data set used was obtained in a monitoring campaign to S. Jacinto outfall, located off the Portuguese west coast near Aveiro region, using an AUV. The Matheron’s classical estimator was used the compute the experimental semivariogram which was fitted to three theoretical models: spherical, exponential and gaussian. The cross-validation procedure suggested the best semivariogram model and ordinary kriging was used to obtain the predictions of salinity at unknown locations. The generated map shows clearly the plume dispersion in the studied area, indicating that the effluent does not reach the near by beaches. Our study suggests that an optimal design for the AUV sampling trajectory from a geostatistical prediction point of view, can help to compute more precise predictions and hence to quantify more accurately dilution. Moreover, since accurate measurements of plume’s dilution are rare, these studies might be very helpful in the future for validation of dispersion models.

Representations of gender in the writings of St. Francis Xavier: an interdisciplinary approach

Francis Xavier’s Letters and Writings are eloquent narratives of a journey that absorbed the Saint’s entire life. His experiences and idiosyncrasies, values and categorizations are presented in a clear literate discourse. The missionary is rarely neutral in his opinions as he sustains his unmistakable and omnipresent objective: the conversion of peoples and the expansion of the Society of Jesus. Parallel with this objective, the reader is introduced to the individuals that Xavier meets or that he summons in his epistolary discourse. Letters and Writings presents us with a structured narrative peopled by all those who are subject to and objects of Xavier’s apostolic mission, by helpful and unhelpful persons of influence, and by leading and secondary actors. What is then the position of women, in the collective sense as well as in the individual sense, in the travels and goals that are the centre of Xavier’s Letters and Writings? What is the role of women, that secondary and suppressed term in the man/woman binomial, a dichotomy similar to the civilized/savage and European/native binomials that punctuate Xavier’s narratives and the historic context of his letters? Women are not absent from his writings, but it would be naïve to argue in favour of the author’s misogyny as much as of his “profound knowledge of the female heart”, to quote from Paulo Durão in "Women in the Letters of Saint Francis Xavier" (1952), the only paper on this subject published so far. We denote four great categories of women in the Letters and Writings: European Women, Converted Women, Women Who Profess another Religion, and Women as the Agents and Objects of Sin, the latter of which traverses the other three categories. They all depend on the context, circumstances and judgements of value that the author chooses to highlight and articulate.

Mapping atmospheric pollutants emissions in European countries

In this paper we present a methodology which enables the graphical representation, in a bi-dimensional Euclidean space, of atmospheric pollutants emissions in European countries. This approach relies on the use of Multidimensional Unfolding (MDU), an exploratory multivariate data analysis technique. This technique illustrates both the relationships between the emitted gases and the gases and their geographical origins. The main contribution of this work concerns the evaluation of MDU solutions. We use simulated data to define thresholds for the model fitting measures, allowing the MDU output quality evaluation. The quality assessment of the model adjustment is thus carried out as a step before interpretation of the gas types and geographical origins results. The MDU maps analysis generates useful insights, with an immediate substantive result and enables the formulation of hypotheses for further analysis and modeling.

Mapping multi-species habitat use for marine conservation planning

Tese de Doutoramento, Ciências do Mar (Biologia Marinha)

Mapping stability : real rational maps of degree zero

In memory of our beloved Professor José Rodrigues Santos de Sousa Ramos (1948-2007), who João Cabral, one of the authors of this paper, had the honor of being his student between 2000 and 2006, we wrote this paper following the research by experimentation, using the new technologies to capture a new insight about a problem, as him so much love to do it. His passion was to create new relations between different fields of mathematics. He was a builder of bridges of knowledge, encouraging the birth of new ways to understand this science. One of the areas that Sousa Ramos researched was the iteration of maps and the description of its behavior, using the symbolic dynamics. So, in this issue of this journal, honoring his memory, we use experimental results to find some stable regions of a specific family of real rational maps, the ones that he worked with João Cabral. In this paper we describe a parameter space (a,b) to the real rational maps fa,b(x) = (x2 −a)/(x2 −b), using some tools of dynamical systems, as the study of the critical point orbit and Lyapunov exponents. We give some results regarding the stability of these family of maps when we iterate it, specially the ones connected to the order 3 of iteration. We hope that our results would help to understand better the behavior of these maps, preparing the ground to a more efficient use of the Kneading Theory on these family of maps, using symbolic dynamics.