The role of flow experience in codesigning open-design assistive devices

This paper describes the theoretical framework of an inclusive participatory design approach which leads to qualitative occupational experiences within the field of community-based rehabilitation. The aim is to support voluntarily controlled activities by applying co-construction theories to disabled users and their dynamic environment. The starting point of this open design process is a threefold interaction involving caregivers, patients and occupational therapists within their local product ecology. Co-creation is used as a set of iterative techniques to steer the patient towards flow experiences. Do-it-Yourself is consecutively applied as physical prototyping, communication language and personal manufacturing process. By implementing this active engagement process disabled people and their carers become conscious actors in providing collaborative maintenance of their own physical, mental and social well-being

MISTIC: mutual information server to infer coevolution

MISTIC (mutual information server to infer coevolution) is a web server for graphical representation of the information contained within a MSA (multiple sequence alignment) and a complete analysis tool for Mutual Information networks in protein families. The server outputs a graphical visualization of several information-related quantities using a circos representation. This provides an integrated view of the MSA in terms of (i) the mutual information (MI) between residue pairs, (ii) sequence conservation and (iii) the residue cumulative and proximity MI scores. Further, an interactive interface to explore and characterize the MI network is provided. Several tools are offered for selecting subsets of nodes from the network for visualization. Node coloring can be set to match different attributes, such as conservation, cumulative MI, proximity MI and secondary structure. Finally, a zip file containing all results can be downloaded. The server is available at http://mistic.leloir.org.ar. In summary, MISTIC allows for a comprehensive, compact, visually rich view of the information contained within an MSA in a manner unique to any other publicly available web server. In particular, the use of circos representation of MI networks and the visualization of the cumulative MI and proximity MI concepts is novel.Fil: Simonetti, Franco Lucio. Fundación Instituto Leloir. Unidad de Bioinformática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Teppa, Elin. Fundación Instituto Leloir. Unidad de Bioinformática; ArgentinaFil: Chernomoretz, Ariel. Fundación Instituto Leloir. Unidad de Bioinformática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Nielsen, Morten. Technical University of Denmark. Center for Biological Sequence Analysis; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Marino Buslje, Cristina . Fundación Instituto Leloir. Unidad de Bioinformática; Argentin

How Did the Spider Cross the River? Behavioral Adaptations for River-Bridging Webs in Caerostris darwini (Araneae: Araneidae)

Interspecific coevolution is well described, but we know significantly less about how multiple traits coevolve within a species, particularly between behavioral traits and biomechanical properties of animals' "extended phenotypes". In orb weaving spiders, coevolution of spider behavior with ecological and physical traits of their webs is expected. Darwin's bark spider (Caerostris darwini) bridges large water bodies, building the largest known orb webs utilizing the toughest known silk. Here, we examine C. darwini web building behaviors to establish how bridge lines are formed over water. We also test the prediction that this spider's unique web ecology and architecture coevolved with new web building behaviors.We observed C. darwini in its natural habitat and filmed web building. We observed 90 web building events, and compared web building behaviors to other species of orb web spiders.Caerostris darwini uses a unique set of behaviors, some unknown in other spiders, to construct its enormous webs. First, the spiders release unusually large amounts of bridging silk into the air, which is then carried downwind, across the water body, establishing bridge lines. Second, the spiders perform almost no web site exploration. Third, they construct the orb capture area below the initial bridge line. In contrast to all known orb-weavers, the web hub is therefore not part of the initial bridge line but is instead built de novo. Fourth, the orb contains two types of radial threads, with those in the upper half of the web doubled. These unique behaviors result in a giant, yet rather simplified web. Our results continue to build evidence for the coevolution of behavioral (web building), ecological (web microhabitat) and biomaterial (silk biomechanics) traits that combined allow C. darwini to occupy a unique niche among spiders

PTMcode v2: a resource for functional associations of post-translational modifications within and between proteins

The post-translational regulation of proteins is mainly driven by two molecular events, their modification by several types of moieties and their interaction with other proteins. These two processes are interdependent and together are responsible for the function of the protein in a particular cell state. Several databases focus on the prediction and compilation of protein-protein interactions (PPIs) and no less on the collection and analysis of protein post-translational modifications (PTMs), however, there are no resources that concentrate on describing the regulatory role of PTMs in PPIs. We developed several methods based on residue co-evolution and proximity to predict the functional associations of pairs of PTMs that we apply to modifications in the same protein and between two interacting proteins. In order to make data available for understudied organisms, PTMcode v2 (http://ptmcode.embl.de) includes a new strategy to propagate PTMs from validated modified sites through orthologous proteins. The second release of PTMcode covers 19 eukaryotic species from which we collected more than 300 000 experimentally verified PTMs (>1 300 000 propagated) of 69 types extracting the post-translational regulation of >100 000 proteins and >100 000 interactions. In total, we report 8 million associations of PTMs regulating single proteins and over 9.4 million interplays tuning PPIs

Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites

In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu) influenza A virus strain neuraminidase for drug treatment and vaccination. We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas. Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site. The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu®), zanamivir (Relenza®) and peramivir; thus, the drugs should remain effective for treatment. However, the antigenic regions of the neuraminidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients

Redundant neural vision systems: competing for collision recognition roles

Ability to detect collisions is vital for future robots that interact with humans in complex visual environments. Lobula giant movement detectors (LGMD) and directional selective neurons (DSNs) are two types of identified neurons found in the visual pathways of insects such as locusts. Recent modelling studies showed that the LGMD or grouped DSNs could each be tuned for collision recognition. In both biological and artificial vision systems, however, which one should play the collision recognition role and the way the two types of specialized visual neurons could be functioning together are not clear. In this modeling study, we compared the competence of the LGMD and the DSNs, and also investigate the cooperation of the two neural vision systems for collision recognition via artificial evolution. We implemented three types of collision recognition neural subsystems – the LGMD, the DSNs and a hybrid system which combines the LGMD and the DSNs subsystems together, in each individual agent. A switch gene determines which of the three redundant neural subsystems plays the collision recognition role. We found that, in both robotics and driving environments, the LGMD was able to build up its ability for collision recognition quickly and robustly therefore reducing the chance of other types of neural networks to play the same role. The results suggest that the LGMD neural network could be the ideal model to be realized in hardware for collision recognition

New methods to measure residues coevolution in proteins

<p>Abstract</p> <p>Background</p> <p>The covariation of two sites in a protein is often used as the degree of their coevolution. To quantify the covariation many methods have been developed and most of them are based on residues position-specific frequencies by using the mutual information (MI) model.</p> <p>Results</p> <p>In the paper, we proposed several new measures to incorporate new biological constraints in quantifying the covariation. The first measure is the mutual information with the amino acid background distribution (MIB), which incorporates the amino acid background distribution into the marginal distribution of the MI model. The modification is made to remove the effect of amino acid evolutionary pressure in measuring covariation. The second measure is the mutual information of residues physicochemical properties (MIP), which is used to measure the covariation of physicochemical properties of two sites. The third measure called MIBP is proposed by applying residues physicochemical properties into the MIB model. Moreover, scores of our new measures are applied to a robust indicator <it>conn(k) </it>in finding the covariation signal of each site.</p> <p>Conclusions</p> <p>We find that incorporating amino acid background distribution is effective in removing the effect of evolutionary pressure of amino acids. Thus the MIB measure describes more biological background information for the coevolution of residues. Besides, our analysis also reveals that the covariation of physicochemical properties is a new aspect of coevolution information.</p

Integration of Evolutionary Features for the Identification of Functionally Important Residues in Major Facilitator Superfamily Transporters

The identification of functionally important residues is an important challenge for understanding the molecular mechanisms of proteins. Membrane protein transporters operate two-state allosteric conformational changes using functionally important cooperative residues that mediate long-range communication from the substrate binding site to the translocation pathway. In this study, we identified functionally important cooperative residues of membrane protein transporters by integrating sequence conservation and co-evolutionary information. A newly derived evolutionary feature, the co-evolutionary coupling number, was introduced to measure the connectivity of co-evolving residue pairs and was integrated with the sequence conservation score. We tested this method on three Major Facilitator Superfamily (MFS) transporters, LacY, GlpT, and EmrD. MFS transporters are an important family of membrane protein transporters, which utilize diverse substrates, catalyze different modes of transport using unique combinations of functional residues, and have enough characterized functional residues to validate the performance of our method. We found that the conserved cores of evolutionarily coupled residues are involved in specific substrate recognition and translocation of MFS transporters. Furthermore, a subset of the residues forms an interaction network connecting functional sites in the protein structure. We also confirmed that our method is effective on other membrane protein transporters. Our results provide insight into the location of functional residues important for the molecular mechanisms of membrane protein transporters