Complementary function and integrated wiring of the evolutionarily distinct Drosophila olfactory subsystems.

To sense myriad environmental odors, animals have evolved multiple, large families of divergent olfactory receptors. How and why distinct receptor repertoires and their associated circuits are functionally and anatomically integrated is essentially unknown. We have addressed these questions through comprehensive comparative analysis of the Drosophila olfactory subsystems that express the ionotropic receptors (IRs) and odorant receptors (ORs). We identify ligands for most IR neuron classes, revealing their specificity for select amines and acids, which complements the broader tuning of ORs for esters and alcohols. IR and OR sensory neurons exhibit glomerular convergence in segregated, although interconnected, zones of the primary olfactory center, but these circuits are extensively interdigitated in higher brain regions. Consistently, behavioral responses to odors arise from an interplay between IR- and OR-dependent pathways. We integrate knowledge on the different phylogenetic and developmental properties of these receptors and circuits to propose models for the functional contributions and evolution of these distinct olfactory subsystems.

Visualització de la interaccio entre la proteïnaG12 i la catenina p120

Els processos de senyalització a través de receptors acoplats a proteïnes G (GPCRs) estan implicats en una gran varietat de processos fisiològics i patològics. Els objectius de la meva recerca es centren en l’estudi de la funció de les proteïnes heterotrimèriques de la família G12, en particular, en el paper que aquestes proteïnes poden tenir en la inducció de la migració cel•lular. Des del seu descobriment, s’han descrit diversos efectors que s’uneixen i es regulen per aquestes proteïnes. Les proteïnes de la família de RhoGEF semblen ser els efectors més directes i que juguen un paper més important en els processos de senyalització de les proteïnes G12. Tanmateix, resultats recents semblen indicar que altres vies independent de l’activació de Rho són també necessàries perquè els efectes fisiològics de les vies de les proteïnes G12 tinguin lloc. En aquest camp, els resultats que he obtingut, juntament amb resultats previs del grup, han descrit una nova via d’activació independent de Rho. Hem trobat que la proteïna G12 s’uneix a una catenina: la catenina p120. La seva unió sembla tenir lloc a través l’extrem N-terminal de la catenina i condueix a la reducció de la fosforilació en algun dels seus residus de tirosina, ja sigui per la quinasa Src o per l’activació a través d’EGF. Per tant, aquests resultats suggereixen que una altra via d’acció de la proteïna G12 seria mitjançant la regulació de la catenina p120 i, com a conseqüència, alguns processos d’adhesió cel•lular es podrien veure afectats. A fi d’entendre millor la regulació i la interacció de la catenina p120 hem iniciat l’estudi de la seva distribució cel•lular en l’espai i temps mitjançant tècniques de microscopia. Així, vam intentar construir una sonda de G12 fluorescent amb GFP. Després de diversos intents i experiments amb proteïnes no funcionals hem aconseguit, amb la col•laboració de T. Meigs, una construcció funcional que activa Rho. Això ens permetrà acabar els experiments de seguiment in vivo.

Accepting Methadone: The Evolution of an Institutional Decision

This is a study of organisational decision making among senior civil servants in the Department of Health (DOH) in relation to the acceptance of methadone maintenance as a valid treatment modality for opiate misuse in Ireland. A qualitative strategy was adopted with an emergent design and grounded theory perspective. The data was collected using a naturalistic mode of inquiry and comprised of documentary analysis and semi-structured interviews. The aspects of decision making chosen for the study were: 1. Identifying the actors involved considering the heretofore dominant 'corporation sole' culture of the Irish public administration. 2. Identifying two (out of the myriad) processes involved in decision making. 3. Identifying what theoretical model(s) of decision making most closely approximates to this case. The findings were as follows: 1. Actors involved at all levels of the decision making could be identified, albeit with some difficulty. This as a result of the strategic management initiative. Previously, it may not have been possible. Stages or phases could not, in this case, be readily identified though limitations of this study may prove significant. 2. Both the processes selected in decision-making in this case were confirmed. Personal and professional support provided by peers and seniors is crucial to decision making. Decision making does occur within networks: these tend to be those that are formally appointed rather than informal ones. 3. The model closest to that of this case was that of incremental decision making within network settings.This resource was contributed by The National Documentation Centre on Drug Use.

Categorization of bibsonomy tags to apply privacy-preserving mechanisms.

In this technical report, we approach one of the practical aspects when it comes to represent users' interests from their tagging activity, namely the categorization of tags into high-level categories of interest. The reason is that the representation of user profiles on the basis of the myriad of tags available on the Web is certainly unfeasible from various practical perspectives; mainly concerningthe unavailability of data to reliably, accurately measure interests across such fine-grained categorization, and, should the data be available, its overwhelming computational intractability. Motivated by this, our study presents the results of a categorization process whereby a collection of tags posted at BibSonomy #http://www.bibsonomy.org# are classified into 5 categories of interest. The methodology used to conduct such categorization is in line with other works in the field.

Hierarchical categorisation of tags for delicious

In the scenario of social bookmarking, a user browsing the Web bookmarks web pages and assigns free-text labels (i.e., tags) to them according to their personal preferences. In this technical report, we approach one of the practical aspects when it comes to represent users' interests from their tagging activity, namely the categorization of tags into high-level categories of interest. The reason is that the representation of user profiles on the basis of the myriad of tags available on the Web is certainly unfeasible from various practical perspectives; mainly concerning the unavailability of data to reliably, accurately measure interests across such fine-grained categorisation, and, should the data be available, its overwhelming computational intractability. Motivated by this, our study presents the results of a categorization process whereby a collection of tags posted at Delicious #http://delicious.com# are classified into 200 subcategories of interest.

Daughter of time: the postmodern midwife (Part 2)

Any effort to make sense of the complexities of contemporary midwifery must deal not only with biomedical and governmental power structures but also with the definitions such structures impose upon midwives and the ramifications of these definitions within and across national and cultural borders. The international definition of a midwife requires graduations from a government-recognized educational program. Those who have not are not considered midwives but are labeled traditional birth attendants. Since there are myriad local names for midwives in myriad languages, the impact of this naming at local levels can be hard to assess. But on the global scale, the ramifications of the distinction between midwives who meet the international definition and those who do not have been profound. Those who do are incorporated into the health care system. Those who do not remain outside of it, and suffer multiple forms of discrimination as a result.

Methods for integration site distribution analyses in animal cell genomes.

The question of where retroviral DNA becomes integrated in chromosomes is important for understanding (i) the mechanisms of viral growth, (ii) devising new anti-retroviral therapy, (iii) understanding how genomes evolve, and (iv) developing safer methods for gene therapy. With the completion of genome sequences for many organisms, it has become possible to study integration targeting by cloning and sequencing large numbers of host-virus DNA junctions, then mapping the host DNA segments back onto the genomic sequence. This allows statistical analysis of the distribution of integration sites relative to the myriad types of genomic features that are also being mapped onto the sequence scaffold. Here we present methods for recovering and analyzing integration site sequences.

Hidden branches: developments in root system architecture.

The root system is fundamentally important for plant growth and survival because of its role in water and nutrient uptake. Therefore, plants rely on modulation of root system architecture (RSA) to respond to a changing soil environment. Although RSA is a highly plastic trait and varies both between and among species, the basic root system morphology and its plasticity are controlled by inherent genetic factors. These mediate the modification of RSA, mostly at the level of root branching, in response to a suite of biotic and abiotic factors. Recent progress in the understanding of the molecular basis of these responses suggests that they largely feed through hormone homeostasis and signaling pathways. Novel factors implicated in the regulation of RSA in response to the myriad endogenous and exogenous signals are also increasingly isolated through alternative approaches such as quantitative trait locus analysis.

Quantifying intracellular protein binding thermodynamics during mechanotransduction based on FRET spectroscopy.

Mechanical force modulates myriad cellular functions including migration, alignment, proliferation, and gene transcription. Mechanotransduction, the transmission of mechanical forces and its translation into biochemical signals, may be mediated by force induced protein conformation changes, subsequently modulating protein signaling. For the paxillin and focal adhesion kinase interaction, we demonstrate that force-induced changes in protein complex conformation, dissociation constant, and binding Gibbs free energy can be quantified by lifetime-resolved fluorescence energy transfer microscopy combined with intensity imaging calibrated by fluorescence correlation spectroscopy. Comparison with in vitro data shows that this interaction is allosteric in vivo. Further, spatially resolved imaging and inhibitor assays show that this protein interaction and its mechano-sensitivity are equal in the cytosol and in the focal adhesions complexes indicating that the mechano-sensitivity of this interaction must be mediated by soluble factors but not based on protein tyrosine phosphorylation.

Towards a resolution of conflicting models of illusory contour processing in humans.

Despite myriad studies, neurophysiologic mechanisms mediating illusory contour (IC) sensitivity remain controversial. Among the competing models one favors feed-forward effects within lower-tier cortices (V1/V2). Another situates IC sensitivity first within higher-tier cortices, principally lateral-occipital cortices (LOC), with later feedback effects in V1/V2. Still others postulate that LOC are sensitive to salient regions demarcated by the inducing stimuli, whereas V1/V2 effects specifically support IC sensitivity. We resolved these discordances by using misaligned line gratings, oriented either horizontally or vertically, to induce ICs. Line orientation provides an established assay of V1/V2 modulations independently of IC presence, and gratings lack salient regions. Electrical neuroimaging analyses of visual evoked potentials (VEPs) disambiguated the relative timing and localization of IC sensitivity with respect to that for grating orientation. Millisecond-by-millisecond analyses of VEPs and distributed source estimations revealed a main effect of grating orientation beginning at 65 ms post-stimulus onset within the calcarine sulcus that was followed by a main effect of IC presence beginning at 85 ms post-stimulus onset within the LOC. There was no evidence for differential processing of ICs as a function of the orientation of the grating. These results support models wherein IC sensitivity occurs first within the LOC.

Iowa Department of Corrections Iowa State Penitentiary Final Operational and Architectural Program

The planning effort for ISP began in 2006 when the IDOC retained the Durrant/PBA team of architects and planners to review the Iowa correctional system. The team conducted two studies in the following two years, the first being the April 2007 Iowa Department of Corrections Systemic Master Plan. Both studies addressed myriad aspects of the correctional system including treatment and re-entry needs and programs, security and training, and staffing.

Institution Reentry Coordinators Proving to be Important Link, Data Download, Iowa Department of Corrections, March 2010

An offender reentry grant program funded through the Governor’s Office of Drug Control Policy supports one reentry coordinator at each of the following institutions: Mount Pleasant Correctional Facility (MPCF), Fort Dodge Correctional Facility and the Clarinda Correctional Facility. The reentry coordinators there engage in a myriad of activities, working with institution educators, counselors and medical personnel, probation/parole officers and counselors, and most importantly the offenders themselves. The program has not been in operation for very long, and only MPCF has operated long enough to be looking at outcomes. The early returns for MPCF show good promise.

Toll-interacting protein modulates colitis susceptibility in mice.

BACKGROUND: The intestinal epithelium accommodates with a myriad of commensals to maintain immunological homeostasis, but the underlying mechanisms regulating epithelial responsiveness to flora-derived signals remain poorly understood. Herein, we sought to determine the role of the Toll/interleukin (IL)-1 receptor regulator Toll-interacting protein (Tollip) in intestinal homeostasis. METHODS: Colitis susceptibility was determined after oral dextran sulfate sodium (DSS) administration or by breeding Tollip on an IL-10 background. The intestinal flora was depleted with 4 antibiotics before DSS exposure to assess its contribution in colitis onset. Bone marrow chimeras were generated to identify the cellular compartment, whereby Tollip may negatively regulate intestinal inflammation in response to DSS. Tollip-dependent epithelial barrier functions were studied in vitro by using Tollip-knockdown in Caco-2 cells and in vivo by immunohistochemistry and fluorescein isothiocyanate-labeled dextran gavage. RESULTS: Genetic ablation of Tollip did not lead to spontaneous intestinal inflammatory disorders. However, Tollip deficiency aggravated spontaneous disease onset in IL-10 mice and increased susceptibility to DSS colitis. Increased colitis severity in Tollip-deficient mice was not improved by bacterial flora depletion using broad-spectrum antibiotics. In addition, DSS exposure of bone marrow chimeric mice revealed a protective role for Tollip in nonhematopoietic cells. Knockdown of Tollip in epithelial cells led to exaggerated NFκ-B activity and proinflammatory cytokine secretion. Finally, DSS-treated Tollip mice showed enhanced intestinal permeability and increased epithelial apoptosis when compared with wild-type controls, a finding that coincided with tight junction alterations on injury. CONCLUSION: Overall, our data show an essential role for Tollip on colitis susceptibility in mice.

Worlds of working poverty : Cross-national variation in the mechanisms that lead to poverty among workers

The objective of this paper is to distinguish between different types of working poverty, on the basis of the mechanisms that produce it. Whereas the poverty literature identifies a myriad of risk factors and of categories of disadvantaged workers, we focus on three immediate causes of working poverty, namely low wage rate, weak labour force attachment, and high needs, the latter mainly due to the presence of children (and sometimes to the increase in needs caused by a divorce). These three mechanisms are the channels through which macroeconomic, demographic and policy factors have a direct bearing on working households. The main assumption tested here is that welfare regimes strongly influence the relative weight of these three mechanisms in producing working poverty, and, hence, the composition of the working-poor population. Our figures confirm this hypothesis and show that low-wage employment is a key factor, but, by far, not the only one and that family policies broadly understood play a decisive role, as well as patterns of labour market participation and integration.

Communicating Highway Safety: What Works, 2002

Few topics in transportation are of greater significance, now and in the future, than making today’s roads safe for those who use them. This study aims to assist the formulation of policy by examining the empirical evidence currently available on the ability of several forms of communication efforts and activities to increase knowledge about and affect attitudes and behavior toward highway safety practices. The objective of this effort is to provide a comparative synthesis of what works and what does not in highway safety campaigns across a large number of topical areas that have a mass media component. This was accomplished by conducting an extensive literature review to determine the current state of knowledge concerning what works and what has significant potential for wide use in future highway safety campaigns. An analytic framework for investigating highway safety campaigns was created. The framework includes (1) the types of media components, (2) the types of collaborations, (3) the context in which the campaign is intended to have impact, (4) the structure or procedural steps into which campaigns are organized, (5) the principles for what works in a campaign, and (6) the desired impact of a campaign on its target audience. The report reveals 25 characteristics of successful communication campaigns, strategies that stand a chance of achieving changes in knowledge, attitude, and behavior. The actual impact of mass communication remains unproven because of a perceived lag in the development of adequate evaluation techniques. Education by itself has not generally resulted in significant changes in the behaviors targeted, but education of the public and advocacy groups has often helped enact necessary legislation, transmit knowledge about the provisions and penalties of laws in ways that increase their deterrent effect, and generate public support for law enforcement programs. Even in such cases, however, when enforcement is inconsistent, public compliance frequently decreases with time. Approaches to traffic safety that emphasize the need for long-term individual- and community-based measures are found to be especially crucial for addressing complex problems like drinking and driving that are determined by a myriad of lifestyle and psychosocial factors.