High resolution, high capacity, spatial specificity in perceptual learning.

Research of perceptual learning has received significant interest due to findings that training on perceptual tasks can yield learning effects that are specific to the stimulus features of that task. However, recent studies have demonstrated that while training a single stimulus at a single location can yield a high-degree of stimulus specificity, training multiple features, or at multiple locations can reveal a broad transfer of learning to untrained features or stimulus locations. We devised a high resolution, high capacity, perceptual learning procedure with the goal of testing whether spatial specificity can be found in cases where observers are highly trained to discriminate stimuli in many different locations in the visual field. We found a surprising degree of location specific learning, where performance was significantly better when target stimuli were presented at 1 of the 24 trained locations compared to when they were placed in 1 of the 12 untrained locations. This result is particularly impressive given that untrained locations were within a couple degrees of visual angle of those that were trained. Given the large number of trained locations, the fact that the trained and untrained locations were interspersed, and the high-degree of spatial precision of the learning, we suggest that these results are difficult to account for using attention or decision strategies and instead suggest that learning may have taken place for each location separately in retinotopically organized visual cortex

Tectonic controls on nearshore sediment accumulation and submarine canyon morphology offshore La Jolla, Southern California

CHIRP seismic and swath bathymetry data acquired offshore La Jolla, California provide an unprecedented three-dimensional view of the La Jolla and Scripps submarine canyons. Shore-parallel patterns of tectonic deformation appear to control nearshore sediment thickness and distribution around the canyons. These shore-parallel patterns allow the impact of local tectonic deformation to be separated from the influence of eustatic sea-level fluctuations. Based on stratal geometry and acoustic character, we identify a prominent angular unconformity inferred to be the transgressive surface and three sedimentary sequences: an acoustically laminated estuarine unit deposited during early transgression, an infilling or “healing-phase” unit formed during the transgression, and an upper transparent unit. Beneath the transgressive surface, steeply dipping reflectors with several dip reversals record faulting and folding along the La Jolla margin. Scripps Canyon is located at the crest of an antiform, where the rocks are fractured and more susceptible to erosion. La Jolla Canyon is located along the northern strand of the Rose Canyon Fault Zone, which separates Cretaceous lithified rocks to the south from poorly cemented Eocene sands and gravels to the north. Isopach and structure contour maps of the three sedimentary units reveal how their thicknesses and spatial distributions relate to regional tectonic deformation. For example, the estuarine unit is predominantly deposited along the edges of the canyons in paleotopographic lows that may have been inlets along barrier beaches during the Holocene sea-level rise. The distribution of the infilling unit is controlled by pre-existing relief that records tectonic deformation and erosional processes. The thickness and distribution of the upper transparent unit are controlled by long-wavelength, tectonically induced relief on the transgressive surface and hydrodynamics

A linguistic approach to assess the dynamics of design team preference in concept selection

This paper addresses the problem of describing the decision-making process of a committee of engineers based upon their verbalized linguistic appraisals of alternatives. First, we show a way to model an individual’s evaluation of an alternative through natural language based on the Systemic-Functional Linguistics system of APPRAISAL. The linguistic model accounts for both the degree of intensity and the uncertainty of expressed evaluations. Second, this multi-dimensional linguistic model is converted into a scalar to represent the degree of intensity and a probability distribution function for the stated evaluation. Finally, we present a Markovian model to calculate the time-varying change in preferential probability, the probability that an alternative is the most preferred alternative. We further demonstrate how preferential probability toward attributes of alternatives correspond to preferential probability toward alternatives. We illustrate the method on two case studies to highlight the time-variant dynamics of preferences toward alternatives and attributes. This research contributes to process tracing in descriptive decision science to understand how engineers actually take decisions.National Science Foundation (U.S.) (Award CMMI-0900255

Phthiocerol Dimycocerosates of M. tuberculosis Participate in Macrophage Invasion by Inducing Changes in the Organization of Plasma Membrane Lipids

Phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), in particular during the early step of infection when bacilli encounter their host macrophages. However, their cellular and molecular mechanisms of action remain unknown. Using Mtb mutants deleted for genes involved in DIM biosynthesis, we demonstrated that DIM participate both in the receptor-dependent phagocytosis of Mtb and the prevention of phagosomal acidification. The effects of DIM required a state of the membrane fluidity as demonstrated by experiments conducted with cholesterol-depleting drugs that abolished the differences in phagocytosis efficiency and phagosome acidification observed between wild-type and mutant strains. The insertion of a new cholesterol-pyrene probe in living cells demonstrated that the polarity of the membrane hydrophobic core changed upon contact with Mtb whereas the lateral diffusion of cholesterol was unaffected. This effect was dependent on DIM and was consistent with the effect observed following DIM insertion in model membrane. Therefore, we propose that DIM control the invasion of macrophages by Mtb by targeting lipid organisation in the host membrane, thereby modifying its biophysical properties. The DIM-induced changes in lipid ordering favour the efficiency of receptor-mediated phagocytosis of Mtb and contribute to the control of phagosomal pH driving bacilli in a protective niche

Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected

Bottom-Up Organizing with Tools from On High: Understanding the Data Practices of Labor Organizers

This paper provides insight into the use of data tools in the American labor movement by analyzing the practices of staff employed by unions to organize alongside union members. We interviewed 23 field-level staff organizers about how they use data tools to evaluate membership. We find that organizers work around and outside of these tools to develop access to data for union members and calibrate data representations to meet local needs. Organizers mediate between local and central versions of the data, and draw on their contextual knowledge to challenge campaign strategy. We argue that networked data tools can compound field organizers' lack of discretion, making it more difficult for unions to assess and act on the will of union membership. We show how the use of networked data tools can lead to less accurate data, and discuss how bottom-up approaches to data gathering can support more accurate membership assessments

Mycobacterium leprae Phenolglycolipid-1 Expressed by Engineered M. bovis BCG Modulates Early Interaction with Human Phagocytes

The species-specific phenolic glycolipid 1 (PGL-1) is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3) for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells

Genome-wide profiling of G protein-coupled receptors in cerebellar granule neurons using high-throughput, real-time PCR

<p>Abstract</p> <p>Background</p> <p>G protein-coupled receptors (GPCRs) are major players in cell communication, regulate a whole range of physiological functions during development and throughout adult life, are affected in numerous pathological situations, and constitute so far the largest class of drugable targets for human diseases. The corresponding genes are usually expressed at low levels, making accurate, genome-wide quantification of their expression levels a challenging task using microarrays.</p> <p>Results</p> <p>We first draw an inventory of all endo-GPCRs encoded in the murine genome. To profile GPCRs genome-wide accurately, sensitively, comprehensively, and cost-effectively, we designed and validated a collection of primers that we used in quantitative RT-PCR experiments. We experimentally validated a statistical approach to analyze genome-wide, real-time PCR data. To illustrate the usefulness of this approach, we determined the repertoire of GPCRs expressed in cerebellar granule neurons and neuroblasts during postnatal development.</p> <p>Conclusions</p> <p>We identified tens of GPCRs that were not detected previously in this cell type; these GPCRs represent novel candidate players in the development and survival of cerebellar granule neurons. The sequences of primers used in this study are freely available to those interested in quantifying GPCR expression comprehensively.</p

First Description of Natural and Experimental Conjugation between Mycobacteria Mediated by a Linear Plasmid

Background: in a previous study, we detected the presence of a Mycobacterium avium species-specific insertion sequence, IS1245, in Mycobacterium kansasii. Both species were isolated from a mixed M. avium-M. kansasii bone marrow culture from an HIV-positive patient. the transfer mechanism of this insertion sequence to M. kansasii was investigated here.Methodology/Principal Findings: A linear plasmid (pMA100) was identified in all colonies isolated from the M. avium-M. kansasii mixed culture carrying the IS1245 element. the linearity of pMA100 was confirmed. Other analyses suggested that pMA100 contained a covalently bound protein in the terminal regions, a characteristic of invertron linear replicons. Partial sequencing of pMA100 showed that it bears one intact copy of IS1245 inserted in a region rich in transposase-related sequences. These types of sequences have been described in other linear mycobacterial plasmids. Mating experiments were performed to confirm that pMA100 could be transferred in vitro from M. avium to M. kansasii. pMA100 was transferred by in vitro conjugation not only to the M. kansasii strain from the mixed culture, but also to two other unrelated M. kansasii clinical isolates, as well as to Mycobacterium bovis BCG Moreau.Conclusions/Significance: Horizontal gene transfer (HGT) is one of most important mechanisms leading to the evolution and diversity of bacteria. This work provides evidence for the first time on the natural occurrence of HGT between different species of mycobacteria. Gene transfer, mediated by a novel conjugative plasmid, was detected and experimentally reproduced.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Cooperacion Interuniversitaria UAM-Banco Santander con America Latina (CEAL), UAM, SpainConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilLab Nacl Comp Cient, Petropolis, BrazilUniv Autonoma Madrid, Fac Med, Dept Prevent Med, Madrid, SpainInst Adolfo Lutz Registro, Nucleo TB & Micobacterioses, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilFAPESP: FAPESP - 06/01533-9Web of Scienc