209 research outputs found

    A habituation account of change detection in same/different judgments

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    We investigated the basis of change detection in a short-term priming task. In two experiments, participants were asked to indicate whether or not a target word was the same as a previously presented cue. Data from an experiment measuring magnetoencephalography failed to find different patterns for “same” and “different” responses, consistent with the claim that both arise from a common neural source, with response magnitude defining the difference between immediate novelty versus familiarity. In a behavioral experiment, we tested and confirmed the predictions of a habituation account of these judgments by comparing conditions in which the target, the cue, or neither was primed by its presentation in the previous trial. As predicted, cue-primed trials had faster response times, and target-primed trials had slower response times relative to the neither-primed baseline. These results were obtained irrespective of response repetition and stimulus–response contingencies. The behavioral and brain activity data support the view that detection of change drives performance in these tasks and that the underlying mechanism is neuronal habituation

    Variational Methods for Biomolecular Modeling

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    Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page

    Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

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    Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

    A frotarsius chatrathi, first tarsiiform primate (? Tarsiidae) from Africa

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    Tarsiiform primates have long been regarded as a Laurasian group, with an extensive fossil record in the Eocene of North America and EuropeI and two important but less well-known records from Asia

    Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study

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    Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation

    Gradual phyletic evolution at the generic level in early Eocene omomyid primates

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    Analysis of dental morphology in over 600 stratigraphically controlled specimens of tarsier-like primates from early Eocene strata in Bighorn Basin, Wyoming, provides important new data for understanding the tempo and mode of evolution in primates

    The osteology of ‘Periptychus carinidens’: a robust, ungulate-like placental mammal (Mammalia: Periptychidae) from the Paleocene of North America

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    Periptychus is the archetypal genus of Periptychidae, a clade of prolific Paleocene 'condylarth' mammals from North America that were among the first placental mammals to radiate after the end-Cretaceous extinction, remarkable for their distinctive dental anatomy. A comprehensive understanding of the anatomy of Periptychus has been hindered by a lack of cranial and postcranial material and only cursory description of existing material. We comprehensively describe the cranial, dental and postcranial anatomy of Periptychus carinidens based on new fossil material from the early Paleocene (Torrejonian) of New Mexico, USA. The cranial anatomy of Periptychus is broadly concurrent with the inferred plesiomorphic eutherian condition, albeit more robust in overall construction. The rostrum is moderately elongate with no constriction, the facial region is broad, and the braincase is small with a well-exposed mastoid on the posterolateral corner and tall sagittal and nuchal crests. The dentition of Periptychus is characterized by strongly crenulated enamel, enlarged upper and lower premolars with a tall centralised paracone/protoconid. The postcranial skeleton of Periptychus is that of a robust, medium-sized (~20 Kg) stout-limbed animal that was incipiently mediportal and adopted a plantigrade stance. The structure of the fore- and hindlimb of Periptychus corresponds to that of a typically terrestrial mammal, while morphological features of the forelimb such as the low tubercles of the humerus, long and prominent deltopectoral crest, pronounced medial epicondyle, and hemispherical capitulum indicate some scansorial and/or fossorial ability. Most striking is the strongly dorsoplantarly compressed astragalus of Periptychus, which in combination with the distal crus and calcaneal morphology indicates a moderately mobile cruropedal joint. The anatomy of Periptychus is unique and lacks any extant analogue; it combines a basic early placental body plan with numerous unique specializations in its dental, cranial and postcranial anatomy that exemplify the ability of mammals to adapt and evolve following catastrophic environmental upheaval

    Sexual dysfunction among married couples living in Kumasi metropolis, Ghana

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    <p>Abstract</p> <p>Background</p> <p>Sexuality and its manifestation constitute some of the most complex of human behaviour and its disorders are encountered in community. Sexual dysfunction is more prevalent in women than in men. While studies examining sexual dysfunction among males and females in Ghana exist, there are no studies relating sexual problems in males and females as dyadic units. This study therefore investigated the prevalence and type of sexual disorders among married couples.</p> <p>Method</p> <p>The study participants consisted of married couples between the ages of 19 and 66 living in the province of Kumasi, Ghana. Socio-demographic information and Golombok-Rust Inventory of Sexual Satisfaction (GRISS) questionnaires were administered to 200 couples who consented to take part in the study. All 28 questions of the GRISS are answered on a five-point (Likert type) scale from "always", through "usually', "sometimes", and "hardly ever", to "never". Responses are summed up to give a total raw score ranging from 28-140. The total score and subscale scores are transformed using a standard nine point scale, with high scores indicating greater problems. Scores of five or more are considered to indicate SD. The study was conducted between July and September 2010.</p> <p>Results</p> <p>Out of a total of 200 married couples, 179 completed their questionnaires resulting in a response rate of 89.5%. The mean age of the participating couples as well as the mean duration of marriage was 34.8 ± 8.6 years and 7.8 ± 7.6 years respectively. The husbands (37.1 ± 8.6) were significantly older (p < 0.0001) than their corresponding wives (32.5 ± 7.9). After adjusting for age, 13-18 years of marriage life poses about 10 times significant risk of developing SD compared to 1-6 years of married life among the wives (OR: 10.8; CI: 1.1 - 49.1; p = 0.04). The total scores (6.0) as well as the percentage above the cut-off (59.2) obtained by the husbands compared to the total score (6.2) and the percentage above cut-off (61.5) obtained by the wives, indicates the likely presence of sexual dysfunction. The prevalence of impotence and premature ejaculation were 60.9% and 65.4% respectively from this study and the prevalence of vaginismus and anorgasmia were 69.3% and 74.9% respectively. The highest prevalence of SD subscales among the men was dissatisfaction with sexual act followed by infrequency, whereas the highest among the women was infrequency followed by anorgasmia. Dissatisfaction with sexual intercourse among men correlated positively with anorgasmia and wife's non-sensuality and infrequency of sex.</p> <p>Conclusion</p> <p>The prevalence of sexual dysfunction in married couples is comparable to prevalence rates in the general male and female population and is further worsened by duration of marriage. This could impact significantly on a couple's self-esteem and overall quality of life.</p
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