510 research outputs found

    Static and Dynamic Autonomic Response with Increasing Nausea Perception

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    Background—Nausea is a commonly occurring symptom typified by epigastric discomfort with urge to vomit. The relationship between autonomic nervous system (ANS) outflow and increasing nausea perception is not fully understood. Methods—Our study employed a nauseogenic visual stimulus (horizontally translating stripes) while 17 female subjects freely rated transitions in nausea level and autonomic outflow was measured (heart rate, HR, heart rate variability, HRV, skin conductance response, SCR, respiratory rate). We also adopted a recent approach to continuous high frequency (HF) HRV estimation to evaluate dynamic cardiovagal modulation. Results—HR increased from baseline for all increasing nausea transitions, especially transition to strong nausea (15.0±11.4 bpm), but decreased (−6.6±4.6 bpm) once the visual stimulus ceased. SCR also increased for all increasing nausea transitions, especially transition to strong nausea (1.76±1.68 μS), but continued to increase (0.52 ± 0.65 μS) once visual stimulation ceased. LF/HF HRV increased following transition to moderate (1.54±2.11 a.u.) and strong (2.57±3.49 a.u.) nausea, suggesting a sympathetic shift in sympathovagal balance. However, dynamic HF HRV suggested that bursts of cardiovagal modulation precede transitions to higher nausea, perhaps influencing subjects to rate higher levels of nausea. No significant change in respiration rate was found. Conclusions—Our results suggest that increasing nausea perception is associated with both increased sympathetic and decreased parasympathetic ANS modulation. These findings corroborate past ANS studies of nausea, applying percept-linked analyses and dynamic estimation of cardiovagal modulation in response to nausea.National Institutes of Health (U.S.) (Grant R01-HL084502)National Institutes of Health (U.S.) (Grant R01-DA015644)National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant K01-AT002166)National Institutes of Health (U.S.) (Grant P01-AT002048)National Institutes of Health (U.S.) (Grant F05-AT003770)National Institutes of Health (U.S.) (Grant K23-DK069614)National Center for Research Resources (U.S.) (P41RR14075)National Center for Research Resources (U.S.) (CRC 1 UL1 RR025758-01)Mental Illness and Neuroscience Discovery (MIND) InstituteInternational Foundation of Functional Gastrointestinal DisordersInstitute of Information Technology Advancement (South Korea)Institute of Information Technology Advancement (South Korea) (Korea IITA- 2008-(C1090-0801-0002)

    Indices of Body Composition and Repeatability of Residual Feed Intake in Growing Columbia Ewes Fed the Same Diet

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    Residual feed intake (RFI), an efficiency measurement based upon the difference in expected and actual feed intake, is used to improve production efficiency of livestock. The purpose of this study was to evaluate the repeatability of ewe RFI measured for two consecutive years, and to investigate the relationship between indices of body composition in yearling ewes and RFI. Two trials, using the same Columbia ewe lambs (n = 17) were conducted in consecutive years (2014, 2015) using the same diet. RFI was calculated for each ewe each year. RFI did not differ (P = 0.77) between years. Each year, ewes were separated into RFI classes (LOW (efficient); MOD (average); HIGH (inefficient)). In 2014, ewe lamb performance did not differ among classes (P > 0.3). In 2015, dry matter intake was greater for HIGH ewes (P < 0.0002). Ribeye area (REA; cm2) and backfat thickness (BF; cm) were measured by ultrasound on day 0 (start of trial), 17, and 45 (end of trial) in 2015 and used to calculate estimates of final body composition. RFI classification did not affect REA or BF (P > 0.25). There was a trend for whole-body muscle mass to differ among RFI classes (P = 0.09), but no other body composition estimates were affected. Results suggest that RFI is repeatable; however, indices of body composition seem to be independent of RFI in Columbia ewes fed the same diet under similar conditions

    Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

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    Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US 4.56persample,versusUS4.56 per sample, versus US 11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings

    Native Environment Modulates Leaf Size and Response to Simulated Foliar Shade across Wild Tomato Species

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    The laminae of leaves optimize photosynthetic rates by serving as a platform for both light capture and gas exchange, while minimizing water losses associated with thermoregulation and transpiration. Many have speculated that plants maximize photosynthetic output and minimize associated costs through leaf size, complexity, and shape, but a unifying theory linking the plethora of observed leaf forms with the environment remains elusive. Additionally, the leaf itself is a plastic structure, responsive to its surroundings, further complicating the relationship. Despite extensive knowledge of the genetic mechanisms underlying angiosperm leaf development, little is known about how phenotypic plasticity and selective pressures converge to create the diversity of leaf shapes and sizes across lineages. Here, we use wild tomato accessions, collected from locales with diverse levels of foliar shade, temperature, and precipitation, as a model to assay the extent of shade avoidance in leaf traits and the degree to which these leaf traits correlate with environmental factors. We find that leaf size is correlated with measures of foliar shade across the wild tomato species sampled and that leaf size and serration correlate in a species-dependent fashion with temperature and precipitation. We use far-red induced changes in leaf length as a proxy measure of the shade avoidance response, and find that shade avoidance in leaves negatively correlates with the level of foliar shade recorded at the point of origin of an accession. The direction and magnitude of these correlations varies across the leaf series, suggesting that heterochronic and/or ontogenic programs are a mechanism by which selective pressures can alter leaf size and form. This study highlights the value of wild tomato accessions for studies of both morphological and light-regulated development of compound leaves, and promises to be useful in the future identification of genes regulating potentially adaptive plastic leaf traits

    Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

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    A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

    Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

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    Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

    Desmoplakin assembly dynamics in four dimensions: multiple phases differentially regulated by intermediate filaments and actin

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    The intermediate filament (IF)–binding protein desmoplakin (DP) is essential for desmosome function and tissue integrity, but its role in junction assembly is poorly understood. Using time-lapse imaging, we show that cell–cell contact triggers three temporally overlapping phases of DP-GFP dynamics: (1) the de novo appearance of punctate fluorescence at new contact zones after as little as 3 min; (2) the coalescence of DP and the armadillo protein plakophilin 2 into discrete cytoplasmic particles after as little as 15 min; and (3) the cytochalasin-sensitive translocation of cytoplasmic particles to maturing borders, with kinetics ranging from 0.002 to 0.04 μm/s. DP mutants that abrogate or enhance association with IFs exhibit delayed incorporation into junctions, altering particle trajectory or increasing particle pause times, respectively. Our data are consistent with the idea that DP assembles into nascent junctions from both diffusible and particulate pools in a temporally overlapping series of events triggered by cell–cell contact and regulated by actin and DP–IF interactions

    Lack of the Receptor for Advanced Glycation End-Products Attenuates E. coli Pneumonia in Mice

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    Background: The receptor for advanced glycation end-products (RAGE) has been suggested to modulate lung injury in models of acute pulmonary inflammation. To study this further, model systems utilizing wild type and RAGE knockout (KO) mice were used to determine the role of RAGE signaling in lipopolysaccharide (LPS) and E. coli induced acute pulmonary inflammation. The effect of intraperitoneal (i.p.) and intratracheal (i.t.) administration of mouse soluble RAGE on E. coli injury was also investigated. Methodology/Principal Findings: C57BL/6 wild type and RAGE KO mice received an i.t. instillation of LPS, E. coli, or vehicle control. Some groups also received i.p. or i.t. administration of mouse soluble RAGE. After 24 hours, the role of RAGE expression on inflammation was assessed by comparing responses in wild type and RAGE KO. RAGE protein levels decreased in wild type lung homogenates after treatment with either LPS or bacteria. In addition, soluble RAGE and HMGB1 increased in the BALF after E. coli instillation. RAGE KO mice challenged with LPS had the same degree of inflammation as wild type mice. However, when challenged with E. coli, RAGE KO mice had significantly less inflammation when compared to wild type mice. Most cytokine levels were lower in the BALF of RAGE KO mice compared to wild type mice after E. coli injury, while only monocyte chemotactic protein-1, MCP-1, was lower after LPS challenge. Neither i.p. nor i.t. administration of mouse soluble RAGE attenuated the severity of E. coli injury in wild type mice. Conclusions/Significance: Lack of RAGE in the lung does not protect against LPS induced acute pulmonary inflammation, but attenuates injury following live E. coli challenge. These findings suggest that RAGE mediates responses to E. coli-associated pathogen-associated molecular pattern molecules other than LPS or other bacterial specific signaling responses. Soluble RAGE treatment had no effect on inflammation. © 2011 Ramsgaard et al

    Molecular Structure of Amyloid Fibrils Controls the Relationship between Fibrillar Size and Toxicity

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    According to the prevailing view, soluble oligomers or small fibrillar fragments are considered to be the most toxic species in prion diseases. To test this hypothesis, two conformationally different amyloid states were produced from the same highly pure recombinant full-length prion protein (rPrP). The cytotoxic potential of intact fibrils and fibrillar fragments generated by sonication from these two states was tested using cultured cells.For one amyloid state, fibril fragmentation was found to enhance its cytotoxic potential, whereas for another amyloid state formed within the same amino acid sequence, the fragmented fibrils were found to be substantially less toxic than the intact fibrils. Consistent with the previous studies, the toxic effects were more pronounced for cell cultures expressing normal isoform of the prion protein (PrP(C)) at high levels confirming that cytotoxicity was in part PrP(C)-dependent. Silencing of PrP(C) expression by small hairpin RNAs designed to silence expression of human PrP(C) (shRNA-PrP(C)) diminished the deleterious effects of the two amyloid states to a different extent, suggesting that the role of PrP(C)-mediated and PrP(C)-independent mechanisms depends on the structure of the aggregates.This work provides a direct illustration that the relationship between an amyloid's physical dimension and its toxic potential is not unidirectional but is controlled by the molecular structure of prion protein (PrP) molecules within aggregated states. Depending on the structure, a decrease in size of amyloid fibrils can either enhance or abolish their cytotoxic effect. Regardless of the molecular structure or size of PrP aggregates, silencing of PrP(C) expression can be exploited to reduce their deleterious effects
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