528 research outputs found
A Deweyan-Based Curriculum for Teaching Ethical Inquiry in the Language Arts
Informed by Dewey’s account of ethical experience and the nature of philosophical inquiry, my theory of ethical inquiry has four components: body-based reasonableness, moral imagination, emotions as judgments, and ethical content. Bodybased reasonableness is thinking that is critical, creative, committed, contextual, and embodied (Sprod, 2001). Exercising embodied reasonableness in aesthetic education means that we pay critical attention and seek to address the ethical and social aspects of art. We pay attention to fiction that will potentially engage students in a constant process of ethical judgment, depicting characters and situations that call for our moral evaluation. In a similar vein, exposure to certain art can sensitize us to the right reasons and objects for our emotions. Vehicles for ethical inquiry are those by which human situations can be understood and are found in the English Language Arts curriculum and the arts, such as: The Odyssey by Homer, Romeo and Juliet by Shakespeare, Prokofiev, and Tchaikovsky, The Joy Luck Club by Tan, and works by the artists Frida Kahlo and Kiki Smith. Highlighted are the issues of body, sexuality and gender, principal areas of ethical concern and central to adolescence. The pedagogy by which students can adequately address ethical concerns is Philosophy for Children, where characters in a narrative text exemplify discursive modes of thought and the conduct of ethical inquiry
A network of filaments detected by Herschel in the Serpens core : a laboratory to test simulations of low-mass star formation
V.R. was partly supported by the DLR grant number 50 OR 1109 and by the Bayerische Gleichstellungsförderung (BGF). This research was partly supported by the Priority Programme 1573 “Physics of the Interstellar Medium” of the German Science Foundation (DFG), the DFG cluster of excellence “Origin and Structure of the Universe” and by the Italian Ministero dell’Istruzione, Università e Ricerca through the grant Progetti Premiali 2012 -iALMA (CUP C52I13000140001). C.E. is partly supported by Spanish Grants AYA 2011-26202 and AYA 2014-55840-P.Context. Filaments represent a key structure during the early stages of the star formation process. Simulations show that filamentary structures commonly formed before and during the formation of cores. Aims. The Serpens core is an ideal laboratory for testing the state of the art of simulations of turbulent giant molecular clouds. Methods. We used Herschel observations of the Serpens core to compute temperatureand column density maps of the region. We selected the early stages of are cent simulation of star-formation, before stellar feedback was initiated, with similar total mass and physical size as the Serpens core. We also derived temperature and column density maps from the simulations. The observed distribution of column densities of the filaments was analyzed, first including and then masking the cores. The same analysis was performed on the simulations as well. Results. A radial network of filaments was detected in the Serpens core. The analyzed simulation shows a striking morphological resemblance to the observed structures. The column density distribution of simulated filaments without cores shows only a log-normal distribution, while the observed filaments show a power-law tail. The power-law tail becomes evident in the simulation if the focus is only the column density distribution of the cores. In contrast, the observed cores show a flat distribution. Conclusions. Even though the simulated and observed filaments are subjectively similar-looking, we find that they behave in very different ways. The simulated filaments are turbulence-dominated regions; the observed filaments are instead self-gravitating structures that will probably fragment into cores.Publisher PDFPeer reviewe
Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism
Inflammation is a predominant aspect of neurodegenerative diseases, manifested by glia activation and expression of pro-inflammatory mediators. Studies on animal models of Parkinson’s disease (PD) suggest that sustained neuroinflammation exacerbates degeneration of the dopaminergic (DA) nigro-striatal pathway. Therefore, insights into the inflammatory mechanisms of PD may help the development of novel therapeutic strategies against this disease. As extracellular matrix metalloproteinases (MMPs) could be major players in the progression of Parkinsonism, we investigated, in the substantia nigra and striatum of mice acutely injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), changes in mRNA expression, protein levels, and cell localization of MMP-9. This protease is mainly neuronal, but early after MPTP injection its mRNA and protein levels, as well as the number of MMP-9-expressing microglia and astrocytes, increase concomitantly to a prominent inflammation. Neuroinflammation and MMP-9+ glia begin to decline within 2 weeks, although protein levels remain higher than control, in association with a partial recovery of DA nigro-striatal circuit. Comparable quantitative studies on MMP-9 knock-out mice, show a significant decrease in both glia activation and loss of DA neurons and fibers, with respect to wild-type. Moreover, in a parallel study on chronically MPTP-injected macaques, we observed that perpetuation of inflammation and high levels of MMP-9 are associated to DA neuron loss. Our data suggest that MMP-9 released by injured neurons favors glia activation; glial cells in turn reinforce their reactive state via autocrine MMP-9 release, contributing to nigro-striatal pathway degeneration. Specific modulation of MMP-9 activity may, therefore, be a strategy to ameliorate harmful inflammatory outcomes in Parkinsonism
Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation
Background
This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG.
Methods
CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI.
Results
A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1–53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL.
Conclusions
More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery
The Rapid Outbursting Star GM Cep: An EX-or in Tr 37?
We present optical, IR and millimeter observations of the solar-type star
13-277, also known as GM Cep, in the 4 Myr-old cluster Tr 37. GM Cep
experiences rapid magnitude variations of more than 2 mag at optical
wavelengths. We explore the causes of the variability, which seem to be
dominated by strong increases in the accretion, being similar to EX-or
episodes. The star shows high, variable accretion rates (up to ~10
Msun/yr), signs of powerful winds, and it is a very fast rotator (Vsini~43
km/s). Its strong mid-IR excesses reveal a very flared disk and/or a remnant
envelope, most likely out of hydrostatic equilibrium. The 1.3 millimeter fluxes
suggest a relatively massive disk (Mdisk~0.1 Msun). Nevertheless, the
millimeter mass is not enough to sustain increased accretion episodes over
large timescales, unless the mass is underestimated due to significant grain
growth. We finally explore the possibility of GM Cep having a binary companion,
which could trigger disk instabilities producing the enhanced accretion
episodes.Comment: 43 pages, including 10 figures, ApJ in pres
Ultrastructure of the organ of Corti in harbor seals (Phoca vitulina)
Ultrastructural descriptions of the inner ear of highly sound-dependent mammalian species are lacking and needed to gain a better understanding of the hearing sense. Here, we present the first morphometric descriptions of the sensory cells of the inner ear in the harbor seal (Phoca vitulina), a mammal with broadly sensitive amphibious hearing. Scanning electron micrographs of the apical surface of the outer hair cells (OHCs) and inner hair cells (IHCs) within the organ of Corti were obtained from five individuals and analyzed by linear and geometric morphometrics. Measurements were taken at regular locations along the cochlea. The spiral shape of the seal cochlea contained two and a half turns. The organ of Corti had an average length of 27.7 mm with 12,628 OHCs (12,400-12,900). Six linear morphometric parameters showed significant patterns of change associated with their location within the cochlear spiral. Likewise, these trends were similarly expressed in cell configuration (cell blocks with 57 landmarks in 12 representative cells) revealed by geometric morphometry. Cell configuration varied predictably with position in the cochlea according to clustering analyses and Procrustes ANOVA (F= 25.936, p<0001). Changes associated with OHCs were primarily responsible for observed changes in cell configuration. An integration trend in cell shape change was also observed in which IHCs and OHCs share features in their morphological variation by the two-block partial least squares analysis (CR=0.987, p<0.001) and the modularity hypothesis (CV=0.99, p=0.05). These descriptive and quantitative findings provide a baseline for the morphology and morphometry of the sensory cells of the organ of Corti in harbor seals, allowing for comparisons between normal and pathological features. This initial morphological description should enable the correlation between position, morphometric features, and frequency coding along the spiral of the inner ear in this species, whose hearing ability is well studied
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
This article belongs to the Special Issue Genetic Advances in Neuromuscular Disorders: From Gene Identification to Gene Therapy.The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients’ clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.This study was granted by FIS PI15/01898, funded by ISCIII and FEDER, ‘Una manera de hacer Europa’ and by Fundación Mutua Madrileña in the “Convocatoria de ayudas a la Investigación en Salud 2015”. It was also funded by an ACCI grant from CIBERER. Daniel Natera-de Benito is the recipient of a grant from the Instituto de Salud Carlos III (Contrato Rio Hortega, CM17/00044)
Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study
Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries
Identification, introgression, and validation of fruit volatile QTLs from a red-fruited wild tomato species
[EN] Volatile organic compounds (VOCs) are major determinants of fruit flavor, a primary objective in tomato breeding. A recombinant inbred line (RIL) population consisting of 169 lines derived from a cross between Solanum lycopersicum and a red-fruited wild tomato species Solanum pimpinellifolium accession (SP) was characterized for VOCs in three different seasons. Correlation and hierarchical cluster analyses were performed on the 52 VOCs identified, providing a tool for the putative assignation of individual compounds to metabolic pathways. Quantitative trait locus (QTL) analysis, based on a genetic linkage map comprising 297 single nucleotide polymorphisms (SNPs), revealed 102 QTLs (75% not described previously) corresponding to 39 different VOCs. The SP alleles exerted a positive effect on most of the underlying apocarotenoid volatile QTLs-regarded as desirable for liking tomato-indicating that alleles inherited from SP are a valuable resource for flavor breeding. An introgression line (IL) population developed from the same parental genotypes provided 12 ILs carrying a single SP introgression and covering 85 VOC QTLs, which were characterized at three locations. The results showed that almost half of the QTLs previously identified in the RILs maintained their effect in an IL form, reinforcing the value of these QTLs for flavor/aroma breeding in cultivated tomato.We thank Erika Moro for valuable help in volatile analysis of the ILs. WB was supported by a fellowship granted by the Universidad de Costa Rica and CSIC-Spain by way of a collaboration agreement between CSIC/UCR. Volatile profiling was performed in the Metabolomic facilities of the IBMCP, CSIC (Spain). This work was supported in part by the Spanish MINECO Project AGL2015-65246-R co-financed by EU FEDER, MINECO Project AGL2011-26957, and the Bilateral agreements of Scientific and Technological Cooperation between the Spanish National Research Council (CSIC) and the Italian National Research Council (CNR). Funding for this project was provided through TRADITOM. TRADITOM has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 634561. Networking activities were supported by COST action Fruit Quality FA 1106.Rambla Nebot, JL.; Medina, A.; Fernández Del Carmen, MA.; Barrantes, W.; Grandillo, S.; Cammareri, M.; López Casado, G.... (2016). Identification, introgression, and validation of fruit volatile QTLs from a red-fruited wild tomato species. Journal of Experimental Botany. 68(3):429-442. https://doi.org/10.1093/jxb/erw455S429442683Alba, J. M., Montserrat, M., & Fernández-Muñoz, R. (2008). 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G., & Klee, H. J. (2010). Carotenoid content impacts flavor acceptability in tomato (Solanum lycopersicum). Journal of the Science of Food and Agriculture, 90(13), 2233-2240. doi:10.1002/jsfa.4076Voorrips, R. E. (2002). MapChart: Software for the Graphical Presentation of Linkage Maps and QTLs. Journal of Heredity, 93(1), 77-78. doi:10.1093/jhered/93.1.77Zanor, M. I., Rambla, J.-L., Chaïb, J., Steppa, A., Medina, A., Granell, A., … Causse, M. (2009). Metabolic characterization of loci affecting sensory attributes in tomato allows an assessment of the influence of the levels of primary metabolites and volatile organic contents. Journal of Experimental Botany, 60(7), 2139-2154. doi:10.1093/jxb/erp086Zorrilla-Fontanesi, Y., Rambla, J.-L., Cabeza, A., Medina, J. J., Sánchez-Sevilla, J. F., Valpuesta, V., … Amaya, I. (2012). Genetic Analysis of Strawberry Fruit Aroma and Identification of O-Methyltransferase FaOMT as the Locus Controlling Natural Variation in Mesifurane Content. Plant Physiology, 159(2), 851-870. doi:10.1104/pp.111.18831
A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality
Background: Accurate estimates of multiple breath washout (MBW) outcomes require correct operation of the device, appropriate distraction of the subject to ensure they breathe in a manner representative of their relaxed tidal breathing pattern, and appropriate interpretation of the acquired data. Based on available recommendations for an acceptable MBW test, we aimed to develop a protocol to systematically evaluate MBW measurements based on these criteria. Methods: 50MBWtest occasions were systematically reviewed for technical elements and whether the breathing pattern was representative of relaxed tidal breathing by an experienced MBW operator. The impact of qualitative and quantitative criteria on inter-observer agreement was assessed across eight MBW operators (n = 20 test occasions, compared using a Kappa statistic). Results: Using qualitative criteria, 46/168 trials were rejected: 16.6%were technically unacceptable and 10.7% were excluded due to inappropriate breathing pattern. Reviewer agreement was good using qualitative criteria and further improved with quantitative criteria from (κ = 0.53– 0.83%) to (κ 0.73–0.97%), but at the cost of exclusion of further test occasions in this retrospective data analysis. Conclusions: The application of the systematic review improved inter-observer agreement but did not affect reported MBW outcomes
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