239 research outputs found
SHOW
"Show" is a collection of poems concerned primarily with sight, both in terms of looking and being looked at. These poems tend find their subjects in the physical world, the world of and around the bodyand the elements at work between the two. Broken into three sections, "Show" moves from a meditation on the natural world to a chronological reflection on childhood events, still often situated in or contending with the natural environment. As these events become more personal, the poems begin to spin out into a different kind of meditation, fixed mainly on various aspects of the human body. Still engaging the natural world, the third section echoes the first, but in a less conventional way: here the poems often take the grotesque as their subjects and find a lure in the distorted and perverse. This course of looking in "Show" culminates in a series of ekphrastic poems
P2X7 receptor activation amplifies lipopolysaccharideinduced vascular hyporeactivity via interleukin-1 beta release
ABSTRACT Lipopolysaccharide (LPS) stimulates cytoplasmic accumulation of pro-interleukin (IL)-1â€. Activation of P2X 7 receptors stimulates conversion of pro-IL-1†into mature IL-1â€, which is then secreted. Because both LPS (in vivo) and IL-1†(in vitro) decrease vascular reactivity to contractile agents, we hypothesized the following: 1) P2X 7 receptor activation contributes to LPS-induced vascular hyporeactivity, and 2) IL-1†mediates this change. Thoracic aortas were obtained from 12-week-old male C57BL/6 mice. The aortic rings were incubated for 24 h in Dulbecco's modified Eagle's medium, LPS, benzoylbenzoyl-ATP (BzATP; P2X 7 receptor agonist), LPS plus BzATP, oxidized ATP (oATP; P2X 7 receptor antagonist), or oATP plus LPS plus BzATP. After the treatment, the rings were either mounted in a myograph for evaluation of contractile activity or homogenized for IL-1†and inducible nitric-oxide synthase (iNOS) protein measurement. In endothelium-intact aortic rings, phenylephrine (PE)-induced contractions were not altered by incubation with LPS or BzATP, but they significantly decreased in aortic rings incubated with LPS plus BzATP. Treatment with oATP or IL-1ra (IL-1†receptor antagonist) reversed LPS plus BzATP-induced hyporeactivity to PE. In the presence of N G -nitro-L-arginine methyl ester or N- ([3-(aminomethyl)phenyl]methyl)ethanimidamide (selective iNOS inhibitor), the vascular hyporeactivity induced by LPS plus BzATP on PE responses was not observed. BzATP augmented LPS-induced IL-1†release and iNOS protein expression, and these effects were also inhibited by oATP. Moreover, incubation of endothelium-intact aortic rings with IL-1†induced iNOS protein expression. Thus, activation of P2X 7 receptor amplifies LPS-induced hyporeactivity in mouse endothelium-intact aorta, which is associated with IL-1â€-mediated release of nitric oxide by iNOS
Long-term culture of patient-derived cardiac organoids recapitulated Duchenne muscular dystrophy cardiomyopathy and disease progression
Duchenne Muscular Dystrophy (DMD) is an X-linked neuromuscular disease which to date is incurable. The major cause of death is dilated cardiomyopathy however, its pathogenesis is unclear as existing cellular and animal models do not fully recapitulate the human disease phenotypes. In this study, we generated cardiac organoids from patient-derived induced pluripotent stem cells (DMD-COs) and isogenic-corrected controls (DMD-Iso-COs) and studied if DMD-related cardiomyopathy and disease progression occur in the organoids upon long-term culture (up to 93 days). Histological analysis showed that DMD-COs lack initial proliferative capacity, displayed a progressive loss of sarcoglycan localization and high stress in endoplasmic reticulum. Additionally, cardiomyocyte deterioration, fibrosis and aberrant adipogenesis were observed in DMD-COs over time. RNA sequencing analysis confirmed a distinct transcriptomic profile in DMD-COs which was associated with functional enrichment in hypertrophy/dilated cardiomyopathy, arrhythmia, adipogenesis and fibrosis pathways. Moreover, five miRNAs were identified to be crucial in this dysregulated gene network. In conclusion, we generated patient-derived cardiac organoid model that displayed DMD-related cardiomyopathy and disease progression phenotypes in long-term culture. We envision the feasibility to develop a more complex, realistic and reliable in vitro 3D human cardiac-mimics to study DMD-related cardiomyopathies
Effect of the Purinergic Inhibitor Oxidized ATP in a Model of Islet Allograft Rejection
The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R+CD4+ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function
Effect of the Purinergic Inhibitor Oxidized ATP in a Model of Islet Allograft Rejection
The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R+CD4+ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function
How are religion and spirituality related to health? A study of physiciansâ perspectives
Background: Despite expansive medical literature regarding spirituality and medicine, little is known about physician beliefs regarding the influence of religion on health
A framework for increasing the value of predictive data-driven models by enriching problem domain characterization with novel features
The need to leverage knowledge through data mining has driven enterprises in a demand for more data. However, there is a gap between the availability of data and the application of extracted knowledge for improving decision support. In fact, more data do not necessarily imply better predictive data-driven marketing models, since it is often the case that the problem domain requires a deeper characterization. Aiming at such characterization, we propose a framework drawn on three feature selection strategies, where the goal is to unveil novel features that can effectively increase the value of data by providing a richer characterization of the problem domain. Such strategies involve encompassing context (e.g., social and economic variables), evaluating past history, and disaggregate the main problem into smaller but interesting subproblems. The framework is evaluated through an empirical analysis for a real bank telemarketing application, with the results proving the benefits of such approach, as the area under the receiver operating characteristic curve increased with each stage, improving previous model in terms of predictive performance.The work of P. Cortez was supported by FCT within the Project Scope
UID/CEC/00319/2013. The authors would like to thank the anonymous reviewers
for their helpful comments.info:eu-repo/semantics/publishedVersio
Quantum metric nonlinear Hall effect in a topological antiferromagnetic heterostructure
Quantum geometry - the geometry of electron Bloch wavefunctions - is central
to modern condensed matter physics. Due to the quantum nature, quantum geometry
has two parts, the real part quantum metric and the imaginary part Berry
curvature. The studies of Berry curvature have led to countless breakthroughs,
ranging from the quantum Hall effect in 2DEGs to the anomalous Hall effect
(AHE) in ferromagnets. However, in contrast to Berry curvature, the quantum
metric has rarely been explored. Here, we report a new nonlinear Hall effect
induced by quantum metric by interfacing even-layered MnBi2Te4 (a PT-symmetric
antiferromagnet (AFM)) with black phosphorus. This novel nonlinear Hall effect
switches direction upon reversing the AFM spins and exhibits distinct scaling
that suggests a non-dissipative nature. Like the AHE brought Berry curvature
under the spotlight, our results open the door to discovering quantum metric
responses. Moreover, we demonstrate that the AFM can harvest wireless
electromagnetic energy via the new nonlinear Hall effect, therefore enabling
intriguing applications that bridges nonlinear electronics with AFM
spintronics.Comment: 19 pages, 4 figures and a Supplementary Materials with 66 pages, 4
figures and 3 tables. Originally submitted to Science on Oct. 5, 202
A Multilab Replication of the Ego Depletion Effect
There is an active debate regarding whether the ego depletion effect is real. A recent preregistered experiment with the Stroop task as the depleting task and the antisaccade task as the outcome task found a medium-level effect size. In the current research, we conducted a preregistered multilab replication of that experiment. Data from 12 labs across the globe (N = 1,775) revealed a small and significant ego depletion effect, d = 0.10. After excluding participants who might have responded randomly during the outcome task, the effect size increased to d = 0.16. By adding an informative, unbiased data point to the literature, our findings contribute to clarifying the existence, size, and generality of ego depletion
Cloning and characterization of XiR1, a locus responsible for dagger nematode resistance in grape
The dagger nematode, Xiphinemaindex, feeds aggressively on grape roots and in the process, vectors grapevine fanleaf virus (GFLV) leading to the severe viral disease known as fanleaf degeneration. Resistance to X. index and GFLV has been the key objective of grape rootstock breeding programs. A previous study found that resistance to X. index derived from Vitis arizonica was largely controlled by a major quantitative trait locus, XiR1 (X. index Resistance 1), located on chromosome 19. The study presented here develops high-resolution genetic and physical maps in an effort to identify the XiR1 gene(s). The mapping was carried out with 1,375 genotypes in three populations derived from D8909-15, a resistant selection from a cross of V. rupestris A. de Serres (susceptible)Â ĂÂ V. arizonica b42-26 (resistant). Resistance to X. index was evaluated on 99 informative recombinants that were identified by screening the three populations with two markers flanking the XiR1 locus. The high-resolution genetic map of XiR1 was primarily constructed with seven DNA markers developed in this study. Physical mapping of XiR1 was accomplished by screening three bacterial artificial chromosome (BAC) libraries constructed from D8909-15, V. vinifera Cabernet Sauvignon and V. arizonica b42-26. A total of 32 BAC clones were identified and the XiR1 locus was delineated within a 115Â kb region. Sequence analysis of three BAC clones identified putative nucleotide binding/leucine-rich repeat (NB-LRR) genes. This is the first report of a closely linked major gene locus responsible for ectoparasitic nematode resistance. The markers developed from this study are being used to expedite the breeding of resistant grape rootstocks
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