719 research outputs found
ROS/TRPA1/CGRP signaling mediates cortical spreading depression
Abstract Objectives The transient receptor potential ankyrin A 1 (TRPA1) channel and calcitonin gene-related peptide (CGRP) are targets for migraine prophylaxis. This study aimed to understand their mechanisms in migraine by investigating the role of TRPA1 in cortical spreading depression (CSD) in vivo and exploring how reactive oxygen species (ROS)/TRPA1/CGRP interplay in regulating cortical susceptibility to CSD. Methods Immunohistochemistry was used for detecting TRPA1 expression. CSD was induced by K+ on the cerebral cortex, monitored using electrophysiology in rats, and intrinsic optical imaging in mouse brain slices, respectively. Drugs were perfused into contralateral ventricle of rats. Lipid peroxidation (malondialdehyde, MDA) analysis was used for indicating ROS level. Results TRPA1 was expressed in cortical neurons and astrocytes of rats and mice. TRPA1 deactivation by an anti-TRPA1 antibody reduced cortical susceptibility to CSD in rats and decreased ipsilateral MDA level induced by CSD. In mouse brain slices, H2O2 facilitated submaximal CSD induction, which disappeared by the antioxidant, tempol and the TRPA1 antagonist, A-967079; Consistently, TRPA1 activation reversed prolonged CSD latency and reduced magnitude by the antioxidant. Further, blockade of CGRP prolonged CSD latency, which was reversed by H2O2 and the TRPA1 agonist, allyl-isothiocyanate, respectively. Conclusions ROS/TRPA1/CGRP signaling plays a critical role in regulating cortical susceptibility to CSD. Inhibition ROS and deactivation of TRPA1 channels may have therapeutic benefits in preventing stress-triggered migraine via CGRP
Improved estimation of glomerular filtration rate (GFR) by comparison of eGFRcystatin C and eGFRcreatinine
Objective. GFR-prediction equations based upon cystatin C and creatinine have better diagnostic performance in estimating GFR than equations based upon only one of the two markers. The present work concerns in what way a comparison between separate estimations of GFR based upon cystatin C (eGFR(cystatin C)) or creatinine (eGFR(creatinine)) can be used to evaluate the diagnostic performance of a combined cystatin C-and creatinine-based estimation of GFR. Methods. The difference between eGFR(cystatin C) and eGFR(creatinine) was compared with measured GFR (iohexol clearance) and a combined cystatin C- and creatinine-based estimation of GFR in a Swedish-Caucasian cohort of 857 adult patients. Results. A difference between eGFR(cystatin C) and eGFR(creatinine) of >= 40% indicated a markedly reduced diagnostic performance of the combined cystatin C- and creatinine-based estimation of GFR. Conclusion. Comparison of the agreement between eGFR(cystatin C) and eGFR(creatinine) can be used to evaluate the diagnostic performance of combined cystatin C-and creatinine-based estimations of GFR. If 'threshold values' for discordance are exceeded, it must be considered whether the clinical context requires the use of an invasive gold standard method to measure GFR. In some clinical contexts either creatinine or cystatin C are known to be invalidated as markers of GFR and in these situations the use of only the cystatin C-or the creatinine-based GFR estimate should be considered when the 'threshold values' are exceeded
Spectral asymmetry for bag boundary conditions
We give an expression, in terms of boundary spectral functions, for the
spectral asymmetry of the Euclidean Dirac operator in two dimensions, when its
domain is determined by local boundary conditions, and the manifold is of
product type. As an application, we explicitly evaluate the asymmetry in the
case of a finite-length cylinder, and check that the outcome is consistent with
our general result. Finally, we study the asymmetry in a disk, which is a
non-product case, and propose an interpretation.Comment: Some minor changes. To appear in Journal of Physics A: Mathematical
and Genera
A Regulatory Module Controlling Homeostasis of a Plant Immune Kinase
Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identified the calcium-dependent protein kinase CPK28 and heterotrimeric G proteins as negative and positive regulators of BIK1 accumulation, respectively. However, mechanisms underlying this regulation remain unknown. Here we show that the plant U-box proteins PUB25 and PUB26 are homologous E3 ligases that mark BIK1 for degradation to negatively regulate immunity. We demonstrate that the heterotrimeric G proteins inhibit PUB25/26 activity to stabilize BIK1, whereas CPK28 specifically phosphorylates conserved residues in PUB25/26 to enhance their activity and promote BIK1 degradation. Interestingly, PUB25/26 specifically target non-activated BIK1, suggesting that activated BIK1 is maintained for immune signaling. Our findings reveal a multi-protein regulatory module that enables robust yet tightly regulated immune responses
Universality, limits and predictability of gold-medal performances at the Olympic Games
Inspired by the Games held in ancient Greece, modern Olympics represent the
world's largest pageant of athletic skill and competitive spirit. Performances
of athletes at the Olympic Games mirror, since 1896, human potentialities in
sports, and thus provide an optimal source of information for studying the
evolution of sport achievements and predicting the limits that athletes can
reach. Unfortunately, the models introduced so far for the description of
athlete performances at the Olympics are either sophisticated or unrealistic,
and more importantly, do not provide a unified theory for sport performances.
Here, we address this issue by showing that relative performance improvements
of medal winners at the Olympics are normally distributed, implying that the
evolution of performance values can be described in good approximation as an
exponential approach to an a priori unknown limiting performance value. This
law holds for all specialties in athletics-including running, jumping, and
throwing-and swimming. We present a self-consistent method, based on normality
hypothesis testing, able to predict limiting performance values in all
specialties. We further quantify the most likely years in which athletes will
breach challenging performance walls in running, jumping, throwing, and
swimming events, as well as the probability that new world records will be
established at the next edition of the Olympic Games.Comment: 8 pages, 3 figures, 1 table. Supporting information files and data
are available at filrad.homelinux.or
Chinese energy and climate policies after Durban: save the Kyoto Protocol
Nowadays, one of the urgent issues regarding global climate change is to discuss the future of the second period of the Kyoto Protocol. However, the divergence of views and opinions among parties in the last Conference of the Parties of the United Nations Framework Convention on Climate Change, held in Durban in December 2011, is still large. One of the bones of contention is whether the emerging developing countries, like China, should make commitments and legally bind themselves to a Green House Gas (GHG) reduction target in near future. As the largest GHG emitting country, China and its energy and climate policies will play an important role in global climate change and will also significantly influence the other countries? policies and the global climate negotiation. In this paper, we review the current differences among parties in the Durban Conference, and we analyze the recent situation, barriers, and future policies in China. Finally we highlight the impact and potential effect of Clean Development Mechanisms in avoiding China?s barriers regarding climate change. Results show that China is making a great effort to mitigate climate change by establishing and reforming its energy and climate policies in order to achieve a low-carbon development. At the same time, more innovation and international collaboration is needed in China to achieve this goal
TUBERCULOSIS INFECTION MIGHT INCREASE THE RISK OF INVASIVE CANDIDIASIS IN AN IMMUNOCOMPETENT PATIENT
Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicans and spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host's immune system and increase the risk of invasive candidiasis in an immunocompetent patient
Timing of Favorable Conditions, Competition and Fertility Interact to Govern Recruitment of Invasive Chinese Tallow Tree in Stressful Environments
The rate of new exotic recruitment following removal of adult invaders (reinvasion pressure) influences restoration
outcomes and costs but is highly variable and poorly understood. We hypothesize that broad variation in average
reinvasion pressure of Triadica sebifera (Chinese tallow tree, a major invader) arises from differences among habitats in
spatiotemporal availability of realized recruitment windows. These windows are periods of variable duration long enough to
permit establishment given local environmental conditions. We tested this hypothesis via a greenhouse mesocosm
experiment that quantified how the duration of favorable moisture conditions prior to flood or drought stress (window
duration), competition and nutrient availability influenced Triadica success in high stress environments. Window duration
influenced pre-stress seedling abundance and size, growth during stress and final abundance; it interacted with other
factors to affect final biomass and germination during stress. Stress type and competition impacted final size and biomass,
plus germination, mortality and changes in size during stress. Final abundance also depended on competition and the
interaction of window duration, stress type and competition. Fertilization interacted with competition and stress to
influence biomass and changes in height, respectively, but did not affect Triadica abundance. Overall, longer window
durations promoted Triadica establishment, competition and drought (relative to flood) suppressed establishment, and
fertilization had weak effects. Interactions among factors frequently produced different effects in specific contexts. Results
support our ‘outgrow the stress’ hypothesis and show that temporal availability of abiotic windows and factors that
influence growth rates govern Triadica recruitment in stressful environments. These findings suggest that native seed
addition can effectively suppress superior competitors in stressful environments. We also describe environmental scenarios
where specific management methods may be more or less effective. Our results enable better niche-based estimates of
local reinvasion pressure, which can improve restoration efficacy and efficiency by informing site selection and optimal
Management
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