Background
Altered metabolism of eicosanoids is a characteristic finding in aspirin‐exacerbated respiratory disease (AERD). Bronchial challenge with lysyl‐aspirin can be used as a confirmatory ...diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions.
Objectives
To investigate the influence of inhaled lysyl‐aspirin on sputum supernatant concentration of eicosanoids during the bronchial challenge test. Subjects with asthma hypersensitive to nonsteroidal anti‐inflammatory drugs were compared with aspirin‐tolerant asthmatic controls.
Methods
Induced sputum was collected before and following bronchial challenge with lysyl‐aspirin. Sputum differential cell count and sputum supernatant concentrations of selected lipoxygenases products: 5‐,12‐,15‐hydroxyeicosatetraenoic acid, cysteinyl leukotrienes, leukotriene B4, 11‐dehydro‐thromboxane B2, and prostaglandins E2, D2, and F2α and their metabolites, were measured using validated methods of chromatography–mass spectrometry.
Results
Aspirin precipitated bronchoconstriction in all AERD subjects, but in none of the aspirin‐tolerant asthmatics. Phenotypes of asthma based on the sputum cytology did not differ between the groups. Baseline sputum eosinophilia correlated with a higher leukotriene D4 (LTD4) and leukotriene E4 (LTE4) concentrations. LTC4, PGE2, and 11‐dehydro‐TXB2 did not differ between the groups, but levels of LTD4, LTE4, and PGD2 were significantly higher in AERD group. Following the challenge, LTD4 and LTE4 increased, while PGE2 and LTB4 decreased in AERD subjects only.
Conclusions
During the bronchial challenge, decrease in PGE2 and its metabolite is accompanied by a surge in bronchoconstrictory cysteinyl leukotrienes produced at the expense of LTB4 in AERD subjects. Bronchial PGE2 inhibition in AERD seems specific and sensitive to a low dose of aspirin.
The statistics of heat exchange between two classical or quantum finite systems initially prepared at different temperatures are shown to obey a fluctuation theorem.
Techniques based on imaging serial sections of brain tissue provide insight into brain structure and function. However, to compare or combine them with results from three dimensional imaging methods, ...reconstruction into a volumetric form is required. Currently, there are no tools for performing such a task in a streamlined way. Here we propose the Possum volumetric reconstruction framework which provides a selection of 2D to 3D image reconstruction routines allowing one to build workflows tailored to one’s specific requirements. The main components include routines for reconstruction with or without using external reference and solutions for typical issues encountered during the reconstruction process, such as propagation of the registration errors due to distorted sections. We validate the implementation using synthetic datasets and actual experimental imaging data derived from publicly available resources. We also evaluate efficiency of a subset of the algorithms implemented. The Possum framework is distributed under MIT license and it provides researchers with a possibility of building reconstruction workflows from existing components, without the need for low-level implementation. As a consequence, it also facilitates sharing and data exchange between researchers and laboratories.
Abstract
The marmoset monkey has become an important primate model in Neuroscience. Here, we characterize salient statistical properties of interareal connections of the marmoset cerebral cortex, ...using data from retrograde tracer injections. We found that the connectivity weights are highly heterogeneous, spanning 5 orders of magnitude, and are log-normally distributed. The cortico-cortical network is dense, heterogeneous and has high specificity. The reciprocal connections are the most prominent and the probability of connection between 2 areas decays with their functional dissimilarity. The laminar dependence of connections defines a hierarchical network correlated with microstructural properties of each area. The marmoset connectome reveals parallel streams associated with different sensory systems. Finally, the connectome is spatially embedded with a characteristic length that obeys a power law as a function of brain volume across rodent and primate species. These findings provide a connectomic basis for investigations of multiple interacting areas in a complex large-scale cortical system underlying cognitive processes.
Superradiance--the cooperative decay of excited dipoles--has recently been discussed in a diverse range of contexts in which coherent coupling of constituent particles governs their cooperative ...dynamics: cavity quantum electrodynamics, quantum phase transitions and plasmonics. Here we observe intense, delayed bursts of coherent radiation from a photo-excited semiconductor and interpret it as superfluorescence, where macroscopic coherence spontaneously appears from initially incoherent electron-hole pairs. The coherence then decays superradiantly, with a concomitant abrupt decrease in population from full inversion to zero. This is the first observation of superfluorescence in a dense semiconductor plasma, where decoherence is much faster than radiative decay, a situation never encountered in atomic cases. Nonetheless, a many-body cooperative state of phased electron-hole 'dipoles' does emerge at high magnetic fields and low temperatures, producing giant superfluorescent pulses. The solid-state realization of superfluorescence resulted in unprecedented controllability, promising tunable sources of coherent pulses. PUBLICATION ABSTRACT
The etiopathogenesis of potentially malignant oral disorders (PMOD) has not been fully understood yet. Recent results suggest that oxidative stress may be involved in the etiology of PMOD. Production ...of oxidants seems to be the major biological effect responsible for tissue injury and inflammatory response to air pollution. The aim of this study was to compare the oxidative stress markers and antioxidant potential in saliva of PMOD subjects and healthy controls in periods of high and low air pollution. Among enrolled 40 participants, there were 20 PMOD patients and 20 healthy volunteers. The exposure to air pollution was assessed by exhaled CO (eCO). Four oxidative status parameters: 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC) were measured in saliva. Measurements were carried out in June (low air pollution) and November (increased air pollution). In both groups, significantly higher concentrations of 8-OHdG (P < 0.001 for PMOD patients and P = 0.001 for healthy controls), MDA (P = 0.002 and P = 0.012 respectively) and eCO (P < 0.001 and P < 0.001 respectively) were observed in periods of high air pollution. The concentration of TAC did not change between visits. The concentration of salivary GSH (P < 0.001 and P < 0.001 for both groups) decreased when compared between consecutive visits. We conclude that exhaled carbon monoxide (reflecting exposure to air pollution) correlated with the oxidative stress markers in patients with PMOD and healthy controls.
Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive learning and positive emotions motivating appetitive learning. The amygdala is a key component of the ...brain emotional system; however, an understanding of how various emotions are differentially processed in the amygdala has yet to be achieved. We report that matrix metalloproteinase-9 (MMP-9, extracellularly operating enzyme) in the central nucleus of the amygdala (CeA) is crucial for appetitive, but not for aversive, learning in mice. The knock-out of MMP-9 impairs appetitively motivated conditioning, but not an aversive one. MMP-9 is present at the excitatory synapses in the CeA with its activity greatly enhanced after the appetitive training. Finally, blocking extracellular MMP-9 activity with its inhibitor TIMP-1 provides evidence that local MMP-9 activity in the CeA is crucial for the appetitive, but not for aversive, learning.
We study the spin-resolved transport through single-level quantum dots strongly coupled to ferromagnetic leads in the Kondo regime, with a focus on contact and material asymmetry-related effects. By ...using the numerical renormalization group method, we analyze the dependence of relevant spectral functions, the linear conductance and the tunnel magnetoresistance on the system asymmetry parameters. In the parallel magnetic configuration of the device the Kondo effect is generally suppressed due to the presence of an exchange field, irrespective of the system's asymmetry. In the antiparallel configuration, on the other hand, the Kondo effect can develop if the system is symmetric. We show that even relatively weak asymmetry may lead to suppression of the Kondo resonance in the antiparallel configuration and thus give rise to nontrivial behavior of the tunnel magnetoresistance. In addition, by using the second-order perturbation theory we derive general formulas for the exchange field in both magnetic configurations of the system.
There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the ...world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.
High-frequency neuronal population oscillations (HFO, 130-180 Hz) are robustly potentiated by subanesthetic doses of ketamine. This frequency band has been recorded in functionally and ...neuroanatomically diverse cortical and subcortical regions, notably ventral striatal areas. However, the locus of generation remains largely unknown. There is compelling evidence that olfactory regions can drive oscillations in distant areas. Here we tested the hypothesis that the olfactory bulb (OB) is a locus for the generation of HFO following a subanesthetic dose of ketamine. The effect of ketamine on the electrophysiological activity of the OB and ventral striatum of male Wistar rats was examined using field potential and unit recordings, local inhibition, naris blockade, current source density and causality estimates. Ketamine-HFO was of larger magnitude and was phase-advanced in the OB relative to ventral striatum. Granger causality analysis was consistent with the OB as the source of HFO. Unilateral local inhibition of the OB and naris blockade both attenuated HFO recorded locally and in the ventral striatum. Within the OB, current source density analysis revealed HFO current dipoles close to the mitral layer and unit firing of mitral/tufted cells was phase locked to HFO. Our results reveal the OB as a source of ketamine-HFO which can contribute to HFO in the ventral striatum, known to project diffusely to many other brain regions. These findings provide a new conceptual understanding on how changes in olfactory system function may have implications for neurological disorders involving NMDA receptor dysfunction such as schizophrenia and depression.
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