The sleep cycle is characterized by alternating non-rapid eye movement (NREM) and rapid eye movement (REM) sleeps. The mechanisms by which this cycle is generated are incompletely understood. We ...found that a transient increase of dopamine (DA) in the basolateral amygdala (BLA) during NREM sleep terminates NREM sleep and initiates REM sleep. DA acts on dopamine receptor D2 (Drd2)-expressing neurons in the BLA to induce the NREM-to-REM transition. This mechanism also plays a role in cataplectic attacks-a pathological intrusion of REM sleep into wakefulness-in narcoleptics. These results show a critical role of DA signaling in the BLA in initiating REM sleep and provide a neuronal basis for sleep cycle generation.
Asthma and chronic obstructive pulmonary disease (COPD) are respiratory diseases associated with airway inflammation, which is the main pathogenesis. Although their causes and characteristics differ, ...in some cases, asthma and COPD may coexist in the same patient in a condition called asthma-COPD overlap (ACO). The prognosis of ACO is more unfavourable than those of asthma or COPD alone, without any treatment strategies demonstrating efficacy. Owing to its intricate spectrum of features, the detailed pathogenesis of how ACO exacerbates respiratory features remains unclear. In this study, we exposed papain-induced asthma model mice to tobacco smoke to establish an ACO mouse model, in which features of airway inflammation observed in both asthma and COPD were incorporated. This model exhibited distinctive mixed and corticosteroid-resistant airway inflammation and emphysematous changes that are characteristic of ACO. The novel mouse model established here is expected to significantly contribute to elucidating the mechanisms of the broad pathologies of ACO and identifying potential therapeutic targets.
•Papain and tobacco smoke exposure induced airway inflammation in asthma-COPD.•Co-exposure induced a mixed set of biomarker expression of asthma and COPD.•Mice co-exposed to papain and tobacco smoke provide a comprehensive model for ACO.
Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to ...elucidate the effect of oral exposure to DON on pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis, which was generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type-2 helper T cells. To evaluate acute exposure to DON, the mice were orally administered vehicle alone, 0.1 mg/kg DON, or 0.3 mg/kg DON 48, 24, and 1 h before the final challenge with TDI. To study subacute exposure, the mice were fed DON-contaminated rodent diet (0.3 ppm) during the experimental period. After the itch behavior and ear-swelling response were monitored, the serum, auricular lymph node, and skin tissue were collected for analyzing immunocyte differentiation, cytokine determination, and histological changes. Acute oral administration of DON significantly enhanced pro-inflammatory responses including ear-swelling response, immunocyte infiltration, and cytokine productions. Histological evaluation supported the occurrence of pro-inflammatory responses. In contrast, acute DON exposure only slightly increased itch behavior. Subacute oral exposure to DON significantly up-regulated the inflammatory responses, but showed almost no effect on pruritic response. In vitro evaluation in dendritic cells and keratinocytes indicated that DON pre-exposure induced a dose-dependent significant increase in cytokine production. Our results imply that both acute and subacute exposures to DON are associated with pro-inflammatory responses in cutaneous allergy.
Abstract
Previously, researchers have demonstrated that mycotoxin deoxynivalenol (DON) significantly enhances immunocyte activation. However, the interaction between DON exposure and immune disorders ...remains unclear. In this study, we aimed to investigate whether acute and subacute oral exposure to DON exacerbates the development of respiratory allergy using a mite allergen (Dermatophagoides farina, Derf)-induced mouse model of asthma. The direct relationship between DON exposure and asthma development was examined following acute oral DON administration (0, 0.1, or 0.3 mg/kg body weight), immediately before the final mite allergen challenge. Simultaneously, the influence of subacute oral exposure via low dose DON contaminated wheat (0.33 ppm) was evaluated using the same settings. To detect the proinflammatory effects of DON exposure, we examined the total and Derf-specific serum IgE levels, histology, number of immunocytes, and cytokine and chemokine secretion. Acute oral DON significantly enhanced the inflammatory responses, including cellular infiltration into bronchoalveolar lavage fluid, infiltration of immunocytes and cytokine production in local lymph nodes, and cytokine levels in lung tissues. Corresponding proinflammatory responses were observed in a mouse group exposed to subacute oral DON. In vivo results were validated by in vitro experiments using the human bronchial epithelial (BEAS-2B) and human eosinophilic leukemia (EOL-1) cell lines. Following exposure to DON, the secretion of interleukin (IL)-1β, IL-6, IL-8, and/or tumor necrosis factor-α in BEAS-2B cells, as well as EoL-1 cells, increased significantly. Our findings indicate that DON exposure is significantly involved in the proinflammatory response observed in respiratory allergy.
In the quest for sustainable energy solutions, perovskite solar cells have emerged as a promising avenue due to their remarkable efficiency and cost-effectiveness. However, their widespread adoption ...is hampered by performance degradation issues primarily attributed to ion migration and vacancy formation within halide perovskite films. To mitigate the impact of ion defects, a passivation layer, which typically acts as a barrier for carriers, is employed. Nonetheless, the requirement for extreme thinness to avoid increasing series resistance complicates the manufacturing process. In this study, we introduced gallium phthalocyanine hydroxide (OHGaPc), a p-type organic semiconductor with Lewis base functionality, as a passivation layer to mitigate performance degradation in perovskite solar cells. We demonstrated that this material passivates halide vacancies by being a Lewis base and promotes efficient charge transport as a p-type semiconductor. This dual functionality of OHGaPc not only enhances the stability and performance of perovskite solar cells but also simplifies the manufacturing process by obviating the need for ultra-thin insulating films. Our findings underscore the significance of leveraging the properties of Lewis bases and p-type semiconductors in improving charge extraction and overall cell efficiency, setting a new direction in the development of durable and efficient perovskite solar cells.
Swift and NuSTAR observations of GW170817 Evans, P. A.; Cenko, S. B.; Kennea, J. A. ...
Science (American Association for the Advancement of Science),
12/2017, Volume:
358, Issue:
6370
Journal Article
Peer reviewed
Open access
With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of ...an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counter part of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Yₑ ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration fromthe heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).
In magnetic resonance imaging (MRI), reducing long scan times is an urgent issue that could be addressed with super-resolution (SR) techniques. Most of the SR networks using deep neural networks ...(DNNs) have been evaluated only based on numeric metrics, and the image restoration quality for individual lesions is not evaluated sufficiently. Here, we evaluated the performances of different types of SR networks using DNNs for brain MRI, in terms of diagnostic performance and image quality. We focused on comparing the performance between generative adversarial networks (GANs) and non-GAN networks. There was a trade-off in such restoration quality between GAN- and non-GAN-based SRs, with the GANs being more accurate in restoring images of anatomical structures but less accurate in restoring those of lesions; non-GANs showed the opposite tendency. The non-GAN SRs were preferable in terms of diagnostic performance and image quality. This result suggested that the evaluation of DNN performance for lesions might be changed drastically by adding a clinical evaluation perspective. The dependence of network architecture on network performance obtained in this study will provide guidance for future development of SR DNN for medical images.
An MSM/Ms strain was established using Japanese wild mice, which exhibit resistance to several phenotypes associated with aging, such as obesity, inflammation, and tumorigenesis, compared to common ...inbred mouse strains. MSM/Ms strain is resistant to age-related hearing loss, and their auditory abilities are sustained for long durations. The age-related hearing loss 3 (ahl3) locus contributes to age-related hearing in MSM/Ms strain. We generated ahl3 congenic strains by transferring a genomic region on chromosome 17 from MSM/Ms mice into C57BL/6J mice. Although C57BL/6J mice develop age-related hearing loss because of the ahl allele of the cadherin 23 gene, the development of middle- to high-frequency hearing loss was significantly delayed in an ahl3 congenic strain. Moreover, the novel age-related hearing loss 10 (ahl10) locus associated with age-related hearing resistance in MSM/Ms strain was mapped to chromosome 12. Although the resistance effects in ahl10 congenic strain were slightly weaker than those in ahl3 congenic strain, slow progression of age-related hearing loss was confirmed in ahl10 congenic strain despite harboring the ahl allele of cadherin 23. These results suggest that causative genes and polymorphisms of the ahl3 and ahl10 loci are important targets for the prevention and treatment of age-related hearing loss.
Transcatheter aortic valve replacement (TAVR)–related coronary artery obstruction prediction remains unsatisfactory despite high mortality and novel preventive therapies.
This study sought to develop ...a predictive model for TAVR-related coronary obstruction in native aortic stenosis.
Preprocedure computed tomography and fluoroscopy images of patients in whom TAVR caused coronary artery obstruction were collected. Central laboratories made measurements, which were compared with unobstructed patients from a single-center database. A multivariate model was developed and validated against a 1:1 propensity-matched subselection of the unobstructed cohort.
Sixty patients with angiographically confirmed coronary obstruction and 1,381 without obstruction were included. In-hospital death was higher in the obstruction cohort (26.7% vs 0.7%; P < 0.001). Annular area and perimeter, coronary height, sinus width, and sinotubular junction height and width were all significantly smaller in the obstructed cohort. Obstruction was most common on the left side (78.3%) and at the level of the coronary artery ostium (92.1%). Coronary artery height and sinus width, but not annulus area, were significant risk factors for obstruction by logistic regression but performed poorly in predicting obstruction. The new multivariate model (coronary obstruction IF cusp height > coronary height, AND virtual valve-to-coronary distance ≤4 mm OR culprit leaflet calcium volume >600 mm3) performed well, with an area under the curve of 0.93 (sensitivity = 0.93, specificity = 0.84) for the left coronary artery and 0.94 (sensitivity = 0.92, specificity = 0.96) for the right.
A novel computed tomography–based multivariate prediction model that can be implemented routinely in real-world practice predicted coronary artery obstruction from TAVR in native aortic stenosis.
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