Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin ...1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation.
Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined ...the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss. Mechanistically, smoke was required to upregulate epithelial-derived IL-33 and simultaneously alter the distribution of the IL-33 receptor ST2. Specifically, smoke decreased ST2 expression on group 2 innate lymphoid cells (ILC2s) while elevating ST2 expression on macrophages and natural killer (NK) cells, thus altering IL-33 responsiveness within the lung. Consequently, upon infection and release, increased local IL-33 significantly amplified type I proinflammatory responses via synergistic modulation of macrophage and NK cell function. Therefore, in COPD, smoke alters the lung microenvironment to facilitate an alternative IL-33-dependent exaggerated proinflammatory response to infection, exacerbating disease.
•IL-33 is upregulated by cigarette smoke and released in response to virus infection•Smoke dampens ST2 expression on ILC2s but enhances ST2 on NK cells and macrophages•IL-33 drives an exacerbated Th1-cell-like inflammatory response to virus infection•IL-33 might play a critical role in pathogen-induced exacerbations of COPD
Smoking is thought to be central to the altered responsiveness to infection in patients with chronic obstructive pulmonary disease (COPD). Humbles and colleagues show that mice lacking interleukin-33 (IL-33) are protected from smoke-induced exaggerated inflammatory responses to virus infection, suggesting that IL-33 is a critical mediator in acute exacerbations of COPD.
In India, increasing lifespan and decreasing fertility rates have resulted in a growing number of older persons. By 2050, people over 60 years of age are predicted to constitute 19.1% of the total ...population. This ageing of the population is expected to be accompanied by a dramatic increase in the prevalence of dementia. The aetiopathogenesis of dementia has been the subject of a number of prospective longitudinal studies in North America and Europe; however, the findings from these studies cannot simply be translated to the Indian population. The population of India is extremely diverse in terms of socio-economic, cultural, linguistic, geographical, lifestyle-related and genetic factors. Indeed, preliminary data from recently initiated longitudinal studies in India indicate that the prevalence of vascular and metabolic risk factors, as well as white matter hyperintensities, differs between urban and rural cohorts. More information on the complex role of vascular risk factors, gender and genetic influences on dementia prevalence and progression in Indian populations is urgently needed. Low-cost, culturally appropriate and scalable interventions need to be developed expeditiously and implemented through public health measures to reduce the growing burden of dementia. Here, we review the literature concerning dementia epidemiology and risk factors in the Indian population and discuss the future work that needs to be performed to put in place public health interventions to mitigate the burden of dementia.
Measurement-based quantum computation offers exponential computational speed-up through simple measurements on a large entangled cluster state. We propose and demonstrate a scalable scheme for the ...generation of photonic cluster states suitable for universal measurement-based quantum computation. We exploit temporal multiplexing of squeezed light modes, delay loops, and beam-splitter transformations to deterministically generate a cylindrical cluster state with a two-dimensional (2D) topological structure as required for universal quantum information processing. The generated state consists of more than 30,000 entangled modes arranged in a cylindrical lattice with 24 modes on the circumference, defining the input register, and a length of 1250 modes, defining the computation depth. Our demonstrated source of two-dimensional cluster states can be combined with quantum error correction to enable fault-tolerant quantum computation.
The traditional approaches to quantum information processing using either discrete or continuous variables can be combined in hybrid protocols for tasks including quantum teleportation, computation, ...entanglement distillation or Bell tests.
The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown.
We sought to examine the effect of ...BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma.
Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters.
BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% 25th-75th interquartile range (IQR), 15.9% to 22.4% and 5.3% 25th-75th IQR, 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 μm 25th-75th IQR, 4.0-4.7 μm and 3.9 μm 25th-75th IQR, 3.7-4.6 μm, P = 0.02), submucosal nerves (1.0 ‰ 25th-75th IQR, 0.7-1.3 ‰ immunoreactivity and 0.3 ‰ 25th-75th IQR, 0.1-0.5 ‰ immunoreactivity, P < .001), ASM-associated nerves (452.6 25th-75th IQR, 196.0-811.2 immunoreactive pixels per mm
and 62.7 25th-75th IQR, 0.0-230.3 immunoreactive pixels per mm
, P = .02), and epithelial neuroendocrine cells (4.9/mm
25th-75th IQR, 0-16.4/mm
and 0.0/mm
25th-75th IQR, 0-0/mm
, P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT.
BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.
This article summarizes the state-of-the-art knowledge gained from field observations and laboratory studies regarding foam as a liquid controlling agent in porous media. Being the least explored ...property of foam, its effect and potential have often been overlooked or simply ignored. The aim with this review is therefore to demonstrate the abilities that foam could have to block, reduce, delay, suppress, or divert water flow in porous media. As a liquid controlling agent in porous media, foam has potential for industrial processes that involve fluid injections or fluid withdrawals in porous geological formations, such as improved/enhanced oil recovery (IOR/EOR), matrix-stimulation treatments, underground storage of CO2, hydrogen, compressed-air or natural gas withdrawal, geothermal energy, and contaminated soil-groundwater remediation processes with unwanted aquifer impacts. Improving the water utilization factor and water management in these applications might result in tremendous energic, economic, and environmental incentives that are worth pursuing. Specific focus in this review is given to the post-foam water injection, which determines the ultimate stability and water-blocking capabilities of the foam treatment. Main parameters and mechanisms that can influence foam stability against water injection/intrusion after generation and placement are assessed and discussed. Unresolved issues are highlighted, which give recommendations for further research and field-scale operations.
Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated ...peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.
Quantum computing can be realized with numerous different hardware platforms and computational protocols. A highly promising, and potentially scalable, idea is to combine a photonic platform with ...measurement-induced quantum information processing. In this approach, gate operations can be implemented through optical measurements on a multipartite entangled quantum state—a so-called cluster state. Previously, a few quantum gates on non-universal or non-scalable cluster states have been performed, but a full set of gates for universal scalable quantum computing has not been realized. Here we propose and demonstrate the deterministic implementation of a multi-mode set of measurement-induced quantum gates in a large two-dimensional optical cluster state using phase-controlled continuous-variable quadrature measurements. Each gate is programmed into the phases of high-efficiency quadrature measurements, which execute the transformations by teleportation through the cluster state. We further execute a small quantum circuit consisting of 10 single-mode gates and 2 two-mode gates on a three-mode input state. Fault-tolerant universal quantum computing is possible with this platform if the cluster-state entanglement is improved and a supply of states with Gottesman–Kitaev–Preskill encoding is available.Measurement-based quantum computing performs quantum gates on entangled states without difficult multi-qubit coherent dynamics. A set of gates sufficient for universal quantum computing has now been implemented on a programmable optical platform.
Background Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing ...airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti-inflammatory treatment. Objective We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects. Methods Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10 healthy control subjects. Bacterial DNA was extracted from and subjected to Illumina MiSeq sequencing of the 16S rDNA V4 region. Eosinophils and neutrophils in the submucosa were quantified by means of immunohistochemical identification and computerized image analysis. Induced sputum was obtained, and airway hyperresponsiveness to mannitol and fraction of exhaled nitric oxide values were measured. Relationships between airway microbial diversity and composition and inflammatory profiles were analyzed. Results In asthmatic patients airway microbial composition was associated with airway eosinophilia and AHR to mannitol but not airway neutrophilia. The overall composition of the airway microbiome of asthmatic patients with the lowest levels of eosinophils but not asthmatic patients with the highest levels of eosinophils deviated significantly from that of healthy subjects. Asthmatic patients with the lowest levels of eosinophils had an altered bacterial abundance profile, with more Neisseria , Bacteroides , and Rothia species and less Sphingomonas , Halomonas , and Aeribacillus species compared with asthmatic patients with more eosinophils and healthy control subjects. Conclusion The level of eosinophilic airway inflammation correlates with variations in the microbiome across asthmatic patients, whereas neutrophilic airway inflammation does not. This warrants further investigation on molecular pathways involved in both patients with eosinophilic and those with noneosinophilic asthma.
PDF
