The Role of the Microbiome in Regulating House Dust Mite-Induced Asthma

Asthma is a complex and highly heterogeneous disease characterized by inflammation of the airways, leading to a host of respiratory symptoms including wheeze and dyspnea. Asthma is the product of multiple interconnected immunological processes and represents a constellation of related, but distinct, disease phenotypes. Disturbingly, the prevalence of the disease has more than doubled since the 1980s, and efforts to understand this increase have led to the consideration of the microbiome, or the communities of microorganisms that dwell on and within us, as a key player in the pathology and regulation of this disease. While recent years have seen an explosion of new research in this area, we are only beginning to untangle to mechanisms by which the microbiome may influence asthma. Utilizing a house dust mite-induced model of experimental asthma, we explored the relationship between the microbiome and the development of both allergic airway disease and the development of tolerance and disease resolution. Herein, we report that HDM exposure has can alter the gut microbiome, producing distinct changes in the microbial community over the course of HDM exposure, but that these effects are not consistent between treatment groups. We demonstrate that oral tolerance is not inducible for HDM, in contrast to a large body of evidence in other experimental allergens such as ovalbumin, suggesting that the inhalational tolerance seen with this allergen forms by independent mechanisms within the lungs. We describe a new, clinically-relevant model of early-life antibiotic exposure that produces heightened asthma severity, including the first evidence that brief exposure to antibiotics after weaning is sufficient to alter the pathophysiology of asthma later in life. Furthermore, we demonstrate that the enhanced disease seen in this model may arise from deficiencies in pulmonary regulatory T Cells driven by loss of diversity in the microbiome. Finally, we explore the ability of antibiotic treatment to influence the development of inhalational tolerance, reporting that lifelong exposure to antibiotics can impair tolerance development through mechanisms that may be mediated by a loss of regulatory T and B Cells

Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells

The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). However, sBr’s effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL), spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes). OVA-specific IgE and OVA TET+ cells were decreased. sBr reduced CD11c+ dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena

ESO-Athena Synergy White Paper

The Advanced Telescope for High ENergy Astrophysics (Athena) is the X-ray observatory mission selected by ESA within its Cosmic Vision 2015-2025 programme to address the Hot and Energetic Universe scientific theme. The ESO-Athena Synergy Team (EAST) has been tasked to single out the potential scientific synergies between Athena and optical/near-infrared (NIR) and sub/mm ground based facilities, in particular those of ESO (i.e., the VLT and ELT, ALMA and APEX), by producing a White Paper to identify and develop the: 1. needs to access ESO ground-based facilities to achieve the formulated Athena science objectives; 2. needs to access Athena to achieve the formulated science objectives of ESO facilities contemporary to Athena; 3. science areas where the synergetic use of Athena and ESO facilities in the late 2020s will result in scientific added value. Community input to the process happened primarily via a dedicated ESO - Athena Synergy Workshop that took place on Sept. 14 - 16, 2016 at ESO, Garching. This White Paper presents the results of the EAST's work, sorted by synergy area, and deals with the following topics: 1. the Hot Universe: Early groups and clusters and their evolution, Physics of the Intracluster medium, Missing baryons in cosmic filaments; 2. the Energetic Universe: Supermassive black hole (SMBH) history, SMBH accretion disks, Active Galactic Nuclei feedback - Molecular outflows, Ultra-fast outflows, Accretion Physics, Transient Science; 3. Observatory Science: Star Formation, Stars. It then discusses the optical-NIR-sub-mm perspective by providing details on VLT/MOONS, the E-ELT instruments, in particular the MOS, VISTA/4MOST, the ESO and ALMA archives, future ALMA and ESO developments, and finally the (likely) ESO - Athena astronomical scene in the 2020s. (abridged)Comment: 70 pages, 16 figure

Receiver design for the REACH global 21-cm signal experiment

We detail the the REACH radiometric system designed to enable measurements of the 21-cm neutral hydrogen line. Included is the radiometer architecture and end-to-end system simulations as well as a discussion of the challenges intrinsic to highly-calibratable system development. Following this, we share laboratory results based on the calculation of noise wave parameters utilising an over-constrained least squares approach demonstrating a calibration RMSE of 80 mK for five hours of integration on a custom-made source with comparable impedance to that of the antenna used in the field. This paper therefore documents the state of the calibrator and data analysis in December 2022 in Cambridge before shipping to South Africa.Comment: 30 pages, 19 figure

Future Science Prospects for AMI

The Arcminute Microkelvin Imager (AMI) is a telescope specifically designed for high sensitivity measurements of low-surface-brightness features at cm-wavelength and has unique, important capabilities. It consists of two interferometer arrays operating over 13.5-18 GHz that image structures on scales of 0.5-10 arcmin with very low systematics. The Small Array (AMI-SA; ten 3.7-m antennas) couples very well to Sunyaev-Zel'dovich features from galaxy clusters and to many Galactic features. The Large Array (AMI-LA; eight 13-m antennas) has a collecting area ten times that of the AMI-SA and longer baselines, crucially allowing the removal of the effects of confusing radio point sources from regions of low surface-brightness, extended emission. Moreover AMI provides fast, deep object surveying and allows monitoring of large numbers of objects. In this White Paper we review the new science - both Galactic and extragalactic - already achieved with AMI and outline the prospects for much more

The XXL Survey: VI. The 1000 brightest X-ray point sources

X-ray extragalactic surveys are ideal laboratories for the study of the evolution and clustering of active galactic nuclei (AGN). The XXL Survey spans two fields of a combined 50 $deg^2$ observed for more than 6Ms with XMM-Newton, occupying the parameter space between deep surveys and very wide area surveys; at the same time it benefits from a wealth of ancillary data. This paper marks the first release of the XXL point source catalogue selected in the 2-10 keV energy band with limiting flux $F_{2-10keV}=4.8\cdot10^{-14}\rm{erg\,s^{-1}\,cm^{-2}}$. We use both public and proprietary data sets to identify the counterparts of the X-ray point-like sources and improved upon the photometric redshift determination for AGN by applying a Random Forest classification trained to identify for each object the optimal photometric redshift model library. We also assign a probability to each source to be a star or an outlier. We model with Bayesian analysis the X-ray spectra assuming a power-law model with the presence of an absorbing medium. We find an average unabsorbed photon index of $\Gamma=1.85$ and average hydrogen column density $\log{N_{H}}=21.07 cm^{-2}$. We find no trend of $\Gamma$ or $N_H$ with redshift and a fraction of 26% absorbed sources ($\log N_{H}>22$). We show that the XXL-1000-AGN number counts extended the number counts of the COSMOS survey to higher fluxes and are fully consistent with the Euclidean expectation. We constrain the intrinsic luminosity function of AGN in the 2-10 keV energy band where the unabsorbed X-ray flux is estimated from the X-ray spectral fit up to z=3. Finally, we demonstrate the presence of a supercluster size structure at redshift 0.14, identified by means of percolation analysis of the XXL-1000-AGN sample. The XXL survey, reaching a medium flux limit and covering a wide area is a stepping stone between current deep fields and planned wide area surveys

Association between thermal responses, medical events, performance, heat acclimation and health status in male and female elite athletes during the 2019 Doha World Athletics Championships

Please read abstract in the article.The World Athletics Health and Science Department.http://bjsm.bmj.comhj2022Sports Medicin

Utjecaj toksičnosti metala na reprodukcijsku funkciju u muškaraca

A combination of genetic, environmental and lifestyle factors contributes to adverse effects on the reproductive health in men. Metals are pervasive in food, water, air, tobacco smoke, and alcoholic beverages. Experimental studies suggest that many metals have adverse effects on the male reproductive function. However, information about reproductive effects of human exposure to metals is scarce and/or inconsistent. This review summarises the information from epidemiological studies of the effects of metal exposure on reproductive function in men. Factors capable of affecting these relationships were identifi ed and discussed. A particular attention is given to the studies considering influence of concomitant exposure to various metals. These studies have generally confirmed that even moderate- to low-level exposure to lead affects certain reproductive parameters, and that exposure to cadmium affects the prostate function and serum testosterone levels. Adverse effects of mercury, manganese, chromium and arsenic on semen quality and altered serum hormone are less well documented. There is no clear evidence that boron exposure may impair reproductive health in men. Only a few studies have investigated reproductive effects of concomitant exposure to several metals and controlled for potential confounders. Future studies should consider the contribution of combined exposure to various metals and/or other factors that may influence individual susceptibility to reproductive health impairment in men.Postoje indikacije da kombinacija genetskih, okolišnih i čimbenika načina života pridonosi uočenom poremećaju reprodukcijskog zdravlja u muškaraca. Metali su široko rasprostranjeni u čovjekovu okolišu te u hrani, vodi, zraku, cigaretnom dimu i alkoholnim pićima. Rezultati eksperimentalnih istraživanja sugeriraju štetne učinke većine ispitivanih metala na mušku reprodukcijsku funkciju. Međutim, odgovarajuća su istraživanja u ljudi oskudna. Ovaj rad sažima rezultate dosadašnjih epidemioloških istraživanja o učincima izloženosti metalima na mušku reprodukcijsku funkciju. Poseban naglasak dan je istraživanjima koja su razmatrala utjecaj istodobne izloženosti različitim metalima uz čimbenike čovjekova načina života i njihovo međudjelovanje na reprodukcijske učinke. Objavljeni rezultati daju dovoljno dokaza o štetnom djelovanju olova i žive na neke reprodukcijske parametre te kadmija na poremećaj prostate i razinu testosterona u serumu, čak u uvjetima umjerene do niske razine izloženosti. Manje je dokaza o štetnom djelovanju na kvalitetu sjemena i razinu spolnih hormona nađeno za mangan. Podaci koji upućuju na moguće štetno djelovanje arsena ili kroma nisu dosljedni, dok o štetnom djelovanju bora na mušku reprodukcijsku funkciju nema jasnih podataka. Utjecaj potencijalno uzročnih varijabli uzet je u obzir samo u nekoliko radova. Stoga buduća istraživanja poremećaja reprodukcijskog zdravlja u muškaraca trebaju razmatrati doprinos istovremene izloženosti različitim metalima koji u kombinaciji s ostalim čimbenicima mogu utjecati na osobnu (pre)osjetljivost

Human native kappa opioid receptor functions not predicted by recombinant receptors: Implications for drug design

International audienc