HAIRY-like Transcription Factors and the Evolution of the Nematode Vulva Equivalence Group

SummaryBackgroundNematode vulva formation provides a paradigm to study the evolution of pattern formation and cell-fate specification. The Caenorhabditis elegans vulva is generated from three of six equipotent cells that form the so-called vulva equivalence group. During evolution, the size of the vulva equivalence group has changed: Panagrellus redivivus has eight, C. elegans six, and Pristionchus pacificus only three cells that are competent to form vulval tissue. In P. pacificus, programmed cell death of individual vulval precursor cells alters the size of the vulva equivalence group.ResultsWe have identified the genes controlling this cell-death event and the molecular mechanism of the reduction of the vulva equivalence group. Mutations in Ppa-hairy, a gene that is unknown from C. elegans, result in the survival of two precursor cells, which expands the vulva equivalence group. Mutations in Ppa-groucho cause a similar phenotype. Ppa-HAIRY and Ppa-GROUCHO form a molecular module that represses the Hox gene Ppa-lin-39 and thereby reduces the size of the vulva equivalence group. The C. elegans genome does not encode a similar hairy-like gene, and no typical HAIRY/GROUCHO module exists.ConclusionsWe conclude that the vulva equivalence group in Pristionchus is patterned by a HAIRY/GROUCHO module, which is absent in Caenorhabditis. Thus, changes in the number, structure, and function of nematode hairy-like transcription factors are involved in the evolutionary alteration of this equivalence group

Impact of the COVID ‐19 pandemic on patients with hidradenitis suppurativa

The COVID-19 pandemic caused collateral damage to patients with acute and chronic conditions. In this mono-centre cross-sectional study, we sought to evaluate the impact of the COVID-19 pandemic on patients with hidradenitis suppurativa (HS). In June 2020, we sent an anonymous survey to 109 patients, who were diagnosed with HS in our outpatient clinic from May 2018 to April 2020. Fifty patients (45.9%) completed and returned the survey. Forty-five participants (90.0%) denied any cancellation of hospitalisation due to the COVID-19 pandemic. Hospitalisation was postponed in 8% of cases and cancelled in 2%. Compared to prior to the pandemic, fewer patients consulted their primary physician for changing wound dressings and more changed the dressings themselves or were assisted by their family members. 13% of patients avoided doctor visits due to fear of COVID-19 and 26.1% minimised doctor visits. The Dermatology Life Quality Index showed a moderate to very severe impact on patients' Quality of Life (mean score = 10.06). Only one patient used telemedicine. Due to limited access to primary care and fear of COVID-19, the pandemic had a detectable impact on the hospital management of patients with HS in our facility. Telemedicine still plays a negligible role in primary wound care

Efficacy and safety of medications for antihistamine-refractory chronic spontaneous urticaria: a systematic review and network meta-analysis

Purpose Most medications for antihistamine-refractory chronic spontaneous urticaria (CSU) have not been compared head-to-head. This systematic review and network meta-analysis evaluates their relative efficacy and safety. Methods Electronic databases were searched until 05 May 2022 for randomized controlled trials investigating systemic medications for antihistamine-refractory CSU. The change in the urticaria activity score over seven days (UAS7) and occurrence of adverse events were compared between treatments using random-effects network meta-analysis models. Results In all, 32 studies with 3641 patients receiving 31 different systemic medical interventions were included. Among currently available drugs, omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os were most effective in reducing the UAS7 with a reduction of −10.45 (95% confidence interval [CI]: −12.35, −8.55) and of −10.40 (95% CI: −19.4, −1.4) compared to placebo. Similar efficacies were shown by the nonapproved agents ligelizumab 72 mg injected every 4 weeks (−11.67, 95% CI: −16.80, −7.15) and fenebrutinib 400 mg daily per os (−9.50, 95% CI: −17.56, −1.44). The odds ratio for the occurrence of an adverse event with placebo as comparator was 1.09 for omalizumab (95% CI: 0.83, 1.42), 2.16 for cyclosporine (95% CI: 0.77, 6.07: GRADE; moderate certainty), 0.89 for ligelizumab (95% CI: 0.47, 1.69), and 2.14 for fenebrutinib (95% CI: 0.62, 7.38) in the mentioned dosages. Conclusion Omalizumab 300 mg injected every 4 weeks and cyclosporine 3–5 mg/kg daily per os are the most effective currently available drugs for antihistamine-refractory CSU. Cyclosporine shows a relatively less favorable safety profile

Airborne observations of peroxy radicals during the EMeRGe campaign in Europe

In this study, airborne measurements of the sum of hydroperoxyl (HO$_2$) and organic peroxy (RO$_2$) radicals that react with nitrogen monoxide (NO) to produce nitrogen dioxide (NO$_2$), coupled with actinometry and other key trace gases measurements, have been used to test the current understanding of the fast photochemistry in the outflow of major population centres. The measurements were made during the airborne campaign of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) project in Europe on board the High Altitude and Long Range Research Aircraft (HALO). The measurements of RO$^∗_2$ on HALO were made using the in situ instrument Peroxy Radical Chemical Enhancement and Absorption Spectrometer (PeRCEAS). RO$^∗_2$ is to a good approximation the sum of peroxy radicals reacting with NO to produce NO$_2$. RO$^∗_2$ mixing ratios up to 120 pptv were observed in air masses of different origins and composition under different local actinometric conditions during seven HALO research flights in July 2017 over Europe. Radical production rates were estimated using knowledge of the photolysis frequencies and the RO$^∗_2$ precursor concentrations measured on board, as well as the relevant rate coefficients. Generally, high RO$^∗_2$ concentrations were measured in air masses with high production rates. In the air masses investigated, RO$^∗_2$ is primarily produced by the reaction of O$^1$D with water vapour and the photolysis of nitrous acid (HONO) and of the oxygenated volatile organic compounds (OVOCs, e.g. formaldehyde (HCHO) and glyoxal (CHOCHO)). Due to their short lifetime in most environments, the RO$^∗_2$ concentrations are expected to be in a photostationary steady state (PSS), i.e. a balance between production and loss rates is assumed. The RO$^∗_2$ production and loss rates and the suitability of PSS assumptions to estimate the RO$^∗_2$ mixing ratios and variability during the airborne observations are discussed. The PSS assumption for RO$^∗_2$ is considered robust enough to calculate RO$^∗_2$ mixing ratios for most conditions encountered in the air masses measured. The similarities and discrepancies between measured and PSS calculated RO$^∗_2$ mixing ratios are discussed. The dominant terminating processes for RO$^∗_2$ in the pollution plumes measured up to 2000 m are the formation of nitrous acid, nitric acid, and organic nitrates. Above2000 m, HO$_2$–HO$_2$ and HO$_2$–RO$_2$ reactions dominate the RO$^∗_2$ removal. RO$^∗_2$ calculations by the PSS analytical expression inside the pollution plumes probed often underestimated the measurements. The underestimation is attributed to the limitations of the PSS equation used for the analysis. In particular, this expression does not account for the yields of RO$^∗_2$ from the oxidation and photolysis of volatile organic compounds, VOCs, and OVOCs other than those measured during the EMeRGe research flights in Europe. In air masses with NO mixing ratios ≤ 50 pptv and low VOC/NO ratios, the RO$^∗_2$ measured is overestimated by the analytical expression. This may be caused by the formation of H$_2$O and O$_2$ from OH and HO$_2$, being about 4 times faster than the rate of the OH oxidation reaction of the dominant OVOCs considered

Metabolic Profiling as Well as Stable Isotope Assisted Metabolic and Proteomic Analysis of RAW 264.7 Macrophages Exposed to Ship Engine Aerosol Emissions: Different Effects of Heavy Fuel Oil and Refined Diesel Fuel

Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO. In order to further understand these effects, as well as to validate these findings in another cell line, we investigated macrophages under the same conditions as a more inflammationrelevant model. An air-liquid interface aerosol exposure system was used to provide a more biologically relevant exposure system compared to submerged experiments, with cells exposed to either the complete aerosol (particle and gas phase), or the gas phase only (with particles filtered out). Data from cytotoxicity assays were integrated with metabolomics and proteomics analyses, including stable isotope-assisted metabolomics, in order to uncover pathways affected by combustion aerosol exposure in macrophages. Through this approach, we determined differing phenotypic effects associated with the different components of aerosol. The particle phase of diluted combustion aerosols was found to induce increased cell death in macrophages, while the gas phase was found more to affect the metabolic profile. In particular, a higher cytotoxicity of DF aerosol emission was observed in relation to the HFO aerosol. Furthermore, macrophage exposure to the gas phase of HFO leads to an induction of a pro-inflammatory metabolic and proteomic phenotype. These results validate the effects found in lung epithelial cells, confirming the role of inflammation and cellular stress in the response to combustion aerosols

Effects of transport on a biomass burning plume from Indochina during EMeRGe-Asia identified by WRF-Chem

The Indochina biomass burning (BB) season in springtime has a substantial environmental impact on the surrounding areas in Asia. In this study, we evaluated the environmental impact of a major long-range BB transport event on 19 March 2018 (a flight of the High Altitude and Long Range Research Aircraft (HALO; https://www.halo-spp.de, last access: 14 February 2023) research aircraft, flight F0319) preceded by a minor event on 17 March 2018 (flight F0317). Aircraft data obtained during the campaign in Asia of the Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales (EMeRGe) were available between 12 March and 7 April 2018. In F0319, results of 1 min mean carbon monoxide (CO), ozone (O$_3$), acetone (ACE), acetonitrile (ACN), organic aerosol (OA), and black carbon aerosol (BC) concentrations were up to 312.0, 79.0, 3.0, and 0.6 ppb and 6.4 and 2.5 µg m$^{−3}$, respectively, during the flight, which passed through the BB plume transport layer (BPTL) between the elevation of 2000–4000 m over the East China Sea (ECS). During F0319, the CO, O$_3$, ACE, ACN, OA, and BC maximum of the 1 min average concentrations were higher in the BPTL by 109.0, 8.0, 1.0, and 0.3 ppb and 3.0 and 1.3 µg m$^{−3}$ compared to flight F0317, respectively. Sulfate aerosol, rather than OA, showed the highest concentration at low altitudes (<1000 m) in both flights F0317 and F0319 resulting from the continental outflow in the ECS. The transport of BB aerosols from Indochina and its impacts on the downstream area were evaluated using a Weather Research Forecasting with Chemistry (WRF-Chem) model. The modeling results tended to overestimate the concentration of the species, with examples being CO (64 ppb), OA (0.3 µg m$^{−3}$), BC (0.2 µg m$^{−3}$), and O$_3$ (12.5 ppb) in the BPTL. Over the ECS, the simulated BB contribution demonstrated an increasing trend from the lowest values on 17 March 2018 to the highest values on 18 and 19 March 2018 for CO, fine particulate matter (PM$_{2.5}$), OA, BC, hydroxyl radicals (OH), nitrogen oxides (NO$_x$), total reactive nitrogen (NO$_y$), and O$_3$; by contrast, the variation of J(O$^1$D) decreased as the BB plume\u27s contribution increased over the ECS. In the lower boundary layer (<1000 m), the BB plume\u27s contribution to most species in the remote downstream areas was <20 %. However, at the BPTL, the contribution of the long-range transported BB plume was as high as 30 %–80 % for most of the species (NO$_y$, NO$_x$, PM$_{2.5}$, BC, OH, O$_3$, and CO) over southern China (SC), Taiwan, and the ECS. BB aerosols were identified as a potential source of cloud condensation nuclei, and the simulation results indicated that the transported BB plume had an effect on cloud water formation over SC and the ECS on 19 March 2018. The combination of BB aerosol enhancement with cloud water resulted in a reduction of incoming shortwave radiation at the surface in SC and the ECS by 5 %–7 % and 2 %–4 %, respectively, which potentially has significant regional climate implications

Mononuclear cell composition and activation in blood and mucosal tissue of eosinophilic esophagitis

IntroductionEosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4+ T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing.MethodsIn this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus.ResultsOur results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4+ T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4+ and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4+ T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE.DiscussionHerein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter