Immune cell profiling reveals natural killer and T cell subpopulations to be associated with atopic dermatitis severity

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a genetically determined impaired epidermal barrier function and predisposition to develop other atopic comorbidities.The role of adaptive and innate immunity, in particular IL- 4 and IL- 13 and T lymphocyte populations in AD pathogenesis are established, but the exact cellular mechanisms are not fully understood. At least partially, this is attributed to technical limitations of flow cytometry, that is, limited channels and signal spillover. Mass cytometry overcomes these limitations and allows advanced bioinformatic methods. An unbiased comprehensive analysis of the total peripheral immune cell pool in AD is not available

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

Postoperative dizziness after cochlear implant surgery: can it be caused by air?

ObjectivesMultiple studies have described the onset and variable incidence of postoperative acute vertigo following cochlear implant (CI) surgery. However, postoperative imaging has not yet been specifically evaluated with special focus on vertigo. The aim of this study is to assess the incidence and causes of new-onset, acute postoperative vertigo following CI surgery using cone beam computed tomography (CBCT).Materials and methodsThis is a retrospective study involving ten patients who experienced postoperative dizziness and ten matched controls without dizziness. All patients received a cochlear implant (CI) between 2020 and 2024. The matching analysis was performed based on the implant, electrode array, and access to the cochlear. We analyzed the postoperative CBCT scans for changes suspicious of air trapping, a so-called pneumolabyrinth in the vestibule using minimal Hounsfield Units (HU).ResultsWe compared postoperative CBCT images for electrode array position monitoring in ten patients with vertigo versus ten patients without vertigo after CI surgery. Among the ten patients with postoperative dizziness, six showed suspicious changes in the vestibule consistent with the presence of air. These air-related changes were observed in the vestibule and, in one patient, additionally in the horizontal semicircular canal. Minimal HU were significantly different and confirmed the suspicion of intravestibular air.ConclusionThis is the first study to describe the suspicion of intravestibular air in CI patients with postoperative vertigo. Therefore, suctioning after the fenestration of the round window membrane or the endosteum after cochleostomy, as well as actions such as bending, pressing, and nose-blowing by the patient, should be strictly avoided. Furthermore, this finding highlights the importance of carefully sealing the electrode array at the cochleostomy site with connective tissue. Risk factors for the development of a pneumolabyrinth with air in the vestibule include intralabyrinthine or intracranial pressure changes, large cochleostomies or a second cochleostomy and electrode placement in the scala tympani

Metalloporphyrins on Oxygen-Passivated Iron: Conformation and Order Beyond the First Layer

On-surface metal porphyrins can undergo electronic and conformational changes that play a crucial role in determining the chemical reactivity of the molecular layer. Therefore, understanding those properties is pivotal for the design and implementation of organic-based devices. Here, by means of photoemission orbital tomography supported by density functional theory calculations, we investigate the electronic and geometrical structure of two metallated tetraphenyl porphyrins (MTPPs), namely ZnTPP and NiTPP, adsorbed on the oxygen-passivated Fe(100)-p(1x1)O surface. Both molecules weakly interact with the surface as no charge transfer is observed. In the case of ZnTPP our data correspond to those of moderately distorted molecules, while NiTPP exhibits a severe saddle-shape deformation. From additional experiments on NiTPP multilayer films, we conclude that this distortion is a consequence of the interaction with the substrate, as the NiTPP macrocycle of the second layer turns out to be flat. We further find that distortions in the MTPP macrocycle are accompanied by an increasing energy gap between the highest occupied molecular orbitals (HOMO and HOMO-1). Our results demonstrate that photoemission orbital tomography can simultaneously probe the energy level alignment, the azimuthal orientation, and the adsorption geometry of complex aromatic molecules even in the multilayer regime

Growth independent rhamnolipid production from glucose using the non-pathogenic Pseudomonas putida KT2440

Wittgens A, Tiso T, Arndt TT, et al. Growth independent rhamnolipid production from glucose using the non-pathogenic Pseudomonas putida KT2440. Microbial Cell Factories. 2011;10(1): 80.**Abstract** **Background** Rhamnolipids are potent biosurfactants with high potential for industrial applications. However, rhamnolipids are currently produced with the opportunistic pathogenPseudomonas aeruginosaduring growth on hydrophobic substrates such as plant oils. The heterologous production of rhamnolipids entails two essential advantages: Disconnecting the rhamnolipid biosynthesis from the complex quorum sensing regulation and the opportunity of avoiding pathogenic production strains, in particularP. aeruginosa. In addition, separation of rhamnolipids from fatty acids is difficult and hence costly. **Results** Here, the metabolic engineering of a rhamnolipid producingPseudomonas putidaKT2440, a strain certified as safety strain using glucose as carbon source to avoid cumbersome product purification, is reported. Notably,P. putidaKT2440 features almost no changes in growth rate and lag-phase in the presence of high concentrations of rhamnolipids (> 90 g/L) in contrast to the industrially important bacteriaBacillus subtilis, Corynebacterium glutamicum, andEscherichia coli. P. putidaKT2440 expressing therhlAB-genes fromP. aeruginosaPAO1 produces mono-rhamnolipids ofP. aeruginosaPAO1 type (mainly C10:C10). The metabolic network was optimized in silico for rhamnolipid synthesis from glucose. In addition, a first genetic optimization, the removal of polyhydroxyalkanoate formation as competing pathway, was implemented. The final strain had production rates in the range ofP. aeruginosaPAO1 at yields of about 0.15 g/gglucosecorresponding to 32% of the theoretical optimum. What's more, rhamnolipid production was independent from biomass formation, a trait that can be exploited for high rhamnolipid production without high biomass formation. **Conclusions** A functional alternative to the pathogenic rhamnolipid producerP. aeruginosawas constructed and characterized.P. putidaKT24C1 pVLT31_rhlABfeatured the highest yield and titer reported from heterologous rhamnolipid producers with glucose as carbon source. Notably, rhamnolipid production was uncoupled from biomass formation, which allows optimal distribution of resources towards rhamnolipid synthesis. The results are discussed in the context of rational strain engineering by using the concepts of synthetic biology like chassis cells and orthogonality, thereby avoiding the complex regulatory programs of rhamnolipid production existing in the natural producerP. aeruginosa. </p

Проект узла гидрирования сернистых соединений

Конструирование аппарата для гидрирования сернистых соединений содержащихся в природном газе, а также исследование методов очистки природного газа.Designing an apparatus for hydrogenating sulfur compounds in natural gas, and studying methods for purifying natural gas

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p < 1 x 10(-8)) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene;rs17663182 p = 4.73 x 10(-9)), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter;rs16928927, p = 2.25 x 10(-8)). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 x 10(-8)) and with all the cognitive traits tested (p = 3.07 x 10(-8)), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p similar to [10(-5)-10(-7)]) and negatively associated with ADHD PRS (p similar to [10(-8)-10(-17)]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p <2.8 x 10(-6)) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atp(T) = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p = 8 x 10(-13)), bipolar disorder (1.53[1.44; 1.63];p = 1 x 10(-43)), schizophrenia (1.36[1.28; 1.45];p = 4 x 10(-22)), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 x 10(-12)), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 x 10(-4)), educational attainment (0.86[0.82; 0.91];p = 2 x 10(-7)), and intelligence (0.72[0.68; 0.76];p = 9 x 10(-29)). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.Peer reviewe

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Search for supersymmetry in final states with photons and missing transverse momentum in proton-proton collisions at 13 TeV

Results are reported of a search for supersymmetry in final states with photons and missing transverse momentum in proton-proton collisions at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb collected at a center-of-mass energy of 13 TeV using the CMS detector. The results are interpreted in the context of models of gauge-mediated supersymmetry breaking. Production cross section limits are set on gluino and squark pair production in this framework. Gluino masses below 1.86 TeV and squark masses below 1.59 TeV are excluded at 95% confidence levelIndividuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract No. 675440 (European Union); the Leventis Foundation; the A.P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation a la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the F.R.S.-FNRS and FWO (Belgium) under the “Excellence of Science — EOS” — be.h project n. 30820817; the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Lendület (“Momentum”) Program and the J´anos Bolyai Research Scholarship of the Hungarian Academy of Sciences, the New National Excellence Program UNKP, the NKFIA research grants 123842, 123959, 124845, 124850 and 125105 (Hungary); the Council of Science and Industrial Research, India; the HOMING PLUS program of the Foundation for Polish Science, cofinanced from European Union, Regional Development Fund, the Mobility Plus program of the Ministry of Science and Higher Education, the National Science Center (Poland), contracts Harmonia 2014/14/M/ST2/00428, Opus 2014/13/B/ST2/02543, 2014/15/B/ST2/03998, and 2015/19/B/ST2/02861, Sonata-bis 2012/07/E/ST2/01406; the National Priorities Research Program by Qatar National Research Fund; the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015-0509 and the Programa Severo Ochoa del Principado de Asturias; the Thalis and Aristeia programs cofinanced by EU-ESF and the Greek NSRF; the Rachadapisek Sompot Fund for Postdoctoral Fellowship, Chulalongkorn University and the Chulalongkorn Academic into Its 2nd Century Project Advancement Project (Thailand); the Welch Foundation, contract C-1845; and the Weston Havens Foundation (U.S.A.)