Fractional Hardy-Sobolev type inequalities for half spaces and John domains

As our main result we prove a variant of the fractional Hardy-Sobolev-Maz'ya inequality for half spaces. This result contains a complete answer to a recent open question by Musina and Nazarov. In the proof we apply a new version of the fractional Hardy-Sobolev inequality that we establish also for more general unbounded John domains than half spaces

MOESM1 of Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b

Additional file 1: Figure S1. Evaluation of changes in H3 PTMs following vitamin C treatment. A) Western blot for several H3 PTMs in ES cells ± vitamin C. B) Immunofluorescence for H3K9me2 and corresponding DAPI staining in untreated and vitamin C-treated ES cells. Merged images show H3K9me2 in green and DAPI staining in red. H3K9me2 immunofluorescence is also shown in Fig. 1e. Scale bar represents 20 μm

MOESM4 of Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b

Additional file 4: Figure S4. Analysis of H3K9me2 at repetitive elements in ES cells treated with vitamin C. ChIP-qPCR for H3K9me2 in ES cells ± vitamin C at the repetitive element families indicated. ChIP for IgG was performed as a negative control. Data are mean ± SD. Asterisks represent P < 0.05 by t test

MOESM2 of Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b

Additional file 2: Figure S2. Analysis of H3K9me2 in G9a and GLP knockout ES cells treated with vitamin C. A) Western blot for H3K9me2 in wild-type parental TT2, G9a knockout, and GLP knockout ES cells ± vitamin C. B) Immunofluorescence for H3K9me2 in GiP ES cells ± vitamin C and untreated wild-type TT2, G9a knockout, and GLP knockout ES cells. GiP ES cells treated with vitamin C show a H3K9me2 staining pattern that is similar to G9a and GLP knockout ES cells. Scale bar represents 20 μm

A randomised, placebo-controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER).

BACKGROUND:The anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate to severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling. OBJECTIVE:To report safety and efficacy results from enrolled participants with available data from CLAVIER. METHODS:We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomised double-blinded treatment with lebrikizumab (n=31) or placebo (n=33). The pre-specified primary endpoint was relative change in airway subepithelial eosinophils per mm2 of basement membrane (cells/mm2 ). Pre-specified secondary and exploratory outcomes included change in IL-13-associated biomarkers and measures of airway remodelling. RESULTS:There was a baseline imbalance in tissue eosinophils and high variability between treatment groups. There was no discernible change in adjusted mean subepithelial eosinophils/mm2 in response to lebrikizumab (95% CI, -82.5%, 97.5%). As previously observed, FEV1 increased after lebrikizumab treatment. Moreover, subepithelial collagen thickness decreased 21.5% after lebrikizumab treatment (95% CI, -32.9%, -10.2%), and fractional exhaled nitric oxide, CCL26, and SERPINB2 mRNA expression in bronchial tissues also reduced. Lebrikizumab was well tolerated, with a safety profile consistent with other lebrikizumab asthma studies. CONCLUSIONS & CLINICAL RELEVANCE:We did not observe reduced tissue eosinophil numbers in association with lebrikizumab treatment. However, in pre-specified exploratory analyses, lebrikizumab treatment was associated with reduced degree of subepithelial fibrosis, a feature of airway remodelling, as well as improved lung function and reduced key pharmacodynamic biomarkers in bronchial tissues. These results reinforce the importance of IL-13 in airway pathobiology and suggest that neutralisation of IL-13 may reduce asthmatic airway remodelling.</div