c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration

AbstractCytoskeleton dynamics are regulated by Src-family tyrosine kinases (SFKs) and c-Abl. We found that the SFK members Hck and c-Fgr regulate tyrosine phosphorylation of c-Abl and c-Abl associates with β1 integrin-bound Hck or c-Fgr in murine macrophages. Studies with selective inhibitors and cells from SFK-deficient mice showed that c-Abl and SFK regulate migration and activation of the small GTPases Cdc42 and Rac in macrophages. Additionally, human neutrophil chemotactic activity was reduced by c-Abl inhibitors, and neutrophils from chronic myeloid leukaemia patients displayed an increased chemotactic ability. Hence, Src-family kinase and c-Abl cross-talk in the regulation of myeloid cell migration.Structured summaryMINT-7296608: Integrin beta-1 (uniprotkb:P09055) physically interacts (MI:0914) with Hck (uniprotkb:P08103), Abl (uniprotkb:P00520) and Fgr (uniprotkb:P14234) by anti bait coimmunoprecipitation (MI:0006) MINT-7296596: Integrin beta-1 (uniprotkb:P09055) physically interacts (MI:0914) with Fgr (uniprotkb:P14234) and Abl (uniprotkb:P00520) by anti bait coimmunoprecipitation (MI:0006

Double-check: validation of diagnostic statistics for PLS-DA models in metabolomics studies

Partial Least Squares-Discriminant Analysis (PLS-DA) is a PLS regression method with a special binary ‘dummy’ y-variable and it is commonly used for classification purposes and biomarker selection in metabolomics studies. Several statistical approaches are currently in use to validate outcomes of PLS-DA analyses e.g. double cross validation procedures or permutation testing. However, there is a great inconsistency in the optimization and the assessment of performance of PLS-DA models due to many different diagnostic statistics currently employed in metabolomics data analyses. In this paper, properties of four diagnostic statistics of PLS-DA, namely the number of misclassifications (NMC), the Area Under the Receiver Operating Characteristic (AUROC), Q2 and Discriminant Q2 (DQ2) are discussed. All four diagnostic statistics are used in the optimization and the performance assessment of PLS-DA models of three different-size metabolomics data sets obtained with two different types of analytical platforms and with different levels of known differences between two groups: control and case groups. Statistical significance of obtained PLS-DA models was evaluated with permutation testing. PLS-DA models obtained with NMC and AUROC are more powerful in detecting very small differences between groups than models obtained with Q2 and Discriminant Q2 (DQ2). Reproducibility of obtained PLS-DA models outcomes, models complexity and permutation test distributions are also investigated to explain this phenomenon. DQ2 and Q2 (in contrary to NMC and AUROC) prefer PLS-DA models with lower complexity and require higher number of permutation tests and submodels to accurately estimate statistical significance of the model performance. NMC and AUROC seem more efficient and more reliable diagnostic statistics and should be recommended in two group discrimination metabolomic studies

Hybrid Halloysite Nanotubes as Smart Carriers for Corrosion Protection

Novel hybrid halloysite nanotubes (HHNTs) were developed and used as smart carriers for corrosion protection of steel. For this purpose, as-received halloysite nanotubes (HNTs) were loaded with a corrosion inhibitor, imidazole (IM), by vacuum encapsulation. In the next step, a layer by layer technique was employed to intercalate another inhibitor, dodecylamine (DDA), in the polyelectrolyte multilayers of polyethylenimine and sulfonated polyether ether ketone, leading to the formation of HHNTs. During this process, IM (5 wt %) was successfully encapsulated into the lumen of HNTs, while DDA (0.4 wt %) was effectively intercalated into the polyelectrolyte layers. Later, the HHNTs (3 wt %) were thoroughly dispersed into the epoxy matrix to develop smart hybrid self-healing polymeric coatings designated as hybrid coatings. For a precise evaluation, epoxy coatings containing as-received HNTs (3 wt %) without any loading denoted to as reference coatings and modified coatings containing HNTs loaded with IM-loaded HNTs (3 wt %) were also developed. A comparative analysis elucidates that the hybrid coatings demonstrate decent thermal stability, improved mechanical properties, and promising anticorrosion properties compared to the reference and modified coatings. The calculated corrosion inhibition efficiencies of the modified and hybrid coatings are 92 and 99.8%, respectively, when compared to the reference coatings. Noticeably, the superior anticorrosion properties of hybrid coatings can be attributed to the synergetic effect of both the inhibitors loaded into HHNTs and their efficient release in response to the localized pH change of the corrosive medium. Moreover, IM shows an active release in both acidic and basic media, which makes it suitable for the protection of steel at the early stages of damage, while DDA being efficiently released in the acidic medium may contribute to impeding the corrosion activity at the later stages of deterioration. The tempting properties of hybrid coatings demonstrate the beneficial role of the development of novel HHNTs and their use as smart carriers in the polymeric matrix for corrosion protection of steel.This publication was made possible by NPRP11S-1226-170132 from Qatar National Research Fund (a member of the Qatar Foundation). Statements made herein are solely the responsibility of the authors. The authors would like to thank the Central laboratory Unit (CLU), Qatar University, for SEM analysis. The authors also acknowledge the support of Core lab-QEERI (HBKU) for proving TEM analysis.Scopu