Lithium attenuates TGF- β_1-induced fibroblasts to myofibroblasts transition in bronchial fibroblasts derived from asthmatic patients

Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs) derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β1-induced fibroblast to myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3β attenuates TGF-β1-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β1/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases

miR-200b downregulates CFTR during hypoxia in human lung epithelial cells

Abstract Background Hypoxic conditions induce the expression of hypoxia-inducible factors (HIFs) that allow cells to adapt to the changing conditions and alter the expression of a number of genes including the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is a low abundance mRNA in airway epithelial cells even during normoxic conditions, but during hypoxia its mRNA expression decreases even further. Methods In the current studies, we examined the kinetics of hypoxia-induced changes in CFTR mRNA and protein levels in two human airway epithelial cell lines, Calu-3 and 16HBE14o-, and in normal primary bronchial epithelial cells. Our goal was to examine the posttranscriptional modifications that affected CFTR expression during hypoxia. We utilized in silico predictive protocols to establish potential miRNAs that could potentially regulate CFTR message stability and identified miR-200b as a candidate molecule. Results Analysis of each of the epithelial cell types during prolonged hypoxia revealed that CFTR expression decreased after 12 h during a time when miR-200b was continuously upregulated. Furthermore, manipulation of the miRNA levels during normoxia and hypoxia using miR-200b mimics and antagomirs decreased and increased CFTR mRNA levels, respectively, and thus established that miR-200b downregulates CFTR message levels during hypoxic conditions. Conclusion The data suggest that miR-200b may be a suitable target for modulating CFTR levels in vivo

Experimental probing of exchange interactions between localized spins in the dilute magnetic insulator (Ga,Mn)N

The sign, magnitude, and range of the exchange couplings between pairs of Mn ions is determined for (Ga,Mn)N and (Ga,Mn)N:Si with x < 3%. The samples have been grown by metalorganic vapor phase epitaxy and characterized by secondary-ion mass spectroscopy; high-resolution transmission electron microscopy with capabilities allowing for chemical analysis, including the annular dark-field mode and electron energy loss spectroscopy; high-resolution and synchrotron x-ray diffraction; synchrotron extended x-ray absorption fine-structure; synchrotron x-ray absorption near-edge structure; infra-red optics and electron spin resonance. The results of high resolution magnetic measurements and their quantitative interpretation have allowed to verify a series of ab initio predictions on the possibility of ferromagnetism in dilute magnetic insulators and to demonstrate that the interaction changes from ferromagnetic to antiferromagnetic when the charge state of the Mn ions is reduced from 3+ to 2+.Comment: 12 pages, 14 figures; This version contains the detailed characterization of the crystal structure as well as of the Mn distribution and charge stat

Conductance spectra of (Nb, Pb, In)/NbP -- superconductor/Weyl semimetal junctions

The possibility of inducing superconductivity in type-I Weyl semimetal through coupling its surface to a superconductor was investigated. A single crystal of NbP, grown by chemical vapor transport method, was carefully characterized by XRD, EDX, SEM, ARPES techniques and by electron transport measurements. The mobility spectrum of the carriers was determined. For the studies of interface transmission, the (001) surface of the crystal was covered by several hundred nm thick metallic layers of either Pb, or Nb, or In. DC current-voltage characteristics and AC differential conductance through the interfaces as a function of the DC bias were investigated. When the metals become superconducting, all three types of junctions show conductance increase, pointing out the Andreev reflection as a prevalent contribution to the subgap conductance. In the case of Pb-NbP and Nb-NbP junctions, the effect is satisfactorily described by modified Blonder-Tinkham-Klapwijk model. The absolute value of the conductance is much smaller than that for the bulk crystal, indicating that the transmission occurs through only a small part of the contact area. An opposite situation occurs in In-NbP junction, where the conductance at the peak reaches the bulk value indicating that almost whole contact area is transmitting and, additionally, a superconducting proximity phase is formed in the material. We interpret this as a result of indium diffusion into NbP, where the metal atoms penetrate the surface barrier and form very transparent superconductor-Weyl semimetal contact inside. However, further diffusion occurring already at room temperature leads to degradation of the effect, so it is observed only in the pristine structures. Despite of this, our observation directly demonstrates possibility of inducing superconductivity in a type-I Weyl semimetal.Comment: Accepted for Phys. Rev. B. 13 pages, 12 figures. Second version with major revisions. The title was changed. One author R. Jakiela added. New inset to Fig. 8(A). New fits in Fig. 8 (B) and Fig. 10 (B). Added figures 12 (C)-(E). Added Fig. 12 (F) with SIMS data. Rewritten chapters III-C-2 and III-C-3. Reference no. 38 removed, 11 new references: 9, 21, 22, 40-44, 46-49 were adde