Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface

The cystic fibrosis transmembrane conductance regulator (CFTR) gene is influenced by the fundamental cellular processes like epithelial differentiation/polarization, regeneration and epithelial–mesenchymal transition. Defects in CFTR protein levels and/or function lead to decreased airway surface liquid layer facilitating microbial colonization and inflammation. The SERPINA1 gene, encoding alpha1-antitrypsin (AAT) protein, is one of the genes implicated in CF, however it remains unknown whether AAT has any influence on CFTR levels. In this study we assessed CFTR protein levels in primary human lung epithelial cells grown at the air-liquid-interface (ALI) alone or pre-incubated with AAT by Western blots and immunohistochemistry. Histological analysis of ALI inserts revealed CFTR- and AAT-positive cells but no AAT-CFTR co-localization. When 0.5 mg/mL of AAT was added to apical or basolateral compartments of pro-inflammatory activated ALI cultures, CFTR levels increased relative to activated ALIs. This finding suggests that AAT is CFTR-modulating protein, albeit its effects may depend on the concentration and the route of administration. Human lung epithelial ALI cultures provide a useful tool for studies in detail how AAT or other pharmaceuticals affect the levels and activity of CFTR.     

Shortwave Infrared Fluorofluorophores for Multicolor In Vivo Imaging**

Developing chemical tools to detect and influence biological processes is a cornerstone of chemical biology. Here we combine two tools which rely on orthogonality– perfluorocarbons and multiplexed shortwave infrared (SWIR) fluorescence imaging– to visualize nanoemulsions in real time in living mice. Drawing inspiration from fluorous and SWIR fluorophore development, we prepared two SWIR-emissive, fluorous-soluble chromenylium polymethine dyes. These are the most red-shifted fluorous fluorophores– “fluorofluorophores”—to date. After characterizing the dyes, their utility was demonstrated by tracking perfluorocarbon nanoemulsion biodistribution in vivo. Using an excitation-multiplexed approach to image two variables simultaneously, we gained insight into the importance of size and surfactant identity on biodistribution.     

Application of a Viscoelastic Material Model in Electro-Mechanics

In this contribution, the numerical modeling of electro-viscoelastic material is considered. The electro-mechanical problem formulated in terms of a symmetrized stress tensor is extended to a viscoelastic material model. For the incorporation of the viscosity model, the logarithmic strain space setting is utilized which mimics the small strain setting. Therefore a rheological model for viscosity from the geometrically linear theory can be used. Numerical examples for a typical uniaxial tensile test show the capability of the method to demonstrate typical relaxation and creep behavior. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Higher Flavor Symmetries in the Standard Model

A study of the generalized global flavor symmetries of the Standard Model is initiated. The presence of nonzero triangle diagrams between the U(3)⁵ flavor currents and the $U{(1)}_Y$ hypercharge current intertwines them in the form of a higher-group which mixes the zero-form flavor symmetries with the one-form magnetic hypercharge symmetry. This higher symmetry structure greatly restricts the possible flavor symmetries that may remain unbroken in any ultraviolet completion that includes magnetic monopoles. In the context of unification, this implies tight constraints on the combinations of fermion species which may be joined into multiplets. Three of four elementary possibilities are reflected in the classic unification models of Georgi–Glashow, $SO(10)$, and Pati–Salam. The final pattern is realized non-trivially in trinification, which exhibits the sense in which Standard Model Yukawa couplings which violate these flavor symmetries may be thought of as spurions of the higher-group. Such modifications of the ultraviolet flavor symmetries are possible only if new vector-like matter is introduced with masses suppressed from the unification scale by the Yukawa couplings.