Enhancement of the Two-channel Kondo Effect in Single-Electron boxes

The charging of a quantum box, coupled to a lead by tunneling through a single resonant level, is studied near the degeneracy points of the Coulomb blockade. Combining Wilson's numerical renormalization-group method with perturbative scaling approaches, the corresponding low-energy Hamiltonian is solved for arbitrary temperatures, gate voltages, tunneling rates, and energies of the impurity level. Similar to the case of a weak tunnel barrier, the shape of the charge step is governed at low temperatures by the non-Fermi-liquid fixed point of the two-channel Kondo effect. However, the associated Kondo temperature TK is strongly modified. Most notably, TK is proportional to the width of the level if the transmission through the impurity is close to unity at the Fermi energy, and is no longer exponentially small in one over the tunneling matrix element. Focusing on a particle-hole symmetric level, the two-channel Kondo effect is found to be robust against the inclusion of an on-site repulsion on the level. For a large on-site repulsion and a large asymmetry in the tunneling rates to box and to the lead, there is a sequence of Kondo effects: first the local magnetic moment that forms on the level undergoes single-channel screening, followed by two-channel overscreening of the charge fluctuations inside the box.Comment: 21 pages, 19 figure

Perspectives in visual imaging for marine biology and ecology: from acquisition to understanding

Durden J, Schoening T, Althaus F, et al. Perspectives in Visual Imaging for Marine Biology and Ecology: From Acquisition to Understanding. In: Hughes RN, Hughes DJ, Smith IP, Dale AC, eds. Oceanography and Marine Biology: An Annual Review. 54. Boca Raton: CRC Press; 2016: 1-72

β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments

How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional analysis of β1- and αv-class integrins expressed in pan-integrin-null fibroblasts seeded on fibronectin. Reconstitution with β1-class integrins promotes myosin-II-independent formation of small peripheral adhesions and cell protrusions, whereas expression of αv-class integrins induces the formation of large focal adhesions. Co-expression of both integrin classes leads to full myosin activation and traction-force development on stiff fibronectin-coated substrates, with αv-class integrins accumulating in adhesion areas exposed to high traction forces. Quantitative proteomics linked αv-class integrins to a GEF-H1–RhoA pathway coupled to the formin mDia1 but not myosin II, and α5β1 integrins to a RhoA–Rock–myosin II pathway. Our study assigns specific functions to distinct fibronectin-binding integrins, demonstrating that α5β1integrins accomplish force generation, whereas αv-class integrins mediate the structural adaptations to forces, which cooperatively enable cells to sense the rigidity of fibronectin-based microenvironments

Conformational control of integrin-subtype selectivity in isodgr peptide motifs: A biological switch

The rearrangement of asparagine to isoaspartate (isoD) is responsible for the deactivation of many functional proteins. However, the isoDGR motif, which is optimally presented as a conformationally controlled cyclic pentapeptide, binds selectively to α5β 1 integrin (see the docking model) with an affinity comparable to that of the peptidic antitumor agent Cilengitide. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Lung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice

Excess macrophage elastase MMP-12 is a major driver of chronic obstructive pulmonary disease. Here the authors show that the endolysosomal ion channel TRPML3 is a regulator of the cellular reuptake of MMP-12, thus neutralizing harmful MMP-12 in the lung.Lung emphysema and chronic bronchitis are the two most common causes of chronic obstructive pulmonary disease. Excess macrophage elastase MMP-12, which is predominantly secreted from alveolar macrophages, is known to mediate the development of lung injury and emphysema. Here, we discovered the endolysosomal cation channel mucolipin 3 (TRPML3) as a regulator of MMP-12 reuptake from broncho-alveolar fluid, driving in two independently generated Trpml3(-/-) mouse models enlarged lung injury, which is further exacerbated after elastase or tobacco smoke treatment. Mechanistically, using a Trpml3(IRES-Cre/eR26-tau GFP) reporter mouse model, transcriptomics, and endolysosomal patch-clamp experiments, we show that in the lung TRPML3 is almost exclusively expressed in alveolar macrophages, where its loss leads to defects in early endosomal trafficking and endocytosis of MMP-12. Our findings suggest that TRPML3 represents a key regulator of MMP-12 clearance by alveolar macrophages and may serve as therapeutic target for emphysema and chronic obstructive pulmonary disease.Proteomic