Light-induced dipolar spectroscopy - A quantitative comparison between LiDEER and LaserIMD

Nanometric distance measurements with EPR spectroscopy yield crucial information on the structure and interactions of macromolecules in complex systems. The range of suitable spin labels for such measurements was recently expanded with a new class of light-inducible labels: the triplet state of porphyrins. Importantly, accurate distance measurements between a triplet label and a nitroxide have been reported with two distinct light-induced spectroscopy techniques, (light-induced) triplet-nitroxide DEER (LiDEER) and laser-induced magnetic dipole spectroscopy (LaserIMD). In this work, we set out to quantitatively compare the two techniques under equivalent conditions at Q band. Since we find that LiDEER using a rectangular pump pulse does not reach the high modulation depth that can be achieved with LaserIMD, we further explore the possibility of improving the LiDEER experiment with chirp inversion pulses. LiDEER employing a broadband pump pulse results in a drastic improvement of the modulation depth. The relative performance of chirp LiDEER and Laser-IMD in terms of modulation-to-noise ratio is found to depend on the dipolar evolution time: While LaserIMD yields higher modulation-to-noise ratios than LiDEER at short dipolar evolution times ({\tau}=2 {\mu}s), the high phase memory time of the triplet spins causes the situation to revert at {\tau}=6 {\mu}s.Comment: 9 pages, 4 figures and supporting information (18 pages, 11 figures

Viability of coaxial atomization for disintegration of cell solutions in cell spray applications

[EN] Treating Leukemia with intravenous stem cell transplantation represents a well-established therapy technique. For applications, that require high local cell concentrations, transplantation by conventional intravenous injection is less potent, due to cell distribution with blood circulation. Instead, spraying them directly onto the injured or diseased area shows promising results in various applications, e.g. superficial treatment of topographically challenging wounds, in situ seeding of cells on implants, deposition of cells in tubular organs for stem cell therapy. The present work aims for a basic knowledge about viability boundaries for coaxial cell-spray atomization and the reciprocal influence between cells in solution and primary breakup mechanics. A generic modular nozzle is developed, to ensures reproducible boundary conditions. Investigations are conducted regarding primary breakup and relations between resulting droplet size distribution and cell survival. Measurements are performed, utilizing microscopic high-speed visualization with suitable image post processing. Cell viability is analyzed using phase contrast microscopy prior and after atomization. A relation between Rayleigh-Taylor instability wavelength and droplet size distributions by means of Sauter mean diameter (SMD) and cell survival rate (CSR) is suggested. A power law is presented, exclusively dependent on dimensionless measures (λ⊥ ∼ Re−1/2We−1/3 ) which is found to be proportional to SMD and CSR.We gratefully acknowledge financial support from the Excellence Initiative of the German federal state governments (Exploratory Research Space, RWTH Aachen University).Bieber, M.; Menzel, S.; Thiebes, A.; Cornelissen, C.; Jockenhoevel, S.; Kneer, R.; Reddemann, M. (2017). Viability of coaxial atomization for disintegration of cell solutions in cell spray applications. En Ilass Europe. 28th european conference on Liquid Atomization and Spray Systems. Editorial Universitat Politècnica de València. 521-528. https://doi.org/10.4995/ILASS2017.2017.4609OCS52152

A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation

Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system