Gutenberg Open

    Ganodermycin, a novel inhibitor of cxcl10 expression from ganoderma applanatum

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    CXCL10 (inducible protein-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells, such as macrophages and T-lymphocytes, and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 cells, a novel compound, designated as Ganodermycin, was isolated from fermentations of the basidiomycete Ganoderma applanatum. The structure was determined by a combination of spectroscopic techniques. Ganodermycin inhibited the lipopolysaccharide (LPS)/interferon (IFN)-gamma-induced CXCL10 promoter activity in transiently transfected MonoMac6 cells in a dose-dependent manner with IC(50) values of 15-20 mu g ml(-1) (53-71 mu M). Ganodermycin also reduced LPS/IFN-gamma-induced CXCL10 protein synthesis and excretion. The Journal of Antibiotics (2011) 64, 683-686; doi:10.1038/ja.2011.64; published online 27 July 201

    Antimodernismus

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    Gasparo Contarini

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    Alfred Loisy

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    The M1 muscarinic acetylcholine receptor subtype is important for retinal neuron survival in aging aging mice

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    Muscarinic acetylcholine receptors have been implicated as potential neuroprotective targets for for glaucoma. We tested the hypothesis that the lack of a single muscarinic receptor subtype leads to to age-dependent neuron reduction in the retinal ganglion cell layer. Mice with targeted disruption of of single muscarinic acetylcholine receptor subtype genes (M1 to M5) and wild-type controls were examined examined at two age categories, 5 and 15 months, respectively. We found no differences in intraocular intraocular pressure between individual mouse groups. Remarkably, in 15-month-old mice devoid of the the M1 receptor, neuron number in the retinal ganglion cell layer and axon number in the optic nerve were markedly reduced. Moreover, mRNA expression for the prooxidative enzyme, NOX2, was increased increased, while mRNA expression for the antioxidative enzymes, SOD1, GPx1 and HO-1, was reduced in aged aged M1 receptor-deficient mice compared to age-matched wild-type mice. In line with these findings findings, the reactive oxygen species level was also elevated in the retinal ganglion cell layer of aged aged M1 receptor-deficient mice. In conclusion, M1 receptor deficiency results in retinal ganglion cell cell loss in aged mice via involvement of oxidative stress. Based on these findings, activation of M1 receptor signaling may become therapeutically useful to promote retinal ganglion cell survival

    Multiphoton microscopy in the diagnostic assessment of pediatric solid tissue in comparison to conventional histopathology : results of the first international online interobserver trial

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    Purpose: Clear resection margins are paramount for good outcome in children undergoing solid tumor resections. Multiphoton microscopy (MPM) can provide high-resolution, real-time, intraoperative microscopic images of tumor tissue. Objective: This prospective international multicenter study evaluates the diagnostic accuracy, feasibility, and interobserver congruence of MPM in diagnosing solid pediatric tissue and tumors for the first time. Material and methods: Representative fresh sections from six different neonatal solid tissues (liver, lung, kidney, adrenal gland, heart muscle, testicle) and two types of typical pediatric solid tumors (neuroblastoma, rhabdomyosarcoma) with adjacent nonneoplastic tissue were imaged with MPM and then presented online with corresponding H&E stained slides of the exact same tissue region. Both image sets of each tissue type were interpreted by 38 randomly selected international attending pediatric pathologists via an online evaluation software. Results: The quality of MPM was sufficient to make the diagnosis of all normal tissue types except cardiac muscle in >94% of assessors with high interobserver congruence and 95% sensitivity. Heart muscle was interpreted as skeletal muscle in 55% of cases. Based on MPM imaging, participating pathologists diagnosed the presented pediatric neoplasms with 100% specificity, although the sensitivity reached only about 50%. Conclusion: Even without prior training, pathologists are able to diagnose normal pediatric tissues with valuable accuracy using MPM. While current MPM imaging protocols are not yet sensitive enough to reliably rule out neuroblastoma or rhabdomyosarcoma, they seem to be specific and therefore useful to confirm a diagnosis intraoperatively. We are confident that improved algorithms, specific training, and more experience with the method will make MPM a valuable future alternative to frozen section analysis

    Polaron spin dynamics in high-mobility polymeric semiconductors

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    Polymeric semiconductors exhibit exceptionally long spin lifetimes, and recently observed micrometre spin diffusion lengths in conjugated polymers demonstrate the potential for organic spintronics devices. Weak spin–orbit and hyperfine interactions lie at the origin of their long spin lifetimes, but the coupling mechanism of a spin to its environment remains elusive. Here, we present a systematic study of polaron spin lifetimes in field-effect transistors with high-mobility conjugated polymers as an active layer. We demonstrate how spin relaxation is governed by the charges’ hopping motion at low temperatures, whereas an Elliott–Yafet-like relaxation due to a transient localization of the carrier wavefunctions is responsible for spin relaxation at high temperatures. In this regime, charge, spin and structural dynamics are intimately related and depend sensitively on the local conformation of polymer backbones and the crystalline packing of the polymer chains
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