CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.

Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria.

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Peer-to-Peer (P2P) techniques for multimedia streaming have been shown to be a good enhancement to the traditional client/server methods when trying to reduce costs and increase robustness. Due to the fact that P2P systems are highly dynamic, the main challenge that has to be addressed remains supporting the general resilience of the system. Various challenges arise when building a resilient P2P streaming system, such as network failures and system dynamics. In this paper, we first classify the different challenges that face P2P streaming and then present and analyze the possible countermeasures. We classify resilience mechanisms as either core mechanisms, which are part of the system, or as cross-layer mechanisms that use information from different communication layers, which might inflict additional costs. We analyze and present resilience mechanisms from an engineering point of view, such that a system engineer can use our analysis as a guide to build a resilient P2P streaming system with different mechanisms and for various application scenarios.

Wavelength meters are widely used for frequency determinations and stabilization purposes since they cover a large wavelength range, provide a high read-out rate and have specified accuracies of up to 10 −8 . More accurate optical frequency measurements can be achieved with frequency combs but only at the price of considerably higher costs and complexity. In the context of precise and accurate frequency determinations for high-resolution laser spectroscopy, the performance of five different wavelength meters was quantified with respect to a frequency comb. The relative precision as well as the absolute accuracy has been investigated in detail, allowing us to give a sophisticated uncertainty margin for the individual instruments. We encountered a prominent substructure on the deviation between both device types with an amplitude of a few MHz that is repeating on the GHz scale. This finally limits the precision of laser scans which are monitored and controlled with wavelength meters. While quantifying its uncertainty margins, we found a high temporal stability in the characteristics of the wavelength meters which enables the preparation of wavelength-dependent adjustment curves for wide-and short-ranged scans. With this method, the absolute accuracy of wavelength meters can be raised up to the MHz level independently from the wavelength of the reference laser used for calibrating the device. Since this technique can be universally applied, it can lead to benefits in all fields of wavelength meter applications.