Encapsulation of Mithramycin in Liposomes in Response to a Transmembrane Gradient of Calcium Ions

The recent discovery that mithramycin(MTR) in aqueous solution forms a high affinity[Ca(MTR)4]2- complex led us to the idea thatCa2+-loaded liposomes might be able to accumulateMTR in their aqueous internal compartment. Wetherefore investigated the uptake of MTR into largeunilamellar vesicles (LUV) containing NaCl orCaCl2. Our data show that MTR was efficientlyaccumulated within LUV made fromdipalmitoylphosphatidylcholine and cholesterol, onlywhen the liposomes contained Ca2+ and wereresuspended in a Ca2+-free medium. A drugencapsulation efficiency as high as 60% was achieved,at a drug to lipid molar ratio of 1/18. The circulardichroism and fluorescence excitation spectra ofliposome-encapsulated MTR (LMTR) displayed strongsimilarities with those of the [Ca(MTR)4]2-complex. LMTR was found to be stable, when submittedto conditions that destabilized the[Ca(MTR)4]2- complex. Upon dilution andincubation for 24 h at 37 °C, MTR-containingliposomes did not release a significant amount of MTR.These properties were attributed to the formation ofa high affinity complex between MTR and Ca2+inthe aqueous compartment of liposomes.     

Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis

Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the development and regulation of immunity to infection is unknown. Here we show that IEC-intrinsic IkappaB kinase (IKK)-beta-dependent gene expression is a critical regulator of responses of dendritic cells and CD4+ T cells in the GI tract. Mice with an IEC-specific deletion of IKK-beta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (T(H)2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40 and tumour necrosis factor-alpha, increased levels of CD4+ T-cell-derived interferon-gamma and interleukin-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKK-beta in IECs to promote CD4+ T(H)2 cell-dependent immunity, identifying an essential function for IECs in tissue-specific conditioning of dendritic cells and limiting type 1 cytokine production in the GI tract. These results indicate that the balance of IKK-beta-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation.     

On the theory of slowing down gracefully

We discuss the transport of a tracer particle through the Bose?CEinstein condensate of a Bose gas. The particle interacts with the atoms in the Bose gas through two-body interactions. In the limiting regime where the particle is very heavy and the Bose gas is very dense, but very weakly interacting (??mean-field limit??), the dynamics of this system corresponds to classical Hamiltonian dynamics. We show that, in this limit, the particle is decelerated by emission of gapless modes into the condensate (Cerenkov radiation). For an ideal gas, the particle eventually comes to rest. In an interacting Bose gas, the particle is decelerated until its speed equals the propagation speed of the Goldstone modes of the condensate. This is a model of ??Hamiltonian friction??. It is also of interest in connection with the phenomenon of ??decoherence?? in quantum mechanics. This note is based on work we have carried out in collaboration with D Egli, I M Sigal and A Soffer.     

Laser spectroscopy with a cooler ring at the esr (GSI) and the TSR (MPI Heidelberg)

At the TSR cooler ring at Heidelberg, laser studies were carried out using singly charged lithium and beryllium ions. Laser spectroscopy of relativistic lithium ions (v=0.04c) yielded signals with a narrow linewidth, suitable for an experimental test of special relativity. A dramatic reduction of the beam temperature, as defined by the longitudinal velocity spread, was achieved via laser cooling in both cases. At the ion energies available at ESR it will become possible to prepare and store bare ions up to U⁹²⁺. Electron cooling was succesfully demonstrated for hydrogen-like Bi⁸²⁺ ions, where a laser experiment is scheduled to study the ground-state hyperfine splitting.