Key determinants of the dual clamp/activator function of Complexin.

Complexin determines magnitude and kinetics of synchronized secretion, but the underlying molecular mechanisms remained unclear. Here, we show that the hydrophobic face of the amphipathic helix at the C-terminus of Complexin II (CpxII, amino acids 115-134) binds to fusion-promoting SNARE proteins, prevents premature secretion, and allows vesicles to accumulate in a release-ready state in mouse chromaffin cells. Specifically, we demonstrate that an unrelated amphipathic helix functionally substitutes for the C-terminal domain (CTD) of CpxII and that amino acid substitutions on the hydrophobic side compromise the arrest of the pre-fusion intermediate.

The SNAP-25 linker supports fusion intermediates by local lipid interactions.

SNAP-25 is an essential component of SNARE complexes driving fast Ca-dependent exocytosis. Yet, the functional implications of the tandem-like structure of SNAP-25 are unclear. Here, we have investigated the mechanistic role of the acylated "linker" domain that concatenates the two SNARE motifs within SNAP-25.

A mechanism for exocytotic arrest by the Complexin C-terminus.

ComplexinII (CpxII) inhibits non-synchronized vesicle fusion, but the underlying mechanisms have remained unclear. Here, we provide evidence that the far C-terminal domain (CTD) of CpxII interferes with SNARE assembly, thereby arresting tonic exocytosis. Acute infusion of a CTD-derived peptide into mouse chromaffin cells enhances synchronous release by diminishing premature vesicle fusion like full-length CpxII, indicating a direct, inhibitory function of the CTD that sets the magnitude of the primed vesicle pool.

Compact and flexible harmonic generator and three-color synthesizer for femtosecond coherent control and time-resolved studies.

Intense, multi-color laser fields permit the control of the ionization of atoms and the steering of electron dynamics. Here, we present the efficient collinear creation of the second and third harmonic of a 790 nm femtosecond laser followed by a versatile field synthesizer for the three color fields' composition. Using the device, we investigate the strong-field ionization of neon by fields composed of the fundamental, and the second or third harmonic.

HFOLD - A program package for calculating two-body MSSM Higgs decays at full one-loop level.

HFOLD (Higgs Full One Loop Decays) is a Fortran program package for calculating all MSSM Higgs two-body decay widths and the corresponding branching ratios at full one-loop level. The package is done in the SUSY Parameter Analysis convention and supports the SUSY Les Houches Accord input and output format. PROGRAM SUMMARY: Program title: HFOLD Catalogue identifier: AEJG_v1_0 Program summary URL:http://cpc.

Determinants governing the potency of STAT3 activation via the individual STAT3-recruiting motifs of gp130.

In recent years, the elucidation of the structures of many signalling molecules has allowed new insights into the molecular mechanisms that govern signal transduction events. In the field of cytokine signalling, the solved structures of cytokine/receptor complexes and of key components involved in signal transduction such as STAT factors or the tyrosine phosphatase SHP2 have broadened our understanding of the molecular basis of the signalling events and provided key information for the rational design of therapeutic approaches to modulate or block cytokine signal transduction. Unfortunately, no structural data on the intracellular parts of cytokine receptors are available.

LPS and TNFalpha induce SOCS3 mRNA and inhibit IL-6-induced activation of STAT3 in macrophages.

Recent findings indicate that cytokine signaling can be modulated by other mediators of simultaneously activated signal transduction pathways. In this study we show that LPS and TNFalpha are potent inhibitors of IL-6-mediated STAT3 activation in human monocyte derived macrophages, rat liver macrophages and RAW 264.7 mouse macrophages but not in human hepatoma cells (HepG2) or in rat hepatocytes.

Oncostatin M differentially regulates tissue inhibitors of metalloproteinases TIMP-1 and TIMP-3 gene expression in human synovial lining cells.

Tissue inhibitor of metalloproteinases (TIMP) 1, 2 and 3 are related proteins that can form complexes with all known matrix metalloproteinases (MMPs). They inhibit the action of MMPs on extracellular matrix components. The balance of MMPs and TIMPs is important for tissue remodeling and its disturbance is believed to play a crucial role in pathophysiological processes such as tumor metastasis, destruction of cartilage and fibrosis.

[Increased expression of the OKM5 antigen in blood monocytes in vitiligo].

In 25 patients suffering from vitiligo, we determined the T-cell profile (OKT3, 4 and 8; anti-Leu7) as well as the peripheral monocytes (OKM5) by means of monoclonal antibodies. Comparing the patients with a control group (n = 8), we found no differences regarding the T-cell count, whereas the expression of OKM5 antigens on peripheral monocytes was significantly elevated in patients with vitiligo.

Metallic dust collectors for low velocity impacts.

Experiments simulating the non-destructive collection of cosmic dust are conducted at the laboratory of the Lehrstuhl fur Raumfahrttechnik (LRT) of the Technische Universitat Munchen (TUM). The electromagnetic accelerator setup is described, which is capable of obtaining an impact velocity between 10 and 400 m/s with particle masses up to 1 g. The evaluation method of the ratio of collected to impacting particles is given.

The kinetics of the formation of rotational isomers in the hydrophobic tail region of phospholipid bilayers.

Very fast structural changes in dipalmitoyl phosphatidylcholine molecules forming a vesicular bilayer were investigated by means of a laser temperature-jump technique. After temperature increases of about 1 K within 1 ns, the solution turbidity increases with a time constant of about 4 ns. This time constant exhibited no appreciable temperature dependence and represents a noncooperative process.

Effects of several lipidosis-including drugs upon the area postrema and adjacent medullary nuclei of adult rats. I. Alterations is perikarya and dendrites.

The present study is concerned with the question of whether or not amphiphilic drugs (chloroquine, quinacrine, perhexiline) that fail to induce general lipidosis in the central nervous system (CNS) of adult rats can produce lipidosis in a circumventricular organ (area postrema) not furnished with a blood-brain barrier. Chlorphentermine known to induce general lipidosis in CNS of adult rats served as reference compound. All drugs, when chronically applied in high oral doses, induced significant perikaryal lipidosis in the area postrema.

Differential effects of chloroquine and of several other amphiphilic cationic drugs upon rat choroid plexus.

Several cationic amphiphilic drugs, each of which is known to induce generalized lipidosis in rats, were compared with respect to their cytological effects on rat choroid plexus epithelium. Chloroquine induced large cytoplasmic vacuoles, whereas the other drugs (quinacrine, 4,4'-diethylaminoethoxyhexestrol, chlorphentermine, iprindole, 1-chloro-amitriptyline, clomipramine) caused formation of lamellated or crystalloid inclusions as usually seen in drug-induced lipidosis. The ultrastructure of the chloroquine-induced vacuoles suggested storage of water-soluble materials (polar lipids and/or non-lipid materials) in addition to non-water-soluble polar lipids.