The SNARE machinery is involved in apical plasma membrane trafficking in MDCK cells.

We have investigated the controversial involvement of components of the SNARE (soluble N-ethyl maleimide-sensitive factor [NSF] attachment protein [SNAP] receptor) machinery in membrane traffic to the apical plasma membrane of polarized epithelial (MDCK) cells. Overexpression of syntaxin 3, but not of syntaxins 2 or 4, caused an inhibition of TGN to apical transport and apical recycling, and leads to an accumulation of small vesicles underneath the apical plasma membrane. All other tested transport steps were unaffected by syntaxin 3 overexpression. Botulinum neurotoxin E, which cleaves SNAP-23, and antibodies against alpha-SNAP inhibit both TGN to apical and basolateral transport in a reconstituted in vitro system. In contrast, we find no evidence for an involvement of N-ethyl maleimide-sensitive factor in TGN to apical transport, whereas basolateral transport is NSF-dependent. We conclude that syntaxin 3, SNAP-23, and alpha-SNAP are involved in apical membrane fusion. These results demonstrate that vesicle fusion with the apical plasma membrane does not use a mechanism that is entirely unrelated to other cellular membrane fusion events, but uses isoforms of components of the SNARE machinery, which suggests that they play a role in providing specificity to polarized membrane traffic

Comparison of electromagnetic and nuclear dissociation of 17Ne^{17}\mathrm{Ne}

The Borromean drip-line nucleus ¹⁷Ne has been suggested to possess a two-proton halo structure in its ground state. In the astrophysical rp-process, where the two-proton capture reaction ¹⁵O(2p,γ) ¹⁷Ne plays an important role, the calculated reaction rate differs by several orders of magnitude between different theoretical approaches. To add to the understanding of the ¹⁷Ne structure we have studied nuclear and electromagnetic dissociation. A 500 MeV/u¹⁷Ne beam was directed toward lead, carbon, and polyethylene targets. Oxygen isotopes in the final state were measured in coincidence with one or two protons. Different reaction branches in the dissociation of ¹⁷Ne were disentangled. The relative populations of s and d states in ¹⁶F were determined for light and heavy targets. The differential cross section for electromagnetic dissociation (EMD) shows a continuous internal energy spectrum in the three-body system ¹⁵O + 2p. The ¹⁷Ne EMD data were compared to current theoretical models. None of them, however, yields satisfactory agreement with the experimental data presented here. These new data may facilitate future development of adequate models for description of the fragmentation process

Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep

BACKGROUND: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. MATERIALS AND METHODS: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. RESULTS: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. CONCLUSIONS: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects

Remineralization of demineralized dentin using a dual analog system.

ObjectiveImproved methods are needed to remineralize dentin caries in order to promote conservation of dentin tissue and minimize the surgical interventions that are currently required for clinical treatment. Here, we test the hypothesis that bulk substrates can be effectively mineralized via a dual analog system proposed by others, using a tripolyphosphate (TPP) "templating analog" and a poly(acrylic acid) (PAA) or poly(aspartic acid) (pAsp) "sequestration analog," the latter of which generates the polymer-induced liquid-precursor (PILP) mineralization process studied in our laboratory.Material & methodsDemineralized human dentin slices were remineralized with and without pre-treatment with TPP, using either PAA or pAsp as the PILP process-directing agent. A control experiment with no polymer present was used for comparison.ResultsNo mineralization was observed in any of the PAA groups. In both the pAsp and no polymer groups, TPP inhibited mineralization on the surfaces of the specimens but promoted mineralization within the interiors. Pre-treatment with TPP enhanced overall mineralization of the pAsp group. However, when analysed via TEM, regions with little mineral were still present.ConclusionPoly(acrylic acid) was unable to remineralize demineralized dentin slices under the conditions employed, even when pre-treated with TPP. However, pre-treatment with TPP enhanced overall mineralization of specimens that were PILP-remineralized using pAsp

The SNARE Protein Syntaxin 3 Confers Specificity for Polarized Axonal Trafficking in Neurons.

Cell polarity and precise subcellular protein localization are pivotal to neuronal function. The SNARE machinery underlies intracellular membrane fusion events, but its role in neuronal polarity and selective protein targeting remain unclear. Here we report that syntaxin 3 is involved in orchestrating polarized trafficking in cultured rat hippocampal neurons. We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips, whereas syntaxin 4 localizes to the somatodendritic plasma membrane. Disruption of a conserved N-terminal targeting motif, which causes mislocalization of syntaxin 3, results in coincident mistargeting of the axonal cargos neuron-glia cell adhesion molecule (NgCAM) and neurexin, but not transferrin receptor, a somatodendritic cargo. Similarly, RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM, demonstrating that syntaxin 3 plays an important role in its targeting. Additionally, overexpression of syntaxin 3 results in increased axonal growth. Our findings suggest an important role for syntaxin 3 in maintaining neuronal polarity and in the critical task of selective trafficking of membrane protein to axons

Quantum computing through electron propagation in the edge states of quantum spin Hall systems

We propose to implement quantum computing based on electronic spin qubits by controlling the propagation of the electron wave packets through the helical edge states of quantum spin Hall systems (QSHs). Specfically, two non-commutative single-qubit gates, which rotate a qubit around z and y axes, can be realized by utilizing gate voltages either on a single QSH edge channel or on a quantum point contact structure. The more challenging two-qubit controlled phase gate can be implemented through the on-demand capacitive Coulomb interaction between two adjacent edge channels from two parallel QSHs. As a result, a universal set of quantum gates can be achieved in an all-electrical way. The fidelity and purity of the two-qubit gate are calculated with both time delay and finite width of the wave packets taken into consideration, which can reach high values with the existing high-quality single electron source

Xenotransplantation: Perspectives and limits

Xenotransplantation faces the dilemma of an unlimited supply of cells, tissues and organs on the one hand and severe obstacles and limits on the other. One reason for the limitations is that the source animal of choice, the pig, and the human recipient separated 90 million years ago during evolution, a time in which biological characteristics such as anatomy, physiology and immunology have had much time to drift far apart. The acceptance of such an evolutionary widely divergent organ, especially the heart of a pig, could evoke refusal of xenotransplantation in conservative and religious patients. New legal aspects of allocation of xenografts have therefore to be reflected upon and appropriate guidelines developed. Inquiries show, however, that the acceptance of all types of porcine organs would be high if the quality of life after receiving such a xenograft is comparable to that after receiving the same allograft. This individual benefit of a xenograft could lead to a disregard of the collective risk in terms of xenozoonoses, often presented as a catastrophic scenarium. Therefore, transplantation societies and ethics committees have published comments and even guidelines for handling future clinical xenotransplantation. All three monotheistic religions and Hinduism support the idea of saving and improving human life with the help of an animal organ. Copyrght (C) 2001 S. Karger AG, Basel