The overall mechanics of fold‐and‐thrust belts and accretionary wedges along compressive plate boundaries is considered to be analogous to that of a wedge of soil or snow in front of a moving bulldozer. The material within the wedge deforms until a critical taper is attained, after which it slides stably, continuing to grow at constant taper as additional material is encountered at the toe. The critical taper is the shape for which the wedge is on the verge of failure under horizontal compression everywhere, including the basal decollement. A wedge of less than critical taper will not slide when pushed but will deform internally, steepening its surface slope until the critical taper is attained. Common silicate sediments and rocks in the upper 10–15 km of the crust have pressure‐dependent brittle compressive strengths which can be approximately represented by the empirical Coulomb failure criterion, modified to account for the weakening effects of pore fluid pressure. A simple analytical theory that predicts the critical tapers of subaerial and submarine Coulomb wedges is developed and tested quantitatively in three ways: First, laboratory model experiments with dry sand match the theory. Second, the known surface slope, basal dip, and pore fluid pressures in the active fold‐and‐thrust belt of western Taiwan are used to determine the effective coefficient of internal friction within the wedge, μ = 1.03, consistent with Byerlee's empirical law of sliding friction, μb = 0.85, on the base. This excess of internal strength over basal friction suggests that although the Taiwan wedge is highly deformed by imbricate thrusting, it is not so pervasively fractured that frictional sliding is always possible on surfaces of optimum orientation. Instead, the overall internal strength apparently is controlled by frictional sliding along suboptimally oriented planes and by the need to fracture some parts of the observed geometrically complex structure for continued deformation. Third, using the above values of μb and μ we predict Hubbert‐Rubey fluid pressure ratios λ = λb for a number of other active subaerial and submarine accretionary wedges based on their observed tapers, finding values everywhere in excess of hydrostatic. These predicted overpressures are reasonable in light of petroleum drilling experience in general and agree with nearby fragmentary well data in specific wedges where they are available. The pressure‐dependent Coulomb wedge theory developed here is expected to break down if the decollement exhibits pressure‐independent plastic behavior because of either temperature or rock type. The effects of this breakdown are observed in the abrupt decrease in taper where wedge thicknesses exceed about 15 km, which is the predicted depth of the brittle‐plastic transition in quartz‐rich rocks for typical geothermal gradients. We conclude that fold‐and‐thrust belts and accretionary wedges have the mechanics of bulldozer wedges in compression and that normal laboratory fracture and frictional strengths are appropriate to mo...

Natural killer (NK) cells destroy virus-infected and tumour cells, apparently without the need for previous antigen stimulation. In part, target cells are recognized by their diminished expression of major histocompatibility complex (MHC) class I molecules, which normally interact with inhibitory receptors on the NK cell surface. NK cells also express triggering receptors that are specific for non-MHC ligands; but the nature of the ligands recognized on target cells is undefined. NKp46 is thought to be the main activating receptor for human NK cells. Here we show that a soluble NKp46-immunoglobulin fusion protein binds to both the haemagglutinin of influenza virus and the haemagglutinin-neuraminidase of parainfluenza virus. In a substantial subset of NK cells, recognition by NKp46 is required to lyse cells expressing the corresponding viral glycoproteins. The binding requires the sialylation of NKp46 oligosaccharides, which is consistent with the known sialic binding capacity of the viral glycoproteins. These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein.

Transmission of HIV-1 via intercellular connections has been estimated as 100-1000 times more efficient than a cell-free process, perhaps in part explaining persistent viral spread in the presence of neutralizing antibodies. Such effective intercellular transfer of HIV-1 could occur through virological synapses or target-cell filopodia connected to infected cells. Here we report that membrane nanotubes, formed when T cells make contact and subsequently part, provide a new route for HIV-1 transmission. Membrane nanotubes are known to connect various cell types, including neuronal and immune cells, and allow calcium-mediated signals to spread between connected myeloid cells. However, T-cell nanotubes are distinct from open-ended membranous tethers between other cell types, as a dynamic junction persists within T-cell nanotubes or at their contact with cell bodies. We also report that an extracellular matrix scaffold allows T-cell nanotubes to adopt variably shaped contours. HIV-1 transfers to uninfected T cells through nanotubes in a receptor-dependent manner. These data lead us to propose that HIV-1 can spread using nanotubular connections formed by short-term intercellular unions in which T cells specialize.

To avoid detection by CTL, HIV encodes mechanisms for removal of class I MHC proteins from the surface of infected cells. However, class I downregulation potentially exposes the virus-infected cell to attack by NK cells. Human lymphoid cells are protected from NK cell cytotoxicity primarily by HLA-C and HLA-E. We present evidence that HIV-1 selectively downregulates HLA-A and HLA-B but does not significantly affect HLA-C or HLA-E. We then identify the residues in HLA-C and HLA-E that protect them from HIV down-regulation. This selective downregulation allows HIV-infected cells to avoid NK cell-mediated lysis and may represent for HIV a balance between escape from CTL and maintenance of protection from NK cells. These results suggest that subpopulations of CTL and NK cells may be uniquely suited for combating HIV.

We report that two classes of membrane nanotubes between human monocyte-derived macrophages can be distinguished by their cytoskeletal structure and their functional properties. Thin membrane nanotubes contained only F-actin, whereas thicker nanotubes, i.e., those > approximately 0.7 microm in diameter, contained both F-actin and microtubules. Bacteria could be trapped and surf along thin, but not thick, membrane nanotubes toward connected macrophage cell bodies. Once at the cell body, bacteria could then be phagocytosed. The movement of bacteria is aided by a constitutive flow of the nanotube surface because streptavidin-coated beads were similarly able to traffic along nanotubes between surface-biotinylated macrophages. Mitochondria and intracellular vesicles, including late endosomes and lysosomes, could be detected within thick, but not thin, membrane nanotubes. Analysis from kymographs demonstrated that vesicles moved in a stepwise, bidirectional manner at approximately 1 microm/s, consistent with their traffic being mediated by the microtubules found only in thick nanotubes. Vesicular traffic in thick nanotubes and surfing of beads along thin nanotubes were both stopped upon the addition of azide, demonstrating that both processes require ATP. However, microtubule destabilizing agents colchicine or nocodazole abrogated vesicular transport but not the flow of the nanotube surface, confirming that distinct cytoskeletal structures of nanotubes give rise to different functional properties. Thus, membrane nanotubes between macrophages are more complex than unvarying ubiquitous membrane tethers and facilitate several means for distal interactions between immune cells.