A genomic interval at 75C1,2 is required for programmed cell death in Drosophila. We identified a new activator of apoptosis, grim, which maps between two previously identified cell death genes in this region reaper {rpr) and head involution defective [hid). Expression of grim RNA coincided with the onset of programmed cell death at all stages of embryonic development, whereas ectopic induction of grim triggered extensive apoptosis in both transgenic animals and in cell culture. Cell killing by grim was blocked by coexpression of p35, a viral product that inactivates ICE-like proteases, and did not require the functions of rpr or hid. The predicted grim protein shares an amino-terminal motif in common with rpr. However, grim was sufficient to elicit apoptosis in at least one context, where rpr was not. The grim gene product might thus function in a parallel circuit of cell death signaling that ultimately activates a common set of downstream apoptotic effectors.

Here we identify a new gene, dark, which encodes a Drosophila homologue of mammalian Apaf-1 and Caenorhabditis elegans CED-4, cell-death proteins. Like Apaf-1, but in contrast to CED-4, Dark contains a carboxy-terminal WD-repeat domain necessary for interactions with the mitochondrial protein cytochrome c. Dark selectively associates with another protein involved in apoptosis, the fly apical caspase, Dredd. Dark-induced cell killing is suppressed by caspase-inhibitory peptides and by a dominant-negative mutant Dredd protein, and enhanced by removal of the WD domain. Loss-of-function mutations in dark attenuate programmed cell deaths during development, causing hyperplasia of the central nervous system, and other abnormalities including ectopic melanotic tumours and defective wings. Moreover, ectopic cell killing by the Drosophila cell-death activators, Reaper, Grim and Hid, is substantially suppressed in dark mutants. These findings establish dark as an important apoptosis effector in Drosophila and raise profound evolutionary considerations concerning the relationship between mitochondrial components and the apoptosis-promoting machinery.

We have successfully applied full-3-D tomography (F3DT) based on a combination of the scattering-integral method (SI-F3DT) and the adjoint-wavefield method (AW-F3DT) to iteratively improve a 3-D starting model, the Southern California Earthquake Center (SCEC) Community Velocity Model version 4.0 (CVM-S4). In F3DT, the sensitivity (Fréchet) kernels are computed using numerical solutions of the 3-D elastodynamic equation and the nonlinearity of the structural inversion problem is accounted for through an iterative tomographic navigation process. More than half-a-million misfit measurements made on about 38,000 earthquake seismograms and 12,000 ambient-noise correlagrams have been assimilated into our inversion. After 26 F3DT iterations, synthetic seismograms computed using our latest model, CVM-S4.26, show substantially better fit to observed seismograms at frequencies below 0.2 Hz than those computed using our 3-D starting model CVM-S4 and the other SCEC CVM, CVM-H11.9, which was improved through 16 iterations of AW-F3DT. CVM-S4.26 has revealed strong crustal heterogeneities throughout Southern California, some of which are completely missing in CVM-S4 and CVM-H11.9 but exist in models obtained from previous crustal-scale 2-D active-source refraction tomography models. At shallow depths, our model shows strong correlation with sedimentary basins and reveals velocity contrasts across major mapped strike-slip and dip-slip faults. At middle to lower crustal depths, structural features in our model may provide new insights into regional tectonics. When combined with physics-based seismic hazard analysis tools, we expect our model to provide more accurate estimates of seismic hazards in Southern California.

Caspases are widely conserved proteases considered to be essential effectors of apoptosis. We identified a novel Drosophila gene, dredd, which shares extensive homology to all members of the caspase gene family. Cells specified for programmed death in development exhibit a striking accumulation of dredd RNA that requires signaling by the death activators REAPER, GRIM, and HID. Furthermore, directed misexpression of each activator was sufficient to drive ectopic accumulation of dredd RNA. Heterozygosity at the dredd locus suppressed apoptosis in transgenic models of reaper- and grim-induced cell killing, demonstrating that levels of dredd product can modulate signaling triggered by these death activators. Finally, expression of REAPER, GRIM, and HID was found to trigger processing of DREDD protein precursor through a mechanism that is insensitive to, and upstream of, known caspase inhibitors. Taken together, these observations establish mechanistic connections between activators of apoptosis and a new downstream death effector in Drosophila.

We deployed a dense linear array of 45 seismometers across and along the San Andreas fault near Parkfield a week after the M 6.0 Parkfield earthquake on 28 September 2004 to record fault-zone seismic waves generated by aftershocks and explosions. Seismic stations and explosions were co-sited with our previous experiment conducted in 2002. The data from repeated shots detonated in the fall of 2002 and 3 months after the 2004 M 6.0 mainshock show ϳ1.0%-1.5% decreases in seismic-wave velocity within an ϳ200-m-wide zone along the fault strike and smaller changes (0.2%-0.5%) beyond this zone, most likely due to the coseismic damage of rocks during dynamic rupture in the 2004 M 6.0 earthquake. The width of the damage zone characterized by larger velocity changes is consistent with the low-velocity waveguide model on the San Andreas fault, near Parkfield, that we derived from fault-zone trapped waves (Li et al., 2004). The damage zone is not symmetric but extends farther on the southwest side of the main fault trace. Waveform crosscorrelations for repeated aftershocks in 21 clusters, with a total of ϳ130 events, located at different depths and distances from the array site show ϳ0.7%-1.1% increases in S-wave velocity within the fault zone in 3 months starting a week after the earthquake. The velocity recovery indicates that the damaged rock has been healing and regaining the strength through rigidity recovery with time, most likely due to the closure of cracks opened during the mainshock. We estimate that the net decrease in seismic velocities within the fault zone was at least ϳ2.5%, caused by the 2004 M 6.0 Parkfield earthquake. The healing rate was largest in the earlier stage of the postmainshock healing process. The magnitude of fault healing varies along the rupture zone, being slightly larger for the healing beneath Middle Mountain, correlating well with an area of large mapped slip. The fault healing is most prominent at depths above ϳ7 km.