The hazard potential of the western segment of the Makran subduction zone, northern Arabian Sea

Evaluating the hazard potential of the Makran subduction zone requires understanding the previous records of the large earthquakes and tsunamis. We address this problem by searching for earthquake and tectonic proxies along the Makran Coast and linking those observations with the available constraints on historical seismicity and the tell-tale characteristics of sea floor morphology. The earthquake of Mw 8.1 of 1945 and the consequent tsunami that originated on the eastern part of the Makran are the only historically known hazardous events in this region. The seismic status of the western part of the subduction zone outside the rupture area of the 1945 earthquake remains an enigma. The near-shore shallow stratigraphy of the central part of Makran near Chabahar shows evidence of seismically induced liquefaction that we attribute to the distant effects of the 1945 earthquake. The coastal sites further westward around Jask are remarkable for the absence of liquefaction features, at least at the shallow level. Although a negative evidence, this possibly implies that the western part of Makran Coast region may not have been impacted by near-field large earthquakes in the recent past-a fact also supported by the analysis of historical data. On the other hand, the elevated marine terraces on the western Makran and their uplift rates are indicative of comparable degree of long-term tectonic activity, at least around Chabahar. The offshore data suggest occurrences of recently active submarine slumps on the eastern part of the Makran, reflective of shaking events, owing to the great 1945 earthquake. The ocean floor morphologic features on the western segment, on the contrary, are much subdued and the prograding delta lobes on the shelf edge also remain intact. The coast on the western Makran, in general, shows indications of progradation and uplift. The various lines of evidence thus suggest that although the western segment is potentially seismogenic, large earthquakes have not occurred there in the recent past, at least during the last 600 years. The recurrence period of earthquakes may range up to 1,000 years or more, an assessment based on the age of the youngest dated coastal ridge. The long elapsed time points to the fact that the western segment may have accumulated sufficient slip to produce a major earthquake.

Mechanistic Insights into the Neutralization of Cytotoxic Abrin by the Monoclonal Antibody D6F10

Abrin, an A/B toxin obtained from the Abrus precatorius plant is extremely toxic and a potential bio-warfare agent. Till date there is no antidote or vaccine available against this toxin. The only known neutralizing monoclonal antibody against abrin, namely D6F10, has been shown to rescue the toxicity of abrin in cells as well as in mice. The present study focuses on mapping the epitopic region to understand the mechanism of neutralization of abrin by the antibody D6F10. Truncation and mutational analysis of abrin A chain revealed that the amino acids 74-123 of abrin A chain contain the core epitope and the residues Thr112, Gly114 and Arg118 are crucial for binding of the antibody. In silico analysis of the position of the mapped epitope indicated that it is present close to the active site cleft of abrin A chain. Thus, binding of the antibody near the active site blocks the enzymatic activity of abrin A chain, thereby rescuing inhibition of protein synthesis by the toxin in vitro. At 1: 10 molar concentration of abrin: antibody, the antibody D6F10 rescued cells from abrin-mediated inhibition of protein synthesis but did not prevent cell attachment of abrin. Further, internalization of the antibody bound to abrin was observed in cells by confocal microscopy. This is a novel finding which suggests that the antibody might function intracellularly and possibly explains the rescue of abrin's toxicity by the antibody in whole cells and animals. To our knowledge, this study is the first report on a neutralizing epitope for abrin and provides mechanistic insights into the poorly understood mode of action of anti-A chain antibodies against several toxins including ricin.