Controls of shear zone rheology and tectonic loading on postseismic creep

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): B10404, doi:10.1029/2003JB002925.Postseismic deformation is well documented in geodetic data collected in the aftermath of large earthquakes. In the postseismic time interval, GPS is most sensitive to creep in the lower crust or upper mantle activated by earthquake-generated stress perturbations. In these regions, deformation may be localized on an aseismic frictional surface or on a ductile shear zone. These two hypotheses imply specific rheologies and therefore time dependence of postseismic creep. Hence postseismic creep constitutes a potential probe into the rheology of aseismic regions of the lithosphere. I present a simple shear zone model of postseismic creep in which the rheology of the creeping element can be varied. In the absence of tectonic loading during the postseismic time interval, the displacement history of the shear zone obeying a power law rheology with stress exponent n follows an analytical relaxation curve parameterized by 1/n. For a frictional surface, postseismic creep follows the same relaxation law in the limit 1/n → 0. A rough estimate of the apparent stress exponent can be obtained from continuous GPS records. Application to data collected after the 1994 Sanriku earthquake yields 1/n ∼ 0.1, which is consistent with dislocation creep mechanisms. However, the records of two other subduction zone events, the 2001 Peru event and the 1997 Kronotski earthquake, and a continental strike-slip earthquake, the 1999 İzmit earthquake, require negative 1/n. Rather than characterizing the shear zone rheology, these negative exponents indicate that reloading of the shear zone by tectonic forces is important. Numerical simulations of postseismic deformation with nonnegligible reloading produce curves that are well fit by the generalized relaxation law with 1/n < 0, although the actual stress exponent of the rheology is positive. While this prevents rheology from being tightly constrained by the studied GPS records, it indicates that reloading is important in the postseismic time interval. In other words, the stress perturbation induced by an earthquake is comparable to the stress supported by ductile shear zones in the interseismic period.This work was supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the USGS, complemented by NSF grants OCE- 9907244, OCE-0327588, EAR-0337678, and a grant from the Deep Ocean Exploration Institute at WHOI to Greg Hirth

Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity

The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/ or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and Cterminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) inconjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons inV1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu593, Trp596 and Lys601. The 136 and/or 142glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection

Importance of Post-Translational Modifications for Functionality of a Chloroplast-Localized Carbonic Anhydrase (CAH1) in Arabidopsis thaliana

Background: The Arabidopsis CAH1 alpha-type carbonic anhydrase is one of the few plant proteins known to be targeted to the chloroplast through the secretory pathway. CAH1 is post-translationally modified at several residues by the attachment of N-glycans, resulting in a mature protein harbouring complex-type glycans. The reason of why trafficking through this non-canonical pathway is beneficial for certain chloroplast resident proteins is not yet known. Therefore, to elucidate the significance of glycosylation in trafficking and the effect of glycosylation on the stability and function of the protein, epitope-labelled wild type and mutated versions of CAH1 were expressed in plant cells. Methodology/Principal Findings: Transient expression of mutant CAH1 with disrupted glycosylation sites showed that the protein harbours four, or in certain cases five, N-glycans. While the wild type protein trafficked through the secretory pathway to the chloroplast, the non-glycosylated protein formed aggregates and associated with the ER chaperone BiP, indicating that glycosylation of CAH1 facilitates folding and ER-export. Using cysteine mutants we also assessed the role of disulphide bridge formation in the folding and stability of CAH1. We found that a disulphide bridge between cysteines at positions 27 and 191 in the mature protein was required for correct folding of the protein. Using a mass spectrometric approach we were able to measure the enzymatic activity of CAH1 protein. Under circumstances where protein N-glycosylation is blocked in vivo, the activity of CAH1 is completely inhibited. Conclusions/Significance: We show for the first time the importance of post-translational modifications such as N-glycosylation and intramolecular disulphide bridge formation in folding and trafficking of a protein from the secretory pathway to the chloroplast in higher plants. Requirements for these post-translational modifications for a fully functional native protein explain the need for an alternative route to the chloroplast.This work was supported by the Swedish Research Council (VR), the Kempe Foundations and Carl Tryggers Foundation to GS, and grant numbers BIO2006-08946 and BIO2009-11340 from the Spanish Ministerio de Ciencia e Innovación (MICINN) to A

Are luminescent bacteria suitable for online detection and monitoring of toxic compounds in drinking water and its sources?

Biosensors based on luminescent bacteria may be valuable tools to monitor the chemical quality and safety of surface and drinking water. In this review, an overview is presented of the recombinant strains available that harbour the bacterial luciferase genes luxCDABE, and which may be used in an online biosensor for water quality monitoring. Many bacterial strains have been described for the detection of a broad range of toxicity parameters, including DNA damage, protein damage, membrane damage, oxidative stress, organic pollutants, and heavy metals. Most lux strains have sensitivities with detection limits ranging from milligrams per litre to micrograms per litre, usually with higher sensitivities in compound-specific strains. Although the sensitivity of lux strains can be enhanced by various molecular manipulations, most reported detection thresholds are still too high to detect levels of individual contaminants as they occur nowadays in European drinking waters. However, lux strains sensing specific toxic effects have the advantage of being able to respond to mixtures of contaminants inducing the same effect, and thus could be used as a sensor for the sum effect, including the effect of compounds that are as yet not identified by chemical analysis. An evaluation of the suitability of lux strains for monitoring surface and drinking water is therefore provided

Structure and Dynamics of a Fusion Peptide Helical Hairpin on the Membrane Surface: Comparison of Molecular Simulations and NMR

The conserved N-terminal residues of the HA2 subunit of influenza hemagglutinin (fusion peptide) are essential for membrane fusion and viral entry. Recent NMR studies showed that the 23-residue fusion peptide forms a helical hairpin that undergoes rocking motion relative to the membrane surface on a nanosecond time scale. To compare with NMR and to obtain a detailed molecular picture of the peptide–membrane interaction, we performed molecular dynamics simulations of the fusion peptide in explicit dimyristoylphosphatidylcholine and with the IMM1 implicit membrane model. To account for low and neutral pH conditions, simulations were performed with acidic groups (E11 and D19) protonated and unprotonated, respectively. The hairpin structure was stable in the simulations, with the N-terminal helix buried more deeply into the hydrophobic membrane interior than the C-terminal helix. Interactions between the tryptophans in the fusion peptide and phospholipid residues contribute to peptide orientation. Higher flexibility of the hairpin was observed in the implicit membrane simulations. Internal correlation functions of backbone N–H vectors were fit to the extended Lipari–Szabo model-free approach to obtain order parameters and correlation times. Good agreement with the NMR results was obtained for orientational fluctuations around the hairpin axis (rotation), but those around the perpendicular axis (tilting) were more limited in the simulations than inferred from the NMR experiments

Arginine in Membranes: The Connection Between Molecular Dynamics Simulations and Translocon-Mediated Insertion Experiments

Several laboratories have carried out molecular dynamics (MD) simulations of arginine interactions with lipid bilayers and found that the energetic cost of placing arginine in lipid bilayers is an order of magnitude greater than observed in molecular biology experiments in which Arg-containing transmembrane helices are inserted across the endoplasmic reticulum membrane by the Sec61 translocon. We attempt here to reconcile the results of the two approaches. We first present MD simulations of guanidinium groups alone in lipid bilayers, and then, to mimic the molecular biology experiments, we present simulations of hydrophobic helices containing single Arg residues at different positions along the helix. We discuss the simulation results in the context of molecular biology results and show that the energetic discrepancy is reduced, but not eliminated, by considering free energy differences between Arg at the interface and at the center of the model helices. The reduction occurs because Arg snorkeling to the interface prevents Arg from residing in the bilayer center where the energetic cost of desolvation is highest. We then show that the problem with MD simulations is that they measure water-to-bilayer free energies, whereas the molecular biology experiments measure the energetics of partitioning from translocon to bilayer, which raises the fundamental question of the relationship between water-to-bilayer and water-to-translocon partitioning. We present two thermodynamic scenarios as a foundation for reconciliation of the simulation and molecular biology results. The simplest scenario is that translocon-to-bilayer partitioning is independent of water-to-bilayer partitioning; there is no thermodynamic cycle connecting the two paths

Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen

Amir Hadanny,1,2 Amit Maliar,1 Gregory Fishlev,1 Yair Bechor,1 Jacob Bergan,1 Mony Friedman,1 Isaac Avni,2,3 Shai Efrati1,2,4,5 1Sagol Center for Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Zerifin, Israel; 2Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; 3Opthalmology Department, Assaf Harofeh Medical Center, Zeirifin, Israel; 4Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel; 5Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel Purpose: Ischemic retinal damage can be reversed by hyperbaric oxygen therapy (HBOT) as long as irreversible infarction damage has not developed. However, the time window till irreversible damage develops is still unknown. The study aim was to evaluate the effect of HBOT and determine possible markers for irreversible retinal damage.Materials and methods: Retrospective analysis of 225 patients treated with HBOT for central retinal artery occlusion (CRAO) in 1999&ndash;2015. One hundred and twenty-eight patients fulfilled inclusion/exclusion criteria: age &gt;18 years, symptoms &lt;20 hours, and best-corrected visual acuity (BCVA) &lt;0.5 logMAR.Results: Time delay from symptoms to treatment was 7.8&plusmn;3.8 hours. The BCVA was significantly improved after HBOT, from 2.14&plusmn;0.50 to 1.61&plusmn;0.78 (P&lt;0.0001). The proportion of patients with clinically meaningful visual improvement was significantly higher in patients without cherry-red spot (CRS) compared to patients with CRS at presentation (86.0% vs 57.6%, P&lt;0.0001). The percentage of patients with final BCVA better than 1.0 was also significantly higher in patients without CRS vs patients with CRS at presentation (61.0% vs 7.1%, P&lt;0.0001). There was no correlation between CRS and the time from symptoms. HBOT was found to be safe, and only 5.5% of patients had minor, reversible, adverse events.Conclusion: HBOT is an effective treatment for non-arteritic CRAO as long as CRS has not formed. The fundus findings, rather than the time delay, should be used as a marker for irreversible damage. Keywords: HBOT, hyperbaric oxygen, central retinal artery occlusion, cherry-red spot, CRAO, retinal ischemi

GPS measurements of current crustal movements along the Dead Sea Fault

A network of 11 continuous GPS stations was constructed in Israel between 1996 and 2001 to monitor current crustal movements across the Dead Sea Fault (DSF). Analysis of the GPS measurements with respect to the ITRF2000 Reference Frame yields time series of daily site positions containing both secular and seasonal variations. Horizontal secular variations (station velocities) are evaluated with respect to the main tectonic element in the region, the DSF. We use six velocity vectors west of the DSF to define the ITRF2000 pole of the Sinai sub‐plate, and rotate the velocity field for all stations into the Sinai reference frame (SRF). The velocity vectors reveal that (1) relative station movements are less than 4 mm/yr; (2) the nine stations located west of the DSF show no statistically significant motion with respect to the SRF; and (3) the two stations located in the Golan Heights (KATZ and ELRO) and a station in Damascus, Syria (UDMC) show 1.7–2.8 mm/yr northward motion with respect to Sinai, indicating a left‐lateral motion along the DSF. Using locked‐fault models, we estimate the current slip rate across the DSF as 3.3 ± 0.4 mm/yr. If we exclude the northern sites (ELRO and UDMC), which are located adjacent to the compressional jog of Mount Hermon, our estimate increases to 3.7 ± 0.4 mm/yr. The calculated ITRF2000 Sinai, Eurasia, and Nubia poles and a published pole for Arabia allow us to calculate the current relative plate motion of Sinai‐Arabia and Sinai‐Nubia