Source model of the 2007 M_w 8.0 Pisco, Peru earthquake: Implications for seismogenic behavior of subduction megathrusts

We use Interferometric Synthetic Aperture Radar, teleseismic body waves, tsunami waveforms recorded by tsunameters, field observations of coastal uplift, subsidence, and runup to develop and test a refined model of the spatiotemporal history of slip during the M_w 8.0 Pisco earthquake of 15 August 2007. Our preferred solution shows two distinct patches of high slip. One patch is located near the epicenter while another larger patch ruptured 60 km further south, at the latitude of the Paracas peninsula. Slip on the second patch started 60 s after slip initiated on the first patch. We observed a remarkable anticorrelation between the coseismic slip distribution and the aftershock distribution determined from the Peruvian seismic network. The proposed source model is compatible with regional runup measurements and open ocean tsunami records. From the latter data set, we identified the 12 min timing error of the tsunami forecast system as being due to a mislocation of the source, caused by the use of only one tsunameter located in a nonoptimal azimuth. The comparison of our source model with the tsunami observations validate that the rupture did not extend to the trench and confirms that the Pisco event is not a tsunami earthquake despite its low apparent rupture velocity (<1.5 km/s). We favor the interpretation that the earthquake consists of two subevents, each with a conventional rupture velocity (2–4 km/s). The delay between the two subevents might reflect the time for the second shock to nucleate or, alternatively, the time it took for afterslip to increase the stress level on the second asperity to a level necessary for static triggering. The source model predicts uplift offshore and subsidence on land with the pivot line following closely the coastline. This pattern is consistent with our observation of very small vertical displacement along the shoreline when we visited the epicentral area in the days following the event. This earthquake represents, to our knowledge, one of the best examples of a link between the geomorphology of the coastline and the pattern of surface deformation induced by large interplate ruptures

CSRP3 mediates polyphenols-induced cardioprotection in hypertension

Berries contain bioactive polyphenols, whose capacity to prevent cardiovascular diseases has been established recently in animal models as well in human clinical trials. However, cellular processes and molecular targets of berries polyphenols remain to be identified. The capacity of a polyphenol-enriched diet (i.e., blueberries, blackberries, raspberries, strawberry tree fruits and Portuguese crowberries berries mixture) to promote animal survival and protect cardiovascular function from salt-induced hypertension was evaluated in a chronic salt-sensitive Dahl rat model. The daily consumption of berries improved survival of Dahl/salt-sensitive rats submitted to high-salt diet and normalized their body weight, renal function and blood pressure. In addition, a prophylactic effect was observed at the level of cardiac hypertrophy and dysfunction, tissue cohesion and cardiomyocyte hypertrophy. Berries also protected the aorta from fibrosis and modulated the expression of aquaporin-1, a channel involved in endothelial water and nitric oxide permeability. Left ventricle proteomics analysis led to the identification of berries and salt metabolites targets, including cystein and glycin-rich protein 3 (CSRP3), a protein involved in myocyte cytoarchitecture. In neonatal rat ventricular cardiomyocytes, CSRP3 was validated as a target of a berries-derived polyphenol metabolite, 4-methylcatechol sulfate, at micromolar concentrations, mimicking physiological conditions of human plasma circulation. Accordingly, siRNA silencing of CSRP3 and 4-methylcatechol sulfate pretreatment reversed cardiomyocyte hypertrophy and CSRP3 overexpression induced by phenylephrine. Our systemic study clearly supports the modulation of CSRP3 by a polyphenol-rich berries diet as an efficient cardioprotective strategy in hypertension-induced heart failure

Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice

<p>Abstract</p> <p>Background</p> <p>The mechanism by which HIV infection leads to a selective depletion of CD4 cells leading to immunodeficiency remains highly debated. Whether the loss of CD4 cells is a direct consequence of virus infection or bystander apoptosis of uninfected cells is also uncertain.</p> <p>Results</p> <p>We have addressed this issue in the humanized mouse model of HIV infection using a HIV variant with a point mutation in the gp41 region of the Env glycoprotein that alters its fusogenic activity. We demonstrate here that a single amino acid change (V38E) altering the cell-to-cell fusion activity of the Env minimizes CD4 loss in humanized mice without altering viral replication. This differential pathogenesis was associated with a lack of bystander apoptosis induction by V38E virus even in the presence of similar levels of infected cells. Interestingly, immune activation was observed with both WT and V38E infection suggesting that the two phenomena are likely not interdependent in the mouse model.</p> <p>Conclusions</p> <p>We conclude that Env fusion activity is one of the determinants of HIV pathogenesis and it may be possible to attenuate HIV by targeting gp41.</p

Triggering of the 2014 M_w7.3 Papanoa earthquake by a slow slip event in Guerrero, Mexico

Since their discovery two decades ago, slow slip events have been shown to play an important role in accommodating strain in subduction zones. However, the physical mechanisms that generate slow slip and the relationships with earthquakes are unclear. Slow slip events have been recorded in the Guerrero segment of the Cocos–North America subduction zone. Here we use inversion of position time series recorded by a continuous GPS network to reconstruct the evolution of aseismic slip on the subduction interface of the Guerrero segment. We find that a slow slip event began in February 2014, two months before the magnitude (M_w) 7.3 Papanoa earthquake on 18 April. The slow slip event initiated in a region adjacent to the earthquake hypocentre and extended into the vicinity of the seismogenic zone. This spatio-temporal proximity strongly suggests that the Papanoa earthquake was triggered by the ongoing slow slip event. We demonstrate that the triggering mechanism could be either static stress increases in the hypocentral region, as revealed by Coulomb stress modelling, or enhanced weakening of the earthquake hypocentral area by the slow slip. We also show that the plate interface in the Guerrero area is highly coupled between slow slip events, and that most of the accumulated strain is released aseismically during the slow slip episodes

Identification of Novel Single Nucleotide Polymorphisms in Inflammatory Genes as Risk Factors Associated with Trachomatous Trichiasis

infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined. = 0.001] with the combination of TNFA (-308A), LTA (252A), VCAM1 (-1594C), SCYA 11 (23T) minor allele, and the combination of TNFA (-308A), IL9 (113M), IL1B (5′UTR-T), and VCAM1 (-1594C). However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3–22), p = 0.001] with the combination of TNFA (-308G), VDR (intron G), IL4R (50V), and ICAM1 (56M) minor allele.Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should be considered in the context of designing global control programs

Seismic and aseismic slip on the Central Peru megathrust

Slip on a subduction megathrust can be seismic or aseismic, with the two modes of slip complementing each other in time and space to accommodate the long-term plate motions. Although slip is almost purely aseismic at depths greater than about 40 km, heterogeneous surface strain suggests that both modes of slip occur at shallower depths, with aseismic slip resulting from steady or transient creep in the interseismic and postseismic periods. Thus, active faults seem to comprise areas that slip mostly during earthquakes, and areas that mostly slip aseismically. The size, location and frequency of earthquakes that a megathrust can generate thus depend on where and when aseismic creep is taking place, and what fraction of the long-term slip rate it accounts for. Here we address this issue by focusing on the central Peru megathrust. We show that the Pisco earthquake, with moment magnitude M_w = 8.0, ruptured two asperities within a patch that had remained locked in the interseismic period, and triggered aseismic frictional afterslip on two adjacent patches. The most prominent patch of afterslip coincides with the subducting Nazca ridge, an area also characterized by low interseismic coupling, which seems to have repeatedly acted as a barrier to seismic rupture propagation in the past. The seismogenic portion of the megathrust thus appears to be composed of interfingering rate-weakening and rate-strengthening patches. The rate-strengthening patches contribute to a high proportion of aseismic slip, and determine the extent and frequency of large interplate earthquakes. Aseismic slip accounts for as much as 50–70% of the slip budget on the seismogenic portion of the megathrust in central Peru, and the return period of earthquakes with M_w = 8.0 in the Pisco area is estimated to be 250  years

Lack of Effective Anti-Apoptotic Activities Restricts Growth of Parachlamydiaceae in Insect Cells

The fundamental role of programmed cell death in host defense is highlighted by the multitude of anti-apoptotic strategies evolved by various microbes, including the well-known obligate intracellular bacterial pathogens Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae. As inhibition of apoptosis is assumed to be essential for a successful infection of humans by these chlamydiae, we analyzed the anti-apoptotic capacity of close relatives that occur as symbionts of amoebae and might represent emerging pathogens. While Simkania negevensis was able to efficiently replicate within insect cells, which served as model for metazoan-derived host cells, the Parachlamydiaceae (Parachlamydia acanthamoebae and Protochlamydia amoebophila) displayed limited intracellular growth, yet these bacteria induced typical features of apoptotic cell death, including formation of apoptotic bodies, nuclear condensation, internucleosomal DNA fragmentation, and effector caspase activity. Induction of apoptosis was dependent on bacterial activity, but not bacterial de novo protein synthesis, and was detectable already at very early stages of infection. Experimental inhibition of host cell death greatly enhanced parachlamydial replication, suggesting that lack of potent anti-apoptotic activities in Parachlamydiaceae may represent an important factor compromising their ability to successfully infect non-protozoan hosts. These findings highlight the importance of the evolution of anti-apoptotic traits for the success of chlamydiae as pathogens of humans and animals

HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase

The Trans-activator protein (Tat) of human immunodeficiency virus (HIV) is a pleiotropic protein involved in different aspects of AIDS pathogenesis. As a number of viral proteins Tat is suspected to disturb mitochondrial function. We prepared pure synthetic full-length Tat by native chemical ligation (NCL), and Tat peptides, to evaluate their direct effects on isolated mitochondria. Submicromolar doses of synthetic Tat cause a rapid dissipation of the mitochondrial transmembrane potential (ΔΨm) as well as cytochrome c release in mitochondria isolated from mouse liver, heart, and brain. Accordingly, Tat decreases substrate oxidation by mitochondria isolated from these tissues, with oxygen uptake being initially restored by adding cytochrome c. The anion-channel inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) protects isolated mitochondria against Tat-induced mitochondrial membrane permeabilization (MMP), whereas ruthenium red, a ryanodine receptor blocker, does not. Pharmacologic inhibitors of the permeability transition pore, Bax/Bak inhibitors, and recombinant Bcl-2 and Bcl-XL proteins do not reduce Tat-induced MMP. We finally observed that Tat inhibits cytochrome c oxidase (COX) activity in disrupted mitochondria isolated from liver, heart, and brain of both mouse and human samples, making it the first described viral protein to be a potential COX inhibitor

Viral Control of Mitochondrial Apoptosis

Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus