Water input and water release from the subducting Nazca Plate along southern Central Chile (33°S-46°S)

The age of the subducting Nazca Plate off Chile increases northward from 0 Ma at the Chile Triple Junction (46°S) to 37 Ma at the latitude of Valparaíso (32°S). Age-related variations in the thermal state of the subducting plate impact on (a) the water influx to the subduction zone, as well as on (b) the volumes of water that are released under the continental fore arc or, alternatively, carried beyond the arc. Southern Central Chile is an ideal setting to study this effect, because other factors for the subduction zone water budget appear constant. We determine the water influx by calculating the crustal water uptake and by modeling the upper mantle serpentinization at the outer rise of the Chile Trench. The water release under fore arc and arc is determined by coupling FEM thermal models of the subducting plate with stability fields of water-releasing mineral reactions for upper and lower crust and hydrated mantle. Results show that both the influx of water stored in, and the outflux of water released from upper crust, lower crust, and mantle vary drastically over segment boundaries. In particular, the oldest and coldest segments carry roughly twice as much water into the subduction zone as the youngest and hottest segments, but their release flux to the fore arc is only about one fourth of the latter. This high variability over a subduction zone of <1500 km length shows that it is insufficient to consider subduction zones as uniform entities in global estimates of subduction zone fluxes

Thermal control of the seismogenic zone of southern central Chile

We developed thermal models for the Chile subduction zone along two profiles at 38.2°S and 42°S within the rupture area of the 1960 M = 9.5 Valdivia earthquake and south of the 2010 M = 8.8 Maule earthquake. The age difference of the subducting Nazca Plate has a major impact on the thermal regime, being much younger and hotter in the south. Seafloor heat flow observations confirm this difference but also indicate that in the southern area, heat advection at the outer rise cools the incoming plate. Heat flow values derived from the depth of gas hydrate bottom-simulating reflectors are in general agreement with probe and borehole measurements. The positions where the plate interface reaches temperatures of 100–150°C and 350–450°C differ between the two profiles. If these temperatures control the updip and downdip limits of the interplate seismogenic zone, the seismogenic zone widens and shifts landward to greater depths from south to north. Observed microseismicity, however, seems to fade at temperatures much lower than 350–450°C. This discrepancy can be explained in three alternative ways: (1) deformation in a thick subduction channel controls the seismic/aseismic transition; (2) microseismicity recorded over a limited time period does not represent the rupture depth of large interface earthquakes; or (3) the serpentinized mantle wedge controls the downdip limit

2-D kinematic restoration of the western Tauern Window using thermochronological constraints

The Tauern Window (TW) in the European Alps has a high tectonic complexity. It is a key area to understand a number of important orogenic processes. During the Cretaceous, subduction and accretion of the Penninic realm beneath the northern margin of Adria (Austroalpine) began, which led to collision between Europe (Subpenninic) and the Adria margin, from Eocene to early Oligocene. This resulted in the Penninic and Subpenninic nappe stack in the southward-dipping orogenic wedge. After the “Tauernkristallisation”-event, indentation of the Dolomites Indenter (Eastern Southern Alps) is heralded in the last deformation stage, which bent the primarily W-E striking, dextral Periadriatic Fault System (PFS) separating the Eastern from the Southern Alps, and finally caused this fault system to be sinistrally offset by the NNE-SSW-striking Giudicarie fault system in the Miocene. This last deformation stage resulted in strong N-S shortening (ca. 70 km) of the western TW in front of the Dolomites indenter as well as W-E extension, which formed the Katschberg and Brenner Normal Faults (eastern and western border of the TW), and to lateral extrusion towards the east involving major strike-slip faults (e.g., Inntal Fault, PFS, SEMP). It is widely assumed that all these processes happened synkinematically exhuming the western TW up to ca. 20 km (derived from the throw of the Brenner Normal Fault and by the metamorphic conditions reached). However, the quantitative deformation history of the western TW, and in particular its Subpenninic core (Venediger Duplex, VD), has never been investigated in detail. Our goal is therefore to quantify the deformation and kinematics accommodated by the VD in a first step by restoring the Brenner Base Tunnel cross-section using the software MOVE (Ptx). Since standard balancing of this structure is not possible due to penetrative deformation, we integrate Zircon Fission Track data (partial annealing zone of 240 – 180°C and closure temperature ca. 210°C) as marker for the transition from brittle to viscous conditions in the felsic rocks of the VD: Any folding in the VD must be older than the ZFT age of the corresponding unit. For this reason, we first displaced the whole duplex structure down along the Sub-Tauern Ramp below the Zircon Fission Track annealing zone. We then unfolded the gneiss cores individually until a symmetrical duplex structure was modeled, which reached 20 km depth. Since the modeling of vertical exhumation, N-S shortening and displacement along the Sub-Tauern Ramp strongly depends on the geothermal gradient (GG), we tested different GG. Resulting exhumation rates related to a GG of 30°C/km and 50°/km fit well with former studies, which means that 30-50°C/km is a reasonable range for the GG during the last deformation stage

OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line–specific Manner

OCI-5/GPC3 is a member of the glypican family. Glypicans are heparan sulfate proteoglycans that are bound to the cell surface through a glycosyl-phosphatidylinositol anchor. It has recently been shown that the OCI-5/GPC3 gene is mutated in patients with the Simpson-Golabi-Behmel Syndrome (SGBS), an X-linked disorder characterized by pre- and postnatal overgrowth and various visceral and skeletal dysmorphisms. Some of these dysmorphisms could be the result of deficient growth inhibition or apoptosis in certain cell types during development. Here we present evidence indicating that OCI-5/GPC3 induces apoptosis in cell lines derived from mesothelioma (II14) and breast cancer (MCF-7). This induction, however, is cell line specific since it is not observed in NIH 3T3 fibroblasts or HT-29 colorectal tumor cells. We also show that the apoptosis-inducing activity in II14 and MCF-7 cells requires the anchoring of OCI-5/GPC3 to the cell membrane. The glycosaminoglycan chains, on the other hand, are not required. MCF-7 cells can be rescued from OCI-5/GPC3–induced cell death by insulin-like growth factor 2. This factor has been implicated in Beckwith-Wiedemann, an overgrowth syndrome that has many similarities with SGBS. The discovery that OCI-5/GPC3 is able to induce apoptosis in a cell line– specific manner provides an insight into the mechanism that, at least in part, is responsible for the phenotype of SGBS patients

Regulatory objectivity in action: Mild cognitive impairment and the collective production of uncertainty

In this paper, we investigate recent changes in the definition and approach to Alzheimer’s disease brought about by growing clinical, therapeutic and regulatory interest in the prodromal or preclinical aspects of this condition. In the last decade, there has been an increased interest in the biomolecular and epidemiological characterization of pre-clinical dementia. It is argued that early diagnosis of dementia, and particularly of Alzheimer‘s disease, will facilitate the prevention of dementing processes and lower the prevalence of the condition in the general population. The search for a diagnostic category or biomarker that would serve this purpose is an ongoing but problematic endeavour for research and clinical communities in this area. In this paper, we explore how clinical and research actors, in collaboration with regulatory institutions and pharmaceutical companies, come to frame these domains as uncertainties and how they re-deploy uncertainty in the ‘collective production’ of new diagnostic conventions and bioclinical standards. While drawing as background on ethnographic, documentary and interview data, the paper proposes an in-depth, contextual analysis of the proceedings of an international meeting organized by the Peripheral and Central Nervous System Drug Advisory Committee of the US Food and Drug Administration to discuss whether or not a particular diagnostic convention — mild cognitive impairment — exists and how best it ought to be studied. Based on this analysis we argue that the deployment of uncertainty is reflexively implicated in bioclinical collectives’ search for rules and conventions, and furthermore that the collective production of uncertainty is central to the ‘knowledge machinery’ of regulatory objectivity

Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome

Glypicans are a family of heparan sulfate proteoglycans that are linked to the cell surface through a glycosyl–phosphatidylinositol anchor. One member of this family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel syndrome (SGBS). These patients display pre- and postnatal overgrowth, and a varying range of dysmorphisms. The clinical features of SGBS are very similar to the more extensively studied Beckwith-Wiedemann syndrome (BWS). Since BWS has been associated with biallelic expression of insulin-like growth factor II (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II. However, there is still no biochemical evidence indicating that GPC3 plays such a role

The CD81 Partner EWI-2wint Inhibits Hepatitis C Virus Entry

Two to three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor