Breakdown of the Potentiality Principle and Its Impact on Global Stem Cell Research

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Focal mechanisms in the southern Aegean from temporary seismic networks – implications for the regional stress field and ongoing deformation processes

The lateral variation of the stress field in the southern Aegean plate and the subducting Hellenic slab is determined from recordings of seismicity obtained with the CYCNET and EGELADOS networks in the years from 2002 to 2007. First motions from 7000 well-located microearthquakes were analysed to produce 540 well-constrained focal mechanisms. They were complemented by another 140 derived by waveform matching of records from larger events. Most of these earthquakes fall into 16 distinct spatial clusters distributed over the southern Aegean region. For each cluster, a stress inversion could be carried out yielding consistent estimates of the stress field and its spatial variation. At crustal levels, the stress field is generally dominated by a steeply dipping compressional principal stress direction except in places where coupling of the subducting slab and overlying plate come into play. Tensional principal stresses are generally subhorizontal. Just behind the forearc, the crust is under arc-parallel tension whereas in the volcanic areas around Kos, Columbo and Astypalea tensional and intermediate stresses are nearly degenerate. Further west and north, in the Santorini–Amorgos graben and in the area of the islands of Mykonos, Andros and Tinos, tensional stresses are significant and point around the NW–SE direction. Very similar stress fields are observed in western Turkey with the tensional axis rotated to NNE–SSW. Intermediate-depth earthquakes below 100 km in the Nisyros region indicate that the Hellenic slab experiences slab-parallel tension at these depths. The direction of tension is close to east–west and thus deviates from the local NW-oriented slab dip presumably owing to the segmentation of the slab. Beneath the Cretan sea, at shallower levels, the slab is under NW–SE compression. Tensional principal stresses in the crust exhibit very good alignment with extensional strain rate principal axes derived from GPS velocities except in volcanic areas, where both appear to be unrelated, and in the forearc where compressional principal stresses are very well aligned with compressional principal strain rates. This finding indicates that, except for volcanic areas, microseismic activity in the southern Aegean is not controlled by small-scale local stresses but rather reflects the regional stress field. The lateral and depth variations of the stress field reflect the various agents that influence tectonics in the Aegean: subduction of the Hellenic slab, incipient collision with continental African lithosphere, roll back of the slab in the southeast, segmentation of the slab, arc volcanism and extension of the Aegean crust

Receiver function images of the Hellenic subduction zone and comparison to microseismicity

New combined P receiver functions and seismicity data obtained from the EGELADOS network employing 65 seismological stations within the Aegean constrained new information on the geometry of the Hellenic subduction zone. The dense network and large data set enabled us to estimate the Moho depth of the continental Aegean plate across the whole area. Presence of a negative contrast at the Moho boundary indicating the serpentinized mantle wedge above the subducting African plate was seen along the entire forearc. Furthermore, low seismicity was observed within the serpentinized mantle wedge. We found a relatively thick continental crust (30–43 km) with a maximum thickness of about 48 km beneath the Peloponnese Peninsula, whereas a thinner crust of about 27–30 km was observed beneath western Turkey. The crust of the overriding plate is thinning beneath the southern and central Aegean and reaches 23–27 km. Unusual low Vp / Vs ratios were estimated beneath the central Aegean, which most likely represent indications on the pronounced felsic character of the extended continental Aegean crust. Moreover, P receiver functions imaged the subducted African Moho as a strong converted phase down to a depth of about 100 km. However, the converted Moho phase appears to be weak for the deeper parts of the African plate suggesting nearly complete phase transitions of crustal material into denser phases. We show the subducting African crust along eight profiles covering the whole southern and central Aegean. Seismicity of the western Hellenic subduction zone was taken from the relocated EHB-ISC catalogue, whereas for the eastern Hellenic subduction zone, we used the catalogues of manually picked hypocentre locations of temporary networks within the Aegean. Accurate hypocentre locations reveal a significant change in the dip angle of the Wadati–Benioff zone (WBZ) from west (~ 25°) to the eastern part (~ 35°) of the Hellenic subduction zone. Furthermore, a zone of high deformation can be characterized by a vertical offset of about 40 km of the WBZ beneath the eastern Cretan Sea. This deformation zone may separate a shallower N-ward dipping slab in the west from a steeper NW-ward dipping slab in the east. In contrast to hypocentre locations, we found very weak evidence for the presence of the slab at larger depths in the P receiver functions, which may result from the strong appearance of the Moho multiples as well as eclogitization of the oceanic crust. The presence of the top of a strong low-velocity zone at about 60 km depth in the central Aegean may be related to the asthenosphere below the Aegean continental lithosphere and above the subducting slab. Thus, the Aegean mantle lithosphere seems to be 30–40 km thick, which means that its thickness increased again since the removal of the mantle lithosphere about 15 to 35 Ma ago

Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1

During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection in an IL-10 reporter mouse line. Using this model, we demonstrated that virus-specific T cells with reduced inflammatory function, particularly Th1 cells, display elevated and sustained IL-10 expression during chronic LCMV infection. Furthermore, ablation of IL-10 from the T cell compartment partially restored T cell function and reduced viral loads in LCMV-infected animals. We found that viral persistence is needed for sustained IL-10 production by Th1 cells and that the transcription factor BLIMP-1 is required for IL-10 expression by Th1 cells. Restimulation of Th1 cells from LCMV-infected mice promoted BLIMP-1 and subsequent IL-10 expression, suggesting that constant antigen exposure likely induces the BLIMP-1/IL-10 pathway during chronic viral infection. Together, these data indicate that effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.This work was supported by an Australian NHMRC Overseas Biomedical Postdoctoral Fellowship (to I.A. Parish); a Yale School of Medicine Brown-Coxe Postdoctoral Fellowship (to I.A. Parish); the Alexander von Humboldt Foundation (SKA2010, to P.A. Lang); a CIHR grant (to P.S. Ohashi); and by the Howard Hughes Medical Institute and NIH grant RO1AI074699 (to S.M. Kaech). P.S. Ohashi holds a Canada Research Chair in Autoimmunity and Tumor immunity

Pumilio-2 Function in the Mouse Nervous System

Coordinated mRNA translation at the synapse is increasingly recognized as a critical mechanism for neuronal regulation. Pumilio, a translational regulator, is known to be involved in neuronal homeostasis and memory formation in Drosophila. Most recently, the mammalian Pumilio homolog Pumilio-2 (Pum2) has been found to play a role in the mammalian nervous system, in particular in regulating morphology, arborization and excitability of neuronal dendrites, in vitro. However, the role of Pum2 in vivo remains unclear. Here, we report our investigation of the functional and molecular consequences of Pum2 disruption in vivo using an array of neurophysiology, behavioral and gene expression profiling techniques. We used Pum2-deficient mice to monitor in vivo brain activity using EEG and to study behavior traits, including memory, locomotor activity and nesting capacities. Because of the suspected role of Pum2 in neuronal excitability, we also examined the susceptibility to seizure induction. Finally, we used a quantitative gene expression profiling assay to identify key molecular partners of Pum2. We found that Pum2-deficient mice have abnormal behavioral strategies in spatial and object memory test. Additionally, Pum2 deficiency is associated with increased locomotor activity and decreased body weight. We also observed environmentally-induced impairment in nesting behavior. Most importantly, Pum2-deficient mice showed spontaneous EEG abnormalities and had lower seizure thresholds using a convulsing dosage of pentylenetetrazole. Finally, some genes, including neuronal ion channels, were differentially expressed in the hippocampus of Pum2-deficient mice. These findings demonstrate that Pum2 serves key functions in the adult mammalian central nervous system encompassing neuronal excitability and behavioral response to environmental challenges

Systemic Inflammation Predicts Alzheimer Pathology in Community Samples without Dementia

Neuroinflammation and oxidative stress (OS) are implicated in the pathophysiology of Alzheimer’s disease (AD). However, it is unclear at what stage of the disease process inflammation first becomes manifest. The aim of this study was to investigate the associations between specific plasma markers of inflammation and OS, tau, and Amyloid-β 38, 40, and 42 levels in cognitively unimpaired middle-age and older individuals. Associations between inflammatory states identified through principal component analysis and AD biomarkers were investigated in middle-age (52–56 years, n = 335, 52% female) and older-age (72–76 years, n = 351, 46% female) participants without dementia. In middle-age, a component reflecting variation in OS was most strongly associated with tau and to a lesser extent amyloid-β levels. In older-age, a similar component to that observed in middle-age was only associated with tau, while another component reflecting heightened inflammation independent of OS, was associated with all AD biomarkers. In middle and older-age, inflammation and OS states are associated with plasma AD biomarkers

Torsion pairs and rigid objects in tubes

We classify the torsion pairs in a tube category and show that they are in bijection with maximal rigid objects in the extension of the tube category containing the Pruefer and adic modules. We show that the annulus geometric model for the tube category can be extended to the larger category and interpret torsion pairs, maximal rigid objects and the bijection between them geometrically. We also give a similar geometric description in the case of the linear orientation of a Dynkin quiver of type A.Comment: 25 pages, 13 figures. Paper shortened. Minor errors correcte

Enhanced TCR-induced Apoptosis in Interferon Regulatory Factor 4–deficient CD4+ Th Cells

Transcription factors of the interferon regulatory factor (IRF) family contribute to the regulation of cell proliferation and apoptosis. Here, we show that CD4+ T helper (Th) cells lacking IRF4 (IRF4−/−) are highly sensitive to apoptosis. After infection of IRF4−/− mice with the protozoan parasite Leishmania major, the lesion-draining lymph nodes developed the prototypic lymphadenopathy of wild-type mice after 4 wk, but demonstrated almost total loss of cellularity and enhanced apoptosis after 7 wk. In vitro, activation of IRF4−/− CD4+ Th cells led to greatly increased apoptosis compared with wild-type cells. Coculture of IRF4−/− and IRF4+/+ CD4+ cells did not increase survival of IRF4−/− CD4+ cells, indicating that the enhanced rate of IRF4−/− Th cell apoptosis was neither transferable nor due to lack of a cytokine. Enhanced CD4+ cell apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95 expression. Removal of endogenous cytokines, notably interleukin (IL)-4, led to increased and equally high levels of IRF4−/− and IRF4+/+ cell apoptosis, whereas the protective activity of exogenous IL-4 was reduced in IRF4−/− CD4+ cells despite normal expression of the IL-4 receptor. Therefore, IRF4 is central in protecting CD4+ cells against proapoptotic stimuli

Cycle-finite module categories

We describe the structure of module categories of finite dimensional algebras over an algebraically closed field for which the cycles of nonzero nonisomorphisms between indecomposable finite dimensional modules are finite (do not belong to the infinite Jacobson radical of the module category). Moreover, geometric and homological properties of these module categories are exhibited