Tectonic mechanisms associated with P-T paths of regional metamorphism: Alternatives to single-cycle thrusting and heating

Abstract Metamorphic pressure ( P) -temperature (T) paths are commonly used as tools to interpret the tectonic history of orogenic belts, those deformed belts of rocks that record past activity along active plate margins. Many studies and reviews relating P -T path development to tectonics have focused on thrusting -thermal relaxation cycles, with special emphasis on collisional processes. Other studies have assumed that P -T paths resulted from a single tectono-metamorphic event that accounted for the entire burial -exhumation history of the rocks. In many cases, such assumptions may prove invalid. This paper speculates on the relationship of tectonic processes other than thrusting -heating to P -T path development. The processes discussed herein include subduction initiation, triple-junction interactions, initiation and shut off of arc volcanism, subcontinental delamination, and hot spot migration. All of these processes may leave a signature in the metamorphic rock record. Examples are presented from a number of localities, most of which are from the Pacific Rim. Although thrustingheating cycles have influenced metamorphic evolution in many orogenic belts, the potential impact of other types of tectonic mechanisms should not be overlooked.

Tectonic wedging, blueschist metamorphism, and exposure of blueschists: Are they compatible?

ABSTRACT Tectonic wedging is currently deforming rocks along the western margin of the Central Valley of California. Structural relations in the strata of the Mesozoic Great Valley Group fore-arc basin indicate that earlier phases of wedging were coeval with subduction and accretion of the Franciscan Complex to the west. The presentday geometry of tectonic wedging is incompatible with blueschist metamorphism in the Franciscan complex because the detachment for the wedge system would have prevented the transport of accretionary-wedge materials to great depth. We propose a sequence of tectonic events that reconciles these tectonic processes

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

World squid fisheries

Peer reviewedPublisher PD

Promotion of testa rupture during garden cress germination involves seed compartment-specific expression and activity of pectin methylesterases

Pectin methylesterase (PME) controls the methylesterification status of pectins and thereby determines the biophysical properties of plant cell walls, which are important for tissue growth and weakening processes. We demonstrate here that tissue-specific and spatiotemporal alterations in cell wall pectin methylesterification occur during the germination of garden cress (Lepidium sativum). These cell wall changes are associated with characteristic expression patterns of PME genes and resultant enzyme activities in the key seed compartments CAP (micropylar endosperm) and RAD (radicle plus lower hypocotyl). Transcriptome and quantitative real-time reverse transcription-polymerase chain reaction analysis as well as PME enzyme activity measurements of separated seed compartments, including CAP and RAD, revealed distinct phases during germination. These were associated with hormonal and compartment-specific regulation of PME group 1, PME group 2, and PME inhibitor transcript expression and total PME activity. The regulatory patterns indicated a role for PME activity in testa rupture (TR). Consistent with a role for cell wall pectin methylesterification in TR, treatment of seeds with PME resulted in enhanced testa permeability and promoted TR. Mathematical modeling of transcript expression changes in germinating garden cress and Arabidopsis (Arabidopsis thaliana) seeds suggested that group 2 PMEs make a major contribution to the overall PME activity rather than acting as PME inhibitors. It is concluded that regulated changes in the degree of pectin methylesterification through CAP- and RAD-specific PME and PME inhibitor expression play a crucial role during Brassicaceae seed germination

The forearc ophiolites of California formed during trench-parallel spreading: Kinematic reconstruction of the western USA Cordillera since the Jurassic

Ophiolites, fragments of oceanic lithosphere exposed on land, are typically found as isolated klippen in intensely deformed fold-thrust belts spanning hundreds to thousands of kilometers along-strike. Ophiolites whose geochemistry indicates that they formed above subduction zones, may have been relics of larger, once-coherent, oceanic lithosphere tracts that formed the leading edge of an upper plate below which subduction occurred; such tracts were subsequently dismembered by deformation and erosion during orogenesis and uplift. However, to what extent the first-order original coherence is maintained between ophiolitic klippen is difficult to assess. Here, we aim to evaluate whether the Jurassic forearc ophiolites overlying subduction complex rocks in California, now scattered over 1000 km and dismembered by the wider San Andreas Fault Zone, still maintain their original lithospheric coherence. To this end we (i) compile available crustal ages from all ophiolite klippen exposed in the Jurassic ophiolite belt of the western United States; (ii) review and kinematically reconstruct post-middle Jurassic deformation that occurred between the modern western coast and the stable North American craton to restore the original positions of the ophiolite fragments relative to each other and to North America, and (iii) perform a paleomagnetic analysis of a sheeted dyke sections of the Mt. Diablo and Josephine ophiolites to estimate the orientation of the spreading axis at which the Jurassic Californian forearc ophiolites formed. The latter analysis reveals that the original ridge orientation likely trended ∼080–260°, near-perpendicular to the orientation of the trench along the western margin of the ophiolite belt. We show that with these constraints, a straightforward ridge-transform system can explain the age distributions of the ophiolites with spreading rates of 6–7 cm/a. Our analysis shows that the Jurassic ophiolites of California may be considered klippen of a single sheet of oceanic lithosphere that accreted at a supra-subduction zone spreading ridge. In addition, we show that kinematic and paleomagnetic analysis of ophiolite belts may provide novel constraints on the kinematic evolution of accretionary orogens and the plates now lost to subduction

Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s) and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress), and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP). Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects.Clinicaltrials.gov NCT01155492

The Interaction of αB-Crystallin with Mature α-Synuclein Amyloid Fibrils Inhibits Their Elongation

αB-Crystallin is a small heat-shock protein (sHsp) that is colocalized with α-synuclein (αSyn) in Lewy bodies—the pathological hallmarks of Parkinson's disease—and is an inhibitor of αSyn amyloid fibril formation in an ATP-independent manner in vitro. We have investigated the mechanism underlying the inhibitory action of sHsps, and here we establish, by means of a variety of biophysical techniques including immunogold labeling and nuclear magnetic resonance spectroscopy, that αB-crystallin interacts with αSyn, binding along the length of mature amyloid fibrils. By measurement of seeded fibril elongation kinetics, both in solution and on a surface using a quartz crystal microbalance, this binding is shown to strongly inhibit further growth of the fibrils. The binding is also demonstrated to shift the monomer-fibril equilibrium in favor of dissociation. We believe that this mechanism, by which a sHsp interacts with mature amyloid fibrils, could represent an additional and potentially generic means by which at least some chaperones protect against amyloid aggregation and limit the onset of misfolding diseases

BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.

T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs. In naive cells, this prevented TCR-driven induction of genes associated with terminal differentiation. Upon effector differentiation, reduced expression of BACH2 and its phosphorylation enabled unrestrained induction of TCR-driven effector programs