Abstract
Geological sources of H
2
and abiotic CH
4
have had a critical role in the evolution of our planet and the development of life and sustainability of the deep subsurface biosphere. Yet the ...origins of these sources are largely unconstrained. Hydration of mantle rocks, or serpentinization, is widely recognized to produce H
2
and favour the abiotic genesis of CH
4
in shallow settings. However, deeper sources of H
2
and abiotic CH
4
are missing from current models, which mainly invoke more oxidized fluids at convergent margins. Here we combine data from exhumed subduction zone high-pressure rocks and thermodynamic modelling to show that deep serpentinization (40–80 km) generates significant amounts of H
2
and abiotic CH
4
, as well as H
2
S and NH
3
. Our results suggest that subduction, worldwide, hosts large sources of deep H
2
and abiotic CH
4
, potentially providing energy to the overlying subsurface biosphere in the forearc regions of convergent margins.
A lack of inversion symmetry coupled with the presence of time‐reversal symmetry endows 2D transition metal dichalcogenides with individually addressable valleys in momentum space at the K and K′ ...points in the first Brillouin zone. This valley addressability opens up the possibility of using the momentum state of electrons, holes, or excitons as a completely new paradigm in information processing. The opportunities and challenges associated with manipulation of the valley degree of freedom for practical quantum and classical information processing applications were analyzed during the 2017 Workshop on Valleytronic Materials, Architectures, and Devices; this Review presents the major findings of the workshop.
Valleytronics offers a new paradigm in information processing based on the optical and electrical manipulation of the valley degree of freedom in 2D materials with broken inversion symmetry. Delivering impactful, real‐world technology based on valleytronics requires a concrete assessment of the advantages over existing technologies and an analysis of the key challenges that must be overcome.
Ocean sediments consist mainly of calcium carbonate and organic matter (phytoplankton debris). Once subducted, some carbon is removed from the slab and returns to the atmosphere as CO
in arc magmas. ...Its isotopic signature is thought to reflect the bulk fraction of inorganic (carbonate) and organic (graphitic) carbon in the sedimentary source. Here we challenge this assumption by experimentally investigating model sediments composed of
C-CaCO
+
C-graphite interacting with water at pressure, temperature and redox conditions of an average slab-mantle interface beneath arcs. We show that oxidative dissolution of graphite is the main process controlling the production of CO
, and its isotopic composition reflects the CO
/CaCO
rather than the bulk graphite/CaCO
(i.e., organic/inorganic carbon) fraction. We provide a mathematical model to relate the arc CO
isotopic signature with the fluid-rock ratios and the redox state in force in its subarc source.
Several studies have shown the differences among chronotypes in the circadian rhythm of different physiological variables. Individuals show variation in their preference for the daily timing of ...activity; additionally, there is an association between chronotype and sleep duration/sleep complaints. Few studies have investigated sleep quality during the week days and weekends in relation to the circadian typology using self-assessment questionnaires or actigraphy. The purpose of this study was to use actigraphy to assess the relationship between the three chronotypes and the circadian rhythm of activity levels and to determine whether sleep parameters respond differently with respect to time (weekdays versus the weekend) in Morning-types (M-types), Neither-types (N-types) and Evening-types (E-types). The morningness-eveningness questionnaire (MEQ) was administered to 502 college students to determine their chronotypes. Fifty subjects (16 M-types, 15 N-types and 19 E-types) were recruited to undergo a 7-days monitoring period with an actigraph (Actiwacth® actometers, CNT, Cambridge, UK) to evaluate their sleep parameters and the circadian rhythm of their activity levels. To compare the amplitude and the acrophase among the three chronotypes, we used a one-way ANOVA followed by the Tukey-Kramer post-hoc test. To compare the Midline Estimating Statistic of Rhythm (MESOR) among the three chronotypes, we used a Kruskal-Wallis non-parametric test followed by pairwise comparisons that were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. The analysis of each sleep parameter was conducted using the mixed ANOVA procedure. The results showed that the chronotype was influenced by sex (χ2 with p = 0.011) and the photoperiod at birth (χ2 with p < 0.05). Though the MESOR and amplitude of the activity levels were not different among the three chronotypes, the acrophases compared by the ANOVA post-hoc test were significantly different (p < 0.001). The ANOVA post-hoc test revealed the presence of a significant difference (p < 0.001) between the M-types (14:32 h) and E-types (16:53 h). There was also a significant interaction between the chronotype and four sleep parameters: Sleep end, Assumed Sleep, Immobility Time and Sleep Efficiency. Sleep Efficiency showed the same patterns as did Assumed Sleep and Immobility Time: the Sleep Efficiency of the E-types was poorer than that of the M- and N-types during weekdays (77.9% ± 7.0 versus 84.1% ± 4.9 and 84.1% ± 5.2) but was similar to that measured in the M- and N-types during the weekend. Sleep Latency and Movement and Fragmentation Index were not different among the three chronotypes and did not change on the weekend compared with weekdays. This study highlights two key findings: first, we observed that the circadian rhythm of activity levels was influenced by the chronotype; second, the chronotype had a significant effect on sleep parameters: the E-types had a reduced sleep quality and quantity compared with the M- and N-types during weekdays, whereas the E-types reached the same levels as the other chronotypes during the weekends. These findings suggest that E-types accumulate a sleep deficit during weekdays due to social and academic commitments and that they recover from this deficit during "free days" on the weekend.
The circadian clock has a critical role in many physiological functions of skeletal muscle and is essential to fully understand the precise underlying mechanisms involved in these complex ...interactions. The importance of circadian expression for structure, function and metabolism of skeletal muscle is clear when observing the muscle phenotype in models of molecular clock disruption. Presently, the maintenance of circadian rhythms is emerging as an important new factor in human health, with disruptions linked to ageing, as well as to the development of many chronic diseases, including sarcopenia. Therefore, the aim of this review is to present the latest findings demonstrating how circadian rhythms in skeletal muscle are important for maintenance of the cellular physiology, metabolism and function of skeletal muscle. Moreover, we will present the current knowledge about the tissue-specific functions of the molecular clock in skeletal muscle.
The metamorphic belt of northern New Caledonia represents one of the best-exposed example of fossil Pacific-type subduction zone and a worldwide reference for high-pressure (H
P
) metamorphism and ...metamorphic mineral isograds, marked by a gradual evolution from very low-grade lawsonite-bearing to high-grade epidote-bearing eclogite assemblages. Despite the general agreement on the progressive increase in metamorphism, open debates hinge on the tectonic meaning of such mineral isograds, either interpreted as fossilized continuous metamorphic gradients or as major tectonic discontinuities. We present a new and extensive metamorphic dataset acquired by means of Raman spectroscopy of carbonaceous material and pseudosection modeling. Additional
PT
estimates were also obtained via traditional thermobarometry. Our dataset indicates the occurrence of two tectonometamorphic domains characterized by distinct patterns and significantly modifies the past tectonic interpretation of the H
P
terranes. The first domain, rich in metasediments, shows a continuous metamorphic gradient starting at ~300 °C and ~0.8 GPa and reaching the blueschist-eclogite transition at 500–520 °C and ~1.8 GPa and is only locally cut by minor tectonic breaks. The second one, rich in metaophiolites, shows a rather constant metamorphism at 520–550 °C and ~2.4 GPa. The two terranes are separated by a conspicuous pressure gap (0.6 GPa, or ~20 km), but no temperature gap exists. We therefore interpret the metamorphic mineral isograds in the blueschist, metasediment-rich unit as a continuous prograde metamorphic gradient corresponding to ~35 km of accreted material (in a cold subduction zone favoring lawsonite stability) later affected by a factor of two decompressional thinning. Only the epidote isograd, which localized strain as a result of fluid release during decompression, reflects regional reequilibrations. Importantly, no significant tectonic break affects the regional distribution of the classical mineral isograds, and the most significant metamorphic break is best depicted by a lithological contrast (metasediment-rich vs. metamafic/ultramafic-rich domains). Comparable patterns are observed in Tethyan-type orogens like the Western Alps or Corsica. This contribution provides useful insights into the mechanisms of exhumation and stacking of H
P
terrains and mountain building of both Pacific and Tethyan orogenic belts.
Although lawsonite‐bearing rocks are rare in exhumed high‐pressure (HP) terranes, they are considered to exert a primary role in subduction dynamics. Recent observations in natural settings have ...shown that fluid–rock interaction at HP conditions, including metasomatism, may lead to unusually high lawsonite amounts even in rocks that originally contained little or no lawsonite. This process may therefore bear important implications for element recycling in subduction zones. A detailed characterization of the geochemical fingerprints associated with lawsonite metasomatism is presented in this contribution. The studied rocks belong to the HP terranes of Alpine Corsica (France), which is the largest documented exposure for lawsonite metasomatism. Metasomatic lawsonite displays complex compositional zoning, including high trace element, Cr and Ti content. The trace element content is much higher compared with the average of non‐metasomatic lawsonite, and is in line with the re‐incorporation of large amounts of trace elements (e.g. REE, Sr, Pb, Th) in the rock during metasomatism, as shown by mass transfer calculations. Our data suggest that serpentinites represented the main fluid source for the metasomatism, with concurrent contribution of other, possibly Ca‐rich lithologies, such as mafic or meta‐sedimentary rocks. We propose that the breakdown of metasomatic lawsonite may contribute to the genesis of magmas and their characteristic geochemical signatures.
Background
Mast cells (MC) are powerful inflammatory immune sentinel cells that drive numerous allergic, inflammatory, and pruritic disorders when activated. MC‐targeted therapies are approved in ...several disorders, yet many patients have limited benefit suggesting the need for approaches that more broadly inhibit MC activity. MCs require the KIT receptor and its ligand stem cell factor (SCF) for differentiation, maturation, and survival. Here we describe CDX‐0159, an anti‐KIT monoclonal antibody that potently suppresses MCs in human healthy volunteers.
Methods
CDX‐0159‐mediated KIT inhibition was tested in vitro using KIT‐expressing immortalized cells and primary human mast cells. CDX‐0159 safety and pharmacokinetics were evaluated in a 13‐week good laboratory practice (GLP)‐compliant cynomolgus macaque study. A single ascending dose (0.3, 1, 3, and 9 mg/kg), double‐blinded placebo‐controlled phase 1a human healthy volunteer study (n = 32) was conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of CDX‐0159.
Results
CDX‐0159 inhibits SCF‐dependent KIT activation in vitro. Fc modifications in CDX‐0159 led to elimination of effector function and reduced serum clearance. In cynomolgus macaques, multiple high doses were safely administered without a significant impact on hematology, a potential concern for KIT inhibitors. A single dose of CDX‐0159 in healthy human subjects was generally well tolerated and demonstrated long antibody exposure. Importantly, CDX‐0159 led to dose‐dependent, profound suppression of plasma tryptase, a MC‐specific protease associated with tissue MC burden, indicative of systemic MC suppression or ablation.
Conclusion
CDX‐0159 administration leads to systemic mast cell ablation and may represent a safe and novel approach to treat mast cell‐driven disorders.
This study presents the preclinical characterization, safety, pharmacokinetic and pharmacodynamic activity in a placebo‐controlled phase 1a healthy volunteer study of CDX‐0159, a specific and potent anti‐KIT inhibitory monoclonal antibody. CDX‐0159 inhibits SCF‐dependent KIT and mast cell activation. In a dose‐dependent manner, CDX‐0159 induces suppression of plasma tryptase – a marker of mast cell burden – showing a potential as a therapeutic strategy in mast cell‐driven disorders.Abbreviations: CDX‐0159, anti‐KIT inhibitory monoclonal antibody; FcR, Fc receptor; KIT, KIT proto‐oncogene, receptor tyrosine kinase; MRGPRX2, mas‐related G protein‐coupled receptor‐X2; SCF, stem cell factor
This contribution reviews the existing data on lawsonite stability and trace element geochemistry, and provides new data for metabasaltic and metasedimentary (quartzite) rocks from New Caledonia, ...Turkey and California. Lawsonite is a major host of REE, Sr, U, Th and Pb in basaltic compositions. Trace element‐rich lawsonite also occurs in metasedimentary rocks, in which comparatively fewer phases compete for trace elements than in metabasaltic rocks. Trace element patterns in lawsonite are influenced by the coexistence or breakdown of allanite, titanite, apatite and garnet that compete for these elements in high‐P metamorphic rocks. Lawsonite is restricted to cool geotherms and therefore is an indicator mineral for subduction‐zone metamorphism. The lawsonite stability field shows a strong dependence on temperature and composition and it is largest in rocks with a high normative anorthite content and, in basaltic systems, carbon content. Along cold geotherms, lawsonite can transport water and trace elements to great depths, providing a source for these elements in the deep mantle. Along warmer geotherms, lawsonite disappears on a continuous reaction, gradually releasing water over a temperature interval of several tens of degrees. During lawsonite breakdown in complex systems, Th and LREE remain trapped in newly formed accessory allanite. However, owing to extreme LREE content, allanite has lower Pb/Ce and Sr/Nd than lawsonite, resulting in a relative enrichment of Sr and Pb compared with Ce and Nd in the fluids produced during lawsonite breakdown. Existing experimental data on the solidus of altered oceanic crust suggest that the lawsonite‐breakdown reaction is within 50 °C of the solidus at sub‐arc pressures of 3–4 GPa.
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