Major Arc Research Articles

Late Tonian (ca. 770-720 Ma) arc activity in the Wuyi domain of the West Cathaysia terrane, South China

The late Tonian tectonic setting of the West Cathaysia terrane in South China is highly controversial and is key to better understanding the timing of amalgamation between the Yangtze Block and the West Cathaysia terrane and the positions of these two terranes in Rodinia and Gondwana. A detailed field-based study was conducted on the petrology, zircon U-Pb geochronology and Lu-Hf isotopes, and whole-rock geochemistry of a series of Neoproterozoic meta-volcanic and meta-sedimentary rocks in the Wuyi domain in the northeastern West Cathaysia terrane. The results indicate that the meta-volcanic rocks formed in an arc setting at 756-740 Ma, and the meta-sedimentary rocks were developed in an arc-related basin with single zircon age peaks of 765-728 Ma. We propose that the late Tonian arc in the Wuyi domain was part of a major arc system in the West Cathaysia terrane. An arc setting for the West Cathaysia terrane is distinct from the continental rift setting for the southeastern margin of the Yangtze Block at the time, supporting an interpretation that the two terranes were not amalgamated until after the late Tonian and occupied separate positions in Rodinia.

Cancerous Conditions Accelerate the Aging of Skeletal Muscle via Mitochondrial DNA Damage.

Skeletal muscle aging and sarcopenia result in similar changes in the levels of aging markers. However, few studies have examined cancer sarcopenia from the perspective of aging. Therefore, this study investigated aging in cancer sarcopenia and explored its causes in vitro and in vivo. In mouse aging, in vitro cachexia, and mouse cachexia models, skeletal muscles showed similar changes in aging markers including oxidative stress, fibrosis, reduced muscle differentiation potential, and telomere shortening. Furthermore, examination of mitochondrial DNA from skeletal muscle revealed a 5 kb deletion in the major arc; truncation of complexes I, IV, and V in the electron transport chain; and reduced oxidative phosphorylation (OXPHOS). The mouse cachexia model demonstrated high levels of high-mobility group box-1 (HMGB1) and tumor necrosis factor-α (TNFα) in cancer ascites. Continuous administration of neutralizing antibodies against HMGB1 and TNFα in this model reduced oxidative stress and abrogated mitochondrial DNA deletion. These results suggest that in cancer sarcopenia, mitochondrial oxidative stress caused by inflammatory cytokines leads to mitochondrial DNA damage, which in turn leads to decreased OXPHOS and the promotion of aging.

Multi-wave characteristics associated with January 15, 2022 Hunga-Tonga volcanic eruption: A global observation

The eruption of Hunga-Tonga Volcano on January 15, 2022 has stimulated a wide spectrum of atmospheric waves globally. To probe the surface deformation pattern, Sentinel-1 Synthetic Aperture Radar (SAR) data has been analyzed. It has been approximated that an overall area of about 2.47 square kilometres experienced deformation in conjunction with this event. To characterize the atmospheric wave propagation, barometric pressure data from 1814 stations distributed all around the globe have been examined. This study encompassed with the propagation characteristics of the waves over four zones including Indian and Polar regions for the first time using barometric data. Time-series observations indicate that the waves propagated globally multiple times. Within the Indian region, three minor arc passages and one major arc passage were identified. In Japan, two minor arc passages and one major arc were present. Conversely, in North America, both minor and major arc passages were detected, occurring a minimum of three times. Moreover, the attributes of these waves, such as their propagation speed and periodicity, were compared across these four regions. The estimated phase speed and periodicity fall within the ranges of approximately 291–314 m/s and 10–180 min, respectively including Polar Regions. These speed and periodicity measurements of the observed waves suggest that the dominant mode of wave propagation generated during the Tonga volcanic eruption is that of Lamb waves. In addition, a slower propagation phase speed of about 226.6 m/s was identified in Japan which corresponds to Pekeris mode of waves.

LATE CAMBRIAN (~490 MA) ARC VOLCANIC ROCKS OF THE NORTH TIANSHAN OF KYRGYZSTAN: AGE CONSTRAINTS FROM U–Pb ZIRCON DATING

In the present contribution, we aim to determine the age of the oldest arc-related volcanic units in the North Tianshan of Kyrgyzstan (NTS) to better understand the early evolution of subduction systems in the western part of the Central Asian Orogenic Belt. We conducted zircon U–Pb dating (LA–ICP–MS) on andesitic tuffs from the Sultansary and Tashtambektor formations, which were previously believed to be of early Cambrian and middle Cambrian to early Ordovician age, respectively. Our results reveal age estimates of 491 ± 3 and 487 ± 3 Ma for these formations, indicating that both units are late Cambrian in age. The volcanic rocks belong to a major magmatic arc with a heterogeneous basement that evolved in the NTS during the late Cambrian and early Ordovician.

Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.

Mitochondrial DNA (mtDNA) replication stalling is considered an initial step in the formation of mtDNA deletions that associate with genetic inherited disorders and aging. However, the molecular details of how stalled replication forks lead to mtDNA deletions accumulation are still unclear. Mitochondrial DNA deletion breakpoints preferentially occur at sequence motifs predicted to form G-quadruplexes (G4s), four-stranded nucleic acid structures that can fold in guanine-rich regions. Whether mtDNA G4s form in vivo and their potential implication for mtDNA instability is still under debate. In here, we developed new tools to map G4s in the mtDNA of living cells. We engineered a G4-binding protein targeted to the mitochondrial matrix of a human cell line and established the mtG4-ChIP method, enabling the determination of mtDNA G4s under different cellular conditions. Our results are indicative of transient mtDNA G4 formation in human cells. We demonstrate that mtDNA-specific replication stalling increases formation of G4s, particularly in the major arc. Moreover, elevated levels of G4 block the progression of the mtDNA replication fork and cause mtDNA loss. We conclude that stalling of the mtDNA replisome enhances mtDNA G4 occurrence, and that G4s not resolved in a timely manner can have a negative impact on mtDNA integrity.

The Acute Effects of Exercise on Saliva-Derived Regional Mitochondrial DNA from Trained Runners

ABSTRACT Introduction/Purpose Research has identified two regions within mitochondrial deoxyribonucleic acid (mtDNA), which seem to be more (major arc; mtMAJ) and less (minor arc; mtMIN) prone to oxidation and mtDNA lesion formation. Oxidation of mtDNA base pairs can result in reduced copy number and has been linked to chronic diseases. Interestingly, exercise can also induce acute copy number reductions; however, in a healthy population, there seems to be a restorative effect (i.e., gaining mtDNA copy numbers) that occurs within a couple of hours to days after exercise. Few have investigated these regional mtDNA changes in trained runners (>90th fitness percentile). Typical mtDNA procedures are invasive and inconvenient, requiring muscle biopsies, and/or blood draws; therefore, a simpler, less invasive method of specimen collection is appealing. The purpose of this study was to examine how salivary-derived molecular (mtMAJ and mtMIN), hormonal (cortisol), and oxidative (8-hydroxy-2′-deoxyguanosine (8-OHdG)) markers change after acute exercise. Methods Trained runners (n = 7; 52 ± 12 miles·wk−1 run in the past year; 28.8 ± 3.3 yr old; height, 1.76 ± 0.07 m; weight, 67.9 ± 11.3 kg; maximum oxygen consumption, 62.4 ± 5.7 mL·kg−1·min−1) completed a 60-min treadmill run at 70% peak oxygen consumption. Saliva samples were collected before exercise, 30 min after exercise (30Post), and 6 h after exercise (6hPost) and analyzed for changes in regional mtDNA via real-time quantitative polymerase chain reaction and stress (cortisol and 8-OHdG) markers using competitive enzyme-linked immunosorbent assays. Results mtMIN copy number decreased 30Post (−44.5%, P = 0.04) and 6hPost (−45.3% P = 0.03), but mtMAJ copy numbers were unchanged after exercise (P = 0.44). Neither of the stress-related saliva biomarkers changed after exercise (cortisol, P = 0.13; 8-OHdG, P = 0.77). Conclusions Saliva-derived DNA findings point to mtMIN, supposedly the more stable of the two regions, as a greater contributor to copy number reductions within our cohort of trained runners. These results contribute to the understanding of aerobic exercise’s influence over saliva-derived, regional mtDNA dynamics.

Secondary structure of the human mitochondrial genome affects formation of deletions

BackgroundAging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded mitochondrial DNA (mtDNA) might play a role in the formation of deletions.ResultsBy analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a “hot spot” where one deletion breakpoint occurred within the region of 6–9 kb and another within 13–16 kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions, can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11 kb and contacting regions between 6–9 kb and 13–16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470–8482 bp (base pair) and a second arm at 13,447–13,459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. A comparison of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging.ConclusionsOverall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.

Large earthquakes along slow converging plate margins: Calabrian Arc paleoseismicity based on the submarine turbidite record

The Calabrian Arc subduction-rollback system hosts seismogenic faults capable of generating earthquakes exceeding magnitude 7. Since earthquakes are the result of long-term geodynamic processes, documenting seismic activity during a sufficiently long time interval is of fundamental importance for hazard scenarios. Instrumental and historical data provide critical information on seismogenesis, but they cover time periods shorter than the recurrence times of large earthquakes, especially in areas with low deformation rates such as Calabria. If onshore paleoseismological studies are fundamental to compile earthquake catalogs, they are sometime affected by the relatively poor continuity of sedimentation in the subaerial environment.In this study we applied the paleoseismological approach to the submarine environment to reconstruct the record of high-energy sedimentary events triggered by seismic activity. We analyzed three gravity cores collected in disconnected sedimentary basins to reconstruct resedimentation processes during the Holocene, integrating inland information for a better assessment of tectonic activity and seismogenesis. Multiproxy analyses of the sedimentary record constrained by radiometric dating allowed reconstructing event stratigraphy and linking resedimented deposits to specific earthquakes.Onshore and offshore data allow to identify large-magnitude earthquakes in the central Calabrian Arc subduction system during the Holocene, with inferred epicenters located either along normal faults onshore and/or related to the slab dynamics. The turbidite record reveals 20 major events during the last 10 ka, with sources including crustal faults in Calabria (i.e. Lakes, Rossano and Cittanova faults). Analyses of sediment samples and high-resolution seismic reflection images allowed identification of different types of resedimented deposits during the last 30–50 ka. The basin-wide occurrence of three megaturbidites/homogenites suggests they are related to megatsunamis sourced by far field earthquakes along the Hellenic Arc. Megaturbidites with a more limited spatial extent are interpreted as subduction-type events in the Calabrian Arc, while thinner seismo-turbidites record the activity of crustal structures including faults onshore. Results suggest a recurrence time of 2–3 ka for major Calabrian Arc events that needs to be considered for a reliable hazard assessment in the Mediterranean region.

Design of a Novel Flexible Robotic Laparoscope Using a Two Degrees-of-Freedom Cable-Driven Continuum Mechanism With Major Arc Notches

Abstract This article presents the design, development, and motion control of a novel flexible robotic laparoscope (FRL). The main structure of the FRL includes a two degrees-of-freedom (DOFs) continuum mechanism driven by two pairs of cable-pulley-driven systems, which are actuated by four miniature linear actuators. A constant-curvature model is employed on the kinematics modeling and analysis of the continuum mechanism with designed major arc notches. The bending control strategy of the continuum mechanism is proposed and realized based on its kinematics model and a feedforward compensation method considering its nonlinearity motion calibration with a suitable initial tension of the driven cables. Besides, the continuum mechanism is made of elastic nylon material through 3D printing technology. An experimental prototype is developed to test the effectiveness and feasibility of the FRL. The experimental results indicate that the FRL has good positioning accuracy and motion performance with potential applications in robot-assisted laparoscopic surgery.

Cell-free mitochondrial DNA deletions in idiopathic, but not LRRK2, Parkinson's disease

Mitochondrial dysfunction happens in both idiopathic (iPD) and LRRK2-related Parkinson's disease (LRRK2-PD). Nonetheless, previous studies suggested that a different type of mitochondrial pathology underlies the neurodegeneration in these two disorders. To further explore this hypothesis, we developed a novel multiplex digital PCR assay that allows the absolute quantification of cell-free mitochondrial DNA (cf-mtDNA) copy number and deletion ratio directly in cerebrospinal fluid (CSF) by simultaneously measuring two opposed regions of the mtDNA circular molecule, one of them in the commonly deleted major arc. The results confirmed that the content of cf-mtDNA in CSF was statistically significantly different between iPD and LRRK2-PD patients. Moreover, we found high cf-mtDNA deletion levels in CSF from patients with iPD, but not LRRK2-PD. The high cf-mtDNA deletion frequency in iPD was validated in an independent cohort. These results indicated that the content and deletion ratio of cf-mtDNA may differentiate iPD from LRRK2-PD, and provides further evidence of the different mitochondrial pathophysiology between these two forms of the disease.

Petrogenesis of the Early Silurian Renda appinite suite in the southeastern Qilian Orogen, NW China: Implications for the evolution of a Proto-Tethys magmatic arc

ABSTRACT Early Paleozoic subduction beneath peri-Gondwana microcontinents formed a major Proto-Tethys magmatic arc system. Appinite suite rocks constitute important components within that magmatic arc. Herein, we report hornblende 40Ar/39Ar and zircon U–Pb geochronology data, zircon Hf isotope, mineral chemistry, whole-rock geochemistry, and Sr–Nd–Pb isotope data for the rocks of hornblende gabbro-diorite-quartz diorite-quartz monzodiorite from the Renda appinite suite and adjacent granite porphyry in the southeastern Qilian Orogen. Hornblende 40Ar/39Ar and zircon U–Pb isotopic data constrain ages of the intrusions of the Renda appinite suite to 439–435 Ma. Rocks in this suite represent the calc-alkalic to alkali-calcic series, and they are enriched in large-ion lithophile elements and depleted in high-field-strength elements. The hornblende gabbros exhibit moderate initial 87Sr/86Sr ratios (0.7046–0.7055) and higher whole-rock εNd(t) (–1.3 to +1.7) and zircon εHf(t) (+7.2 to +11.2) values relative to the other rocks of the suite (0.7047–0.7064, – 7.7 to – 1.1, and – 6.6 to +6.8, respectively) as well as Pb isotopic features similar to EM2 lithospheric mantle. These geochemical characteristics suggest that the Renda appinite suite originates from partial melting of an enriched lithospheric mantle, with subsequent fractional crystallization and hybridization with crustal components. The granite porphyry formed by partial melting of the crust coeval with the emplacement of juvenile magma. This study suggests emplacement occurred during a short-lived collision with slab failure (breakoff) after latest stage (cessation) of Proto-Tethys oceanic subduction along the northern side of the southeastern Qilian Orogen. The heat supplied by the asthenospheric upwelling through a gap in the subducted slab induced melting in lithospheric mantle and deep crust producing Renda appinite suite rocks and granite porphyry.

Mesozoic exhumation of the Jueluotage area, Eastern Tianshan, NW China: constraints from (U–Th)/He and fission-track thermochronology

AbstractThe Jueluotage area, which is located in the southern branch of the Eastern Tianshan and northeast of the Tarim Basin, represents a vital locality for investigating intracontinental reactivation induced by the tectonic events at the Eurasian plate margin. This study applies zircon and apatite (U–Th)/He and apatite fission-track thermochronology to the Jueluotage area in the Eastern Tianshan. Our data and thermal history modelling show that the Jueluotage area experienced Triassic–Early Jurassic (˜240–180 Ma) cooling, reflecting the closure of the North Tianshan Ocean and subsequent far-field effects of collision/accretion of the Qiangtang Block and Kunlun terrane. Following this period of fast cooling, a differential exhumation process occurred between the various tectonic belts in the Jueluotage area. The Aqishan–Yamansu belt was exposed at the surface during the Triassic–Early Jurassic cooling phase and experienced subsequent burial, which continued until Early Cretaceous time when a pulse of exhumation occurred. However, the major fault zones (Kanggurtag ductile shear zone and Aqikkuduk Fault) and Central Tianshan arc have remained tectonically stable since Early Jurassic time. No Cenozoic rapid cooling was recorded by the low-temperature thermochronology results in this study, indicating that much of the Jueluotage area was exhumed to the upper crust in the late Mesozoic period.

The Acute Effects of Exercise and Temperature on Regional mtDNA.

A reduced mitochondrial DNA (mtDNA) copy number, the ratio of mitochondrial DNA to genomic DNA (mtDNA:gDNA), has been linked with dysfunctional mitochondria. Exercise can acutely induce mtDNA damage manifested as a reduced copy number. However, the influence of a paired (exercise and temperature) intervention on regional mtDNA (MINor Arc and MAJor Arc) are unknown. Thus, the purpose of this study was to determine the acute effects of exercise in cold (7 °C), room temperature (20 °C), and hot (33 °C) ambient temperatures, on regional mitochondrial copy number (MINcn and MAJcn). Thirty-four participants (24.4 ± 5.1 yrs, 87.1 ± 22.1 kg, 22.3 ± 8.5 %BF, and 3.20 ± 0.59 L·min−1 VO2peak) cycled for 1 h (261.1 ± 22.1 W) in either 7 °C, 20 °C, or 33 °C ambient conditions. Muscle biopsy samples were collected from the vastus lateralis to determine mtDNA regional copy numbers via RT-qPCR. mtDNA is sensitive to the stressors of exercise post-exercise (MIN fold change, −1.50 ± 0.11; MAJ fold change, −1.70 ± 0.12) and 4-h post-exercise (MIN fold change, −0.82 ± 0.13; MAJ fold change, −1.54 ± 0.11). The MAJ Arc seems to be more sensitive to heat, showing a temperature-trend (p = 0.056) for a reduced regional copy number ratio after exercise in the heat (fold change −2.81 ± 0.11; p = 0.019). These results expand upon our current knowledge of the influence of temperature and exercise on the acute remodeling of regional mtDNA.

Hybrid a free arc into constraint-arc to improve arc pressure control behavior

Decoupling the arc pressure and heat output improves the controllability of the arc. In this study, an innovative torch was successfully developed for this purpose by adding an outer electrode under the orifice to a conventional plasma arc welding (PAW) torch. The arc rooting from the added electrode merges with the main/PAW arc forming a hybrid arc system with two cathodes and one anode. While the major arc is constrained, the added arc is allowing to change the anode heat while the pressure is still primarily controlled by the main arc. The coupling behavior was experimentally studied through analysis arc column image and arc pressure measurement. The results show that the added free arc formed by the outer electrode is fully absorbed and coupled into the constraint arc to form a single hybrid arc. The arc pressure peak value in the hybrid arc is little sensitive to outer free arc current compared with that by adjusting the center constraint arc current. Because the sided outer tungsten electrode is isolated to the center inner tungsten electrode and the cooper nozzle in the arcing torch system, the range of arc current applied by the outer tungsten electrode is large. The torch system provides a novel arc plasma generation method to improve the control precision in manufacturing process.

Влияние величины деформации в грудном отделе позвоночника на морфологическую картину параспинальных мышц у больных с идиопатическим сколиозом тяжелой степени

Introduction Morphological, biochemical and histopathological characteristics of paraspinal muscles have been well described in patients with idiopathic scoliosis. However, there is a paucity of literature on morphological picture of paraspinal muscles in patients with severe idiopathic scoliosis. Objective To explore how the magnitude of thoracic spine deformity affects morphological characteristics of paraspinal muscles in patients with severe idiopathic scoliosis. Material and methods A total 21 patients with idiopathic scoliosis were reviewed. The patients were assigned to two groups depending on magnitude of preoperative thoracic spine deformity. A major group consisted of patients with scoliosis of ≥ 60º (n = 11) and control group included patients with a curve < 60º (n=10). Biopsy samples were taken from muscle fragments (multifidus muscle) at the apex of the curve (major arc) at the Th6-Th10 level on the convex side while approaching to the posterior spinal structures during surgical correction of kyphoscoliosis using light microscope. The specimens were examined histologically with light microscope. Results Patients with severe idiopathic scoliosis (≥ 60º) showed evident muscle fiber atrophy and dystrophy of different extent. There were nucleus free areas and homogenized muscle fragments observed with connective tissue layers being swollen and frayed with multiple fibroblasts seen in nearly all the samples. Arterial walls were normally fibrotized. Structural changes ranged from minimal with a curve of 60º to degrading muscles with the fibers replaced by fat and connective tissues with a curve angle of 145º. Conclusion Morphological characteristics of paraspinal muscles have been shown to be severely affected by the magnitude of thoracic spine deformity in patients with severe idiopathic scoliosis. The findings should be considered in surgical correction of kyphoscoliosis with special focus on postoperative vascular and neurotropic therapy to allow wound healing and lower complication rate.

Triplex and other DNA motifs show motif-specific associations with mitochondrial DNA deletions and species lifespan

The “theory of resistant biomolecules” posits that long-lived species show resistance to molecular damage at the level of their biomolecules. Here, we test this hypothesis in the context of mitochondrial DNA (mtDNA) as it implies that predicted mutagenic DNA motifs should be inversely correlated with species maximum lifespan (MLS).First, we confirmed that guanine-quadruplex and direct repeat (DR) motifs are mutagenic, as they associate with mtDNA deletions in the human major arc of mtDNA, while also adding mirror repeat (MR) and intramolecular triplex motifs to a growing list of potentially mutagenic features. What is more, triplex motifs showed disease-specific associations with deletions and an apparent interaction with guanine-quadruplex motifs.Surprisingly, even though DR, MR and guanine-quadruplex motifs were associated with mtDNA deletions, their correlation with MLS was explained by the biased base composition of mtDNA. Only triplex motifs negatively correlated with MLS even after adjusting for body mass, phylogeny, mtDNA base composition and effective number of codons.Taken together, our work highlights the importance of base composition for the comparative biogerontology of mtDNA and suggests that future research on mitochondrial triplex motifs is warranted.

Chapter 1.2 Antarctic volcanism: volcanology and palaeoenvironmental overview

Abstract Since Jurassic time ( c. 200 Ma), Antarctica has had a greater diversity of volcanism than other southern continents. It includes: (1) voluminous mafic and felsic volcanism associated with the break-up of Gondwana; (2) a long-lived continental margin volcanic arc, including back-arc alkaline volcanism linked to slab rollback; (3) small-volume mafic alkaline volcanism associated with slab-window formation; and (4) one of Earth's major continental rift zones, the West Antarctic Rift System (WARS), with its numerous large alkaline central volcanoes. Several of Antarctica's volcanoes are still active. This chapter is a review of the major volcanic episodes and their principal characteristics, in their tectonic, volcanological and palaeoenvironmental contexts. Jurassic Gondwana break-up was associated with large-scale volcanism that caused global environmental changes and associated mass extinctions. The volcanic arc was a major extensional arc characterized by alternating volcanic flare-ups and lulls. The Neogene rift-related alkaline volcanism is dominated by effusive glaciovolcanic eruptions, overwhelmingly as both pāhoehoe- and ‘a‘ā-sourced lava-fed deltas. The rift is conspicuously poor in pyroclastic rocks due to the advection and removal of tephra erupted during glacial intervals. Volcanological investigations of the Neogene volcanism have also significantly increased our knowledge of the critical parameters and development of the Antarctic Ice Sheet.

Sedimentary and volcanic record of the nascent Izu-Bonin-Mariana arc from IODP Site U1438

Abstract The oldest known, intact sedimentary record of a nascent intraoceanic arc was recovered in a ∼100-m-thick unit (IV) above ca. 49 Ma basaltic basement at International Ocean Discovery Program Site U1438 in the Amami Sankaku Basin. During deposition of Unit IV the site was located ∼250 km from the plate edge, where Izu-Bonin-Mariana subduction initiated at 52 Ma. Basement basalts are overlain by a mudstone-dominated subunit (IVC) with a thin basal layer of dark brown metalliferous mudstone followed by mudstone with sparse, graded laminae of amphibole- and biotite-bearing tuffaceous sandstone and siltstone. Amphibole and zircon ages from these laminae suggest that the intermediate subduction-related magmatism that sourced them initiated at ca. 47 Ma soon after basement formation. Overlying volcaniclastic, sandy, gravity-flow deposits (subunit IVB) have a different provenance; shallow water fauna and tachylitic glass fragments indicate a source volcanic edifice that rose above the carbonate compensation depth and may have been emergent. Basaltic andesite intervals in upper subunit IVB have textures suggesting emplacement as intrusions into unconsolidated sediment on a volcanic center with geochemical and petrological characteristics of mafic, differentiated island arc magmatism. Distinctive Hf-Nd isotope characteristics similar to the least-radiogenic Izu-Bonin-Mariana boninites support a relatively old age for the basaltic andesites similar to detrital amphibole dated at 47 Ma. The absence of boninites at that time may have resulted from the position of Site U1438 at a greater distance from the plate edge. The upper interval of mudstone with tuffaceous beds (subunit IVA) progresses upsection into Unit III, part of a wedge of sediment fed by growing arc-axis volcanoes to the east. At Site U1438, in what was to become a reararc position, the succession of early extensional basaltic magmatism associated with spontaneous subduction initiation is followed by a rapid transition into potentially widespread subduction-related magmatism and sedimentation prior to the onset of focused magmatism and major arc building.

Hyperbolicity of asymmetric lemon billiards * *XJ is supported in part by the NSF Grant DMS-1854232.

Asymmetric lemon billiards was introduced in Chen et al (2013 Chaos 23 043137), where the billiard table Q(r, b, R) is the intersection of two round disks with radii r ⩽ R, respectively, and b measures the distance between the two centres. It is conjectured Bunimovich et al (2016 Commun. Math. Phys. 341 781–803) that the asymmetric lemon billiards is hyperbolic when the arc Γ r is a major arc and R is large. In this paper we prove this conjecture for sufficiently large R.

Mitochondrial Mechanisms of LRRK2 G2019S Penetrance.

Several mutations in leucine-rich repeat kinase-2 (LRRK2) have been associated with Parkinson's disease (PD). The most common substitution, G2019S, interferes with LRRK2 kinase activity, which is regulated by autophosphorylation. Yet, the penetrance of this gain-of-function mutation is incomplete, and thus far, few factors have been correlated with disease status in carriers. This includes (i) LRRK2 autophosphorylation in urinary exosomes, (ii) serum levels of the antioxidant urate, and (iii) abundance of mitochondrial DNA (mtDNA) transcription-associated 7S DNA. In light of a mechanistic link between LRRK2 kinase activity and mtDNA lesion formation, we previously investigated mtDNA integrity in fibroblasts from manifesting (LRRK2+/PD+) and non-manifesting carriers (LRRK2+/PD−) of the G2019S mutation as well as from aged-matched controls. In our published study, mtDNA major arc deletions correlated with PD status, with manifesting carriers presenting the highest levels. In keeping with these findings, we now further explored mitochondrial features in fibroblasts derived from LRRK2+/PD+ (n = 10), LRRK2+/PD− (n = 21), and control (n = 10) individuals. In agreement with an accumulation of mtDNA major arc deletions, we also detected reduced NADH dehydrogenase activity in the LRRK2+/PD+ group. Moreover, in affected G2019S carriers, we observed elevated mitochondrial mass and mtDNA copy numbers as well as increased expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates antioxidant signaling. Taken together, these results implicate mtDNA dyshomeostasis—possibly as a consequence of impaired mitophagy—in the penetrance of LRRK2-associated PD. Our findings are a step forward in the pursuit of unveiling markers that will allow monitoring of disease progression of LRRK2 mutation carriers.