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Tectonic deformation of blocks neighboring fault zones has been thought to aid in accommodating regional displacements. In general, these block‐bounding faults possess continuous geometry and similar kinematics. However, the northwestern boundary of the Tianshan Mountains (NWBTS) involves two groups of faults that strike NW and NE. GPS velocities show that contemporary deformation takes place in a zone of 300 km wide in the NWBTS and is roughly dominated by left‐lateral shear. Left‐lateral shear motion of ∼5–6 mm/yr along the NWBTS is accommodated by right‐lateral slip and counterclockwise rotation of fault wallrocks on the NW‐striking faults and left‐lateral faulting on the NE‐striking faults. Present‐day deformation associated with the ongoing India‐Eurasia collision in the NWBTS is best described as the opposite sense of strike‐slip faulting and crustal rotation. The difference in lithospheric strengthening between the Kazakh Platform and Tianshan deflects strain toward the northeast and drives the dynamic process in this region. Plain Language Summary: The NWBTS has undergone notable tectonic deformation, which involves two groups of NW‐striking and NE‐striking faults instead of displacement only along a major bounding fault. How the two groups of faults interact to bound this deformation boundary belt and accommodate the regional strain associated with the ongoing India‐Eurasia collision remains unclear. Investigating the fault kinematics and strain distribution is essential for understanding the interactions between active tectonic blocks and determining crustal deformation patterns and dynamic mechanisms in this region. In this study, we utilize the latest GPS data from Wang and Shen (2020), https://doi.org/10.1029/2019jb018774 to define the kinematics and deformation rates of the major faults in the NWBTS. Left‐lateral shear of ∼5–6 mm/yr along the NE‐trending NWBTS is accommodated by right‐lateral faulting of the NW‐striking faults and left‐lateral faulting of the NE‐striking faults, which can be interpreted as a pattern resembling the opposite sense of strike‐slip faulting and crustal rotation of the surrounding rock. Our results provide clear evidence of how active deformation is distributed in this area and the tectonic role of the different faults in regional deformation. Key Points: Northwestern boundary of the Tianshan Mountains involves two groups of faults that strike NW and NEFault kinematics and deformation rates of the major faults are determined based on the GPS dataCrustal deformation in the NWBTS can be interpreted as a pattern resembling the opposite sense of strike‐slip faulting and crustal rotation [ABSTRACT FROM AUTHOR]

Mibavademab (previously known as REGN4461), a fully human monoclonal antibody, is being investigated for the treatment of conditions associated with leptin deficiency. Here, we report pharmacokinetics (PKs), pharmacodynamics, and immunogenicity from a phase I study in healthy participants (NCT03530514). In part A, lean or overweight healthy participants were randomized to single‐ascending‐dose cohorts of 0.3, 1.0, 3.0, 10, and 30 mg/kg intravenous (i.v.), or 300 and 600 mg subcutaneous doses of mibavademab or placebo. In part B, overweight or obese participants were randomized to receive multiple doses of mibavademab (15 mg/kg i.v. loading dose and 10 mg/kg i.v. at weeks 3, 6, and 9) or placebo, stratified by body mass index and baseline leptin levels: low leptin (<5 ng/mL) or relatively low leptin (5–8 ng/mL in men and 5–24 ng/mL in women). Fifty‐six and 55 participants completed the single‐ascending‐dose and multiple‐dose parts, respectively. In the single‐ascending‐dose cohorts, mibavademab PKs were nonlinear with target‐mediated elimination, greater than dose‐proportional increases in exposure, and there were no dose‐dependent differences in total soluble leptin receptor (sLEPR) levels in serum over time. Following multiple‐dose administration of mibavademab in participants with leptin <8 ng/mL, lower mean mibavademab concentrations, higher mean total sLEPR concentrations, and larger mean decreases in body weight than in the relatively low leptin cohorts were observed. Baseline leptin was correlated with mibavademab PKs and pharmacodynamics. No treatment‐emergent anti‐mibavademab antibodies were observed in any mibavademab‐treated participant. Results from this study collectively inform further development of mibavademab to treat conditions associated with leptin deficiency. [ABSTRACT FROM AUTHOR]

Itepekimab is a monoclonal antibody that targets interleukin (IL‐33) and has been shown to reduce airway inflammation and associated tissue damage in preclinical studies. We assessed the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamic profiles of single‐ascending and multiple‐ascending doses of itepekimab in two randomized, double‐blind, placebo‐controlled phase I studies. Healthy adults (N = 40) were randomized to the single‐dose study and patients with moderate asthma (N = 23) to the multiple‐dose study. Itepekimab was administered intravenously (0.3, 1, 3, or 10 mg/kg infusion) or subcutaneously (150 mg) in the single‐dose study and subcutaneously (75 or 150 mg weekly for 4 weeks) in the multiple‐dose study. Itepekimab exhibited linear PKs across studies and dose‐proportional increases in mean maximum concentration in serum and area under the concentration–time curve following single intravenous or multiple subcutaneous doses. Itepekimab demonstrated mean subcutaneous bioavailability of 59–73% and a long terminal half‐life (30.0–31.6 days). IL‐33 concentrations in most healthy participants and patients with asthma were undetectable at baseline. Following administration of itepekimab in both studies, total IL‐33 concentrations increased and blood eosinophils decreased, both with durable effect. Itepekimab was well‐tolerated in both studies with no detection of treatment‐emergent anti‐drug antibody responses. [ABSTRACT FROM AUTHOR]

We studied the 2019 Mw6.4 and Mw7.1 Ridgecrest, California, earthquake sequence, using Sentinel‐1 and ALOS‐2 coseismic interferograms and subpixel offsets to retrieve the three‐dimensional (3‐D) surface displacements. By inverting the 3‐D displacements, optimal dip angles of the earthquake faults and the slip model were obtained. The interferometric synthetic aperture radar‐based slip model supplemented with the analysis of GPS data shows that the Mw6.4 event ruptured two orthogonal faults and its major geodetic moment was released by sinistral motion on a NE‐SW trending fault that dips 78° NW. Right‐lateral slip on NW‐SE trending subvertical faults was responsible for the Mw7.1 earthquake. Postseismic analysis with U.S. Geological Survey earthquake catalog and GPS time series at site P595 shows that the postseismic surface deformation following the Mw7.1 event has similar temporal patterns with the postseismic moment release, but requires more energy. This implies that the early aftershocks were likely controlled by rapid afterslip following the mainshock. Key Points: The 3‐D surface displacements of the 2019 Ridgecrest earthquakes are derived from Sentinel‐1 and ALOS‐2 InSAROrthogonal fault ruptures of the Mw6.4 event are revealed by using GPS horizontal measurementsThe rapid decay of aftershocks is explained by the afterslip following the mainshocks [ABSTRACT FROM AUTHOR]

Paleomagnetic studies on the syncollisional magmatic eruptions provide a direct way to understand when and where the Paleo‐Tethys closed. We report a well‐dated paleomagnetic pole from the southern Lancangjiang volcanic belt in western Yunnan of China. Stable Characteristic Remanent Magnetizations (ChRMs) were isolated from 21 sites at high temperatures following step‐wise thermal demagnetization. The data pass fold, reversal, and conglomerate tests and are interpreted to be primary thermal remanent magnetizations. The new paleomagnetic pole (46.1°N/176.2°E, K=44.9, A95=4.8°, N=21) yields a paleolatitude of 26.0 ± 4.8°N at the reference site (23.0°N/100.4°E) in the southern Lancangjiang area. This direct paleo‐latitudinal constraint on the Paleo‐Tethys suture zone in western Yunnan indicates that the north branch of the Paleo‐Tethys Ocean closed no later than the Carnian Age of Late Triassic, and confirms a geographic linkage between the North Qiangtang and Indochina Blocks at least during the Early Permian to Late Triassic. Plain Language Summary: The Asian continent is formed by the amalgamation of continental blocks such as the Tarim, North China, South China, Indochina, and Qiangtang. However, questions remained to answer: When did the ocean between them close? How did they drift from the south hemisphere to the north? In this study, we present a paleomagnetic constraint on the Paleo‐Tethys suture zone to quantify when and where the Paleo‐Tethys Ocean closed. The Paleo‐Tethys Ocean closed no later than the early Late Triassic at ~26°N. The Indochina and North Qiangtang drifted together from the south hemisphere to the north during the Permian‐Triassic. Key Points: The southern Lancangjiang volcanic belt formed at a paleolatitude of ~26ºN during the Carnian Stage of the Late TriassicThe north branch of the Paleo‐Tethys closed no later than the Carnian Stage of the Late TriassicA Permo‐Triassic geographic linkage between Indochina and N‐Qiangtang is confirmed [ABSTRACT FROM AUTHOR]

Tropomyosin (Tpm) binds along actin filaments and regulates myosin binding to control muscle contraction. Tropomodulin binds to the pointed end of a filament and regulates actin dynamics, which maintains the length of a thin filament. To define the structural determinants of these Tpm functions, we examined the effects of two congenital myopathy mutations, A4V and R91C, in the Tpm gene, TPM3, which encodes the Tpm3.12 isoform, specific for slow‐twitch muscle fibers. Mutation A4V is located in the tropomodulin‐binding, N‐terminal region of Tpm3.12. R91C is located in the actin‐binding period 3 and directly interacts with actin. The A4V and R91C mutations resulted in a 2.5‐fold reduced affinity of Tpm3.12 homodimers for F‐actin in the absence and presence of troponin, and a two‐fold decrease in actomyosin ATPase activation in the presence of Ca2+. Actomyosin ATPase inhibition in the absence of Ca2+ was not affected. The Ca2+ sensitivity of ATPase activity was decreased by R91C, but not by A4V. In vitro, R91C altered the ability of tropomodulin 1 (Tmod1) to inhibit actin polymerization at the pointed end of the filaments, which correlated with the reduced affinity of Tpm3.12‐R91C for Tmod1. Molecular dynamics simulations of Tpm3.12 in complex with F‐actin suggested that both mutations reduce the affinity of Tpm3.12 for F‐actin binding by perturbing the van der Waals energy, which may be attributable to two different molecular mechanisms—a reduced flexibility of Tpm3.12‐R91C and an increased flexibility of Tpm3.12‐A4V. [ABSTRACT FROM AUTHOR]

Abstract: We reveal transient surface deformation following the 2017 Mw7.3 Sarpol Zahab (Iran) earthquake using Interferometric Synthetic Aperture Radar (InSAR) measurements. Based on the coseismic interferograms derived from the Advanced Land Observing Satellite‐2 (ALOS‐2) data, the preferred slip model of the earthquake has a centroid depth of 14.5 ± 4 km and suggests that a basement fault is most likely responsible for the 2017 earthquake in the northwest Zagros fold‐thrust belt zone. Two slip asperities with a maximum slip of 6 m separated by 16 km are observed in the best fitting slip model. The accumulated afterslip in the first month after the mainshock determined from the Sentinel‐1 postseismic interferograms reveals a slip distribution that lies immediately updip of the coseismic slip, implying that frictional properties of the fault vary along the rupture patch. The Bamo Mount in the earthquake area was uplifted by approximately 1 m during the earthquake. We suggest that local topographic growth from both seismic and aseismic faulting behaviors is common within the Zagros fold‐thrust belt zone based on our findings regarding the 2017 earthquake and other significant events in the region. [ABSTRACT FROM AUTHOR]