bluuebunny/crossref_metadata_2025 huggingface dataset:
Driver of Energetic Electron Precipitation in the Vicinity of Ganymede
Authors: Li W. , Ma Q. , Shen X.‐C. , Zhang X.‐J. , Mauk B. H. , Clark G. , Allegrini F. , Kurth W. S. , Hospodarsky G. B. , Sulaiman A. , Nordheim T. A. , Bolton S. J.
Published: December 2022

The driver of energetic electron precipitation into Ganymede's atmosphere has been an outstanding open problem. During the Juno flyby of Ganymede on 7 June 2021, Juno observed significant downward‐going electron fluxes inside the bounce loss cone of Ganymede's polar magnetosphere. Concurrently, Juno detected intense whistler‐mode waves, both in the quasi‐parallel and highly oblique directions with respect to the magnetic field line. We use quasi‐linear model to quantify energetic electron precipitation driven by quasi‐parallel and very oblique whistler‐mode waves, respectively, in the vicinity of Ganymede. The data‐model comparison indicates that in Ganymede's lower‐latitude (higher‐latitude) polar region, quasi‐parallel whistler‐mode waves play a dominant role in precipitating higher‐energy electrons above ∼100s eV (∼1 keV), whereas highly oblique waves are important for precipitating lower‐energy electrons below 100s eV (∼1 keV). Our result provides new evidence of whistler‐mode waves as a potential primary driver of precipitating energetic electrons into Ganymede's atmosphere.
Ultra‐Slow Discharges That Precede Lightning Initiation
Authors: Sterpka C. , Dwyer J. , Liu N. , Demers N. , Hare B. M. , Scholten O. , ter Veen S.
Published: December 2022

We report on ultra‐slowly propagating discharge events with speeds in the range 1–13 km/s, much lower than any known lightning process. The propagation speeds of these discharges are orders of magnitude slower than leader or streamer speeds, but faster than the ion drift speed. For one particular event, a lightning leader forms about 40 ms later within 50 m of the discharge, likely within the same high field region. A second slow event forms 9 ms prior to the initiation, and leads into the negative leader. Most slow events appear to not be directly involved with lightning initiation. This suggests that the classic streamer cascade model of initiation is not always a definitive process. In this work we describe these discharge events displaying unique behavior, their relation to common lightning discharges, and their implications for lightning initiation.
Trade Wind Boundary Layer Turbulence and Shallow Precipitating Convection: New Insights Combining SAR Images, Satellite Brightness Temperature, and Airborne In Situ Measurements
Authors: Brilouet P.‐E. , Bouniol D. , Couvreux F. , Ayet A. , Granero‐Belinchon C. , Lothon M. , Mouche A.
Published: December 2022

The imprint of marine atmospheric boundary layer (MABL) dynamical structures on sea surface roughness, as seen from Sentinel‐1 synthetic aperture radar (SAR) acquisitions, is investigated. We focus on 13 February 2020, a case study of the elucidating the role of clouds‐circulation coupling in climate field campaign. For suppressed conditions, convective rolls imprint on sea surface roughness is confirmed through the intercomparison with MABL turbulent organization deduced from airborne measurements. A discretization of the SAR wide swath into 25 × 25 km2 tiles then allows us to capture the spatial variability of the turbulence organization varying from rolls to cells. Second, we objectively detect cold pools within the SAR image and combine them with geostationary brightness temperature. The geometrical or physically‐based metrics of cold pools are correlated to cloud properties. This provides a promising methodology to analyze the dynamics of convective systems as seen from below and above.
Turbulence Signatures in High‐Latitude Ionospheric Scintillation
Authors: Meziane K. , Hamza A. M. , Jayachandran P. T.
Published: December 2022

Ground‐based amplitude measurements of Global Navigation Satellite System signal during ionospheric scintillation are analyzed using prevalent data analysis tools developed in the fields of fluid and plasma turbulence. One such tool is the structure function of order q, with q = 1 to q = 6, which reduces to the computation of the second‐order difference in the GPS signal amplitude at various time lags, and allows for the exploration of dominant length scales in the propagation medium. We report the existence of a range where the structure function is linear with respect to time lag. This linear time segment could be considered as an analog to the inertial range in the context of neutral and plasma turbulence theory. Quantitatively, the slope of the structure function in the linear range is in good agreement with the scaling exponent determined from in situ measurements of the electrostatic potential at low altitude (E‐region) and the electron density at the topside ionosphere (F‐region). This in turn suggests the conjecture that scintillation could be considered a proxy for ionospheric turbulence. Furthermore, we have found that the probability distribution function of the second‐order difference in the signal amplitude has non‐Gaussian features at large time lags; a result that seems inconsistent with equilibrium statistical physics which suggests a Gaussian distribution for the conventional random‐walk processes. This could indicate that intermittency may occur at large time lags.
Constraining the Crustal and Mantle Conductivity Structures Beneath Islands by a Joint Inversion of Multi‐Source Magnetic Transfer Functions
Authors: Chen Chaojian , Kuvshinov Alexey , Kruglyakov Mikhail , Munch Federico , Rigaud Rafael
Published: December 2022

In this study, we present a tool to simultaneously invert multi‐source magnetic transfer functions (TFs), including tippers, solar global‐to‐local TFs originating from the signals due to ionospheric source, and global Q‐responses originating from the signals due to magnetospheric source. We jointly invert the aforementioned TFs to constrain the local conductivity structures beneath three islands in the Atlantic (Tristan da Cunha), Indian (Cocos), and Pacific (Oahu) Oceans. The recovered conductivity profiles appeared to be consistent with the presence of upper mantle plumes beneath the Tristan da Cunha and Oahu Islands. Our results indicate resistive lithosphere of different thicknesses beneath considered three islands. Besides, new conductivity profiles suggest warmer‐than‐average mantle temperatures and the presence of a small fraction of melt beneath Tristan da Cunha Island. At the same time, the conductivities beneath Cocos Island are in good agreement with estimates expected for ambient mantle conditions.
Climatology of Clear‐Air Turbulence in Upper Troposphere and Lower Stratosphere in the Northern Hemisphere Using ERA5 Reanalysis Data
Authors: Lee Ju Heon , Kim Jung‐Hoon , Sharman Robert D. , Kim Joowan , Son Seok‐Woo
Published: December 2022

Spatial and temporal distributions of Clear‐Air Turbulence (CAT) in the Northern Hemisphere were investigated using 41 years (1979–2019) of the European Centre for Medium‐range Weather Forecast Reanalysis version 5 (ERA5) data. We used two groups of CAT diagnostics to determine occurrence frequencies: (a) commonly used empirical turbulence indices (TI1, TI2, and TI3) and their components [vertical wind shear (VWS), deformation, ‐divergence, and divergence tendency], and (b) theoretical instability indicators [Richardson number (Ri), potential vorticity (PV), and Brunt‐Vӓisӓlӓ frequency]. The empirical indices showed high frequencies of moderate‐or‐greater (MOG)‐level CAT potential over the East Asian, Eastern Pacific, and Northwestern Atlantic regions in winter. Over East Asia, the entrance region of strong upper‐level jets showed the highest frequencies in TI1, TI2, and TI3 due mainly to strong VWS. The Eastern Pacific and Northwestern Atlantic areas near the exit region of jets had relatively high frequencies of these indices and also Ri. PV frequency was high on the southern side of jet primarily due to negative relative vorticity. Long‐term increasing trends of MOG‐level CAT potential also appeared in those three regions mainly due to warming in lower latitudes. The most significant increasing trend was found over East Asia, due to the strengthening of the East Asian jet and increased VWS due to the strong meridional temperature gradients in the mid‐troposphere induced by warming in the tropics and cooling in eastern Eurasia. These trends over East Asia, if continued, are expected to be of importance to efficient aviation operations across the northwestern Pacific Ocean.
Hydrothermal Alteration of Ultramafic Rocks in Ladon Basin, Mars—Insights From CaSSIS, HiRISE, CRISM, and CTX
Authors: Mège Daniel , Gurgurewicz Joanna , Massironi Matteo , Pozzobon Riccardo , Tognon Gloria , Pajola Maurizio , Tornabene Livio L. , Lucchetti Alice , Baschetti Beatrice , Davis Joel M. , Hauber Ernst , De Toffoli Barbara , Douté Sylvain , Keszthelyi Laszlo , Marinangeli Lucia , Perry Jason , Pommerol Antoine , Pompilio Loredana , Rossi Angelo Pio , Seelos Frank , Sauro Francesco , Ziethe Ruth , Cremonese Gabriele , Thomas Nicolas
Published: December 2022

The evolution of the Ladon basin has been marked by intense geological activity and the discharge of huge volumes of water from the Martian highlands to the lowlands in the late Noachian and Hesperian. We explore the potential of the ExoMars Trace Gas Orbiter/Color and Stereo Surface Imaging System color image data set for geological interpretation and show that it is particularly effective for geologic mapping in combination with other data sets such as HiRISE, Context, and Compact Reconnaissance Imaging Spectrometer for Mars. The study area displays dark lobate flows of upper Hesperian to early Amazonian age, which were likely extruded from a regional extensional fault network. Spectral analysis suggests that these flows and the underlying rocks are ultramafic. Two distinct altered levels are observed below the lobate flows. The upper, yellow‐orange level shows hundreds of structurally controlled narrow ridges reminiscent of ridges of listwanite, a suite of silicified, fracture‐controlled silica‐carbonate rocks derived from an ultramafic source and from serpentine. In addition to serpentinite, the detected mineral assemblages may include chlorite, carbonates, and talc. Kaolin minerals are detected in the lower, white level, which could have formed by groundwater alteration of plagioclase in the volcanic pile. Volcanism, tectonics, hydrothermal activity, and kaolinization are interpreted to be coeval, with hydrothermal activity and kaolinization controlled by the interactions between the aquifer and the hot, ultramafic lobate flows. Following our interpretations, East Ladon may host the first listwanite ridges described on Mars, involving a hydrothermal system rooted in a Hesperian aquifer and affecting ultramafic rocks from a magmatic source yet to be identified.
Satellite Remote Sensing of Global Land Surface Temperature: Definition, Methods, Products, and Applications
Authors: Li Zhao‐Liang , Wu Hua , Duan Si‐Bo , Zhao Wei , Ren Huazhong , Liu Xiangyang , Leng Pei , Tang Ronglin , Ye Xin , Zhu Jinshun , Sun Yingwei , Si Menglin , Liu Meng , Li Jiahao , Zhang Xia , Shang Guofei , Tang Bo‐Hui , Yan Guangjian , Zhou Chenghu
Published: December 2022

Land surface temperature (LST) is a crucial parameter that reflects land–atmosphere interaction and has thus attracted wide interest from geoscientists. Owing to the rapid development of Earth observation technologies, remotely sensed LST is playing an increasingly essential role in various fields. This review aims to summarize the progress in LST estimation algorithms and accelerate its further applications. Thus, we briefly review the most‐used thermal infrared (TIR) LST estimation algorithms. More importantly, this review provides a comprehensive collection of the widely used TIR‐based LST products and offers important insights into the uncertainties in these products with respect to different land cover conditions via a systematic intercomparison analysis of several representative products. In addition to the discussion on product accuracy, we address problems related to the spatial discontinuity, spatiotemporal incomparability, and short time span of current LST products by introducing the most effective methods. With the aim of overcoming these challenges in available LST products, much progress has been made in developing spatiotemporal seamless LST data, which significantly promotes the successful applications of these products in the field of surface evapotranspiration and soil moisture estimation, agriculture drought monitoring, thermal environment monitoring, thermal anomaly monitoring, and climate change. Overall, this review encompasses the most recent advances in TIR‐based LST and the state‐of‐the‐art of applications of LST products at various spatial and temporal scales, identifies critical further research needs and directions to advance and optimize retrieval methods, and promotes the application of LST to improve the understanding of surface thermal dynamics and exchanges.
Analog Models of Lithospheric‐Scale Rifting Monitored in an X‐Ray CT Scanner
Authors: Zwaan F. , Schreurs G.
Published: December 2022

Rifting and continental break‐up are fundamental tectonic processes, the understanding of which is of prime importance. However, the vast temporal and spatial scales involved pose major limitations to researchers. Analog tectonic modeling represents a great means to mitigate these limitations, but studying the complex internal deformation of lithospheric‐scale models remains a challenge. We therefore present a novel method for lithospheric‐scale rifting models that are uniquely monitored in an X‐ray CT scanner, which combined with digital image correlation (DIC) techniques, provides unparalleled insights into model deformation. Our first models illustrate how the degree of coupling between competent lithospheric layers, which are separated by a weak lower crustal layer, strongly impacts rift system development. Low coupling isolates the upper crust from the upper lithospheric mantle layer below, preventing an efficient transfer of deformation between both layers. By contrast, fast rifting increases coupling, so that deformation in the mantle is efficiently transferred to the upper crust, inducing either a symmetric or asymmetric (double) rift system. Furthermore, oblique divergence may lead to en echelon graben arrangements and delayed exhumation of the lower crustal layer. The successful application of our novel modeling approach, yielding these first‐order insights, provides a clear incentive to continue running lithospheric‐scale rifting models, and to apply advanced monitoring techniques to extract as much information from models as possible. There is indeed a broad range of opportunities for follow‐up studies within (and beyond) the field of rift tectonics.
Experimental Analysis of Intermittent Pumping Effects on Seawater Intrusion
Authors: Zhu Shumei , Zhou Zhifang , Werner Adrian D. , Chen Yongqiang
Published: December 2022

Time fluctuations of groundwater flux are known to affect solute transport and thus the width and penetration of seawater intrusion. Yet, most theoretical and laboratory studies of the mixed‐convective processes accompanying seawater intrusion assume constant extraction rates, even though real‐world pumping is usually intermittent. In this study, dynamic changes to an experimental saltwater wedge caused by intermittent pumping were explored using sand tank experiments and numerical simulation. Three different aquifer systems were assessed: a homogeneous unconfined aquifer, and two stratified systems (aquifer‐aquitard‐aquifer), with the latter having an aquitard of lower permeability. Both fully and partially penetrating wells were used. The effects of the pumping period and no‐pumping period were explored, with nine laboratory experiments performed in total. The overall finding is that the impact of intermittent pumping is non‐trivial. Under the laboratory conditions, where head was prescribed inland (representative of a surface water body) intermittent pumping allowed larger volumes of freshwater to be extracted before well salinization. This reflects that non‐pumping periods allow the aquifer to recover. Additional experiments and numerical modeling, which reproduced reasonably well the experimental observations, showed that well salinization could be avoided altogether with sufficient periods of recovery. Numerical models were also used to compare intermittent and constant pumping for the same total extraction rate, showing that intermittent pumping caused earlier well salinization compared to constant pumping, although the aquifer contained a greater mass of salt under constant pumping.
Controlling Factors of the Spatial‐Temporal Fluctuations in Evapotranspiration Along an Elevation Gradient Across Humid Montane Ecosystems
Authors: Hu Zhaoyong , Sun Shouqin , Sun Xiangyang , Lin Shan , Song Chunlin , Wang Genxu
Published: December 2022

Diverse meteorological and vegetation conditions at different elevations and years lead to varied contributions of evapotranspiration (ET) to water yield in montane areas. However, how physical and biological factors affect interannual and elevational ET fluctuations in energy‐limited montane ecosystems remains unclear. Therefore, we quantified the spatial‐temporal patterns of ET and separated physical and biological controls on ET fluctuations using 5‐year (2015–2019) eddy‐covariance data and perturbation analysis on Mount Gongga, Southwest China. Coefficients of variations of annual ET were 0.85%–4.33%, suggesting the remarkable interannual consistencies of ET in all studied zones. In forest zones, decreased precipitation (P) contributed more than 85% of ET reduction in the severe dry year, while the decreased vapor pressure deficit and available energy accounted for 88%, 78%, and 87% of transpiration reductions in broadleaf forest, broadleaf and coniferous forest and coniferous forest, respectively, in the wet year. In shrubland, the positive influence from biological factors (41.37 mm) surpassed the negative impact from physical conditions (−16.46 mm), resulting in an increase in ET in the wet year. Mean annual ET was highest at 2,200 m a.s.l., 15.04% higher than that at 3,996 m a.s.l. From perturbation analysis, elevational ET fluctuations were smaller in low‐elevation (12.31 mm) and middle‐elevation (−31.18 mm) zones than that in high‐elevation zone (−99.86 mm). Large elevational ET reduction in high‐elevation zone mainly resulted from decreased P and leaf area index. In humid montane areas, although ET is predicted to increase, how interannual and elevational ET respond to climate changes should be considered separately.
Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
Authors: Mansouri Larry , Thorvaldsdottir Birna , Sutton Lesley-Ann , Karakatsoulis Georgios , Meggendorfer Manja , Parker Helen , Nadeu Ferran , Brieghel Christian , Laidou Stamatia , Moia Riccardo , Rossi Davide , Catherwood Mark , Kotaskova Jana , Delgado Julio , Rodríguez-Vicente Ana E. , Benito Rocío , Rigolin Gian Matteo , Bonfiglio Silvia , Scarfo Lydia , Mattsson Mattias , Davis Zadie , Gogia Ajay , Rani Lata , Baliakas Panagiotis , Foroughi-Asl Hassan , Jylhä Cecilia , Skaftason Aron , Rapado Inmaculada , Miras Fatima , Martinez-Lopez Joaquín , de la Serna Javier , Rivas Jesús María Hernández , Thornton Patrick , Larráyoz María José , Calasanz María José , Fésüs Viktória , Mátrai Zoltán , Bödör Csaba , Smedby Karin E. , Espinet Blanca , Puiggros Anna , Gupta Ritu , Bullinger Lars , Bosch Francesc , Tazón-Vega Bárbara , Baran-Marszak Fanny , Oscier David , Nguyen-Khac Florence , Zenz Thorsten , Terol Maria Jose , Cuneo Antonio , Hernández-Sánchez María , Pospisilova Sarka , Mills Ken , Gaidano Gianluca , Niemann Carsten U. , Campo Elias , Strefford Jonathan C. , Ghia Paolo , Stamatopoulos Kostas , Rosenquist Richard
Published: December 2022

Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
UHRF1-mediated ferroptosis promotes pulmonary fibrosis via epigenetic repression of GPX4 and FSP1 genes
Authors: Liu Yi , Cheng Demin , Wang Yue , Xi Sichuan , Wang Ting , Sun Wenqing , Li Guanru , Ma Dongyu , Zhou Siyun , Li Ziwei , Ni Chunhui
Published: December 2022

Pulmonary fibrosis (PF), as an end-stage clinical phenotype of interstitial lung diseases (ILDs), is frequently initiated after alveolar injury, in which ferroptosis has been identified as a critical event aggravating the pathophysiological progression of this disease. Here in, a comprehensive analysis of two mouse models of pulmonary fibrosis developed in our lab demonstrated that lung damage-induced ferroptosis of alveolar epithelial Type2 cells (AEC2) significantly accumulates during the development of pulmonary fibrosis while ferroptosis suppressor genes GPX4 and FSP1 are dramatically inactivated. Mechanistically, upregulation of de novo methylation regulator Uhrf1 sensitively elevates CpG site methylation levels in promoters of both GPX4 and FSP1 genes and induces the epigenetic repression of both genes, subsequently leading to ferroptosis in chemically interfered AEC2 cells. Meanwhile, specific inhibition of UHRF1 highly arrests the ferroptosis formation and blocks the progression of pulmonary fibrosis in both of our research models. This study first, to our knowledge, identified the involvement of Uhrf1 in mediating the ferroptosis of chemically injured AEC2s via de novo promoter-specific methylation of both GPX4 and FSP1 genes, which consequently accelerates the process of pulmonary fibrosis. The above findings also strongly suggested Uhrf1 as a novel potential target in the treatment of pulmonary fibrosis.
SLC1A5 enhances malignant phenotypes through modulating ferroptosis status and immune microenvironment in glioma
Authors: Han Liying , Zhou Jinpeng , Li Leiyang , Wu Xun , Shi Yingwu , Cui Wenxing , Zhang Shenghao , Hu Qing , Wang Jin , Bai Hao , Liu Haixiao , Guo Chengxuan , Cao Haiyan , Chao Min , Hu Yaqin , Mou Yueyang , Jiao Yang , Feng Dayun , Wang Liang , Qu Yan
Published: December 2022

Glioma is the most common type of primary malignant tumor in the central nervous system with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is a novel and distinct type of programmed cell death, playing a regulatory role in the progression of tumors. However, the role of ferroptosis or ferroptosis-related genes (FRGs) in glioma progression has not been extensively studied. In our study, a novel ferroptosis-related prognostic model, including 7 genes, was established, in which patients classified into the high-risk group had more immuno-suppressive status and worse prognosis. Among these 7 genes, we screened solute carrier family 1 member 5 (SLC1A5), an FRG, as a possible new target for glioma treatment. Our results showed that the expression of SLC1A5 was significantly upregulated in glioblastoma tissues compared with the low-grade gliomas. In addition, SLC1A5 knockdown could significantly inhibit glioma cell proliferation and invasion, and reduce the sensitivity of ferroptosis via the GPX4-dependent pathway. Furthermore, SLC1A5 was found to be related to immune response and SLC1A5 knockdown decreased the infiltration and M2 polarization of tumor-associated macrophages. Pharmacological inhibition of SLC1A5 by V9302 was confirmed to promote the efficacy of anti-PD-1 therapy. Overall, we developed a novel prognostic model for glioma based on the seven-FRGs signature, which could apply to glioma prognostic and immune status prediction. Besides, SLC1A5 in the model could regulate the proliferation, invasion, ferroptosis and immune state in glioma, and be applied as a prognostic biomarker and potential therapeutic target for glioma.
Engineering inducible biomolecular assemblies for genome imaging and manipulation in living cells
Authors: Peng Qin , Huang Ziliang , Sun Kun , Liu Yahan , Yoon Chi Woo , Harrison Reed E. S. , Schmitt Danielle L. , Zhu Linshan , Wu Yiqian , Tasan Ipek , Zhao Huimin , Zhang Jin , Zhong Sheng , Chien Shu , Wang Yingxiao
Published: December 2022

Genome architecture and organization play critical roles in cell life. However, it remains largely unknown how genomic loci are dynamically coordinated to regulate gene expression and determine cell fate at the single cell level. We have developed an inducible system which allows Simultaneous Imaging and Manipulation of genomic loci by Biomolecular Assemblies (SIMBA) in living cells. In SIMBA, the human heterochromatin protein 1α (HP1α) is fused to mCherry and FRB, which can be induced to form biomolecular assemblies (BAs) with FKBP-scFv, guided to specific genomic loci by a nuclease-defective Cas9 (dCas9) or a transcriptional factor (TF) carrying tandem repeats of SunTag. The induced BAs can not only enhance the imaging signals at target genomic loci using a single sgRNA, either at repetitive or non-repetitive sequences, but also recruit epigenetic modulators such as histone methyltransferase SUV39H1 to locally repress transcription. As such, SIMBA can be applied to simultaneously visualize and manipulate, in principle, any genomic locus with controllable timing in living cells.
A randomized trial of oral gamma aminobutyric acid (GABA) or the combination of GABA with glutamic acid decarboxylase (GAD) on pancreatic islet endocrine function in children with newly diagnosed type 1 diabetes
Authors: Martin Alexandra , Mick Gail J. , Choat Heather M. , Lunsford Alison A. , Tse Hubert M. , McGwin Gerald G. , McCormick Kenneth L.
Published: December 2022

Gamma aminobutyric acid(GABA) is synthesized by glutamate decarboxylase(GAD) in β-cells. Regarding Type 1 diabetes(T1D), animal/islet-cell studies found that GABA promotes insulin secretion, inhibits α-cell glucagon and dampens immune inflammation, while GAD immunization may also preserve β-cells. We evaluated the safety and efficacy of oral GABA alone, or combination GABA with GAD, on the preservation of residual insulin secretion in recent-onset T1D. Herein we report a single-center, double-blind, one-year, randomized trial in 97 children conducted March 2015 to June 2019(NCT02002130). Using a 2:1 treatment:placebo ratio, interventions included oral GABA twice-daily(n = 41), or oral GABA plus two-doses GAD-alum(n = 25), versus placebo(n = 31). The primary outcome, preservation of fasting/meal-stimulated c-peptide, was not attained. Of the secondary outcomes, the combination GABA/GAD reduced fasting and meal-stimulated serum glucagon, while the safety/tolerability of GABA was confirmed. There were no clinically significant differences in glycemic control or diabetes antibody titers. Given the low GABA dose for this pediatric trial, future investigations using higher-dose or long-acting GABA formulations, either alone or with GAD-alum, could be considered, although GABA alone or in combination with GAD-alum did nor preserve beta-cell function in this trial.
Peptidoglycan recycling mediated by an ABC transporter in the plant pathogen Agrobacterium tumefaciens
Authors: Gilmore Michael C. , Cava Felipe
Published: December 2022

During growth and division, the bacterial cell wall peptidoglycan (PG) is remodelled, resulting in the liberation of PG muropeptides which are typically reinternalized and recycled. Bacteria belonging to the Rhizobiales and Rhodobacterales orders of the Alphaproteobacteria lack the muropeptide transporter AmpG, despite having other key PG recycling enzymes. Here, we show that an alternative transporter, YejBEF-YepA, takes over this role in the Rhizobiales phytopathogen Agrobacterium tumefaciens. Muropeptide import by YejBEF-YepA governs expression of the β-lactamase AmpC in A. tumefaciens, contributing to β-lactam resistance. However, we show that the absence of YejBEF-YepA causes severe cell wall defects that go far beyond lowered AmpC activity. Thus, contrary to previously established Gram-negative models, PG recycling is vital for cell wall integrity in A. tumefaciens. YepA is widespread in the Rhizobiales and Rhodobacterales, suggesting that YejBEF-YepA-mediated PG recycling could represent an important but overlooked aspect of cell wall biology in these bacteria.
Centrifugal multimaterial 3D printing of multifunctional heterogeneous objects
Authors: Cheng Jianxiang , Wang Rong , Sun Zechu , Liu Qingjiang , He Xiangnan , Li Honggeng , Ye Haitao , Yang Xingxin , Wei Xinfeng , Li Zhenqing , Jian Bingcong , Deng Weiwei , Ge Qi
Published: December 2022

There are growing demands for multimaterial three-dimensional (3D) printing to manufacture 3D object where voxels with different properties and functions are precisely arranged. Digital light processing (DLP) is a high-resolution fast-speed 3D printing technology suitable for various materials. However, multimaterial 3D printing is challenging for DLP as the current multimaterial switching methods require direct contact onto the printed part to remove residual resin. Here we report a DLP-based centrifugal multimaterial (CM) 3D printing method to generate large-volume heterogeneous 3D objects where composition, property and function are programmable at voxel scale. Centrifugal force enables non-contact, high-efficiency multimaterial switching, so that the CM 3D printer can print heterogenous 3D structures in large area (up to 180 mm × 130 mm) made of materials ranging from hydrogels to functional polymers, and even ceramics. Our CM 3D printing method exhibits excellent capability of fabricating digital materials, soft robots, and ceramic devices.
Deconstructing body axis morphogenesis in zebrafish embryos using robot-assisted tissue micromanipulation
Authors: Özelçi Ece , Mailand Erik , Rüegg Matthias , Oates Andrew C. , Sakar Mahmut Selman
Published: December 2022

Classic microsurgical techniques, such as those used in the early 1900s by Mangold and Spemann, have been instrumental in advancing our understanding of embryonic development. However, these techniques are highly specialized, leading to issues of inter-operator variability. Here we introduce a user-friendly robotic microsurgery platform that allows precise mechanical manipulation of soft tissues in zebrafish embryos. Using our platform, we reproducibly targeted precise regions of tail explants, and quantified the response in real-time by following notochord and presomitic mesoderm (PSM) morphogenesis and segmentation clock dynamics during vertebrate anteroposterior axis elongation. We find an extension force generated through the posterior notochord that is strong enough to buckle the structure. Our data suggest that this force generates a unidirectional notochord extension towards the tailbud because PSM tissue around the posterior notochord does not let it slide anteriorly. These results complement existing biomechanical models of axis elongation, revealing a critical coupling between the posterior notochord, the tailbud, and the PSM, and show that somite patterning is robust against structural perturbations.
Simultaneous profiling of histone modifications and DNA methylation via nanopore sequencing
Authors: Yue Xue , Xie Zhiyuan , Li Moran , Wang Kai , Li Xiaojing , Zhang Xiaoqing , Yan Jian , Yin Yimeng
Published: December 2022

The interplay between histone modifications and DNA methylation drives the establishment and maintenance of the cellular epigenomic landscape, but it remains challenging to investigate the complex relationship between these epigenetic marks across the genome. Here we describe a nanopore-sequencing-based-method, nanoHiMe-seq, for interrogating the genome-wide localization of histone modifications and DNA methylation from single DNA molecules. nanoHiMe-seq leverages a nonspecific methyltransferase to exogenously label adenine bases proximal to antibody-targeted modified nucleosomes in situ. The labelled adenines and the endogenous methylated CpG sites are simultaneously detected on individual nanopore reads using a hidden Markov model, which is implemented in the nanoHiMe software package. We demonstrate the utility, robustness and sensitivity of nanoHiMe-seq by jointly profiling DNA methylation and histone modifications at low coverage depths, concurrently determining phased patterns of DNA methylation and histone modifications, and probing the intrinsic connectivity between these epigenetic marks across the genome.
Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus
Authors: Wu Lei , Xie Xinqiang , Li Ying , Liang Tingting , Zhong Haojie , Yang Lingshuang , Xi Yu , Zhang Jumei , Ding Yu , Wu Qingping
Published: December 2022

The gut microbiota plays an important role in human health and longevity, and the gut microbiota of centenarians shows unique characteristics. Nowadays, most microbial research on longevity is usually limited to the bioinformatics level, lacking validating information on culturing functional microorganisms. Here, we combined metagenomic sequencing and large-scale in vitro culture to reveal the unique gut microbial structure of the world’s longevity town—Jiaoling, China, centenarians and people of different ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was explored and validated in vivo. 247 healthy Cantonese natives of different ages participated in the study, including 18 centenarians. Compared with young adults, the gut microbiota of centenarians exhibits higher microbial diversity, xenobiotics biodegradation and metabolism, oxidoreductases, and multiple species (the potential probiotics Lactobacillus, Akkermansia, the methanogenic Methanobrevibacter, gut butyrate-producing members Roseburia, and SCFA-producing species uncl Clostridiales, uncl Ruminococcaceae) known to be beneficial to host metabolism. These species are constantly changing with age. We also isolated 2055 strains from these samples by large-scale in vitro culture, most of which were detected by metagenomics, with clear complementarity between the two approaches. We also screened an age-related gut-resident Lactobacillus with independent intellectual property rights, and its metabolite (L-ascorbic acid) and itself have good antioxidant effects. Our findings underscore the existence of age-related trajectories in the human gut microbiota, and that distinct gut microbiota and gut-resident as antioxidant systems may contribute to health and longevity.
Electric-controlled tunable thermal switch based on Janus monolayer MoSSe
Authors: Wei Donghai , Zhou E , Zheng Xiong , Wang Huimin , Shen Chen , Zhang Hongbin , Qin Zhenzhen , Qin Guangzhao
Published: December 2022

The high-performance, wide-range tunable thermal switches play a significant role in the thermal management, high-power-density intelligent devices, energy systems, etc. However, traditional thermal switch components, such as thermal diodes, suffer from poor stability, small adjustability, low time efficiency, and difficult implementation. Herein, we propose the superior electric-controlled thermal switch (ECTS) based on Janus monolayer MoSSe. The high-effective and asymmetric regulation of the thermal conductivity driven by electric field demonstrates a wide-range adjustable thermal switch ratio, where the peak value reaches 2.09 under the electric field of 0.04 VÅ−1. The underlying mechanism is revealed by electronic structures that the interactions between electrons and phonons are renormalized due to the electric field driving charge density redistribution, which ultimately modulates the phonon anharmonicity. The high-efficiency adjustable ECTS component is expected to provide new inspiration for next-generation thermal management and information processing.
Germline genetic variation and predicting immune checkpoint inhibitor induced toxicity
Authors: Chin Ik Shin , Khan Aman , Olsson-Brown Anna , Papa Sophie , Middleton Gary , Palles Claire
Published: December 2022

Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of various cancer types. ICIs reinstate T-cell function to elicit an anti-cancer immune response. The resulting immune response can however have off-target effects which manifest as autoimmune type serious immune-related adverse events (irAE) in ~10–55% of patients treated. It is currently challenging to predict both who will experience irAEs and to what severity. Identification of patients at high risk of serious irAE would revolutionise patient care. While the pathogenesis driving irAE development is still unclear, host genetic factors are proposed to be key determinants of these events. This review presents current evidence supporting the role of the host genome in determining risk of irAE. We summarise the spectrum and timing of irAEs following treatment with ICIs and describe currently reported germline genetic variation associated with expression of immuno-modulatory factors within the cancer immunity cycle, development of autoimmune disease and irAE occurrence. We propose that germline genetic determinants of host immune function and autoimmune diseases could also explain risk of irAE development. We also endorse genome-wide association studies of patients being treated with ICIs to identify genetic variants that can be used in polygenic risk scores to predict risk of irAE.
Identification of microbes coexisting with Legionella spp. in bathwaters
Authors: Okunaga Masaki , Kushiro Kenta , Horie Ryohei , Kondo Akihiro , Abe Takashi
Published: December 2022

In Japan, bathwaters are a potential source of legionellosis; therefore, the bathwater in public facilities must be regularly tested for Legionella spp. Currently, Legionella spp. is detected using the culture method, which is time-consuming and has limited accuracy. Moreover, the reproductive environment of Legionella spp. in bathwater remains unclear. Here, we investigated the environment in which Legionella spp. reproduce by analyzing the bathwater microbiota and its relationship with Legionella spp. We identified the microbiota of 112 bathwater samples collected from bathing facilities by sequencing 16S and 18S rRNA genes. Differences in the microbiota were observed between samples that tested positive and negative for Legionella spp., according to 16S rRNA sequencing and culture methods. Methyloversatilis, Cupriavidus, Phenylobacterium, Vermamoeba, and Aspidisca were highly correlated with Legionella spp. Our results support the development of strategies against legionellosis and elucidate the relationships between Legionella spp. and the coexisting microbiota in various environments.
Immobilization of silver nanoparticles on cellulose nanofibrils incorporated into nanofiltration membrane for enhanced desalination performance
Authors: He Ming , Li Wei-Dong , Chen Jia-Chuan , Zhang Zhi-Guo , Wang Xiao-Fa , Yang Gui-Hua
Published: December 2022

Nanofiltration (NF) membranes circumventing global water scarcity with excellent separation and antibacterial performances are highly desirable for efficient water treatment but remain a great challenge. Herein, a nanofiltration membrane was fabricated by in situ immobilizing silver nanoparticles (AgNPs) on sulfated cellulose nanofibril incorporated during interfacial polymerization. AgNPs were confirmed to be uniformly distributed and in situ grown on sulfated cellulose nanofibril (SCNF) due to its abundant sulfate and hydroxyl groups by mixing them with anhydrous piperazine solution as inorganic phase and homophenyl chloride n-hexane solution as the organic phase on the surface of a polyethersulfone microporous membrane. The attributes of SCNF, excellent hydrophilicity, and highly negative charges enhanced both the rejection and water permeability. As the SCNF charge increased, the roughness of SCNF increased and the contact angle decreased, and the maximum values were 203 nm and 17.67°, respectively. Among all the composite NF membranes, H-SCNF/Ag-0.01 had better rejection of Na2SO4and NaCl, with a maximum rejection of 97.11% and 32.55%, respectively. Meanwhile, it also maintained high water permeability. Antibacterial experiments indicated that the composite NF membrane had effective inhibition againstEscherichia coliand exhibited an expected slow-release capability of Ag+, which made it have long-term antibacterial properties. It was estimated that the antibacterial effect could last for 90 days. This work demonstrated that AgNPs in situ immobilization on SCNF could be used as promising nanofillers for designing advanced functional NF membranes.
A speech corpus of Quechua Collao for automatic dimensional emotion recognition
Authors: Paccotacya-Yanque Rosa Y. G. , Huanca-Anquise Candy A. , Escalante-Calcina Judith , Ramos-Lovón Wilber R. , Cuno-Parari Álvaro E.
Published: December 2022

Automatic speech emotion recognition is an important research topic for human-computer interaction and affective computing. Over ten million people speak the Quechua language throughout South America, and one of the most known variants is the Quechua Collao one. However, this language can be considered a low resource for machine emotion recognition, creating a barrier for Quechua speakers who want to use this technology. Therefore, the contribution of this work is a 15 hours speech corpus in Quechua Collao, which is made publicly available to the research community. The corpus was created from a set of words and sentences explicitly collected for this task, divided into nine categorical emotions: happy, sad, bored, fear, sleepy, calm, excited, angry, and neutral. The annotation was performed on a 5-value discrete scale according to 3 dimensions: valence, arousal, and dominance. To demonstrate the usefulness of the corpus, we have performed speech emotion recognition using machine learning methods and neural networks.
Transition1x - a dataset for building generalizable reactive machine learning potentials
Authors: Schreiner Mathias , Bhowmik Arghya , Vegge Tejs , Busk Jonas , Winther Ole
Published: December 2022

Machine Learning (ML) models have, in contrast to their usefulness in molecular dynamics studies, had limited success as surrogate potentials for reaction barrier search. This is primarily because available datasets for training ML models on small molecular systems almost exclusively contain configurations at or near equilibrium. In this work, we present the dataset Transition1x containing 9.6 million Density Functional Theory (DFT) calculations of forces and energies of molecular configurations on and around reaction pathways at the ωB97x/6–31 G(d) level of theory. The data was generated by running Nudged Elastic Band (NEB) with DFT on 10k organic reactions of various types while saving intermediate calculations. We train equivariant graph message-passing neural network models on Transition1x and cross-validate on the popular ANI1x and QM9 datasets. We show that ML models cannot learn features in transition state regions solely by training on hitherto popular benchmark datasets. Transition1x is a new challenging benchmark that will provide an important step towards developing next-generation ML force fields that also work far away from equilibrium configurations and reactive systems.
A Raman spectral reference library of potential anthropogenic and biological ocean polymers
Authors: Miller Emily A. , Yamahara Kevan M. , French Chris , Spingarn Neil , Birch James M. , Van Houtan Kyle S.
Published: December 2022

Microplastics have been extensively documented in marine ecosystems and food webs with devastating impacts. To solve this global crisis, identifying the polymer composition is key for resolving the material origin, geographic source, and ecosystem life cycle of ocean plastics. Visually based techniques, importantly, are not diagnostic. Raman spectroscopy is an increasingly preferred identification method for its accuracy and reduced likelihood of misinterpretation, though it can be inaccessible due to cost of paywalled spectral libraries and availability of relevant polymer spectra for comparison. Here, we provide an open-access reference library of high-quality, broad-spectrum Raman spectra of major polymer categories germane to marine environments. The library includes high-quality spectra from: (a) pristine anthropogenic polymers newly sourced from manufacturers (n = 40), (b) weathered anthropogenic polymers collected from used consumer, beachcast, agricultural, and fishery sources (n = 22), and (c) biological polymers representing diverse marine taxa, trophic levels, and tissues (n = 17). We hope this reference library can help this rapidly expanding scientific community and facilitate progress in the global plastic pollution crisis.
Chromosome-level genome assembly of the Siberian chipmunk (Tamias sibiricus)
Authors: Li Ran , Zhang Mingfei , Cha Muha , Xiang Jishan , Yi Xianfeng
Published: December 2022

Tamias sibiricus is regarded as one predominant scatter-hoarder that stores their food items both in small scattered caches and underground larder-hoards. This unique behavior, though providing essential seed dispersal services for many plant species worldwide, relies highly on accurate spatial memory and acute sense of olfaction. Here, we assembled a chromosome-scale genome of T. sibiricus using Illumina sequencing, PacBio sequencing and chromosome structure capture technique. The genome was 2.64 Gb in size with scaffold N50 length of 172.61 Mb. A total of 2.59 Gb genome data was anchored and orientated onto 19 chromosomes (ranging from 28.70 to 222.90 Mb) with a mounting rate of up to 98.03%. Meanwhile, 25,311 protein-coding genes were predicted with an average gene length of 32,936 bp, and 94.73% of these genes were functionally annotated. This reference genome will be a valuable resource for in-depth studies on basic biological possess and environmental adaptation of the Siberian chipmunk, as well as promoting comparative genomic analyses with other species within Rodentia.