bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpretation of Anhysteretic Remanent Magnetization Carriers in Magnetofossil‐Rich Marine Sediments
Authors: Zhang Qiang , Roberts Andrew P. , Ge Shulan , Liu Yanguang , Liu Jianxing , Liu Shuangchi , Tang Xu , Wang Haosen , Wang Dunfan , Li Jinhua , Liu Qingsong
Published: November 2022

The anhysteretic remanent magnetization (ARM) is an important magnetic parameter for quantifying the concentration of “fine”, mostly sub‐micron ferrimagnetic particles in rocks and sediments. A sound understanding of ARM carriers is needed to interpret magnetic and environmental information in sedimentary archives. This is often not achieved for marine sediments, which routinely contain several magnetic mineral components. Here, we analyze marine sediment records over different timescales for four sediment cores from the Eastern Pacific Ocean (Hole 1218A), the Antarctic margin (core P4‐1), the Arctic Ocean (core ARC5‐ICE4), and the South China Sea (core L07), using coercivity spectra analyses of ARM, first‐order reversal curve principal component analysis (FORC‐PCA), transmission electron microscopy (TEM), and unmixing of isothermal remanent magnetization (IRM) curves. By combining rock magnetic and TEM results, we find that the ARM is mainly carried by non‐interacting single domain (SD) biogenic magnetite (magnetofossils) in the studied sediments over all timescales. Low‐coercivity magnetic particles (detrital and fine‐grained extracellular magnetite) also contribute to the bulk ARM. Variable magnetofossil chain structures are detected and have a significant influence on ARM data interpretation. Quantitative FORC‐PCA endmember analyses based on quantile contours and coercivity distributions provide valuable information on the nature of endmembers and improve ARM data interpretation. We provide an integrated strategy to help reduce interpretational ambiguities related to ARM in future studies.
MarsQuakeNet: A More Complete Marsquake Catalog Obtained by Deep Learning Techniques
Authors: Dahmen Nikolaj L. , Clinton John F. , Meier Men‐Andrin , Stähler Simon C. , Ceylan Savas , Kim Doyeon , Stott Alexander E. , Giardini Domenico
Published: November 2022

NASA's Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) seismometer has been recording Martian seismicity since early 2019, and to date, over 1,300 marsquakes have been cataloged by the Marsquake Service (MQS). Due to typically low signal‐to‐noise ratios (SNR) of marsquakes, their detection and analysis remain challenging: while event amplitudes are relatively low, the background noise has large diurnal and seasonal variations and contains various signals originating from the interactions of the local atmosphere with the lander and seismometer system. Since noise can resemble marsquakes in a number of ways, the use of conventional detection methods for catalog curation is limited. Instead, MQS finds events through manual data inspection. Here, we present MarsQuakeNet (MQNet), a deep convolutional neural network for the detection of marsquakes and the removal of noise contamination. Based on three‐component seismic data, MQNet predicts segmentation masks that identify and separate event and noise energy in time‐frequency domain. As the number of cataloged MQS events is small, we combine synthetic event waveforms with recorded noise to generate a training data set. We apply MQNet to the entire continuous 20 samples‐per‐second waveform data set available to date (>1,000 Martian days), for automatic event detection and for retrieving denoised amplitudes. The algorithm reproduces all high quality, as well as majority of low quality events in the manual, carefully curated MQS catalog. Furthermore, MQNet detects ∼60% additional events that were previously unknown with mostly low SNR, that are verified in manual review. Our analysis on the event rate confirms seasonal trends and shows a substantial increase in the second Martian year.
Comparable Bulk Radar Attenuation Characteristics Across Both Martian Polar Layered Deposits
Authors: Abu Hashmeh N. , Whitten J. L. , Russell A. T. , Putzig N. E. , Campbell B. A.
Published: November 2022

The dust‐laden and predominantly water ice south polar layered deposits (SPLD) exhibit unique radar behavior at Shallow Radar (SHARAD) frequencies that is not seen in the NPLD. A vertically extensive scattering phenomenon leads to diffuse echoes that obscure radar stratigraphy within the SPLD, referred to as “fog.” Here, we use 2‐D and 3‐D SHARAD data to measure the areal extent in which the SPLD basal interface can be identified. We also measure reflected power of SPLD basal reflectors and compare those values to ice thickness, regional geomorphology, and the presence of radar echo scattering, to constrain any influence these factors may have on the propagation of radio waves and detectability of the base. Approximately 33% of the area in which the basal interface is observed in Mars Advanced Radar for Subsurface and Ionosphere Sounding data is also detected in SHARAD data. As expected, basal power shows a negative correlation with ice thickness, but the effects of radar fog are less clear. Areas of “column” radar fog patterns exhibit higher average basal power values than regions without radar fog, and areas with only near‐surface radar fog have the lowest average basal power values. Our study results suggest that these diffuse echoes may not be associated with radio wave attenuation. Average loss tangent for the SPLD (0.0019 ± 0.0012) indicates no distinguishable difference from previously reported NPLD values in terms of bulk loss properties. We speculate that the SPLD's infrequent reflections compared to the NPLD may be due to the former's dust being less densely packed together to facilitate radar detection.
Investigating the Impacts of Ionospheric Irregularities on Precise Point Positioning Over China and Its Mechanism
Authors: Li Wei , Song Shuli , Zhou Weili , Cheng Na , Yu Chao
Published: November 2022

The impacts of ionospheric irregularities on precise point positioning (PPP) have been commonly noticed in the field of the ionosphere and the precise application of the Global Navigation Satellite System. But few attentions have been paid to how ionospheric irregularities deteriorate the performance of PPP. Aiming at exploring the mechanism of degradation of PPP solutions during the period of ionospheric irregularities, this paper investigates the impacts of ionospheric irregularities on the performance of kinematic PPP. The experiment uses GPS observation data sampled at the 30‐s interval over China on the days of 2014, 2015, and 2017 covering some active space weather, for example, solar and geomagnetic activities. The results show that the ionospheric irregularities caused increased positioning errors (decimeter‐ to meter‐level), enlarged phase residuals (decimeter‐level), and increased the number of detected cycle slips in PPP processing in low latitude regions of China. By proposing a novel strategy that compares the number of detected cycle slips from 30 s‐sampling interval data and 1s‐sampling interval data at the same station in an “aligned” mode, we present direct evidence of the existence of the falsely detected cycle slips in 30 s‐sampling interval data by the traditional cycle‐slip detection threshold in PPP processing. We reveal that the unnecessary and frequent reinitialization of ambiguity induced by the falsely detected cycle slips is dominantly responsible for the degradation of kinematic PPP solutions during the period of ionospheric irregularities. Our findings pointed out the direction for the improvement of kinematic PPP performance in the environment of ionospheric irregularities.
Mouse models of Kras activation in gastric cancer
Authors: Won Yoonkyung , Choi Eunyoung
Published: November 2022

Gastric cancer has one of the highest incidence rates and is one of the leading causes of cancer-related mortality worldwide. Sequential steps within the carcinogenic process are observed in gastric cancer as well as in pancreatic cancer and colorectal cancer. Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most well-known oncogene and can be constitutively activated by somatic mutations in the gene locus. For over 2 decades, the functions of Kras activation in gastrointestinal (GI) cancers have been studied to elucidate its oncogenic roles during the carcinogenic process. Different approaches have been utilized to generate distinct in vivo models of GI cancer, and a number of mouse models have been established using Kras-inducible systems. In this review, we summarize the genetically engineered mouse models in which Kras is activated with cell-type and/or tissue-type specificity that are utilized for studying carcinogenic processes in gastric cancer as well as pancreatic cancer and colorectal cancer. We also provide a brief description of histological phenotypes and characteristics of those mouse models and the current limitations in the gastric cancer field to be investigated further.
Sensitive surface plasmon resonance label-free biosensor on a fiber end-facet
Authors: Fan Xudong
Published: November 2022

An advanced and cost-effective method was developed to fabricate a high-quality quasi-3D plasmonic crystal biosensor on an optical fiber end-facet.
Recent trends in photoelectrochemical water splitting: the role of cocatalysts
Authors: Kumar Mohit , Meena Bhagatram , Subramanyam Palyam , Suryakala Duvvuri , Subrahmanyam Challapalli
Published: November 2022

Environmental degradation due to the carbon emissions from burning fossil fuels has triggered the need for sustainable and renewable energy. Hydrogen has the potential to meet the global energy requirement due to its high energy density; moreover, it is also clean burning. Photoelectrochemical (PEC) water splitting is a method that generates hydrogen from water by using solar radiation. Despite the advantages of PEC water splitting, its applications are limited by poor efficiency due to the recombination of charge carriers, high overpotential, and sluggish reaction kinetics. The synergistic effect of using different strategies with cocatalyst decoration is promising to enhance efficiency and stability. Transition metal-based cocatalysts are known to improve PEC efficiency by reducing the barrier to charge transfer. Recent developments in novel cocatalyst design have led to significant advances in the fundamental understanding of improved reaction kinetics and the mechanism of hydrogen evolution. To highlight key important advances in the understanding of surface reactions, this review provides a detailed outline of very recent reports on novel PEC system design engineering with cocatalysts. More importantly, the role of cocatalysts in surface passivation and photovoltage, and photocurrent enhancement are highlighted. Finally, some challenges and potential opportunities for designing efficient cocatalysts are discussed.
Quantification of human contribution to soil moisture-based terrestrial aridity
Authors: Wang Yaoping , Mao Jiafu , Hoffman Forrest M. , Bonfils Céline J. W. , Douville Hervé , Jin Mingzhou , Thornton Peter E. , Ricciuto Daniel M. , Shi Xiaoying , Chen Haishan , Wullschleger Stan D. , Piao Shilong , Dai Yongjiu
Published: November 2022

Current knowledge of the spatiotemporal patterns of changes in soil moisture-based terrestrial aridity has considerable uncertainty. Using Standardized Soil Moisture Index (SSI) calculated from multi-source merged data sets, we find widespread drying in the global midlatitudes, and wetting in the northern subtropics and in spring between 45°N–65°N, during 1971–2016. Formal detection and attribution analysis shows that human forcings, especially greenhouse gases, contribute significantly to the changes in 0–10 cm SSI during August–November, and 0–100 cm during September–April. We further develop and apply an emergent constraint method on the future SSI’s signal-to-noise (S/N) ratios and trends under the Shared Socioeconomic Pathway 5-8.5. The results show continued significant presence of human forcings and more rapid drying in 0–10 cm than 0–100 cm. Our findings highlight the predominant human contributions to spatiotemporally heterogenous terrestrial aridification, providing a basis for drought and flood risk management.
A click chemistry amplified nanopore assay for ultrasensitive quantification of HIV-1 p24 antigen in clinical samples
Authors: Wei Xiaojun , Wang Xiaoqin , Zhang Zehui , Luo Yuanyuan , Wang Zixin , Xiong Wen , Jain Piyush K. , Monnier John R. , Wang Hui , Hu Tony Y. , Tang Chuanbing , Albrecht Helmut , Liu Chang
Published: November 2022

Despite major advances in HIV testing, ultrasensitive detection of early infection remains challenging, especially for the viral capsid protein p24, which is an early virological biomarker of HIV-1 infection. Here, To improve p24 detection in patients missed by immunological tests that dominate the diagnostics market, we show a click chemistry amplified nanopore (CAN) assay for ultrasensitive quantitative detection. This strategy achieves a 20.8 fM (0.5 pg/ml) limit of detection for HIV-1 p24 antigen in human serum, demonstrating 20~100-fold higher analytical sensitivity than nanocluster-based immunoassays and clinically used enzyme-linked immunosorbent assay, respectively. Clinical validation of the CAN assay in a pilot cohort shows p24 quantification at ultra-low concentration range and correlation with CD4 count and viral load. We believe that this strategy can improve the utility of p24 antigen in detecting early infection and monitoring HIV progression and treatment efficacy, and also can be readily modified to detect other infectious diseases.
Three-dimensional skyrmionic cocoons in magnetic multilayers
Authors: Grelier Matthieu , Godel Florian , Vecchiola Aymeric , Collin Sophie , Bouzehouane Karim , Fert Albert , Cros Vincent , Reyren Nicolas
Published: November 2022

Three-dimensional spin textures emerge as promising quasi-particles for encoding information in future spintronic devices. The third dimension provides more malleability regarding their properties and more flexibility for potential applications. However, the stabilization and characterization of such quasi-particles in easily implementable systems remain a work in progress. Here we observe a three-dimensional magnetic texture that sits in the interior of magnetic thin films aperiodic multilayers and possesses a characteristic ellipsoidal shape. Interestingly, these objects that we call skyrmionic cocoons can coexist with more standard tubular skyrmions going through all the multilayer as evidenced by the existence of two very different contrasts in room temperature magnetic force microscopy. The presence of these novel skyrmionic textures as well as the understanding of their layer resolved chiral and topological properties have been investigated by micromagnetic simulations. Finally, we show that the skyrmionic cocoons can be electrically detected using magneto-transport measurements.
Continuous generation of topological defects in a passively driven nematic liquid crystal
Authors: Mur Maruša , Kos Žiga , Ravnik Miha , Muševič Igor
Published: November 2022

Synthetic active matter is emerging as the prime route for the realisation of biological mechanisms such as locomotion, active mixing, and self-organisation in soft materials. In particular, passive nematic complex fluids are known to form out-of-equilibrium states with topological defects, but their locomotion, activation and experimental realization has been developed and understood to only a limited extent. Here, we report that the concentration-driven flow of small molecules triggers turbulent flow in the thin film of a nematic liquid crystal that continuously generates pairs of topological defects with an integer topological charge. The diffusion results in the formation of counter-rotating vortex rolls in the liquid crystal, which above a velocity threshold transform into a turbulent flow with continuous generation and annihilation of the defect pairs. The pairs of defects are created by the self-amplifying splay instability between the vortices, until a pair of oppositely charged defects is formed.
Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology
Authors: Lam Max , Chen Chia-Yen , Hill W. David , Xia Charley , Tian Ruoyu , Levey Daniel F. , Gelernter Joel , Stein Murray B. , Hatoum Alexander S. , Huang Hailiang , Malhotra Anil K. , Runz Heiko , Ge Tian , Lencz Todd
Published: November 2022

Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identify collective segments of the genome, which we call “meta-loci”, showing differential pleiotropic patterns for psychopathology relative to either cognitive task performance (CTP) or performance on a non-cognitive factor (NCF) derived from educational attainment. We observe that neurodevelopmental gene sets expressed during the prenatal-early childhood period predominate in CTP-relevant meta-loci, while post-natal gene sets are more involved in NCF-relevant meta-loci. Further, we demonstrate that neurodevelopmental gene sets are dissociable across CTP meta-loci with respect to their spatial distribution across the brain. Additionally, we find that GABA-ergic, cholinergic, and glutamatergic genes drive pleiotropic relationships within dissociable meta-loci.
Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations
Authors: Thorpe Harry A. , Tourrette Elise , Yahara Koji , Vale Filipa F. , Liu Siqi , Oleastro Mónica , Alarcon Teresa , Perets Tsachi-Tsadok , Latifi-Navid Saeid , Yamaoka Yoshio , Martinez-Gonzalez Beatriz , Karayiannis Ioannis , Karamitros Timokratis , Sgouras Dionyssios N. , Elamin Wael , Pascoe Ben , Sheppard Samuel K. , Ronkainen Jukka , Aro Pertti , Engstrand Lars , Agreus Lars , Suerbaum Sebastian , Thorell Kaisa , Falush Daniel
Published: November 2022

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.
Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice
Authors: Xie Kan , Fuchs Helmut , Scifo Enzo , Liu Dan , Aziz Ahmad , Aguilar-Pimentel Juan Antonio , Amarie Oana Veronica , Becker Lore , da Silva-Buttkus Patricia , Calzada-Wack Julia , Cho Yi-Li , Deng Yushuang , Edwards A. Cole , Garrett Lillian , Georgopoulou Christina , Gerlini Raffaele , Hölter Sabine M. , Klein-Rodewald Tanja , Kramer Michael , Leuchtenberger Stefanie , Lountzi Dimitra , Mayer-Kuckuk Phillip , Nover Lena L. , Oestereicher Manuela A. , Overkott Clemens , Pearson Brandon L. , Rathkolb Birgit , Rozman Jan , Russ Jenny , Schaaf Kristina , Spielmann Nadine , Sanz-Moreno Adrián , Stoeger Claudia , Treise Irina , Bano Daniele , Busch Dirk H. , Graw Jochen , Klingenspor Martin , Klopstock Thomas , Mock Beverly A. , Salomoni Paolo , Schmidt-Weber Carsten , Weiergräber Marco , Wolf Eckhard , Wurst Wolfgang , Gailus-Durner Valérie , Breteler Monique M. B. , Hrabě de Angelis Martin , Ehninger Dan
Published: November 2022

Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice. For each phenotype, we establish lifetime profiles to determine when age-dependent change is first detectable relative to the young adult baseline. We examine key lifespan regulators (putative anti-aging interventions; PAAIs) for a possible countering of aging. Importantly, unlike most previous studies, we include in our study design young treated groups of animals, subjected to PAAIs prior to the onset of detectable age-dependent phenotypic change. Many PAAI effects influence phenotypes long before the onset of detectable age-dependent change, but, importantly, do not alter the rate of phenotypic change. Hence, these PAAIs have limited effects on aging.
An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice
Authors: Vollmer Kelsey M. , Green Lisa M. , Grant Roger I. , Winston Kion T. , Doncheck Elizabeth M. , Bowen Christopher W. , Paniccia Jacqueline E. , Clarke Rachel E. , Tiller Annika , Siegler Preston N. , Bordieanu Bogdan , Siemsen Benjamin M. , Denton Adam R. , Westphal Annaka M. , Jhou Thomas C. , Rinker Jennifer A. , McGinty Jacqueline F. , Scofield Michael D. , Otis James M.
Published: November 2022

Suppression of dangerous or inappropriate reward-motivated behaviors is critical for survival, whereas therapeutic or recreational opioid use can unleash detrimental behavioral actions and addiction. Nevertheless, the neuronal systems that suppress maladaptive motivated behaviors remain unclear, and whether opioids disengage those systems is unknown. In a mouse model using two-photon calcium imaging in vivo, we identify paraventricular thalamostriatal neuronal ensembles that are inhibited upon sucrose self-administration and seeking, yet these neurons are tonically active when behavior is suppressed by a fear-provoking predator odor, a pharmacological stressor, or inhibitory learning. Electrophysiological, optogenetic, and chemogenetic experiments reveal that thalamostriatal neurons innervate accumbal parvalbumin interneurons through synapses enriched with calcium permeable AMPA receptors, and activity within this circuit is necessary and sufficient for the suppression of sucrose seeking regardless of the behavioral suppressor administered. Furthermore, systemic or intra-accumbal opioid injections rapidly dysregulate thalamostriatal ensemble dynamics, weaken thalamostriatal synaptic innervation of downstream neurons, and unleash reward-seeking behaviors in a manner that is reversed by genetic deletion of thalamic µ-opioid receptors. Overall, our findings reveal a thalamostriatal to parvalbumin interneuron circuit that is both required for the suppression of reward seeking and rapidly disengaged by opioids.
dcHiC detects differential compartments across multiple Hi-C datasets
Authors: Chakraborty Abhijit , Wang Jeffrey G. , Ay Ferhat
Published: November 2022

The compartmental organization of mammalian genomes and its changes play important roles in distinct biological processes. Here, we introduce dcHiC, which utilizes a multivariate distance measure to identify significant changes in compartmentalization among multiple contact maps. Evaluating dcHiC on four collections of bulk and single-cell contact maps from in vitro mouse neural differentiation (n = 3), mouse hematopoiesis (n = 10), human LCLs (n = 20) and post-natal mouse brain development (n = 3 stages), we show its effectiveness and sensitivity in detecting biologically relevant changes, including those orthogonally validated. dcHiC reported regions with dynamically regulated genes associated with cell identity, along with correlated changes in chromatin states, subcompartments, replication timing and lamin association. With its efficient implementation, dcHiC enables high-resolution compartment analysis as well as standalone browser visualization, differential interaction identification and time-series clustering. dcHiC is an essential addition to the Hi-C analysis toolbox for the ever-growing number of bulk and single-cell contact maps. Available at: https://github.com/ay-lab/dcHiC.
Explosive percolation yields highly-conductive polymer nanocomposites
Authors: Meloni Manuela , Large Matthew J. , González Domínguez José Miguel , Victor-Román Sandra , Fratta Giuseppe , Istif Emin , Tomes Oliver , Salvage Jonathan P. , Ewels Christopher P. , Pelaez-Fernandez Mario , Arenal Raul , Benito Ana , Maser Wolfgang K. , King Alice A. K. , Ajayan Pulickel M. , Ogilvie Sean P. , Dalton Alan B.
Published: November 2022

Explosive percolation is an experimentally-elusive phenomenon where network connectivity coincides with onset of an additional modification of the system; materials with correlated localisation of percolating particles and emergent conductive paths can realise sharp transitions and high conductivities characteristic of the explosively-grown network. Nanocomposites present a structurally- and chemically-varied playground to realise explosive percolation in practically-applicable systems but this is yet to be exploited by design. Herein, we demonstrate composites of graphene oxide and synthetic polymer latex which form segregated networks, leading to low percolation threshold and localisation of conductive pathways. In situ reduction of the graphene oxide at temperatures of <150 °C drives chemical modification of the polymer matrix to produce species with phenolic groups, which are known crosslinking agents. This leads to conductivities exceeding those of dense-packed networks of reduced graphene oxide, illustrating the potential of explosive percolation by design to realise low-loading composites with dramatically-enhanced electrical transport properties.
Protein control of photochemistry and transient intermediates in phytochromes
Authors: Salvadori Giacomo , Macaluso Veronica , Pellicci Giulia , Cupellini Lorenzo , Granucci Giovanni , Mennucci Benedetta
Published: November 2022

Phytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded chromophore, triggering large conformational changes in the protein. Despite numerous experimental and computational studies, the role of chromophore-protein interactions in controlling the mechanism and timescale of the process remains elusive. Here, we combine nonadiabatic surface hopping trajectories and adiabatic molecular dynamics simulations to reveal the molecular details of such control for the Deinococcus radiodurans bacteriophytochrome. Our simulations reveal that chromophore photoisomerization proceeds through a hula-twist mechanism whose kinetics is mainly determined by the hydrogen bond of the chromophore with a close-by histidine. The resulting photoproduct relaxes to an early intermediate stabilized by a tyrosine, and finally evolves into a late intermediate, featuring a more disordered binding pocket and a weakening of the aspartate-to-arginine salt-bridge interaction, whose cleavage is essential to interconvert the phytochrome to the active state.
Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans
Authors: Setty Hagar , Salzberg Yehuda , Karimi Shadi , Berent-Barzel Elisheva , Krieg Michael , Oren-Suissa Meital
Published: November 2022

How sensory perception is processed by the two sexes of an organism is still only partially understood. Despite some evidence for sexual dimorphism in auditory and olfactory perception, whether touch is sensed in a dimorphic manner has not been addressed. Here we find that the neuronal circuit for tail mechanosensation in C. elegans is wired differently in the two sexes and employs a different combination of sex-shared sensory neurons and interneurons in each sex. Reverse genetic screens uncovered cell- and sex-specific functions of the alpha-tubulin mec-12 and the sodium channel tmc-1 in sensory neurons, and of the glutamate receptors nmr-1 and glr-1 in interneurons, revealing the underlying molecular mechanisms that mediate tail mechanosensation. Moreover, we show that only in males, the sex-shared interneuron AVG is strongly activated by tail mechanical stimulation, and accordingly is crucial for their behavioral response. Importantly, sex reversal experiments demonstrate that the sexual identity of AVG determines both the behavioral output of the mechanosensory response and the molecular pathways controlling it. Our results present extensive sexual dimorphism in a mechanosensory circuit at both the cellular and molecular levels.
Impaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration
Authors: Lin Chujiao , Yang Qiyuan , Guo Dongsheng , Xie Jun , Yang Yeon-Suk , Chaugule Sachin , DeSouza Ngoc , Oh Won-Taek , Li Rui , Chen Zhihao , John Aijaz A. , Qiu Qiang , Zhu Lihua Julie , Greenblatt Matthew B. , Ghosh Sankar , Li Shaoguang , Gao Guangping , Haynes Cole , Emerson Charles P. , Shim Jae-Hyuck
Published: November 2022

Although skeletal progenitors provide a reservoir for bone-forming osteoblasts, the major energy source for their osteogenesis remains unclear. Here, we demonstrate a requirement for mitochondrial oxidative phosphorylation in the osteogenic commitment and differentiation of skeletal progenitors. Deletion of Evolutionarily Conserved Signaling Intermediate in Toll pathways (ECSIT) in skeletal progenitors hinders bone formation and regeneration, resulting in skeletal deformity, defects in the bone marrow niche and spontaneous fractures followed by persistent nonunion. Upon skeletal fracture, Ecsit-deficient skeletal progenitors migrate to adjacent skeletal muscle causing muscle atrophy. These phenotypes are intrinsic to ECSIT function in skeletal progenitors, as little skeletal abnormalities were observed in mice lacking Ecsit in committed osteoprogenitors or mature osteoblasts. Mechanistically, Ecsit deletion in skeletal progenitors impairs mitochondrial complex assembly and mitochondrial oxidative phosphorylation and elevates glycolysis. ECSIT-associated skeletal phenotypes were reversed by in vivo reconstitution with wild-type ECSIT expression, but not a mutant displaying defective mitochondrial localization. Collectively, these findings identify mitochondrial oxidative phosphorylation as the prominent energy-driving force for osteogenesis of skeletal progenitors, governing musculoskeletal integrity.
Design and directed evolution of noncanonical β-stereoselective metalloglycosidases
Authors: Jeong Woo Jae , Song Woon Ju
Published: November 2022

Metallohydrolases are ubiquitous in nearly all subclasses of hydrolases, utilizing metal elements to activate a water molecule and facilitate its subsequent dissociation of diverse chemical bonds. However, such a catalytic role of metal ions is rarely found with glycosidases that hydrolyze the glycosidic bonds in sugars. Herein, we design metalloglycosidases by constructing a hydrolytically active Zn-binding site within a barrel-shaped outer membrane protein OmpF. Structure- and mechanism-based redesign and directed evolution have led to the emergence of Zn-dependent glycosidases with catalytic proficiency of 2.8 × 109and high β-stereoselectivity. Biochemical characterizations suggest that the Zn-binding site constitutes a key catalytic motif along with at least one adjacent acidic residue. This work demonstrates that unprecedented metalloenzymes can be tailor-made, expanding the scope of inorganic reactivities in proteinaceous environments, resetting the structural and functional diversity of metalloenzymes, and providing the potential molecular basis of unidentified metallohydrolases and novel whole-cell biocatalysts.
Evaluation of telehealth support in an integrated respiratory clinic
Authors: Fox Lauren , Heiden Emily , Chauhan Milan A. J. , Longstaff Jayne M. , Balls Lara , De Vos Ruth , Neville Daniel M. , Jones Thomas L. , Leung Anthony W. , Morrison Lydia , Rupani Hitasha , Brown Thomas P. , Stores Rebecca , Chauhan Anoop J.
Published: November 2022

Supporting self-management is key in improving disease control, with technology increasingly utilised. We hypothesised the addition of telehealth support following assessment in an integrated respiratory clinic could reduce unscheduled healthcare visits in patients with asthma and COPD. Following treatment optimisation, exacerbation-prone participants or those with difficulty in self-management were offered telehealth support. This comprised automated twice-weekly telephone calls, with a specialist nurse triaging alerts. We performed a matched cohort study assessing additional benefits of the telehealth service, matching by: confirmed diagnosis, age, sex, FEV1 percent predicted, smoking status and ≥1 exacerbation in the last year. Thirty-four telehealth participants were matched to twenty-nine control participants. The telehealth cohort generated 165 alerts, with 29 participants raising at least one alert; 88 (53.5%) alerts received a call discussing self-management, of which 35 (21%) received definitive advice that may otherwise have required an unscheduled healthcare visit. There was a greater reduction in median exacerbation rate across both telehealth groups at 6 months post-intervention (1 to 0, p < 0.001) but not in control groups (0.5 to 0.0, p = 0.121). Similarly, there was a significant reduction in unscheduled GP visits across the telehealth groups (1.5 to 0.0, p < 0.001), but not the control groups (0.5 to 0.0, p = 0.115). These reductions led to cost-savings across all groups, but greater in the telehealth cohorts. The addition of telehealth support to exacerbation-prone patients with asthma or COPD, following comprehensive assessment and treatment optimisation, proved beneficial in reducing exacerbation frequency and unscheduled healthcare visits and thus leads to significant cost-savings for the NHS.

Clinical Trial Registration: ClinicalTrials.gov: NCT03096509
Sensory and metabolite migration from tilapia skin to soup during the boiling process: fast and then slow
Authors: Chen Jiahui , Nie Yinghua , Xu Jiamin , Huang Shudan , Sheng Jie , Wang Xichang , Zhong Jian
Published: November 2022

This study mainly studied sensory and metabolite migration from the skin to the soup in the boiling process of tilapia skin using content analysis, electronic nose technique, electronic tongue technique, and metabolomics technique based on ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-time-of-flight-mass spectrometry. The content changes, flavor changes, taste changes, metabolite numbers and differential metabolite numbers for both tilapia skin and soup mainly occurred in the initial 30 min. Moreover, the initial 10 min was the key period for the metabolite changes in the boiling process. Further, the differential metabolites in these three periods (0–10, 10–30, and 30–60 min) were identified to show the metabolites migration process. Six (adenine, gingerol, terephthalic acid, vanillin, pentanenitrile, and 2-pyrrolidinonede) and seven (butyramide, lysope(0:0/20:4(5z,8z,11z,14z)), lysope(22:6(4z,7z,10z,13z,16z,19z)/0:0), linoleic acid, N-acetylneuraminic acid, L-threose, and benzoin) chemicals were screened out in the differential metabolites of tilapia skin and soup, respectively, with Variable Importance in the Projection of >1 and p value of <0.05. This work would be beneficial to understand the sensory and metabolite migration in the preparation process of fish soup and provided a metabolomic analysis route to analyze metabolites migration in food.
Simulated redistricting plans for the analysis and evaluation of redistricting in the United States
Authors: McCartan Cory , Kenny Christopher T. , Simko Tyler , Garcia George , Wang Kevin , Wu Melissa , Kuriwaki Shiro , Imai Kosuke
Published: November 2022

This article introduces the 50stateSimulations, a collection of simulated congressional districting plans and underlying code developed by the Algorithm-Assisted Redistricting Methodology (ALARM) Project. The 50stateSimulationsallow for the evaluation of enacted and other congressional redistricting plans in the United States. While the use of redistricting simulation algorithms has become standard in academic research and court cases, any simulation analysis requires non-trivial efforts to combine multiple data sets, identify state-specific redistricting criteria, implement complex simulation algorithms, and summarize and visualize simulation outputs. We have developed a complete workflow that facilitates this entire process of simulation-based redistricting analysis for the congressional districts of all 50 states. The resulting 50stateSimulationsinclude ensembles of simulated 2020 congressional redistricting plans and necessary replication data. We also provide the underlying code, which serves as a template for customized analyses. All data and code are free and publicly available. This article details the design, creation, and validation of the data.
Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease
Authors: Wang Shiyou , Ding Peiwen , Yuan Jingnan , Wang Haoyu , Zhang Xiuqing , Chen Dongsheng , Ma Dongli , Zhang Xingliang , Wang Fei
Published: November 2022

Understanding the phenotypic and functional diversity of cerebral cortical GABAergic neurons requires a comprehensive analysis of key transcriptional signatures and neuronal subtype identity. However, the diversity and conservation of GABAergic neurons across multiple mammals remain unclear. Here, we collected the single-nucleus RNA sequencing (snRNA-seq) datasets of cerebral cortex from human, macaque, mouse, and pig to identify the conserved neuronal cell types across species. After systematic analysis of the heterogeneity of GABAergic neurons, we defined four major conserved GABAergic neuron subclasses (Inc SST, Inc LAMP5, Inc PVALB, and Inc VIP) across species. We characterized the species-enriched subclasses of GABAergic neurons from four mammals, such as Inc Meis2 in mouse. Then, we depicted the genetic regulatory network (GRNs) of GABAergic neuron subclasses, which showed the conserved and species-specific GRNs for GABAergic neuron cell types. Finally, we investigated the GABAergic neuron subclass-specific expression modules of Alzheimer’s disease (AD)-related genes in GABAergic neuron cell types. Overall, our study reveals the conserved and divergent GABAergic neuron subclasses and GRNs across multiple species and unravels the gene expression modules of AD-risk genes in GABAergic neuron subclasses, facilitating the GABAergic neurons research and clinical treatment.
Characterizing the effect of demographics, cardiorespiratory factors, and inter-subject variation on maternal heart rate variability in pregnancy with statistical modeling: a retrospective observational analysis
Authors: Bester M. , Joshi R. , Linders A. , Mischi M. , van Laar J. O. E. H. , Vullings R.
Published: November 2022

Pregnancy complications are associated with insufficient adaptation of the maternal autonomic nervous system to the physiological demands of pregnancy. Consequently, assessing maternal heart rate variability (mHRV)—which reflects autonomic regulation—is a promising tool for detecting early deterioration in maternal health. However, before mHRV can be used to screen for complications, an understanding of the factors influencing mHRV during healthy pregnancy is needed. In this retrospective observational study, we develop regression models to unravel the effects of maternal demographics (age, body mass index (BMI), gestational age (GA), and parity), cardiorespiratory factors (heart rate and breathing rate), and inter-subject variation on mHRV. We develop these models using two datasets which are comprised of, respectively, single measurements in 290 healthy pregnant women and repeated measurements (median = 8) in 29 women with healthy pregnancies. Our most consequential finding is that between one-third and two-thirds of the variation in mHRV can be attributed to inter-subject variability. Additionally, median heart rate dominantly affects mHRV (p < 0.001), while BMI and parity have no effect. Moreover, we found that median breathing rate, age, and GA all impact mHRV (p < 0.05). These results suggest that personalized, long-term monitoring would be necessary for using mHRV for obstetric screening.
Optimised extreme gradient boosting model for short term electric load demand forecasting of regional grid system
Authors: Qinghe Zhao , Wen Xiang , Boyan Huang , Jong Wang , Junlong Fang
Published: November 2022

Load forecast provides effective and reliable guidance for power construction and grid operation. It is essential for the power utility to forecast the exact in-future coming energy demand. Advanced machine learning methods can support competently for load forecasting, and extreme gradient boosting is an algorithm with great research potential. But there is less research about the energy time series itself as only an internal variable, especially for feature engineering of time univariate. And the machine learning tuning is another issue to applicate boosting method in energy demand, which has more significant effects than improving the core of the model. We take the extreme gradient boosting algorithm as the original model and combine the Tree-structured Parzen Estimator method to design the TPE-XGBoost model for completing the high-performance single-lag power load forecasting task. We resample the power load data of the Île-de-France Region Grid provided by Réseau de Transport d’Électricité in the day, train and optimise the TPE-XGBoost model by samples from 2016 to 2018, and test and evaluate in samples of 2019. The optimal window width of the time series data is determined in this study through Discrete Fourier Transform and Pearson Correlation Coefficient Methods, and five additional date features are introduced to complete feature engineering. By 500 iterations, TPE optimisation ensures nine hyperparameters’ values of XGBoost and improves the models obviously. In the dataset of 2019, the TPE-XGBoost model we designed has an excellent performance of MAE = 166.020 and MAPE = 2.61%. Compared with the original model, the two metrics are respectively improved by 14.23 and 14.14%; compared with the other eight machine learning algorithms, the model performs with the best metrics as well.
Mental health in myasthenia gravis patients and its impact on caregiver burden
Authors: Marbin Derin , Piper Sophie K. , Lehnerer Sophie , Harms Ulrike , Meisel Andreas
Published: November 2022

Psychiatric comorbidities are relevant in patients with Myasthenia gravis (MG). Also, MG patients experience a reduced health-related quality of life (HRQoL). We aimed to quantify the impact of depression as well as self-perceived MG severity on HRQoL and caregivers' burden. In this cross-sectional study, we used a survey encompassing demographic, disease-related information, and standardized questionnaires to assess symptoms of depression, anxiety, HRQoL (MG Quality of Life scale; MG-QoL15), and caregiver burden (Burden Scale for Family Caregivers; BSFC). Data from 1399 participating patients (96%) and 1042 caregivers (65%) were eligible for further analysis. Symptoms of depression and anxiety disorder were indicated by 31% and 36% of patients. Self-reported MG severity (MG severity) and MG-QoL15 scores were strongly associated (estimated marginal means for severe versus mild MG severity = 18 95% CI [16; 21]; p ≤ 0.001). Adjusting for symptoms of depression decreased the estimated strength of this association (estimated marginal means for severe versus mild MG severity = 15 [13; 17]; p ≤ 0.001). Caregiver burden was associated to MG disease severity (estimated marginal means for severe vs. mild MG severity = 0.16 [0.13; 0,19); p ≤ 0.001) and also negatively influenced by symptoms of depression (estimated marginal means = 0.12 [0.09; 0.15]). Symptoms of depression and anxiety disorder in MG are frequent. Beyond MG severity, symptoms of depression have negative effects on HRQoL as well as on caregivers’ burden. Diagnosis and treatment of psychiatric comorbidities should be considered an important element in MG care. Screening tools for mental health conditions should be implemented at least in specialized MG centers.
The burden of rheumatoid arthritis in the Middle East and North Africa region, 1990–2019
Authors: Mousavi Seyed Ehsan , Nejadghaderi Seyed Aria , Khabbazi Alireza , Alizadeh Mahasti , Sullman Mark J. M. , Kaufman Jay S. , Collins Gary S. , Safiri Saeid
Published: November 2022

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. The present study reported the burden of RA in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex, and socio-demographic index (SDI). Publicly available data from the Global Burden of Disease (GBD) 2019 study was used to report the modelled point prevalence, annual incidence, and disability-adjusted life-years (DALYs) of RA, as counts and age-standardised rates with their corresponding 95% uncertainty intervals (UIs). In 2019, RA had an age-standardised point prevalence of 120.6 per 100,000 population (107.0–135.7) and an annual incidence rate of 5.9 (5.2–6.6) in MENA, which have increased 28.3% and 25.2%, respectively, since 1990. In 2019, the number of DALYs due to RA in the region was 103.6 thousand (74.2–136.7), with an age-standardised rate of 19.0 (13.9–24.9) DALYs per 100,000 population, which has increased by 18.6% since 1990 (6.7–28.2). The highest point prevalence was found in females aged 50–54, and in males aged 45–49. The highest number of DALYs was observed in the 50–54 age group. The MENA DALY rate was lower than the global rate (19.0 vs. 39.6 per 100,000), but the rate was higher in all age groups in 2019, when compared with 1990. In addition, from 1990 to 2019 an increased burden from RA was associated with an increase in SDI. In line with global trends, the burden of RA in the MENA region showed a steady increase from 1990 to 2019. This highlights the increasing need for updating the available health data to design more accurate guidelines to enable the early detection and treatment of RA in the MENA countries.
Utilizing birch leaf extract in pickling liquid as a sustainable source of corrosion inhibitor for pipeline steel
Authors: Mohsen Q. , Deyab M. A.
Published: November 2022

This study set out to determine the effectiveness of birch leaves extract (BLE) as a corrosion inhibitor against X52 pipeline steel in the pickling solution. Chemical and electrochemical techniques, as well as scanning electron microscope (SEM), Fourier-transform infrared (FT-IR), and adsorption isotherms were used in the research. Various triterpenoids, including betulin, betulinic acid, oleanolic acid, sitosterol, and kaempferol, are unquestionably involved in the corrosion inhibition mechanism, according to the high-performance-liquid-chromatography (HPLC) analysis. The 95% efficiency of the produced BLE extract (at optimum concentration 400 mg L−1) significantly reduced the corrosion rate of X52 pipeline steel in the pickling solution. The adsorption of BLE extract molecules on the X52-steel surface was demonstrated by SEM and FT-IR analysis. The adsorption activity follows the Langmuir adsorption theory.