bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of state anxiety on event construction and elaboration during episodic future thinking
Authors: Zhou Bin , Li Yajing , Hu Zhiguo
Published: January 2024

Episodic future thinking (EFT) is a fundamental cognitive capacity that enables individuals to mentally simulate and prepare for possible future events. This capacity involves two distinct phases: construction and elaboration. How state anxiety affects the event construction and elaboration in EFT remains unclear. Therefore, the present study aims to address this issue by adopting a verbal cueing paradigm, taking into account familiarity and emotional valence. To induce state anxiety, our study employed a mental arithmetic task coupled with immediate feedback and the investigator’s supervision. Cue words were associated with either high-familiar or low-familiar future events, as well as different emotional valences (positive, neutral or negative). In the cueing task, each participant was required to construct a specific episodic event and then elaborate on it based on the provided cues. Subsequently, subjective ratings of the imagined event were collected after each imagination. The results revealed that individuals experiencing state anxiety took longer to elaborate events compared to the control group. Notably, there were asymmetric results in high- and low-familiarity conditions when considering cue words with different emotional valence. Overall, this study suggests that the influence of state anxiety on EFT is constrained to the elaboration phase and does not extend to the construction phase.
Identifying and Constraining Marsh-Type Transitions in Response to Increasing Erosion over the Past Century
Authors: Ellis Alisha M. , Smith Christopher G. , Smith Kathryn E. L. , Jacobs Jessica A.
Published: January 2024

Marsh environments, characterized by their flora and fauna, change laterally in response to shoreline erosion, water levels and inundation, and anthropogenic activities. The Grand Bay coastal system (USA) has undergone multiple large-scale geomorphic and hydrologic changes resulting in altered sediment supply, depositional patterns, and degraded barrier islands, leaving wetland salt marshes vulnerable to increased wave activity. Two shore-perpendicular transect sites, one along a low-activity shoreline and the other in a high activity area of the same bay-marsh complex, were sampled to investigate how the marshes within 50 m of the modern shoreline have responded to different levels of increased wave activity over the past century. Surface sediments graded finer and more organic with increased distance from the shoreline while cores generally exhibited a coarsening upwards grain-size trend; all cores contained multiple large sedimentological shifts. 210Pb-based mass accumulation rates over the last two decades were greater than the long-term (centurial) average at each site with the fastest accumulation rates of 7.81 ± 1.58 and 7.79 ± 1.63 kg/m2/year at the sites nearest the shoreline. A shoreline change analysis of three time-slices (1848–2017, 1957–2017, 2016–2017) shows increased erosion at both sites since 1848 with modern rates of −0.95 and −0.88 m/year. Downcore sedimentology, mass accumulation rates, and shoreline change rates paired with foraminiferal biofacies and identification of local estuarine indicator species, Paratrochammina simplissima, aided in identifying paleo marsh types, their relative proximity to the shoreline, and sediment provenance. The high-energy marsh site transitioned from middle marsh to low marsh in the 1960s, and the low-energy marsh site transitioned later, at the end of the twentieth and early twenty-first century, due to its more protected location. Marsh type transition corresponds chronologically with the coarsening upwards grain-size trend observed and the degradation of Grand Batture Island; since its submergence, signatures of multiple storm event have been preserved downcore.
Practical Approaches Towards Transparent and Stable Bilateral Teleoperation Under Time-Varying Network Delay
Authors: Wang Chunpeng , Luo Rui , Whitney John Peter , Padir Taskin
Published: January 2024

In real-life teleoperation scenarios, the presence of time-varying network delays, particularly in wireless networks, poses significant challenges in maintaining stability in a bilateral teleoperation system. Various approaches have been proposed in the past to address stability concerns; however, these often come at the expense of system transparency. Nevertheless, increasing transparency is crucial in a teleoperation system to enable precise and safe operations, as well as to provide real-time decision-making capabilities for the operator. This paper presents our comprehensive approaches to maximize teleoperation transparency by minimizing system impedance, enhance the wave variable method to handle time-varying network delays, and alleviate non-smooth effects caused by network jitters in bilateral teleoperation. The proposed methodologies take into account the real-world challenges and considerations to ensure the practical applicability and effectiveness of the teleoperation system. Throughout these implementations, passivity analysis is employed to ensure system stability, guaranteeing a reliable and safe teleoperation experience. The proposed approaches were successfully validated in Team Northeastern’s Avatar telepresence system, which achieved the 3rd place in ANA Avatar XPRIZE challenge.
Identifying locals vs non-locals using 87Sr/86Sr isotope analysis: a multimethod approach in the homogeneous environments of the Arabian Gulf
Authors: Littleton Judith , Smith Caitlin Bonham
Published: January 2024

Archaeological strontium isotope investigations of the movement of peoples and animals rely on different methods to characterize a “local” strontium range. In geologically homogenous regions or regions where the creation of isoscapes using proxies is hampered, statistical methods are useful for identifying individuals likely to be local or non-local. We demonstrate how a multi-method approach can be used to evaluate local strontium isotope ranges in Bahrain, an archipelago in the Arabian Gulf. Combining the enamel samples analyzed for this paper (62 human and domesticate herbivore individuals) with previously published faunal 87Sr/86Sr values from Bahrain (20 domesticated herbivores), we found that different statistical methods identified different numbers of individuals as local and were predicated on different assumptions about the distribution of the data. Compared to the standard approach using 2σ of the sample mean, the statistical approaches used in this manuscript identified more potential non-local or securely non-local individuals. Between 18.5 and 44.4% of the non-human animals were identified as non-local, indicating the trade of animals and why using faunal (herbivore) samples alone to characterize a local range is problematic in trading centers. The identification of between 13.7 and 32.9% of the humans as non-local is consistent with other studies of movement in archaeological populations of the Gulf and makes sense given the prominent role of trade in Bahrain from the Early Dilmun to Islamic periods. We argue that statistical approaches to identifying probable non-locals can be used where detailed isoscape data are hard to obtain, but that such results need to be evaluated within the specific archaeological context.
Correlation of DNA methylation of DNMT3A and TET2 with oral squamous cell carcinoma
Authors: Li Xueming , Li Zaikun , Gao Qingxi , Peng Yanan , Yu Yang , Hu Tenglong , Wang Wei
Published: January 2024

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Abnormal epigenetic modifications, including DNA methylation, are hallmarks of cancer and implicated in the development of various tumors. DNA methylation is catalyzed by the DNA methyltransferase and ten-eleven translocation dioxygenase families, with DNMT3A and TET2 being the most widely studied members, respectively. The correlation of methylation β values and clinical features was conducted in patients with OSCC in The Cancer Genome Atlas database. DNA methylation and protein expression levels of DNMT3A and TET2 in tissues were analyzed with methylation-specific polymerase chain reaction (MSP) and western blotting. To evaluate the effects of DNMT3A and TET2 on the biological characteristics of OSCC, cell proliferation was assessed with 5-ethynyl-2'-deoxyuridine, and cell migration capacity was quantified with wound healing and transwell assays. A survival analysis was performed with the Kaplan–Meier approach. The correlation between different methylation β values and clinical features was revealed. MSP revealed varying methylation degrees of DNMT3A and TET2 in OSCC tissues. Furthermore, western blotting showed that the protein expression levels were significantly different in cancer and surrounding healthy tissue samples. In vitro experiments demonstrated that DNMT3A knockdown and TET2 overexpression could inhibit the proliferation and migration of OSCC. Survival analysis revealed that patients with high DNMT3A methylation levels showed higher survival rates.
On Kleinian mock modular forms
Authors: Alfes Claudia , Mertens Michael H.
Published: January 2024

We give an explicit and computationally efficient construction of harmonic weak Maass forms which map to weight 2 newforms under the $$\xi $$
ξ
-operator. Our work uses a new non-analytic completion of the Kleinian $$\zeta $$
ζ
-function from the theory of Abelian functions.
Randomly Censored Kumaraswamy Distribution
Authors: Chaturvedi Aditi
Published: January 2024

In this paper, inferential procedures based on classical and Bayesian framework for the Kumaraswamy distribution under random censoring model are studied. We first propose estimators for the distribution parameters, reliability function, failure rate function, and Mean time to system failure based on the maximum likelihood estimation method. Then, we calculate asymptotic confidence intervals for the parameters based on the observed Fisher’s information matrix. Also, for the parameters and reliability characteristics, Bayesian estimates are derived using the importance sampling and Gibbs sampling procedures. Highest posterior density credible intervals for the parameters are constructed using Markov Chain Monte Carlo method. Expected time on test of experiment with random censoring is also calculated. A simulation study is conducted to compare the efficiency of the derived estimates. Finally, the analysis of a real data set is presented for the illustration purpose.
Introducción a los modelos de ecuaciones estructurales
Authors: Manzano Patiño Abigail Patricia
Published: January 2024

Los modelos de ecuaciones estructurales (SEM) son una herramienta estadística multivariada que permite estudiar la relación que hay entre variables latentes y observadas. Este artículo tiene el propósito de introducir, de forma sencilla y no muy teórica, a los SEM. Se describen los tipos de modelos, su representación gráfica, su identificabilidad, las técnicas de estimación de parámetros y la valoración de su ajuste. Se incluye además un ejemplo para ilustrar esta metodología estadística.
Sexualisierte Gewalt und Trauma
Authors: Tschan Werner
Published: January 2024

Menschen reagieren auf Vorfälle sexualisierter Gewalt oft mit Rat- und Hilflosigkeit. In Fällen der Anklage stellen Opferaussagen häufig das einzige Beweismittel dar, wodurch eine gerechte Strafverfolgung erschwert und weitere Belastungen für die Betroffenen entstehen können. Noch immer prägen Schweigen, Bagatellisierung und mangelnde Verantwortungsübernahme den Umgang mit sexualisierter Gewalt. Bei den oft als unvorhersehbare Einzelfälle wahrgenommenen Taten handelt es sich tatsächlich um systemische Delikte, die besonders in Institutionen und Organisationen begünstigte Bedingungen vorfinden, wie das Praxishandbuch schnörkellos und eindrücklich verdeutlicht.
Anhand zahlreicher Beispiele schafft der erfahrene Psychiater und Psychotherapeut Werner Tschan einen facettenreichen Überblick der Problematik. Das Praxishandbuch richtet sich an Pflege-, Gesundheits-, Sozial-, Trainings-, und Erziehungsberufe. Es bietet ihnen umfangreiche Informationen, die sie im Umgang mit sexualisierter Gewalt in ihrer Tätigkeit unterstützen. Es betont, wie bedeutend fundiertes Wissen über sexualisierte Gewalt ist, um Betroffene zu stärken und zu schützen. Der Autor
• beschreibt psychische und physische Folgen für Betroffene
• zerstreut stereotype Vorstellungen über Täter und Opfer
• erläutert Schutz- und Behandlungsmöglichkeiten
• ermutigt zu gegenseitigem Austausch von Wissen und Erfahrung
• ruft zu einer Kultur des Hinschauens auf.

Aus dem Inhalt

• Traumafolgestörungen nach Gewalterfahrungen
• Behandlung und Stabilisierungstechniken
• Bedeutung für das Gesundheitswesen, die Sozial- und Erziehungswissenschaften sowie den Sport- und Freizeitbereich
• Kompetenzen der Fachkräfte
• Berufsrisiko: sekundäre Traumatisierung
.
Bulimia nervosa
Authors: Reich Günter , Kronmüller Klaus-Thomas
Published: January 2024

Bulimia nervosa ist eine schwer zu behandelnde Erkrankung, insbesondere bei Jugendlichen und jungen Erwachsenen. Der vorliegende Band stellt ein manualisiertes psychodynamisches Vorgehen zur Behandlung dieses Störungsbildes bei dieser Patientengruppe vor. Einleitend werden das Krankheitsbild der Bulimia nervosa, Epidemiologie, Komorbidität, körperliche Folgen sowie Persönlichkeits- und Entstehungsfaktoren dargestellt. Nach einem Überblick über gängige psychotherapeutische Entstehungsmodelle der Bulimie wird das diesem Manual zugrunde liegende psychodynamische Krankheitsverständnis ausführlich vorgestellt. Die detaillierte Darstellung der einzelnen Behandlungsschritte veranschaulicht das konkrete störungsorientierte Vorgehen auf der Struktur-, Konflikt- und Beziehungsebene. Dabei wird die Bearbeitung der jeweiligen Schwerpunkte anhand von Praxisbeispielen illustriert und Interventionsmöglichkeiten werden aufgezeigt. Eine ausführliche Falldarstellung skizziert einen exemplarischen Behandlungsverlauf. Das beschriebene Vorgehen ist für eine tiefenpsychologisch fundierte Psychotherapie mit ca. 60 Stunden ausgelegt, kann aber auch in kürzeren oder längeren Therapien angewendet werden. Die Wirksamkeit wurde in einer randomisiert-kontrollierten Vergleichsstudie empirisch belegt. Hilfreiche Arbeitsmaterialien ergänzen den Band und können nach erfolgter Registrierung von der Hogrefe Website heruntergeladen werden.
Attention-Deficit/Hyperactivity Disorder in Adults
Authors: Daly Brian P. , Silverstein Steven M. , Brown Ronald T.
Published: January 2024

The new edition of this popular text incorporates the latest research on assessment and treatment practices for adults with attention-deficit/hyperactivity disorder (ADHD). The presentation of symptoms may differ considerably in adulthood and without appropriate symptom management, ADHD can significantly interfere in many aspects of life. When properly identified and diagnosed, however, outcomes in adults with ADHD who receive appropriate treatment are encouraging.
This volume is both a compact “how to” reference for use by professionals in their daily work and an ideal educational reference for students, informing the reader of all aspects involved in the assessment and management of ADHD in adults. This edition also explores how psychosocial adversity factors impact the development and functional impairments associated with ADHD and highlights strategies used in the multimodal treatment of ADHD in adults. Best practice approaches are offered for common problems encountered when carrying out treatments.
A companion volume Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents is also available.
Enhancing Severe Weather Prediction With Microwave All‐Sky Radiance Assimilation: The 10 August 2020 Midwest Derecho
Authors: Zhang Yunji , Chen Xingchao , Stensrud David J. , Clothiaux Eugene E.
Published: January 2024

In this study, we assimilated microwave (MW) all‐sky radiances from low‐Earth‐orbiting satellites and examined their impact on the analyses and forecasts of weather hazards associated with the 10 August 2020 Midwest derecho. Compared with the baseline that assimilated conventional surface and upper‐air observations and infrared (IR) all‐sky radiances from geostationary satellites, the addition of MW all‐sky radiances improved the analyzed and forecasted convection‐stratiform structures of the derecho. Results show that MW all‐sky radiances provided additional information, compared with IR radiances, on hydrometeors within the storm, leading to improved forecasts out to 2 hr with quantitatively more accurate surface gusts. This is the first study to assimilate MW all‐sky radiances for a severe weather event using a convection‐permitting numerical weather prediction model (our model resembles NOAA's High‐Resolution Rapid Refresh), and the results suggest promising avenues for improving severe weather forecasts worldwide in the future.
The Land Wet‐Bulb Temperature Increases Faster Than the Sea Surface Temperature
Authors: Chu Haoran , Cao Chang , Wang Wei , Xiao Wei , Zhang Keer , Zhang Mi , Lee Xuhui
Published: January 2024

Vapor buildup in the atmosphere and faster warming over land than over ocean are ubiquitous features of climate change. This combination is a threat to society because the associated heat stress may exceed the limit for human survival. The heat stress due to high humidity and high temperature is quantified with the wet‐bulb temperature (Tw). A common view is that the land Tw should change at the same rate as the ocean surface temperature (Ts). Using climate model data and atmospheric observations, we show that the land Tw increases 17% faster than Ts. This amplification arises from stronger downward longwave radiation (L↓) at the surface in a warmer climate, which causes moist static energy to accumulate in the atmospheric boundary layer. We also find that L↓ is a better predictor of Tw than Ts at interannual to decadal time scales. These relationships are robust across climates and across model simulations.
Bayesian Inversion, Uncertainty Analysis and Interrogation Using Boosting Variational Inference
Authors: Zhao Xuebin , Curtis Andrew
Published: January 2024

Geoscientists use observed data to estimate properties of the Earth's interior. This often requires non‐linear inverse problems to be solved and uncertainties to be estimated. Bayesian inference solves inverse problems under a probabilistic framework, in which uncertainty is represented by a so‐called posterior probability distribution. Recently, variational inference has emerged as an efficient method to estimate Bayesian solutions. By seeking the closest approximation to the posterior distribution within any chosen family of distributions, variational inference yields a fully probabilistic solution. It is important to define expressive variational families so that the posterior distribution can be represented accurately. We introduce boosting variational inference (BVI) as a computationally efficient means to construct a flexible approximating family comprising all possible finite mixtures of simpler component distributions. We use Gaussian mixture components due to their fully parametric nature and the ease with which they can be optimized. We apply BVI to seismic travel time tomography and full waveform inversion, comparing its performance with other methods of solution. The results demonstrate that BVI achieves reasonable efficiency and accuracy while enabling the construction of a fully analytic expression for the posterior distribution. Samples that represent major components of uncertainty in the solution can be obtained analytically from each mixture component. We demonstrate that these samples can be used to solve an interrogation problem: to assess the size of a subsurface target structure. To the best of our knowledge, this is the first method in geophysics that provides both analytic and reasonably accurate probabilistic solutions to fully non‐linear, high‐dimensional Bayesian full waveform inversion problems.
Measurements and Modeling of the Interhemispheric Differences of Atmospheric Chlorinated Very Short‐Lived Substances
Authors: Roozitalab Behrooz , Emmons Louisa K. , Hornbrook Rebecca S. , Kinnison Douglas E. , Fernandez Rafael P. , Li Qinyi , Saiz‐Lopez Alfonso , Hossaini Ryan , Cuevas Carlos A. , Hills Alan J. , Montzka Stephen A. , Blake Donald R. , Brune William H. , Veres Patrick R. , Apel Eric C.
Published: January 2024

Chlorinated very short‐lived substances (Cl‐VSLS) are ubiquitous in the troposphere and can contribute to the stratospheric chlorine budget. In this study, we present measurements of atmospheric dichloromethane (CH2Cl2), tetrachloroethene (C2Cl4), chloroform (CHCl3), and 1,2‐dichloroethane (1,2‐DCA) obtained during the National Aeronautics and Space Administration (NASA) Atmospheric Tomography (ATom) global‐scale aircraft mission (2016–2018), and use the Community Earth System Model (CESM) updated with recent chlorine chemistry to further investigate their global tropospheric distribution. The measured global average Cl‐VSLS mixing ratios, from 0.2 to 13 km altitude, were 46.6 ppt (CH2Cl2), 9.6 ppt (CHCl3), 7.8 ppt (1,2‐DCA), and 0.84 ppt (C2Cl4) measured by the NSF NCAR Trace Organic Analyzer (TOGA) during ATom. Both measurements and model show distinct hemispheric gradients with the mean measured Northern to Southern Hemisphere (NH/SH) ratio of 2 or greater for all four Cl‐VSLS. In addition, the TOGA profiles over the NH mid‐latitudes showed general enhancements in the Pacific basin compared to the Atlantic basin, with up to ∼18 ppt difference for CH2Cl2 in the mid troposphere. We tagged regional source emissions of CH2Cl2 and C2Cl4 in the model and found that Asian emissions dominate the global distributions of these species both at the surface (950 hPa) and at high altitudes (150 hPa). Overall, our results confirm relatively high mixing ratios of Cl‐VSLS in the UTLS region and show that the CESM model does a reasonable job of simulating their global abundance but we also note the uncertainties with Cl‐VSLS emissions and active chlorine sources in the model. These findings will be used to validate future emission inventories and to investigate the fast convective transport of Cl‐VSLS to the UTLS region and their impact on stratospheric ozone.
Comparison of Short‐Term Cloud Feedbacks at Top of the Atmosphere and the Surface in Observations and AMIP6 Models
Authors: Wang Xiaocong , Miao Hao , Feng Juan , Liu Yimin
Published: January 2024

We compared short‐term cloud feedback, defined at the top of the atmosphere (TOA), the atmospheric column (ATM), and the surface (SFC), between observations and models participating in Atmospheric Model Intercomparison Project Phase 6 (AMIP6) for the period 2000–2014. The globally averaged net cloud feedbacks observed at TOA, ATM, and SFC are −0.06 ± 0.63, −0.17 ± 0.70, and 0.11 ± 0.81 W m−2 K−1, respectively. While most models produced TOA cloud feedbacks that agreed with the observations within uncertainty ranges, the intermodel spread at SFC and within ATM was relatively larger. This demonstrates that models are diverse in how their TOA feedback is distributed between ATM and SFC. Because short‐term cloud feedback is mainly driven by El Niño–Southern Oscillation (ENSO), the global‐mean cloud feedback was further decomposed into components from the ENSO and non‐ENSO regions. Results show that cloud feedback in these two regions tends to be inversely related. Compared to observations, almost all models overestimated the longwave cloud feedback in the ENSO region due to the overestimation of cloud amount changes for high‐topped clouds. For these models, it is the offset between deviations in ENSO and non‐ENSO regions that leads to the overall agreement of global mean with observations. Sensitivity tests show that the main conclusions still hold when alternative kernels are used in estimating cloud feedback.
Eccentricity Forcing of the Hydrological Cycle in East Asia During the Early Eocene Climatic Optimum (EECO)
Authors: Zhang Ruiyao , Huang Chunju , Kemp David B. , Zhang Ze , Wang Zhixiang , Zhang Xiaoyue , Zhao Deai , Jin Simin , Zhang Rui
Published: January 2024

The Early Eocene Climatic Optimum (EECO) may be a potentially useful analog for future global warming under high CO2 concentrations. However, a paucity of orbital‐scale terrestrial records limits our understanding of how the hydrological cycle responded during this protracted (∼4 Myr) interval of global warmth. In this study, we combine zircon U‐Pb dating and cyclostratigraphy to establish a high‐resolution astronomical timescale spanning the EECO (∼52.9 Ma to ∼49.9 Ma) through a >1 km fluviolacustrine succession from the Gonjo Basin, Southeast Tibet. Our results suggest that hydroclimate variability in the region during this interval was strongly controlled by eccentricity forcing (∼405 Kyr, ∼135–100 Kyr, and possibly ∼200 Kyr cycles). The dominance of eccentricity forcing in our record is consistent with coeval marine records, and indicates that modulation of low‐latitude summer insolation through nonlinear interactions with the global carbon cycle likely controlled hydroclimate and paleolake level in the Gonjo basin during the EECO. Our study offers new perspectives for the forcing mechanisms of terrestrial hydroclimate changes of East Asia in response to subtle changes in insolation during the EECO.
A Transfer Learning Method to Generate Synthetic Synoptic Magnetograms
Authors: Li Xiaoyue , Senthamizh Pavai Valliappan , Shukhobodskaia Daria , Butala Mark D. , Rodriguez Luciano , Magdalenic Jasmina , Delouille Véronique
Published: January 2024

Current magnetohydrodynamics (MHD) models largely rely on synoptic magnetograms, such as the ones produced by the Global Oscillation Network Group (GONG). Magnetograms are currently available mostly from the front side of the Sun, which significantly reduces the accuracy of MHD modeling. Extreme Ultraviolet (EUV) images can instead be obtained from other vantage points. To investigate the potential, we explore the possibility of using EUV information from the Atmospheric Imaging Assembly (AIA) to directly generate the input for the state‐of‐the‐art 3D MHD model European Heliospheric FORecasting Information Asset (EUHFORIA). Toward this goal, we develop a method called Transfer‐Solar‐GAN which combines a conditional generative adversarial network with a transfer learning approach to overcome training data set limitations. The source domain data set is constructed from multiple pairs of the central portion of co‐registered AIA and Helioseismic and Magnetic Imager (HMI) line of sight (LOS) full‐disk images, while the target domain is constructed from pairs of portions of AIA and GONG sine‐latitude synoptic maps that we call segments. We evaluate Transfer‐Solar‐GAN by comparing modeled and measured solar wind velocity and magnetic field density parameters at the L1 Lagrange point and along the Parker Solar Probe (PSP) trajectory which were determined with EUHFORIA using both empirical GONG and artificial‐intelligence (AI)‐synthetic synoptic magnetograms as inputs. Our results demonstrate that the Transfer‐Solar‐GAN model can provide the necessary information to run solar physics models by EUV information. Our proposed model is trained with only 528 paired image segments and enforces a reliable data division strategy.
RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification
Authors: Wang Xiaochen , Ling Rongsong , Peng Yurong , Qiu Weiqiong , Chen Demeng
Published: January 2024

Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac4C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac4C modification sites, thereby providing a potent sequencing tool for tRNA-ac4C research. Our findings expand the repertoire of tRNA ac4C modifications and identify a role of tRNA ac4C in the regulation of mRNA translation in HNSCC.
Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study
Authors: Tose Keima , Takamura Tsunehiko , Isobe Masanori , Hirano Yoshiyuki , Sato Yasuhiro , Kodama Naoki , Yoshihara Kazufumi , Maikusa Norihide , Moriguchi Yoshiya , Noda Tomomi , Mishima Ryo , Kawabata Michiko , Noma Shun’ichi , Takakura Shu , Gondo Motoharu , Kakeda Shingo , Takahashi Masatoshi , Ide Satoru , Adachi Hiroaki , Hamatani Sayo , Kamashita Rio , Sudo Yusuke , Matsumoto Koji , Nakazato Michiko , Numata Noriko , Hamamoto Yumi , Shoji Tomotaka , Muratsubaki Tomohiko , Sugiura Motoaki , Murai Toshiya , Fukudo Shin , Sekiguchi Atsushi
Published: January 2024

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303.
Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss
Authors: Xie Xudong , Cheng Peng , Hu Liangcong , Zhou Wu , Zhang Detai , Knoedler Samuel , Liu Guodong , Xiong Yuan , Xue Hang , Hu Yiqiang , Kern Barbara , Obed Doha , Panayi Adriana C. , Chen Lang , Yan Chenchen , Lin Ze , Dai Guandong , Mi Bobin , Zhang Yingze , Liu Guohui
Published: January 2024

The clinical role and underlying mechanisms of valproic acid (VPA) on bone homeostasis remain controversial. Herein, we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density (BMD) in both patients and mice. This effect was attributed to VPA-induced elevation in osteoclast formation and activity. Through RNA-sequencing, we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro, and further, a marked upregulation of mature miR-6359 (miR-6359) in vivo was demonstrated using quantitative real-time PCR (qRT-PCR) and miR-6359 fluorescent in situ hybridization (miR-6359-FISH). Specifically, the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils, T lymphocytes, monocytes and bone marrow-derived mesenchymal stem cells (BMSCs) following VPA stimulation, which influenced osteoclast differentiation and bone-resorptive activity. Additionally, VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species (ROS) production by silencing the SIRT3 protein expression, followed by activation of the MAPK signaling pathway, which enhanced osteoclast formation and activity, thereby accelerating bone loss. Currently, there are no medications that can effectively treat VPA-induced bone loss. Therefore, we constructed engineered small extracellular vesicles (E-sEVs) targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif (CGGGAGC) in the 3’-end of the anti-miR-6359 sequence. We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss, but not on ovariectomy (OVX) and glucocorticoid-induced osteoporotic models, deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.
Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities
Authors: Arzua Thiago , Yan Yasheng , Liu Xiaojie , Dash Ranjan K. , Liu Qing-Song , Bai Xiaowen
Published: January 2024

Alcohol consumption during pregnancy can significantly impact the brain development of the fetus, leading to long-term cognitive and behavioral problems. However, the underlying mechanisms are not well understood. In this study, we investigated the acute and chronic effects of binge-like alcohol exposure during the third trimester equivalent in postnatal day 7 (P7) mice on brain cell viability, synapse activity, cognitive and behavioral performance, and gene expression profiles at P60. Our results showed that alcohol exposure caused neuroapoptosis in P7 mouse brains immediately after a 6-hour exposure. In addition, P60 mice exposed to alcohol during P7 displayed impaired learning and memory abilities and anxiety-like behaviors. Electrophysiological analysis of hippocampal neurons revealed an excitatory/inhibitory imbalance in alcohol-treated P60 mice compared to controls, with decreased excitation and increased inhibition. Furthermore, our bioinformatic analysis of 376 dysregulated genes in P60 mouse brains following alcohol exposure identified 50 synapse-related and 23 mitochondria-related genes. These genes encoded proteins located in various parts of the synapse, synaptic cleft, extra-synaptic space, synaptic membranes, or mitochondria, and were associated with different biological processes and functions, including the regulation of synaptic transmission, transport, synaptic vesicle cycle, metabolism, synaptogenesis, mitochondrial activity, cognition, and behavior. The dysregulated synapse and mitochondrial genes were predicted to interact in overlapping networks. Our findings suggest that altered synaptic activities and signaling networks may contribute to alcohol-induced long-term cognitive and behavioral impairments in mice, providing new insights into the underlying synaptic and mitochondrial molecular mechanisms and potential neuroprotective strategies.
Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control
Authors: Wible Daric J. , Parikh Zalak , Cho Eun Jeong , Chen Miao-Der , Jeter Collene R. , Mukhopadhyay Somshuvra , Dalby Kevin N. , Varadarajan Shankar , Bratton Shawn B.
Published: January 2024

p38 mitogen-activated protein kinases (MAPKs) participate in autophagic signaling; and previous reports suggest that pyridinyl imidazole p38 MAPK inhibitors, including SB203580 and SB202190, induce cell death in some cancer cell-types through unrestrained autophagy. Subsequent studies, however, have suggested that the associated cytoplasmic vacuolation resulted from off-target inhibition of an unidentified enzyme. Herein, we report that SB203580-induced vacuolation is rapid, reversible, and relies on the class III phosphatidylinositol 3-kinase (PIK3C3) complex and the production of phosphatidylinositol 3-phosphate [PI(3)P] but not on autophagy per se. Rather, vacuolation resulted from the accumulation of Rab7 on late endosome and lysosome (LEL) membranes, combined with an osmotic imbalance that triggered severe swelling in these organelles. Inhibition of PIKfyve, the lipid kinase that converts PI(3)P to PI(3,5)P2 on LEL membranes, produced a similar phenotype in cells; therefore, we performed in vitro kinase assays and discovered that both SB203580 and SB202190 directly inhibited recombinant PIKfyve. Cancer cells treated with either drug likewise displayed significant reductions in the endogenous levels of PI(3,5)P2. Despite these results, SB203580-induced vacuolation was not entirely due to off-target inhibition of PIKfyve, as a drug-resistant p38α mutant suppressed vacuolation; and combined genetic deletion of both p38α and p38β dramatically sensitized cells to established PIKfyve inhibitors, including YM201636 and apilimod. The rate of vacuole dissolution (i.e., LEL fission), following the removal of apilimod, was also significantly reduced in cells treated with BIRB-796, a structurally unrelated p38 MAPK inhibitor. Thus, our studies indicate that pyridinyl imidazole p38 MAPK inhibitors induce cytoplasmic vacuolation through the combined inhibition of both PIKfyve and p38 MAPKs, and more generally, that p38 MAPKs act epistatically to PIKfyve, most likely to promote LEL fission.
Self-encapsulated ionic fibers based on stress-induced adaptive phase transition for non-contact depth-of-field camouflage sensing
Authors: Liu Ying , Wang Chan , Liu Zhuo , Qu Xuecheng , Gai Yansong , Xue Jiangtao , Chao Shengyu , Huang Jing , Wu Yuxiang , Li Yusheng , Luo Dan , Li Zhou
Published: January 2024

Ionically conductive fibers have promising applications; however, complex processing techniques and poor stability limit their practicality. To overcome these challenges, we proposed a stress-induced adaptive phase transition strategy to conveniently fabricate self-encapsulated hydrogel-based ionically conductive fibers (se-HICFs). se-HICFs can be produced simply by directly stretching ionic hydrogels with ultra-stretchable networks (us-IHs) or by dip-drawing from molten us-IHs. During this process, stress facilitated the directional migration and evaporation of water molecules in us-IHs, causing a phase transition in the surface layer of ionic fibers to achieve self-encapsulation. The resulting sheath-core structure of se-HICFs enhanced mechanical strength and stability while endowing se-HICFs with powerful non-contact electrostatic induction capabilities. Mimicking nature, se-HICFs were woven into spider web structures and camouflaged in wild environments to achieve high spatiotemporal resolution 3D depth-of-field sensing for different moving media. This work opens up a convenient route to fabricate stable functionalized ionic fibers.
A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer
Authors: Eglenen-Polat Buse , Kowash Ryan R. , Huang Hai-Cheng , Siteni Silvia , Zhu Mingrui , Chen Kenian , Bender Matthew E. , Mender Ilgen , Stastny Victor , Drapkin Benjamin J. , Raj Prithvi , Minna John D. , Xu Lin , Shay Jerry W. , Akbay Esra A.
Published: January 2024

There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation. Here we utilize a nucleoside analog, 6-Thio-2’-deoxyguanosine (6TdG) currently in phase II clinical trials, that is preferentially incorporated by telomerase into telomeres leading to telomere dysfunction. Using preclinical mouse and human derived models we find low intermittent doses of 6TdG inhibit tumor growth and reduce metastatic burden. Anti-tumor efficacy correlates with a reduction in a subpopulation of cancer initiating like cells (CICs) identified by their expression of L1CAM/CD133 and highest telomerase activity. 6TdG treatment also leads to activation of innate and adaptive anti-tumor responses. Mechanistically, 6TdG depletes CICs and induces type-I interferon signaling leading to tumor immune visibility by activating tumor cell STING signaling. We also observe increased sensitivity to irradiation after 6TdG treatment in both syngeneic and humanized SCLC xenograft models both of which are dependent on the presence of host immune cells. This study underscores the immune-enhancing and metastasis-reducing effects of 6TdG, employing a range of complementary in vitro and in vivo SCLC preclinical models providing a potential therapeutic approach to SCLC.
Structure of the M. tuberculosis DnaK−GrpE complex reveals how key DnaK roles are controlled
Authors: Xiao Xiansha , Fay Allison , Molina Pablo Santos , Kovach Amanda , Glickman Michael S. , Li Huilin
Published: January 2024

The molecular chaperone DnaK is essential for viability of Mycobacterium tuberculosis (Mtb). DnaK hydrolyzes ATP to fold substrates, and the resulting ADP is exchanged for ATP by the nucleotide exchange factor GrpE. It has been unclear how GrpE couples DnaK’s nucleotide exchange with substrate release. Here we report a cryo-EM analysis of GrpE bound to an intact Mtb DnaK, revealing an asymmetric 1:2 DnaK−GrpE complex. The GrpE dimer ratchets to modulate both DnaK nucleotide-binding domain and the substrate-binding domain. We further show that the disordered GrpE N-terminus is critical for substrate release, and that the DnaK−GrpE interface is essential for protein folding activity both in vitro and in vivo. Therefore, the Mtb GrpE dimer allosterically regulates DnaK to concomitantly release ADP in the nucleotide-binding domain and substrate peptide in the substrate-binding domain.
Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle
Authors: Mapel Xena Marie , Kadri Naveen Kumar , Leonard Alexander S. , He Qiongyu , Lloret-Villas Audald , Bhati Meenu , Hiltpold Maya , Pausch Hubert
Published: January 2024

Breeding bulls are well suited to investigate inherited variation in male fertility because they are genotyped and their reproductive success is monitored through semen analyses and thousands of artificial inseminations. However, functional data from relevant tissues are lacking in cattle, which prevents fine-mapping fertility-associated genomic regions. Here, we characterize gene expression and splicing variation in testis, epididymis, and vas deferens transcriptomes of 118 mature bulls and conduct association tests between 414,667 molecular phenotypes and 21,501,032 genome-wide variants to identify 41,156 regulatory loci. We show broad consensus in tissue-specific and tissue-enriched gene expression between the three bovine tissues and their human and murine counterparts. Expression- and splicing-mediating variants are more than three times as frequent in testis than epididymis and vas deferens, highlighting the transcriptional complexity of testis. Finally, we identify genes (WDR19, SPATA16, KCTD19, ZDHHC1) and molecular phenotypes that are associated with quantitative variation in male fertility through transcriptome-wide association and colocalization analyses.
Pangenome graphs improve the analysis of structural variants in rare genetic diseases
Authors: Groza Cristian , Schwendinger-Schreck Carl , Cheung Warren A. , Farrow Emily G. , Thiffault Isabelle , Lake Juniper , Rizzo William B. , Evrony Gilad , Curran Tom , Bourque Guillaume , Pastinen Tomi
Published: January 2024

Rare DNA alterations that cause heritable diseases are only partially resolvable by clinical next-generation sequencing due to the difficulty of detecting structural variation (SV) in all genomic contexts. Long-read, high fidelity genome sequencing (HiFi-GS) detects SVs with increased sensitivity and enables assembling personal and graph genomes. We leverage standard reference genomes, public assemblies (n = 94) and a large collection of HiFi-GS data from a rare disease program (Genomic Answers for Kids, GA4K, n = 574 assemblies) to build a graph genome representing a unified SV callset in GA4K, identify common variation and prioritize SVs that are more likely to cause genetic disease (MAF < 0.01). Using graphs, we obtain a higher level of reproducibility than the standard reference approach. We observe over 200,000 SV alleles unique to GA4K, including nearly 1000 rare variants that impact coding sequence. With improved specificity for rare SVs, we isolate 30 candidate SVs in phenotypically prioritized genes, including known disease SVs. We isolate a novel diagnostic SV in KMT2E, demonstrating use of personal assemblies coupled with pangenome graphs for rare disease genomics. The community may interrogate our pangenome with additional assemblies to discover new SVs within the allele frequency spectrum relevant to genetic diseases.
Persistent warm-eddy transport to Antarctic ice shelves driven by enhanced summer westerlies
Authors: Gao Libao , Yuan Xiaojun , Cai Wenju , Guo Guijun , Yu Weidong , Shi Jiuxin , Qiao Fangli , Wei Zexun , Williams Guy D.
Published: January 2024

The offshore ocean heat supplied to the Antarctic continental shelves by warm eddies has the potential to greatly impact the melting rates of ice shelves and subsequent global sea level rise. While featured in modeling and some observational studies, the processes around how these warm eddies form and overcome the dynamic sub-surface barrier of the Antarctic Slope Front over the upper continental slope has not yet been clarified. Here we report on the detailed observations of persistent eddies carrying warm modified Circumpolar Deep Water (CDW) onto the continental shelf of Prydz Bay, East Antarctica, using subsurface mooring and hydrographic section data from 2013-2015. We show the warm-eddy transport is most active when the summer westerlies strengthen, which promotes the upwelling of CDW and initiates eddy formation and intrusions. Our study highlights the important role of warm eddies in the melting of Antarctica’s ice shelves, both now and into the future.
Electrophotocatalytic hydrogenation of imines and reductive functionalization of aryl halides
Authors: Kang Wen-Jie , Zhang Yanbin , Li Bo , Guo Hao
Published: January 2024

The open-shell catalytically active species, like radical cations or radical anions, generated by one-electron transfer of precatalysts are widely used in energy-consuming redox reactions, but their excited-state lifetimes are usually short. Here, a closed-shell thioxanthone-hydrogen anion species (3), which can be photochemically converted to a potent and long-lived reductant, is generated under electrochemical conditions, enabling the electrophotocatalytic hydrogenation. Notably, TfOH can regulate the redox potential of the active species in this system. In the presence of TfOH, precatalyst (1) reduction can occur at low potential, so that competitive H2 evolution can be inhibited, thus effectively promoting the hydrogenation of imines. In the absence of TfOH, the reducing ability of the system can reach a potency even comparable to that of Na0 or Li0, thereby allowing the hydrogenation, borylation, stannylation and (hetero)arylation of aryl halides to construct C−H, C−B, C−Sn, and C−C bonds.