bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding depression: a comprehensive multi-cohort exploration of blood DNA methylation using machine learning and deep learning approaches
Authors: Sokolov Aleksandr V. , Schiöth Helgi B. 
Published: July 2024

AbstractThe causes of depression are complex, and the current diagnosis methods rely solely on psychiatric evaluations with no incorporation of laboratory biomarkers in clinical practices. We investigated the stability of blood DNA methylation depression signatures in six different populations using six public and two domestic cohorts (n = 1942) conducting mega-analysis and meta-analysis of the individual studies. We evaluated 12 machine learning and deep learning strategies for depression classification both in cross-validation (CV) and in hold-out tests using merged data from 8 separate batches, constructing models with both biased and unbiased feature selection. We found 1987 CpG sites related to depression in both mega- and meta-analysis at the nominal level, and the associated genes were nominally related to axon guidance and immune pathways based on enrichment analysis and eQTM data. Random forest classifiers achieved the highest performance (AUC 0.73 and 0.76) in CV and hold-out tests respectively on the batch-level processed data. In contrast, the methylation showed low predictive power (all AUCs < 0.57) for all classifiers in CV and no predictive power in hold-out tests when used with harmonized data. All models achieved significantly better performance (>14% gain in AUCs) with pre-selected features (selection bias), with some of the models (joint autoencoder-classifier) reaching AUCs of up to 0.91 in the final testing regardless of data preparation. Different algorithmic feature selection approaches may outperform limma, however, random forest models perform well regardless of the strategy. The results provide an overview over potential future biomarkers for depression and highlight many important methodological aspects for DNA methylation-based depression profiling including the use of machine learning strategies.
Effects of oxytocin receptor agonism on acquisition and expression of pair bonding in male prairie voles
Authors: Johnson Michael C. , Zweig Jonathan A. , Zhang Yangmiao , Nunez Louis , Ryabinina Olga P. , Hibert Marcel , Ryabinin Andrey E. 
Published: July 2024

AbstractThere is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (Microtus ochrogaster), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4hr cohabitation. In contrast, while animals injected with vehicle after the 4hr cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2hr-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.
PRMT1 promotes Warburg effect by regulating the PKM2/PKM1 ratio in non-small cell lung cancer
Authors: Peng Lu , Zhao Yujiao , Tan Jiang , Hou Jingyao , Jin Xin , Liu Dong-Xu , Huang Baiqu , Lu Jun 
Published: July 2024

AbstractAbnormal epigenetic modifications are involved in the regulation of Warburg effect in tumor cells. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have critical functions in cellular responses. PRMTs are deregulated in a variety of cancers, but their precise roles in Warburg effect in cancer is largely unknown. Experiments from the current study showed that PRMT1 was highly expressed under conditions of glucose sufficiency. PRMT1 induced an increase in the PKM2/PKM1 ratio through upregulation of PTBP1, in turn, promoting aerobic glycolysis in non-small cell lung cancer (NSCLC). The PRMT1 level in p53-deficient and p53-mutated NSCLC remained relatively unchanged while the expression was reduced in p53 wild-type NSCLC under conditions of glucose insufficiency. Notably, p53 activation under glucose-deficient conditions could suppress USP7 and further accelerate the polyubiquitin-dependent degradation of PRMT1. Melatonin, a hormone that inhibits glucose intake, markedly suppressed cell proliferation of p53 wild-type NSCLC, while a combination of melatonin and the USP7 inhibitor P5091 enhanced the anticancer activity in p53-deficient NSCLC. Our collective findings support a role of PRMT1 in the regulation of Warburg effect in NSCLC. Moreover, combination treatment with melatonin and the USP7 inhibitor showed good efficacy, providing a rationale for the development of PRMT1-based therapy to improve p53-deficient NSCLC outcomes.
FADD regulates adipose inflammation, adipogenesis, and adipocyte survival
Authors: Tang Jianlei , Ma Yue , Li Meilin , Liu Xiangpeng , Wang Yuting , Zhang Jie , Shu Hui , Liu Zhiwei , Zhang Chi , Fu Lei , Hu Ji , Zhang Yong , Jia Zhihao , Feng Yu 
Published: July 2024

AbstractAdipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.
AI-NERD: Elucidation of relaxation dynamics beyond equilibrium through AI-informed X-ray photon correlation spectroscopy
Authors: Horwath James P. , Lin Xiao-Min , He Hongrui , Zhang Qingteng , Dufresne Eric M. , Chu Miaoqi , Sankaranarayanan Subramanian K.R.S. , Chen Wei , Narayanan Suresh , Cherukara Mathew J. 
Published: July 2024

AbstractUnderstanding and interpreting dynamics of functional materials in situ is a grand challenge in physics and materials science due to the difficulty of experimentally probing materials at varied length and time scales. X-ray photon correlation spectroscopy (XPCS) is uniquely well-suited for characterizing materials dynamics over wide-ranging time scales. However, spatial and temporal heterogeneity in material behavior can make interpretation of experimental XPCS data difficult. In this work, we have developed an unsupervised deep learning (DL) framework for automated classification of relaxation dynamics from experimental data without requiring any prior physical knowledge of the system. We demonstrate how this method can be used to accelerate exploration of large datasets to identify samples of interest, and we apply this approach to directly correlate microscopic dynamics with macroscopic properties of a model system. Importantly, this DL framework is material and process agnostic, marking a concrete step towards autonomous materials discovery.
Beta activity in human anterior cingulate cortex mediates reward biases
Authors: Xiao Jiayang , Adkinson Joshua A. , Myers John , Allawala Anusha B. , Mathura Raissa K. , Pirtle Victoria , Najera Ricardo , Provenza Nicole R. , Bartoli Eleonora , Watrous Andrew J. , Oswalt Denise , Gadot Ron , Anand Adrish , Shofty Ben , Mathew Sanjay J. , Goodman Wayne K. , Pouratian Nader , Pitkow Xaq , Bijanki Kelly R. , Hayden Benjamin , Sheth Sameer A. 
Published: July 2024

AbstractThe rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12–30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.
Analytical realization of complex thermal meta-devices
Authors: Li Weichen , Sigmund Ole , Zhang Xiaojia Shelly 
Published: July 2024

AbstractFourier’s law dictates that heat flows from warm to cold. Nevertheless, devices can be tailored to cloak obstacles or even reverse the heat flow. Mathematical transformation yields closed-form equations for graded, highly anisotropic thermal metamaterial distributions needed for obtaining such functionalities. For simple geometries, devices can be realized by regular conductor distributions; however, for complex geometries, physical realizations have so far been challenging, and sub-optimal solutions have been obtained by expensive numerical approaches. Here we suggest a straightforward and highly efficient analytical de-homogenization approach that uses optimal multi-rank laminates to provide closed-form solutions for any imaginable thermal manipulation device. We create thermal cloaks, rotators, and concentrators in complex domains with close-to-optimal performance and esthetic elegance. The devices are fabricated using metal 3D printing, and their omnidirectional thermal functionalities are investigated numerically and validated experimentally. The analytical approach enables next-generation free-form thermal meta-devices with efficient synthesis, near-optimal performance, and concise patterns.
Temporal dynamics of climate change exposure and opportunities for global marine biodiversity
Authors: Meyer Andreas Schwarz , Pigot Alex L. , Merow Cory , Kaschner Kristin , Garilao Cristina , Kesner-Reyes Kathleen , Trisos Christopher H. 
Published: July 2024

AbstractClimate change is exposing marine species to unsuitable temperatures while also creating new thermally suitable habitats of varying persistence. However, understanding how these different dynamics will unfold over time remains limited. We use yearly sea surface temperature projections to estimate temporal dynamics of thermal exposure (when temperature exceeds realised species’ thermal limits) and opportunity (when temperature at a previously unsuitable site becomes suitable) for 21,696 marine species globally until 2100. Thermal opportunities are projected to arise earlier and accumulate gradually, especially in temperate and polar regions. Thermal exposure increases later and occurs more abruptly, mainly in the tropics. Assemblages tend to show either high exposure or high opportunity, but seldom both. Strong emissions reductions reduce exposure around 100-fold whereas reductions in opportunities are halved. Globally, opportunities are projected to emerge faster than exposure until mid-century when exposure increases more rapidly under a high emissions scenario. Moreover, across emissions and dispersal scenarios, 76%-97% of opportunities are projected to persist until 2100. These results indicate thermal opportunities could be a major source of marine biodiversity change, especially in the near- and mid-term. Our work provides a framework for predicting where and when thermal changes will occur to guide monitoring efforts.
Large-scale whole-exome sequencing analyses identified protein-coding variants associated with immune-mediated diseases in 350,770 adults
Authors: Yang Liu , Ou Ya-Nan , Wu Bang-Sheng , Liu Wei-Shi , Deng Yue-Ting , He Xiao-Yu , Chen Yi-Lin , Kang Jujiao , Fei Chen-Jie , Zhu Ying , Tan Lan , Dong Qiang , Feng Jianfeng , Cheng Wei , Yu Jin-Tai 
Published: July 2024

AbstractThe genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves’ disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.
Robust structural superlubricity under gigapascal pressures
Authors: Sun Taotao , Gao Enlai , Jia Xiangzheng , Bian Jinbo , Wang Zhou , Ma Ming , Zheng Quanshui , Xu Zhiping 
Published: July 2024

AbstractStructural superlubricity (SSL) is a state of contact with no wear and ultralow friction. SSL has been characterized at contact with van der Waals (vdW) layered materials, while its stability under extreme loading conditions has not been assessed. By designing both self-mated and non-self-mated vdW contacts with materials chosen for their high strengths, we report outstanding robustness of SSL under very high pressures in experiments. The incommensurate self-mated vdW contact between graphite interfaces can maintain the state of SSL under a pressure no lower than 9.45 GPa, and the non-self-mated vdW contact between a tungsten tip and graphite substrate remains stable up to 3.74 GPa. Beyond this critical pressure, wear is activated, signaling the breakdown of vdW contacts and SSL. This unexpectedly strong pressure-resistance and wear-free feature of SSL breaks down the picture of progressive wear. Atomistic simulations show that lattice destruction at the vdW contact by pressure-assisted bonding triggers wear through shear-induced tearing of the single-atomic layers. The correlation between the breakdown pressure and material properties shows that the bulk modulus and the first ionization energy are the most relevant factors, indicating the combined structural and electronic effects. Impressively, the breakdown pressures defined by the SSL interface could even exceed the strength of materials in contact, demonstrating the robustness of SSL. These findings offer a fundamental understanding of wear at the vdW contacts and guide the design of SSL-enabled applications.
pH drives electron density fluctuations that enhance electric field-induced liquid flow
Authors: Pullanchery S. , Kulik S. , Schönfeldová T. , Egan C. K. , Cassone G. , Hassanali A. , Roke S. 
Published: July 2024

AbstractLiquid flow along a charged interface is commonly described by classical continuum theory, which represents the electric double layer by uniformly distributed point charges. The electrophoretic mobility of hydrophobic nanodroplets in water doubles in magnitude when the pH is varied from neutral to mildly basic (pH 7 → 11). Classical continuum theory predicts that this increase in mobility is due to an increased surface charge. Here, by combining all-optical measurements of surface charge and molecular structure, as well as electronic structure calculations, we show that surface charge and molecular structure at the nanodroplet surface are identical at neutral and mildly basic pH. We propose that the force that propels the droplets originates from two factors: Negative charge on the droplet surface due to charge transfer from and within water, and anisotropic gradients in the fluctuating polarization induced by the electric field. Both charge density fluctuations couple with the external electric field, and lead to droplet flow. Replacing chloride by hydroxide doubles both the charge conductivity via the Grotthuss mechanism, and the droplet mobility. This general mechanism deeply impacts a plethora of processes in biology, chemistry, and nanotechnology and provides an explanation of how pH influences hydrodynamic phenomena and the limitations of classical continuum theory currently used to rationalize these effects.
Single-cell total-RNA profiling unveils regulatory hubs of transcription factors
Authors: Niu Yichi , Luo Jiayi , Zong Chenghang 
Published: July 2024

AbstractRecent development of RNA velocity uses master equations to establish the kinetics of the life cycle of RNAs from unspliced RNA to spliced RNA (i.e., mature RNA) to degradation. To feed this kinetic analysis, simultaneous measurement of unspliced RNA and spliced RNA in single cells is greatly desired. However, the majority of single-cell RNA-seq chemistry primarily captures mature RNA species to measure gene expressions. Here, we develop a one-step total-RNA chemistry-based single-cell RNA-seq method: snapTotal-seq. We benchmark this method with multiple single-cell RNA-seq assays in their performance in kinetic analysis of cell cycle by RNA velocity. Next, with LASSO regression between transcription factors, we identify the critical regulatory hubs mediating the cell cycle dynamics. We also apply snapTotal-seq to profile the oncogene-induced senescence and identify the key regulatory hubs governing the entry of senescence. Furthermore, from the comparative analysis of unspliced RNA and spliced RNA, we identify a significant portion of genes whose expression changes occur in spliced RNA but not to the same degree in unspliced RNA, indicating these gene expression changes are mainly controlled by post-transcriptional regulation. Overall, we demonstrate that snapTotal-seq can provide enriched information about gene regulation, especially during the transition between cell states.
Laboratory infrared spectra and fragmentation chemistry of sulfur allotropes
Authors: Ferrari Piero , Berden Giel , Redlich Britta , Waters Laurens B. F. M. , Bakker Joost M. 
Published: July 2024

AbstractSulfur is one of six life-essential elements, but its path from interstellar clouds to planets and their atmospheres is not well known. Astronomical observations in dense clouds have so far been able to trace only 1 percent of cosmic sulfur, in the form of gas phase molecules and volatile ices, with the missing sulfur expected to be locked in a currently unidentified form. The high sulfur abundances inferred in icy and rocky solar system bodies indicate that an efficient pathway must exist from volatile atomic sulfur in the diffuse interstellar medium to some form of refractory sulfur. One hypothesis is the formation of sulfur allotropes, particularly of the stable S8. However, experimental information about sulfur allotropes under astrochemically relevant conditions, needed to constrain their abundance, is lacking. Here, we report the laboratory far-infrared spectra of sulfur allotropes and examine their fragmentation pathways. The spectra, including that of cold, isolated S8 with three bands at 53.5, 41.3 and 21.1 µm, form a benchmark for computational modelling, which show a near-perfect match with the experiments. The experimental fragmentation pathways of sulfur allotropes, key information for astrochemical formation/destruction models, evidence a facile fragmentation of S8. These findings suggest the presence of sulfur allotropes distributions in interstellar space or in the atmosphere of planets, dependent on the environmental conditions.
Direct observation of twisted stacking domains in the van der Waals magnet CrI3
Authors: Jang Myeongjin , Lee Sol , Cantos-Prieto Fernando , Košić Ivona , Li Yue , McCray Arthur R. C. , Jung Min-Hyoung , Yoon Jun-Yeong , Boddapati Loukya , Deepak Francis Leonard , Jeong Hu Young , Phatak Charudatta M. , Santos Elton J. G. , Navarro-Moratalla Efrén , Kim Kwanpyo 
Published: July 2024

AbstractVan der Waals (vdW) stacking is a powerful technique to achieve desired properties in condensed matter systems through layer-by-layer crystal engineering. A remarkable example is the control over the twist angle between artificially-stacked vdW crystals, enabling the realization of unconventional phenomena in moiré structures ranging from superconductivity to strongly correlated magnetism. Here, we report the appearance of unusual 120° twisted faults in vdW magnet CrI3 crystals. In exfoliated samples, we observe vertical twisted domains with a thickness below 10 nm. The size and distribution of twisted domains strongly depend on the sample preparation methods, with as-synthesized unexfoliated samples showing tenfold thicker domains than exfoliated samples. Cooling induces changes in the relative populations among different twisting domains, rather than the previously assumed structural phase transition to the rhombohedral stacking. The stacking disorder induced by sample fabrication processes may explain the unresolved thickness-dependent magnetic coupling observed in CrI3.