bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wintertime Brine Discharge at the Surface of a Cold Polar Glacier and the Unexpected Absence of Associated Seismicity
Authors: Carr C. G. , Carmichael J. D. , Pettit E. C. 
Published: February 2022

AbstractA subglacial groundwater system beneath Taylor Glacier, Antarctica, discharges hypersaline, iron‐rich brine episodically at the glacier surface to create Blood Falls. However, the triggering mechanism for these brine release events is not yet understood. Identifying which fracture processes are observed seismically can help us better characterize the hydrological system at Taylor Glacier, and more generally, provide us with a broader understanding of englacial hydrologic activity in cold glaciers. We document wintertime brine discharge using time‐lapse photography. Subfreezing air temperatures during the brine discharge indicate that surface melt‐induced hydrofracture is an unlikely trigger for brine release. Further, we analyze local seismic data to test a hypothesis that fracturing generates elevated surface wave energy preceding and/or coinciding with brine release events. Our results show no discernible elevated Rayleigh wave activity prior to or during Blood Falls brine release. Instead, we find a pattern of seismic events dominated by a seasonal signal, with more Rayleigh events occurring in the summer than the winter from the Blood Falls source area. We calculate that the volumetric opening of cracks that would generate Rayleigh waves at our detection limits are of similar size to myriad cracks in glacier ice, lake ice, and frozen sediment in the terminus area. We therefore propose that any fracturing coincident with brine release activity likely consists of a series of smaller opening events that are masked by other seismicity in the local environment.
Molecular regulations of circadian rhythm and implications for physiology and diseases
Authors: Fagiani Francesca , Di Marino Daniele , Romagnoli Alice , Travelli Cristina , Voltan Davide , Di Cesare Mannelli Lorenzo , Racchi Marco , Govoni Stefano , Lanni Cristina 
Published: February 2022

AbstractThe term “circadian rhythms” describes endogenous oscillations with ca. 24-h period associated with the earth’s daily rotation and light/dark cycle. Such rhythms reflect the existence of an intrinsic circadian clock that temporally orchestrates physiological processes to adapt the internal environment with the external cues. At the molecular level, the circadian clock consists of multiple sets of transcription factors resulting in autoregulatory transcription-translation feedback loops. Notably, in addition to their primary role as generator of circadian rhythm, the biological clock plays a key role in controlling physiological functions of almost all tissues and organs. It regulates several intracellular signaling pathways, ranging from cell proliferation, DNA damage repair and response, angiogenesis, metabolic and redox homeostasis, to inflammatory and immune response. In this review, we summarize findings showing the crosstalk between the circadian molecular clock and some key intracellular pathways, describing a scenario wherein their reciprocal regulation impinges upon several aspects of mammalian physiology. Moreover, based on evidence indicating that circadian rhythms can be challenged by environmental factors, social behaviors, as well as pre-existing pathological conditions, we discuss implications of circadian misalignment in human pathologies, such as cancer and inflammatory diseases. Accordingly, disruption of circadian rhythm has been reported to affect several physiological processes that are relevant to human diseases. Expanding our understanding of this field represents an intriguing and transversal medicine challenge in order to establish a circadian precision medicine.
Parallel profiling of antigenicity alteration and immune escape of SARS-CoV-2 Omicron and other variants
Authors: Sun Cong , Kang Yin-Feng , Liu Yuan-Tao , Kong Xiang-Wei , Xu Hui-Qin , Xiong Dan , Xie Chu , Liu Yi-Hao , Peng Sui , Feng Guo-Kai , Liu Zheng , Zeng Mu-Sheng 
Published: February 2022

AbstractSARS-CoV-2 variants have evolved a variety of critical mutations, leading to antigenicity changes and immune escape. The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines. Here, we profiled the mutations of Omicron and other various circulating SARS-CoV-2 variants in parallel by computational interface analysis and in vitro experimental assays. We identified critical mutations that lead to antigenicity changes and diminished neutralization efficiency of a panel of 14 antibodies due to diverse molecular mechanisms influencing the antigen-antibody interaction. Our study identified that Omicron exhibited extraordinary potency in immune escape compared to the other variants of concern, and explores the application of computational interface analysis in SARS-CoV-2 mutation surveillance and demonstrates its potential for the early identification of concerning variants, providing preliminary guidance for neutralizing antibody therapy.
Inhibition of mitoNEET attenuates LPS-induced inflammation and oxidative stress
Authors: Lee Seunghee , Seok Byeong Geun , Lee Seon-Jin , Chung Su Wol 
Published: February 2022

AbstractMitoNEET (mitochondrial protein containing Asn–Glu–Glu–Thr (NEET) sequence) is a 2Fe–2S cluster-containing integral membrane protein that resides in the mitochondrial outer membrane and participates in a redox-sensitive signaling and Fe–S cluster transfer. Thus, mitoNEET is a key regulator of mitochondrial oxidative capacity and iron homeostasis. Moreover, mitochondrial dysfunction and oxidative stress play critical roles in inflammatory diseases such as sepsis. Increased iron levels mediated by mitochondrial dysfunction lead to oxidative damage and generation of reactive oxygen species (ROS). Increasing evidence suggests that targeting mitoNEET to reverse mitochondrial dysfunction deserves further investigation. However, the role of mitoNEET in inflammatory diseases is unknown. Here, we investigated the mechanism of action and function of mitoNEET during lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Levels of mitoNEET protein increased during microbial or LPS-induced sepsis. Pharmacological inhibition of mitoNEET using mitoNEET ligand-1 (NL-1) decreased the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in animal models of sepsis, as well as LPS-induced inflammatory responses by macrophages in vitro. Inhibition of mitoNEET using NL-1 or mitoNEET shRNA abrogated LPS-induced ROS formation and mitochondrial dysfunction. Furthermore, mitochondrial iron accumulation led to generation of LPS-induced ROS, a process blocked by NL-1 or shRNA. Taken together, these data suggest that mitoNEET could be a key therapeutic molecule that targets mitochondrial dysfunction during inflammatory diseases and sepsis.
Role of mTORC1 activity during early retinal development and lamination in human-induced pluripotent stem cell‐derived retinal organoids
Authors: Lee Si Hyung , Han Jung Woo , Yang Jin Young , Jun Hyoung Oh , Bang Ji Hong , Shin Heejeong , Choi Ji Hye , Lee Jongwoo , Madrakhimov Sanjar Batirovich , Chung Kyung Hwun , Chang Hun Soo , Lyu Jungmook , Park Tae Kwann 
Published: February 2022

AbstractRetinal organoids derived from human-induced pluripotent stem cells (hiPSC) are powerful tools for studying retinal development as they model spatial and temporal differentiation of retinal cell types. Vertebrate retinal development involves a delicate and coordinated process of retinal progenitor cell (RPC) differentiation, and the mammalian target of rapamycin complex 1 (mTORC1) has been reported to play a significant role in this complex process. Herein, using hiPSC-derived retinal organoids, we identify the time-dependent role of mTORC1 in retinal development, specifically in retinal ganglion cell (RGC) differentiation and the retinal lamination process, during the early stages of retinal organoid (RO) development. mTORC1 activity in ROs was the highest at 40 days of differentiation. MHY1485-induced hyperactivation of mTORC1 during this period resulted in a significant increase in the overall size of ROs compared to the untreated controls and rapamycin-treated Ros; there was also a marked increase in proliferative activity within the inner and outer layers of ROs. Moreover, the MHY1485-treated ROs showed a significant increase in the number of ectopic RGCs in the outer layers (indicating disruption of retinal laminar structure), with robust expression of HuC/D-binding proteins in the inner layers. These results demonstrate that mTORC1 plays a critical role in the development of hiPSC-derived ROs, especially during the early stages of differentiation.
ECM1 modified HF-MSCs targeting HSC attenuate liver cirrhosis by inhibiting the TGF-β/Smad signaling pathway
Authors: Liu Qi , Lv Chengqian , Huang Qianqian , Zhao Lei , Sun Xiaoli , Ning Dandan , Liu Jingyang , Jiang Yanan , Jin Shizhu 
Published: February 2022

AbstractHair follicle-derived mesenchymal stem cells (HF-MSCs) show considerable therapeutic potential for liver cirrhosis (LC). To improve the effectiveness of naïve HF-MSC treatments on LC, we used bioinformatic tools to identify an exogenous gene targeting HSCs among the differentially expressed genes (DEGs) in LC to modify HF-MSCs. Extracellular matrix protein 1 (ECM1) was identified as a DEG that was significantly downregulated in the cirrhotic liver. Then, ECM1-overexpressing HF-MSCs (ECM1-HF-MSCs) were transplanted into mice with LC to explore the effectiveness and correlated mechanism of gene-overexpressing HF-MSCs on LC. The results showed that ECM1-HF-MSCs significantly improved liver function and liver pathological injury in LC after cell therapy relative to the other treatment groups. Moreover, we found that ECM1-HF-MSCs homed to the injured liver and expressed the hepatocyte-specific surface markers ALB, CK18, and AFP. In addition, hepatic stellate cell (HSC) activation was significantly inhibited in the cell treatment groups in vivo and in vitro, especially in the ECM1-HF-MSC group. Additionally, TGF-β/Smad signal inhibition was the most significant in the ECM1-HF-MSC group in vivo and in vitro. The findings indicate that the genetic modification of HF-MSCs with bioinformatic tools may provide a broad perspective for precision treatment of LC.
Therapeutic effects of eperisone on pulmonary fibrosis via preferential suppression of fibroblast activity
Authors: Tanaka Ken-ichiro , Shimoda Mikako , Sugizaki Toshifumi , Ikeda Maki , Takafuji Ayaka , Kawahara Masahiro , Yamakawa Naoki , Mizushima Tohru 
Published: February 2022

AbstractAlthough the exact pathogenesis of idiopathic pulmonary fibrosis (IPF) is still unknown, the transdifferentiation of fibroblasts into myofibroblasts and the production of extracellular matrix components such as collagen, triggered by alveolar epithelial cell injury, are important mechanisms of IPF development. In the lungs of IPF patients, apoptosis is less likely to be induced in fibroblasts than in alveolar epithelial cells, and this process is involved in the pathogenesis of IPF. We used a library containing approved drugs to screen for drugs that preferentially reduce cell viability in LL29 cells (lung fibroblasts from an IPF patient) compared with A549 cells (human alveolar epithelial cell line). After screening, we selected eperisone, a central muscle relaxant used in clinical practice. Eperisone showed little toxicity in A549 cells and preferentially reduced the percentage of viable LL29 cells, while pirfenidone and nintedanib did not have this effect. Eperisone also significantly inhibited transforming growth factor-β1-dependent transdifferentiation of LL29 cells into myofibroblasts. In an in vivo study using ICR mice, eperisone inhibited bleomycin (BLM)-induced pulmonary fibrosis, respiratory dysfunction, and fibroblast activation. In contrast, pirfenidone and nintedanib were less effective than eperisone in inhibiting BLM-induced pulmonary fibrosis under this experimental condition. Finally, we showed that eperisone did not induce adverse effects in the liver and gastrointestinal tract in the BLM-induced pulmonary fibrosis model. Considering these results, we propose that eperisone may be safer and more therapeutically beneficial for IPF patients than current therapies.
Hsa_circ_0134111 promotes intervertebral disc degeneration via sponging miR-578
Authors: Yan Peng , Sun Chong , Luan Liangrui , Han Jialuo , Qu Yang , Zhou Chuanli , Xu Derong 
Published: February 2022

AbstractIntervertebral disc degeneration (IDD) is a chronic degenerative and age-dependent process characterized by aberrant apoptosis, proliferation, synthesis, and catabolism of the extracellular matrix of the nucleus pulposus (NP) cells. Recently, studies showed that circular RNAs play important roles in the development of many diseases. However, the role of circRNAs in IDD development remains unknown. We showed that circ_0134111 level was overexpressed in IDD tissue samples as compar-ed to control tissues. The upregulation of circ_0134111 was more drastic in the moderate and severe IDD cases than in those with mild IDD. In addition, we showed that interleukin-1β and tumor necrosis factor-α exposure significantly enhanced circ_0134111 expression in NP cells. Furthermore, ectopic expression of circ_0134111 induced proliferation, pro-inflammatory cytokine secretion, and ECM degradation in the NP cells. We also showed that circ_0134111 directly interacted with microRNA (miR)-578 in NP cells where elevated expression of circ_0134111 enhanced the ADAMTS-5 and MMP-9 expression. Moreover, miR-578 expression was significantly decreased in IDD patients and the miR-578 expression was negatively correlated with circ_0134111 expression in the IDD samples. Interleukin-1β and tumor necrosis factor-α exposure significantly decreased miR-578 levels in NP cells, in which ectopic miR-578 expression inhibited cell growth, pro-inflammatory cytokine expression, and ECM degradation. Finally, we showed that circ_0134111 overexpression induced the IDD-related phenotypic changes through inhibiting miR-578. These data suggested that circ_0134111 could promote the progression of IDD through enhancing aberrant NP cell growth, inflammation, and ECM degradation partly via regulating miR-578.
Alternative splicing in seasonal plasticity and the potential for adaptation to environmental change
Authors: Steward Rachel A. , de Jong Maaike A. , Oostra Vicencio , Wheat Christopher W. 
Published: February 2022

AbstractSeasonal plasticity is accomplished via tightly regulated developmental cascades that translate environmental cues into trait changes. Little is known about how alternative splicing and other posttranscriptional molecular mechanisms contribute to plasticity or how these mechanisms impact how plasticity evolves. Here, we use transcriptomic and genomic data from the butterfly Bicyclus anynana, a model system for seasonal plasticity, to compare the extent of differential expression and splicing and test how these axes of transcriptional plasticity differ in their potential for evolutionary change. Between seasonal morphs, we find that differential splicing affects a smaller but functionally unique set of genes compared to differential expression. Further, we find strong support for the novel hypothesis that spliced genes are more susceptible than differentially expressed genes to erosion of genetic variation due to selection on seasonal plasticity. Our results suggest that splicing plasticity is especially likely to experience genetic constraints that could affect the potential of wild populations to respond to rapidly changing environments.
Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants
Authors: Saville James W. , Mannar Dhiraj , Zhu Xing , Srivastava Shanti S. , Berezuk Alison M. , Demers Jean-Philippe , Zhou Steven , Tuttle Katharine S. , Sekirov Inna , Kim Andrew , Li Wei , Dimitrov Dimiter S. , Subramaniam Sriram 
Published: February 2022

AbstractThe Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this study, we assess structural and biochemical aspects of viral fitness for these two variants using cryo-electron microscopy (cryo-EM), ACE2-binding and antibody neutralization analyses. Both variants demonstrate escape of antibodies targeting the N-terminal domain, an important immune hotspot for neutralizing epitopes. Compared to wild-type and Kappa lineages, Delta variant spike proteins show modest increase in ACE2 affinity, likely due to enhanced electrostatic complementarity at the RBD-ACE2 interface, which we characterize by cryo-EM. Unexpectedly, Kappa variant spike trimers form a structural head-to-head dimer-of-trimers assembly, which we demonstrate is a result of the E484Q mutation and with unknown biological implications. The combination of increased antibody escape and enhanced ACE2 binding provides an explanation, in part, for the rapid global dominance of the Delta variant.
Few-layer bismuth selenide cathode for low-temperature quasi-solid-state aqueous zinc metal batteries
Authors: Zhao Yuwei , Lu Yue , Li Huiping , Zhu Yongbin , Meng You , Li Na , Wang Donghong , Jiang Feng , Mo Funian , Long Changbai , Guo Ying , Li Xinliang , Huang Zhaodong , Li Qing , Ho Johnny C. , Fan Jun , Sui Manling , Chen Furong , Zhu Wenguang , Liu Weishu , Zhi Chunyi 
Published: February 2022

AbstractThe performances of rechargeable batteries are strongly affected by the operating environmental temperature. In particular, low temperatures (e.g., ≤0 °C) are detrimental to efficient cell cycling. To circumvent this issue, we propose a few-layer Bi2Se3 (a topological insulator) as cathode material for Zn metal batteries. When the few-layer Bi2Se3 is used in combination with an anti-freeze hydrogel electrolyte, the capacity delivered by the cell at −20 °C and 1 A g−1 is 1.3 larger than the capacity at 25 °C for the same specific current. Also, at 0 °C the Zn | |few-layer Bi2Se3 cell shows capacity retention of 94.6% after 2000 cycles at 1 A g−1. This behaviour is related to the fact that the Zn-ion uptake in the few-layer Bi2Se3 is higher at low temperatures, e.g., almost four Zn2+ at 25 °C and six Zn2+ at −20 °C. We demonstrate that the unusual performance improvements at low temperatures are only achievable with the few-layer Bi2Se3 rather than bulk Bi2Se3. We also show that the favourable low-temperature conductivity and ion diffusion capability of few-layer Bi2Se3 are linked with the presence of topological surface states and weaker lattice vibrations, respectively.
Physics-informed deep learning for solving phonon Boltzmann transport equation with large temperature non-equilibrium
Authors: Li Ruiyang , Wang Jian-Xun , Lee Eungkyu , Luo Tengfei 
Published: February 2022

AbstractPhonon Boltzmann transport equation (BTE) is a key tool for modeling multiscale phonon transport, which is critical to the thermal management of miniaturized integrated circuits, but assumptions about the system temperatures (i.e., small temperature gradients) are usually made to ensure that it is computationally tractable. To include the effects of large temperature non-equilibrium, we demonstrate a data-free deep learning scheme, physics-informed neural network (PINN), for solving stationary, mode-resolved phonon BTE with arbitrary temperature gradients. This scheme uses the temperature-dependent phonon relaxation times and learns the solutions in parameterized spaces with both length scale and temperature gradient treated as input variables. Numerical experiments suggest that the proposed PINN can accurately predict phonon transport (from 1D to 3D) under arbitrary temperature gradients. Moreover, the proposed scheme shows great promise in simulating device-level phonon heat conduction efficiently and can be potentially used for thermal design.
High-throughput SNPs dataset reveal restricted population connectivity of marine gastropod within the narrow distribution range of peripheral oceanic islands
Authors: Yamazaki Daishi , Ito Shun , Miura Osamu , Sasaki Tetsuro , Chiba Satoshi 
Published: February 2022

AbstractMolecular studies based on the high resolution genetic markers help us to grasp the factor shaping the genetic structure of marine organisms. Ecological factors linking to life history traits have often explained the process of genetic structuring in open and connectable oceanic environments. Besides, population genetic divergence can be affected by fragmented habitat, oceanic current, and past geographical events. In the present study, we demonstrated the genetic differentiation of marine gastropod Monodonta sp. within a narrow range of peripheral oceanic islands, the Ogasawara Islands. Genetic analyses were performed not only with a mitochondrial DNA marker but also with a high-throughput SNPs dataset obtained by ddRAD-seq. The results of the mtDNA analyses did not show genetic divergence among populations, while the SNPs dataset detected population genetic differentiation. Population demographic analyses and gene flow estimation suggested that the genetic structure was formed by sea level fluctuation associated with the past climatic change and regulated by temporal oceanographic conditions. These findings provide important insights into population genetic patterns in open and connectable environments.
Droplet digital PCR assay provides intrahepatic HBV cccDNA quantification tool for clinical application
Authors: Hayashi Sanae , Isogawa Masanori , Kawashima Keigo , Ito Kyoko , Chuaypen Natthaya , Morine Yuji , Shimada Mitsuo , Higashi-Kuwata Nobuyo , Watanabe Takehisa , Tangkijvanich Pisit , Mitsuya Hiroaki , Tanaka Yasuhito 
Published: February 2022

AbstractThe persistence of covalently closed circular DNA (cccDNA) poses a major obstacle to curing chronic hepatitis B (CHB). Here, we used droplet digital PCR (ddPCR) for cccDNA quantitation. The cccDNA-specific ddPCR showed high accuracy with the dynamic range of cccDNA detection from 101 to 105 copies/assay. The ddPCR had higher sensitivity, specificity and precisely than qPCR. The results of ddPCR correlated closely with serum HB core-related antigen and HB surface antigen (HBsAg) in 24 HBV-infected human-liver-chimeric mice (PXB-mice). We demonstrated that in 2 PXB-mice after entecavir treatment, the total cccDNA content did not change during liver repopulation, although the cccDNA content per hepatocyte was reduced after the treatment. In the 6 patients with HBV-related hepatocellular carcinoma, ddPCR detected cccDNA in both tumor and non-tumor tissues. In 13 HBeAg-negative CHB patients with pegylated interferon alpha-2a, cccDNA contents from paired biopsies were more significantly reduced in virological response (VR) than in non-VR at week 48 (p = 0.0051). Interestingly, cccDNA levels were the lowest in VR with HBsAg clearance but remained detectable after the treatment. Collectively, ddPCR revealed that cccDNA content is stable during hepatocyte proliferation and persists at quantifiable levels, even after serum HBsAg clearance.