bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Search for Large‐Scale Variations in the Fine‐Scale Structure of Earth's Inner Core
Authors: Wu Sin‐Mei , Pang Guanning , Koper Keith D. , Euler Garrett 
Published: September 2022

AbstractA hemispherical pattern in inner core attenuation (Q) has been observed from the apparent Q of inner core transmitted waves (PKPDF). How the elastic scattering (QSC) originating from kilometer‐scale inner core heterogeneities relates to large‐scale apparent Q variations remains elusive. Such inner core scattered (ICS) energy is characterized by emergent, long‐lasting, high‐frequency (1–4 Hz) coda immediately following pre‐critical reflections (PKiKP) from the inner core boundary (ICB). In this study, we develop a framework to systematically investigate ICS and examine its hemispherical pattern using data from two arrays that sample opposing sides of the Pacific quasi‐hemispherical boundary. We use all the viable data from earthquakes (Mw ≥ 5.8) within the past 2–3 decades recorded at distances of 50°–75° by YKA and ILAR—small‐aperture (∼10–20 km) seismic arrays situated in northwestern North America. Two independent waveform stripping methods are applied to extract ICS from the background energy, and various stacks are performed to identify ICS and its spatial pattern. We found that individual beams lacking clear evidence of PKiKP coda waves reveal ICS characteristics when stacked together, implying that ICS is ubiquitous. We used a modified phonon‐based simulation to reinforce the idea that ICS is primarily created by volumetric heterogeneity within the inner core as opposed to ICB topography. With simplified two‐layer ICS models, our results suggest that ICS within the eastern quasi‐hemisphere is slightly stronger than in the western quasi‐hemisphere, although intra‐hemispherical variations are as significant, and our sampling is limited to patches of the northern hemisphere.
BMS794833 inhibits macrophage efferocytosis by directly binding to MERTK and inhibiting its activity
Authors: Bae Seung-Hyun , Kim Jung-Hoon , Park Tae Hyun , Lee Kyeong , Lee Byung Il , Jang Hyonchol 
Published: September 2022

AbstractMyeloid epithelial reproductive proto-oncogene tyrosine kinase (MERTK) plays an essential role in modulating cancer immune tolerance by regulating macrophage efferocytosis. Studies are underway to develop small-molecule chemicals that inhibit MERTK as cancer immunotherapeutic agents, but these efforts are in their early stages. This study identified BMS794833, whose primary targets are MET and VEGFR2, as a potent MERTK inhibitor and developed a real-time efferocytosis monitoring system. The X-ray cocrystal structure revealed that BMS794833 was in contact with the ATP-binding pocket and the allosteric back pocket, rendering MERTK inactive. Homogeneous time-resolved fluorescence kinetic and Western blotting analyses showed that BMS794833 competitively inhibited MERTK activity in vitro and inhibited the autophosphorylation of MERTK in macrophages. We developed a system to monitor MERTK-dependent efferocytosis in real time, and using this system, we confirmed that BMS794833 significantly inhibited the efferocytosis of differentiated macrophages. Finally, BMS794833 significantly inhibited efferocytosis in vivo in a mouse model. These data show that BMS794833 is a type II MERTK inhibitor that regulates macrophage efferocytosis. In addition, the real-time efferocytosis monitoring technology developed in this study has great potential for future applications.
The schizophrenia-associated missense variant rs13107325 regulates dendritic spine density
Authors: Li Shiwu , Ma Changguo , Li Yifan , Chen Rui , Liu Yixing , Wan Li Pear , Xiong Qiuxia , Wang Chuang , Huo Yongxia , Dang Xinglun , Yang Yongfeng , Lv Luxian , Chen Xi , Sheng Nengyin , Li Wenqiang , Luo Xiong-Jian 
Published: September 2022

AbstractThe missense variant rs13107325 (C/T, p.Ala391Thr) in SLC39A8 consistently showed robust association with schizophrenia in recent genome-wide association studies (GWASs), suggesting the potential pathogenicity of this non-synonymous risk variant. Nevertheless, how this missense variant confers schizophrenia risk remains unknown. Here we constructed a knock-in mouse model (by introducing a threonine at the 393th amino acid of mouse SLC39A8 (SLC39A8-p.393T), which corresponds to rs13107325 (p.Ala391Thr) of human SLC39A8) to explore the potential roles and biological effects of this missense variant in schizophrenia pathogenesis. We assessed multiple phenotypes and traits (associated with rs13107325) of the knock-in mice, including body and brain weight, concentrations of metal ions (including cadmium, zinc, manganese, and iron) transported by SLC39A8, blood lipids, proliferation and migration of neural stem cells (NSCs), cortical development, behaviors and cognition, transcriptome, dendritic spine density, and synaptic transmission. Many of the tested phenotypes did not show differences in SLC39A8-p.393T knock-in and wild-type mice. However, we found that zinc concentration in brain and blood of SLC39A8-p.393T knock-in mice was dysregulated compared with wild-types, validating the functionality of rs13107325. Further analysis indicated that cortical dendritic spine density of the SLC39A8-p.393T knock-in mice was significantly decreased compared with wild-types, indicating the important role of SLC39A8-p.393T in dendritic spine morphogenesis. These results indicated that SLC39A8-p.393T knock-in resulted in decreased dendritic spine density, thus mimicking the dendritic spine pathology observed in schizophrenia. Our study indicates that rs13107325 might confer schizophrenia risk by regulating zinc concentration and dendritic spine density, a featured characteristic that was frequently reported to be decreased in schizophrenia.
CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport
Authors: Jiang Ruiwei , Tang Xiaofang , Pan Jiale , Li Gaizhen , Yang Ningjie , Tang Yedong , Bi Shilei , Cai Han , Chen Qionghua , Chen Dunjin , Wang Haibin , Kong Shuangbo 
Published: September 2022

AbstractCiliated and secretory cells are two major cell types that comprise the oviduct epithelia. Accumulating evidences support a role of oviductal multiciliated epithelia for embryo transport, however the mechanisms underlying this specialized cell type differentiation remain elusive. Here, we report that CDC42 depletion in oviduct epithelia hampers the morphogenesis of multiciliated cell, and results in embryo retention, leading to early pregnancy failure. Utilizing the oviduct organoid model, we further observed that CDC42 guides secretory cells transition into multiciliated cells independent of its GTPase activity and the well-known Notch pathway. Further exploration uncovered the AKT as a novel indispensable regulator for multiciliated cells differentiation, whose activity was maintained by CDC42 through interacting with the p110β. Consistently, re-activating AKT partially incites multiciliated cells differentiation in Cdc42 knockout oviductal organoids. Finally, low levels of CDC42 and phospho-AKT with reduced multiciliated cells in the oviduct are observed in women with ectopic pregnancy. Collectively, we provide previously unappreciated evidence that CDC42-AKT signaling is a critical determinant for morphogenesis of oviduct multiciliated cell, which possesses the clinical application in understanding the pathology of ectopic pregnancy and facilitating the development of prevention strategies.
A dual role of lola in Drosophila ovary development: regulating stem cell niche establishment and repressing apoptosis
Authors: Zhao Ting , Xiao Yanhong , Huang Bo , Ran Mao-Jiu , Duan Xin , Wang Yu-Feng , Lu Yuzhen , Yu Xiao-Qiang 
Published: September 2022

AbstractIn Drosophila ovary, niche is composed of somatic cells, including terminal filament cells (TFCs), cap cells (CCs) and escort cells (ECs), which provide extrinsic signals to maintain stem cell renewal or initiate cell differentiation. Niche establishment begins in larval stages when terminal filaments (TFs) are formed, but the underlying mechanism for the development of TFs remains largely unknown. Here we report that transcription factor longitudinals lacking (Lola) is essential for ovary morphogenesis. We showed that Lola protein was expressed abundantly in TFCs and CCs, although also in other cells, and lola was required for the establishment of niche during larval stage. Importantly, we found that knockdown expression of lola induced apoptosis in adult ovary, and that lola affected adult ovary morphogenesis by suppressing expression of Regulator of cullins 1b (Roc1b), an apoptosis-related gene that regulates caspase activation during spermatogenesis. These findings significantly expand our understanding of the mechanisms controlling niche establishment and adult oogenesis in Drosophila.
KCTD9 inhibits the Wnt/β-catenin pathway by decreasing the level of β-catenin in colorectal cancer
Authors: Yao Hanhui , Ren Delong , Wang Yichun , Wu Liang , Wu Yang , Wang Wei , Li Qidong , Liu Lianxin 
Published: September 2022

AbstractColorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. However, the molecular mechanisms underlying CRC progression remain to be further defined to improve patient outcomes. In this study, we found that KCTD9, a member of the potassium channel tetramerization domain-containing (KCTD) gene family, was commonly downregulated in CRC tissues and that KCTD9 expression was negatively correlated with the clinical CRC stage. Survival analysis showed that patients whose tumors expressed low KCTD9 levels had poorer outcomes. Functional analyses revealed that KCTD9 overexpression inhibited CRC cell proliferation and metastasis, whereas KCTD9 knockdown promoted CRC cell proliferation and metastasis in both in vitro and in vivo models. Manipulating KCTD9 levels in CRC cells via overexpression or knockdown showed KCTD9 expression positively influenced the degradation of β-catenin levels leading to inhibition of Wnt signaling and reductions in Wnt pathway target gene expression. Mechanistically, we found KCTD9 associated with ZNT9 (Zinc Transporter 9), a coactivator of β-catenin-mediated gene transcription. The overexpression of KCTD9 or knockdown of ZNT9 in CRC cells increased the polyubiquitination and proteasomal degradation of β-catenin. In turn, the KCTD9-ZNT9 interaction disrupted interactions between β-catenin and ZNT9, thereby leading to decreased β-catenin target gene expression and the inhibition of Wnt signaling. In conclusion, our findings propose that KCTD9 functions as a tumor suppressor that inhibits CRC cell proliferation and metastasis by inactivating the Wnt/β-catenin pathway. Moreover, its frequent downregulation in CRC suggests KCTD9 as a potential prognostic and therapeutic target in CRC.
Astrocytic SARM1 promotes neuroinflammation and axonal demyelination in experimental autoimmune encephalomyelitis through inhibiting GDNF signaling
Authors: Jin Lingting , Zhang Jingjing , Hua Xin , Xu Xingxing , Li Jia , Wang Jiaojiao , Wang Mianxian , Liu Huitao , Qiu Haoyu , Chen Man , Zhang Xu , Wang Ying , Huang Zhihui 
Published: September 2022

AbstractAstrocytes are important components of the innate immune response in the central nervous system (CNS), involving in the inflammatory and neurotoxic responses that occur in CNS diseases, such as multiple sclerosis (MS). Recent studies have shown that SARM1 plays a critical role in axonal degeneration and inflammation. However, the detailed role of astrocytic SARM1 in MS remains unclear. Here, we established the MS model of mice - experimental autoimmune encephalomyelitis (EAE) and found that SARM1 was upregulated in astrocytes of the spinal cords of EAE mice. Moreover, conditional knockout of astrocytic SARM1 (SARM1GFAP-CKO mice, SARM1Aldh1L1-CKO mice) delayed EAE with later onset, alleviated the inflammatory infiltration, and inhibited the demyelination and neuronal death. Mechanically, RNA-seq revealed that the expression of glial-derived neurotrophic factor (GDNF) was upregulated in SARM1−/− astrocytes. Western blot and immunostaining further confirmed the upregulation of GDNF in spinal cord astrocytes of SARM1GFAP-CKO EAE mice. Interestingly, the downregulation of GDNF by streptozotocin (STZ, a drug used to downregulate GDNF) treatment worsened the deficits of SARM1GFAP-CKO EAE mice. These findings identify that astrocytic SARM1 promotes neuroinflammation and axonal demyelination in EAE by inhibiting the expression of GDNF, reveal the novel role of SARM1/GDNF signaling in EAE, and provide new therapeutic ideas for the treatment of MS.
Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
Authors: Kieu Trinh-Le-Vi , Pierre Léa , Derangère Valentin , Perrey Sabrina , Truntzer Caroline , Jalil Antoine , Causse Sébastien , Groetz Emma , Dumont Adélie , Guyard Laura , Arnould Laurent , de Barros Jean-Paul Pais , Apetoh Lionel , Rébé Cédric , Limagne Emeric , Jourdan Tony , Demizieux Laurent , Masson David , Thomas Charles , Ghiringhelli François , Rialland Mickaël 
Published: September 2022

AbstractMetastatic breast cancer cannot be cured, and alteration of fatty acid metabolism contributes to tumor progression and metastasis. Here, we were interested in the elongation of very long-chain fatty acids protein 5 (Elovl5) in breast cancer. We observed that breast cancer tumors had a lower expression of Elovl5 than normal breast tissues. Furthermore, low expression of Elovl5 is associated with a worse prognosis in ER+ breast cancer patients. In accordance with this finding, decrease of Elovl5 expression was more pronounced in ER+ breast tumors from patients with metastases in lymph nodes. Although downregulation of Elovl5 expression limited breast cancer cell proliferation and cancer progression, suppression of Elovl5 promoted EMT, cell invasion and lung metastases in murine breast cancer models. The loss of Elovl5 expression induced upregulation of TGF-β receptors mediated by a lipid-droplet accumulation-dependent Smad2 acetylation. As expected, inhibition of TGF-β receptors restored proliferation and dampened invasion in low Elovl5 expressing cancer cells. Interestingly, the abolition of lipid-droplet formation by inhibition of diacylglycerol acyltransferase activity reversed induction of TGF-β receptors, cell invasion, and lung metastasis triggered by Elovl5 knockdown. Altogether, we showed that Elovl5 is involved in metastasis through lipid droplets-regulated TGF-β receptor expression and is a predictive biomarker of metastatic ER+ breast cancer.
Redox regulation of the immune response
Authors: Morris Gerwyn , Gevezova Maria , Sarafian Victoria , Maes Michael 
Published: September 2022

AbstractThe immune-inflammatory response is associated with increased nitro-oxidative stress. The aim of this mechanistic review is to examine: (a) the role of redox-sensitive transcription factors and enzymes, ROS/RNS production, and the activity of cellular antioxidants in the activation and performance of macrophages, dendritic cells, neutrophils, T-cells, B-cells, and natural killer cells; (b) the involvement of high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), paraoxonase-1 (PON1), and oxidized phospholipids in regulating the immune response; and (c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor-κB, HIF1α, the mechanistic target of rapamycin, the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, mitogen-activated protein kinases, 5' AMP-activated protein kinase, and peroxisome proliferator-activated receptor. The performance and survival of individual immune cells is under redox control and depends on intracellular and extracellular levels of ROS/RNS. They are heavily influenced by cellular antioxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2, and the HDL/ApoA1/PON1 complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.
Influenza A virus use of BinCARD1 to facilitate the binding of viral NP to importin α7 is counteracted by TBK1-p62 axis-mediated autophagy
Authors: Wang Xuyuan , Jiang Li , Wang Guangwen , Shi Wenjun , Hu Yuzhen , Wang Bo , Zeng Xianying , Tian Guobin , Deng Guohua , Shi Jianzhong , Liu Liling , Li Chengjun , Chen Hualan 
Published: September 2022

AbstractAs a major component of the viral ribonucleoprotein (vRNP) complex in influenza A virus (IAV), nucleoprotein (NP) interacts with isoforms of importin α family members, leading to the import of itself and vRNP complex into the nucleus, a process pivotal in the replication cycle of IAV. In this study, we found that BinCARD1, an isoform of Bcl10-interacting protein with CARD (BinCARD), was leveraged by IAV for efficient viral replication. BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity. Moreover, we found that BinCARD1 interacted with NP to promote NP binding to importin α7, an adaptor in the host nuclear import pathway. However, we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3, and that TBK1 appeared to degrade BinCARD1. We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage, which was recognized by the TBK1-p62 axis for autophagic degradation. Overall, our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication, and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.
Genetic, maternal, and environmental influences on sociality in a pedigreed primate population
Authors: Godoy Irene , Korsten Peter , Perry Susan E. 
Published: September 2022

AbstractVarious aspects of sociality in mammals (e.g., dyadic connectedness) are linked with measures of biological fitness (e.g., longevity). How within- and between-individual variation in relevant social traits arises in uncontrolled wild populations is challenging to determine but is crucial for understanding constraints on the evolution of sociality. We use an advanced statistical method, known as the ‘animal model’, which incorporates pedigree information, to look at social, genetic, and environmental influences on sociality in a long-lived wild primate. We leverage a longitudinal database spanning 20 years of observation on individually recognized white-faced capuchin monkeys (Cebus capucinus imitator), with a multi-generational pedigree. We analyze two measures of spatial association, using repeat sampling of 376 individuals (mean: 53.5 months per subject, range: 6–185 months per subject). Conditioned on the effects of age, sex, group size, seasonality, and El Niño–Southern Oscillation phases, we show low to moderate long-term repeatability (across years) of the proportion of time spent social (posterior mode [95% Highest Posterior Density interval]: 0.207 [0.169, 0.265]) and of average number of partners (0.144 [0.113, 0.181]) (latent scale). Most of this long-term repeatability could be explained by modest heritability (h2social: 0.152 [0.094, 0.207];h2partners: 0.113 [0.076, 0.149]) with small long-term maternal effects (m2social: 0.000 [0.000, 0.045];m2partners: 0.000 [0.000, 0.041]). Our models capture the majority of variance in our behavioral traits, with much of the variance explained by temporally changing factors, such as group of residence, highlighting potential limits to the evolvability of our trait due to social and environmental constraints.
Active learning of reactive Bayesian force fields applied to heterogeneous catalysis dynamics of H/Pt
Authors: Vandermause Jonathan , Xie Yu , Lim Jin Soo , Owen Cameron J. , Kozinsky Boris 
Published: September 2022

AbstractAtomistic modeling of chemically reactive systems has so far relied on either expensive ab initio methods or bond-order force fields requiring arduous parametrization. Here, we describe a Bayesian active learning framework for autonomous “on-the-fly” training of fast and accurate reactive many-body force fields during molecular dynamics simulations. At each time-step, predictive uncertainties of a sparse Gaussian process are evaluated to automatically determine whether additional ab initio training data are needed. We introduce a general method for mapping trained kernel models onto equivalent polynomial models whose prediction cost is much lower and independent of the training set size. As a demonstration, we perform direct two-phase simulations of heterogeneous H2turnover on the Pt(111) catalyst surface at chemical accuracy. The model trains itself in three days and performs at twice the speed of a ReaxFF model, while maintaining much higher fidelity to DFT and excellent agreement with experiment.
An image interaction approach to quantum-phase engineering of two-dimensional materials
Authors: Di Giulio Valerio , Gonçalves P. A. D. , García de Abajo F. Javier 
Published: September 2022

AbstractTuning electrical, optical, and thermal material properties is central for engineering and understanding solid-state systems. In this scenario, atomically thin materials are appealing because of their sensitivity to electric and magnetic gating, as well as to interlayer hybridization. Here, we introduce a radically different approach to material engineering relying on the image interaction experienced by electrons in a two-dimensional material when placed in proximity of an electrically neutral structure. We theoretically show that electrons in a semiconductor atomic layer acquire a quantum phase resulting from the image potential induced by the presence of a neighboring periodic array of conducting ribbons, which in turn modifies the optical, electrical, and thermal properties of the monolayer, giving rise to additional interband optical absorption, plasmon hybridization, and metal-insulator transitions. Beyond its fundamental interest, material engineering based on the image interaction represents a disruptive approach to tailor the properties of atomic layers for application in nanodevices.
Protein import motor complex reacts to mitochondrial misfolding by reducing protein import and activating mitophagy
Authors: Michaelis Jonas Benjamin , Brunstein Melinda Elaine , Bozkurt Süleyman , Alves Ludovico , Wegner Martin , Kaulich Manuel , Pohl Christian , Münch Christian 
Published: September 2022

AbstractMitophagy is essential to maintain mitochondrial function and prevent diseases. It activates upon mitochondria depolarization, which causes PINK1 stabilization on the mitochondrial outer membrane. Strikingly, a number of conditions, including mitochondrial protein misfolding, can induce mitophagy without a loss in membrane potential. The underlying molecular details remain unclear. Here, we report that a loss of mitochondrial protein import, mediated by the pre-sequence translocase-associated motor complex PAM, is sufficient to induce mitophagy in polarized mitochondria. A genome-wide CRISPR/Cas9 screen for mitophagy inducers identifies components of the PAM complex. Protein import defects are able to induce mitophagy without a need for depolarization. Upon mitochondrial protein misfolding, PAM dissociates from the import machinery resulting in decreased protein import and mitophagy induction. Our findings extend the current mitophagy model to explain mitophagy induction upon conditions that do not affect membrane polarization, such as mitochondrial protein misfolding.