bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D GUMICS Simulations of Northward IMF Magnetotail Structure
Authors: Fryer L. J. , Fear R. C. , Gingell I. L. , Coxon J. C. , Palmroth M. , Hoilijoki S. , Janhunen P. , Kullen A. , Cassak P. A. 
Published: July 2023

AbstractThis study presents a re‐evaluation of the Kullen and Janhunen (2004, https://doi.org/10.5194/angeo-22-951-2004) global northward interplanetary magnetic field (IMF) simulation, using the Grand Unified Magnetosphere–Ionosphere Coupling Simulation version 4 (GUMICS‐4), a global MHD model. We investigate the dynamic coupling between northward IMF conditions and the Earth’s magnetotail and compare the results to observation‐based mechanisms for the formation of transpolar arcs. The results of this study reveal that under northward IMF conditions (and northward IMF initialization), a large closed field line region forms in the magnetotail, with similarities to transpolar arc structures observed from spacecraft data. This interpretation is supported by the simultaneous increase of closed flux measured in the magnetotail. However, the reconnection configuration differs in several respects from previously theorized magnetotail structures that have been inferred from both observations and simulations results and associated with transpolar arcs. We observe that dawn–dusk lobe regions form as a result of high‐latitude reconnection during the initialization stages, which later come into contact as the change in the IMF By component causes the magnetotail to twist. We conclude that in the GUMICS simulation, transpolar arc‐like structures are formed as a result of reconnection in the magnetotail, rather than high‐latitude reconnection or due to the mapping of the plasma sheet through a twisted magnetotail as interpreted from previous analysis of GUMICS simulations.
Decadal Indian Ocean Influence on the ENSO‐Indian Monsoon Teleconnection Mostly Apparent
Authors: Bódai Tamás , Aneesh Sundaresan , Lee June‐Yi , Lee Sun‐Seon 
Published: July 2023

Abstract“Decadal influence” on the El Niño–Southern Oscillation‐Indian summer monsoon teleconnection has been much studied but with plurality and ambiguity about the concept of influence. Here (a) we provide formal definitions of the apparent influence of a specific factor on the teleconnection, as correlation coefficients, which enable us to test them as null‐hypotheses. Using the recently released Community Earth System Model v2 Large Ensemble data, we show that a 50% chance for the detection of the apparent Indian Ocean influence under stationary conditions might take 2,000 years of data. However, (b) we find that this influence is mostly apparent, causally not dominant, indeed, as it originates more dominantly from fluctuations of the decadal moving window El Niño–Southern Oscillation variability, which causally influences an Indian Ocean Dipole‐like moving window mean state. (c) We also show that unattributed so‐called “decadal influence,” defined as a deviation from a linear regression model of the teleconnection as a null‐hypothesis, cannot be detected in twentieth century observations in South Asia even regionally. However, as a new insight, we find our new simple influence concept as a significant correlation coefficient to be possibly consistent with such a null‐hypothesis.
Tree‐Ring Derived Avalanche Frequency and Climate Associations in a High‐Latitude, Maritime Climate
Authors: Peitzsch E. H. , Hood E. , Harley J. R. , Stahle D. K. , Kichas N. E. , Wolken G. J. 
Published: July 2023

AbstractSnow avalanches are a natural hazard in mountainous areas worldwide with severe impacts that include fatalities, damage to infrastructure, disruption to commerce, and landscape disturbance. Understanding long‐term avalanche frequency patterns, and associated climate and weather influences, improves our understanding of how climate change may affect avalanche activity. We used dendrochronological techniques to evaluate the historical frequency of large magnitude avalanches (LMAs) in the high‐latitude climate of southeast Alaska, United States. We collected 434 cross sections throughout six avalanche paths near Juneau, Alaska. This resulted in 2706 identified avalanche growth disturbances between 1720 and 2018, which allowed us to reconstruct 82 years with LMA activity across three sub‐regions. By combining this tree‐ring‐derived avalanche data set with a suite of climate and atmospheric variables and applying a generalized linear model to fit a binomial regression, we found that February and March precipitation and the Oceanic Niño Index (ONI) were significant predictors of LMA activity in the study area. Specifically, LMA activity occurred during winters with substantial February and March precipitation and neutral or negative (cold) ONI values, while years not characterized by LMAs occur more frequently during warm winters (positive ONI values). Our examination of the climate‐avalanche relationship in southeast Alaska sheds light on important climate variables and physical processes associated with LMA years. These results can be used to inform long‐term infrastructure planning and avalanche mitigation operations in an urban area, such as Juneau, where critical infrastructure is subject to substantial avalanche hazard.
ChatGPT for shaping the future of dentistry: the potential of multi-modal large language model
Authors: Huang Hanyao , Zheng Ou , Wang Dongdong , Yin Jiayi , Wang Zijin , Ding Shengxuan , Yin Heng , Xu Chuan , Yang Renjie , Zheng Qian , Shi Bing 
Published: July 2023

AbstractThe ChatGPT, a lite and conversational variant of Generative Pretrained Transformer 4 (GPT-4) developed by OpenAI, is one of the milestone Large Language Models (LLMs) with billions of parameters. LLMs have stirred up much interest among researchers and practitioners in their impressive skills in natural language processing tasks, which profoundly impact various fields. This paper mainly discusses the future applications of LLMs in dentistry. We introduce two primary LLM deployment methods in dentistry, including automated dental diagnosis and cross-modal dental diagnosis, and examine their potential applications. Especially, equipped with a cross-modal encoder, a single LLM can manage multi-source data and conduct advanced natural language reasoning to perform complex clinical operations. We also present cases to demonstrate the potential of a fully automatic Multi-Modal LLM AI system for dentistry clinical application. While LLMs offer significant potential benefits, the challenges, such as data privacy, data quality, and model bias, need further study. Overall, LLMs have the potential to revolutionize dental diagnosis and treatment, which indicates a promising avenue for clinical application and research in dentistry.
N-Acetyltransferase 9 ameliorates Aβ42-mediated neurodegeneration in the Drosophila eye
Authors: Deshpande Prajakta , Chimata Anuradha Venkatakrishnan , Snider Emily , Singh Aditi , Kango-Singh Madhuri , Singh Amit 
Published: July 2023

AbstractAlzheimer’s disease (AD), a progressive neurodegenerative disorder, manifests as accumulation of amyloid-beta-42 (Aβ42) plaques and intracellular accumulation of neurofibrillary tangles (NFTs) that results in microtubule destabilization. Targeted expression of human Aβ42 (GMR > Aβ42) in developing Drosophila eye retinal neurons results in Aβ42 plaque(s) and mimics AD-like extensive neurodegeneration. However, there remains a gap in our understanding of the underlying mechanism(s) for Aβ42-mediated neurodegeneration. To address this gap in information, we conducted a forward genetic screen, and identified N-acetyltransferase 9 (Mnat9) as a genetic modifier of GMR > Aβ42 neurodegenerative phenotype. Mnat9 is known to stabilize microtubules by inhibiting c-Jun-N- terminal kinase (JNK) signaling. We found that gain-of-function of Mnat9 rescues GMR > Aβ42 mediated neurodegenerative phenotype whereas loss-of-function of Mnat9 exhibits the converse phenotype of enhanced neurodegeneration. Here, we propose a new neuroprotective function of Mnat9 in downregulating the JNK signaling pathway to ameliorate Aβ42-mediated neurodegeneration, which is independent of its acetylation activity. Transgenic flies expressing human NAT9 (hNAT9), also suppresses Aβ42-mediated neurodegeneration thereby suggesting functional conservation in the interaction of fly Mnat9 or hNAT9 with JNK-mediated neurodegeneration. These studies add to the repertoire of molecular mechanisms that mediate cell death response following accumulation of Aβ42 and may provide new avenues for targeting neurodegeneration.
UCHL1 facilitates protein aggregates clearance to enhance neural stem cell activation in spinal cord injury
Authors: Ding Lu , Chu Weiwei , Xia Yu , Shi Ming , Li Tian , Zhou Feng-Quan , Deng David Y. B. 
Published: July 2023

AbstractActivation of endogenous neural stem cells (NSCs) is greatly significant for the adult neurogenesis; however, it is extremely limited in the spinal cord after injury. Recent evidence suggests that accumulation of protein aggregates impairs the ability of quiescent NSCs to activate. Ubiquitin c-terminal hydrolase l-1 (UCHL1), an important deubiquitinating enzyme, plays critical roles in protein aggregations clearance, but its effects on NSC activation remains unknown. Here, we show that UCHL1 promotes NSC activation by clearing protein aggregates through ubiquitin-proteasome approach. Upregulation of UCHL1 facilitated the proliferation of spinal cord NSCs after spinal cord injury (SCI). Based on protein microarray analysis of SCI cerebrospinal fluid, it is further revealed that C3+ neurotoxic reactive astrocytes negatively regulated UCHL1 and proteasome activity via C3/C3aR signaling, led to increased abundances of protein aggregations and decreased NSC proliferation. Furthermore, blockade of reactive astrocytes or C3/C3aR pathway enhanced NSC activation post-SCI by reserving UCHL1 and proteasome functions. Together, this study elucidated a mechanism regulating NSC activation in the adult spinal cord involving the UCHL1-proteasome approach, which may provide potential molecular targets and new insights for NSC fate regulation.
Administration of AG490 decreases the senescence of umbilical cord-mesenchymal stem cells and promotes the cytotherapeutic effect in liver fibrosis
Authors: Jiang Chenhao , Chen Huaxin , Kang Yinqian , He Xinyi , Huang Jianyang , Lu Tongyu , Sui Xin , Chen Haitian , Xiao Jiaqi , Zhang Jiebin , Zhang Hanwen , Zheng Jun , Yang Yang , Yao Jia , Cai Jianye , Zhang Yingcai 
Published: July 2023

AbstractThe therapeutic potential of umbilical cord-mesenchymal stem cell (UC-MSC) transplantation in liver fibrosis has been highlighted. However, the fate of transplanted MSCs in the fibrotic microenvironment remains unclear. In this study, we aim to uncover the fate of transplanted MSCs and develop targeting strategies that could enhance the therapeutic efficacy of MSC therapy in liver fibrosis. We used human UC-MSCs as the study object. For in vitro experiments, we stimulated UC-MSCs with several fibrotic-related factors (Liver fibrotic Factors, LF), including TGFβ, TNFα and IFNγ for downstream investigations. We co-cultured LF-treated UC-MSCs with hepatic stellate cell line LX-2 to assess the anti-fibrotic effect. We showed that upon LF stimulation, UC-MSCs exhibited reduced anti-fibrotic activity and underwent rapid senescence. Pathway analysis showed that JAK/STAT3 signaling was highly activated upon LF stimulation, which significantly elevated senescence-associated secretory phenotype (SASP) and senescence in UC-MSCs and could be reversed by a specific JAK inhibitor AG490. Moreover, using both carbon tetrachloride (CCl4) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induce fibrosis models, we demonstrated that AG490 pretreatment promoted UC-MSCs survival within the fibrotic liver microenvironment and exhibited enhance therapeutic efficacy. Overall, we showed that targeting MSC senescence in vivo through AG490 pretreatment could enhance the anti-fibrotic activities of UC-MSCs.
Research progress on post-translational modification of proteins and cardiovascular diseases
Authors: Cheng XueLi , Wang Kai , Zhao Yan , Wang Kun 
Published: July 2023

AbstractCardiovascular diseases (CVDs) such as atherosclerosis, myocardial remodeling, myocardial ischemia-reperfusion (I/R) injury, heart failure, and oxidative stress are among the greatest threats to human health worldwide. Cardiovascular pathogenesis has been studied for decades, and the influence of epigenetic changes on CVDs has been extensively studied. Post-translational modifications (PTMs), including phosphorylation, glycosylation, methylation, acetylation, ubiquitination, ubiquitin-like and nitrification, play important roles in the normal functioning of the cardiovascular system. Over the past decade, with the application of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), an increasing number novel acylation modifications have been discovered, including propionylation, crotonylation, butyrylation, succinylation, lactylation, and isonicotinylation. Each change in protein conformation has the potential to alter protein function and lead to CVDs, and this process is usually reversible. This article summarizes the mechanisms underlying several common PTMs involved in the occurrence and development of CVDs.
Ionizing radiation triggers mitophagy to enhance DNA damage in cancer cells
Authors: Ren Yanxian , Yang Pengfei , Li Chenghao , Wang Wen-an , Zhang Tianyi , Li Jin , Li Haining , Dong Chunlu , Meng Wenbo , Zhou Heng 
Published: July 2023

AbstractRadiotherapy is an important cancer treatment strategy that causes DNA damage in tumor cells either directly or indirectly. Autophagy is a physiological process linked to DNA damage. Mitophagy is a form of autophagy, which specifically targets and eliminates impaired mitochondria, thereby upholding cellular homeostasis. However, the connection between DNA damage and mitophagy has yet to be fully elucidated. We found that mitophagy, as an upstream signal, increases ionizing radiation-induced DNA damage by downregulating or overexpressing key mitophagy proteins Parkin and BNIP3. Enhancing the basal level of mitophagy in conjunction with X-ray irradiation can potentially diminish cell cycle arrest at the G2/M phase, substantially elevate the accumulation of γ-H2AX, 53BP1, and PARP1 foci within the nucleus, augment DNA damage, and facilitate the demise of tumor cells. Consequently, this approach prolongs the survival of melanoma-bearing mice. The findings of this study are anticipated to offer a therapeutic approach for enhancing the therapeutic effectiveness of radiotherapy.
Host susceptibility and structural and immunological insight of S proteins of two SARS-CoV-2 closely related bat coronaviruses
Authors: Ou Xiuyuan , Xu Ge , Li Pei , Liu Yan , Zan Fuwen , Liu Pan , Hu Jiaxin , Lu Xing , Dong Siwen , Zhou Yao , Mu Zhixia , Wu Zhiqiang , Wang Jianwei , Jin Qi , Liu Pinghuang , Lu Jian , Wang Xiangxi , Qian Zhaohui 
Published: July 2023

AbstractThe bat coronaviruses (CoV) BANAL-20-52 and BANAL-20-236 are two newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely related coronaviruses (SC2r-CoV) and the genome of BANAL-20-52 shares the highest homology with SARS-CoV-2. However, the risk of their potential zoonotic transmission has not been fully evaluated. Here, we determined their potential host susceptibility among 13 different bat species and 26 different animal species, and found that both might have extensive host ranges, indicating high zoonotic transmission potential. We also determined the cryo-EM structures of BANAL-20-52 and BANAL-20-236 S proteins at pH 5.5 and the complex of BANAL-20-236 S1 and Rhinolophus affinis ACE2, and found that both trimeric S proteins adopt all three receptor binding domains (RBDs) in “closed” conformation and are more compact than SARS-CoV-2. Strikingly, the unique sugar moiety at N370 of bat SC2r-CoVs acts like a “bolt” and crosses over two neighboring subunits, facilitating the S proteins in the locked conformation and underpinning the architecture stability. Removal of the glycosylation at N370 by a T372A substitution substantially enhances virus infectivity but becomes highly sensitive to trypsin digestion at pH 5.5, a condition roughly mimicking the insectivorous bat’s stomach digestion. In contrast, WT S proteins of SC2r-CoVs showed considerable resistance to trypsin digestion at pH 5.5, indicating that the highly conserved T372 in bat CoVs might result from the selective advantages in stability during the fecal-oral transmission over A372. Moreover, the results of cross-immunogenicity among S proteins of SARS-CoV-2, BANAL-20-52, and BANAL-20-236 showed that A372 pseudoviruses are more sensitive to anti-S sera than T372, indicating that immune evasion might also play a role in the natural selection of T372 over A372 during evolution. Finally, residues 493 and 498 of the S protein affect host susceptibility, and residue 498 also influences the immunogenicity of the S protein. Together, our findings aid a better understanding of the molecular basis of CoV entry, selective evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts of these viruses to prevent potential outbreaks.
Generation of out-of-plane polarized spin current by spin swapping
Authors: Hazra Binoy K. , Pal Banabir , Jeon Jae-Chun , Neumann Robin R. , Göbel Börge , Grover Bharat , Deniz Hakan , Styervoyedov Andriy , Meyerheim Holger , Mertig Ingrid , Yang See-Hun , Parkin Stuart S. P. 
Published: July 2023

AbstractThe generation of spin currents and their application to the manipulation of magnetic states is fundamental to spintronics. Of particular interest are chiral antiferromagnets that exhibit properties typical of ferromagnetic materials even though they have negligible magnetization. Here, we report the generation of a robust spin current with both in-plane and out-of-plane spin polarization in epitaxial thin films of the chiral antiferromagnet Mn3Sn in proximity to permalloy thin layers. By employing temperature-dependent spin-torque ferromagnetic resonance, we find that the chiral antiferromagnetic structure of Mn3Sn is responsible for an in-plane polarized spin current that is generated from the interior of the Mn3Sn layer and whose temperature dependence follows that of this layer’s antiferromagnetic order. On the other hand, the out-of-plane polarized spin current is unrelated to the chiral antiferromagnetic structure and is instead the result of scattering from the Mn3Sn/permalloy interface. We substantiate the later conclusion by performing studies with several other non-magnetic metals all of which are found to exhibit out-of-plane polarized spin currents arising from the spin swapping effect.
NPC1-dependent alterations in KV2.1–CaV1.2 nanodomains drive neuronal death in models of Niemann-Pick Type C disease
Authors: Casas Maria , Murray Karl D. , Hino Keiko , Vierra Nicholas C. , Simó Sergi , Trimmer James S. , Dixon Rose E. , Dickson Eamonn J. 
Published: July 2023

AbstractLysosomes communicate through cholesterol transfer at endoplasmic reticulum (ER) contact sites. At these sites, the Niemann Pick C1 cholesterol transporter (NPC1) facilitates the removal of cholesterol from lysosomes, which is then transferred to the ER for distribution to other cell membranes. Mutations in NPC1 result in cholesterol buildup within lysosomes, leading to Niemann-Pick Type C (NPC) disease, a progressive and fatal neurodegenerative disorder. The molecular mechanisms connecting NPC1 loss to NPC-associated neuropathology remain unknown. Here we show both in vitro and in an animal model of NPC disease that the loss of NPC1 function alters the distribution and activity of voltage-gated calcium channels (CaV). Underlying alterations in calcium channel localization and function are KV2.1 channels whose interactions drive calcium channel clustering to enhance calcium entry and fuel neurotoxic elevations in mitochondrial calcium. Targeted disruption of KV2–CaVinteractions rescues aberrant CaV1.2 clustering, elevated mitochondrial calcium, and neurotoxicity in vitro. Our findings provide evidence that NPC is a nanostructural ion channel clustering disease, characterized by altered distribution and activity of ion channels at membrane contacts, which contribute to neurodegeneration.
Subunit gating resulting from individual protonation events in Kir2 channels
Authors: Maksaev Grigory , Bründl-Jirout Michael , Stary-Weinzinger Anna , Zangerl-Plessl Eva-Maria , Lee Sun-Joo , Nichols Colin G. 
Published: July 2023

AbstractInwardly rectifying potassium (Kir) channels open at the ‘helix bundle crossing’ (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K+ ion occupancy, and K+ conductance. Ion channel gating and conductance are classically understood as separate processes. The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as ‘gated’ substates.
Enantioselectivity of discretized helical supramolecule consisting of achiral cobalt phthalocyanines via chiral-induced spin selectivity effect
Authors: Aizawa Hiroki , Sato Takuro , Maki-Yonekura Saori , Yonekura Koji , Takaba Kiyofumi , Hamaguchi Tasuku , Minato Taketoshi , Yamamoto Hiroshi M. 
Published: July 2023

AbstractEnantioselectivity of helical aggregation is conventionally directed either by its homochiral ingredients or by introduction of chiral catalysis. The fundamental question, then, is whether helical aggregation that consists only of achiral components can obtain enantioselectivity in the absence of chiral catalysis. Here, by exploiting enantiospecific interaction due to chiral-induced spin selectivity (CISS) that has been known to work to enantio-separate a racemic mixture of chiral molecules, we demonstrate the enantioselectivity in the assembly of mesoscale helical supramolecules consisting of achiral cobalt phthalocyanines. The helical nature in our supramolecules is revealed to be mesoscopically incorporated by dislocation-induced discretized twists, unlike the case of chiral molecules whose chirality are determined microscopically by chemical bond. The relevance of CISS effect in the discretized helical supramolecules is further confirmed by the appearance of spin-polarized current through the system. These observations mean that the application of CISS-based enantioselectivity is no longer limited to systems with microscopic chirality but is expanded to the one with mesoscopic chirality.