bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volume Transport Time Series and Variability of the North Atlantic Eastern Boundary Current at Goban Spur
Authors: Moritz Martin , Jochumsen Kerstin , Kieke Dagmar , Klein Birgit , Klein Holger , Köllner Manuela , Rhein Monika 
Published: July 2021

AbstractThe Eastern Boundary Current is an essential part of the water mass exchange between the subtropical and subpolar North Atlantic. Here, we study the offshore branch of the European Shelf Current (ESC) over the Goban Spur slope area off Ireland. Our analysis is based on current measurements obtained from a multiyear mooring effort, complemented by ship‐board observations along a hydrographic section, satellite‐derived estimates of absolute dynamic topography with geostrophic currents, and float trajectories. These data serve to quantify the offshore branch of the ESC on intraannual to interannual timescales. From the moored observations, we derive a mean poleward along‐slope volume flux of 3.7 0.7 Sv for the period 2017–2019. Using a multilinear regression model and geostrophic surface velocities, we extend the time series to the period 1993–2019 and obtain a long‐term mean transport of 3.2 0.4 Sv. Both time series show strong variability ranging from −7.5 to 15.7 Sv. The variability is linked to a dynamic eddy field, especially a stationary cyclonic circulation pattern near the mooring array, and meandering of current branches originating from the North Atlantic Current.We find no evidence of a consistent deep boundary current extending from the shelf break to the position of the offshore mooring (4,500 m depth), but confirm a persistent along‐slope flow at the shallower slope (1,500 m depth). Geostrophic surface velocities and float trajectories reveal that the offshore branch of the ESC does not follow a clear northward path from the eastern subtropical regions but rather indicate the intermittent character of the flow.
SARS-CoV-2 test positivity rate in Reno, Nevada: association with PM2.5 during the 2020 wildfire smoke events in the western United States
Authors: Kiser Daniel , Elhanan Gai , Metcalf William J. , Schnieder Brendan , Grzymski Joseph J. 
Published: July 2021

Abstract
Background
Air pollution has been linked to increased susceptibility to SARS-CoV-2. Thus, it has been suggested that wildfire smoke events may exacerbate the COVID-19 pandemic.

Objectives
Our goal was to examine whether wildfire smoke from the 2020 wildfires in the western United States was associated with an increased rate of SARS-CoV-2 infections in Reno, Nevada.

Methods
We conducted a time-series analysis using generalized additive models to examine the relationship between the SARS-CoV-2 test positivity rate at a large regional hospital in Reno and ambient PM2.5 from 15 May to 20 Oct 2020.

Results
We found that a 10 µg/m3 increase in the 7-day average PM2.5 concentration was associated with a 6.3% relative increase in the SARS-CoV-2 test positivity rate, with a 95% confidence interval (CI) of 2.5 to 10.3%. This corresponded to an estimated 17.7% (CI: 14.4–20.1%) increase in the number of cases during the time period most affected by wildfire smoke, from 16 Aug to 10 Oct.

Significance
Wildfire smoke may have greatly increased the number of COVID-19 cases in Reno. Thus, our results substantiate the role of air pollution in exacerbating the pandemic and can help guide the development of public preparedness policies in areas affected by wildfire smoke, as wildfires are likely to coincide with the COVID-19 pandemic in 2021.
CtBP1/2 differentially regulate genomic stability and DNA repair pathway in high-grade serous ovarian cancer cell
Authors: He YingYing , He Zhicheng , Lin Jian , Chen Cheng , Chen Yuanzhi , Liu Shubai 
Published: July 2021

AbstractThe C-terminal binding proteins (CtBPs), CtBP1 and CtBP2, are transcriptional co-repressor that interacts with multiple transcriptional factors to modulate the stability of chromatin. CtBP proteins were identified with overexpression in the high-grade serous ovarian carcinoma (HGSOC). However, little is known about CtBP proteins’ regulatory roles in genomic stability and DNA repair in HGSOC. In this study, we combined whole-transcriptome analysis with multiple research methods to investigate the role of CtBP1/2 in genomic stability. Several key functional pathways were significantly enriched through whole transcription profile analysis of CtBP1/2 knockdown SKOV3 cells, including DNA damage repair, apoptosis, and cell cycle. CtBP1/2 knockdown induced cancer cell apoptosis, increased genetic instability, and enhanced the sensitivity to DNA damage agents, such as γ-irradiation and chemotherapy drug (Carboplatin and etoposide). The results of DNA fiber assay revealed that CtBP1/2 contribute differentially to the integrity of DNA replication track and stability of DNA replication recovery. CtBP1 protects the integrity of stalled forks under metabolic stress condition during prolonged periods of replication, whereas CtBP2 acts a dominant role in stability of DNA replication recovery. Furthermore, CtBP1/2 knockdown shifted the DSBs repair pathway from homologous recombination (HR) to non-homologous end joining (NHEJ) and activated DNA-PK in SKOV3 cells. Interesting, blast through TCGA tumor cases, patients with CtBP2 genetic alternation had a significantly longer overall survival time than unaltered patients. Together, these results revealed that CtBP1/2 play a different regulatory role in genomic stability and DSBs repair pathway bias in serous ovarian cancer cells. It is possible to generate novel potential targeted therapy strategy and translational application for serous ovarian carcinoma patients with a predictable better clinical outcome.
Retinoblastoma cell-derived exosomes promote angiogenesis of human vesicle endothelial cells through microRNA‐92a-3p
Authors: Chen Shuilian , Chen Xi , Luo Qian , Liu Xuan , Wang Xiao , Cui Zedu , He Anqi , He Shengyu , Jiang Zihua , Wu Nandan , Chen Pei , Yu Keming , Zhuang Jing 
Published: July 2021

AbstractExosomes derived from tumor cells play a key role in tumor development. In the present study, we identified the bioactivity of exosomes released from WERI-Rb1 retinoblastoma cells in tumor angiogenesis, as well as the underlying mechanism, through biochemical methods and animal experiments. Our in vitro data showed that exosomes could be engulfed by human vesicle endothelial cells (HUVECs), significantly promote cell viability and induce an inflammatory response in HUVECs by increasing the expression of a series of related genes, such as IL-1, IL-6, IL-8, MCP-1, VCAM1, and ICAM1. Significant increases in migration and tube formation were also observed in the HUVECs incubated with exosomes. Moreover, experiments with a nude mouse xenotransplantation model showed that exosomes injected near tumors could be strongly absorbed by tumor cells. The numbers of endothelial cells and blood vessels were significantly increased in tumor tissues treated with exosomes compared to control tissues. Furthermore, to reveal the mechanism underlying exosome-mediated angiogenesis in retinoblastoma, we analyzed the levels of 12 microRNAs in the exosomes. Specifically, our data showed that miR-92a-3p was enriched in RB exosomes. Accordingly, miR-92a-3p was increased in the HUVECs incubated with these exosomes. After treatment with a miR-92a-3p inhibitor, the promoting effect of exosomes on the migration and tube formation of HUVECs was significantly abrogated. The expression of the angiogenesis-related genes mentioned above was markedly decreased in HUVECs. Similarly, treatment with a microRNA mimic also demonstrated that miR-92a-3p was involved in the angiogenesis of HUVECs. More importantly, bioinformatics analysis predicted that Krüppel-like factor 2 (KLF2), a member of the KLF family of zinc-finger transcription factors, might be an active target of miR-92a-3p. Notably, this prediction was confirmed both in vitro and in vivo. Thus, our work suggests that exosomal miR-92a-3p is involved in tumor angiogenesis and might be a promising therapeutic candidate for retinoblastoma.
Induced TRIM21 ISGylation by IFN-β enhances p62 ubiquitination to prevent its autophagosome targeting
Authors: Jin Jie , Meng Xianbin , Huo Yi , Deng Haiteng 
Published: July 2021

AbstractThe tripartite motif-containing protein 21 (TRIM21) plays important roles in autophagy and innate immunity. Here, we found that HECT and RLD domain containing E3 ubiquitin protein ligase 5 (HERC5), as an interferon-stimulated gene 15 (ISG15) E3 ligase, catalyzes the ISGylation of TRIM21 at the Lys260 and Lys279 residues. Moreover, IFN-β also induces TRIM21 ISGylation at multiple lysine residues, thereby enhancing its E3 ligase activity for K63-linkage-specific ubiquitination and resulting in increased levels of TRIM21 and p62 K63-linked ubiquitination. The K63-linked ubiquitination of p62 at Lys7 prevents its self-oligomerization and targeting to the autophagosome. Taken together, our study suggests that the ISGylation of TRIM21 plays a vital role in regulating self-oligomerization and localization of p62 in the autophagy induced by IFN-β.
miR-301a-3p induced by endoplasmic reticulum stress mediates the occurrence and transmission of trastuzumab resistance in HER2-positive gastric cancer
Authors: Guo Jing , Zhong Xuxian , Tan Qinglin , Yang Shengnan , Liao Jiaqi , Zhuge Jinke , Hong Ziyang , Deng Qiong , Zuo Qiang 
Published: July 2021

AbstractTrastuzumab resistance negatively influences the clinical efficacy of the therapy for human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC), and the underlying mechanisms remain elusive. Exploring the mechanisms and finding effective approaches to address trastuzumab resistance are of great necessity. Here, we confirmed that endoplasmic reticulum (ER) stress-induced trastuzumab resistance by up-regulating miR-301a-3p in HER2-positive GC cells. Moreover, we elucidated that miR-301a-3p mediated trastuzumab resistance by down-regulating the expression of leucine-rich repeats and immunoglobulin-like domains containing protein 1 (LRIG1) and subsequently activating the expression of insulin-like growth factor 1 receptor (IGF-1R) and fibroblast growth factor receptor 1 (FGFR1) under ER stress. We also found that intercellular transfer of miR-301a-3p by exosomes disseminated trastuzumab resistance. The present study demonstrated that exosomal miR-301a-3p could serve as a non-invasive biomarker for trastuzumab resistance, which was maybe a novel potential therapeutic target to overcome trastuzumab resistance and improve the curative effect of trastuzumab in HER2-positive GC patients.
Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines
Authors: Zheng Jiashuo , Sato Mami , Mishima Eikan , Sato Hideyo , Proneth Bettina , Conrad Marcus 
Published: July 2021

AbstractSorafenib, a protein kinase inhibitor approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma, has been repeatedly reported to induce ferroptosis by possibly involving inhibition of the cystine/glutamate antiporter, known as system xc−. Using a combination of well-defined genetically engineered tumor cell lines and canonical small molecule ferroptosis inhibitors, we now provide unequivocal evidence that sorafenib does not induce ferroptosis in a series of tumor cell lines unlike the cognate system xc− inhibitors sulfasalazine and erastin. We further show that only a subset of tumor cells dies by ferroptosis upon sulfasalazine and erastin treatment, implying that certain cell lines appear to be resistant to system xc− inhibition, while others undergo ferroptosis-independent cell death. From these findings, we conclude that sorafenib does not qualify as a bona fide ferroptosis inducer and that ferroptosis induced by system xc− inhibitors can only be achieved in a fraction of tumor cell lines despite robust expression of SLC7A11, the substrate-specific subunit of system xc−.
Structure of the trypanosome paraflagellar rod and insights into non-planar motility of eukaryotic cells
Authors: Zhang Jiayan , Wang Hui , Imhof Simon , Zhou Xueting , Liao Shiqing , Atanasov Ivo , Hui Wong H. , Hill Kent L. , Zhou Z. Hong 
Published: July 2021

AbstractEukaryotic flagella (synonymous with cilia) rely on a microtubule-based axoneme, together with accessory filaments to carryout motility and signaling functions. While axoneme structures are well characterized, 3D ultrastructure of accessory filaments and their axoneme interface are mostly unknown, presenting a critical gap in understanding structural foundations of eukaryotic flagella. In the flagellum of the protozoan parasite Trypanosoma brucei (T. brucei), the axoneme is accompanied by a paraflagellar rod (PFR) that supports non-planar motility and signaling necessary for disease transmission and pathogenesis. Here, we employed cryogenic electron tomography (cryoET) with sub-tomographic averaging, to obtain structures of the PFR, PFR-axoneme connectors (PACs), and the axonemal central pair complex (CPC). The structures resolve how the 8 nm repeat of the axonemal tubulin dimer interfaces with the 54 nm repeat of the PFR, which consist of proximal, intermediate, and distal zones. In the distal zone, stacked “density scissors” connect with one another to form a “scissors stack network (SSN)” plane oriented 45° to the axoneme axis; and ~370 parallel SSN planes are connected by helix-rich wires into a paracrystalline array with ~90% empty space. Connections from these wires to the intermediate zone, then to overlapping layers of the proximal zone and to the PACs, and ultimately to the CPC, point to a contiguous pathway for signal transmission. Together, our findings provide insights into flagellum-driven, non-planar helical motility of T. brucei and have broad implications ranging from cell motility and tensegrity in biology, to engineering principles in bionics.
Huntingtin fibrils with different toxicity, structure, and seeding potential can be interconverted
Authors: Mario Isas J. , Pandey Nitin K. , Xu Hui , Teranishi Kazuki , Okada Alan K. , Fultz Ellisa K. , Rawat Anoop , Applebaum Anise , Meier Franziska , Chen Jeannie , Langen Ralf , Siemer Ansgar B. 
Published: July 2021

AbstractThe first exon of the huntingtin protein (HTTex1) important in Huntington’s disease (HD) can form cross-β fibrils of varying toxicity. We find that the difference between these fibrils is the degree of entanglement and dynamics of the C-terminal proline-rich domain (PRD) in a mechanism analogous to polyproline film formation. In contrast to fibril strains found for other cross-β fibrils, these HTTex1 fibril types can be interconverted. This is because the structure of their polyQ fibril core remains unchanged. Further, we find that more toxic fibrils of low entanglement have higher affinities for protein interactors and are more effective seeds for recombinant HTTex1 and HTTex1 in cells. Together these data show how the structure of a framing sequence at the surface of a fibril can modulate seeding, protein-protein interactions, and thereby toxicity in neurodegenerative disease.
Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery
Authors: Walter Corvin , Marada Adinarayana , Suhm Tamara , Ernsberger Ralf , Muders Vera , Kücükköse Cansu , Sánchez-Martín Pablo , Hu Zehan , Aich Abhishek , Loroch Stefan , Solari Fiorella Andrea , Poveda-Huertes Daniel , Schwierzok Alexandra , Pommerening Henrike , Matic Stanka , Brix Jan , Sickmann Albert , Kraft Claudine , Dengjel Jörn , Dennerlein Sven , Brummer Tilman , Vögtle F.-Nora , Meisinger Chris 
Published: July 2021

AbstractThe translocase of the outer mitochondrial membrane TOM constitutes the organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, TOM presents the ideal target to adjust the mitochondrial proteome upon changing cellular demands. Here, we identify that the import receptor TOM70 is targeted by the kinase DYRK1A and that this modification plays a critical role in the activation of the carrier import pathway. Phosphorylation of TOM70Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase. This enables transfer of receptor-bound precursors to the translocation pore and initiates their import. Consequently, loss of TOM70Ser91 phosphorylation results in a strong decrease in import capacity of metabolite carriers. Inhibition of DYRK1A impairs mitochondrial structure and function and elicits a protective transcriptional response to maintain a functional import machinery. The DYRK1A-TOM70 axis will enable insights into disease mechanisms caused by dysfunctional DYRK1A, including autism spectrum disorder, microcephaly and Down syndrome.
IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes
Authors: James Olivia J. , Vandereyken Maud , Marchingo Julia M. , Singh Francois , Bray Susan E. , Wilson Jamie , Love Andrew G. , Swamy Mahima 
Published: July 2021

AbstractIntestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect and maintain the intestinal barrier. IEL respond to epithelial cell-derived IL-15, which is complexed to the IL-15 receptor α chain (IL-15/Rα). IL-15 is essential both for maintaining IEL homeostasis and inducing IEL responses to epithelial stress, which has been associated with Coeliac disease. Here, we apply quantitative mass spectrometry to IL-15/Rα-stimulated IEL to investigate how IL-15 directly regulates inflammatory functions of IEL. IL-15/Rα drives IEL activation through cell cycle regulation, upregulation of metabolic machinery and expression of a select repertoire of cell surface receptors. IL-15/Rα selectively upregulates the Ser/Thr kinases PIM1 and PIM2, which are essential for IEL to proliferate, grow and upregulate granzyme B in response to inflammatory IL-15. Notably, IEL from patients with Coeliac disease have high PIM expression. Together, these data indicate PIM kinases as important effectors of IEL responses to inflammatory IL-15.
A chalcogenide-cluster-based semiconducting nanotube array with oriented photoconductive behavior
Authors: Tang Jiaqi , Wang Xiang , Zhang Jiaxu , Wang Jing , Yin Wanjian , Li Dong-Sheng , Wu Tao 
Published: July 2021

AbstractThe interesting physical and chemical properties of carbon nanotubes (CNTs) have prompted the search for diverse inorganic nanotubes with different compositions to expand the number of available nanotechnology applications. Among these materials, crystalline inorganic nanotubes with well-defined structures and uniform sizes are suitable for understanding structure–activity relationships. However, their preparation comes with large synthetic challenges owing to their inherent complexity. Herein, we report the example of a crystalline nanotube array based on a supertetrahedral chalcogenide cluster, K3[K(Cu2Ge3Se9)(H2O)] (1). To the best of our knowledge, this nanotube array possesses the largest diameter of crystalline inorganic nanotubes reported to date and exhibits an excellent structure-dependent electric conductivity and an oriented photoconductive behavior. This work represents a significant breakthrough both in terms of the structure of cluster-based metal chalcogenides and in the conductivity of crystalline nanotube arrays (i.e., an enhancement of ~4 orders of magnitude).
Mediation of lubricated air films using spatially periodic dielectrophoretic effect
Authors: Vo Quoc , Tran Tuan 
Published: July 2021

AbstractA stone thrown in a lake captures air as it collides with water and sinks; likewise a rain drop falling on a flat surface traps air bubbles underneath and creates a spectacular splash. These natural occurrences, from bubble entrapment to liquid ejection, happen as air fails to escape from the closing gap between liquid and solid surfaces. Trapping of air is devastating for casting, coating, painting, and printing industries, or those intolerant of water entry noise. Attempts to eliminate the interfering air rely on either reducing the ambient pressure or modifying the solid surfaces. The former approach is inflexible in its implementation, while the latter one is inherently limited by the wetting speed of liquid or the draining capacity of air passages created on the solid. Here, we present a “divide and conquer” approach to split the thin air gap into tunnels and subsequently squeeze air out from the tunnels against its viscous resistance using spatially periodic dielectrophoretic force. We confirm the working principles by demonstrating suppression of both bubble entrapment and splash upon impacts of droplets on solid surfaces.
Arabidopsis MORC proteins function in the efficient establishment of RNA directed DNA methylation
Authors: Xue Yan , Zhong Zhenhui , Harris C. Jake , Gallego-Bartolomé Javier , Wang Ming , Picard Colette , Cao Xueshi , Hua Shan , Kwok Ivy , Feng Suhua , Jami-Alahmadi Yasaman , Sha Jihui , Gardiner Jason , Wohlschlegel James , Jacobsen Steven E. 
Published: July 2021

AbstractThe Microrchidia (MORC) family of ATPases are required for transposable element (TE) silencing and heterochromatin condensation in plants and animals, and C. elegans MORC-1 has been shown to topologically entrap and condense DNA. In Arabidopsis thaliana, mutation of MORCs has been shown to reactivate silent methylated genes and transposons and to decondense heterochromatic chromocenters, despite only minor changes in the maintenance of DNA methylation. Here we provide the first evidence localizing Arabidopsis MORC proteins to specific regions of chromatin and find that MORC4 and MORC7 are closely co-localized with sites of RNA-directed DNA methylation (RdDM). We further show that MORC7, when tethered to DNA by an artificial zinc finger, can facilitate the establishment of RdDM. Finally, we show that MORCs are required for the efficient RdDM mediated establishment of DNA methylation and silencing of a newly integrated FWA transgene, even though morc mutations have no effect on the maintenance of preexisting methylation at the endogenous FWA gene. We propose that MORCs function as a molecular tether in RdDM complexes to reinforce RdDM activity for methylation establishment. These findings have implications for MORC protein function in a variety of other eukaryotic organisms.
Evidence for one-dimensional chiral edge states in a magnetic Weyl semimetal Co3Sn2S2
Authors: Howard Sean , Jiao Lin , Wang Zhenyu , Morali Noam , Batabyal Rajib , Kumar-Nag Pranab , Avraham Nurit , Beidenkopf Haim , Vir Praveen , Liu Enke , Shekhar Chandra , Felser Claudia , Hughes Taylor , Madhavan Vidya 
Published: July 2021

AbstractThe physical realization of Chern insulators is of fundamental and practical interest, as they are predicted to host the quantum anomalous Hall (QAH) effect and topologically protected chiral edge states which can carry dissipationless current. Current realizations of the QAH state often require complex heterostructures and sub-Kelvin temperatures, making the discovery of intrinsic, high temperature QAH systems of significant interest. In this work we show that time-reversal symmetry breaking Weyl semimetals, being essentially stacks of Chern insulators with inter-layer coupling, may provide a new platform for the higher temperature realization of robust chiral edge states. We present combined scanning tunneling spectroscopy and theoretical investigations of the magnetic Weyl semimetal, Co3Sn2S2. Using modeling and numerical simulations we find that depending on the strength of the interlayer coupling, chiral edge states can be localized on partially exposed kagome planes on the surfaces of a Weyl semimetal. Correspondingly, our dI/dV maps on the kagome Co3Sn terraces show topological states confined to the edges which display linear dispersion. This work provides a new paradigm for realizing chiral edge modes and provides a pathway for the realization of higher temperature QAH effect in magnetic Weyl systems in the two-dimensional limit.