bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-coding RNAs in necroptosis, pyroptosis and ferroptosis in cancer metastasis
Authors: Liu Yan , Chen Qiuyun , Zhu Yanan , Wang Tiying , Ye Lijuan , Han Lei , Yao Zhihong , Yang Zuozhang 
Published: August 2021

AbstractDistant metastasis is the main cause of death for cancer patients. Recently, the newly discovered programmed cell death includes necroptosis, pyroptosis, and ferroptosis, which possesses an important role in the process of tumor metastasis. At the same time, it is widely reported that non-coding RNA precisely regulates programmed death and tumor metastasis. In the present review, we summarize the function and role of necroptosis, pyrolysis, and ferroptosis involving in cancer metastasis, as well as the regulatory factors, including non-coding RNAs, of necroptosis, pyroptosis, and ferroptosis in the process of tumor metastasis.
GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis
Authors: Kremer Daniel M. , Nelson Barbara S. , Lin Lin , Yarosz Emily L. , Halbrook Christopher J. , Kerk Samuel A. , Sajjakulnukit Peter , Myers Amy , Thurston Galloway , Hou Sean W. , Carpenter Eileen S. , Andren Anthony C. , Nwosu Zeribe C. , Cusmano Nicholas , Wisner Stephanie , Mbah Nneka E. , Shan Mengrou , Das Nupur K. , Magnuson Brian , Little Andrew C. , Savani Milan R. , Ramos Johanna , Gao Tina , Sastra Stephen A. , Palermo Carmine F. , Badgley Michael A. , Zhang Li , Asara John M. , McBrayer Samuel K. , di Magliano Marina Pasca , Crawford Howard C. , Shah Yatrik M. , Olive Kenneth P. , Lyssiotis Costas A. 
Published: August 2021

AbstractCancer metabolism is rewired to support cell survival in response to intrinsic and environmental stressors. Identification of strategies to target these adaptions is an area of active research. We previously described a cytosolic aspartate aminotransaminase (GOT1)-driven pathway in pancreatic cancer used to maintain redox balance. Here, we sought to identify metabolic dependencies following GOT1 inhibition to exploit this feature of pancreatic cancer and to provide additional insight into regulation of redox metabolism. Using pharmacological methods, we identify cysteine, glutathione, and lipid antioxidant function as metabolic vulnerabilities following GOT1 withdrawal. We demonstrate that targeting any of these pathways triggers ferroptosis, an oxidative, iron-dependent form of cell death, in GOT1 knockdown cells. Mechanistically, we reveal that GOT1 inhibition represses mitochondrial metabolism and promotes a catabolic state. Consequently, we find that this enhances labile iron availability through autophagy, which potentiates the activity of ferroptotic stimuli. Overall, our study identifies a biochemical connection between GOT1, iron regulation, and ferroptosis.
Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation
Authors: Tan Xiaohong , Tong Lu , Li Lin , Xu Jinjin , Xie Shaofang , Ji Lei , Fu Junjiang , Liu Qingwu , Shen Shihui , Liu Yun , Xiao Yanhui , Gao Feiran , Moses Robb E. , Bardeesy Nabeel , Wang Yanxiao , Zhang Jishuai , Tang Longying , Li Lei , Wong Kwok-kin , Song Dianwen , Yang Xiao , Liu Jian , Li Xiaotao 
Published: August 2021

AbstractSMAD4 is mutated in human lung cancer, but the underlying mechanism by which Smad4 loss-of-function (LOF) accelerates lung cancer metastasis is yet to be elucidated. Here, we generate a highly aggressive lung cancer mouse model bearing conditional KrasG12D, p53fl/fl LOF and Smad4fl/fl LOF mutations (SPK), showing a much higher incidence of tumor metastases than the KrasG12D, p53fl/fl (PK) mice. Molecularly, PAK3 is identified as a downstream effector of Smad4, mediating metastatic signal transduction via the PAK3-JNK-Jun pathway. Upregulation of PAK3 by Smad4 LOF in SPK mice is achieved by attenuating Smad4-dependent transcription of miR-495 and miR-543. These microRNAs (miRNAs) directly bind to the PAK3 3′UTR for blockade of PAK3 production, ultimately regulating lung cancer metastasis. An inverse correlation between Smad4 and PAK3 pathway components is observed in human lung cancer. Our study highlights the Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer.
Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking
Authors: Wu Lin-Ping , Ficker Mario , Christensen Jørn B. , Simberg Dmitri , Trohopoulos Panagiotis N. , Moghimi Seyed M. 
Published: August 2021

AbstractComplement is an enzymatic humoral pattern-recognition defence system of the body. Non-specific deposition of blood biomolecules on nanomedicines triggers complement activation through the alternative pathway, but complement-triggering mechanisms of nanomaterials with dimensions comparable to or smaller than many globular blood proteins are unknown. Here we study this using a library of <6 nm poly(amido amine) dendrimers bearing different end-terminal functional groups. Dendrimers are not sensed by C1q and mannan-binding lectin, and hence do not trigger complement activation through these pattern-recognition molecules. While, pyrrolidone- and carboxylic acid-terminated dendrimers fully evade complement response, and independent of factor H modulation, binding of amine-terminated dendrimers to a subset of natural IgM glycoforms triggers complement activation through lectin pathway-IgM axis. These findings contribute to mechanistic understanding of complement surveillance of dendrimeric materials, and provide opportunities for dendrimer-driven engineering of complement-safe nanomedicines and medical devices.
Malaria parasites both repress host CXCL10 and use it as a cue for growth acceleration
Authors: Ofir-Birin Yifat , Ben Ami Pilo Hila , Cruz Camacho Abel , Rudik Ariel , Rivkin Anna , Revach Or-Yam , Nir Netta , Block Tamin Tal , Abou Karam Paula , Kiper Edo , Peleg Yoav , Nevo Reinat , Solomon Aryeh , Havkin-Solomon Tal , Rojas Alicia , Rotkopf Ron , Porat Ziv , Avni Dror , Schwartz Eli , Zillinger Thomas , Hartmann Gunther , Di Pizio Antonella , Quashie Neils Ben , Dikstein Rivka , Gerlic Motti , Torrecilhas Ana Claudia , Levy Carmit , Nolte-‘t Hoen Esther N. M. , Bowie Andrew G. , Regev-Rudzki Neta 
Published: August 2021

AbstractPathogens are thought to use host molecular cues to control when to initiate life-cycle transitions, but these signals are mostly unknown, particularly for the parasitic disease malaria caused by Plasmodium falciparum. The chemokine CXCL10 is present at high levels in fatal cases of cerebral malaria patients, but is reduced in patients who survive and do not have complications. Here we show a Pf ‘decision-sensing-system’ controlled by CXCL10 concentration. High CXCL10 expression prompts P. falciparum to initiate a survival strategy via growth acceleration. Remarkably, P. falciparum inhibits CXCL10 synthesis in monocytes by disrupting the association of host ribosomes with CXCL10 transcripts. The underlying inhibition cascade involves RNA cargo delivery into monocytes that triggers RIG-I, which leads to HUR1 binding to an AU-rich domain of the CXCL10 3’UTR. These data indicate that when the parasite can no longer keep CXCL10 at low levels, it can exploit the chemokine as a cue to shift tactics and escape.
A ligand-insensitive UNC5B splicing isoform regulates angiogenesis by promoting apoptosis
Authors: Pradella Davide , Deflorian Gianluca , Pezzotta Alex , Di Matteo Anna , Belloni Elisa , Campolungo Daniele , Paradisi Andrea , Bugatti Mattia , Vermi William , Campioni Matteo , Chiapparino Antonella , Scietti Luigi , Forneris Federico , Giampietro Costanza , Volf Nina , Rehman Michael , Zacchigna Serena , Paronetto Maria Paola , Pistocchi Anna , Eichmann Anne , Mehlen Patrick , Ghigna Claudia 
Published: August 2021

AbstractThe Netrin-1 receptor UNC5B is an axon guidance regulator that is also expressed in endothelial cells (ECs), where it finely controls developmental and tumor angiogenesis. In the absence of Netrin-1, UNC5B induces apoptosis that is blocked upon Netrin-1 binding. Here, we identify an UNC5B splicing isoform (called UNC5B-Δ8) expressed exclusively by ECs and generated through exon skipping by NOVA2, an alternative splicing factor regulating vascular development. We show that UNC5B-Δ8 is a constitutively pro-apoptotic splicing isoform insensitive to Netrin-1 and required for specific blood vessel development in an apoptosis-dependent manner. Like NOVA2, UNC5B-Δ8 is aberrantly expressed in colon cancer vasculature where its expression correlates with tumor angiogenesis and poor patient outcome. Collectively, our data identify a mechanism controlling UNC5B’s necessary apoptotic function in ECs and suggest that the NOVA2/UNC5B circuit represents a post-transcriptional pathway regulating angiogenesis.
Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19
Authors: Nouailles Geraldine , Wyler Emanuel , Pennitz Peter , Postmus Dylan , Vladimirova Daria , Kazmierski Julia , Pott Fabian , Dietert Kristina , Muelleder Michael , Farztdinov Vadim , Obermayer Benedikt , Wienhold Sandra-Maria , Andreotti Sandro , Hoefler Thomas , Sawitzki Birgit , Drosten Christian , Sander Leif E. , Suttorp Norbert , Ralser Markus , Beule Dieter , Gruber Achim D. , Goffinet Christine , Landthaler Markus , Trimpert Jakob , Witzenrath Martin 
Published: August 2021

AbstractIn COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.
Clinal genomic analysis reveals strong reproductive isolation across a steep habitat transition in stickleback fish
Authors: Haenel Quiterie , Oke Krista B. , Laurentino Telma G. , Hendry Andrew P. , Berner Daniel 
Published: August 2021

AbstractHow ecological divergence causes strong reproductive isolation between populations in close geographic contact remains poorly understood at the genomic level. We here study this question in a stickleback fish population pair adapted to contiguous, ecologically different lake and stream habitats. Clinal whole-genome sequence data reveal numerous genome regions (nearly) fixed for alternative alleles over a distance of just a few hundred meters. This strong polygenic adaptive divergence must constitute a genome-wide barrier to gene flow because a steep cline in allele frequencies is observed across the entire genome, and because the cline center closely matches the habitat transition. Simulations confirm that such strong divergence can be maintained by polygenic selection despite high dispersal and small per-locus selection coefficients. Finally, comparing samples from near the habitat transition before and after an unusual ecological perturbation demonstrates the fragility of the balance between gene flow and selection. Overall, our study highlights the efficacy of divergent selection in maintaining reproductive isolation without physical isolation, and the analytical power of studying speciation at a fine eco-geographic and genomic scale.
The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model
Authors: Yuste-Checa Patricia , Trinkaus Victoria A. , Riera-Tur Irene , Imamoglu Rahmi , Schaller Theresa F. , Wang Huping , Dudanova Irina , Hipp Mark S. , Bracher Andreas , Hartl F. Ulrich 
Published: August 2021

AbstractSpreading of aggregate pathology across brain regions acts as a driver of disease progression in Tau-related neurodegeneration, including Alzheimer’s disease (AD) and frontotemporal dementia. Aggregate seeds released from affected cells are internalized by naïve cells and induce the prion-like templating of soluble Tau into neurotoxic aggregates. Here we show in a cellular model system and in neurons that Clusterin, an abundant extracellular chaperone, strongly enhances Tau aggregate seeding. Upon interaction with Tau aggregates, Clusterin stabilizes highly potent, soluble seed species. Tau/Clusterin complexes enter recipient cells via endocytosis and compromise the endolysosomal compartment, allowing transfer to the cytosol where they propagate aggregation of endogenous Tau. Thus, upregulation of Clusterin, as observed in AD patients, may enhance Tau seeding and possibly accelerate the spreading of Tau pathology.
High efficiency blue organic light-emitting diodes with below-bandgap electroluminescence
Authors: Vasilopoulou Maria , Mohd Yusoff Abd. Rashid bin , Daboczi Matyas , Conforto Julio , Gavim Anderson Emanuel Ximim , da Silva Wilson Jose , Macedo Andreia Gerniski , Soultati Anastasia , Pistolis George , Schneider Fabio Kurt , Dong Yifan , Jacoutot Polina , Rotas Georgios , Jang Jin , Vougioukalakis Georgios C. , Chochos Christos L. , Kim Ji-Seon , Gasparini Nicola 
Published: August 2021

AbstractBlue organic light-emitting diodes require high triplet interlayer materials, which induce large energetic barriers at the interfaces resulting in high device voltages and reduced efficiencies. Here, we alleviate this issue by designing a low triplet energy hole transporting interlayer with high mobility, combined with an interface exciplex that confines excitons at the emissive layer/electron transporting material interface. As a result, blue thermally activated delay fluorescent organic light-emitting diodes with a below-bandgap turn-on voltage of 2.5 V and an external quantum efficiency (EQE) of 41.2% were successfully fabricated. These devices also showed suppressed efficiency roll-off maintaining an EQE of 34.8% at 1000 cd m−2. Our approach paves the way for further progress through exploring alternative device engineering approaches instead of only focusing on the demanding synthesis of organic compounds with complex structures.
Global variation in the fraction of leaf nitrogen allocated to photosynthesis
Authors: Luo Xiangzhong , Keenan Trevor F. , Chen Jing M. , Croft Holly , Colin Prentice I. , Smith Nicholas G. , Walker Anthony P. , Wang Han , Wang Rong , Xu Chonggang , Zhang Yao 
Published: August 2021

AbstractPlants invest a considerable amount of leaf nitrogen in the photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase-oxygenase (RuBisCO), forming a strong coupling of nitrogen and photosynthetic capacity. Variability in the nitrogen-photosynthesis relationship indicates different nitrogen use strategies of plants (i.e., the fraction nitrogen allocated to RuBisCO; fLNR), however, the reason for this remains unclear as widely different nitrogen use strategies are adopted in photosynthesis models. Here, we use a comprehensive database of in situ observations, a remote sensing product of leaf chlorophyll and ancillary climate and soil data, to examine the global distribution in fLNR using a random forest model. We find global fLNR is 18.2 ± 6.2%, with its variation largely driven by negative dependence on leaf mass per area and positive dependence on leaf phosphorus. Some climate and soil factors (i.e., light, atmospheric dryness, soil pH, and sand) have considerable positive influences on fLNR regionally. This study provides insight into the nitrogen-photosynthesis relationship of plants globally and an improved understanding of the global distribution of photosynthetic potential.
Periodically modulated skyrmion strings in Cu2OSeO3
Authors: Burn D. M. , Brearton R. , Ran K. J. , Zhang S. L. , van der Laan G. , Hesjedal T. 
Published: August 2021

AbstractMagnetic skyrmions are vortex-like spin textures, which are usually treated as two-dimensional objects. In their lattice state, they form well-ordered, hexagonal structures, which have been studied in great detail. To obtain a three-dimensional (3D) skyrmion crystal, these planes can be envisaged to be stacked up forming skyrmion strings in the third dimension. Here, we report the observation of a 3D skyrmion phase in Cu2OSeO3 by carrying out reciprocal space mapping in resonant elastic x-ray scattering. We observe regions in the magnetic field-cooling phase diagram in which the skyrmion phase apparently coexists with the conical phase. However, such a coexistence is forbidden due to symmetry arguments. Instead, the skyrmion strings themselves are periodically modulated along their axes, as confirmed by micromagnetic simulations. The periodic modulation is in fact a necessary consequence of the evolution of the skyrmion phase out of the conical state and should therefore be a universal property of skyrmion strings in chiral helimagnets.
Benefit of COVID-19 vaccination accounting for potential risk compensation
Authors: Ioannidis John P. A. 
Published: August 2021

AbstractPeople receiving COVID-19 vaccines may subsequently markedly increase their previously suppressed exposure risk. A simple model can evaluate the benefit of vaccination to the vaccinated (index) person and others exposed to that person; and calculate the amount of risk compensation required to eliminate all the benefits or to halve the benefit. As shown, 2.5-fold increase in exposure will eliminate the benefit of a vaccine of moderate efficacy (E = 0.6) unless the probability of infection in the population of interest is very high. With very high vaccine efficacy (E = 0.95), substantial benefit is maintained except in situations where there is a very low probability of infection in the population. If the vaccine efficacy decreases to 0.8, the benefit gets eroded easily with modest risk compensation. Risk compensation may markedly affect the benefit of COVID-19 vaccination, especially if vaccine efficacy in real-life or specific high-risk populations (e.g., nursing home residents) is not very high.
Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis
Authors: Kabinger Florian , Stiller Carina , Schmitzová Jana , Dienemann Christian , Kokic Goran , Hillen Hauke S. , Höbartner Claudia , Cramer Patrick 
Published: August 2021

AbstractMolnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β-d-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp–RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir.
Numerical study on the influence of wall temperature gradient on aerodynamic characteristics of low aspect ratio flying wing configuration
Authors: Lin Peng , Liu Xueqiang , Xiong Neng , Wang Xiaobing , Shang Ma , Liu Guangyuan , Tao Yang 
Published: August 2021

AbstractWith the aim for a low-aspect-ratio flying wing configuration, this study explores the influence of wall temperature gradient on the laminar and turbulent boundary layers of aircraft surface and determines the effect on the transition Reynolds number and wall friction drag. A four-equation turbulence model with transition mode is used to numerically simulate the flow around the model. The variation of wall friction coefficient, transition Reynolds number, and turbulent boundary layer flow with wall temperature are emphatically investigated. Results show that when the wall temperature increases from 288 to 500 K, the boundary layer transition Reynolds number for the wing section increased by approximately 28% and the surface friction drags decreases by approximately 10.7%. The hot wall enhances the viscous effects of the laminar temperature boundary layer, reduces the Reynolds shear stress and turbulent kinetic energy, and increases the flow stability. However, the velocity gradient and shear stress in the bottom of the turbulent boundary layer decreases, which leads to reduced friction shear stress on the wall surface. Therefore, for the low-aspect-ratio flying wing model, the hot wall can delay the boundary layer transition and reduce the friction drag coefficient in the turbulent region.
Longitudinal consistency of source-space spectral power and functional connectivity using different magnetoencephalography recording systems
Authors: Boon Lennard I. , Tewarie Prejaas , Berendse Henk W. , Stam Cornelis J. , Hillebrand Arjan 
Published: August 2021

AbstractLongitudinal analyses of magnetoencephalography (MEG) data are essential for a full understanding of the pathophysiology of brain diseases and the development of brain activity over time. However, time-dependent factors, such as the recording environment and the type of MEG recording system may affect such longitudinal analyses. We hypothesized that, using source-space analysis, hardware and software differences between two recordings systems may be overcome, with the aim of finding consistent neurophysiological results. We studied eight healthy subjects who underwent three consecutive MEG recordings over 7 years, using two different MEG recordings systems; a 151-channel VSM-CTF system for the first two time points and a 306-channel Elekta Vectorview system for the third time point. We assessed the within (longitudinal) and between-subject (cross-sectional) consistency of power spectra and functional connectivity matrices. Consistency of within-subject spectral power and functional connectivity matrices was good and was not significantly different when using different MEG recording systems as compared to using the same system. Importantly, we confirmed that within-subject consistency values were higher than between-subject values. We demonstrated consistent neurophysiological findings in healthy subjects over a time span of seven years, despite using data recorded on different MEG systems and different implementations of the analysis pipeline.