bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline
Authors: Fang Wenting , Xiao Naian , Zeng Guirong , Bi Daode , Dai Xiaoman , Mi Xue , Ye Qinyong , Chen Xiaochun , Zhang Jing 
Published: October 2021

AbstractPopulation-based studies reveal that apolipoprotein E (APOE)ε4 gene allele is closely associated with late-life depression (LLD). However, its exact role and underlying mechanism remain obscure. The current study found that aged apoE4-targeted replacement (TR) mice displayed obvious depression-like behavior when compared with age-matched apoE3-TR mice. Furthermore, apoE4 increased stress-induced depression-like behaviors, accompanied by declines in the hippocampal 5-HT (1A) radioligand [18F] MPPF uptake evidenced by positron emission tomography (PET). In [18F]-fluorodeoxyglucose PET ([18F]-FDG PET) analyses, the FDG uptake in the prefrontal cortex, temporal cortex and hippocampus of apoE4-TR mice significantly declined when compared with that of apoE3-TR mice after acute stress. Further biochemical analysis revealed that ATP levels in the prefrontal cortex of apoE4-TR mice decreased during aging or stress process and ATP supplementation effectively rescued the depression-like behaviors of elderly apoE4-TR mice. In primary cultured astrocytes from the cortex of apoE-TR mice, apoE4, when compared with apoE3, obviously decreased the mitochondrial membrane potential, mitochondrial respiration, and glycolysis in a culture time-dependent manner. Our findings highlight that apoE4 is a potential risk factor of depression in elderly population by impairing the glucose metabolism, reducing ATP level, and damaging mitochondrial functions in astrocytes, which indicates that in clinical settings ATP supplementation may be effective for elderly depression patients with apoE4 carrier.
Aberrantly reduced expression of miR-342-5p contributes to CCND1-associated chronic myeloid leukemia progression and imatinib resistance
Authors: Wu Yi-Ying , Lai Hsing-Fan , Huang Tzu-Chuan , Chen Yu-Guang , Ye Ren-Hua , Chang Ping-Ying , Lai Shiue-Wei , Chen Yeu-Chin , Lee Cho-Hao , Liu Wei-Nung , Dai Ming-Shen , Chen Jia-Hong , Ho Ching-Liang , Chiu Yi-Lin 
Published: October 2021

AbstractChronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome, and the current standard of care is the use of tyrosine kinase inhibitors (TKI). However, some patients will not achieve a molecular response and may progress to blast crisis, and the underlying mechanisms remain to be clarified. In this study, next-generation sequencing was used to explore endogenous miRNAs in CML patients versus healthy volunteers, and miR-342-5p was identified as the primary target. We found that miR-342-5p was downregulated in CML patients and had a significant inhibitory effect on cell proliferation in CML. Through a luciferase reporter system, miR-342-5p was reported to target the 3’-UTR domain of CCND1 and downregulated its expression. Furthermore, overexpression of miR-342-5p enhanced imatinib-induced DNA double-strand breaks and apoptosis. Finally, by analyzing clinical databases, we further confirmed that miR-342-5p was associated with predicted molecular responses in CML patients. In conclusion, we found that both in vivo and in vitro experiments and database cohorts showed that miR-342-5p plays a key role in CML patients, indicating that miR-342-5p may be a potential target for future CML treatment or prognostic evaluation.
The spliceosome factor sart3 regulates hematopoietic stem/progenitor cell development in zebrafish through the p53 pathway
Authors: Zhao Yan , Wu Mei , Li Jing , Meng Ping , Chen Jiakui , Huang Zhibin , Xu Jin , Wen Zilong , Zhang Wenqing , Zhang Yiyue 
Published: October 2021

AbstractHematopoietic stem cells (HSCs) possess the potential for self-renew and the capacity, throughout life, to differentiate into all blood cell lineages. Yet, the mechanistic basis for HSC development remains largely unknown. In this study, we characterized a zebrafish smu471 mutant with hematopoietic stem/progenitor cell (HSPC) defects and found that sart3 was the causative gene. RNA expression profiling of the sart3smu471 mutant revealed spliceosome and p53 signaling pathway to be the most significantly enriched pathways in the sart3smu471 mutant. Knock down of p53 rescued HSPC development in the sart3smu471 mutant. Interestingly, the p53 inhibitor, mdm4, had undergone an alternative splicing event in the mutant. Restoration of mdm4 partially rescued HSPC deficiency. Thus, our data suggest that HSPC proliferation and maintenance require sart3 to ensure the correct splicing and expression of mdm4, so that the p53 pathway is properly inhibited to prevent definitive hematopoiesis failure. This study expands our knowledge of the regulatory mechanisms that impact HSPC development and sheds light on the mechanistic basis and potential therapeutic use of sart3 in spliceosome-mdm4-p53 related disorders.
Ferroptosis in liver disease: new insights into disease mechanisms
Authors: Wu Jing , Wang Yi , Jiang Rongtao , Xue Ran , Yin Xuehong , Wu Muchen , Meng Qinghua 
Published: October 2021

AbstractCharacterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other well-known cell death. In recent years, ferroptosis has been quickly gaining attention in the field of liver diseases, as the liver is predisposed to oxidative injury and generally, excessive iron accumulation is a primary characteristic of most major liver diseases. In the current review, we first delineate three cellular defense mechanisms against ferroptosis (GPx4 in the mitochondria and cytosol, FSP1 on plasma membrane, and DHODH in mitochondria), along with four canonical modulators of ferroptosis (system Xc−, nuclear factor erythroid 2-related factor 2, p53, and GTP cyclohydrolase-1). Next, we review recent progress of ferroptosis studies delineating molecular mechanisms underlying the pathophysiology of several common liver diseases including ischemia/reperfusion-related injury (IRI), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hemochromatosis (HH), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). Furthermore, we also highlight both challenges and promises that emerged from recent studies that should be addressed and pursued in future investigations before ferroptosis regulation could be adopted as an effective therapeutic target in clinical practice.
Antarctic ozone hole modifies iodine geochemistry on the Antarctic Plateau
Authors: Spolaor Andrea , Burgay François , Fernandez Rafael P. , Turetta Clara , Cuevas Carlos A. , Kim Kitae , Kinnison Douglas E. , Lamarque Jean-François , de Blasi Fabrizio , Barbaro Elena , Corella Juan Pablo , Vallelonga Paul , Frezzotti Massimo , Barbante Carlo , Saiz-Lopez Alfonso 
Published: October 2021

AbstractPolar stratospheric ozone has decreased since the 1970s due to anthropogenic emissions of chlorofluorocarbons and halons, resulting in the formation of an ozone hole over Antarctica. The effects of the ozone hole and the associated increase in incoming UV radiation on terrestrial and marine ecosystems are well established; however, the impact on geochemical cycles of ice photoactive elements, such as iodine, remains mostly unexplored. Here, we present the first iodine record from the inner Antarctic Plateau (Dome C) that covers approximately the last 212 years (1800-2012 CE). Our results show that the iodine concentration in ice remained constant during the pre-ozone hole period (1800-1974 CE) but has declined twofold since the onset of the ozone hole era (~1975 CE), closely tracking the total ozone evolution over Antarctica. Based on ice core observations, laboratory measurements and chemistry-climate model simulations, we propose that the iodine decrease since ~1975 is caused by enhanced iodine re-emission from snowpack due to the ozone hole-driven increase in UV radiation reaching the Antarctic Plateau. These findings suggest the potential for ice core iodine records from the inner Antarctic Plateau to be as an archive for past stratospheric ozone trends.
Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity
Authors: Achdout Hagit , Vitner Einat. B. , Politi Boaz , Melamed Sharon , Yahalom-Ronen Yfat , Tamir Hadas , Erez Noam , Avraham Roy , Weiss Shay , Cherry Lilach , Bar-Haim Erez , Makdasi Efi , Gur David , Aftalion Moshe , Chitlaru Theodor , Vagima Yaron , Paran Nir , Israely Tomer 
Published: October 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The continued spread of SARS-CoV-2 increases the probability of influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine the disease outcome of influenza A virus (IAV) and SARS-CoV-2 coinfection in K18-hACE2 mice. Our data indicate enhance susceptibility of IAV-infected mice to developing severe disease upon coinfection with SARS-CoV-2 two days later. In contrast to nonfatal influenza and lower mortality rates due to SARS-CoV-2 alone, this coinfection results in severe morbidity and nearly complete mortality. Coinfection is associated with elevated influenza viral loads in respiratory organs. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevents severe disease and mortality. This protection is antibody-dependent. These data experimentally support the necessity of seasonal influenza vaccination for reducing the risk of severe influenza/COVID-19 comorbidity during the COVID-19 pandemic.
An ethylene biosynthesis enzyme controls quantitative variation in maize ear length and kernel yield
Authors: Ning Qiang , Jian Yinan , Du Yanfang , Li Yunfu , Shen Xiaomeng , Jia Haitao , Zhao Ran , Zhan Jimin , Yang Fang , Jackson David , Liu Lei , Zhang Zuxin 
Published: October 2021

AbstractMaize ear size and kernel number differ among lines, however, little is known about the molecular basis of ear length and its impact on kernel number. Here, we characterize a quantitative trait locus, qEL7, to identify a maize gene controlling ear length, flower number and fertility. qEL7 encodes 1-aminocyclopropane-1- carboxylate oxidase2 (ACO2), a gene that functions in the final step of ethylene biosynthesis and is expressed in specific domains in developing inflorescences. Confirmation of qEL7 by gene editing of ZmACO2 leads to a reduction in ethylene production in developing ears, and promotes meristem and flower development, resulting in a ~13.4% increase in grain yield per ear in hybrids lines. Our findings suggest that ethylene serves as a key signal in inflorescence development, affecting spikelet number, floral fertility, ear length and kernel number, and also provide a tool to improve grain productivity by optimizing ethylene levels in maize or in other cereals.
A study of real-world micrograph data quality and machine learning model robustness
Authors: Zhong Xiaoting , Gallagher Brian , Eves Keenan , Robertson Emily , Mundhenk T. Nathan , Han T. Yong-Jin 
Published: October 2021

AbstractMachine-learning (ML) techniques hold the potential of enabling efficient quantitative micrograph analysis, but the robustness of ML models with respect to real-world micrograph quality variations has not been carefully evaluated. We collected thousands of scanning electron microscopy (SEM) micrographs for molecular solid materials, in which image pixel intensities vary due to both the microstructure content and microscope instrument conditions. We then built ML models to predict the ultimate compressive strength (UCS) of consolidated molecular solids, by encoding micrographs with different image feature descriptors and training a random forest regressor, and by training an end-to-end deep-learning (DL) model. Results show that instrument-induced pixel intensity signals can affect ML model predictions in a consistently negative way. As a remedy, we explored intensity normalization techniques. It is seen that intensity normalization helps to improve micrograph data quality and ML model robustness, but microscope-induced intensity variations can be difficult to eliminate.
Environmental screening and ligand-field effects to magnetism in CrI3 monolayer
Authors: Soriano D. , Rudenko A. N. , Katsnelson M. I. , Rösner M. 
Published: October 2021

AbstractWe study the microscopic origin of magnetism in suspended and dielectrically embedded CrI3 monolayer by down-folding minimal generalized Hubbard models from ab initio calculations using the constrained random phase approximation. These models are capable of describing the formation of localized magnetic moments in CrI3 and of reproducing electronic properties of direct ab initio calculations. Utilizing the magnet force theorem, we find a multi-orbital super-exchange mechanism as the origin of magnetism in CrI3 resulting from an interplay between ferro- and anti-ferromagnetic Cr-Cr d coupling channels, which is decisively affected by the ligand p orbitals. We show how environmental screening, such as resulting from encapsulation with hexagonal boron nitride, affects the Coulomb interaction in the film and how this controls its magnetic properties. Driven by a non-monotonic interplay between nearest and next-nearest neighbor exchange interactions we find the magnon dispersion and the Curie temperature to be non-trivially affected by the environmental screening.
Impact of convection on the damping of an oscillating droplet during viscosity measurement using the ISS-EML facility
Authors: Xiao Xiao , Brillo Jürgen , Lee Jonghyun , Hyers Robert W. , Matson Douglas M. 
Published: October 2021

AbstractOscillating droplet experiments are conducted using the Electromagnetic Levitation (EML) facility under microgravity conditions. The droplet of molten metal is internally stirred concurrently with the pulse excitation initiating shape oscillations, allowing viscosity measurement of the liquid melts based on the damping rate of the oscillating droplet. We experimentally investigate the impact of convection on the droplet’s damping behavior. The effective viscosity arises and increases as the internal convective flow becomes transitional or turbulent, up to 2–8 times higher than the intrinsic molecular viscosity. The enhanced effective viscosity decays when the stirring has stopped, and an overshoot decay pattern is identified at higher Reynolds numbers, which presents a faster decay rate as the constraint of flow domain size becomes influential. By discriminating the impact of convection on the viscosity results, the intrinsic viscosity can be evaluated with improved measurement accuracy.
Multipartite entanglement of billions of motional atoms heralded by single photon
Authors: Li Hang , Dou Jian-Peng , Pang Xiao-Ling , Zhang Chao-Ni , Yan Zeng-Quan , Yang Tian-Huai , Gao Jun , Li Jia-Ming , Jin Xian-Min 
Published: October 2021

AbstractQuantum theory does not prevent entanglement from being created and observed in macroscopic physical systems, in reality however, the accessible scale of entanglement is still very limited due to decoherence effects. Recently, entanglement has been observed among atoms from thousands to millions levels in extremely low-temperature and well isolated systems. Here, we create multipartite entanglement of billions of motional atoms in a quantum memory at room temperature and certify the genuine entanglement via M-separability witness associated with photon statistics. The information contained in a single photon is found strongly correlated with the excitation shared by the motional atoms, which intrinsically address the large system and therefore stimulate the multipartite entanglement. Remarkably, our heralded and quantum memory built-in entanglement generation allows us to directly observe the dynamic evolution of entanglement depth and further to reveal the effects of decoherence. Our results verify the existence of genuine multipartite entanglement among billions of motional atoms at ambient conditions, significantly extending the boundary of the accessible scale of entanglement.
Preparation and characterization of graphitic carbon nitride-supported l-arginine as a highly efficient and recyclable catalyst for the one-pot synthesis of condensation reactions
Authors: Ghafuri Hossein , Tajik Zeinab , Ghanbari Nastaran , Hanifehnejad Peyman 
Published: October 2021

AbstractIn this work, graphitic carbon nitride-supported l-arginine (g-C3N4@l-arginine) nanocatalyst was synthesized and evaluated using FT-IR, EDX, XRD, TGA, and FESEM analyses. The performance of the prepared nanocatalyst was examined in the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives. The novel g-C3N4@l-arginine nanocatalyst showed high thermal stability, easy separation from reaction media, the capability to be used in various multicomponent reactions, and acceptable reusability.
A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
Authors: Dornbierer Dario A. , Yerlikaya Firat , Wespi Rafael , Boxler Martina I. , Voegel Clarissa D. , Schnider Laura , Arslan Aslihan , Baur Diego M. , Baumgartner Markus R. , Binz Tina Maria , Kraemer Thomas , Landolt Hans-Peter 
Published: October 2021

AbstractSleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation’s ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.Trials registration: NCT04975360.
Free versus bound entanglement, a NP-hard problem tackled by machine learning
Authors: Hiesmayr Beatrix C. 
Published: October 2021

AbstractEntanglement detection in high dimensional systems is a NP-hard problem since it is lacking an efficient way. Given a bipartite quantum state of interest free entanglement can be detected efficiently by the PPT-criterion (Peres-Horodecki criterion), in contrast to detecting bound entanglement, i.e. a curious form of entanglement that can also not be distilled into maximally (free) entangled states. Only a few bound entangled states have been found, typically by constructing dedicated entanglement witnesses, so naturally the question arises how large is the volume of those states. We define a large family of magically symmetric states of bipartite qutrits for which we find $$82\%$$

82
%

to be free entangled, $$2\%$$

2
%

to be certainly separable and as much as $$10\%$$

10
%

to be bound entangled, which shows that this kind of entanglement is not rare. Via various machine learning algorithms we can confirm that the remaining $$6\%$$

6
%

of states are more likely to belonging to the set of separable states than bound entangled states. Most important we find via dimension reduction algorithms that there is a strong two-dimensional (linear) sub-structure in the set of bound entangled states. This revealed structure opens a novel path to find and characterize bound entanglement towards solving the long-standing problem of what the existence of bound entanglement is implying.
Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
Authors: Nedosekin Dmitry A. , Chen TsungYen , Ayyadevara Srinivas , Zharov Vladimir P. , Shmookler Reis Robert J. 
Published: October 2021

AbstractAggregation of proteins is a prominent hallmark of virtually all neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Little progress has been made in their treatment to slow or prevent the formation of aggregates by post-translational modification and regulation of cellular responses to misfolded proteins. Here, we introduce a label-free, laser-based photothermal treatment of polyglutamine (polyQ) aggregates in a C. elegans nematode model of huntingtin-like polyQ aggregation. As a proof of principle, we demonstrated that nanosecond laser pulse-induced local photothermal heating can directly disrupt the aggregates so as to delay their accumulation, maintain motility, and extend the lifespan of treated nematodes. These beneficial effects were validated by confocal photothermal, fluorescence, and video imaging. The results obtained demonstrate that our theranostics platform, integrating photothermal therapy without drugs or other chemicals, combined with advanced imaging to monitor photothermal ablation of aggregates, initiates systemic recovery and thus validates the concept of aggregate-disruption treatments for neurodegenerative diseases in humans.
Cas9-mediated genome editing reveals a significant contribution of calcium signaling pathways to anhydrobiosis in Pv11 cells
Authors: Miyata Yugo , Fuse Hiroto , Tokumoto Shoko , Hiki Yusuke , Deviatiiarov Ruslan , Yoshida Yuki , Yamada Takahiro G. , Cornette Richard , Gusev Oleg , Shagimardanova Elena , Funahashi Akira , Kikawada Takahiro 
Published: October 2021

AbstractPv11 is an insect cell line established from the midge Polypedilum vanderplanki, whose larval form exhibits an extreme desiccation tolerance known as anhydrobiosis. Pv11 itself is also capable of anhydrobiosis, which is induced by trehalose treatment. Here we report the successful construction of a genome editing system for Pv11 cells and its application to the identification of signaling pathways involved in anhydrobiosis. Using the Cas9-mediated gene knock-in system, we established Pv11 cells that stably expressed GCaMP3 to monitor intracellular Ca2+ mobilization. Intriguingly, trehalose treatment evoked a transient increase in cytosolic Ca2+ concentration, and further experiments revealed that the calmodulin–calcineurin–NFAT pathway contributes to tolerance of trehalose treatment as well as desiccation tolerance, while the calmodulin–calmodulin kinase–CREB pathway conferred only desiccation tolerance on Pv11 cells. Thus, our results show a critical contribution of the trehalose-induced Ca2+ surge to anhydrobiosis and demonstrate temporally different roles for each signaling pathway.