bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tea consumption and risk of incident dementia: A prospective cohort study of 377 592 UK Biobank participants
Authors: Hu He-Ying , Wu Bang-Sheng , Ou Ya-Nan , Ma Ya-Hui , Huang Yu-Yuan , Cheng Wei , Tan Lan , Yu Jin-Tai 
Published: April 2022

AbstractAs a widely consumed beverage, tea boasts diverse health benefits. Herein, we aimed to investigate the association between tea consumption and dementia risk. We conducted a prospective cohort study with 377 592 UK Biobank participants during a 9-year follow-up. Cox regression models adjusted for age, sex, ethnicity, Townsend deprivation index, education, body mass index, lifestyle factors, dietary factors and apolipoprotein E4 status were used to examine the association of tea consumption with dementia risk. Subgroup analyses stratified by age, sex and forms of dementia (Alzheimer’s disease [AD] and vascular dementia [VD]) were performed. Moreover, the restricted cubic splines were used to calculate the nonlinear relationship between daily dosage of tea and dementia risk. After adjustment for all covariates, tea drinkers were 16% (95% confidence interval: 8–23) less likely to develop dementia compared with non-drinkers. Moderate consumption (1–6 cups/day) of tea exerted significant protective effects. Subgroup analyses showed that mid-aged participants or males benefited more from tea consumption. Moreover, moderate drinkers had a 16–19% lower hazard of AD and a 25–29% lower hazard of VD. Furthermore, a U-shaped association between tea consumption and dementia risk was shown (Pnon-linearity = 7E−04), and the consumption of around three cups per day showed the strongest protective effect. Within 3 cups/day, drinking one extra cup of tea per day brought a 6% reduction of incidence. In conclusion, moderate consumption of tea was significantly associated with a reduced risk of dementia, suggesting that tea consumption could be a modifiable lifestyle factor for dementia.
Targeting NAD+: is it a common strategy to delay heart aging?
Authors: Yuan Yang , Liang Bing , Liu Xin-Lin , Liu Wen-Jing , Huang Bing-Huan , Yang Shan-Bo , Gao Yuan-Zhen , Meng Jing-Sen , Li Meng-Jiao , Ye Ting , Wang Chuan-Zhi , Hu Xiao-Kun , Xing Dong-Ming 
Published: April 2022

AbstractHeart aging is the main susceptible factor to coronary heart disease and significantly increases the risk of heart failure, especially when the aging heart is suffering from ischemia-reperfusion injury. Numerous studies with NAD+ supplementations have suggested its use in anti-aging treatment. However, systematic reviews regarding the overall role of NAD+ in cardiac aging are scarce. The relationship between NAD+ signaling and heart aging has yet to be clarified. This review comprehensively summarizes the current studies on the role of NAD+ signaling in delaying heart aging from the following aspects: the influence of NAD+ supplementations on the aging heart; the relationship and cross-talks between NAD+ signaling and other cardiac aging-related signaling pathways; Importantly, the therapeutic potential of targeting NAD+ in delaying heart aging will be discussed. In brief, NAD+ plays a vital role in delaying heart aging. However, the abnormalities such as altered glucose and lipid metabolism, oxidative stress, and calcium overload could also interfere with NAD+ function in the heart. Therefore, the specific physiopathology of the aging heart should be considered before applying NAD+ supplementations. We believe that this article will help augment our understanding of heart aging mechanisms. In the meantime, it provides invaluable insights into possible therapeutic strategies for preventing age-related heart diseases in clinical settings.
TLR2/caspase-5/Panx1 pathway mediates necrosis-induced NLRP3 inflammasome activation in macrophages during acute kidney injury
Authors: Liu Chongbin , Shen Yanting , Huang Liuwei , Wang Jun 
Published: April 2022

AbstractAcute kidney injury (AKI) is characterized by necroinflammation formed by necrotic tubular epithelial cells (TECs) and interstitial inflammation. In necroinflammation, macrophages are key inflammatory cells and can be activated and polarized into proinflammatory macrophages. Membranous Toll-like receptors (TLRs) can cooperate with intracellular NOD-like receptor protein 3 (NLRP3) to recognize danger signals from necrotic TECs and activate proinflammatory macrophages by assembling NLRP3 inflammasome. However, the cooperation between TLRs and NLRP3 is still unclear. Using conditioned medium from necrotic TECs, we confirmed that necrotic TECs could release danger signals to activate NLRP3 inflammasome in macrophages. We further identified that necrotic TECs-induced NLRP3 inflammasome activation was dependent on ATP secretion via Pannexin-1 (Panx1) channel in macrophages. Next, we verified that TLR2 was required for the activation of Panx1 and NLRP3 in macrophages. Mechanistically, we indicated that caspase-5 mediated TLR2-induced Panx1 activation. In addition, we showed that necrotic TECs-induced activation of TLR2/caspase-5/Panx1 axis could be decreased in macrophages when TECs was protected by N-acetylcysteine (NAC). Overall, we demonstrate that danger signals from necrotic TECs could activate NLRP3 inflammasome in macrophages via TLR2/caspase-5/Panx1 axis during AKI.
Excitations in a superconducting Coulombic energy gap
Authors: Estrada Saldaña Juan Carlos , Vekris Alexandros , Pavešić Luka , Krogstrup Peter , Žitko Rok , Grove-Rasmussen Kasper , Nygård Jesper 
Published: April 2022

AbstractCooper pairing and Coulomb repulsion are antagonists, producing distinct energy gaps in superconductors and Mott insulators. When a superconductor exchanges unpaired electrons with a quantum dot, its gap is populated by a pair of electron–hole symmetric Yu-Shiba-Rusinov excitations between doublet and singlet many-body states. The fate of these excitations in the presence of a strong Coulomb repulsion in the superconductor is unknown, but of importance in applications such as topological superconducting qubits and multi-channel impurity models. Here we couple a quantum dot to a superconducting island with a tunable Coulomb repulsion. We show that a strong Coulomb repulsion changes the singlet many-body state into a two-body state. It also breaks the electron–hole energy symmetry of the excitations, which thereby lose their Yu-Shiba-Rusinov character.
T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling
Authors: Chin Shu Shien , Guillen Erik , Chorro Laurent , Achar Sooraj , Ng Karina , Oberle Susanne , Alfei Francesca , Zehn Dietmar , Altan-Bonnet Grégoire , Delahaye Fabien , Lauvau Grégoire 
Published: April 2022

AbstractCognate antigen signal controls CD8+ T cell priming, expansion size and effector versus memory cell fates, but it is not known if and how it modulates the functional features of memory CD8+ T cells. Here we show that the strength of T cell receptor (TCR) signaling controls the requirement for interleukin-2 (IL-2) signals to form a pool of memory CD8+ T cells that competitively re-expand upon secondary antigen encounter. Combining strong TCR and intact IL-2 signaling during priming synergistically induces genome-wide chromatin accessibility in regions targeting a wide breadth of biological processes, consistent with greater T cell functional fitness. Chromatin accessibility in promoters of genes encoding for stem cell, cell cycle and calcium-related proteins correlates with faster intracellular calcium accumulation, initiation of cell cycle and more robust expansion. High-dimensional flow-cytometry analysis of these T cells also highlights higher diversity of T cell subsets and phenotypes with T cells primed with stronger TCR and IL-2 stimulation than those primed with weaker strengths of TCR and/or IL-2 signals. These results formally show that epitope selection in vaccine design impacts memory CD8+ T cell epigenetic programming and function.
Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes
Authors: Jahed Zeinab , Yang Yang , Tsai Ching-Ting , Foster Ethan P. , McGuire Allister F. , Yang Huaxiao , Liu Aofei , Forro Csaba , Yan Zen , Jiang Xin , Zhao Ming-Tao , Zhang Wei , Li Xiao , Li Thomas , Pawlosky Annalisa , Wu Joseph C. , Cui Bianxiao 
Published: April 2022

AbstractDrug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.
A computational theory of the subjective experience of flow
Authors: Melnikoff David E. , Carlson Ryan W. , Stillman Paul E. 
Published: April 2022

AbstractFlow is a subjective state characterized by immersion and engagement in one’s current activity. The benefits of flow for productivity and health are well-documented, but a rigorous description of the flow-generating process remains elusive. Here we develop and empirically test a theory of flow’s computational substrates: the informational theory of flow. Our theory draws on the concept of mutual information, a fundamental quantity in information theory that quantifies the strength of association between two variables. We propose that the mutual information between desired end states and means of attaining them — $$I({M;E})$$
I

(

M
;
E

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— gives rise to flow. We support our theory across five experiments (four preregistered) by showing, across multiple activities, that increasing $$I({M;E})$$
I

(

M
;
E

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increases flow and has important downstream benefits, including enhanced attention and enjoyment. We rule out alternative constructs including alternative metrics of associative strength, psychological constructs previously shown to predict flow, and various forms of instrumental value.
Mesoscopic landscape of cortical functions revealed by through-skull wide-field optical imaging in marmoset monkeys
Authors: Song Xindong , Guo Yueqi , Li Hongbo , Chen Chenggang , Lee Jong Hoon , Zhang Yang , Schmidt Zachary , Wang Xiaoqin 
Published: April 2022

AbstractThe primate cerebral cortex is organized into specialized areas representing different modalities and functions along a continuous surface. The functional maps across the cortex, however, are often investigated a single modality at a time (e.g., audition or vision). To advance our understanding of the complex landscape of primate cortical functions, here we develop a polarization-gated wide-field optical imaging method for measuring cortical functions through the un-thinned intact skull in awake marmoset monkeys (Callithrix jacchus), a primate species featuring a smooth cortex. Using this method, adjacent auditory, visual, and somatosensory cortices are noninvasively parcellated in individual subjects with detailed tonotopy, retinotopy, and somatotopy. An additional pure-tone-responsive tonotopic gradient is discovered in auditory cortex and a face-patch sensitive to motion in the lower-center visual field is localized near an auditory region representing frequencies of conspecific vocalizations. This through-skull landscape-mapping approach provides new opportunities for understanding how the primate cortex is organized and coordinated to enable real-world behaviors.
Chalcogenide optomemristors for multi-factor neuromorphic computation
Authors: Sarwat Syed Ghazi , Moraitis Timoleon , Wright C. David , Bhaskaran Harish 
Published: April 2022

AbstractNeuromorphic hardware that emulates biological computations is a key driver of progress in AI. For example, memristive technologies, including chalcogenide-based in-memory computing concepts, have been employed to dramatically accelerate and increase the efficiency of basic neural operations. However, powerful mechanisms such as reinforcement learning and dendritic computation require more advanced device operations involving multiple interacting signals. Here we show that nano-scaled films of chalcogenide semiconductors can perform such multi-factor in-memory computation where their tunable electronic and optical properties are jointly exploited. We demonstrate that ultrathin photoactive cavities of Ge-doped Selenide can emulate synapses with three-factor neo-Hebbian plasticity and dendrites with shunting inhibition. We apply these properties to solve a maze game through on-device reinforcement learning, as well as to provide a single-neuron solution to linearly inseparable XOR implementation.
Ebola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association
Authors: Zhu Lin , Gao Ting , Huang Yi , Jin Jing , Wang Di , Zhang Leike , Jin Yanwen , Li Ping , Hu Yong , Wu Yan , Liu Hainan , Dong Qincai , Wang Guangfei , Zheng Tong , Song Caiwei , Bai Yu , Zhang Xun , Liu Yaoning , Yang Weihong , Xu Ke , Zou Gang , Zhao Lei , Cao Ruiyuan , Zhong Wu , Xia Xianzhu , Xiao Gengfu , Liu Xuan , Cao Cheng 
Published: April 2022

AbstractEbola virus (EBOV), one of the deadliest viruses, is the cause of fatal Ebola virus disease (EVD). The underlying mechanism of viral replication and EBOV-related hemorrhage is not fully understood. Here, we show that EBOV VP35, a cofactor of viral RNA-dependent RNA polymerase, binds human A kinase interacting protein (AKIP1), which consequently activates protein kinase A (PKA) and the PKA-downstream transcription factor CREB1. During EBOV infection, CREB1 is recruited into EBOV ribonucleoprotein complexes in viral inclusion bodies (VIBs) and employed for viral replication. AKIP1 depletion or PKA-CREB1 inhibition dramatically impairs EBOV replication. Meanwhile, the transcription of several coagulation-related genes, including THBD and SERPINB2, is substantially upregulated by VP35-dependent CREB1 activation, which may contribute to EBOV-related hemorrhage. The finding that EBOV VP35 hijacks the host PKA-CREB1 signal axis for viral replication and pathogenesis provides novel potential therapeutic approaches against EVD.
Engineering artificial photosynthetic life-forms through endosymbiosis
Authors: Cournoyer Jay , Altman Sarah D. , Gao Yang-le , Wallace Catherine L. , Zhang Dianwen , Lo Guo-Hsuen , Haskin Noah T. , Mehta Angad P. 
Published: April 2022

Abstract
The evolutionary origin of the photosynthetic eukaryotes drastically altered the evolution of complex lifeforms and impacted global ecology. The endosymbiotic theory suggests that photosynthetic eukaryotes evolved due to endosymbiosis between non-photosynthetic eukaryotic host cells and photosynthetic cyanobacterial or algal endosymbionts. The photosynthetic endosymbionts, propagating within the cytoplasm of the host cells, evolved, and eventually transformed into chloroplasts. Despite the fundamental importance of this evolutionary event, we have minimal understanding of this remarkable evolutionary transformation. Here, we design and engineer artificial, genetically tractable, photosynthetic endosymbiosis between photosynthetic cyanobacteria and budding yeasts. We engineer various mutants of model photosynthetic cyanobacteria as endosymbionts within yeast cells where, the engineered cyanobacteria perform bioenergetic functions to support the growth of yeast cells under defined photosynthetic conditions. We anticipate that these genetically tractable endosymbiotic platforms can be used for evolutionary studies, particularly related to organelle evolution, and also for synthetic biology applications.
Sign-problem free quantum stochastic series expansion algorithm on a quantum computer
Authors: Tan Kok Chuan , Bhowmick Dhiman , Sengupta Pinaki 
Published: April 2022

AbstractA quantum implementation of the Stochastic Series Expansion (SSE) Monte Carlo method is proposed, and is shown to offer significant advantages over classical implementations of SSE. In particular, for problems where classical SSE encounters the sign problem, the cost of implementing a Monte Carlo iteration scales only linearly with system size in quantum SSE, while it may scale exponentially with system size in classical SSE. In cases where classical SSE can be efficiently implemented, quantum SSE still offers an advantage by allowing for more general observables to be measured.
Improved virtual extensometer measurement method in complex multi-fracture situation
Authors: Chai Jing , Ouyang Yibo , Liu Jinxuan , Zhang Dingding , Du Wengang , Yang Jianfeng , Liu Yongliang , Ma Zhe 
Published: April 2022

AbstractTo overcome the limitation of the virtual extensometer method in measuring the crack opening displacement (COD) in the process of complex multi-crack propagation of rock, the measurement error of Digital Image Correlation (DIC) local deformation is theoretically analyzed. An improved virtual extensometer method for measuring the COD is proposed, which considers the temporal and spatial characteristics of crack development in the process of complex crack propagation. The accuracy of the proposed method is verified by the strain localization band numerical simulation test and indoor single crack simulation test. Furthermore, the method is applied to the two-dimensional similarity simulation test of simulating complex multi-fractures in rock stratum. The COD obtained by the traditional and improved methods is compared with the measured COD. The results show that in the case of multiple complex cracks, to obtain the COD accurately, the relative distance between the virtual extensometer measuring point and the crack should be greater than half of the sum of the width of the crack strain localization zone and the subset size. With the development of the crack, the relative distance between the virtual extensometer measuring point and the crack should increase with the increase of the width of the crack strain localization zone. The error of the COD measured by the traditional method increases with fracture development, and the maximum is 21.20%. The maximum relative error between the COD measured by the improved method and the measured crack opening is 3.61%. The research results improve the accuracy of the virtual extensometer in measuring the COD under complex multi-crack conditions.
Hamiltonian of a flux qubit-LC oscillator circuit in the deep–strong-coupling regime
Authors: Yoshihara F. , Ashhab S. , Fuse T. , Bamba M. , Semba K. 
Published: April 2022

AbstractWe derive the Hamiltonian of a superconducting circuit that comprises a single-Josephson-junction flux qubit inductively coupled to an LC oscillator, and we compare the derived circuit Hamiltonian with the quantum Rabi Hamiltonian, which describes a two-level system coupled to a harmonic oscillator. We show that there is a simple, intuitive correspondence between the circuit Hamiltonian and the quantum Rabi Hamiltonian. While there is an overall shift of the entire spectrum, the energy level structure of the circuit Hamiltonian up to the seventh excited states can still be fitted well by the quantum Rabi Hamiltonian even in the case where the coupling strength is larger than the frequencies of the qubit and the oscillator, i.e., when the qubit-oscillator circuit is in the deep–strong-coupling regime. We also show that although the circuit Hamiltonian can be transformed via a unitary transformation to a Hamiltonian containing a capacitive coupling term, the resulting circuit Hamiltonian cannot be approximated by the variant of the quantum Rabi Hamiltonian that is obtained using an analogous procedure for mapping the circuit variables onto Pauli and harmonic oscillator operators, even for relatively weak coupling. This difference between the flux and charge gauges follows from the properties of the qubit Hamiltonian eigenstates.
Pedigree derived mutation rate across the entire mitochondrial genome of the Norfolk Island population
Authors: Connell J. R. , Benton M. C. , Lea R. A. , Sutherland H. G. , Chaseling J. , Haupt L. M. , Wright K. M. , Griffiths L. R. 
Published: April 2022

AbstractEstimates of mutation rates for various regions of the human mitochondrial genome (mtGenome) vary widely, depending on whether they are inferred using a phylogenetic approach or obtained directly from pedigrees. Traditionally, only the control region, or small portions of the coding region have been targeted for analysis due to the cost and effort required to produce whole mtGenome Sanger profiles. Here, we report one of the first pedigree derived mutation rates for the entire human mtGenome. The entire mtGenome from 225 individuals originating from Norfolk Island was analysed to estimate the pedigree derived mutation rate and compared against published mutation rates. These individuals were from 45 maternal lineages spanning 345 generational events. Mutation rates for various portions of the mtGenome were calculated. Nine mutations (including two transitions and seven cases of heteroplasmy) were observed, resulting in a rate of 0.058 mutations/site/million years (95% CI 0.031–0.108). These mutation rates are approximately 16 times higher than estimates derived from phylogenetic analysis with heteroplasmy detected in 13 samples (n = 225, 5.8% individuals). Providing one of the first pedigree derived estimates for the entire mtGenome, this study provides a better understanding of human mtGenome evolution and has relevance to many research fields, including medicine, anthropology and forensics.
Topology dependence of skyrmion Seebeck and skyrmion Nernst effect
Authors: Weißenhofer Markus , Nowak Ulrich 
Published: April 2022

AbstractWe explore the dynamics of skyrmions with various topological charges induced by a temperature gradient in an ultra-thin insulating magnetic film. Combining atomistic spin simulations and analytical calculations we find a topology-dependent skyrmion Seebeck effect: while skyrmions and antiskyrmions move to the hot regime, a topologically trivial localized spin structure moves to the cold regime. We further reveal the emergence of a skyrmion Nernst effect, i.e. finite, topology-dependent velocities transverse to the direction of the temperature gradient. These findings are in agreement with accompanying simulations of skyrmionic motion induced by monochromatic magnon currents, allowing us to demonstrate that the magnonic spin Seebeck effect is responsible for both, skyrmion Seebeck and Nernst effect. Furthermore we employ scattering theory together with Thiele’s equation to identify linear momentum transfer from the magnons to the skyrmion as the dominant contribution and to demonstrate that the direction of motion depends on the topological magnon Hall effect and the topological charge of the skyrmion.