bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the Eastern Equatorial Pacific Seasonal Cycle by Tropical Instability Waves
Authors: Maillard L. , Boucharel J. , Stuecker M. F. , Jin F.‐F. , Renault L. 
Published: November 2022

AbstractFeedbacks from tropical instability waves (TIWs) on the seasonal cycle of the eastern Pacific Ocean are studied using two eddy‐rich ocean simulations, with and without TIWs. By warming the equatorial waters by up to 0.4°C through nonlinear advection in boreal summer and fall, TIWs reduce the amplitude of the seasonal cycle in upper ocean temperatures. In addition, TIWs stabilize the upper part of the Equatorial Undercurrent (EUC) through enhanced barotropic energy conversion, leading to a year‐round weakening by −0.15 m s−1 and preventing an unrealistic re‐intensification in boreal fall usually found in non‐eddy resolving models. A coarser simulation at 1‐degree horizontal resolution fails to reproduce the TIW‐induced nonlinear warming of equatorial waters, but succeeds in inhibiting the EUC re‐intensification. This suggests a threshold effect in TIW strength, associated with the model's ability to simulate eddies, which may be responsible for long‐standing biases displayed by global climate models in this region.
Induction of Nanog in neural progenitor cells for adaptive regeneration of ischemic brain
Authors: Jung Gyung-Ah , Kim Jin-A , Park Hwan-Woo , Lee Hyemi , Chang Mi-Sook , Cho Kyung-Ok , Song Byeong-Wook , Kim Hyun-Ju , Kwon Yunhee Kim , Oh Il-Hoan 
Published: November 2022

AbstractNANOG plays a key role in cellular plasticity and the acquisition of the stem cell state during reprogramming, but its role in the regenerative process remains unclear. Here, we show that the induction of NANOG in neuronal cells is necessary for the physiological initiation of neuronal regeneration in response to ischemic stress. Specifically, we found that NANOG was preferentially expressed in undifferentiated neuronal cells, and forced expression of Nanog in neural progenitor cells (NPCs) promoted their self-renewing expansion both in ex-vivo slice cultures and in vitro limiting dilution analysis. Notably, the upstream region of the Nanog gene contains sequence motifs for hypoxia-inducible factor-1 alpha (HIF-1α). Therefore, cerebral neurons exposed to hypoxia significantly upregulated NANOG expression selectively in primitive (CD133+) cells, but not in mature cells, leading to the expansion of NPCs. Notably, up to 80% of the neuronal expansion induced by hypoxia was attributed to NANOG-expressing neuronal cells, whereas knockdown during hypoxia abolished this expansion and was accompanied by the downregulation of other pluripotency-related genes. Moreover, the number of NANOG-expressing neuronal cells were transiently increased in response to ischemic insult, predominantly in the infarct area of brain regions undergoing neurogenesis, but not in non-neurogenic loci. Together, these findings reveal a functional effect of NANOG-induction for the initiation of adaptive neuronal regeneration among heterogeneous NPC subsets, pointing to cellular plasticity as a potential link between regeneration and reprogramming processes.
Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1
Authors: Peng Jinfeng , Zhao Jiajia , Tang Qingming , Wang Jinyu , Song Wencheng , Lu Xiaofeng , Huang Xiaofei , Chen Guangjin , Zheng Wenhao , Zhang Luoying , Han Yunyun , Yan Chunze , Wan Qian , Chen Lili 
Published: November 2022

AbstractBone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Hypodopaminergic state of the nigrostriatal pathway drives compulsive alcohol use
Authors: Goutaudier Raphaël , Joly Fanny , Mallet David , Bartolomucci Magali , Guicherd Denis , Carcenac Carole , Vossier Frédérique , Dufourd Thibault , Boulet Sabrina , Deransart Colin , Chovelon Benoit , Carnicella Sebastien 
Published: November 2022

AbstractThe neurobiological mechanisms underlying compulsive alcohol use, a cardinal feature of alcohol use disorder, remain elusive. The key modulator of motivational processes, dopamine (DA), is suspected to play an important role in this pathology, but its exact role remains to be determined. Here, we found that rats expressing compulsive-like alcohol use, operationalized as punishment-resistant self-administration, showed a decrease in DA levels restricted to the dorsolateral territories of the striatum, the main output structure of the nigrostriatal DA pathway. We then causally demonstrated that chemogenetic-induced selective hypodopaminergia of this pathway resulted in compulsive-like alcohol self-administration in otherwise resilient rats, accompanied by the emergence of alcohol withdrawal-like motivational impairments (i.e., impaired motivation for a natural reinforcer). Finally, the use of the monoamine stabilizer OSU6162, previously reported to correct hypodopaminergic states, transiently decreased compulsive-like alcohol self-administration in vulnerable rats. These results suggest a potential critical role of tonic nigrostriatal hypodopaminergic states in alcohol addiction and provide new insights into our understanding of the neurobiological mechanisms underlying compulsive alcohol use.
Targeting glutamine metabolism in hepatic stellate cells alleviates liver fibrosis
Authors: Yin Xiaochun , Peng Jin , Gu Lihong , Liu Yan , Li Xihan , Wu Jinhui , Xu Bing , Zhuge Yuzheng , Zhang Feng 
Published: November 2022

AbstractGlutamine metabolism plays an essential role in cell growth, and glutamate dehydrogenase (GDH) is a key enzyme. GDH promotes the metabolism of glutamate and glutamine to generate ATP, which is profoundly increased in multiple human cancers. Through in vitro and in vivo experiments, we verified that the small-molecule GDH inhibitor EGCG slowed the progression of fibrosis by inhibiting GDH enzyme activity and glutamine metabolism. SIRT4 is a mitochondrial enzyme with NAD that promotes ADP ribosylation and downregulates GDH activity. The role of SIRT4 in liver fibrosis and the related mechanisms are unknown. In this study, we measured the expression of SIRT4 and found that it was downregulated in liver fibrosis. Modest overexpression of SIRT4 protected the liver from fibrosis by inhibiting the transformation of glutamate to 2-ketoglutaric acid (α-KG) in the tricarboxylic acid cycle (TCA), thereby reducing the proliferative activity of hepatic stellate cells (HSCs). Collectively, our study reveals that SIRT4 controls GDH enzyme activity and expression, targeting glutamine metabolism in HSCs and alleviating liver fibrosis.
Air quality impacts of crop residue burning in India and mitigation alternatives
Authors: Lan Ruoyu , Eastham Sebastian D. , Liu Tianjia , Norford Leslie K. , Barrett Steven R. H. 
Published: November 2022

AbstractCrop residue burning contributes to poor air quality and imposes a health burden on India. Despite government bans and other interventions, this practice remains widespread. Here we estimate the impact of changes in agricultural emissions on air quality across India and quantify the potential benefit of district-level actions using an adjoint modeling approach. From 2003 to 2019, we find that agricultural residue burning caused 44,000–98,000 particulate matter exposure-related premature deaths annually, of which Punjab, Haryana, and Uttar Pradesh contribute 67–90%. Due to a combination of relatively high downwind population density, agricultural output, and cultivation of residue-intensive crops, six districts in Punjab alone contribute to 40% of India-wide annual air quality impacts from residue burning. Burning two hours earlier in Punjab alone could avert premature deaths up to 9600 (95% CI: 8000–11,000) each year, valued at 3.2 (95% CI: 0.49–7.3) billion US dollars. Our findings support the use of targeted and potentially low-cost interventions to mitigate crop residue burning in India, pending further research regarding cost-effectiveness and feasibility.
Calcium-mediated rapid movements defend against herbivorous insects in Mimosa pudica
Authors: Hagihara Takuma , Mano Hiroaki , Miura Tomohiro , Hasebe Mitsuyasu , Toyota Masatsugu 
Published: November 2022

AbstractAnimals possess specialized systems, e.g., neuromuscular systems, to sense the environment and then move their bodies quickly in response. Mimosa pudica, the sensitive plant, moves its leaves within seconds in response to external stimuli; e.g., touch or wounding. However, neither the plant-wide signaling network that triggers these rapid movements nor the physiological roles of the movements themselves have been determined. Here by simultaneous recording of cytosolic Ca2+ and electrical signals, we show that rapid changes in Ca2+ coupled with action and variation potentials trigger rapid movements in wounded M. pudica. Furthermore, pharmacological manipulation of cytosolic Ca2+ dynamics and CRISPR-Cas9 genome editing technology revealed that an immotile M. pudica is more vulnerable to attacks by herbivorous insects. Our findings provide evidence that rapid movements based on propagating Ca2+ and electrical signals protect this plant from insect attacks.
Safety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents
Authors: Wang Lei , Wu Zhiwei , Ying Zhifang , Li Minjie , Hu Yuansheng , Shu Qun , Li Jing , Wang Huixian , Zhang Hengming , Jiao Wenbin , Wang Lin , Zhao Yuliang , Gao Qiang 
Published: November 2022

AbstractData on safety and immunity elicited by a third booster dose of inactivated COVID-19 vaccine in children and adolescents are scarce. Here we conducted a study based on a double-blind, randomised, placebo-controlled phase 2 clinical trial (NCT04551547) to assess the safety and immunogenicity of a third dose of CoronaVac. In this study, 384 participants in the vaccine group were assigned to two cohorts. One received the third dose at a 10-months interval (cohort 1) and the other one at a 12-months interval (cohort 2). The primary endpoint is safety and immunogenicity following a third dose of CoronaVac. The secondary endpoint is antibody persistence following the primary two-dose schedule. Severities of local and systemic adverse reactions reported within 28 days after dose 3 were mild and moderate in both cohorts. A third dose of CoronaVac increased GMTs to 681.0 (95%CI: 545.2–850.7) in cohort 1 and 745.2 (95%CI: 577.0–962.3) in cohort 2. Seropositivity rates against the prototype were 100% on day 28 after dose 3. Seropositivity rates against the Omicron variant were 90.6% (cohort 1) and 91.5% (cohort 2). A homologous booster dose of CoronaVac is safe and induces a significant neutralising antibody levels increase in children and adolescents.
Transposable elements orchestrate subgenome-convergent and -divergent transcription in common wheat
Authors: Zhang Yuyun , Li Zijuan , Liu Jinyi , Zhang Yu’e , Ye Luhuan , Peng Yuan , Wang Haoyu , Diao Huishan , Ma Yu , Wang Meiyue , Xie Yilin , Tang Tengfei , Zhuang Yili , Teng Wan , Tong Yiping , Zhang Wenli , Lang Zhaobo , Xue Yongbiao , Zhang Yijing 
Published: November 2022

AbstractThe success of common wheat as a global staple crop was largely attributed to its genomic diversity and redundancy due to the merge of different genomes, giving rise to the major question how subgenome-divergent and -convergent transcription is mediated and harmonized in a single cell. Here, we create a catalog of genome-wide transcription factor-binding sites (TFBSs) to assemble a common wheat regulatory network on an unprecedented scale. A significant proportion of subgenome-divergent TFBSs are derived from differential expansions of particular transposable elements (TEs) in diploid progenitors, which contribute to subgenome-divergent transcription. Whereas subgenome-convergent transcription is associated with balanced TF binding at loci derived from TE expansions before diploid divergence. These TFBSs have retained in parallel during evolution of each diploid, despite extensive unbalanced turnover of the flanking TEs. Thus, the differential evolutionary selection of paleo- and neo-TEs contribute to subgenome-convergent and -divergent regulation in common wheat, highlighting the influence of TE repertory plasticity on transcriptional plasticity in polyploid.
Promoting anti-tumor immunity by targeting TMUB1 to modulate PD-L1 polyubiquitination and glycosylation
Authors: Shi Chengyu , Wang Ying , Wu Minjie , Chen Yu , Liu Fangzhou , Shen Zheyuan , Wang Yiran , Xie Shaofang , Shen Yingying , Sang Lingjie , Zhang Zhen , Gao Zerui , Yang Luojia , Qu Lei , Yang Zuozhen , He Xinyu , Guo Yu , Pan Chenghao , Che Jinxin , Ju Huaiqiang , Liu Jian , Cai Zhijian , Yan Qingfeng , Yu Luyang , Wang Liangjing , Dong Xiaowu , Xu Pinglong , Shao Jianzhong , Liu Yang , Li Xu , Wang Wenqi , Zhou Ruhong , Zhou Tianhua , Lin Aifu 
Published: November 2022

AbstractImmune checkpoint blockade therapies targeting the PD-L1/PD-1 axis have demonstrated clear clinical benefits. Improved understanding of the underlying regulatory mechanisms might contribute new insights into immunotherapy. Here, we identify transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) as a modulator of PD-L1 post-translational modifications in tumor cells. Mechanistically, TMUB1 competes with HECT, UBA and WWE domain-containing protein 1 (HUWE1), a E3 ubiquitin ligase, to interact with PD-L1 and inhibit its polyubiquitination at K281 in the endoplasmic reticulum. Moreover, TMUB1 enhances PD-L1 N-glycosylation and stability by recruiting STT3A, thereby promoting PD-L1 maturation and tumor immune evasion. TMUB1 protein levels correlate with PD-L1 expression in human tumor tissue, with high expression being associated with poor patient survival rates. A synthetic peptide engineered to compete with TMUB1 significantly promotes antitumor immunity and suppresses tumor growth in mice. These findings identify TMUB1 as a promising immunotherapeutic target.
Global and regional ecological boundaries explain abrupt spatial discontinuities in avian frugivory interactions
Authors: Martins Lucas P. , Stouffer Daniel B. , Blendinger Pedro G. , Böhning-Gaese Katrin , Buitrón-Jurado Galo , Correia Marta , Costa José Miguel , Dehling D. Matthias , Donatti Camila I. , Emer Carine , Galetti Mauro , Heleno Ruben , Jordano Pedro , Menezes Ícaro , Morante-Filho José Carlos , Muñoz Marcia C. , Neuschulz Eike Lena , Pizo Marco Aurélio , Quitián Marta , Ruggera Roman A. , Saavedra Francisco , Santillán Vinicio , Sanz D’Angelo Virginia , Schleuning Matthias , da Silva Luís Pascoal , Ribeiro da Silva Fernanda , Timóteo Sérgio , Traveset Anna , Vollstädt Maximilian G. R. , Tylianakis Jason M. 
Published: November 2022

AbstractSpecies interactions can propagate disturbances across space via direct and indirect effects, potentially connecting species at a global scale. However, ecological and biogeographic boundaries may mitigate this spread by demarcating the limits of ecological networks. We tested whether large-scale ecological boundaries (ecoregions and biomes) and human disturbance gradients increase dissimilarity among plant-frugivore networks, while accounting for background spatial and elevational gradients and differences in network sampling. We assessed network dissimilarity patterns over a broad spatial scale, using 196 quantitative avian frugivory networks (encompassing 1496 plant and 1004 bird species) distributed across 67 ecoregions, 11 biomes, and 6 continents. We show that dissimilarities in species and interaction composition, but not network structure, are greater across ecoregion and biome boundaries and along different levels of human disturbance. Our findings indicate that biogeographic boundaries delineate the world’s biodiversity of interactions and likely contribute to mitigating the propagation of disturbances at large spatial scales.
Region-specific denoising identifies spatial co-expression patterns and intra-tissue heterogeneity in spatially resolved transcriptomics data
Authors: Wang Linhua , Maletic-Savatic Mirjana , Liu Zhandong 
Published: November 2022

AbstractSpatially resolved transcriptomics is a relatively new technique that maps transcriptional information within a tissue. Analysis of these datasets is challenging because gene expression values are highly sparse due to dropout events, and there is a lack of tools to facilitate in silico detection and annotation of regions based on their molecular content. Therefore, we develop a computational tool for detecting molecular regions and region-based Missing value Imputation for Spatially Transcriptomics (MIST). We validate MIST-identified regions across multiple datasets produced by 10x Visium Spatial Transcriptomics, using manually annotated histological images as references. We benchmark MIST against a spatial k-nearest neighboring baseline and other imputation methods designed for single-cell RNA sequencing. We use holdout experiments to demonstrate that MIST accurately recovers spatial transcriptomics missing values. MIST facilitates identifying intra-tissue heterogeneity and recovering spatial gene-gene co-expression signals. Using MIST before downstream analysis thus provides unbiased region detections to facilitate annotations with the associated functional analyses and produces accurately denoised spatial gene expression profiles.
Replication collisions induced by de-repressed S-phase transcription are connected with malignant transformation of adult stem cells
Authors: Zhang Ting , Künne Carsten , Ding Dong , Günther Stefan , Guo Xinyue , Zhou Yonggang , Yuan Xuejun , Braun Thomas 
Published: November 2022

AbstractTranscription replication collisions (TRCs) constitute a major intrinsic source of genome instability but conclusive evidence for a causal role of TRCs in tumor initiation is missing. We discover that lack of the H4K20-dimethyltransferase KMT5B (also known as SUV4-20H1) in muscle stem cells de-represses S-phase transcription by increasing H4K20me1 levels, which induces TRCs and aberrant R-loops in oncogenic genes. The resulting replication stress and aberrant mitosis activate ATR-RPA32-P53 signaling, promoting cellular senescence, which turns into rapid rhabdomyosarcoma formation when p53 is absent. Inhibition of S-phase transcription ameliorates TRCs and formation of R-loops in Kmt5b-deficient MuSCs, validating the crucial role of H4K20me1-dependent, tightly controlled S-phase transcription for preventing collision errors. Low KMT5B expression is prevalent in human sarcomas and associated with tumor recurrence, suggesting a common function of KMT5B in sarcoma formation. The study uncovers decisive functions of KMT5B for maintaining genome stability by repressing S-phase transcription via control of H4K20me1 levels.
Third primary SARS-CoV-2 mRNA vaccines enhance antibody responses in most patients with haematological malignancies
Authors: Cook Lucy B. , O’Dell Gillian , Vourvou Eleni , Palanicawandar Renuka , Marks Sasha , Milojkovic Dragana , Apperley Jane F. , Loaiza Sandra , Claudiani Simone , Bua Marco , Hockings Catherine , Macdonald Donald , Chaidos Aris , Pavlu Jiri , Cooper Nichola , Fidler Sarah , Randell Paul , Innes Andrew J. 
Published: November 2022

AbstractSARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have reduced hospitalisations and deaths, but vaccine efficacy in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. The MARCH database is a retrospective observational study of serological responses in patients with blood disorders. Here we present data on 381 patients with haematological malignancies. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued suboptimal vaccine responses who may benefit from additional doses, prophylactic extended half-life neutralising monoclonal therapies (nMAB) or prompt nMAB treatment in the event of SARS-CoV-2 infection.
Accurate graphene quantum Hall arrays for the new International System of Units
Authors: He Hans , Cedergren Karin , Shetty Naveen , Lara-Avila Samuel , Kubatkin Sergey , Bergsten Tobias , Eklund Gunnar 
Published: November 2022

AbstractGraphene quantum Hall effect (QHE) resistance standards have the potential to provide superior realizations of three key units in the new International System of Units (SI): the ohm, the ampere, and the kilogram (Kibble Balance). However, these prospects require different resistance values than practically achievable in single graphene devices (~12.9 kΩ), and they need bias currents two orders of magnitude higher than typical breakdown currents IC ~ 100 μA. Here we present experiments on quantization accuracy of a 236-element quantum Hall array (QHA), demonstrating RK/236 ≈ 109 Ω with 0.2 part-per-billion (nΩ/Ω) accuracy with IC ≥ 5 mA (~1 nΩ/Ω accuracy for IC = 8.5 mA), using epitaxial graphene on silicon carbide (epigraphene). The array accuracy, comparable to the most precise universality tests of QHE, together with the scalability and reliability of this approach, pave the road for wider use of graphene in the new SI and beyond.
Critical role of hydrogen sorption kinetics in electrocatalytic CO2 reduction revealed by on-chip in situ transport investigations
Authors: Mu Zhangyan , Han Na , Xu Dan , Tian Bailin , Wang Fangyuan , Wang Yiqi , Sun Yamei , Liu Cheng , Zhang Panke , Wu Xuejun , Li Yanguang , Ding Mengning 
Published: November 2022

AbstractPrecise understanding of interfacial metal−hydrogen interactions, especially under in operando conditions, is crucial to advancing the application of metal catalysts in clean energy technologies. To this end, while Pd-based catalysts are widely utilized for electrochemical hydrogen production and hydrogenation, the interaction of Pd with hydrogen during active electrochemical processes is complex, distinct from most other metals, and yet to be clarified. In this report, the hydrogen surface adsorption and sub-surface absorption (phase transition) features of Pd and its alloy nanocatalysts are identified and quantified under operando electrocatalytic conditions via on-chip electrical transport measurements, and the competitive relationship between electrochemical carbon dioxide reduction (CO2RR) and hydrogen sorption kinetics is investigated. Systematic dynamic and steady-state evaluations reveal the key impacts of local electrolyte environment (such as proton donors with different pKa) on the hydrogen sorption kinetics during CO2RR, which offer additional insights into the electrochemical interfaces and optimization of the catalytic systems.