bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sub-nanometer confinement enables facile condensation of gas electrolyte for low-temperature batteries
Authors: Cai Guorui , Yin Yijie , Xia Dawei , Chen Amanda A. , Holoubek John , Scharf Jonathan , Yang Yangyuchen , Koh Ki Hwan , Li Mingqian , Davies Daniel M. , Mayer Matthew , Han Tae Hee , Meng Ying Shirley , Pascal Tod A. , Chen Zheng 
Published: June 2021

AbstractConfining molecules in the nanoscale environment can lead to dramatic changes of their physical and chemical properties, which opens possibilities for new applications. There is a growing interest in liquefied gas electrolytes for electrochemical devices operating at low temperatures due to their low melting point. However, their high vapor pressure still poses potential safety concerns for practical usages. Herein, we report facile capillary condensation of gas electrolyte by strong confinement in sub-nanometer pores of metal-organic framework (MOF). By designing MOF-polymer membranes (MPMs) that present dense and continuous micropore (~0.8 nm) networks, we show significant uptake of hydrofluorocarbon molecules in MOF pores at pressure lower than the bulk counterpart. This unique property enables lithium/fluorinated graphite batteries with MPM-based electrolytes to deliver a significantly higher capacity than those with commercial separator membranes (~500 mAh g−1 vs. <0.03 mAh g−1) at −40 °C under reduced pressure of the electrolyte.
MOCCASIN: a method for correcting for known and unknown confounders in RNA splicing analysis
Authors: Slaff Barry , Radens Caleb M. , Jewell Paul , Jha Anupama , Lahens Nicholas F. , Grant Gregory R. , Thomas-Tikhonenko Andrei , Lynch Kristen W. , Barash Yoseph 
Published: June 2021

AbstractThe effects of confounding factors on gene expression analysis have been extensively studied following the introduction of high-throughput microarrays and subsequently RNA sequencing. In contrast, there is a lack of equivalent analysis and tools for RNA splicing. Here we first assess the effect of confounders on both expression and splicing quantifications in two large public RNA-Seq datasets (TARGET, ENCODE). We show quantification of splicing variations are affected at least as much as those of gene expression, revealing unwanted sources of variations in both datasets. Next, we develop MOCCASIN, a method to correct the effect of both known and unknown confounders on RNA splicing quantification and demonstrate MOCCASIN’s effectiveness on both synthetic and real data. Code, synthetic and corrected datasets are all made available as resources.
β-Arrestin-1 is required for adaptive β-cell mass expansion during obesity
Authors: Barella Luiz F. , Rossi Mario , Pydi Sai P. , Meister Jaroslawna , Jain Shanu , Cui Yinghong , Gavrilova Oksana , Fulgenzi Gianluca , Tessarollo Lino , Wess Jürgen 
Published: June 2021

AbstractObesity is the key driver of peripheral insulin resistance, one of the key features of type 2 diabetes (T2D). In insulin-resistant individuals, the expansion of beta-cell mass is able to delay or even prevent the onset of overt T2D. Here, we report that beta-arrestin-1 (barr1), an intracellular protein known to regulate signaling through G protein-coupled receptors, is essential for beta-cell replication and function in insulin-resistant mice maintained on an obesogenic diet. Specifically, insulin-resistant beta-cell-specificbarr1knockout mice display marked reductions in beta-cell mass and the rate of beta-cell proliferation, associated with pronounced impairments in glucose homeostasis. Mechanistic studies suggest that the observed metabolic deficits are due to reduced Pdx1 expression levels caused by beta-cell barr1 deficiency. These findings indicate that strategies aimed at enhancing barr1 activity and/or expression in beta-cells may prove useful to restore proper glucose homeostasis in T2D.
Multi-target mode of action of silver against Staphylococcus aureus endows it with capability to combat antibiotic resistance
Authors: Wang Haibo , Wang Minji , Xu Xiaohan , Gao Peng , Xu Zeling , Zhang Qi , Li Hongyan , Yan Aixin , Kao Richard Yi-Tsun , Sun Hongzhe 
Published: June 2021

AbstractThe rapid emergence of drug resistant Staphylococcus aureus (S. aureus) poses a serious threat to public health globally. Silver (Ag)-based antimicrobials are promising to combat antibiotic resistant S. aureus, yet their molecular targets are largely elusive. Herein, we separate and identify 38 authentic Ag+-binding proteins in S. aureus at the whole-cell scale. We then capture the molecular snapshot on the dynamic action of Ag+ against S. aureus and further validate that Ag+ could inhibit a key target 6-phosphogluconate dehydrogenase through binding to catalytic His185 by X-ray crystallography. Significantly, the multi-target mode of action of Ag+ (and nanosilver) endows its sustainable antimicrobial efficacy, leading to enhanced efficacy of conventional antibiotics and resensitization of MRSA to antibiotics. Our study resolves the long-standing question of the molecular targets of silver in S. aureus and offers insights into the sustainable bacterial susceptibility of silver, providing a potential approach for combating antimicrobial resistance.
Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade
Authors: Khan Zia , Hammer Christian , Carroll Jonathan , Di Nucci Flavia , Acosta Sergio Ley , Maiya Vidya , Bhangale Tushar , Hunkapiller Julie , Mellman Ira , Albert Matthew L. , McCarthy Mark I. , Chandler G. Scott 
Published: June 2021

AbstractActivation of systemic immune responses using PD-1 checkpoint inhibitors is an essential approach to cancer therapy. Yet, the extent of benefit relative to risk of immune related adverse events (irAE) varies widely among patients. Here, we study endocrine irAE from 7 clinical trials across 6 cancers where atezolizumab (anti-PD-L1) was combined with chemotherapies and compared to standard of care. We show that atezolizumab-induced thyroid dysfunction is associated with longer survival. We construct a polygenic risk score (PRS) for lifetime risk of hypothyroidism using a GWAS from the UK Biobank and apply this PRS to genetic data collected from 2,616 patients of European ancestry from these trials. Patients with high PRS are at increased risk of atezolizumab-induced thyroid dysfunction and lower risk of death in triple negative breast cancer. Our results indicate that genetic variation associated with thyroid autoimmunity interacts with biological pathways driving the systemic immune response to PD-1 blockade.
Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation
Authors: Karampelias Christos , Rezanejad Habib , Rosko Mandy , Duan Likun , Lu Jing , Pazzagli Laura , Bertolino Philippe , Cesta Carolyn E. , Liu Xiaojing , Korbutt Gregory S. , Andersson Olov 
Published: June 2021

AbstractDiabetes can be caused by an insufficiency in β-cell mass. Here, we performed a genetic screen in a zebrafish model of β-cell loss to identify pathways promoting β-cell regeneration. We found that both folate receptor 1 (folr1) overexpression and treatment with folinic acid, stimulated β-cell differentiation in zebrafish. Treatment with folinic acid also stimulated β-cell differentiation in cultures of neonatal pig islets, showing that the effect could be translated to a mammalian system. In both zebrafish and neonatal pig islets, the increased β-cell differentiation originated from ductal cells. Mechanistically, comparative metabolomic analysis of zebrafish with/without β-cell ablation and with/without folinic acid treatment indicated β-cell regeneration could be attributed to changes in the pyrimidine, carnitine, and serine pathways. Overall, our results suggest evolutionarily conserved and previously unknown roles for folic acid and one-carbon metabolism in the generation of β-cells.
The regulatory landscape of Arabidopsis thaliana roots at single-cell resolution
Authors: Dorrity Michael W. , Alexandre Cristina M. , Hamm Morgan O. , Vigil Anna-Lena , Fields Stanley , Queitsch Christine , Cuperus Josh T. 
Published: June 2021

AbstractThe scarcity of accessible sites that are dynamic or cell type-specific in plants may be due in part to tissue heterogeneity in bulk studies. To assess the effects of tissue heterogeneity, we apply single-cell ATAC-seq to Arabidopsis thaliana roots and identify thousands of differentially accessible sites, sufficient to resolve all major cell types of the root. We find that the entirety of a cell’s regulatory landscape and its transcriptome independently capture cell type identity. We leverage this shared information on cell identity to integrate accessibility and transcriptome data to characterize developmental progression, endoreduplication and cell division. We further use the combined data to characterize cell type-specific motif enrichments of transcription factor families and link the expression of family members to changing accessibility at specific loci, resolving direct and indirect effects that shape expression. Our approach provides an analytical framework to infer the gene regulatory networks that execute plant development.
Nutrients cause consolidation of soil carbon flux to small proportion of bacterial community
Authors: Stone Bram W. , Li Junhui , Koch Benjamin J. , Blazewicz Steven J. , Dijkstra Paul , Hayer Michaela , Hofmockel Kirsten S. , Liu Xiao-Jun Allen , Mau Rebecca L. , Morrissey Ember M. , Pett-Ridge Jennifer , Schwartz Egbert , Hungate Bruce A. 
Published: June 2021

AbstractNutrient amendment diminished bacterial functional diversity, consolidating carbon flow through fewer bacterial taxa. Here, we show strong differences in the bacterial taxa responsible for respiration from four ecosystems, indicating the potential for taxon-specific control over soil carbon cycling. Trends in functional diversity, defined as the richness of bacteria contributing to carbon flux and their equitability of carbon use, paralleled trends in taxonomic diversity although functional diversity was lower overall. Among genera common to all ecosystems, Bradyrhizobium, the Acidobacteria genus RB41, and Streptomyces together composed 45–57% of carbon flow through bacterial productivity and respiration. Bacteria that utilized the most carbon amendment (glucose) were also those that utilized the most native soil carbon, suggesting that the behavior of key soil taxa may influence carbon balance. Mapping carbon flow through different microbial taxa as demonstrated here is crucial in developing taxon-sensitive soil carbon models that may reduce the uncertainty in climate change projections.
Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
Authors: van Eeuwen Trevor , Shim Yoonjung , Kim Hee Jong , Zhao Tingting , Basu Shrabani , Garcia Benjamin A. , Kaplan Craig D. , Min Jung-Hyun , Murakami Kenji 
Published: June 2021

AbstractThe versatile nucleotide excision repair (NER) pathway initiates as the XPC–RAD23B–CETN2 complex first recognizes DNA lesions from the genomic DNA and recruits the general transcription factor complex, TFIIH, for subsequent lesion verification. Here, we present a cryo-EM structure of an NER initiation complex containing Rad4–Rad23-Rad33 (yeast homologue of XPC–RAD23B–CETN2) and 7-subunit coreTFIIH assembled on a carcinogen-DNA adduct lesion at 3.9–9.2 Å resolution. A ~30-bp DNA duplex could be mapped as it straddles between Rad4 and the Ssl2 (XPB) subunit of TFIIH on the 3' and 5' side of the lesion, respectively. The simultaneous binding with Rad4 and TFIIH was permitted by an unwinding of DNA at the lesion. Translocation coupled with torque generation by Ssl2 and Rad4 would extend the DNA unwinding at the lesion and deliver the damaged strand to Rad3 (XPD) in an open form suitable for subsequent lesion scanning and verification.
An in-memory computing architecture based on two-dimensional semiconductors for multiply-accumulate operations
Authors: Wang Yin , Tang Hongwei , Xie Yufeng , Chen Xinyu , Ma Shunli , Sun Zhengzong , Sun Qingqing , Chen Lin , Zhu Hao , Wan Jing , Xu Zihan , Zhang David Wei , Zhou Peng , Bao Wenzhong 
Published: June 2021

AbstractIn-memory computing may enable multiply-accumulate (MAC) operations, which are the primary calculations used in artificial intelligence (AI). Performing MAC operations with high capacity in a small area with high energy efficiency remains a challenge. In this work, we propose a circuit architecture that integrates monolayer MoS2 transistors in a two-transistor–one-capacitor (2T-1C) configuration. In this structure, the memory portion is similar to a 1T-1C Dynamic Random Access Memory (DRAM) so that theoretically the cycling endurance and erase/write speed inherit the merits of DRAM. Besides, the ultralow leakage current of the MoS2 transistor enables the storage of multi-level voltages on the capacitor with a long retention time. The electrical characteristics of a single MoS2 transistor also allow analog computation by multiplying the drain voltage by the stored voltage on the capacitor. The sum-of-product is then obtained by converging the currents from multiple 2T-1C units. Based on our experiment results, a neural network is ex-situ trained for image recognition with 90.3% accuracy. In the future, such 2T-1C units can potentially be integrated into three-dimensional (3D) circuits with dense logic and memory layers for low power in-situ training of neural networks in hardware.
Light regulates stomatal development by modulating paracrine signaling from inner tissues
Authors: Wang Shenqi , Zhou Zimin , Rahiman Rini , Lee Grace Sheen Yee , Yeo Yuan Kai , Yang Xin , Lau On Sun 
Published: June 2021

AbstractDevelopmental outcomes are shaped by the interplay between intrinsic and external factors. The production of stomata—essential pores for gas exchange in plants—is extremely plastic and offers an excellent system to study this interplay at the cell lineage level. For plants, light is a key external cue, and it promotes stomatal development and the accumulation of the master stomatal regulator SPEECHLESS (SPCH). However, how light signals are relayed to influence SPCH remains unknown. Here, we show that the light-regulated transcription factor ELONGATED HYPOCOTYL 5 (HY5), a critical regulator for photomorphogenic growth, is present in inner mesophyll cells and directly binds and activates STOMAGEN. STOMAGEN, the mesophyll-derived secreted peptide, in turn stabilizes SPCH in the epidermis, leading to enhanced stomatal production. Our work identifies a molecular link between light signaling and stomatal development that spans two tissue layers and highlights how an environmental signaling factor may coordinate growth across tissue types.
Transforming absolute value to categorical choice in primate superior colliculus during value-based decision making
Authors: Zhang Beizhen , Kan Janis Ying Ying , Yang Mingpo , Wang Xiaochun , Tu Jiahao , Dorris Michael Christopher 
Published: June 2021

AbstractValue-based decision making involves choosing from multiple options with different values. Despite extensive studies on value representation in various brain regions, the neural mechanism for how multiple value options are converted to motor actions remains unclear. To study this, we developed a multi-value foraging task with varying menu of items in non-human primates using eye movements that dissociates value and choice, and conducted electrophysiological recording in the midbrain superior colliculus (SC). SC neurons encoded “absolute” value, independent of available options, during late fixation. In addition, SC neurons also represent value threshold, modulated by available options, different from conventional motor threshold. Electrical stimulation of SC neurons biased choices in a manner predicted by the difference between the value representation and the value threshold. These results reveal a neural mechanism directly transforming absolute values to categorical choices within SC, supporting highly efficient value-based decision making critical for real-world economic behaviors.
Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer’s disease
Authors: Fitz Nicholas F. , Nam Kyong Nyon , Wolfe Cody M. , Letronne Florent , Playso Brittany E. , Iordanova Bistra E. , Kozai Takashi D. Y. , Biedrzycki Richard J. , Kagan Valerian E. , Tyurina Yulia Y. , Han Xianlin , Lefterov Iliya , Koldamova Radosveta 
Published: June 2021

AbstractAPOE and Trem2 are major genetic risk factors for Alzheimer’s disease (AD), but how they affect microglia response to Aβ remains unclear. Here we report an APOE isoform-specific phospholipid signature with correlation between human APOEε3/3 and APOEε4/4 AD brain and lipoproteins from astrocyte conditioned media of APOE3 and APOE4 mice. Using preclinical AD mouse models, we show that APOE3 lipoproteins, unlike APOE4, induce faster microglial migration towards injected Aβ, facilitate Aβ uptake, and ameliorate Aβ effects on cognition. Bulk and single-cell RNA-seq demonstrate that, compared to APOE4, cortical infusion of APOE3 lipoproteins upregulates a higher proportion of genes linked to an activated microglia response, and this trend is augmented by TREM2 deficiency. In vitro, lack of TREM2 decreases Aβ uptake by APOE4-treated microglia only, suggesting TREM2-APOE interaction. Our study elucidates phenotypic and transcriptional differences in microglial response to Aβ mediated by APOE3 or APOE4 lipoproteins in preclinical models of AD.
Hippocampal place cell sequences differ during correct and error trials in a spatial memory task
Authors: Zheng Chenguang , Hwaun Ernie , Loza Carlos A. , Colgin Laura Lee 
Published: June 2021

AbstractTheta rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We investigated whether such coordination of hippocampal place cell sequences is disrupted during error trials in a delayed match-to-place task. As a reward location was learned across trials, place cell sequences developed that represented temporally compressed paths to the reward location during the approach to the reward location. Less compressed paths were represented on error trials as an incorrect stop location was approached. During rest periods of correct but not error trials, place cell sequences developed a bias to replay representations of paths ending at the correct reward location. These results support the hypothesis that coordination of place cell sequences by theta rhythms and sharp wave-ripples develops as a reward location is learned and may be important for the successful performance of a spatial memory task.
Vapor-phased fabrication and modulation of cell-laden scaffolding materials
Authors: Wu Chih-Yu , Wu Ting-Ying , Guan Zhen-Yu , Wang Peng-Yuan , Yang Yen-Ching , Huang Chao-Wei , Lin Tzu-Hung , Chen Hsien-Yeh 
Published: June 2021

AbstractBottom–up approaches using building blocks of modules to fabricate scaffolds for tissue engineering applications have enabled the fabrication of structurally complex and multifunctional materials allowing for physical and chemical flexibility to better mimic the native extracellular matrix. Here we report a vapor-phased fabrication process for constructing three-dimensional modulated scaffold materials via simple steps based on controlling mass transport of vapor sublimation and deposition. We demonstrate the fabrication of scaffolds comprised of multiple biomolecules and living cells with built-in boundaries separating the distinct compartments containing defined biological configurations and functions. We show that the fabricated scaffolds have mass production potential. We demonstrate overall >80% cell viability of encapsulated cells and that modulated scaffolds exhibit enhanced cell proliferation, osteogenesis, and neurogenesis, which can be assembled into various geometric configurations. We perform cell co-culture experiments to show independent osteogenesis and angiogenesis activities from separate compartments in one scaffold construct.
OPG/TRAIL ratio as a predictive biomarker of mortality in patients with type A acute aortic dissection
Authors: Lu Jie , Li Ping , Ma Ke , Li Yang , Yuan Hui , Zhu Junming , Duan Weixun , Ou Jingsong , Huang Yonghong , Wu Long , Pan Xueliang , Zhang Hui , Du Jie , Li Yulin 
Published: June 2021

AbstractFollowing hospital discharge, patients with type A acute aortic dissection (TA-AAD) may present an increase in mortality risk. However, little is known about specific biomarkers associated with post-discharge survival, and there is a paucity of prognostic markers associated with TA-AAD. Here, we identify nine candidate proteins specific for patietns with TA-AAD in a cross-sectional dataset by unbiased protein screening and in-depth bioinformatic analyses. In addition, we explore their association with short-term and long-term mortality in a derivation cohort of patients with TA-AAD, including an internal (n = 300) and external (n = 236) dataset. An elevated osteoprotegerin (OPG)/tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) ratio was the strongest predictor of overall, 30-day, post-30-day mortality in both datasets and was confirmed to be a strong predictor of mortality in an independent validation cohort (n = 400). Based on OPG/TRAIL ratio-guided risk stratification, patients at high risk (>33) had a higher 1-year mortality (55.6% vs. 4.3%; 68.2% vs. 2.6%) than patients at low risk (<4) in both cohorts. In Conclusion, we show that an elevated OPG/TRAIL ratio is associated with a significant increase in short-term and long-term mortality in patients with TA-AAD.
Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells
Authors: Cifarelli Vincenza , Appak-Baskoy Sila , Peche Vivek S. , Kluzak Andrew , Shew Trevor , Narendran Ramkumar , Pietka Kathryn M. , Cella Marina , Walls Curtis W. , Czepielewski Rafael , Ivanov Stoyan , Randolph Gwendalyn J. , Augustin Hellmut G. , Abumrad Nada A. 
Published: June 2021

AbstractDisruption of lymphatic lipid transport is linked to obesity and type 2 diabetes (T2D), but regulation of lymphatic vessel function and its link to disease remain unclear. Here we show that intestinal lymphatic endothelial cells (LECs) have an increasing CD36 expression from lymphatic capillaries (lacteals) to collecting vessels, and that LEC CD36 regulates lymphatic integrity and optimizes lipid transport. Inducible deletion of CD36 in LECs in adult mice (Cd36ΔLEC) increases discontinuity of LEC VE-cadherin junctions in lacteals and collecting vessels. Cd36ΔLEC mice display slower transport of absorbed lipid, more permeable mesenteric lymphatics, accumulation of inflamed visceral fat and impaired glucose disposal. CD36 silencing in cultured LECs suppresses cell respiration, reduces VEGF-C-mediated VEGFR2/AKT phosphorylation and destabilizes VE-cadherin junctions. Thus, LEC CD36 optimizes lymphatic junctions and integrity of lymphatic lipid transport, and its loss in mice causes lymph leakage, visceral adiposity and glucose intolerance, phenotypes that increase risk of T2D.