bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone methyltransferase MLL1 drives renal tubular cell apoptosis by p53-dependent repression of E-cadherin during cisplatin-induced acute kidney injury
Authors: Zhang Chunyun , Guan Yingjie , Zou Jianan , Yang Xu , Bayliss Georgia , Zhuang Shougang 
Published: September 2022

AbstractMixed lineage leukemia 1 (MLL1) is a histone H3 lysine 4 (H3K4) methyltransferase that interacts with WD repeat domain 5 (WDR5) to regulate cell survival, proliferation, and senescence. The role of MLL1 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we demonstrate that MLL1, WDR5, and trimethylated H3K4 (H3K4me3) were upregulated in renal tubular cells of cisplatin-induced AKI in mice, along with increased phosphorylation of p53 and decreased expression of E-cadherin. Administration of MM102, a selective MLL1/WDR5 complex inhibitor, improved renal function and attenuated tubular injury and apoptosis, while repressing MLL1, WDR5, and H3K4me3, dephosphorylating p53 and preserving E-cadherin. In cultured mouse renal proximal tubular cells (RPTCs) exposed to cisplatin, treatment with MM102 or transfection with siRNAs for either MLL1 or WDR5 also inhibited apoptosis and p53 phosphorylation while preserving E-cadherin expression; p53 inhibition with Pifithrin-α lowered cisplatin-induced apoptosis without affecting expression of MLL1, WDR5, and H3K4me3. Interestingly, silencing of E-cadherin offset MM102’s cytoprotective effects, but had no effect on p53 phosphorylation. These findings suggest that MLL1/WDR5 activates p53, which, in turn, represses E-cadherin, leading to apoptosis during cisplatin-induced AKI. Further studies showed that MM102 effectively inhibited cisplatin-triggered DNA damage response (DDR), as indicated by dephosphorylation of ataxia telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR) proteins, dephosphorylation of checkpoint kinase 1 and 2 (Chk1 and Chk2); depression of γ-H2AX; and restrained cell cycle arrest, as evidenced by decreased expression of p21 and phospho-histone H3 at serine 10 in vitro and in vivo. Overall, we identify MLL1 as a novel DDR regulator that drives cisplatin-induced RPTC apoptosis and AKI by modulating the MLL1/WDR5-/ATR/ATM-Chk-p53-E-cadherin axis. Targeting the MLL1/WDR5 complex may have a therapeutic potential for the treatment of AKI.
TREM2/β-catenin attenuates NLRP3 inflammasome-mediated macrophage pyroptosis to promote bacterial clearance of pyogenic bacteria
Authors: Wang Yi , Cao Can , Zhu Yanting , Fan Huifeng , Liu Qiaojuan , Liu Yiting , Chen Kang , Wu Yongjian , Liang Siping , Li Meiyu , Li Lexi , Liu Xi , Zhang Yuanqing , Wu Chenglin , Lu Gen , Wu Minhao 
Published: September 2022

AbstractTriggering receptors expressed on myeloid cells 2 (TREM2) is considered a protective factor to protect host from bacterial infection, while how it elicits this role is unclear. In the present study, we demonstrate that deficiency of triggering receptors expressed on myeloid cells 2 (TREM2) significantly enhanced macrophage pyroptosis induced by four common pyogenic bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Escherichia coli. TREM2 deficiency also decreased bacterial killing ratio of macrophage, while Caspase-1 or GSDMD inhibition promoted macrophage-mediated clearance to these bacteria. Further study demonstrated that the effect of TREM2 on macrophage pyroptosis and bacterial eradication mainly dependents on the activated status of NLRP3 inflammasome. Moreover, as the key downstream of TREM2, β-catenin phosphorylated at Ser675 by TREM2 signal and accumulated in nucleus and cytoplasm. β-catenin mediated the effect of TREM2 on NLRP3 inflammasome and macrophage pyroptosis by reducing NLRP3 expression, and inhibiting inflammasome complex assembly by interacting with ASC. Collectively, TREM2/β-catenin inhibits NLRP3 inflammasome to regulate macrophage pyroptosis, and enhances macrophage-mediated pyogenic bacterial clearance.
Long read genome assemblies complemented by single cell RNA-sequencing reveal genetic and cellular mechanisms underlying the adaptive evolution of yak
Authors: Gao Xue , Wang Sheng , Wang Yan-Fen , Li Shuang , Wu Shi-Xin , Yan Rong-Ge , Zhang Yi-Wen , Wan Rui-Dong , He Zhen , Song Ren-De , Zhao Xin-Quan , Wu Dong-Dong , Yang Qi-En 
Published: September 2022

AbstractWild yak (Bos mutus) and domestic yak (Bos grunniens) are adapted to high altitude environment and have ecological, economic, and cultural significances on the Qinghai-Tibetan Plateau (QTP). Currently, the genetic and cellular bases underlying adaptations of yak to extreme conditions remains elusive. In the present study, we assembled two chromosome-level genomes, one each for wild yak and domestic yak, and screened structural variants (SVs) through the long-read data of yak and taurine cattle. The results revealed that 6733 genes contained high-FST SVs. 127 genes carrying special type of SVs were differentially expressed in lungs of the taurine cattle and yak. We then constructed the first single-cell gene expression atlas of yak and taurine cattle lung tissues and identified a yak-specific endothelial cell subtype. By integrating SVs and single-cell transcriptome data, we revealed that the endothelial cells expressed the highest proportion of marker genes carrying high-FST SVs in taurine cattle lungs. Furthermore, we identified pathways which were related to the medial thickness and formation of elastic fibers in yak lungs. These findings provide new insights into the high-altitude adaptation of yak and have important implications for understanding the physiological and pathological responses of large mammals and humans to hypoxia.
Neolithic culinary traditions revealed by cereal, milk and meat lipids in pottery from Scottish crannogs
Authors: Hammann Simon , Bishop Rosie R. , Copper Mike , Garrow Duncan , Greenwood Caitlin , Hewson Lanah , Sheridan Alison , Sturt Fraser , Whelton Helen L. , Cramp Lucy J. E. 
Published: September 2022

AbstractCereal cultivation in Britain dates back to ca. 4000 BCE, probably introduced by migrant farmers from continental Europe. Widespread evidence for livestock appears in the archaeozoological record, also reflected by ubiquitous dairy lipids in pottery organic residues. However, despite archaeobotanical evidence for domesticated plants (such as cereals), organic residue evidence has been near-absent. Our approach, targeting low-abundance cereal-specific markers, has now revealed evidence for cereals (indicating wheat) in Neolithic pottery from Scottish ‘crannogs’, dating to ca. 3600 – 3300 BCE. Their association with dairy products suggests cereals may have been regularly prepared together as a milk-based gruel. We also observed a strong association between the occurrence of dairy products and smaller-mouthed vessels. Here, we demonstrate that cereal-specific markers can survive in cooking pots for millennia, revealing the consumption of specific cereals (wheat) that are virtually absent from the archaeobotanical record for this region and illuminating culinary traditions among early farming communities.
Hydrogen production from the air
Authors: Guo Jining , Zhang Yuecheng , Zavabeti Ali , Chen Kaifei , Guo Yalou , Hu Guoping , Fan Xiaolei , Li Gang Kevin 
Published: September 2022

AbstractGreen hydrogen produced by water splitting using renewable energy is the most promising energy carrier of the low-carbon economy. However, the geographic mismatch between renewables distribution and freshwater availability poses a significant challenge to its production. Here, we demonstrate a method of direct hydrogen production from the air, namely, in situ capture of freshwater from the atmosphere using hygroscopic electrolyte and electrolysis powered by solar or wind with a current density up to 574 mA cm−2. A prototype of such has been established and operated for 12 consecutive days with a stable performance at a Faradaic efficiency around 95%. This so-called direct air electrolysis (DAE) module can work under a bone-dry environment with a relative humidity of 4%, overcoming water supply issues and producing green hydrogen sustainably with minimal impact to the environment. The DAE modules can be easily scaled to provide hydrogen to remote, (semi-) arid, and scattered areas.
Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus
Authors: Zhao Fangzhu , Berndsen Zachary T. , Pedreño-Lopez Nuria , Burns Alison , Allen Joel D. , Barman Shawn , Lee Wen-Hsin , Chakraborty Srirupa , Gnanakaran Sandrasegaram , Sewall Leigh M. , Ozorowski Gabriel , Limbo Oliver , Song Ge , Yong Peter , Callaghan Sean , Coppola Jessica , Weisgrau Kim L. , Lifson Jeffrey D. , Nedellec Rebecca , Voigt Thomas B. , Laurino Fernanda , Louw Johan , Rosen Brandon C. , Ricciardi Michael , Crispin Max , Desrosiers Ronald C. , Rakasz Eva G. , Watkins David I. , Andrabi Raiees , Ward Andrew B. , Burton Dennis R. , Sok Devin 
Published: September 2022

AbstractSIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.
On the origin of elasticity and heat conduction anisotropy of liquid crystal elastomers at gigahertz frequencies
Authors: Cang Yu , Liu Jiaqi , Ryu Meguya , Graczykowski Bartlomiej , Morikawa Junko , Yang Shu , Fytas George 
Published: September 2022

AbstractLiquid crystal elastomers that offer exceptional load-deformation response at low frequencies often require consideration of the mechanical anisotropy only along the two symmetry directions. However, emerging applications operating at high frequencies require all five true elastic constants. Here, we utilize Brillouin light spectroscopy to obtain the engineering moduli and probe the strain dependence of the elasticity anisotropy at gigahertz frequencies. The Young’s modulus anisotropy,E||/E⊥~2.6, is unexpectedly lower than that measured by tensile testing, suggesting disparity between the local mesogenic orientation and the larger scale orientation of the network strands. Unprecedented is the robustness ofE||/E⊥to uniaxial load that it does not comply with continuously transformable director orientation observed in the tensile testing. Likewise, the heat conductivity is directional,κ||/κ⊥~3.0 withκ⊥= 0.16 Wm−1K−1. Conceptually, this work reveals the different length scales involved in the thermoelastic anisotropy and provides insights for programming liquid crystal elastomers on-demand for high-frequency applications.
O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis
Authors: Soria Leandro R. , Makris Georgios , D’Alessio Alfonso M. , De Angelis Angela , Boffa Iolanda , Pravata Veronica M. , Rüfenacht Véronique , Attanasio Sergio , Nusco Edoardo , Arena Paola , Ferenbach Andrew T. , Paris Debora , Cuomo Paola , Motta Andrea , Nitzahn Matthew , Lipshutz Gerald S. , Martínez-Pizarro Ainhoa , Richard Eva , Desviat Lourdes R. , Häberle Johannes , van Aalten Daan M. F. , Brunetti-Pierri Nicola 
Published: September 2022

AbstractLife-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases.
Multistability and anomalies in oscillator models of lossy power grids
Authors: Delabays Robin , Jafarpour Saber , Bullo Francesco 
Published: September 2022

AbstractThe analysis of dissipatively coupled oscillators is challenging and highly relevant in power grids. Standard mathematical methods are not applicable, due to the lack of network symmetry induced by dissipative couplings. Here we demonstrate a close correspondence between stable synchronous states in dissipatively coupled oscillators, and the winding partition of their state space, a geometric notion induced by the network topology. Leveraging this winding partition, we accompany this article with an algorithms to compute all synchronous solutions of complex networks of dissipatively coupled oscillators. These geometric and computational tools allow us to identify anomalous behaviors of lossy networked systems. Counterintuitively, we show that loop flows and dissipation can increase the system’s transfer capacity, and that dissipation can promote multistability. We apply our geometric framework to compute power flows on the IEEE RTS-96 test system, where we identify two high voltage solutions with distinct loop flows.
Small-molecule ionic liquid-based adhesive with strong room-temperature adhesion promoted by electrostatic interaction
Authors: Zhang Jun , Wang Wenxiang , Zhang Yan , Wei Qiang , Han Fei , Dong Shengyi , Liu Dongqing , Zhang Shiguo 
Published: September 2022

AbstractLow-molecular-weight adhesives (LMWAs) possess many unique features compared to polymer adhesives. However, fabricating LMWAs with adhesion strengths higher than those of polymeric materials is a significant challenge, mainly because of the relatively weak and unbalanced cohesion and interfacial adhesion. Herein, an ionic liquid (IL)-based adhesive with high adhesion strength is demonstrated by introducing an IL moiety into a Y-shaped molecule replete with hydrogen bonding (H-bonding) interactions. The IL moieties not only destroyed the rigid and ordered H-bonding networks, releasing more free groups to form hydrogen bonds (H-bonds) at the substrate/adhesive interface, but also provided electrostatic interactions that improved the cohesion energy. The synthesized IL-based adhesive, Tri-HT, could directly form thin coatings on various substrates, with high adhesion strengths of up to 12.20 MPa. Advanced adhesives with electrical conductivity, self-healing behavior, and electrically-controlled adhesion could also be fabricated by combining Tri-HT with carbon nanotubes.
Determining levels of linguistic deficit by applying cluster analysis to the aphasia quotient of Western Aphasia Battery in post-stroke aphasia
Authors: Yan Zhijie , Wei Dongshuai , Xu Shuo , Zhang Jingna , Yang Chunsheng , He Xinyuan , Li Chong , Zhang Yongli , Chen Mengye , Li Xiaofang , Jia Jie 
Published: September 2022

AbstractThe aphasia quotient of Western Aphasia Battery (WAB-AQ) has been used as an inclusion criterion and as an outcome measure in clinical, research, or community settings. The WAB-AQ is also commonly used to measure recovery. This study aimed to quantitatively determine levels of the linguistic deficit by using a cluster analysis of the WAB-AQ in post-stroke aphasia (PSA). 308 patients were extracted from the database. Cutoff scores are defined by mean overlap WAB-AQ scores of clusters by systematic cluster analysis, the method of which is the farthest neighbor element, and the metrics are square Euclidean distance and Pearson correlation, performed on the full sample of WAB-AQ individual subitem scores. A 1-way analysis of variance, with post hoc comparisons conducted, was used to determine whether clusters had significant differences. Three clusters were identified. The scores for severe, moderate, and mild linguistic deficit levels ranged from 0 to 30, 30.1 to 50.3, and 50.4 to 93.7, respectively. For PSA, the cluster analysis of WAB-AQ supports a 3-impairment level classification scheme.
Effect of artifacts upon the pressure reactivity index
Authors: Rozanek Martin , Skola Josef , Horakova Lenka , Trukhan Valeriia 
Published: September 2022

AbstractThe pressure reactivity index (PRx) is a parameter for the assessment of cerebrovascular autoregulation, but its calculation is affected by artifacts in the source biosignals—intracranial pressure (ICP) and arterial blood pressure. We sought to describe the most common short-duration artifacts and their effect on the PRx. A retrospective analysis of 935 h of multimodal monitoring data was conducted, and five types of artifacts, characterized by their shape, duration, and amplitude, were identified: rectangular, fast impulse, isoline drift, saw tooth, and constant ICP value. Subsequently, all types of artifacts were mathematically modeled and inserted into undisturbed segments of biosignals. Fast impulse, the most common artifact, did not alter the PRx index significantly when inserted into one or both signals. Artifacts present in one signal exceeded the threshold PRx in less than 5% of samples, except for isoline drift. Compared to that, the shortest rectangular artifact inserted into both signals changed PRx to a value above the set threshold in 55.4% of cases. Our analysis shows that the effect of individual artifacts on the PRx index is variable, depending on their occurrence in one or both signals, duration, and shape. This different effect suggests that potentially not all artifacts need to be removed.
Effective nonlinear responses of three-phase magnetoelectric composites
Authors: Lin Chien-hong , Liu Fang-Yu 
Published: September 2022

AbstractA computational method, dubbed simplified unit-cell micromechanics model, is generalized and applied to establish the effective nonlinear responses of three-phase magnetoelectric composites that are composed of two distinct magnetostrictive and piezoelectric phases embedded in elastic polymer matrices. The nature of nonlinear constitutive behavior of each constituent is expected to significantly influence the overall responses of the composites. To obtain the effective nonlinear responses, a mathematical linearization is first introduced to perform the constitutive linearization for the nonlinear materials, and the resulting constitutive equations are then unified and nested into the micromechanics model followed by iterations in order to minimize errors from the linearization process. For the purpose of comparison, we also reformulate the well-established Mori–Tanaka micromechanics model insofar as its mathematical structure is aligned with that of the simplified unit-cell model. Numerical results are first validated against limited experimental measurements available in literature. Parametric studies are then conducted in order to reveal the effect of phase constitutive laws, volume fractions, and geometries on the overall nonlinear responses of there-phase magnetoelectric composites. The contributions of this work complement those of earlier studies that prevalently devoted to two-phase magnetoelectric composites and linear magneto-electro-elastic coupled responses only.
The effect of the association between CETP variant type and alcohol consumption on cholesterol level differs according to the ALDH2 variant type
Authors: Yoo Min-Gyu , Yun Ji Ho , Koo Soo Kyung , Lee Hye-Ja 
Published: September 2022

AbstractAlcohol consumption is associated with a high increased lipid profile and this association may depend on genetic risk factors. In this study, we aimed to assess the effects of genetic variation associated with alcohol consumption on lipid profiles using data from two Korean population studies. We performed a genotype association study using the HEXA (n = 51,349) and KNHANES (n = 9158) data. Genotype analyses of the two sets of Korean population data showed associations of increased total cholesterol and high-density lipoprotein (HDL)-cholesterol with CETP rs708272. The HEXA and KNHANES populations revealed differences in HDL cholesterol according to the presence of CETP rs708272, independent of ALDH2 rs671 and alcohol consumption. In contrast, total cholesterol levels were associated with alcohol consumption and ALDH2 rs671 in men with CETP rs708272 (CT and TT genotypes). Furthermore, in drinkers with ALDH2 rs671 (GA and AA genotypes), higher total cholesterol was associated with the CETP rs708272 TT minor homozygous genotype based on both HEXA and KNHANES data. Our findings demonstrated that alcohol consumption and genetic variation in either CETP or ALDH2 may be associated with cholesterol levels. We hope these findings will provide a better understanding of the relationship between alcohol consumption and cholesterol according to each individual’s genetic background.
Alternative stopping rules to limit tree expansion for random forest models
Authors: Little Mark P. , Rosenberg Philip S. , Arsham Aryana 
Published: September 2022

AbstractRandom forests are a popular type of machine learning model, which are relatively robust to overfitting, unlike some other machine learning models, and adequately capture non-linear relationships between an outcome of interest and multiple independent variables. There are relatively few adjustable hyperparameters in the standard random forest models, among them the minimum size of the terminal nodes on each tree. The usual stopping rule, as proposed by Breiman, stops tree expansion by limiting the size of the parent nodes, so that a node cannot be split if it has less than a specified number of observations. Recently an alternative stopping criterion has been proposed, stopping tree expansion so that all terminal nodes have at least a minimum number of observations. The present paper proposes three generalisations of this idea, limiting the growth in regression random forests, based on the variance, range, or inter-centile range. The new approaches are applied to diabetes data obtained from the National Health and Nutrition Examination Survey and four other datasets (Tasmanian Abalone data, Boston Housing crime rate data, Los Angeles ozone concentration data, MIT servo data). Empirical analysis presented herein demonstrate that the new stopping rules yield competitive mean square prediction error to standard random forest models. In general, use of the intercentile range statistic to control tree expansion yields much less variation in mean square prediction error, and mean square prediction error is also closer to the optimal. The Fortran code developed is provided in the Supplementary Material.