bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity
Authors: Umansky Carla , Morellato Agustín E. , Rieckher Matthias , Scheidegger Marco A. , Martinefski Manuela R. , Fernández Gabriela A. , Pak Oleg , Kolesnikova Ksenia , Reingruber Hernán , Bollini Mariela , Crossan Gerry P. , Sommer Natascha , Monge María Eugenia , Schumacher Björn , Pontel Lucas B. 
Published: February 2022

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking, likely contributing to the onset of the human DNA repair condition Fanconi Anaemia. Mutations in the genes coding for FA detoxifying enzymes underlie a human inherited bone marrow failure syndrome (IBMFS), even in the presence of functional DNA repair, raising the question of whether FA causes relevant cellular damage beyond genotoxicity. Here, we report that FA triggers cellular redox imbalance in human cells and inCaenorhabditis elegans. Mechanistically, FA reacts with the redox-active thiol group of glutathione (GSH), altering the GSH:GSSG ratio and causing oxidative stress. FA cytotoxicity is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), which metabolizes FA-GSH products, lastly yielding reduced GSH. Furthermore, we show that GSH synthesis protects human cells from FA, indicating an active role of GSH in preventing FA toxicity. These findings might be relevant for patients carrying mutations in FA-detoxification systems and could suggest therapeutic benefits from thiol-rich antioxidants like N-acetyl-L-cysteine.
Protein sequence design with a learned potential
Authors: Anand Namrata , Eguchi Raphael , Mathews Irimpan I. , Perez Carla P. , Derry Alexander , Altman Russ B. , Huang Po-Ssu 
Published: February 2022

AbstractThe task of protein sequence design is central to nearly all rational protein engineering problems, and enormous effort has gone into the development of energy functions to guide design. Here, we investigate the capability of a deep neural network model to automate design of sequences onto protein backbones, having learned directly from crystal structure data and without any human-specified priors. The model generalizes to native topologies not seen during training, producing experimentally stable designs. We evaluate the generalizability of our method to ade novoTIM-barrel scaffold. The model produces novel sequences, and high-resolution crystal structures of two designs show excellent agreement with in silico models. Our findings demonstrate the tractability of an entirely learned method for protein sequence design.
Physiological synaptic activity and recognition memory require astroglial glutamine
Authors: Cheung Giselle , Bataveljic Danijela , Visser Josien , Kumar Naresh , Moulard Julien , Dallérac Glenn , Mozheiko Daria , Rollenhagen Astrid , Ezan Pascal , Mongin Cédric , Chever Oana , Bemelmans Alexis-Pierre , Lübke Joachim , Leray Isabelle , Rouach Nathalie 
Published: February 2022

AbstractPresynaptic glutamate replenishment is fundamental to brain function. In high activity regimes, such as epileptic episodes, this process is thought to rely on the glutamate-glutamine cycle between neurons and astrocytes. However the presence of an astroglial glutamine supply, as well as its functional relevance in vivo in the healthy brain remain controversial, partly due to a lack of tools that can directly examine glutamine transfer. Here, we generated a fluorescent probe that tracks glutamine in live cells, which provides direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions. This mobilization is mediated by connexin43, an astroglial protein with both gap-junction and hemichannel functions, and is essential for synaptic transmission and object recognition memory. Our findings uncover an indispensable recruitment of astroglial glutamine in physiological synaptic activity and memory via an unconventional pathway, thus providing an astrocyte basis for cognitive processes.
In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue
Authors: Silva-Pinheiro Pedro , Nash Pavel A. , Van Haute Lindsey , Mutti Christian D. , Turner Keira , Minczuk Michal 
Published: February 2022

AbstractMitochondria host key metabolic processes vital for cellular energy provision and are central to cell fate decisions. They are subjected to unique genetic control by both nuclear DNA and their own multi-copy genome - mitochondrial DNA (mtDNA). Mutations in mtDNA often lead to clinically heterogeneous, maternally inherited diseases that display different organ-specific presentation at any stage of life. For a long time, genetic manipulation of mammalian mtDNA has posed a major challenge, impeding our ability to understand the basic mitochondrial biology and mechanisms underpinning mitochondrial disease. However, an important new tool for mtDNA mutagenesis has emerged recently, namely double-stranded DNA deaminase (DddA)-derived cytosine base editor (DdCBE). Here, we test this emerging tool for in vivo use, by delivering DdCBEs into mouse heart using adeno-associated virus (AAV) vectors and show that it can install desired mtDNA edits in adult and neonatal mice. This work provides proof-of-concept for use of DdCBEs to mutagenize mtDNA in vivo in post-mitotic tissues and provides crucial insights into potential translation to human somatic gene correction therapies to treat primary mitochondrial disease phenotypes.
A Mediator-cohesin axis controls heterochromatin domain formation
Authors: Haarhuis Judith H. I. , van der Weide Robin H. , Blomen Vincent A. , Flach Koen D. , Teunissen Hans , Willems Laureen , Brummelkamp Thijn R. , Rowland Benjamin D. , de Wit Elzo 
Published: February 2022

AbstractThe genome consists of regions of transcriptionally active euchromatin and more silent heterochromatin. We reveal that the formation of heterochromatin domains requires cohesin turnover on DNA. Stabilization of cohesin on DNA through depletion of its release factor WAPL leads to a near-complete loss of heterochromatin domains. We observe the opposite phenotype in cells deficient for subunits of the Mediator-CDK module, with an almost binary partition of the genome into dense H3K9me3 domains, and regions devoid of H3K9me3 spanning the rest of the genome. We suggest that the Mediator-CDK module might contribute to gene expression by limiting the formation of dense heterochromatin domains. WAPL deficiency prevents the formation of heterochromatin domains, and allows for gene expression even in the absence of the Mediator-CDK subunit MED12. We propose that cohesin and Mediator affect heterochromatin in different ways to enable the correct distribution of epigenetic marks, and thus to ensure proper gene expression.
Inflammatory cytokines and distant recurrence in HER2-negative early breast cancer
Authors: Sparano Joseph A. , O’Neill Anne , Graham Noah , Northfelt Donald W. , Dang Chau T. , Wolff Antonio C. , Sledge George W. , Miller Kathy D. 
Published: February 2022

AbstractSystemic inflammation is believed to contribute to the distant recurrence of breast cancer. We evaluated serum samples obtained at diagnosis from 249 case:control pairs with stage II-III Her2-negative breast cancer with or without subsequent distant recurrence. Conditional logistic regression analysis, with models fit via maximum likelihood, were used to estimate hazard ratios (HRs) and test for associations of cytokines with distant recurrence risk. The only biomarker associated with a significantly increased distant recurrence risk when adjusted for multiple testing was the proinflammatory cytokine IL-6 (HR 1.37, 95% confidence intervals [CI] 1.15, 1.65, p = 0.0006). This prospective-retrospective study provides evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk.
Cooperative control of perpendicular magnetic anisotropy via crystal structure and orientation in freestanding SrRuO3 membranes
Authors: Lu Zengxing , Yang Yongjie , Wen Lijie , Feng Jiatai , Lao Bin , Zheng Xuan , Li Sheng , Zhao Kenan , Cao Bingshan , Ren Zeliang , Song Dongsheng , Du Haifeng , Guo Yuanyuan , Zhong Zhicheng , Hao Xianfeng , Wang Zhiming , Li Run-Wei 
Published: February 2022

AbstractFlexible magnetic materials with robust and controllable perpendicular magnetic anisotropy (PMA) are highly desirable for developing flexible high-performance spintronic devices. However, it is still challenge to fabricate PMA films on polymers directly. Here, we report a facile method for synthesizing single-crystal freestanding SrRuO3 membranes with controlled crystal structure and orientation using water-soluble Ca3-xSrxAl2O6 sacrificial layers. Through cooperative effect of crystal structure and orientation, flexible membranes reveal highly tunable magnetic anisotropy from in-plane to out-of-plane with a remarkable PMA energy of 7 × 106 erg·cm−3. First-principle calculations reveal that the underlying mechanism of PMA modulation is intimately correlated with structure-controlled Ru 4d-orbital occupation, as well as spin-orbital matrix element differences, dependent on the crystal orientation. In addition, even after 10,000 bending cycles, the PMA keeps stable, indicating a robust magnetism reliability in the prepared films. This work provides a feasible approach to prepare the flexible oxide films with strong and controllable PMA.
Garment embedded sweat-activated batteries in wearable electronics for continuous sweat monitoring
Authors: Huang Xingcan , Liu Yiming , Zhou Jingkun , Nejad Sina Khazaee , Wong Tsz Hung , Huang Ya , Li Hu , Yiu Chun Ki , Park Wooyoung , Li Jian , Su Jingyou , Zhao Ling , Yao Kuanming , Wu Mengge , Gao Zhan , Li Dengfeng , Li Jiyu , Shi Rui , Yu Xinge 
Published: February 2022

AbstractThin, soft, and skin-integrated electronic system has great advantages for realizing continuous human healthcare monitoring. Here, we report an ultra-thin, flexible, and garment-based microelectronics powered by sweat-activated batteries (SABs) and applications of powering biosensors and microelectronic systems for real time sweat monitoring. The SAB cell is ultra-thin (1.25 mm) with excellent biocompatibility. The SAB has good electricity output with high capacity (14.33 mAh) and maximum power density (3.17 mW cm−2) after being activated by the sweat volume of 0.045 mL cm−2, which could continuously power 120 light emitting diodes over 3 h. The outputs could maintain stable after repeatable bending. Wireless microelectronics system could be continuously powered by the SABs for 3 h to monitor sweat and physiological information, including sweat Na+ concentration, pH, and skin impedance. The reported integrated system provides a potential for solving the power issues of flexible wearable electronics and realizing personalized medicine.
Classical and quantum chaos in chirally-driven, dissipative Bose-Hubbard systems
Authors: Dahan Daniel , Arwas Geva , Grosfeld Eytan 
Published: February 2022

AbstractWe study the dissipative Bose-Hubbard model on a small ring of sites in the presence of a chiral drive and explore its long-time dynamical structure using the mean-field equations and by simulating the quantum master equation. Remarkably, for large enough drivings, we find that the system admits, in a wide range of parameters, a chaotic attractor at the mean-field level, which manifests as a complex Wigner function on the quantum level. The latter is shown to have the largest weight around the approximate region of phase space occupied by the chaotic attractor. We demonstrate that this behavior could be revealed via measurement of various bosonic correlation functions. In particular, we employ open system methods to calculate the out-of-time-ordered correlator, whose exponential growth signifies a positive quantum Lyapunov exponent in our system. This can open a pathway to the study of chaotic dynamics in interacting systems of photons.
Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans
Authors: Fujita Suguru , Karasawa Yasuaki , Fujii Masashi , Hironaka Ken-ichi , Uda Shinsuke , Kubota Hiroyuki , Inoue Hiroshi , Sumitomo Yohei , Hirayama Akiyoshi , Soga Tomoyoshi , Kuroda Shinya 
Published: February 2022

AbstractOral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion. We characterized temporal patterns of blood molecules by four features: (i) the decomposability into “amplitude” and “rate” components, (ii) the similarity of temporal patterns among individuals, (iii) the relation of molecules over time among individuals, and (iv) the similarity of temporal patterns among molecules. Glucose and glucose metabolism-related hormones indicated a rapid increase, and citrulline and lipids, which indicated a rapid decrease, returned to fasting levels faster than amino acids. Compared to glucose metabolism-related molecules and lipids, amino acids showed similar temporal patterns among individuals. The four features of temporal patterns of blood molecules by oral glucose ingestion characterize the differences among individuals and among molecules.
Rs12976445 polymorphism is associated with the risk of post-SAH re-bleeding by modulating the expression of microRNA-125 and ET-1
Authors: Xiong Wenping , Yao Weiqi , Gao Zeyuan , Liu Kui 
Published: February 2022

AbstractThis study aimed to study the association between rs12976445 polymorphism and the incidence of IA re-bleeding. Genotype and allele frequency analysis was performed to study the association between rs12976445 polymorphism and the risk of IA re-bleeding. Western blot, ELISA and real-time RT-PCR were conducted to measure the relative expression of miR-125a, ET1 mRNA and ET1 protein. Computational analysis and luciferase assays were utilized to investigate the association between the expression of miR-125a and ET1 mRNA. No significant differences were observed between IA patients with or without symptoms of re-bleeding. Subsequent analyses indicated that the T allele was significantly associated with the reduced risk of IA re-bleeding. In patients carrying the CC genotype, miR-125a level was up-regulated while ET1 mRNA/protein levels were reduced compared with those in patients carrying the CT or TT genotype. And ET1 mRNA was identified as a virtual target gene of miR-125a with a potential miR-125a binding site located on its 3’UTR. Accordingly, the ET mRNA/protein levels could be suppressed by the transfection of miR-125a precursors, but the transfection of ET1 siRNA exhibited no effect on the expression of miR-125a. Therefore, an increased level of miR-125a can lead to the increased risk of IA re-bleeding. Since miR-125a level is higher in CC-genotyped patients, it can be concluded that the presence of T allele in the rs12976445 polymorphism is associated with a lower risk of IA re-bleeding, and miR-125a may be used as a novel diagnostic and therapeutic target for IA rupture.
Nanostrucutured MnO2-TiN nanotube arrays for advanced supercapacitor electrode material
Authors: Ren Peng , Chen Chao , Yang Xiuchun 
Published: February 2022

AbstractThe capacitance of MnO2 supercapacitors (SCs) is not high as expected due to its low conductivity of MnO2. The synergistic effects of MnO2 with high theoretical specific capacitance and TiN with high theoretical conductivity can extremely enhance the electrochemical performance of the MnO2-TiN electrode material. In this work, we synthesized different nanostructured and crystalline-structured MnO2 modified TiN nanotube arrays electrode materials by hydrothermal method and explained the formation mechanism of different nanostructured and crystalline-structured MnO2. The influences of MnO2 nanostructures and crystalline-structures on the electrochemical performance has been contrasted and discussed. The specific capacitance of δ-MnO2 nanosheets-TiN nanotube arrays can reach 689.88 F g−1, the highest value among these samples TN-MO-SS, TN-MO-S, TN-MO-SR, TN-MO-RS, and TN-MO-R. The reason is explained based on MnO2 nanostructure and crystalline-structure and electron/ion transport properties. The specific capacitance retention rates are 97.2% and 82.4% of initial capacitance after 100 and 500 cycles, respectively, indicating an excellent charging-discharging cycle stability.
Volatile organic compound profiling to explore primary graft dysfunction after lung transplantation
Authors: Stefanuto Pierre-Hugues , Romano Rosalba , Rees Christiaan A. , Nasir Mavra , Thakuria Louit , Simon Andre , Reed Anna K. , Marczin Nandor , Hill Jane E. 
Published: February 2022

AbstractPrimary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Delineating basic mechanisms and molecular signatures of PGD remain a fundamental challenge. This pilot study examines if the pulmonary volatile organic compound (VOC) spectrum relate to PGD and postoperative outcomes. The VOC profiles of 58 bronchoalveolar lavage fluid (BALF) and blind bronchial aspirate samples from 35 transplant patients were extracted using solid-phase-microextraction and analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. The support vector machine algorithm was used to identify VOCs that could differentiate patients with severe from lower grade PGD. Using 20 statistically significant VOCs from the sample headspace collected immediately after transplantation (< 6 h), severe PGD was differentiable from low PGD with an AUROC of 0.90 and an accuracy of 0.83 on test set samples. The model was somewhat effective for later time points with an AUROC of 0.80. Three major chemical classes in the model were dominated by alkylated hydrocarbons, linear hydrocarbons, and aldehydes in severe PGD samples. These VOCs may have important clinical and mechanistic implications, therefore large-scale study and potential translation to breath analysis is recommended.
Perlite is a suitable model material for experiments investigating breathing in high density snow
Authors: Roubik Karel , Sykora Karel , Sieger Ladislav , Ort Vaclav , Horakova Lenka , Walzel Simon 
Published: February 2022

AbstractOutdoor breathing trials with simulated avalanche snow are fundamental for the research of the gas exchange under avalanche snow, which supports the development of the international resuscitation guidelines. However, these studies have to face numerous problems, including unstable weather and variable snow properties. This pilot study examines a mineral material perlite as a potential snow model for studies of ventilation and gas exchange parameters. Thirteen male subjects underwent three breathing phases—into snow, wet perlite and dry perlite. The resulting trends of gas exchange parameters in all tested materials were similar and when there was a significant difference observed, the trends in the parameters for high density snow used in the study lay in between the trends in dry and wet perlite. These findings, together with its stability and accessibility year-round, make perlite a potential avalanche snow model material. Perlite seems suitable especially for simulation and preparation of breathing trials assessing gas exchange under avalanche snow, and potentially for testing of new avalanche safety equipment before their validation in real snow.The study was registered in ClinicalTrials.gov on January 22, 2018; the registration number is NCT03413878.
Inferring the energy sensitivity and band gap of electronic transport in a network of carbon nanotubes
Authors: Tang Shuang 
Published: February 2022

AbstractSince the industrialization of single-phase nanomaterial-based devices is still challenging, intensive research focus has been given to complex materials consisting of multiple nanoscale entities, including networks and matrices of nanowires, nanotubes, nanoribbons, or other large molecules; among these complex materials, networks of carbon nanotubes are a typical example. Detailed knowledge of the energy sensitivity and band gap of electronic transport in such a material system is difficult to detect, despite its importance in electronic, energetic and sensing applications. Here, we propose a new methodology to obtain these quantities using the measured Seebeck coefficient at a certain temperature but different Fermi levels. We discover that the network consisting of semiconducting (11,10)-carbon nanotubes actually exhibits metallic transport at room temperature. It is also interesting to verify that intrananotube ballistic transport is dominant over diffusive scattering by long-range disorder, as well as the quantum hopping resistance at the contact points. The transport asymmetry ratio between the holes and electrons (1.75) is similar to the value observed in pristine graphene samples (1.50).
Topological and enzymatic analysis of human Alg2 mannosyltransferase reveals its role in lipid-linked oligosaccharide biosynthetic pathway
Authors: Xiang Meng-Hai , Xu Xin-Xin , Wang Chun-Di , Chen Shuai , Xu Si , Xu Xiang-Yang , Dean Neta , Wang Ning , Gao Xiao-Dong 
Published: February 2022

AbstractN-glycosylation starts with the biosynthesis of lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER). Alg2 mannosyltransferase adds both the α1,3- and α1,6-mannose (Man) onto ManGlcNAc2-pyrophosphate-dolichol (M1Gn2-PDol) in either order to generate the branched M3Gn2-PDol product. The well-studied yeast Alg2 interacts with ER membrane through four hydrophobic domains. Unexpectedly, we show that Alg2 structure has diverged between yeast and humans. Human Alg2 (hAlg2) associates with the ER via a single membrane-binding domain and is markedly more stable in vitro. These properties were exploited to develop a liquid chromatography-mass spectrometry quantitative kinetics assay for studying purified hAlg2. Under physiological conditions, hAlg2 prefers to transfer α1,3-Man onto M1Gn2 before adding the α1,6-Man. However, this bias is altered by an excess of GDP-Man donor or an increased level of M1Gn2 substrate, both of which trigger production of the M2Gn2(α-1,6)-PDol. These results suggest that Alg2 may regulate the LLO biosynthetic pathway by controlling accumulation of M2Gn2 (α-1,6) intermediate.
Substantial loss of isoprene in the surface ocean due to chemical and biological consumption
Authors: Simó Rafel , Cortés-Greus Pau , Rodríguez-Ros Pablo , Masdeu-Navarro Marta 
Published: February 2022

AbstractIsoprene contributes to the formation of ozone and secondary organic aerosol in the atmosphere, and thus influences cloud albedo and climate. Isoprene is ubiquitous in the surface open ocean where it is produced by phytoplankton, however emissions from the global ocean are poorly constrained, in part due to a lack of knowledge of oceanic sink or degradation terms. Here, we present analyses of ship-based seawater incubation experiments with samples from the Mediterranean, Atlantic, tropical Pacific and circum-Antarctic and Subantarctic oceans to determine chemical and biological isoprene consumption in the surface ocean. We find the total isoprene loss to be comprised of a constant chemical loss rate of 0.05 ± 0.01 d−1 and a biological consumption rate that varied between 0 and 0.59 d−1 (median 0.03 d−1) and was correlated with chlorophyll-a concentration. We suggest that isoprene consumption rates in the surface ocean are of similar magnitude or greater than ventilation rates to the atmosphere, especially in chlorophyll-a rich waters.