bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modular operation of microfluidic chips for highly parallelized cell culture and liquid dosing via a fluidic circuit board
Authors: Vollertsen A. R. , de Boer D. , Dekker S. , Wesselink B. A. M. , Haverkate R. , Rho H. S. , Boom R. J. , Skolimowski M. , Blom M. , Passier R. , van den Berg A. , van der Meer A. D. , Odijk M. 
Published: November 2020

AbstractMicrofluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing. To achieve this, systems typically integrate all functions into a single, monolithic device as a “one size fits all” solution. However, this approach limits the end users’ (re)design flexibility and complicates the addition of new functions to the system. To address this challenge, we propose and demonstrate a modular and standardized plug-and-play fluidic circuit board (FCB) for operating microfluidic building blocks (MFBBs), whereby both the FCB and the MFBBs contain integrated valves. A single FCB can parallelize up to three MFBBs of the same design or operate MFBBs with entirely different architectures. The operation of the MFBBs through the FCB is fully automated and does not incur the cost of an extra external footprint. We use this modular platform to control three microfluidic large-scale integration (mLSI) MFBBs, each of which features 64 microchambers suitable for cell culturing with high spatiotemporal control. We show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) for multiple days in the chambers of this MFBB. Moreover, we also use the same FCB to control an MFBB for liquid dosing with a high dynamic range. Our results demonstrate that MFBBs with different designs can be controlled and combined on a single FCB. Our novel modular approach to operating an automated microfluidic system for parallelized cell culture will enable greater experimental flexibility and facilitate the cooperation of different chips from different labs.
Lkb1 suppresses amino acid-driven gluconeogenesis in the liver
Authors: Just Pierre-Alexandre , Charawi Sara , Denis Raphaël G. P. , Savall Mathilde , Traore Massiré , Foretz Marc , Bastu Sultan , Magassa Salimata , Senni Nadia , Sohier Pierre , Wursmer Maud , Vasseur-Cognet Mireille , Schmitt Alain , Le Gall Morgane , Leduc Marjorie , Guillonneau François , De Bandt Jean-Pascal , Mayeux Patrick , Romagnolo Béatrice , Luquet Serge , Bossard Pascale , Perret Christine 
Published: November 2020

AbstractExcessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect is observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion is associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic, proteomic and pharmacological approaches, we identify the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.
Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease
Authors: Olah Marta , Menon Vilas , Habib Naomi , Taga Mariko F. , Ma Yiyi , Yung Christina J. , Cimpean Maria , Khairallah Anthony , Coronas-Samano Guillermo , Sankowski Roman , Grün Dominic , Kroshilina Alexandra A. , Dionne Danielle , Sarkis Rani A. , Cosgrove Garth R. , Helgager Jeffrey , Golden Jeffrey A. , Pennell Page B. , Prinz Marco , Vonsattel Jean Paul G. , Teich Andrew F. , Schneider Julie A. , Bennett David A. , Regev Aviv , Elyaman Wassim , Bradshaw Elizabeth M. , De Jager Philip L. 
Published: November 2020

AbstractThe extent of microglial heterogeneity in humans remains a central yet poorly explored question in light of the development of therapies targeting this cell type. Here, we investigate the population structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures. Using single cell RNA sequencing, we find that some subsets are enriched for disease-related genes and RNA signatures. We confirm the presence of four of these microglial subpopulations histologically and illustrate the utility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the cortex of individuals with Alzheimer’s disease (AD). Histologically, these cluster 7 microglia are reduced in frequency in AD tissue, and we validate this observation in an independent set of single nucleus data. Thus, our live human microglia identify a range of subtypes, and we prioritize one of these as being altered in AD.
High pressure synthesis of phosphine from the elements and the discovery of the missing (PH3)2H2 tile
Authors: Ceppatelli Matteo , Scelta Demetrio , Serrano-Ruiz Manuel , Dziubek Kamil , Garbarino Gaston , Jacobs Jeroen , Mezouar Mohamed , Bini Roberto , Peruzzini Maurizio 
Published: November 2020

AbstractHigh pressure reactivity of phosphorus and hydrogen is relevant to fundamental chemistry, energy conversion and storage, and materials science. Here we report the synthesis of (PH3)2H2, a crystalline van der Waals (vdW) compound (I4cm) made of PH3and H2molecules, in a Diamond Anvil Cell by direct catalyst-free high pressure (1.2 GPa) and high temperature (T ≲ 1000 K) chemical reaction of black phosphorus and liquid hydrogen, followed by room T compression above 3.5 GPa. Group 15 elements were previously not known to form H2-containing vdW compounds of their molecular hydrides. The observation of (PH3)2H2, identified by synchrotron X-ray diffraction and vibrational spectroscopy (FTIR, Raman), therefore represents the discovery of a previously missing tile, specifically corresponding to P for pnictogens, in the ability of non-metallic elements to form such compounds. Significant chemical implications encompass reactivity of the elements under extreme conditions, with the observation of the P analogue of the Haber-Bosch reaction for N, fundamental bond theory, and predicted high pressure superconductivity in P-H systems.
Organo–organic and organo–mineral interfaces in soil at the nanometer scale
Authors: Possinger Angela R. , Zachman Michael J. , Enders Akio , Levin Barnaby D. A. , Muller David A. , Kourkoutis Lena F. , Lehmann Johannes 
Published: November 2020

AbstractThe capacity of soil as a carbon (C) sink is mediated by interactions between organic matter and mineral phases. However, previously proposed layered accumulation of organic matter within aggregate organo–mineral microstructures has not yet been confirmed by direct visualization at the necessary nanometer-scale spatial resolution. Here, we identify disordered micrometer-size organic phases rather than previously reported ordered gradients in C functional groups. Using cryo-electron microscopy with electron energy loss spectroscopy (EELS), we show organo–organic interfaces in contrast to exclusively organo–mineral interfaces. Single-digit nanometer-size layers of C forms were detected at the organo–organic interface, showing alkyl C and nitrogen (N) enrichment (by 4 and 7%, respectively). At the organo–mineral interface, 88% (72–92%) and 33% (16–53%) enrichment of N and oxidized C, respectively, indicate different stabilization processes than at organo–organic interfaces. However, N enrichment at both interface types points towards the importance of N-rich residues for greater C sequestration.
Asymmetric polyamide nanofilms with highly ordered nanovoids for water purification
Authors: Yuan Bingbing , Zhao Shengchao , Hu Ping , Cui Jiabao , Niu Q. Jason 
Published: November 2020

AbstractTailor-made structure and morphology are critical to the highly permeable and selective polyamide membranes used for water purification. Here we report an asymmetric polyamide nanofilm having a two-layer structure, in which the lower is a spherical polyamide dendrimer porous layer, and the upper is a polyamide dense layer with highly ordered nanovoids structure. The dendrimer porous layer was covalently assembled in situ on the surface of the polysulfone (PSF) support by a diazotization-coupling reaction, and then the asymmetric polyamide nanofilm with highly ordered hollow nanostrips structure was formed by interfacial polymerization (IP) thereon. Tuning the number of the spherical dendrimer porous layers and IP time enabled control of the nanostrips morphology in the polyamide nanofilm. The asymmetric polyamide membrane exhibits a water flux of 3.7−4.3 times that of the traditional monolayer polyamide membrane, showing an improved divalent salt rejection rate (more than 99%), which thus surpasses the upper bound line of the permeability−selectivity performance of the existing various structural polyamide membranes. We estimate that this work might inspire the preparation of highly permeable and selective reverse osmosis (RO), organic solvent nanofiltration (OSNF) and pervaporation (PV) membranes.
BETs inhibition attenuates oxidative stress and preserves muscle integrity in Duchenne muscular dystrophy
Authors: Segatto Marco , Szokoll Roberta , Fittipaldi Raffaella , Bottino Cinzia , Nevi Lorenzo , Mamchaoui Kamel , Filippakopoulos Panagis , Caretti Giuseppina 
Published: November 2020

AbstractDuchenne muscular dystrophy (DMD) affects 1 in 3500 live male births. To date, there is no effective cure for DMD, and the identification of novel molecular targets involved in disease progression is important to design more effective treatments and therapies to alleviate DMD symptoms. Here, we show that protein levels of the Bromodomain and extra-terminal domain (BET) protein BRD4 are significantly increased in the muscle of the mouse model of DMD, the mdx mouse, and that pharmacological inhibition of the BET proteins has a beneficial outcome, tempering oxidative stress and muscle damage. Alterations in reactive oxygen species (ROS) metabolism are an early event in DMD onset and they are tightly linked to inflammation, fibrosis, and necrosis in skeletal muscle. By restoring ROS metabolism, BET inhibition ameliorates these hallmarks of the dystrophic muscle, translating to a beneficial effect on muscle function. BRD4 direct association to chromatin regulatory regions of the NADPH oxidase subunits increases in the mdx muscle and JQ1 administration reduces BRD4 and BRD2 recruitment at these regions. JQ1 treatment reduces NADPH subunit transcript levels in mdx muscles, isolated myofibers and DMD immortalized myoblasts. Our data highlight novel functions of the BET proteins in dystrophic skeletal muscle and suggest that BET inhibitors may ameliorate the pathophysiology of DMD.
muscat detects subpopulation-specific state transitions from multi-sample multi-condition single-cell transcriptomics data
Authors: Crowell Helena L. , Soneson Charlotte , Germain Pierre-Luc , Calini Daniela , Collin Ludovic , Raposo Catarina , Malhotra Dheeraj , Robinson Mark D. 
Published: November 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) has become an empowering technology to profile the transcriptomes of individual cells on a large scale. Early analyses of differential expression have aimed at identifying differences between subpopulations to identify subpopulation markers. More generally, such methods compare expression levels across sets of cells, thus leading to cross-condition analyses. Given the emergence of replicated multi-condition scRNA-seq datasets, an area of increasing focus is making sample-level inferences, termed here as differential state analysis; however, it is not clear which statistical framework best handles this situation. Here, we surveyed methods to perform cross-condition differential state analyses, including cell-level mixed models and methods based on aggregated pseudobulk data. To evaluate method performance, we developed a flexible simulation that mimics multi-sample scRNA-seq data. We analyzed scRNA-seq data from mouse cortex cells to uncover subpopulation-specific responses to lipopolysaccharide treatment, and provide robust tools for multi-condition analysis within themuscatR package.
Visible-light photoredox-catalyzed C–O bond cleavage of diaryl ethers by acridinium photocatalysts at room temperature
Authors: Tan Fang-Fang , He Xiao-Ya , Tian Wan-Fa , Li Yang 
Published: November 2020

AbstractCleavage of C–O bonds in lignin can afford the renewable aryl sources for fine chemicals. However, the high bond energies of these C–O bonds, especially the 4-O-5-type diaryl ether C–O bonds (~314 kJ/mol) make the cleavage very challenging. Here, we report visible-light photoredox-catalyzed C–O bond cleavage of diaryl ethers by an acidolysis with an aryl carboxylic acid and a following one-pot hydrolysis. Two molecules of phenols are obtained from one molecule of diaryl ether at room temperature. The aryl carboxylic acid used for the acidolysis can be recovered. The key to success of the acidolysis is merging visible-light photoredox catalysis using an acridinium photocatalyst and Lewis acid catalysis using Cu(TMHD)2. Preliminary mechanistic studies indicate that the catalytic cycle occurs via a rare selective electrophilic attack of the generated aryl carboxylic radical on the electron-rich aryl ring of the diphenyl ether. This transformation is applied to a gram-scale reaction and the model of 4-O-5 lignin linkages.
Neoadjuvant FLOT versus SOX phase II randomized clinical trial for patients with locally advanced gastric cancer
Authors: Sah Birendra Kumar , Zhang Benyan , Zhang Huan , Li Jian , Yuan Fei , Ma Tao , Shi Min , Xu Wei , Zhu Zhenglun , Liu Wentao , Yan Chao , Li Chen , Liu Bingya , Yan Min , Zhu Zhenggang 
Published: November 2020

AbstractNeoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.
Direct binding of TFEα opens DNA binding cleft of RNA polymerase
Authors: Jun Sung-Hoon , Hyun Jaekyung , Cha Jeong Seok , Kim Hoyoung , Bartlett Michael S. , Cho Hyun-Soo , Murakami Katsuhiko S. 
Published: November 2020

AbstractOpening of the DNA binding cleft of cellular RNA polymerase (RNAP) is necessary for transcription initiation but the underlying molecular mechanism is not known. Here, we report on the cryo-electron microscopy structures of the RNAP, RNAP-TFEα binary, and RNAP-TFEα-promoter DNA ternary complexes from archaea, Thermococcus kodakarensis (Tko). The structures reveal that TFEα bridges the RNAP clamp and stalk domains to open the DNA binding cleft. Positioning of promoter DNA into the cleft closes it while maintaining the TFEα interactions with the RNAP mobile modules. The structures and photo-crosslinking results also suggest that the conserved aromatic residue in the extended winged-helix domain of TFEα interacts with promoter DNA to stabilize the transcription bubble. This study provides a structural basis for the functions of TFEα and elucidates the mechanism by which the DNA binding cleft is opened during transcription initiation in the stalk-containing RNAPs, including archaeal and eukaryotic RNAPs.
Data-science ready, multisite, human diffusion MRI white-matter-tract statistics
Authors: Lerma-Usabiaga Garikoitz , Mukherjee Pratik , Perry Michael L. , Wandell Brian A. 
Published: November 2020

AbstractThe white matter tracts in the living human brain are critical for healthy function, and the diffusion MRI measured in these tracts is correlated with diverse behavioral measures. The technical skills required to analyze diffusion MRI data are complex: data acquisition requires MRI sequence development and acquisition expertise, analyzing raw-data into meaningful summary statistics requires computational neuroimaging and neuroanatomy expertise. The human white matter study field will advance faster if the tract summaries are available in plain data-science-ready format for non-diffusion MRI experts, such as statisticians, computer graphic researchers or data scientists in general. Here, we share a curated and processed dataset from three different MRI centers in a format that is data-science ready. The multisite data we share include measures of within and between MRI center variation in white-matter-tract diffusion measurements. Along with the dataset description and summary statistics, we describe the state-of-the-art computational system that guarantees reproducibility and provenance from the original scanner output.
Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2
Authors: Behmard Esmaeil , Soleymani Bijan , Najafi Ali , Barzegari Ebrahim 
Published: November 2020

AbstractCoronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease’s associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.
Impact of osmotic stress on the phosphorylation and subcellular location of Listeria monocytogenes stressosome proteins
Authors: Dessaux Charlotte , Guerreiro Duarte N. , Pucciarelli M. Graciela , O’Byrne Conor P. , García-del Portillo Francisco 
Published: November 2020

AbstractListeria monocytogenes responds to environmental stress using a supra-macromolecular complex, the stressosome, to activate the stress sigma factor SigB. The stressosome structure, inferred from in vitro-assembled complexes, consists of the core proteins RsbR (here renamed RsbR1) and RsbS and, the kinase RsbT. The active complex is proposed to be tethered to the membrane and to support RsbR1/RsbS phosphorylation by RsbT and the subsequent release of RsbT following signal perception. Here, we show in actively-growing cells that L. monocytogenes RsbR1 and RsbS localize mostly in the cytosol in a fully phosphorylated state regardless of osmotic stress. RsbT however distributes between cytosolic and membrane-associated pools. The kinase activity of RsbT on RsbR1/RsbS and its requirement for maximal SigB activation in response to osmotic stress were demonstrated in vivo. Cytosolic RsbR1 interacts with RsbT, while this interaction diminishes at the membrane when RsbR1 paralogues (RsbR2, RsbR3 and RsbL) are present. Altogether, the data support a model in which phosphorylated RsbR1/RsbS may sustain basal SigB activity in unstressed cells, probably assuring a rapid increase in such activity in response to stress. Our findings also suggest that in vivo the active RsbR1-RsbS-RsbT complex forms only transiently and that membrane-associated RsbR1 paralogues could modulate its assembly.
Cage bedding modifies metabolic and gut microbiota profiles in mouse studies applying dietary restriction
Authors: Gregor A. , Fragner L. , Trajanoski S. , Li W. , Sun X. , Weckwerth W. , König J. , Duszka K. 
Published: November 2020

AbstractExperiments involving food restriction are common practice in metabolic research. Under fasted conditions, mice supplement their diet with cage bedding. We aimed at identifying metabolic and microbiota-related parameters affected by the bedding type. We exposed mice housed with wooden, cellulose, or corncob cage beddings to ad libitum feeding, caloric restriction (CR), or over-night (ON) fasting. Additionally, two subgroups of the ON fast group were kept without any bedding or on a metal grid preventing coprophagy. Mice under CR supplemented their diet substantially with bedding; however, the amount varied depending on the kind of bedding. Bedding-related changes in body weight loss, fat loss, cecum size, stomach weight, fecal output, blood ghrelin levels as well as a response to glucose oral tolerance test were recorded. As fiber is fermented by the gut bacteria, the type of bedding affects gut bacteria and fecal metabolites composition of CR mice. CR wood and cellulose groups showed distinct cecal metabolite and microbiome profiles when compared to the CR corncob group. While all ad libitum fed animal groups share similar profiles. We show that restriction-related additional intake of bedding-derived fiber modulates multiple physiological parameters. Therefore, the previous rodent studies on CR, report the combined effect of CR and increased fiber consumption.