bluuebunny/crossref_metadata_2025_split huggingface dataset:
STK11 is required for the normal program of ciliated cell differentiation in airways
Authors: Chu Qiqi , Yao Changfu , Qi Xiangbing , Stripp Barry Raymond , Tang Nan 
Published: July 2019

AbstractThe functional properties of mucosal surfaces are dependent on establishing the correct proportions of specialized epithelial cell types. Multiciliated cells (also known as ciliated cells) are evolutionarily conserved and functionally indispensable epithelial cells, as suggested by the link between ciliated cell dysfunction and chronic human disease. Ciliated cell differentiation is an ordered process that involves initial cell fate determination and multiciliogenesis. STK11, a serine/threonine kinase, has been reported to be downregulated in human diseases associated with ciliopathies and functions as a tumor suppressor. Here, we show that STK11 is a physiological factor for the normal program of ciliated cell differentiation by phosphorylating MARK3, which directly suppresses ERK1/2 mediated pRB inactivation. Loss of Stk11 in airway progenitors impairs the differentiation of ciliated cells in both embryonic and adult airways. Our study establishes that STK11/MARK3/ERK1/2 signaling cascade is a key regulator to integrate ciliated cell fate commitment and the subsequent process of multiciliogenesis.
Disentangling conical intersection and coherent molecular dynamics in methyl bromide with attosecond transient absorption spectroscopy
Authors: Timmers Henry , Zhu Xiaolei , Li Zheng , Kobayashi Yuki , Sabbar Mazyar , Hollstein Maximilian , Reduzzi Maurizio , Martínez Todd J. , Neumark Daniel M. , Leone Stephen R. 
Published: July 2019

AbstractAttosecond probing of core-level electronic transitions provides a sensitive tool for studying valence molecular dynamics with atomic, state, and charge specificity. In this report, we employ attosecond transient absorption spectroscopy to follow the valence dynamics of strong-field initiated processes in methyl bromide. By probing the 3d core-to-valence transition, we resolve the strong field excitation and ensuing fragmentation of the neutral σ* excited states of methyl bromide. The results provide a clear signature of the non-adiabatic passage of the excited state wavepacket through a conical intersection. We additionally observe competing, strong field initiated processes arising in both the ground state and ionized molecule corresponding to vibrational and spin-orbit motion, respectively. The demonstrated ability to resolve simultaneous dynamics with few-femtosecond resolution presents a clear path forward in the implementation of attosecond XUV spectroscopy as a general tool for probing competing and complex molecular phenomena with unmatched temporal resolution.
Zebrafish preserve global germline DNA methylation while sex-linked rDNA is amplified and demethylated during feminisation
Authors: Ortega-Recalde Oscar , Day Robert C. , Gemmell Neil J. , Hore Timothy A. 
Published: July 2019

AbstractThe germline is the only cellular lineage capable of transferring genetic information from one generation to the next. Intergenerational transmission of epigenetic memory through the germline, in the form of DNA methylation, has been proposed; however, in mammals this is largely prevented by extensive epigenetic erasure during germline definition. Here we report that, unlike mammals, the continuously-defined ‘preformed’ germline of zebrafish does not undergo genome-wide erasure of DNA methylation during development. Our analysis also uncovers oocyte-specific germline amplification and demethylation of an 11.5-kb repeat region encoding 45S ribosomal RNA (fem-rDNA). The peak of fem-rDNA amplification coincides with the initial expansion of stage IB oocytes, the poly-nucleolar cell type responsible for zebrafish feminisation. Given that fem-rDNA overlaps with the only zebrafish locus identified thus far as sex-linked, we hypothesise fem-rDNA expansion could be intrinsic to sex determination in this species.
Membrane protein-regulated networks across human cancers
Authors: Lin Chun-Yu , Lee Chia-Hwa , Chuang Yi-Hsuan , Lee Jung-Yu , Chiu Yi-Yuan , Wu Lee Yan-Hwa , Jong Yuh-Jyh , Hwang Jenn-Kang , Huang Sing-Han , Chen Li-Ching , Wu Chih-Hsiung , Tu Shih-Hsin , Ho Yuan-Soon , Yang Jinn-Moon 
Published: July 2019

AbstractAlterations in membrane proteins (MPs) and their regulated pathways have been established as cancer hallmarks and extensively targeted in clinical applications. However, the analysis of MP-interacting proteins and downstream pathways across human malignancies remains challenging. Here, we present a systematically integrated method to generate a resource of cancer membrane protein-regulated networks (CaMPNets), containing 63,746 high-confidence protein–protein interactions (PPIs) for 1962 MPs, using expression profiles from 5922 tumors with overall survival outcomes across 15 human cancers. Comprehensive analysis of CaMPNets links MP partner communities and regulated pathways to provide MP-based gene sets for identifying prognostic biomarkers and druggable targets. For example, we identify CHRNA9 with 12 PPIs (e.g., ERBB2) can be a therapeutic target and find its anti-metastasis agent, bupropion, for treatment in nicotine-induced breast cancer. This resource is a study to systematically integrate MP interactions, genomics, and clinical outcomes for helping illuminate cancer-wide atlas and prognostic landscapes in tumor homo/heterogeneity.
Non-Abelian gauge field optics
Authors: Chen Yuntian , Zhang Ruo-Yang , Xiong Zhongfei , Hang Zhi Hong , Li Jensen , Shen Jian Qi , Chan C. T. 
Published: July 2019

AbstractThe concept of gauge field is a cornerstone of modern physics and the synthetic gauge field has emerged as a new way to manipulate particles in many disciplines. In optics, several schemes of Abelian synthetic gauge fields have been proposed. Here, we introduce a new platform for realizing synthetic SU(2) non-Abelian gauge fields acting on two-dimensional optical waves in a wide class of anisotropic materials and discover novel phenomena. We show that a virtual non-Abelian Lorentz force arising from material anisotropy can induce light beams to travel along Zitterbewegung trajectories even in homogeneous media. We further design an optical non-Abelian Aharonov–Bohm system which results in the exotic spin density interference effect. We can extract the Wilson loop of an arbitrary closed optical path from a series of gauge fixed points in the interference fringes. Our scheme offers a new route to study SU(2) gauge field related physics using optics.
Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
Authors: Argemi Josepmaria , Latasa Maria U. , Atkinson Stephen R. , Blokhin Ilya O. , Massey Veronica , Gue Joel P. , Cabezas Joaquin , Lozano Juan J. , Van Booven Derek , Bell Aaron , Cao Sheng , Vernetti Lawrence A. , Arab Juan P. , Ventura-Cots Meritxell , Edmunds Lia R. , Fondevila Constantino , Stärkel Peter , Dubuquoy Laurent , Louvet Alexandre , Odena Gemma , Gomez Juan L. , Aragon Tomas , Altamirano Jose , Caballeria Juan , Jurczak Michael J. , Taylor D. Lansing , Berasain Carmen , Wahlestedt Claes , Monga Satdarshan P. , Morgan Marsha Y. , Sancho-Bru Pau , Mathurin Philippe , Furuya Shinji , Lackner Carolin , Rusyn Ivan , Shah Vijay H. , Thursz Mark R. , Mann Jelena , Avila Matias A. , Bataller Ramon 
Published: July 2019

AbstractAlcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.
Microinvasion by Streptococcus pneumoniae induces epithelial innate immunity during colonisation at the human mucosal surface
Authors: Weight Caroline M. , Venturini Cristina , Pojar Sherin , Jochems Simon P. , Reiné Jesús , Nikolaou Elissavet , Solórzano Carla , Noursadeghi Mahdad , Brown Jeremy S. , Ferreira Daniela M. , Heyderman Robert S. 
Published: July 2019

AbstractControl ofStreptococcus pneumoniaecolonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving herd protection. Here, we use an experimental human pneumococcal carriage model (EHPC) to show thatS. pneumoniaecolonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epithelium shaped the host transcriptomic response in vitro. Using epithelial modules from a human epithelial cell model that recapitulates our in vivo findings, comprising of innate signalling and regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. Our results indicate that, rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances inflammatory and innate immune responses associated with clearance.
A zwitterionic near-infrared fluorophore for real-time ureter identification during laparoscopic abdominopelvic surgery
Authors: de Valk Kim S. , Handgraaf Henricus J. , Deken Marion M. , Sibinga Mulder Babs G. , Valentijn Adrianus R. , Terwisscha van Scheltinga Anton G. , Kuil Joeri , van Esdonk Michiel J. , Vuijk Jaap , Bevers Rob F. , Peeters Koen C. , Holman Fabian A. , Frangioni John V. , Burggraaf Jacobus , Vahrmeijer Alexander L. 
Published: July 2019

AbstractIatrogenic injury of the ureters is a feared complication of abdominal surgery. Zwitterionic near-infrared fluorophores are molecules with geometrically-balanced, electrically-neutral surface charge, which leads to renal-exclusive clearance and ultralow non-specific background binding. Such molecules could solve the ureter mapping problem by providing real-time anatomic and functional imaging, even through intact peritoneum. Here we present the first-in-human experience of this chemical class, as well as the efficacy study in patients undergoing laparoscopic abdominopelvic surgery. The zwitterionic near-infrared fluorophore ZW800-1 is safe, has pharmacokinetic properties consistent with an ideal blood pool agent, and rapid elimination into urine after a single low-dose intravenous injection. Visualization of structure and function of the ureters starts within minutes after ZW800-1 injection and lasts several hours. Zwitterionic near-infrared fluorophores add value during laparoscopic abdominopelvic surgeries and could potentially decrease iatrogenic urethral injury. Moreover, ZW800-1 is engineered for one-step covalent conjugatability, creating possibilities for developing novel targeted ligands.
Programmable graphene nanobubbles with three-fold symmetric pseudo-magnetic fields
Authors: Jia Pengfei , Chen Wenjing , Qiao Jiabin , Zhang Miao , Zheng Xiaohu , Xue Zhongying , Liang Rongda , Tian Chuanshan , He Lin , Di Zengfeng , Wang Xi 
Published: July 2019

AbstractGraphene nanobubbles (GNBs) have attracted much attention due to the ability to generate large pseudo-magnetic fields unattainable by ordinary laboratory magnets. However, GNBs are always randomly produced by the reported protocols, therefore, their size and location are difficult to manipulate, which restricts their potential applications. Here, using the functional atomic force microscopy (AFM), we demonstrate the ability to form programmable GNBs. The precision of AFM facilitates the location definition of GNBs, and their size and shape are tuned by the stimulus bias of AFM tip. With tuning the tip voltage, the bubble contour can gradually transit from parabolic to Gaussian profile. Moreover, the unique three-fold symmetric pseudo-magnetic field pattern with monotonous regularity, which is only theoretically predicted previously, is directly observed in the GNB with an approximately parabolic profile. Our study may provide an opportunity to study high magnetic field regimes with the designed periodicity in two dimensional materials.
High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes
Authors: Singh Mandeep , Al-Eryani Ghamdan , Carswell Shaun , Ferguson James M. , Blackburn James , Barton Kirston , Roden Daniel , Luciani Fabio , Giang Phan Tri , Junankar Simon , Jackson Katherine , Goodnow Christopher C. , Smith Martin A. , Swarbrick Alexander 
Published: July 2019

AbstractHigh-throughput single-cell RNA sequencing is a powerful technique but only generates short reads from one end of a cDNA template, limiting the reconstruction of highly diverse sequences such as antigen receptors. To overcome this limitation, we combined targeted capture and long-read sequencing of T-cell-receptor (TCR) and B-cell-receptor (BCR) mRNA transcripts with short-read transcriptome profiling of barcoded single-cell libraries generated by droplet-based partitioning. We show that Repertoire and Gene Expression by Sequencing (RAGE-Seq) can generate accurate full-length antigen receptor sequences at nucleotide resolution, infer B-cell clonal evolution and identify alternatively spliced BCR transcripts. We apply RAGE-Seq to 7138 cells sampled from the primary tumor and draining lymph node of a breast cancer patient to track transcriptome profiles of expanded lymphocyte clones across tissues. Our results demonstrate that RAGE-Seq is a powerful method for tracking the clonal evolution from large numbers of lymphocytes applicable to the study of immunity, autoimmunity and cancer.
Cerebellar disruption impairs working memory during evidence accumulation
Authors: Deverett Ben , Kislin Mikhail , Tank David W. , Wang Samuel S.-H. 
Published: July 2019

AbstractTo select actions based on sensory evidence, animals must create and manipulate representations of stimulus information in memory. Here we report that during accumulation of somatosensory evidence, optogenetic manipulation of cerebellar Purkinje cells reduces the accuracy of subsequent memory-guided decisions and causes mice to downweight prior information. Behavioral deficits are consistent with the addition of noise and leak to the evidence accumulation process. We conclude that the cerebellum can influence the accurate maintenance of working memory.
Patient-derived pancreas-on-a-chip to model cystic fibrosis-related disorders
Authors: Shik Mun Kyu , Arora Kavisha , Huang Yunjie , Yang Fanmuyi , Yarlagadda Sunitha , Ramananda Yashaswini , Abu-El-Haija Maisam , Palermo Joseph J. , Appakalai Balamurugan N. , Nathan Jaimie D. , Naren Anjaparavanda P. 
Published: July 2019

AbstractCystic fibrosis (CF) is a genetic disorder caused by defective CF Transmembrane Conductance Regulator (CFTR) function. Insulin producing pancreatic islets are located in close proximity to the pancreatic duct and there is a possibility of impaired cell-cell signaling between pancreatic ductal epithelial cells (PDECs) and islet cells as causative in CF. To study this possibility, we present an in vitro co-culturing system, pancreas-on-a-chip. Furthermore, we present an efficient method to micro dissect patient-derived human pancreatic ducts from pancreatic remnant cell pellets, followed by the isolation of PDECs. Here we show that defective CFTR function in PDECs directly reduced insulin secretion in islet cells significantly. This uniquely developed pancreatic function monitoring tool will help to study CF-related disorders in vitro, as a system to monitor cell-cell functional interaction of PDECs and pancreatic islets, characterize appropriate therapeutic measures and further our understanding of pancreatic function.
An electrostatic spectral neighbor analysis potential for lithium nitride
Authors: Deng Zhi , Chen Chi , Li Xiang-Guo , Ong Shyue Ping 
Published: July 2019

AbstractMachine-learned interatomic potentials based on local environment descriptors represent a transformative leap over traditional potentials based on rigid functional forms in terms of prediction accuracy. However, a challenge in their application to ionic systems is the treatment of long-ranged electrostatics. Here, we present a highly accurate electrostatic Spectral Neighbor Analysis Potential (eSNAP) for ionic α-Li3N, a prototypical lithium superionic conductor of interest as a solid electrolyte or coating for rechargeable lithium-ion batteries. We show that the optimized eSNAP model substantially outperforms traditional Coulomb–Buckingham potential in the prediction of energies and forces, as well as various properties, such as lattice constants, elastic constants, and phonon dispersion curves. We also demonstrate the application of eSNAP in long-time, large-scale Li diffusion studies in Li3N, providing atomistic insights into measures of concerted ionic motion (e.g., the Haven ratio) and grain boundary diffusion. This work aims at providing an approach to developing quantum-accurate force fields for multi-component ionic systems under the SNAP formalism, enabling large-scale atomistic simulations for such systems.
Solvent-Assisted Paper Spray Ionization Mass Spectrometry (SAPSI-MS) for the Analysis of Biomolecules and Biofluids
Authors: Riboni Nicoló , Quaranta Alessandro , Motwani Hitesh V. , Österlund Nicklas , Gräslund Astrid , Bianchi Federica , Ilag Leopold L. 
Published: July 2019

AbstractPaper Spray Ionization (PSI) is commonly applied for the analysis of small molecules, including drugs, metabolites, and pesticides in biological fluids, due to its high versatility, simplicity, and low costs. In this study, a new setup called Solvent Assisted Paper Spray Ionization (SAPSI), able to increase data acquisition time, signal stability, and repeatability, is proposed to overcome common PSI drawbacks. The setup relies on an integrated solution to provide ionization potential and constant solvent flow to the paper tip. Specifically, the ion source was connected to the instrument fluidics along with the voltage supply systems, ensuring a close control over the ionization conditions. SAPSI was successfully applied for the analysis of different classes of biomolecules: amyloidogenic peptides, proteins, and N-glycans. The prolonged analysis time allowed real-time monitoring of processes taking places on the paper tip, such as amyloid peptides aggregation and disaggregation phenomena. The enhanced signal stability allowed to discriminate protein species characterized by different post translational modifications and adducts with electrophilic compounds, both in aqueous solutions and in biofluids, such as serum and cerebrospinal fluid, without any sample pretreatment. In the next future, application to clinical relevant modifications, could lead to the development of quick and cost-effective diagnostic tools.
Different Antioxidant Efficacy of Two MnII-Containing Superoxide Anion Scavengers on Hypoxia/Reoxygenation-Exposed Cardiac Muscle Cells
Authors: Becatti Matteo , Bencini Andrea , Nistri Silvia , Conti Luca , Fabbrini Maria Giulia , Lucarini Laura , Ghini Veronica , Severi Mirko , Fiorillo Claudia , Giorgi Claudia , Sorace Lorenzo , Valtancoli Barbara , Bani Daniele 
Published: July 2019

AbstractOxidative stress due to excess superoxide anion ($${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$

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) produced by dysfunctional mitochondria is a key pathogenic event of aging and ischemia-reperfusion diseases. Here, a new $${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$

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-scavenging MnII complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing 2 quinoline units (MnQ2), designed to improve complex stability and cell permeability, was compared to parental MnII complex with methyls replacing quinolines (MnM2). MnQ2 was more stable than MnM2 (log K = 19.56(8) vs. 14.73(2) for the equilibrium Mn2+ + L2−, where L = Q2 and M2) due to the involvement of quinoline in metal binding and to the hydrophobic features of the ligand which improve metal desolvation upon complexation. As oxidative stress model, H9c2 rat cardiomyoblasts were subjected to hypoxia-reoxygenation. MnQ2 and MnM2 (10 μmol L−1) were added at reoxygenation for 1 or 2 h. The more lipophilic MnQ2 showed more rapid cell and mitochondrial penetration than MnM2. Both MnQ2 and MnM2 abated endogenous ROS and mitochondrial $${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$

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, decreased cell lipid peroxidation, reduced mitochondrial dysfunction, in terms of efficiency of the respiratory chain and preservation of membrane potential (Δψ) and permeability, decreased the activation of pro-apoptotic caspases 9 and 3, and increased cell viability. Of note, MnQ2 was more effective than MnM2 to exert cytoprotective anti-oxidant effects in the short term. Compounds with redox-inert ZnII replacing the functional MnII were ineffective. This study provides clues which further our understanding of the structure-activity relationships of MnII-chelates and suggests that MnII-polyamino-polycarboxylate macrocycles could be developed as new anti-oxidant drugs.
Pharmacological manipulation of DNA methylation normalizes maternal behavior, DNA methylation, and gene expression in dams with a history of maltreatment
Authors: Keller Samantha M. , Doherty Tiffany S. , Roth Tania L. 
Published: July 2019

AbstractThe quality of parental care received during development profoundly influences an individual’s phenotype, including that of maternal behavior. We previously found that female rats with a history of maltreatment during infancy mistreat their own offspring. One proposed mechanism through which early-life experiences influence behavior is via epigenetic modifications. Indeed, our lab has identified a number of brain epigenetic alterations in female rats with a history of maltreatment. Here we sought to investigate the role of DNA methylation in aberrant maternal behavior. We administered zebularine, a drug known to alter DNA methylation, to dams exposed during infancy to the scarcity-adversity model of low nesting resources, and then characterized the quality of their care towards their offspring. First, we replicate that dams with a history of maltreatment mistreat their own offspring. Second, we show that maltreated-dams treated with zebularine exhibit lower levels of adverse care toward their offspring. Third, we show that administration of zebularine in control dams (history of nurturing care) enhances levels of adverse care. Lastly, we show altered methylation and gene expression in maltreated dams normalized by zebularine. These findings lend support to the hypothesis that epigenetic alterations resulting from maltreatment causally relate to behavioral outcomes.