bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial network complexity emerges from fission/fusion dynamics
Authors: Zamponi Nahuel , Zamponi Emiliano , Cannas Sergio A. , Billoni Orlando V. , Helguera Pablo R. , Chialvo Dante R. 
Published: January 2018

AbstractMitochondrial networks exhibit a variety of complex behaviors, including coordinated cell-wide oscillations of energy states as well as a phase transition (depolarization) in response to oxidative stress. Since functional and structural properties are often interwinded, here we characterized the structure of mitochondrial networks in mouse embryonic fibroblasts using network tools and percolation theory. Subsequently we perturbed the system either by promoting the fusion of mitochondrial segments or by inducing mitochondrial fission. Quantitative analysis of mitochondrial clusters revealed that structural parameters of healthy mitochondria laid in between the extremes of highly fragmented and completely fusioned networks. We confirmed our results by contrasting our empirical findings with the predictions of a recently described computational model of mitochondrial network emergence based on fission-fusion kinetics. Altogether these results offer not only an objective methodology to parametrize the complexity of this organelle but also support the idea that mitochondrial networks behave as critical systems and undergo structural phase transitions.
A Gaussian extension for Diffraction Enhanced Imaging
Authors: Arfelli Fulvia , Astolfo Alberto , Rigon Luigi , Menk Ralf Hendrik 
Published: January 2018

AbstractUnlike conventional x-ray attenuation one of the advantages of phase contrast x-ray imaging is its capability of extracting useful physical properties of the sample. In particular the possibility to obtain information from small angle scattering about unresolvable structures with sub-pixel resolution sensitivity has drawn attention for both medical and material science applications. We report on a novel algorithm for the analyzer based x-ray phase contrast imaging modality, which allows the robust separation of absorption, refraction and scattering effects from three measured x-ray images. This analytical approach is based on a simple Gaussian description of the analyzer transmission function and this method is capable of retrieving refraction and small angle scattering angles in the full angular range typical of biological samples. After a validation of the algorithm with a simulation code, which demonstrated the potential of this highly sensitive method, we have applied this theoretical framework to experimental data on a phantom and biological tissues obtained with synchrotron radiation. Owing to its extended angular acceptance range the algorithm allows precise assessment of local scattering distributions at biocompatible radiation doses, which in turn might yield a quantitative characterization tool with sufficient structural sensitivity on a submicron length scale.
Tribological Properties of Ultrananocrystalline Diamond Films: Mechanochemical Transformation of Sliding Interfaces
Authors: Rani Revati , Panda Kalpataru , Kumar Niranjan , Titovich Kozakov Alexey , Ivanovich Kolesnikov Vladimir , Vyacheslavovich Sidashov Andrey , Lin I-Nan 
Published: January 2018

AbstractImproving the tribological properties of materials in ambient and high vacuum tribo-conditions is useful for inter-atmospheric applications. Highly-hydrogenated and less-hydrogenated ultrananocrystalline diamond (UNCD) films with distinct microstructural characteristics were deposited on Ti–6Al–4 V alloy, by optimizing the plasma conditions in the chemical vapor deposition. Both the UNCD films showed less friction coefficient in ambient atmospheric tribo-contact conditions due to the passivation. This provides chemical stability to UNCD films under the tribo-mechanical stressed conditions which limits the transferlayer formation and conversion of UNCD phase into graphitization/amorphization. However, in the high vacuum tribo-conditions, highly-hydrogenated UNCD films showed low friction value which gradually increased to the higher magnitude at longer sliding cycles. The low friction coefficient was indicative of passivation provided by the hydrogen network intrinsically present in the UNCD films. It gradually desorbs and the dangling bonds are progressively activated in the contact regime, leading to a gradual increase in the friction value. In contrast, less-hydrogenated UNCD films do not exhibit low friction regime in high vacuum conditions due to the lack of internal passivation. In this case, the conversion of UNCD to amorphized carbon structure in the wear tracks and amorphous carbon (a-C) tribofilm formation on ball scars were observed.
Xeno-free pre-vascularized spheroids for therapeutic applications
Authors: Bauman E. , Feijão T. , Carvalho D. T. O. , Granja P. L. , Barrias C. C. 
Published: January 2018

AbstractSpheroid culture has gained increasing popularity, arising as a promising tool for regenerative medicine applications. Importantly, spheroids may present advantages over single-cell suspensions in cell-based therapies (CT). Unfortunately, most growth media used for spheroid culture contain animal origin-components, such as fetal bovine serum (FBS). The presence of FBS compromises the safety of CT and presents economic and ethical constraints. SCC (supplement for cell culture) is a novel xeno-free (XF) industrial cell culture supplement, derived from well-controlled pooled human plasma and processed under good manufacturing practice rules. Here, we developed a XF SCC-based formulation for 2D-culture of outgrowth endothelial cells (OEC), and then used it for generating co-culture spheroids of OEC and mesenchymal stem cells (MSC). XF MSC-OEC spheroids were characterized in detail and compared to spheroids cultured in FBS-supplemented medium. XF spheroids presented comparable integrity, size and morphology as the reference culture. The use of both media resulted in spheroids with similar structure, abundant extracellular matrix deposition and specific patterns of OEC distribution and organization. Notably, XF spheroids presented significantly enhanced angiogenic potential, both in vitro (fibrin sprouting assay) and in vivo (CAM assay). These findings are particularly promising in the context of potential therapeutic applications.
Probing the molecular basis of hERG drug block with unnatural amino acids
Authors: Macdonald Logan C. , Kim Robin Y. , Kurata Harley T. , Fedida David 
Published: January 2018

AbstractRepolarization of the cardiac action potential is primarily mediated by two voltage-dependent potassium currents:IKrandIKs. The voltage-gated potassium channel that gives rise toIKr, Kv11.1 (hERG), is uniquely susceptible to high-affinity block by a wide range of drug classes. Pore residues Tyr652 and Phe656 are critical to potent drug interaction with hERG. It is considered that the molecular basis of this broad-spectrum drug block phenomenon occurs through interactions specific to the aromatic nature of the side chains at Tyr652 and Phe656. In this study, we used nonsense suppression to incorporate singly and doubly fluorinated phenylalanine residues at Tyr652 and Phe656 to assess cation-π interactions in hERG terfenadine, quinidine, and dofetilide block. Incorporation of these unnatural amino acids was achieved with minimal alteration to channel activation or inactivation gating. Our assessment of terfenadine, quinidine, and dofetilide block did not reveal evidence of a cation-π interaction at either aromatic residue, but, interestingly, shows that certain fluoro-Phe substitutions at position 652 result in weaker drug potency.
Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis
Authors: Koseki Jun , Konno Masamitsu , Asai Ayumu , Colvin Hugh , Kawamoto Koichi , Nishida Naohiro , Sakai Daisuke , Kudo Toshihiro , Satoh Taroh , Doki Yuichiro , Mori Masaki , Ishii Hideshi 
Published: January 2018

AbstractThe significance of mitochondrial metabolism in cancer cells has recently been gaining attention. Among other findings, One-carbon folate metabolism has been reported to be closely associated with cellular characteristics in cancer. To study molecular targets for efficient cancer therapy, we investigated the association between the expressions of genes that code enzymes involved in one-carbon metabolism and survival rate of patients with adenocarcinomas of the colorectum and lung. Patients with high expression of genes that control the metabolic cycle of tetrahydrofolate (THF) in mitochondria, SHMT2, MTHFD2, and ALDH1L2, have a shorter overall survival rate compared with patients with low expression of these genes. Our results revealed that these genes could be novel and more promising anticancer targets than dihydrofolate reductase (DHFR), the current target of drug therapy linked with folate metabolism, suggesting the rationale of drug discovery in cancer medicine.
A new macrofaunal limit in the deep biosphere revealed by extreme burrow depths in ancient sediments
Authors: Cobain S. L. , Hodgson D. M. , Peakall J. , Wignall P. B. , Cobain M. R. D. 
Published: January 2018

AbstractMacrofauna is known to inhabit the top few 10s cm of marine sediments, with rare burrows up to two metres below the seabed. Here, we provide evidence from deep-water Permian strata for a previously unrecognised habitat up to at least 8 metres below the sediment-water interface. Infaunal organisms exploited networks of forcibly injected sand below the seabed, forming living traces and reworking sediment. This is the first record that shows sediment injections are responsible for hosting macrofaunal life metres below the contemporaneous seabed. In addition, given the widespread occurrence of thick sandy successions that accumulate in deep-water settings, macrofauna living in the deep biosphere are likely much more prevalent than considered previously. These findings should influence future sampling strategies to better constrain the depth range of infaunal animals living in modern deep-sea sands. One Sentence Summary: The living depth of infaunal macrofauna is shown to reach at least 8 metres in new habitats associated with sand injections.
Estimating the capacity for production of formamide by radioactive minerals on the prebiotic Earth
Authors: Adam Zachary R. , Hongo Yayoi , Cleaves H. James , Yi Ruiqin , Fahrenbach Albert C. , Yoda Isao , Aono Masashi 
Published: January 2018

AbstractWater creates special problems for prebiotic chemistry, as it is thermodynamically favorable for amide and phosphodiester bonds to hydrolyze. The availability of alternative solvents with more favorable properties for the formation of prebiotic molecules on the early Earth may have helped bypass this so-called “water paradox”. Formamide (FA) is one such solvent, and can serve as a nucleobase precursor, but it is difficult to envision how FA could have been generated in large quantities or accumulated in terrestrial surface environments. We report here the conversion of aqueous acetonitrile (ACN) via hydrogen cyanide (HCN) as an intermediate into FA by γ-irradiation under conditions mimicking exposure to radioactive minerals. We estimate that a radioactive placer deposit could produce 0.1‒0.8 mol FA km−2 year−1. A uraninite fission zone comparable to the Oklo reactors in Gabon can produce 0.1‒1 mol m−2 year−1, orders of magnitude greater than other scenarios of FA production or delivery for which reaching sizeable concentrations of FA are problematic. Radioactive mineral deposits may be favorable settings for prebiotic compound formation through emergent geologic processes and FA-mediated organic chemistry.
Extracellular Total Electrolyte Concentration Imaging for Electrical Brain Stimulation (EBS)
Authors: Sajib Saurav Z. K. , Lee Mun Bae , Kim Hyung Joong , Woo Eung Je , Kwon Oh In 
Published: January 2018

AbstractTechniques for electrical brain stimulation (EBS), in which weak electrical stimulation is applied to the brain, have been extensively studied in various therapeutic brain functional applications. The extracellular fluid in the brain is a complex electrolyte that is composed of different types of ions, such as sodium (Na+), potassium (K+), and calcium (Ca+). Abnormal levels of electrolytes can cause a variety of pathological disorders. In this paper, we present a novel technique to visualize the total electrolyte concentration in the extracellular compartment of biological tissues. The electrical conductivity of biological tissues can be expressed as a product of the concentration and the mobility of the ions. Magnetic resonance electrical impedance tomography (MREIT) investigates the electrical properties in a region of interest (ROI) at low frequencies (below 1 kHz) by injecting currents into the brain region. Combining with diffusion tensor MRI (DT-MRI), we analyze the relation between the concentration of ions and the electrical properties extracted from the magnetic flux density measurements using the MREIT technique. By measuring the magnetic flux density induced by EBS, we propose a fast non-iterative technique to visualize the total extracellular electrolyte concentration (EEC), which is a fundamental component of the conductivity. The proposed technique directly recovers the total EEC distribution associated with the water transport mobility tensor.
Thrombospondin-1 secreted by human umbilical cord blood-derived mesenchymal stem cells rescues neurons from synaptic dysfunction in Alzheimer’s disease model
Authors: Kim Dong Hyun , Lim Hoon , Lee Dahm , Choi Soo Jin , Oh Wonil , Yang Yoon Sun , Oh Jeong Su , Hwang Hyun Ho , Jeon Hong Bae 
Published: January 2018

AbstractAlzheimer’s disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Aβ) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs’ secretome co-cultured with Aβ42-treated mouse hippocampal neurons. Thrombospondin-1 (TSP-1), a protein secreted by hUCB-MSCs in in vitro and 5XFAD AD mouse models, was selected for study. Treatment with exogenous recombinant TSP-1 or co-cultures with hUCB-MSCs significantly increased expression of synaptic-density markers, such as synaptophysin (SYP) and post-synaptic density protein-95 (PSD-95) in Aβ42-treated mouse hippocampal neurons. Knockdown of TSP-1 expression in hUCB-MSCs through small interfering RNA (siRNA) abolished the reversal of Aβ42-induced hippocampal synaptic-density loss. We demonstrate that the rescue effect of hUCB-MSC-secreted TSP-1 was mediated by neuroligin-1 (NLGN1) or α2δ-1 receptors. Interestingly, NLGN1 and α2δ-1 expression, which was reduced in Aβ42-treated hippocampal neurons, increased in co-cultures with hUCB-MSCs or exogenous TSP-1. Together, these findings suggest that hUCB-MSCs can attenuate Aβ42-induced synaptic dysfunction by regulating TSP-1 release, thus providing a potential alternative therapeutic option for early-stage AD.
Tumor suppressor activity of miR-451: Identification of CARF as a new target
Authors: Li Ling , Gao Ran , Yu Yue , Kaul Zeenia , Wang Jia , Kalra Rajkumar S. , Zhang Zhenya , Kaul Sunil C. , Wadhwa Renu 
Published: January 2018

AbstractmicroRNAs (miRs) have recently emerged as small non-coding regulators of gene expression. We performed a loss-of-function screening by recruiting retrovirus mediated arbitrary manipulation of genome coupled with escape of cells from 5-Aza-2′-deoxycytidine (5-Aza-dC)-induced senescence. miRNA pool from cells that emerged from 5-Aza-dC-induced senescence was subjected to miR-microarray analysis with respect to the untreated control. We identified miR-451 as one of the upregulated miRs and characterized its functional relevance to drug resistance, cell growth, tumor suppressor proteins p53 and pRb, and stress response. We report that miR-451 caused growth arrest in cells leading to their resistance to 5-Aza-dC-induced senescence. Decrease in cyclin D1, CDK4 and phosphorylated pRB supported the growth arrest in miR-451 transfected cells. We demonstrate that Collaborator of ARF (CARF) protein is a new target of miR-451 that intermediates its function in tumor suppressor and stress signaling.
Role of cobalt cations in short range antiferromagnetic Co3O4 nanoparticles: a thermal treatment approach to affecting phonon and magnetic properties
Authors: Gawali Swati R. , Gandhi Ashish Chhaganlal , Gaikwad Shrikrushna Shivaji , Pant Jayashree , Chan Ting-Shan , Cheng Chia-Liang , Ma Yuan-Ron , Wu Sheng Yun 
Published: January 2018

AbstractWe report the phonon and magnetic properties of various well-stabilized Co3O4 nanoparticles. The net valence in cobalt (II)/(III) cation can be obtained by subtracting the Co2+ ions in tetrahedral interstices and Co3+ ions in the octahedral interstices, respectively, which will possess spatial inhomogeneity of its magnetic moment via Co2+ in tetrahedra and Co3+ in octahedral configurations in the normal spinel structure. Furthermore, the distribution of Co2+/Co3+ governed by various external (magnetic field and temperature) and internal (particle size and slightly distorted CoO6 octahedra) sources, have led to phenomena such as a large redshift of phonon-phonon interaction and short-range magnetic correlation in the inverse spinel structure. The outcome of our study is important in terms of the future development of magnetic semiconductor spintronic devices of Co3O4.
Fis is a global regulator critical for modulation of virulence factor production and pathogenicity of Dickeya zeae
Authors: Lv Mingfa , Chen Yufan , Liao Lisheng , Liang Zhibin , Shi Zurong , Tang Yingxin , Ye Sixuan , Zhou Jianuan , Zhang Lianhui 
Published: January 2018

AbstractDickeya zeaeis the causal agent of rice foot rot disease, which has recently become a great threat to rice planting countries and regions. The pathogen produces a family of phytotoxins named zeamines that is critical for bacterial virulence, but little is known about the signaling pathways and regulatory mechanisms that govern zeamine production. In this study, we showed that a conserved transcriptional regulator Fis is involved in the regulation of zeamine production inD. zeaestrain EC1. Deletion mutants were markedly attenuated in the virulence against rice seed germination. Transcriptome and phenotype analyses showed that Fis is a potent global transcriptional regulator modulating various virulence traits, including production of extracellular enzymes and exopolysaccharides, swimming and swarming motility, biofilm formation and cell aggregation. DNA gel retardation analysis showed that Fis directly regulates the transcription of key virulence genes and the genes encoding Vfm quorum sensing system through DNA/protein interaction. Our findings unveil a key regulator associated with the virulence ofD. zeaeEC1, and present useful clues for further elucidation of the regulatory complex and signaling pathways which govern the virulence of this important pathogen.
Room temperature stable film formation of π-conjugated organic molecules on 3d magnetic substrate
Authors: Inami Eiichi , Shimasaki Mikio , Yorimitsu Hideki , Yamada Toyo Kazu 
Published: January 2018

AbstractAn important step toward molecule-based electronics is to realize a robust and well-ordered molecular network at room temperature. To this end, one key challenge is tuning the molecule–substrate electronic interactions that influence not only the molecular selfassembly but also the stability of the resulting structures. In this study, we investigate the film formation of π-conjugated metal-free phthalocyanine molecules on a 3d-bcc-Fe(001) whisker substrate at 300 K by using ultra-high-vacuum scanning tunneling microscopy. On bare Fe(001), hybridization between the molecular π and the Fe(001) d-states prevents the molecular assembly, resulting in the disordered patchy structures. The second- and third-layer molecules form densely packed films, while the morphologies show clear difference. The second-layer molecules partially form p(5 × 5)-ordered films with the rectangular edges aligned along the [100] and [010] directions, while the edges of the third-layer films are rounded. Remarkably, such film morphologies are stable even at 300 K. These findings suggest that the molecular self-assembly and the resulting morphologies in the second and third layers are affected by the substrate bcc(001), despite that the Fe-d states hybridize only with the first-layer molecules. The possible mechanism is discussed with the kinetic Monte Carlo simulation.
Functional Isolation of Tumor-Initiating Cells using Microfluidic-Based Migration Identifies Phosphatidylserine Decarboxylase as a Key Regulator
Authors: Chen Yu-Chih , Humphries Brock , Brien Riley , Gibbons Anne E. , Chen Yu-Ting , Qyli Tonela , Haley Henry R. , Pirone Matthew E. , Chiang Benjamin , Xiao Annie , Cheng Yu-Heng , Luan Yi , Zhang Zhixiong , Cong Jason , Luker Kathryn E. , Luker Gary D. , Yoon Euisik 
Published: January 2018

AbstractIsolation of tumor-initiating cells currently relies on markers that do not reflect essential biologic functions of these cells. We proposed to overcome this limitation by isolating tumor-initiating cells based on enhanced migration, a function tightly linked to tumor-initiating potential through epithelial-to-mesenchymal transition (EMT). We developed a high-throughput microfluidic migration platform with automated cell tracking software and facile recovery of cells for downstream functional and genetic analyses. Using this device, we isolated a small subpopulation of migratory cells with significantly greater tumor formation and metastasis in mouse models. Whole transcriptome sequencing of migratory versus non-migratory cells from two metastatic breast cancer cell lines revealed a unique set of genes as key regulators of tumor-initiating cells. We focused on phosphatidylserine decarboxylase (PISD), a gene downregulated by 8-fold in migratory cells. Breast cancer cells overexpressing PISD exhibited reduced tumor-initiating potential in a high-throughput microfluidic mammosphere device and mouse xenograft model. PISD regulated multiple aspects of mitochondria, highlighting mitochondrial functions as therapeutic targets against cancer stem cells. This research establishes not only a novel microfluidic technology for functional isolation of tumor-initiating cells regardless of cancer type, but also a new approach to identify essential regulators of these cells as targets for drug development.