bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTORC1 activity is essential for erythropoiesis and B cell lineage commitment
Authors: Malik Natasha , Dunn Karen M. , Cassels Jennifer , Hay Jodie , Estell Christopher , Sansom Owen J. , Michie Alison M. 
Published: November 2019

AbstractMechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that mediates phosphoinositide-3-kinase (PI3K)/AKT signalling. This pathway is involved in a plethora of cellular functions including protein and lipid synthesis, cell migration, cell proliferation and apoptosis. In this study, we proposed to delineate the role of mTORC1 in haemopoietic lineage commitment using knock out (KO) mouse and cell line models. Mx1-cre and Vav-cre expression systems were used to specifically target Raptorfl/fl (mTORC1), either in all tissues upon poly(I:C) inoculation, or specifically in haemopoietic stem cells, respectively. Assessment of the role of mTORC1 during the early stages of development in Vav-cre+Raptorfl/fl mice, revealed that these mice do not survive post birth due to aberrations in erythropoiesis resulting from an arrest in development at the megakaryocyte-erythrocyte progenitor stage. Furthermore, Raptor-deficient mice exhibited a block in B cell lineage commitment. The essential role of Raptor (mTORC1) in erythrocyte and B lineage commitment was confirmed in adult Mx1-cre+Raptorfl/fl mice upon cre-recombinase induction. These studies were supported by results showing that the expression of key lineage commitment regulators, GATA1, GATA2 and PAX5 were dysregulated in the absence of mTORC1-mediated signals. The regulatory role of mTOR during erythropoiesis was confirmed in vitro by demonstrating a reduction of K562 cell differentiation towards RBCs in the presence of established mTOR inhibitors. While mTORC1 plays a fundamental role in promoting RBC development, we showed that mTORC2 has an opposing role, as Rictor-deficient progenitor cells exhibited an elevation in RBC colony formation ex vivo. Collectively, our data demonstrate a critical role played by mTORC1 in regulating the haemopoietic cell lineage commitment.
Machine Learning to Quantitate Neutrophil NETosis
Authors: Elsherif Laila , Sciaky Noah , Metts Carrington A. , Modasshir Md. , Rekleitis Ioannis , Burris Christine A. , Walker Joshua A. , Ramadan Nadeem , Leisner Tina M. , Holly Stephen P. , Cowles Martis W. , Ataga Kenneth I. , Cooper Joshua N. , Parise Leslie V. 
Published: November 2019

AbstractWe introduce machine learning (ML) to perform classification and quantitation of images of nuclei from human blood neutrophils. Here we assessed the use of convolutional neural networks (CNNs) using free, open source software to accurately quantitate neutrophil NETosis, a recently discovered process involved in multiple human diseases. CNNs achieved >94% in performance accuracy in differentiating NETotic from non-NETotic cells and vastly facilitated dose-response analysis and screening of the NETotic response in neutrophils from patients. Using only features learned from nuclear morphology, CNNs can distinguish between NETosis and necrosis and between distinct NETosis signaling pathways, making them a precise tool for NETosis detection. Furthermore, by using CNNs and tools to determine object dispersion, we uncovered differences in NETotic nuclei clustering between major NETosis pathways that is useful in understanding NETosis signaling events. Our study also shows that neutrophils from patients with sickle cell disease were unresponsive to one of two major NETosis pathways. Thus, we demonstrate the design, performance, and implementation of ML tools for rapid quantitative and qualitative cell analysis in basic science.
Maximal information transmission is compatible with ultrasensitive biological pathways
Authors: Micali Gabriele , Endres Robert G. 
Published: November 2019

AbstractCells are often considered input-output devices that maximize the transmission of information by converting extracellular stimuli (input) via signaling pathways (communication channel) to cell behavior (output). However, in biological systems outputs might feed back into inputs due to cell motility, and the biological channel can change by mutations during evolution. Here, we show that the conventional channel capacity obtained by optimizing the input distribution for a fixed channel may not reflect the global optimum. In a new approach we analytically identify both input distributions and input-output curves that optimally transmit information, given constraints from noise and the dynamic range of the channel. We find a universal optimal input distribution only depending on the input noise, and we generalize our formalism to multiple outputs (or inputs). Applying our formalism toEscherichia colichemotaxis, we find that its pathway is compatible with optimal information transmission despite the ultrasensitive rotary motors.
PD-1+ melanocortin receptor dependent-Treg cells prevent autoimmune disease
Authors: Muhammad Fauziyya , Wang Dawei , Montieth Alyssa , Lee Stacey , Preble Janine , Foster C. Stephen , Larson Theresa A. , Ding Kai , Dvorak Justin D. , Lee Darren J. 
Published: November 2019

AbstractExperimental autoimmune uveoretinitis (EAU) is a mouse model of human autoimmune uveitis marked by ocular autoantigen-specific regulatory immunity in the spleen. The melanocortin 5 receptor (MC5r) and adenosine 2 A receptor (A2Ar) are required for induction of post-EAU regulatory T cells (Tregs) which provide resistance to EAU. We show that blocking the PD-1/PD-L1 pathway prevented suppression of EAU by post-EAU Tregs. A2Ar induction of PD-1+FoxP3+ Tregs in uveitis patients was similar compared to healthy controls, but was significantly reduced with melanocortin stimulation. Further, lower body mass index correlated with responsiveness to stimulation of this pathway. These observations indicate an importance of the PD-1/PD-L1 pathway to provide resistance to relapsing uveitis and shows a reduced capacity of uveitis patients to induce Tregs when stimulated through melanocortin receptors, but that it is possible to bypass this part of the pathway through direct stimulation of A2Ar.
The peptide AC 2 isolated from Bacillus-treated Trapa japonica fruit extract rescues DHT (dihydrotestosterone)-treated human dermal papilla cells and mediates mTORC1 signaling for autophagy and apoptosis suppression
Authors: Nam Gun He , Jo Kyung-Jo , Park Ye-Seul , Kawk Hye Won , Yoo Je-Geun , Jang Jin Dong , Kang Sang Moon , Kim Sang-Yong , Kim Young-Min 
Published: November 2019

AbstractThe Trapa japonica fruit is a natural plant growing in ponds with its roots in the mud. It has long been used as a home remedy for many diseases; however, a major problem with this kind of natural extract is the multicomponents-multitargets for diseases. Such problems make it difficult to identify the mechanism of action. Another problem is quality control and consistency. The aim of this research was to isolate a single bioactive compound (peptide) derived from the Trapa japonica fruit. The research was conducted with various experimental techniques, such as fermentation and liquid chromatography, to isolate a peptide. We isolated the AC 2 peptide from Trapa japonica fruit and found it to be promising on human dermal papilla cells. Dihydrotestosterone (DHT) stresses human dermal papilla cells and is a major cause of hair loss resulting from hormones and environmental factors. The purpose of this research was to develop an understanding of the mechanism by which the AC 2 peptide rescues dihydrotestosterone (DHT)-treated human dermal papilla cells. We explored the effects of the AC 2 peptide on the cell biological functions of human dermal papilla cells (HDPs). HDPs were treated with the AC 2 peptide and DHT. Then, a cytotoxicity assay, flow cytometry, Western blot, immunoprecipitation, and 3D cell culture for immunohistochemistry were conducted to investigate the mTORC1 pathway and suppression of autophagy and apoptosis. In addition, we also synthesized the AC2 peptide as an alternative to the expensive and difficult isolation and purification procedures and confirmed its potential in biomedical applications. We also validated the effects of the synthetic AC2 peptide as well as the isolated and purified AC2 peptide and established their similarity. Although extensive research has been carried out on natural extracts, few single studies have isolated and separated a bioactive peptide (single compound).
Computed terahertz near-field mapping of molecular resonances of lactose stereo-isomer impurities with sub-attomole sensitivity
Authors: Moon Kiwon , Do Youngwoong , Park Hongkyu , Kim Jeonghoi , Kang Hyuna , Lee Gyuseok , Lim Jin-Ha , Kim Jin-Woo , Han Haewook 
Published: November 2019

AbstractTerahertz near-field microscopy (THz-NFM) could locally probe low-energy molecular vibration dynamics below diffraction limits, showing promise to decipher intermolecular interactions of biomolecules and quantum matters with unique THz vibrational fingerprints. However, its realization has been impeded by low spatial and spectral resolutions and lack of theoretical models to quantitatively analyze near-field imaging. Here, we show that THz scattering-type scanning near-field optical microscopy (THz s-SNOM) with a theoretical model can quantitatively measure and image such low-energy molecular interactions, permitting computed spectroscopic near-field mapping of THz molecular resonance spectra. Using crystalline-lactose stereo-isomer (anomer) mixtures (i.e., α-lactose (≥95%, w/w) and β-lactose (≤4%, w/w)), THz s-SNOM resolved local intermolecular vibrations of both anomers with enhanced spatial and spectral resolutions, yielding strong resonances to decipher conformational fingerprint of the trace β-anomer impurity. Its estimated sensitivity was ~0.147 attomoles in ~8 × 10−4 μm3 interaction volume. Our THz s-SNOM platform offers a new path for ultrasensitive molecular fingerprinting of complex mixtures of biomolecules or organic crystals with markedly enhanced spatio-spectral resolutions. This could open up significant possibilities of THz technology in many fields, including biology, chemistry and condensed matter physics as well as semiconductor industries where accurate quantitative mappings of trace isomer impurities are critical but still challenging.
Addition of MnO2 in synthesis of nano-rod erdite promoted tetracycline adsorption
Authors: Zhu Suiyi , Liu Yanwen , Huo Yang , Chen Yu , Qu Zhan , Yu Yang , Wang Zhihua , Fan Wei , Peng Juwei , Wang Zhaofeng 
Published: November 2019

AbstractErdite is a rare sulphide mineral found in mafic and alkaline rocks. Only weakly crystallised fibrous erdite has been artificially synthesised via evaporation or the hydrothermal method, and the process generally requires 1–3 days and large amounts of energy to complete. In this study, well-crystallised erdite nanorods were produced within 3 h by using MnO2 as an auxiliary reagent in a one-step hydrothermal method. Results showed that erdite could synthesised in nanorod form with a diameter of approximately 200 nm and lengths of 0.5–3 μm by adding MnO2; moreover, the crystals grew with increasing MnO2 addition. Without MnO2, erdite particles were generated in irregular form. The capacity of the erdite nanorods for tetracycline (TC) adsorption was 2613.3 mg/g, which is higher than those of irregular erdite and other reported adsorbents. The major adsorption mechanism of the crystals involves a coordinating reaction between the −NH2 group of TC and the hydroxyl group of Fe oxyhydroxide produced from erdite hydrolysis. To the best of our knowledge, this study is the first to synthesise erdite nanorods and use them in TC adsorption. Erdite nanorods may be developed as a new material in the treatment of TC-containing wastewater.
Comparative genomic analysis of eutherian connexin genes
Authors: Premzl Marko 
Published: November 2019

AbstractThe eutherian connexins were characterized as protein constituents of gap junctions implicated in cell-cell communications between adjoining cells in multiple cell types, regulation of major physiological processes and disease pathogeneses. However, conventional connexin gene and protein classifications could be regarded as unsuitable in descriptions of comprehensive eutherian connexin gene data sets, due to ambiguities and inconsistencies in connexin gene and protein nomenclatures. Using eutherian comparative genomic analysis protocol and 35 public eutherian reference genomic sequence data sets, the present analysis attempted to update and revise comprehensive eutherian connexin gene data sets, and address and resolve major discrepancies in their descriptions. Among 631 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated, in aggregate, 349 connexin complete coding sequences. The most comprehensive curated eutherian connexin gene data set described 21 major gene clusters, 4 of which included evidence of differential gene expansions. For example, the present gene annotations initially described human CXNK1 gene and annotated 22 human connexin genes. Phylogenetic tree calculations and calculations of pairwise nucleotide sequence identity patterns proposed revised and updated phylogenetic classification of eutherian connexin genes. Therefore, the present study integrating gene annotations, phylogenetic analysis and protein molecular evolution analysis proposed new nomenclature of eutherian connexin genes and proteins.
Computational redesign of the Escherichia coli ribose-binding protein ligand binding pocket for 1,3-cyclohexanediol and cyclohexanol
Authors: Tavares Diogo , Reimer Artur , Roy Shantanu , Joublin Aurélie , Sentchilo Vladimir , van der Meer Jan Roelof 
Published: November 2019

AbstractBacterial periplasmic-binding proteins have been acclaimed as general biosensing platform, but their range of natural ligands is too limited for optimal development of chemical compound detection. Computational redesign of the ligand-binding pocket of periplasmic-binding proteins may yield variants with new properties, but, despite earlier claims, genuine changes of specificity to non-natural ligands have so far not been achieved. In order to better understand the reasons of such limited success, we revisited here the Escherichia coli RbsB ribose-binding protein, aiming to achieve perceptible transition from ribose to structurally related chemical ligands 1,3-cyclohexanediol and cyclohexanol. Combinations of mutations were computationally predicted for nine residues in the RbsB binding pocket, then synthesized and tested in an E. coli reporter chassis. Two million variants were screened in a microcolony-in-bead fluorescence-assisted sorting procedure, which yielded six mutants no longer responsive to ribose but with 1.2–1.5 times induction in presence of 1 mM 1,3-cyclohexanediol, one of which responded to cyclohexanol as well. Isothermal microcalorimetry confirmed 1,3-cyclohexanediol binding, although only two mutant proteins were sufficiently stable upon purification. Circular dichroism spectroscopy indicated discernable structural differences between these two mutant proteins and wild-type RbsB. This and further quantification of periplasmic-space abundance suggested most mutants to be prone to misfolding and/or with defects in translocation compared to wild-type. Our results thus affirm that computational design and library screening can yield RbsB mutants with recognition of non-natural but structurally similar ligands. The inherent arisal of protein instability or misfolding concomitant with designed altered ligand-binding pockets should be overcome by new experimental strategies or by improved future protein design algorithms.
P band intermediate state (PBIS) tailors photoluminescence emission at confined nanoscale interface
Authors: Yang Taiqun , Shan Bingqian , Huang Fang , Yang Songqiu , Peng Bo , Yuan Enhui , Wu Peng , Zhang Kun 
Published: November 2019

AbstractThe availability of a range of excited states has endowed low dimensional quantum nanostructures with interesting luminescence properties. However, the origin of photoluminescence emission is still not fully understood, which has limited its practical application. Here we judiciously manipulate the delicate surface ligand interactions at the nanoscale interface of a single metal nanocluster, the superlattice, and mesoporous materials. The resulting interplay of various noncovalent interactions leads to a precise modulation of emission colors and quantum yield. A new p-band state, resulting from the strong overlapping of p orbitals of the heteroatoms (O, N, and S) bearing on the targeting ligands though space interactions, is identified as a dark state to activate the triplet state of the surface aggregated chromophores. The UV-Visible spectra calculated by time-dependent density functional theory (TD-DFT) are in quantitative agreement with the experimental adsorption spectra. The energy level of the p-band center is very sensitive to the local proximity ligand chromophores at heterogeneous interfaces.
Individual skyrmion manipulation by local magnetic field gradients
Authors: Casiraghi Arianna , Corte-León Héctor , Vafaee Mehran , Garcia-Sanchez Felipe , Durin Gianfranco , Pasquale Massimo , Jakob Gerhard , Kläui Mathias , Kazakova Olga 
Published: November 2019

AbstractMagnetic skyrmions are topologically protected spin textures, stabilised in systems with strong Dzyaloshinskii-Moriya interaction (DMI). Several studies have shown that electrical currents can move skyrmions efficiently through spin-orbit torques. While promising for technological applications, current-driven skyrmion motion is intrinsically collective and accompanied by undesired heating effects. Here we demonstrate a new approach to control individual skyrmion positions precisely, which relies on the magnetic interaction between sample and a magnetic force microscopy (MFM) probe. We investigate perpendicularly magnetised X/CoFeB/MgO multilayers, where for X = W or Pt the DMI is sufficiently strong to allow for skyrmion nucleation in an applied field. We show that these skyrmions can be manipulated individually through the local field gradient generated by the scanning MFM probe with an unprecedented level of accuracy. Furthermore, we show that the probe stray field can assist skyrmion nucleation. Our proof-of-concepts results pave the way towards achieving current-free skyrmion control.
Moracin attenuates LPS-induced inflammation in nucleus pulposus cells via Nrf2/HO-1 and NF-κB/TGF-β pathway
Authors: Gu Ronghe , Huang Zonggui , Liu Huijiang , Qing Qiwen , Zhuan Zou , Yang Lijing , Su Zhongyi , Huang Weiguo 
Published: November 2019

Abstract
The present study was designed to investigate the protective effect of moracin on primary culture of nucleus pulposus cells in intervertebral disc and explore the underlying mechanism. Moracin treatment significantly inhibited the LPS-induced inflammatory cytokine accumulation (IL-1β, IL-6 and TNF-α) in nucleus pulposus cells. And moracin also dramatically decreased MDA activity, and increased the levels of SOD and CAT induced by LPS challenge. Moreover, the expressions of Nrf-2 and HO-1 were decreased and the protein levels of p-NF-κBp65, p-IκBα, p-smad-3 and TGF-β were increased by LPS challenge, which were significantly reversed after moracin treatments. Moracin treatments also decreased the levels of matrix degradation enzymes (MMP-3, MMP-13) as indicated by RT-PCR analysis. However, Nrf-2 knockdown abolished these protective effects of moracin. Together, our results demonstrated the ability of moracin to antagonize LPS-mediated inflammation in primary culture of nucleus pulposus in intervertebral disc by partly regulating the Nrf2/HO-1 and NF-κB/TGF-β pathway in nucleus pulposus cells.
Design of an ultra‐small UHF RFID tag for embedded applications in metallic objects
Authors: Do Kim Young 
Published: November 2019

A small UHF RFID tag for embedded applications in the metallic objects was proposed. Using the high dielectric ceramic as a tag antenna substrate and the folded tag antenna structure reduces the total RFID tag size compared to the conventional tag designs. The tuning slot length on ceramic top patch is used to match conjugate impedance. The proposed RFID tag antenna exhibits a reasonable radiation gain in the metal embedded environments. The maximum read range of the fabricated RFID tag in the different commercial RFID handheld reader set‐up are 40 and 60 cm, respectively.
Scientistsʼ Warning on Climate Change and Medicinal Plants
Authors: Applequist Wendy L. , Brinckmann Josef A. , Cunningham Anthony B. , Hart Robbie E. , Heinrich Michael , Katerere David R. , van Andel Tinde 
Published: November 2019

AbstractThe recent publication of a World Scientistsʼ Warning to Humanity highlighted the fact that climate change, absent strenuous mitigation or adaptation efforts, will have profound negative effects for humanity and other species, affecting numerous aspects of life. In this paper, we call attention to one of these aspects, the effects of climate change on medicinal plants. These plants provide many benefits for human health, particularly in communities where Western medicine is unavailable. As for other species, their populations may be threatened by changing temperature and precipitation regimes, disruption of commensal relationships, and increases in pests and pathogens, combined with anthropogenic habitat fragmentation that impedes migration. Additionally, medicinal species are often harvested unsustainably, and this combination of pressures may push many populations to extinction. A second issue is that some species may respond to increased environmental stresses not only with declines in biomass production but with changes in chemical content, potentially affecting quality or even safety of medicinal products. We therefore recommend actions including conservation and local cultivation of valued plants, sustainability training for harvesters and certification of commercial material, preservation of traditional knowledge, and programs to monitor raw material quality in addition to, of course, efforts to mitigate climate change.
Study on Closure of Skull Base Defect Post–Endoscopic Endonasal Transsphenoid Pituitary Surgery: A Novel Flap Design
Authors: Gopi Gokul , Sarkar Saurav , Mohakud Sudipta , Patnaik Ashis , Bansal Sumit , Preetam C. , Sahu Rabi Narayan , Parida Pradipta Ku 
Published: November 2019

Abstract
Objective This study was aimed to compare the closure of skull base defect in endoscopic endonasal transsphenoid surgery of pituitary tumors, using bipedicled nasal septal flap versus fascial closure. The study hypothesis being that bipedicled nasal septal flap is better, compared with fascial closure of skull base defect post–endoscopic endonasal transsphenoid surgery of pituitary tumors.
Methods All the eligible patients were randomly divided into two groups and then randomly allocated to the surgeons. In one group, fat and fascia lata was used for closure of the skull base defect and nasal septal flap was not harvested whereas in the other, nasal septal flap was used for closure.
Results There was a statistically significant difference in postoperative cerebrospinal fluid leak between the two groups. Patients who had undergone flap repair had lower incidence of postoperative cerebrospinal fluid (CSF) leak. Duration of postoperative hospital stay was also less among the group who underwent flap repair (statistically significant).
Conclusion Bipedicled nasal septal flap serves an excellent cover for the skull base defect following endoscopic endonasal transsphenoidal pituitary surgery. It can prevent postoperative CSF leak even in cases where tissue glue is not used.