bluuebunny/crossref_metadata_2025_split huggingface dataset:
LARP7 family proteins have conserved function in telomerase assembly
Authors: Collopy Laura C. , Ware Tracy L. , Goncalves Tomas , í Kongsstovu Sunnvør , Yang Qian , Amelina Hanna , Pinder Corinne , Alenazi Ala , Moiseeva Vera , Pearson Siân R. , Armstrong Christine A. , Tomita Kazunori 
Published: February 2018

AbstractUnderstanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2–8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved factor in telomere maintenance.
The tumour microenvironment creates a niche for the self-renewal of tumour-promoting macrophages in colon adenoma
Authors: Soncin Irene , Sheng Jianpeng , Chen Qi , Foo Shihui , Duan Kaibo , Lum Josephine , Poidinger Michael , Zolezzi Francesca , Karjalainen Klaus , Ruedl Christiane 
Published: February 2018

AbstractCirculating CCR2+monocytes are crucial for maintaining the adult tissue-resident F4/80hiMHCIIhimacrophage pool in the intestinal lamina propria. Here we show that a subpopulation of CCR2-independent F4/80hiMHCIIlowmacrophages, which are the most abundant F4/80hicells in neonates, gradually decline in number in adulthood; these macrophages likely represent the fetal contribution to F4/80hicells. In colon adenomas ofApcMin/+mice, F4/80hiMHCIIlowmacrophages are not only preserved, but become the dominant subpopulation among tumour-resident macrophages during tumour progression. Furthermore, these pro-tumoural F4/80hiMHCIIlowand F4/80hiMHCIIhimacrophages can self-renew in the tumour and maintain their numbers mostly independent from bone marrow contribution. Analyses of colon adenomas indicate that CSF1 may be a key facilitator of macrophage self-renewal. In summary, the tumour microenvironment creates an isolated niche for tissue-resident macrophages that favours macrophage survival and self-renewal.
IL-6/STAT3 pathway induced deficiency of RFX1 contributes to Th17-dependent autoimmune diseases via epigenetic regulation
Authors: Zhao Ming , Tan Yixin , Peng Qiao , Huang Cancan , Guo Yu , Liang Gongping , Zhu Bochen , Huang Yi , Liu Aiyun , Wang Zijun , Li Mengying , Gao Xiaofei , Wu Ruifang , Wu Haijing , Long Hai , Lu Qianjin 
Published: February 2018

AbstractEpigenetic modifications affect the differentiation of T cell subsets and the pathogenesis of autoimmune diseases, but many mechanisms of epigenetic regulation of T cell differentiation are unclear. Here we show reduced expression of the transcription factor RFX1 in CD4+ T cells from patients with systemic lupus erythematosus, which leads to IL-17A overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 tri-methylation. Conditional deletion of Rfx1 in mice exacerbates experimental autoimmune encephalomyelitis and pristane-induced lupus-like syndrome and increases induction of Th17 cells. In vitro, Rfx1 deficiency increases the differentiation of naive CD4+ T cells into Th17 cells, but this effect can be reversed by forced expression of Rfx1. Importantly, RFX1 functions downstream of STAT3 and phosphorylated STAT3 can inhibit RFX1 expression, highlighting a non-canonical pathway that regulates differentiation of Th17 cells. Collectively, our findings identify a unique role for RFX1 in Th17-related autoimmune diseases.
No tension between assembly models of super massive black hole binaries and pulsar observations
Authors: Middleton Hannah , Chen Siyuan , Del Pozzo Walter , Sesana Alberto , Vecchio Alberto 
Published: February 2018

AbstractPulsar timing arrays are presently the only means to search for the gravitational wave stochastic background from super massive black hole binary populations, considered to be within the grasp of current or near-future observations. The stringent upper limit from the Parkes Pulsar Timing Array has been interpreted as excluding (>90% confidence) the current paradigm of binary assembly through galaxy mergers and hardening via stellar interaction, suggesting evolution is accelerated or stalled. Using Bayesian hierarchical modelling we consider implications of this upper limit for a range of astrophysical scenarios, without invoking stalling, nor more exotic physical processes. All scenarios are fully consistent with the upper limit, but (weak) bounds on population parameters can be inferred. Recent upward revisions of the black hole–galaxy bulge mass relation are disfavoured at 1.6σ against lighter models. Once sensitivity improves by an order of magnitude, a non-detection will disfavour the most optimistic scenarios at 3.9σ.
A quantum optical study of thresholdless lasing features in high-β nitride nanobeam cavities
Authors: Jagsch Stefan T. , Triviño Noelia Vico , Lohof Frederik , Callsen Gordon , Kalinowski Stefan , Rousseau Ian M. , Barzel Roy , Carlin Jean-François , Jahnke Frank , Butté Raphaël , Gies Christopher , Hoffmann Axel , Grandjean Nicolas , Reitzenstein Stephan 
Published: February 2018

AbstractExploring the limits of spontaneous emission coupling is not only one of the central goals in the development of nanolasers, it is also highly relevant regarding future large-scale photonic integration requiring energy-efficient coherent light sources with a small footprint. Recent studies in this field have triggered a vivid debate on how to prove and interpret lasing in the high-β regime. We investigate close-to-ideal spontaneous emission coupling in GaN nanobeam lasers grown on silicon. Such nanobeam cavities allow for efficient funneling of spontaneous emission from the quantum well gain material into the laser mode. By performing a comprehensive optical and quantum-optical characterization, supported by microscopic modeling of the nanolasers, we identify high-β lasing at room temperature and show a lasing transition in the absence of a threshold nonlinearity at 156 K. This peculiar characteristic is explained in terms of a temperature and excitation power-dependent interplay between zero-dimensional and two-dimensional gain contributions.
Childhood epilepsy and ADHD comorbidity in an Indian tertiary medical center outpatient population
Authors: Choudhary Anita , Gulati Sheffali , Sagar Rajesh , Sankhyan Naveen , Sripada Kam 
Published: February 2018

AbstractThis study aimed to assess the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) and its characteristics and risk factors in children with epilepsy at a tertiary medical center in New Delhi. Children with active epilepsy, aged 6 to 12 years, were assessed for ADHD using DSM-IV-TR criteria. Epilepsy and psychiatric characteristics, sociodemographic indicators, and use of antiepileptic drugs were analyzed for differences between the ADHD and non-ADHD groups. Among the 73 children with epilepsy, 23% (n = 17) had comorbid ADHD, of whom 59% (n = 10) had predominantly inattentive type, 35% (n = 6) combined type, and 6% (n = 1) predominantly hyperactive-impulsive type. Lower IQ scores, epileptiform EEG activity, not attending school, and male sex were significantly associated with comorbid ADHD in children with epilepsy. Groups were similar in terms of age, socioeconomic indicators, family history of psychiatric disorders, seizure frequency in the last six months, seizure etiology, and seizure type. Epilepsy is a common pediatric neurological condition with frequent psychiatric comorbidities, including ADHD. Specialists should collaborate to optimize treatment for children with epilepsy and ADHD, especially for families in developing countries where the burden of disease can be great.
Epothilone B Speeds Corneal Nerve Regrowth and Functional Recovery through Microtubule Stabilization and Increased Nerve Beading
Authors: Wang Hanqing , Xiao Chengju , Dong Dong , Lin Cuipei , Xue Yunxia , Liu Jun , Wu Mingjuan , He Jingxin , Fu Ting , Pan Hongwei , Jiao Xinwei , Lu Dingli , Li Zhijie 
Published: February 2018

AbstractThe successful restoration of corneal innervation and function after a corneal injury is a clinically challenging issue. Structural and functional recovery after a nerve injury involves a complex series of steps in which microtubules play a key role. The aim of the current study was to investigate the effects of epothilone B (EpoB), a microtubule-stabilizing agent, on corneal innervation and the functional recovery of the corneal nerve in mice after corneal epithelial abrasion. The pretreatment of mice with EpoB has a remarkable effect on the stabilization of beta-III tubulin, as demonstrated by substantial increases in the visualization of beta-III tubulin, nerve beading, corneal reinnervation, and reaction to stimuli. Furthermore, a pharmacokinetic analysis showed that EpoB remains at a high concentration in the cornea and the trigeminal ganglion for at least 6 days after administration. In addition, the administration of EpoB at 24 hours after corneal abrasion has a marked therapeutic effect on nerve regrowth and functional recovery. In conclusion, EpoB treatment may have therapeutic utility for improving corneal reinnervation and restoring sensitivity following corneal injury.
Dielectric Jump and Negative Electrostriction in Metallosupramolecular Ionic Crystals
Authors: Yamashita Satoshi , Nakazawa Yasuhiro , Yamanaka Shusuke , Okumura Mitsutaka , Kojima Tatsuhiro , Yoshinari Nobuto , Konno Takumi 
Published: February 2018

AbstractIn natural ionic solids, cationic and anionic species are alternately arranged to minimize electrostatic energy. Aggregation of identical ionic species is commonly prohibited due to the repulsive, long-range nature of Coulombic interactions. Recently, we synthesized unique ionic solids, [AuI4CoIII2(dppe)2(d-pen)4]X2·nH2O (dppe = 1,2-bis(diphenylphosphino)ethane, d-pen = d-penicillaminate), in which complex cations are self-assembled into a cationic supramolecular octahedron, while monovalent or divalent inorganic anions are aggregated into an anomalous anionic cluster accommodating several water molecules. This quite unusual aggregation manner originates from various molecular-level non-Coulombic interactions such as hydrogen bonds and CH-π interactions; thus, this class of ionic solids is referred to as non-Coulombic ionic solids, abbreviated as NCISs. Herein, we report that the NCISs with a peculiar charge-separated (CS) structure in a cubic lattice show a negative, isotropic electrostriction phenomenon that has never been found in any ionic solids, as well as an anomalously large relaxer-like dielectric jump phenomenon reaching to an application level of ε′/ε0 ~ 105. The appearance of these phenomena was explained by the cooperative dynamics of inorganic anions and dipolar water molecules in the pliable anionic clusters that are surrounded by a rather robust cationic metallosupramolecular framework with a meso-scopic scale.
Nonlinear effects for three-terminal heat engine and refrigerator
Authors: Wang Rongqian , Lu Jincheng , Wang Chen , Jiang Jian-Hua 
Published: February 2018

AbstractThe three-terminal heat device that consists of an electronic cavity and couples to a heat bath is studied both as a heat engine and as a refrigerator. We investigate the characteristic performance in the linear and nonlinear regime for both setups. It is our focus here to analyze how the efficiency of the heat engine and coefficient of performance of the refrigerator are affected by the nonlinear transport. With such considerations, the maximum efficiency and power are then optimized for various energy levels, temperatures and other parameters.
TGFβ1 reinforces arterial aging in the vascular smooth muscle cell through a long-range regulation of the cytoskeletal stiffness
Authors: Zhu Wanqu , Kim Byoung Choul , Wang Mingyi , Huang Jessie , Isak Abraham , Bexiga Natalia M. , Monticone Robert , Ha Taekjip , Lakatta Edward G. , An Steven S. 
Published: February 2018

AbstractHere we report exquisitely distinct material properties of primary vascular smooth muscle (VSM) cells isolated from the thoracic aorta of adult (8 months) vs. aged (30 months) F344XBN rats. Individual VSM cells derived from the aged animals showed a tense internal network of the actin cytoskeleton (CSK), exhibiting increased stiffness (elastic) and frictional (loss) moduli than those derived from the adult animals over a wide frequency range of the imposed oscillatory deformation. This discrete mechanical response was long-lived in culture and persistent across a physiological range of matrix rigidity. Strikingly, the pro-fibrotic transforming growth factor β1 (TGFβ1) emerged as a specific modifier of age-associated VSM stiffening in vitro. TGFβ1 reinforced the mechanical phenotype of arterial aging in VSM cells on multiple time and length scales through clustering of mechanosensitive α5β1 and αvβ3 integrins. Taken together, these studies identify a novel nodal point for the long-range regulation of VSM stiffness and serve as a proof-of-concept that the broad-based inhibition of TGFβ1 expression, or TGFβ1 signal transduction in VSM, may be a useful therapeutic approach to mitigate the pathologic progression of central arterial wall stiffening associated with aging.
Identification of novel cell-impermeant fluorescent substrates for testing the function and drug interaction of Organic Anion-Transporting Polypeptides, OATP1B1/1B3 and 2B1
Authors: Patik Izabel , Székely Virág , Német Orsolya , Szepesi Áron , Kucsma Nóra , Várady György , Szakács Gergely , Bakos Éva , Özvegy-Laczka Csilla 
Published: February 2018

AbstractOrganic Anion-Transporting Polypeptides are multispecific membrane proteins that regulate the passage of crucial endobiotics and drugs across pharmacological barriers. OATP1B1 and OATP1B3 have been described to play a major role in the hepatic uptake of statins, antivirals and various chemotherapeutics; whereas the pharmacological role of the ubiquitously expressed OATP2B1 is less well characterized. According to current industry standards, in vitro testing for susceptibility to OATP1B1 and 1B3 mediated transport is recommended for drug candidates that are eliminated in part via the liver. Here we show that human OATP1B1, 1B3 and 2B1 transport a series of commercially available viability dyes that are generally believed to be impermeable to intact cells. We demonstrate that the intracellular accumulation of Zombie Violet, Live/Dead Green, Cascade Blue and Alexa Fluor 405 is specifically increased by OATPs. Inhibition of Cascade Blue or Alexa Fluor 405 uptake by known OATP substrates/inhibitors yielded IC50 values in agreement with gold-standard radioligand assays. The fluorescence-based assays described in this study provide a new tool for testing OATP1B/2B1 drug interactions.
Continuous depth profile of the rock strength in the Nankai accretionary prism based on drilling performance parameters
Authors: Hamada Yohei , Kitamura Manami , Yamada Yasuhiro , Sanada Yoshinori , Sugihara Takamitsu , Saito Saneatsu , Moe Kyaw , Hirose Takehiro 
Published: February 2018

AbstractA new method for evaluating the in situ rock strength beneath the seafloor is proposed and applied to the Nankai Trough accretionary prism. The depth-continuous in situ rock strength is a critical parameter for numerous studies in earth science, particularly for seismology and tectonics at plate convergence zones; yet, measurements are limited owing to a lack of drilled cores. Here, we propose a new indicator of strength, the equivalent strength (EST), which is determined only by drilling performance parameters such as drill string rotational torque, bit depth, and string rotational speed. A continuous depth profile of EST was drawn from 0 to 3000 m below the seafloor (mbsf) across the forearc basin and accretionary prism in the Nankai Trough. The EST did not show a significant increase around the forearc basin–accretionary prism boundary, but it did show a clear increase within the prism, ca. below 1500 mbsf. This result may indicate that even the shallow accretionary prism has been strengthened by horizontal compression derived from plate subduction. The EST is a potential parameter to continuously evaluate the in situ rock strength during drilling, and its accuracy of the absolute value can be improved by combining with laboratory drilling experiments.
Conserved, unstructured regions in Pseudomonas aeruginosa PilO are important for type IVa pilus function
Authors: Leighton T. L. , Mok M. C. , Junop M. S. , Howell P. L. , Burrows L. L. 
Published: February 2018

AbstractPseudomonas aeruginosa uses long, thin fibres called type IV pili (T4P) for adherence to surfaces, biofilm formation, and twitching motility. A conserved subcomplex of PilMNOP is required for extension and retraction of T4P. To better understand its function, we attempted to co-crystallize the soluble periplasmic portions of PilNOP, using reductive surface methylation to promote crystal formation. Only PilOΔ109 crystallized; its structure was determined to 1.7 Å resolution using molecular replacement. This new structure revealed two novel features: a shorter N-terminal α1-helix followed by a longer unstructured loop, and a discontinuous β-strand in the second αββ motif, mirroring that in the first motif. PISA analysis identified a potential dimer interface with striking similarity to that of the PilO homolog EpsM from the Vibrio cholerae type II secretion system. We identified highly conserved residues within predicted unstructured regions in PilO proteins from various Pseudomonads and performed site-directed mutagenesis to assess their role in T4P function. R169D and I170A substitutions decreased surface piliation and twitching motility without disrupting PilO homodimer formation. These residues could form important protein-protein interactions with PilN or PilP. This work furthers our understanding of residues critical for T4aP function.
Effects of the Ketogenic diet in overweight divers breathing Enriched Air Nitrox
Authors: Bosco Gerardo , Rizzato Alex , Quartesan Silvia , Camporesi Enrico , Mangar Devanand , Paganini Matteo , Cenci Lorenzo , Malacrida Sandro , Mrakic-Sposta Simona , Moretti Sara , Paoli Antonio 
Published: February 2018

AbstractCentral Nervous System Oxygen Toxicity (CNS-OT) is one of the most harmful effects of Enriched Air Nitrox (EAN) diving. Protective factors of the Ketogenic Diet (KD) are antioxidant activity, the prevention of mitochondrial damage and anti-inflammatory mechanisms. We aimed to investigate if a short-term KD may reduce oxidative stress and inflammation during an hyperoxic dive. Samples from six overweight divers (mean ± SD, age: 55.2 ± 4.96 years; BMI: 26.7 ± 0.86 kg/m2) were obtained a) before and after a dive breathing Enriched Air Nitrox and performing 20-minute mild underwater exercise, b) after a dive (same conditions) performed after 7 days of KD. We measured urinary 8-isoprostane and 8-OH-2-deoxyguanosine and plasmatic IL-1β, IL-6 and TNF-α levels. The KD was successful in causing weight loss (3.20 ± 1.31 Kgs, p < 0.01) and in limiting lipid peroxidation (3.63 ± 1.16 vs. 1.11 ± 0.22; p < 0.01) and inflammatory response (IL-1β = 105.7 ± 25.52 vs. 57.03 ± 16.32, p < 0.05; IL-6 = 28.91 ± 4.351 vs. 14.08 ± 1.74, p < 0.001; TNF-α = 78.01 ± 7.69 vs. 64.68 ± 14.56, p < 0.05). A short-term KD seems to be effective in weight loss, in decreasing inflammation and protective towards lipid peroxidation during hyperoxic diving.
Ileal pouch of ulcerative colitis and familial adenomatous polyposis patients exhibit modulation of autophagy markers
Authors: Paiva Nielce Maria , Pascoal Lívia Bitencourt , Negreiros Leandro Minatel Vidal , Portovedo Mariana , Coope Andressa , Ayrizono Maria de Lourdes Setsuko , Coy Claudio Saddy Rodrigues , Milanski Marciane , Leal Raquel Franco 
Published: February 2018

AbstractTotal retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment. Pouchitis is one of the most common complications after this procedure. Defects in autophagy have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. Sixteen patients with IP in “J” shape, asymptomatic and with endoscopically normal IP were evaluated. The control group consisted of eight patients with normal colonoscopy. There was a significant decrease in the transcriptional levels ofATG5, MAP1LC3AandBAXin the FAP group. There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group. Although the LC3II levels by immunoblot were higher in the UC group, LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group. Corroborating these results, there was an increase of p62 by immunoblot in the UC group. These findings indicated a modulation of macroautophagy markers in the IP, which may explain the mucosa inflammation predisposition.
Ethyl-substitutive Thioflavin T as a highly-specific fluorescence probe for detecting G-quadruplex structure
Authors: Guan Ai-jiao , Zhang Xiu-Feng , Sun Xin , Li Qian , Xiang Jun-Feng , Wang Li-Xia , Lan Ling , Yang Feng-Min , Xu Shu-Juan , Guo Xiao-Meng , Tang Ya-Lin 
Published: February 2018

AbstractG-quadruplex has attracted considerable attention due to their prevalent distribution in functional genomic regions and transcripts, which can importantly influence biological processes such as regulation of telomere maintenance, gene transcription and gene translation. Artificial receptor study has been developed for accurate identification of G-quadruplex from DNA species, since it is important for the G-quadruplex related basic research, clinical diagnosis, and therapy. Herein, fluorescent dye ThT-E, a derivative of the known fluorescence probe Thioflavin T (ThT), was designed and synthesized to effectively differentiate various G-quadruplex structures from other nucleic acid forms. Compared with methyl groups in ThT, three ethyl groups were introduced to ThT-E, which leads to strengthened affinity, selectivity and little inducing effect on the G-quadruplex formation. More importantly, ThT-E could be served as a visual tool to directly differentiate G-quadruplex solution even with naked eyes under illumination of ultraviolet light. Thus, this probe reported herein may hold great promise for high-throughput assay to screen G-quadruplex, which may widely apply to G-quadruplex-based potential diagnosis and therapy.