bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recapitulation of HDV infection in a fully permissive hepatoma cell line allows efficient drug evaluation
Authors: Lempp Florian A. , Schlund Franziska , Rieble Lisa , Nussbaum Lea , Link Corinna , Zhang Zhenfeng , Ni Yi , Urban Stephan 
Published: May 2019

AbstractHepatitis delta virus (HDV) depends on the helper function of hepatitis B virus (HBV), which provides the envelope proteins for progeny virus secretion. Current infection-competent cell culture models do not support assembly and secretion of HDV. By stably transducing HepG2 cells with genes encoding the NTCP-receptor and the HBV envelope proteins we produce a cell line (HepNB2.7) that allows continuous secretion of infectious progeny HDV following primary infection. Evaluation of antiviral drugs shows that the entry inhibitor Myrcludex B (IC50: 1.4 nM) and interferon-α (IC50: 28 IU/ml, but max. 60–80% inhibition) interfere with primary infection. Lonafarnib inhibits virus secretion (IC50: 36 nM) but leads to a substantial intracellular accumulation of large hepatitis delta antigen and replicative intermediates, accompanied by the induction of innate immune responses. This work provides a cell line that supports the complete HDV replication cycle and presents a convenient tool for antiviral drug evaluation.
iSuRe-Cre is a genetic tool to reliably induce and report Cre-dependent genetic modifications
Authors: Fernández-Chacón Macarena , Casquero-García Verónica , Luo Wen , Francesca Lunella Federica , Ferreira Rocha Susana , Del Olmo-Cabrera Sergio , Benedito Rui 
Published: May 2019

AbstractMost biomedical research aimed at understanding gene function uses the Cre-Lox system, which consists of the Cre recombinase-dependent deletion of genes containing LoxP sites. This system enables conditional genetic modifications because the expression and activity of the recombinase Cre/CreERT2 can be regulated in space by tissue-specific promoters and in time by the ligand tamoxifen. Since the precise Cre-Lox recombination event is invisible, methods were developed to report Cre activity and are widely used. However, numerous studies have shown that expression of a given Cre activity reporter cannot be assumed to indicate deletion of other LoxP-flanked genes of interest. Here, we report the generation of an inducible dual reporter-Cre mouse allele, iSuRe-Cre. By significantly increasing Cre activity in reporter-expressing cells, iSuRe-Cre provides certainty that these cells have completely recombined floxed alleles. This genetic tool increases the ease, efficiency, and reliability of conditional mutagenesis and gene function analysis.
A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages
Authors: Feng Yanxian , Mu Ruoyu , Wang Zhenzhen , Xing Panfei , Zhang Junfeng , Dong Lei , Wang Chunming 
Published: May 2019

AbstractSwitching macrophages from a pro-tumor type to an anti-tumor state is a promising strategy for cancer immunotherapy. Existing agents, many derived from bacterial components, have safety or specificity concerns. Here, we postulate that the structures of the bacterial signals can be mimicked by using non-toxic biomolecules of simple design. Based on bioactivity screening, we devise a glucomannan polysaccharide with acetyl modification at a degree of 1.8 (acGM-1.8), which specifically activates toll-like receptor 2 (TLR2) signaling and consequently induces macrophages into an anti-tumor phenotype. For acGM-1.8, the degree of acetyl modification, glucomannan pattern, and acetylation-induced assembly are three crucial factors for its bioactivity. In mice, intratumoral injection of acGM-1.8 suppresses the growth of two tumor models, and this polysaccharide demonstrates higher safety than four classical TLR agonists. In summary, we report the design of a new, safe, and specific TLR2 agonist that can generate macrophages with strong anti-tumor potential in mice.
A Feature based Reconstruction Model for Fluorescence Microscopy Image Denoising
Authors: Maji Suman Kumar , Yahia Hussein 
Published: May 2019

AbstractThe advent of Fluorescence Microscopy over the last few years have dramatically improved the problem of visualization and tracking of specific cellular objects for biological inference. But like any other imaging system, fluorescence microscopy has its own limitations. The resultant images suffer from the effect of noise due to both signal dependent and signal independent factors, thereby limiting the possibility of biological inferencing. Denoising is a class of image processing algorithms that aim to remove noise from acquired images and has gained wide attention in the field of fluorescence microscopy image restoration. In this paper, we propose an image denoising algorithm based on the concept of feature extraction through multifractal decomposition and then estimate a noise free image from the gradients restricted to these features. Experimental results over simulated and real fluorescence microscopy data prove the merit of the proposed approach, both visually and quantitatively.
The Small GTPase Rac1 Increases Cell Surface Stiffness and Enhances 3D Migration Into Extracellular Matrices
Authors: Kunschmann Tom , Puder Stefanie , Fischer Tony , Steffen Anika , Rottner Klemens , Mierke Claudia Tanja 
Published: May 2019

AbstractMembrane ruffling and lamellipodia formation promote the motility of adherent cells in two-dimensional motility assays by mechano-sensing of the microenvironment and initiation of focal adhesions towards their surroundings. Lamellipodium formation is stimulated by small Rho GTPases of the Rac subfamily, since genetic removal of these GTPases abolishes lamellipodium assembly. The relevance of lamellipodial or invadopodial structures for facilitating cellular mechanics and 3D cell motility is still unclear. Here, we hypothesized that Rac1 affects cell mechanics and facilitates 3D invasion. Thus, we explored whether fibroblasts that are genetically deficient for Rac1 (lacking Rac2 and Rac3) harbor altered mechanical properties, such as cellular deformability, intercellular adhesion forces and force exertion, and exhibit alterations in 3D motility. Rac1 knockout and control cells were analyzed for changes in deformability by applying an external force using an optical stretcher. Five Rac1 knockout cell lines were pronouncedly more deformable than Rac1 control cells upon stress application. Using AFM, we found that cell-cell adhesion forces are increased in Rac1 knockout compared to Rac1-expressing fibroblasts. Since mechanical deformability, cell-cell adhesion strength and 3D motility may be functionally connected, we investigated whether increased deformability of Rac1 knockout cells correlates with changes in 3D motility. All five Rac1 knockout clones displayed much lower 3D motility than Rac1-expressing controls. Moreover, force exertion was reduced in Rac1 knockout cells, as assessed by 3D fiber displacement analysis. Interference with cellular stiffness through blocking of actin polymerization by Latrunculin A could not further reduce invasion of Rac1 knockout cells. In contrast, Rac1-expressing controls treated with Latrunculin A were again more deformable and less invasive, suggesting actin polymerization is a major determinant of observed Rac1-dependent effects. Together, we propose that regulation of 3D motility by Rac1 partly involves cellular mechanics such as deformability and exertion of forces.
Improving medication adherence in adult kidney transplantation (IMAKT): A pilot randomised controlled trial
Authors: Low Jac Kee , Manias Elizabeth , Crawford Kimberley , Walker Rowan , Mulley William R. , Toussaint Nigel D. , Dooley Michael , Kennedy Elaine , Smith Catherine L. , Nalder Michelle , Yip Doris , Williams Allison 
Published: May 2019

AbstractResources to support long-term medication adherence in kidney transplantation are limited. This study aimed to determine the efficacy of an intervention designed for kidney transplant recipients to enhance medication adherence. A single-blind, multi-site, 12-month pilot randomised controlled trial was conducted at all five public hospitals providing adult kidney transplantation in Victoria, Australia. Participants were recruited at 4 to 6 weeks post-transplantation. Thirty-five participants were randomly assigned to a 3-month intervention, involving a face-to-face meeting (a medication review and a consumer-centred video) and health coaching every two weeks. Thirty-six were randomised to receive usual care. All participants were followed for nine months post-intervention. There were no differences in adherence between groups measured by Medication Event Monitoring System (MEMS), however, it was underutilised by 42% of participants. Based on the self-reported Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©) score, the percentage of adherent participants decreased significantly between baseline and 3 to 12 months in the control group (p-values < 0.001) whilst the percentage of adherent participants in the intervention group remained constant over time. No group differences were detected in other outcomes. Due to the complex medication regimen, developing and testing a medication adherence intervention is difficult in kidney transplantation.
Enhanced remyelination during late pregnancy: involvement of the GABAergic system
Authors: Kalakh Samah , Mouihate Abdeslam 
Published: May 2019

AbstractPregnant women with MS experience fewer relapses, especially during the third trimester. In this study, we explore the cellular and molecular events that bring about the protective effect of late pregnancy on the course of de/remyelination in rats. Using cellular, molecular, and ultrastructural methods, we explored remyelination in response to a focal demyelination in the corpus callosum of late pregnant, virgin, and postpartum rats. We further explored the role of GABAAreceptor (GABAAR) in the promyelinating effect observed during late pregnancy. Remyelination in response to a gliotoxin-induced demyelination in the corpus callosum was enhanced in late pregnant rats when compared to that seen in virgin and postpartum rats. This pregnancy-associated promyelinating effect was lost when either the GABAAR was blocked or when 5α-reductase, the rate limiting enzyme for the endogenous GABAAR activator allopregnanolone, was inhibited. Taken together, these data suggest that the pregnancy-associated pro-myelination operates, at least in part, through a GABAergic activated system.
Development of a novel multiphysical approach for the characterization of mechanical properties of musculotendinous tissues
Authors: Kammoun Malek , Ternifi Redouane , Dupres Vincent , Pouletaut Philippe , Même Sandra , Même William , Szeremeta Frederic , Landoulsi Jessem , Constans Jean-Marc , Lafont Frank , Subramaniam Malayannan , Hawse John R. , Bensamoun Sabine F. 
Published: May 2019

AbstractAt present, there is a lack of well-validated protocols that allow for the analysis of the mechanical properties of muscle and tendon tissues. Further, there are no reports regarding characterization of mouse skeletal muscle and tendon mechanical properties in vivo using elastography thereby limiting the ability to monitor changes in these tissues during disease progression or response to therapy. Therefore, we sought to develop novel protocols for the characterization of mechanical properties in musculotendinous tissues using atomic force microscopy (AFM) and ultrasound elastography. Given that TIEG1 knockout (KO) mice exhibit well characterized defects in the mechanical properties of skeletal muscle and tendon tissue, we have chosen to use this model system in the present study. Using TIEG1 knockout and wild-type mice, we have devised an AFM protocol that does not rely on the use of glue or chemical agents for muscle and tendon fiber immobilization during acquisition of transversal cartographies of elasticity and topography. Additionally, since AFM cannot be employed on live animals, we have also developed an ultrasound elastography protocol using a new linear transducer, SLH20-6 (resolution: 38 µm, footprint: 2.38 cm), to characterize the musculotendinous system in vivo. This protocol allows for the identification of changes in muscle and tendon elasticities. Such innovative technological approaches have no equivalent to date, promise to accelerate our understanding of musculotendinous mechanical properties and have numerous research and clinical applications.
High fidelity fibre-based physiological sensing deep in tissue
Authors: Choudhary Tushar R. , Tanner Michael G. , Megia-Fernandez Alicia , Harrington Kerrianne , Wood Harry A. , Marshall Adam , Zhu Patricia , Chankeshwara Sunay V. , Choudhury Debaditya , Monro Graham , Ucuncu Muhammed , Yu Fei , Duncan Rory R. , Thomson Robert R. , Dhaliwal Kevin , Bradley Mark 
Published: May 2019

AbstractPhysiological sensing deep in tissue remains a clinical challenge. Here a flexible miniaturised sensing optrode providing a platform to perform minimally invasive in vivo in situ measurements is reported. Silica microspheres covalently coupled with a high density of ratiometrically configured fluorophores were deposited into etched pits on the distal end of a 150 µm diameter multicore optical fibre. With this platform, photonic measurements of pH and oxygen concentration with high precision in the distal alveolar space of the lung are reported. We demonstrated the phenomenon that high-density deposition of carboxyfluorescein covalently coupled to silica microspheres shows an inverse shift in fluorescence in response to varying pH. This platform delivered fast and accurate measurements (±0.02 pH units and ±0.6 mg/L of oxygen), near instantaneous response time and a flexible architecture for addition of multiple sensors.
Influences of age, mental workload, and flight experience on cognitive performance and prefrontal activity in private pilots: a fNIRS study
Authors: Causse Mickaël , Chua Zarrin K. , Rémy Florence 
Published: May 2019

AbstractThe effects of aging on cognitive performance must be better understood, especially to protect older individuals who are engaged in risky activities (e.g. aviation). Current literature on executive functions suggests that brain compensatory mechanisms may counter cognitive deterioration due to aging, at least up to certain task load levels. The present study assesses this hypothesis in private pilots engaged in two executive tasks from the standardized CANTAB battery, namely Spatial Working Memory (SWM) and One Touch Stockings of Cambridge (OTS). Sixty-one pilots from three age groups (young, middle-aged, older) performed these two tasks from low to very high difficulty levels, beyond those reported in previous aging studies. A fNIRS headband measured changes in oxyhemoglobin (HbO2) in the prefrontal cortex. Results confirmed an overall effect of the difficulty level in the three age groups, with a decline in task performance and an increase in prefrontal HbO2 signal. Performance of older relative to younger pilots was impaired in both tasks, with the greatest impairment observed for the highest-load Spatial Working Memory task. Consistent with this behavioral deficit in older pilots, a plateau of prefrontal activity was observed at this highest-load level, suggesting that a ceiling in neural resources was reached. When behavioral performance was either equivalent between age groups or only slightly impaired in the older group, there were not any age-related differences in prefrontal activity. Finally, older pilots with extensive flying experience tend to show better preserved spatial working memory performance when compared to mildly-experienced of the same age group. The present findings are discussed in the frames of HAROLD and CRUNCH theoretical models of cognitive and neural aging, evoking the possibility that piloting expertise may contribute to preserve executive functions throughout adulthood.
A Simplified, Graded, Electrodiagnostic Criterion for Guillain-Barré Syndrome That Incorporates Sensory Nerve Conduction Studies
Authors: Umapathi Thirugnanam , Lim Christen Sheng Jie , Ng Brandon Chin Jie , Goh Eunice Jin Hui , Ohnmar O. 
Published: May 2019

AbstractTraditional electrodiagnostic (EDX) criteria for Guillain-Barré Syndrome (GBS), e.g. those delineated by Ho et al. and Hadden et al., rely on motor nerve conduction studies (NCS), and focus on differentiating GBS subtypes instead of the accurate diagnosis of GBS. Sensory studies, including the sural-sparing pattern, are not routinely used in GBS EDX. We studied the utility of a simplified criterion that utilizes sensory NCS. Motor and sensory NCS abnormalities were defined by comparing against age and height adjusted norms derived from 245 controls. We considered the sural-sparing pattern a positive diagnostic feature. We analyzed 109 prospectively validated GBS patients and graded them as “Definite”, “Probable” and “Possible” based on the number of motor and sensory abnormalities detected. Using proposed EDX criteria, 35.8%, 43.1%, 11.9% of all GBS patients were considered “Definite”, “Probable” or “Possible” respectively; whereas traditional EDX criteria only diagnosed 49.5% of cases. 27.5%, 35.3% and 21.6% of patients with the Miller-Fisher Syndrome (MFS) subtype of GBS were considered “Definite”, “Probable” or “Possible” respectively. In comparison, traditional criteria only detected 15.7% of cases. Our proposed EDX criterion, that includes sensory NCS, improves and grades the diagnostic certainty of GBS, especially MFS.
Synergistic Role of Oxidative Stress and Blood-Brain Barrier Permeability as Injury Mechanisms in the Acute Pathophysiology of Blast-induced Neurotrauma
Authors: Kuriakose Matthew , Younger Daniel , Ravula Arun Reddy , Alay Eren , Rama Rao Kakulavarapu V. , Chandra Namas 
Published: May 2019

AbstractBlast-induced traumatic brain injury (bTBI) has been recognized as the common mode of neurotrauma amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from our laboratory have identified enhanced blood-brain barrier (BBB) permeability as a significant, sub-acute (four hours post-blast) pathological change in bTBI. We also found that NADPH oxidase (NOX)-mediated oxidative stress occurs at the same time post-blast when the BBB permeability changes. We therefore hypothesized that oxidative stress is a major causative factor in the BBB breakdown in the sub-acute stages. This work therefore examined the role of NOX1 and its downstream effects on BBB permeability in the frontal cortex (a region previously shown to be the most vulnerable) immediately and four hours post-blast exposure. Rats were injured by primary blast waves in a compressed gas-driven shock tube at 180 kPa and the BBB integrity was assessed by extravasation of Evans blue and changes in tight junction proteins (TJPs) as well as translocation of macromolecules from blood to brain and vice versa. NOX1 abundance was also assessed in neurovascular endothelial cells. Blast injury resulted in increased extravasation and reduced levels of TJPs in tissues consistent with our previous observations. NOX1 levels were significantly increased in endothelial cells followed by increased superoxide production within 4 hours of blast. Blast injury also increased the levels/activation of matrix metalloproteinase 3 and 9. To test the role of oxidative stress, rats were administered apocynin, which is known to inhibit the assembly of NOX subunits and arrests its function. We found apocynin completely inhibited dye extravasation as well as restored TJP levels to that of controls and reduced matrix metalloproteinase activation in the sub-acute stages following blast. Together these data strongly suggest that NOX-mediated oxidative stress contributes to enhanced BBB permeability in bTBI through a pathway involving increased matrix metalloproteinase activation.
Predation risk is a function of alternative prey availability rather than predator abundance in a tropical savanna woodland ecosystem
Authors: Nordberg Eric J. , Schwarzkopf Lin 
Published: May 2019

AbstractTypically, factors influencing predation risk are viewed only from the perspective of predators or prey populations but few studies have examined predation risk in the context of a food web. We tested two competing hypotheses regarding predation: (1) predation risk is dependent on predator density; and (2) predation risk is dependent on the availability of alternative prey sources. We use an empirical, multi-level, tropical food web (birds–lizards–invertebrates) and a mensurative experiment (seasonal fluctuations in abundance and artificial lizards to estimate predation risk) to test these hypotheses. Birds were responsible for the majority of attacks on artificial lizards and were more abundant in the wet season. Artificial lizards were attacked more frequently in the dry than the wet season despite a greater abundance of birds in the wet season. Lizard and invertebrate (alternative prey) abundances showed opposing trends; lizards were more abundant in the dry while invertebrates were more abundant in the wet season. Predatory birds attacked fewer lizards when invertebrate prey abundance was highest, and switched to lizard prey when invertebrate abundance reduced, and lizard abundance was greatest. Our study suggests predation risk is not predator density-dependent, but rather dependent on the abundance of invertebrate prey, supporting the alternative prey hypothesis.
The risk factors of glycemic control, blood pressure control, lipid control in Chinese patients with newly diagnosed type 2 diabetes _ A nationwide prospective cohort study
Authors: Cai Xiaoling , Hu Dayi , Pan Changyu , Li Guangwei , Lu Juming , Ji Qiuhe , Su Benli , Tian Haoming , Qu Shen , Weng Jianping , Zhang Danyi , Xu Jie , Ji Linong 
Published: May 2019

AbstractNationwide data on glycemic control, blood pressure (BP) control and lipid control in patients with newly diagnosed type 2 diabetes were vacant in China. The aim of this study was to assess the clinical outcomes for these patients. This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes less than 6 months were enrolled. Hemoglobin A1c (HbA1c) levels, BP levels and lipid levels were collected at baseline and the follow-ups. This study was registered atwww.clinicaltrials.gov(NCT01525693). A total of 5770 participants from 79 hospitals across six geographic regions of China were recruited. After 12 months of treatment, 68.5% of these patients achieved HbA1c <7.0%; 83.7% reached BP <140/90 mmHg; 48.2% met low density lipoprotein cholesterol (LDL-c) <2.6 mmol/L; and 29.5% of patients reached the combined three therapeutic targets. Compared to those patients with baseline HbA1c <7.0%, patients with baseline HbA1c ≥7.0% had higher failure rate to reach glycemic control (relative risk (RR) = 2.04, p < 0.001), BP control (RR = 1.21, p < 0.001) and LDL-c control (RR = 1.11, p < 0.001). Obese patients had higher possibilities of failure in glucose control (RR = 1.05, p = 0.004), BP control (RR = 1.62, p < 0.001) and lipid control (RR = 1.09, p = 0.001) than patients with normal weight. The active smokers were more likely to fail in glycemic control than non-smokers (RR = 1.06, p = 0.002), and patients with physical activities were less likely to fail in lipid control than patients without exercises (RR = 0.93, p = 0.008). This study outlined the burdens of glycemic control, blood pressure control, lipid control in newly diagnosed type 2 diabetic patients in China, identified gaps in the quality of care and risk-factor control and revealed the factors influencing these gaps.