bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance
Authors: Zhu Bin , Xiao Yanzi , Yeager Meredith , Clifford Gary , Wentzensen Nicolas , Cullen Michael , Boland Joseph F. , Bass Sara , Steinberg Mia K. , Raine-Bennett Tina , Lee DongHyuk , Burk Robert D. , Pinheiro Maisa , Song Lei , Dean Michael , Nelson Chase W. , Burdett Laurie , Yu Kai , Roberson David , Lorey Thomas , Franceschi Silvia , Castle Philip E. , Walker Joan , Zuna Rosemary , Schiffman Mark , Mirabello Lisa 
Published: February 2020

AbstractHPV16 causes half of cervical cancers worldwide; for unknown reasons, most infections resolve within two years. Here, we analyze the viral genomes of 5,328 HPV16-positive case-control samples to investigate mutational signatures and the role of human APOBEC3-induced mutations in viral clearance and cervical carcinogenesis. We identify four de novo mutational signatures, one of which matches the COSMIC APOBEC-associated signature 2. The viral genomes of the precancer/cancer cases are less likely to contain within-host somatic HPV16 APOBEC3-induced mutations (Fisher’s exact test,P= 6.2 x 10−14), and have a 30% lower nonsynonymous APOBEC3 mutation burden compared to controls. We replicate the low prevalence of HPV16 APOBEC3-induced mutations in 1,749 additional cases. APOBEC3 mutations also historically contribute to the evolution of HPV16 lineages. We demonstrate that cervical infections with a greater burden of somatic HPV16 APOBEC3-induced mutations are more likely to be benign or subsequently clear, suggesting they may reduce persistence, and thus progression, within the host.
Whole-cell imaging of plasma membrane receptors by 3D lattice light-sheet dSTORM
Authors: Wäldchen Felix , Schlegel Jan , Götz Ralph , Luciano Michael , Schnermann Martin , Doose Sören , Sauer Markus 
Published: February 2020

AbstractThe molecular organization of receptors in the plasma membrane of cells is paramount for their functionality. We combined lattice light-sheet (LLS) microscopy with three-dimensional (3D) single-molecule localization microscopy (dSTORM) and single-particle tracking to quantify the expression and distribution, and mobility of CD56 receptors on whole fixed and living cells, finding that CD56 accumulated at cell–cell interfaces. For comparison, we investigated two other receptors, CD2 and CD45, which showed different expression levels and distributions in the plasma membrane. Overall, 3D-LLS-dSTORM enabled imaging and single-particle tracking of plasma membrane receptors with single-molecule sensitivity unperturbed by surface effects. Our results demonstrate that receptor distribution and mobility are largely unaffected by contact to the coverslip but the measured localization densities are in general lower at the basal plasma membrane due to partial limited accessibility for antibodies.
Controlled depolymerization of cellulose by light-driven lytic polysaccharide oxygenases
Authors: Bissaro Bastien , Kommedal Eirik , Røhr Åsmund K. , Eijsink Vincent G. H. 
Published: February 2020

AbstractLytic polysaccharide (mono)oxygenases (LPMOs) perform oxidative cleavage of polysaccharides, and are key enzymes in biomass processing and the global carbon cycle. It has been shown that LPMO reactions may be driven by light, using photosynthetic pigments or photocatalysts, but the mechanism behind this highly attractive catalytic route remains unknown. Here, prompted by the discovery that LPMOs catalyze a peroxygenase reaction more efficiently than a monooxygenase reaction, we revisit these light-driven systems, using an LPMO from Streptomyces coelicolor (ScAA10C) as model cellulolytic enzyme. By using coupled enzymatic assays, we show that H2O2 is produced and necessary for efficient light-driven activity of ScAA10C. Importantly, this activity is achieved without addition of reducing agents and proportional to the light intensity. Overall, the results highlight the importance of controlling fluxes of reactive oxygen species in LPMO reactions and demonstrate the feasibility of light-driven, tunable enzymatic peroxygenation to degrade recalcitrant polysaccharides.
Mesenchymal stromal cell derived CCL2 is required for accelerated wound healing
Authors: Whelan Derek S. , Caplice Noel M. , Clover Anthony J. P. 
Published: February 2020

AbstractMesenchymal stromal cells (MSC) have immunomodulatory effects impacting macrophages, promoting polarisation towards a reparative phenotype. CCL2 is a potent cytokine involved in the recruitment of macrophages. We hypothesised that MSC derived CCL2 may be involved in the MSC therapeutic effect by facilitating macrophage repolarisation. To further delineate this mechanism, MSC isolated from CCL2 deficient mice (MSC-KO) were applied to excisional wounds in wild-type (WT) mice. CCL2 deficiency in MSC completely abrogated the therapeutic response compared to MSC-WT. MSC-KO were unable to repolarise macrophages to the same extent as WT and this was accompanied by a reduced angiogenesis and re-epithelialisation of the wounds at day 10. This study demonstrates that MSC derived CCL2 is required for MSC induced accelerated wound healing. The role of CCL2 in the interaction between MSC and Macrophages has not been previously demonstrated in accelerated wound healing. CCL2 has a potent effect on the ability to reduce the inflammatory response through local recruitment of macrophages. This research highlights CCL2 as a possible target for augmentation of MSC therapy to enhance therapeutic potential.
Association between physical activity and Nocturnal Leg Cramps in patients over 60 years old: a case-control study
Authors: Delacour Chloé , Chambe Juliette , Lefebvre François , Bodot Claire , Bigerel Elodie , Epifani Laetitia , Granda Céline , Haller Dagmar M. , Maisonneuve Hubert 
Published: February 2020

AbstractNocturnal Legs Cramps are a frequent disorder, which have a negative impact on quality of life, particularly among patients over 60 years old. Lifestyle factors such as alcohol consumption have been shown to be associated with Nocturnal Leg Cramps. This study aimed to explore the association between nocturnal leg cramps and a sedentary lifestyle among elderly patients. A case-control study was conducted with a Bayesian approach for sensitivity analysis. Patients over 60 years old consulting their family doctor were recruited in the Alsace region, France. Cases were matched with controls free from cramps for age, sex, medical history and medications known to trigger cramps. The level of physical activity was assessed using the Dijon Physical Activity Score (DPAS). We performed univariate and multivariate analyses adjusting for alcohol consumption. 272 participants were matched into 136 pairs. 11% of all were sedentary persons. Adjusting for alcohol consumption, we observed an association between Nocturnal Leg Cramps and a sedentary lifestyle OR = 9.84 (95% credibility interval [1.74; 101.9]; posterior probability 99.68%). Our findings represent an additional argument to promote physical activity to patients over 60 years old. They also highlight the need to develop and evaluate physical activity interventions in the treatment of Nocturnal Legs Cramps.
Root Physiological Traits and Transcriptome Analyses Reveal that Root Zone Water Retention Confers Drought Tolerance to Opisthopappus taihangensis
Authors: Yang Yongjuan , Guo Yanhong , Zhong Jian , Zhang Tengxun , Li Dawei , Ba Tingting , Xu Ting , Chang Lina , Zhang Qixiang , Sun Ming 
Published: February 2020

AbstractOpisthopappus taihangensis (Ling) Shih, as a relative of chrysanthemum, mainly survives on the cracks of steep slopes and cliffs. Due to the harsh environment in which O. taihangensis lives, it has evolved strong adaptive traits to drought stress. The root system first perceives soil water deficiency, triggering a multi-pronged response mechanism to maintain water potential; however, the drought tolerance mechanism of O. taihangensis roots remains unclear. Therefore, roots were selected as materials to explore the physiological and molecular responsive mechanisms. We found that the roots had a stronger water retention capacity than the leaves. This result was attributed to ABA accumulation, which promoted an increased accumulation of proline and trehalose to maintain cell osmotic pressure, activated SOD and POD to scavenge ROS to protect root cell membrane structure and induced suberin depositions to minimize water backflow to dry soil. Transcriptome sequencing analyses further confirmed that O. taihangensis strongly activated genes involved in the ABA signalling pathway, osmolyte metabolism, antioxidant enzyme activity and biosynthesis of suberin monomer. Overall, these results not only will provide new insights into the drought response mechanisms of O. taihangensis but also will be helpful for future drought breeding programmes of chrysanthemum.
Arbuscular mycorrhizal fungi promote the growth of plants in the mining associated clay
Authors: Song Ziheng , Bi Yinli , Zhang Jian , Gong Yunli , Yang Huihui 
Published: February 2020

AbstractIt is urgent to restore the ecological function in open-pit mining areas on grassland in Eastern China. The open-pit mines have abundant of mining associated clay, which is desirable for using as a soil source for ecological restoration. The mining associated clay in Hulunbuir district, Inner Mongolia was selected and mixed with a sandy soil at a ratio of 1:1 (S_C soil). Also, effects of arbuscular mycorrhizal fungi (AMF) inoculation on soil functions were studied. The aboveground and underground biomass of maize in S_C soil was 1.49 and 2.41 times higher than that of clay soil, respectively. In the topsoil and S_C soil, the growth hormone (IAA) and cytokinin (CTK) levels of maize were higher than that of clay, while abscission acid (ABA) levels were lower. The inoculation with AMF could significantly improve the biomass of maize and enhance the stress resistance of plants. Through structural equation model (SEM) analyses, it was found that the soil type and AMF inoculation had the most direct impact on maize growth and biomass content. These finds extend our knowledge regarding a low-cost method for physical and biological improvement of mining associated clay, and to provide theoretical support for large-scale application in the future.
Matrix protease production, epithelial-to-mesenchymal transition marker expression and invasion of glioblastoma cells in response to osmotic or hydrostatic pressure
Authors: Pu Wenjun , Qiu Jiawen , Riggins Gregory J. , Parat Marie-Odile 
Published: February 2020

AbstractBoth hydrostatic and osmotic pressures are altered in the tumour microenvironment. Glioblastoma (GBM) is a brain tumour with high invasiveness and poor prognosis. We hypothesized that physical and osmotic forces regulate glioblastoma (GBM) invasiveness. The osmotic pressure of GBM cell culture medium was adjusted using sodium chloride or water. Alternatively, cells were subjected to increased hydrostatic force. The proteolytic profile and epithelial–mesenchymal transition (EMT) were investigated using zymography and real-time qPCR. The EMT markers assessed were Snail-1, Snail-2, N-cadherin, Twist and vimentin. Invasion was investigated in vitro using extracellular matrix-coated Transwell inserts. In response to osmotic and mechanical pressure, GBM cell lines U87 and U251 and patient-derived neural oncospheres upregulated the expression of urokinase-type plasminogen activator (uPA) and/or matrix metalloproteinases (MMPs) as well as some of the EMT markers tested. The adherent cell lines invaded more when placed in media of increased osmolality. Therefore, GBM respond to osmotic or mechanical pressure by increasing matrix degrading enzyme production, and adopting a phenotype reminiscent of EMT. Better understanding the molecular and cellular mechanisms by which increased pressure promotes GBM invasiveness may help to develop innovative therapeutic approaches.
Healthcare utilization among children and young people with life-limiting conditions: Exploring palliative care needs using National Health Insurance claims data
Authors: Kim Cho Hee , Song In Gyu , Kim Min Sun , Lee Jin Yong , Lim Nam Gu , Shin Hee Young 
Published: February 2020

AbstractPaediatric palliative care (PPC) is regarded as standard care for children and young people (CYP) with life-limiting conditions (LLCs). There is a lack of knowledge about the rate of CYP with LLCs, hampering the development of PPC. This retrospective study aimed to examine population-based statistics of South Korean CYP with LLCs and the pattern of healthcare use and costs in their last year of life, analysing the National Health Insurance Service claims database for the period 2013–2015. In 2015, the number of CYP (≤24 years old) living with LLCs was 133,177, with those who died accounting for 1,032. Prevalence of LLC and mortality rate per 100,000 were highest among under-1-age group (2,151.7 and 82.7, respectively). In the last year of life, 91.8% of deceased CYP with LLCs were hospitalized at least once and the average length of stay was 101.2 days (standard deviation = 104.1). Deceased CYP with cancer spent more on healthcare than non-cancer CYP (64,266 vs. 40,694 US dollar, p < 0.001). The average relevance index for CYP death related to LLCs was 55.9%. Our results provide baseline information on healthcare utilization and expenditure among CYP with LLCs, which is crucial data for designing evidence-based PPC policy and services.
Small-scale mechanical behavior of a eutectic high entropy alloy
Authors: Muskeri Saideep , Hasannaeimi Vahid , Salloom Riyadh , Sadeghilaridjani Maryam , Mukherjee Sundeep 
Published: February 2020

AbstractEutectic high entropy alloys, with lamellar arrangement of solid solution phases, represent a new paradigm for simultaneously achieving high strength and ductility, thereby circumventing this well-known trade-off in conventional alloys. However, dynamic strengthening mechanisms and phase-boundary interactions during external loading remain unclear for these eutectic systems. In this study, small-scale mechanical behavior was evaluated for AlCoCrFeNi2.1 eutectic high entropy alloy, consisting of a lamellar arrangement of L12 and B2 solid-solution phases. The ultimate tensile strength was 1165 MPa with ductility of ~18% and ultimate compressive strength was 1863 MPa with a total compressive fracture strain of ~34%. Dual mode fracture was observed with ductile failure for L12 phase and brittle mode for B2 phase. Phase-specific mechanical tests using nano-indentation and micro-pillar compression showed higher hardness and strength and larger strain rate sensitivity for B2 compared with L12. Micro-pillars on B2 phase deformed by plastic barreling while L12 micro-pillars showed high density of slip steps due to activation of more slip systems and homogenous plastic flow. Mixed micro-pillars containing both the phases exhibited dual yielding behavior while the interface between L12 and B2 was well preserved without any sign of separation or cracking. Phase-specific friction analysis revealed higher coefficient of friction for B2 compared to L12. These results will pave the way for fundamental understanding of phase-specific contribution to bulk mechanical response of concentrated alloys and help in designing structural materials with high fracture toughness.
Essential oils against bacterial isolates from cystic fibrosis patients by means of antimicrobial and unsupervised machine learning approaches
Authors: Ragno Rino , Papa Rosanna , Patsilinakos Alexandros , Vrenna Gianluca , Garzoli Stefania , Tuccio Vanessa , Fiscarelli ErsiliaVita , Selan Laura , Artini Marco 
Published: February 2020

AbstractRecurrent and chronic respiratory tract infections in cystic fibrosis (CF) patients result in progressive lung damage and represent the primary cause of morbidity and mortality. Staphylococcus aureus (S. aureus) is one of the earliest bacteria in CF infants and children. Starting from early adolescence, patients become chronically infected with Gram-negative non-fermenting bacteria, and Pseudomonas aeruginosa (P. aeruginosa) is the most relevant and recurring. Intensive use of antimicrobial drugs to fight lung infections inevitably leads to the onset of antibiotic resistant bacterial strains. New antimicrobial compounds should be identified to overcome antibiotic resistance in these patients. Recently interesting data were reported in literature on the use of natural derived compounds that inhibited in vitro S. aureus and P. aeruginosa bacterial growth. Essential oils, among these, seemed to be the most promising. In this work is reported an extensive study on 61 essential oils (EOs) against a panel of 40 clinical strains isolated from CF patients. To reduce the in vitro procedure and render the investigation as convergent as possible, machine learning clusterization algorithms were firstly applied to pick-up a fewer number of representative strains among the panel of 40. This approach allowed us to easily identify three EOs able to strongly inhibit bacterial growth of all bacterial strains. Interestingly, the EOs antibacterial activity is completely unrelated to the antibiotic resistance profile of each strain. Taking into account the results obtained, a clinical use of EOs could be suggested.
Scanning laser optical tomography resolves developmental neurotoxic effects on pioneer neurons
Authors: Bode Karsten , Nolte Lena , Kamin Hannes , Desens Michael , Ulmann Arthur , Bergmann Gregor A. , Betker Philine , Reitmeier Jennifer , Ripken Tammo , Stern Michael , Meyer Heiko , Bicker Gerd 
Published: February 2020

AbstractDevelopmental neurotoxic compounds impair the developing human nervous system at lower doses than those affecting adults. Standardized test methods for assessing developmental neurotoxicity (DNT) require the use of high numbers of laboratory animals. Here, we use a novel assay that is based on the development of an intact insect embryo in serum-free culture. Neural pathways in the leg of embryonic locusts are established by a pair of afferent pioneer neurons, extending axons along a well-defined pathway to the central nervous system. After exposure to test chemicals, we analyze pioneer neuron shape with conventional fluorescence microscopy and compare it to 3D images, obtained by scanning laser optical tomography (SLOT) and processed by a segmentation algorithm. The segmented SLOT images resolve the 3D structure of the pioneers, recognize pathfinding defects and are thus advantageous for detecting DNT-positive compounds. The defects in axon elongation and pathfinding of pioneer axons caused by two DNT-positive reference compounds (methylmercury chloride; sodium(meta)arsenite) are compared to the biochemically measured general viability of the embryo. Using conventional fluorescence microscopy to establish concentration-response curves of axon elongation, we show that this assay identifies methylmercury chloride and the pro-apoptotic compound staurosporine as developmental neurotoxicants.
Femtosecond Laser-assisted Preparation of Conjunctival Autograft for Pterygium Surgery
Authors: Liu Yu-Chi , Ji Angel Jung Se , Tan Tien-En , Fuest Matthias , Mehta Jodhbir S. 
Published: February 2020

AbstractFemtosecond laser-assisted conjunctival autografts (CAG) preparation was recently proposed. This study reports the outcomes of the first clinical trial on the use of laser to prepare CAG in pterygium surgery, and to compare the outcomes with those of manual technique. Forty eyes undergoing primary pterygium excision with laser-assisted CAG transplantation were prospectively included (L group). Two historical matched cohorts whose CAGs were prepared manually were compared (n = 78 eyes by the same experienced surgeon, M group; n = 78 eyes by trainees; TM group). We found the laser-created CAGs had only 11 μm deviation from the targeted thickness. The best-corrected visual acuity improved, and the astigmatism significantly decreased after surgery, with comparable efficacy across 3 groups. The 1-year recurrence rate was 2.5%, 3.8% and 7.7% in the L, M and TM groups, respectively (P = 0.12). There was no significant difference between the L and M groups in the complication rate (5.0% and 1.3%, respectively), surgical time (19.4 ± 5.1 and 19.1 ± 6.2 minutes, respectively), and postoperative discomfort scores (0.1 ± 0.3 and 0.2 ± 0.3, respectively), but these outcomes were significantly less favorable in the TM group. The results of this first comparative clinical trial suggest that femtosecond laser-assisted CAG preparation can be considered as an alternative technique for CAGs preparation.
Prognostic value of VISTA in solid tumours: a systematic review and meta-analysis
Authors: He Xin-Lin , Zhou Ying , Lu Huan-Zi , Li Qun-Xing , Wang Zhi 
Published: February 2020

AbstractIn the last few years, V-domain Ig-containing suppressor of T cell activation(VISTA) has been reported as a prognostic biomarker in articles including various solid tumours. However, their conclusions have been controversial. For this reason, we performed this meta-analysis to further verify the prognostic value of VISTA in solid tumours. All relevant literature was identified from PubMed, Embase, the Cochrane Library and Web of Science. Ten studies, including 2, 440 patients, were eligible for the analysis. The pooled results showed that high expression of VISTA was associated with favourable overall survival (OS) than that seen with low expression of VISTA (7 studies, hazard ratio (HR) = 0.75, 95% confidence interval (CI): 0.66–0.86, P < 0.001). In addition, high expression of VISTA significantly correlated with high numbers of CD8 (+) tumour infiltrating lymphocytes (TILs) (3 studies, risk ratio (RR) = 1.80, 95% CI: 1.41–2.31, P < 0.001). In conclusion, these results indicate that VISTA is a potential prognostic biomarker in solid tumours.
Physiological responses of maca (Lepidium meyenii Walp.) plants to UV radiation in its high-altitude mountain ecosystem
Authors: Huarancca Reyes Thais , Esparza Eliana , Crestani Gaia , Limonchi Fabián , Cruz Rudi , Salinas Norma , Scartazza Andrea , Guglielminetti Lorenzo , Cosio Eric 
Published: February 2020

AbstractUltraviolet (UV) radiation is a small fraction of the solar spectrum, which acts as a key environmental modulator of plant function affecting metabolic regulation and growth. Plant species endemic to the Andes are well adapted to the harsh features of high-altitude climate, including high UV radiation. Maca (Lepidium meyenii Walpers) is a member of Brassicaceae family native to the central Andes of Peru, which grows between 3500 and 4500 m of altitude, where only highland grasses and few hardy bushes can survive. Even though maca has been the focus of recent researches, mainly due to its nutraceutical properties, knowledge regarding its adaptation mechanisms to these particular natural environmental conditions is scarce. In this study, we manipulated solar UV radiation by using UV-transmitting (Control) or blocking (UV-block) filters under field conditions (4138 m above the sea level) in order to understand the impact of UV on morphological and physiological parameters of maca crops over a complete growing season. Compared to the UV-blocking filter, under control condition a significant increase of hypocotyl weight was observed during the vegetative phase together with a marked leaf turnover. Although parameters conferring photosynthetic performance were not altered by UV, carbohydrate allocation between above and underground organs was affected. Control condition did not influence the content of secondary metabolites such as glucosinolates and phenolic compounds in hypocotyls, while some differences were observed in the rosettes. These differences were mainly related to leaf turnover and the protection of new young leaves in control plants. Altogether, the data suggest that maca plants respond to strong UV radiation at high altitudes by a coordinated remobilization and relocation of metabolites between source and sink organs via a possible UV signaling pathway.