bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative study on nutrient depletion-induced lipidome adaptations in Staphylococcus haemolyticus and Staphylococcus epidermidis
Authors: Luo Yu , Javed Muhammad Afzal , Deneer Harry 
Published: January 2018

AbstractStaphylococcus species are emerging opportunistic pathogens that cause outbreaks of hospital and community-acquired infections. Some of these bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) are difficult to treat due to their resistance to multiple antibiotics. We carried out a comparative study on the lipidome adaptations in response to starvation in the two most common coagulase-negative Staphylococcus species: a S. epidermidis strain sensitive to ampicillin and erythromycin and a S. haemolyticus strain resistant to both. The predominant fatty acid composition in glycerolipids was (17:0–15:0) in both bacteria. During the exponential phase, the two bacterial lipidomes were similar. Both were dominated by diacylglycerol (DAG), phosphatidylglycerol (PG), lysyl-phosphatidylglycerol (Lysyl-PG) and Diglucosyl-diacylglycerol (DGDG). Alanyl-PG was detected in small amounts in both bacterial lipids. N-succinyl-lysyl-PG was detected only in S. haemolyticus, while lysyl-DAG only in S. epidermidis. As the two bacteria entered stationary phase, both lipidomes became essentially nitrogen-free. Both bacteria accumulated large amounts of free fatty acids. Strikingly, the lipidome of S. epidermidis became dominated by cardiolipin (CL), while that of S. haemolyticus was simplified to DGDG and PG. The S. epidermidis strain also produced acyl-phosphatidylglycerol (APG) in the stationary phase.
Eis, a novel family of arylalkylamine N-acetyltransferase (EC 2.3.1.87)
Authors: Pan Qian , Zhao Feng-Lan , Ye Bang-Ce 
Published: January 2018

AbstractEnhanced intracellular survival (Eis) proteins were found to enhance the intracellular survival of mycobacteria in macrophages by acetylating aminoglycoside antibiotics to confer resistance to these antibiotics and by acetylating DUSP16/MPK-7 to suppress host innate immune defenses. Eis homologs composing of two GCN5 N-acetyltransferase regions and a sterol carrier protein fold are found widely in gram-positive bacteria. In this study, we found that Eis proteins have an unprecedented ability to acetylate many arylalkylamines, are a novel type of arylalkylamine N-acetyltransferase AANAT (EC 2.3.1.87). Sequence alignment and phyletic distribution analysis confirmed Eis belongs to a new aaNAT-like cluster. Among the cluster, we studied three typical Eis proteins: Eis_Mtb from Mycobacterium tuberculosis, Eis_Msm from Mycobacterium smegmatis, and Eis_Sen from Saccharopolyspora erythraea. Eis_Mtb prefers to acetylate histamine and octopamine, while Eis_Msm uses tyramine and octopamine as substrates. Unlike them, Eis_Sen exihibits good catalytic efficiencies for most tested arylalkylamines. Considering arylalkylamines such as histamine plays a fundamental role in immune reactions, future work linking of AANAT activity of Eis proteins to their physiological function will broaden our understanding of gram-positive pathogen-host interactions. These findings shed insights into the molecular mechanism of Eis, and reveal potential clinical implications for many gram-positive pathogens.
Radium tracing nutrient inputs through submarine groundwater discharge in the global ocean
Authors: Cho Hyung-Mi , Kim Guebuem , Kwon Eun Young , Moosdorf Nils , Garcia-Orellana Jordi , Santos Isaac R. 
Published: January 2018

AbstractRiverine and atmospheric inputs are often considered as the main terrestrial sources of dissolved inorganic nitrogen (DIN), phosphorus (DIP), and silicon (DSi) in the ocean. However, the fluxes of nutrients via submarine groundwater discharge (SGD) often exceed riverine inputs in different local and regional scale settings. In this study, we provide a first approximation of global nutrient fluxes to the ocean via total SGD, including pore water fluxes, by combining a global compilation of nutrient concentrations in groundwater and the SGD-derived 228Ra fluxes. In order to avoid overestimations in calculating SGD-derived nutrient fluxes, the endmember value of nutrients in global groundwater was chosen from saline groundwater samples (salinity >10) which showed relatively lower values over all regions. The results show that the total SGD-derived fluxes of DIN, DIP, and DSi could be approximately 1.4-, 1.6-, and 0.7-fold of the river fluxes to the global ocean (Indo-Pacific and Atlantic Oceans), respectively. Although significant portions of these SGD-derived nutrient fluxes are thought to be recycled within sediment-aquifer systems over various timescales, SGD-derived nutrient fluxes should be included in the global ocean budget in order to better understand dynamic interactions at the land-ocean interface.
Phenotypic co-receptor tropism and Maraviroc sensitivity in HIV-1 subtype C from East Africa
Authors: Siddik Abu Bakar , Haas Alexandra , Rahman Md Shanawazur , Aralaguppe Shambhu Ganeshappa , Amogne Wondwossen , Bader Joelle , Klimkait Thomas , Neogi Ujjwal 
Published: January 2018

AbstractGenotypic tropism testing (GTT) for co-receptor usage is a recommended tool for clinical practice before administration of the CCR5-antagonist maraviroc. For some isolates, phenotypic tropism testing (PTT) revealed discordant results with GTT. In this study, we performed a comparative study between GTT and PTT in HIV-1C from East Africa (HIV-1CEA) and compared the data with HIV-1B and 01_AE and described the maraviroc susceptibility in the CCR5-tropic strains. Patient-derived HIV-1 envgp120 region was cloned into a modified pNL4-3 plasmid expressing the luciferase gene. rPhenotyping dissected single clones from 31 HIV-1CEA infected patients and four strains with known phenotype. Additionally, 68 clones from 18 patients (HIV-1B: 5, 01_AE: 7, HIV-1CEA: 6) were used to determine the PTT in GHOST cell line. The respective V3-sequences were used for GTT. R5-tropic strains from HIV-1CEA (n = 20) and non-C (n = 12) were tested for maraviroc sensitivity in TZMbl cell line. The GTT falsely called a higher proportion of X4-tropic strains in HIV-1CET compared to PTT by both rPhenotyping and the GHOST-cell assay. When multiple clones were tested in a subset of patients’ samples, both dual-tropic and R5-tropic strains were identified for HIV-1C. Relatively higher EC50 values were observed in HIV-1C strains than the non-C strains (p = 0.002).
Corium lavas: structure and properties of molten UO2-ZrO2 under meltdown conditions
Authors: Alderman O. L. G. , Benmore C. J. , Weber J. K. R. , Skinner L. B. , Tamalonis A. J. , Sendelbach S. , Hebden A. , Williamson M. A. 
Published: January 2018

AbstractIn the exceedingly rare event of nuclear reactor core meltdown, uranium dioxide fuel reacts with Zircaloy cladding to produce eutectic melts which can subsequently be oxidized by coolant/moderator water. Oxidized corium liquids in the xUO2·(100 − x)ZrO2 system were produced via laser melting of UO2-ZrO2 mixtures to temperatures in excess of 3000 K. Contamination was avoided by floating the droplets on a gas stream within an aerodynamic levitator and in-situ high-energy x-ray diffraction experiments allowed structural details to be elucidated. Molecular dynamics simulations well reproduced diffraction and density data, and show less compositional variation in thermal expansion and viscosity than suggested by existing measurements. As such, corium liquids maintain their highly penetrating nature irrespective of the amount of oxidized cladding dissolved in the molten fuel. Metal-oxygen coordination numbers vary with both composition and temperature. The former is due to mismatch in native values, nUO(x = 100) ≈ 7 and nZrO(x = 0) ≈ 6, and the requirement for oxygen site stabilization. The latter provides a thermal expansion mechanism.
Prediction of HIV-1 and HIV-2 proteins by using Chou’s pseudo amino acid compositions and different classifiers
Authors: Mei Juan , Zhao Ji 
Published: January 2018

AbstractHuman immunodeficiency virus (HIV) is the retroviral agent that causes acquired immune deficiency syndrome (AIDS). The number of HIV caused deaths was about 4 million in 2016 alone; it was estimated that about 33 million to 46 million people worldwide living with HIV. The HIV disease is especially harmful because the progressive destruction of the immune system prevents the ability of forming specific antibodies and to maintain an efficacious killer T cell activity. Successful prediction of HIV protein has important significance for the biological and pharmacological functions. In this study, based on the concept of Chou’s pseudo amino acid (PseAA) composition and increment of diversity (ID), support vector machine (SVM), logisitic regression (LR), and multilayer perceptron (MP) were presented to predict HIV-1 proteins and HIV-2 proteins. The results of the jackknife test indicated that the highest prediction accuracy and CC values were obtained by the SVM and MP were 0.9909 and 0.9763, respectively, indicating that the classifiers presented in this study were suitable for predicting two groups of HIV proteins.
Genetic targeting of Purkinje fibres by Sema3a-CreERT2
Authors: Li Yan , Tian Xueying , Zhao Huan , He Lingjuan , Zhang Shaohua , Huang Xiuzhen , Zhang Hui , Miquerol Lucile , Zhou Bin 
Published: January 2018

AbstractThe maintenance of the heart rhythm and the conduction of excitatory signals require changing excitatory signals via electrical activity and coordination by communication between working and conductive cardiomyocytes. Understanding how the ventricular conduction system is established provides novel insights into the pathophysiological progress of cardiac arrhythmias. However, the major hurdle in this field is the lack of a specific genetic tool that targets the Purkinje fibres of the ventricular conduction system and no other types of cardiomyocytes or coronary vessels. Here, we generated a Sema3a-CreERT2 knock-in mouse line to test its specificity for genetically labelled Purkinje fibres. We found that Sema3a was expressed in the subendocardial layer of the trabecular myocardium in the embryonic heart and was restricted to the Purkinje fibres in the adult heart. A fate mapping study based on the Sema3a-CreERT2 line revealed that the Sema3a+ cardiomyocytes were restricted to the fate of Purkinje fibres in the perinatal but not the embryonic stage. Collectively, our study provides a new genetic tool, i.e., Sema3a-CreERT2, for studying the molecular mechanisms that regulate the function of Purkinje fibres.
Fibroblast-associated tumour microenvironment induces vascular structure-networked tumouroid
Authors: Lee Sang Woo , Kwak Hyeong Seob , Kang Myoung-Hee , Park Yun-Yong , Jeong Gi Seok 
Published: January 2018

AbstractIn vitro three-dimensional (3D) tumour models mimic natural cancer tissue in vivo, bridging the gap between conventional 2D in vitro testing and animal models. Stromal and cancer tissues with extracellular matrix (ECM) can provide a tumour microenvironment (TME) with cell-to-cell and cell-to-ECM interactions. These interactions induce the exchange of biophysical factors, contributing to the progression, metastasis, and drug resistance of cancer. Here, we describe a 3D in vitro lung cancer model cultured in a microfluidic channel that is able to confirm the role and function of various stromal cells in tumourigenesis, thereby representing an in vivo-like TME. We founded that biophysical factors contribute to the role of fibroblast cells in tumour formation, especially, producing a nascent vessel-like tubular structure, resulting in the formation of vascularized tumour tissue. Fibroblast cells altered the gene expression of the cancer cells to enhance metastasis, survival, and angiogenesis. The device could be used for developing and screening anti-cancer drugs through the formation of the same multicellular tumour spheroids under TME interactions. We believe this microfluidic system provides interaction of TME for cancer research by culturing stromal tissue.
Updating the genomic taxonomy and epidemiology of Campylobacter hyointestinalis
Authors: Wilkinson David A. , O’Donnell Andrew J. , Akhter Rukhshana N. , Fayaz Ahmed , Mack Hamish J. , Rogers Lynn E. , Biggs Patrick J. , French Nigel P. , Midwinter Anne C. 
Published: January 2018

AbstractCampylobacter hyointestinalis is a member of an emerging group of zoonotic Campylobacter spp. that are increasingly identified in both gastric and non-gastric disease in humans. Here, we discovered C. hyointestinalis in three separate classes of New Zealand ruminant livestock; cattle, sheep and deer. To investigate the relevance of these findings we performed a systematic literature review on global C. hyointestinalis epidemiology and used comparative genomics to better understand and classify members of the species. We found that C. hyointestinalis subspecies hyointestinalis has an open pangenome, with accessory gene contents involved in many essential processes such as metabolism, virulence and defence. We observed that horizontal gene transfer is likely to have played an overwhelming role in species diversification, favouring a public-goods-like mechanism of gene ‘acquisition and resampling’ over a tree-of-life-like vertical inheritance model of evolution. As a result, simplistic gene-based inferences of taxonomy by similarity are likely to be misleading. Such genomic plasticity will also mean that local evolutionary histories likely influence key species characteristics, such as host-association and virulence. This may help explain geographical differences in reported C. hyointestinalis epidemiology and limits what characteristics may be generalised, requiring further genomic studies of C. hyointestinalis in areas where it causes disease.
Tracking hidden organic carbon in rocks using chemometrics and hyperspectral imaging
Authors: Pisapia Céline , Jamme Frédéric , Duponchel Ludovic , Ménez Bénédicte 
Published: January 2018

AbstractFinding traces of life or organic components of prebiotic interest in the rock record is an appealing goal for numerous fields in Earth and space sciences. However, this is often hampered by the scarceness and highly heterogeneous distribution of organic compounds within rocks. We assess here an innovative analytical strategy combining Synchrotron radiation-based Fourier-Transform Infrared microspectroscopy (S-FTIR) and multivariate analysis techniques to track and characterize organic compounds at the pore level in complex oceanic rocks. S-FTIR hyperspectral images are analysed individually or as multiple image combinations (multiset analysis) using Principal Component Analyses (PCA) and Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS). This approach allows extracting simultaneously pure organic and mineral spectral signatures and determining their spatial distributions and relationships. MCR-ALS analysis provides resolved S-FTIR signatures of 8 pure mineral and organic components showing the close association at a micrometric scale of organic compounds and secondary clays formed during rock alteration and known to catalyse organic synthesis. These results highlights the potential of the serpentinizing oceanic lithosphere to generate and preserve organic compounds of abiotic origin, in favour of the hydrothermal theory for the origin of life.
Integrating Functional Analysis in the Next-Generation Sequencing Diagnostic Pipeline of RASopathies
Authors: Leung Gordon K. C. , Luk H. M. , Tang Vincent H. M. , Gao W. W. , Mak Christopher C. Y. , Yu Mullin H. C. , Wong W. L. , Chu Yoyo W. Y. , Yang W. L. , Wong Wilfred H. S. , Ma Alvin C. H. , Leung Anskar Y. H. , Jin D. Y. , Chan Kelvin Y. K. , Allanson Judith , Lo Ivan F. M. , Chung Brian H. Y. 
Published: January 2018

AbstractRASopathies are a group of heterogeneous conditions caused by germline mutations in RAS/MAPK signalling pathway genes. With next-generation sequencing (NGS), sequencing capacity is no longer a limitation to molecular diagnosis. Instead, the rising number of variants of unknown significance (VUSs) poses challenges to clinical interpretation and genetic counselling. We investigated the potential of an integrated pipeline combining NGS and the functional assessment of variants for the diagnosis of RASopathies. We included 63 Chinese patients with RASopathies that had previously tested negative for PTPN11 and HRAS mutations. In these patients, we performed a genetic analysis of genes associated with RASopathies using a multigene NGS panel and Sanger sequencing. For the VUSs, we evaluated evidence from genetic, bioinformatic and functional data. Twenty disease-causing mutations were identified in the 63 patients, providing a primary diagnostic yield of 31.7%. Four VUSs were identified in five patients. The functional assessment supported the pathogenicity of the RAF1 and RIT1 VUSs, while the significance of two VUSs in A2ML1 remained unclear. In summary, functional analysis improved the diagnostic yield from 31.7% to 36.5%. Although technically demanding and time-consuming, a functional genetic diagnostic analysis can ease the clinical translation of these findings to aid bedside interpretation.
Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
Authors: Coleman Verena , Sa-Nguanmoo Piangkwan , Koenig Jeannette , Schulz Tim J. , Grune Tilman , Klaus Susanne , Kipp Anna P. , Ost Mario 
Published: January 2018

AbstractMitochondrial dysfunction is usually associated with various metabolic disorders and ageing. However, salutary effects in response to mild mitochondrial perturbations have been reported in multiple organisms, whereas molecular regulators of cell-autonomous stress responses remain elusive. We addressed this question by asking whether the nuclear factor erythroid-derived-like 2 (Nrf2), a transcription factor and master regulator of cellular redox status is involved in adaptive physiological responses including muscle mitohormesis. Using a transgenic mouse model with skeletal muscle-specific mitochondrial uncoupling and oxidative phosphorylation (OXPHOS) inefficiency (UCP1-transgenic, TG) we show that additional genetic ablation of Nrf2 abolishes an adaptive muscle NAD(P)H quinone dehydrogenase 1 (NQO1) and catalase induction. Deficiency of Nrf2 also leads to decreased mitochondrial respiratory performance although muscle functional integrity, fiber-type profile and mitochondrial biogenesis were not significantly altered. Importantly, Nrf2 ablation did not abolish the induction of key genes and proteins of muscle integrated stress response including the serine, one-carbon cycle, and glycine synthesis (SOG) pathway in TG mice while further increasing glutathione peroxidase (GPX) activity linked to increased GPX1 protein levels. Conclusively, our results tune down the functions controlled by Nrf2 in muscle mitohormesis and oxidative stress defense during mitochondrial OXPHOS inefficiency.
Epidemic spreading in modular time-varying networks
Authors: Nadini Matthieu , Sun Kaiyuan , Ubaldi Enrico , Starnini Michele , Rizzo Alessandro , Perra Nicola 
Published: January 2018

AbstractWe investigate the effects of modular and temporal connectivity patterns on epidemic spreading. To this end, we introduce and analytically characterise a model of time-varying networks with tunable modularity. Within this framework, we study the epidemic size of Susceptible-Infected-Recovered, SIR, models and the epidemic threshold of Susceptible-Infected-Susceptible, SIS, models. Interestingly, we find that while the presence of tightly connected clusters inhibits SIR processes, it speeds up SIS phenomena. In this case, we observe that modular structures induce a reduction of the threshold with respect to time-varying networks without communities. We confirm the theoretical results by means of extensive numerical simulations both on synthetic graphs as well as on a real modular and temporal network.
Poisson statistics-mediated particle/cell counting in microwell arrays
Authors: Ahrberg Christian D. , Lee Jong Min , Chung Bong Geun 
Published: January 2018

AbstractPrecise determination of particle or cell numbers is of importance for a wide array of applications in environmental studies, medical and biological applications, or manufacturing and monitoring applications in industrial production processes. A number of techniques ranging from manual counting to sophisticated equipment (e.g., flow cytometry) are available for this task. However, these methods are either labour intensive, prone to error, or require expensive equipment. Here, we present a fast, simple method for determining the number density of cells or microparticles using a microwell array. We analyze the light transmission of the microwells and categorize the microwells into two groups. As particles/cells contained in a microwell locally reduce the light transmission, these wells displayed a lower average transmission compared to unoccupied microwells. The number density of particles/cells can be calculated by Poisson statistics from the ratio of occupied to unoccupied microwells. Following this approach, the number densities of two different types of microparticles, as well as HeLa and E. Coli cells, ranging over four orders of magnitude were determined. Through the microwell array defined by microfabrication, a simple image recognition algorithm can be used with the formation of aggregates or irregular shaped samples providing no additional difficulty to the microwell recognition. Additionally, this method can be carried out using only simple equipment and data analysis automated by a computer program.
Advanced machine learning in action: identification of intracranial hemorrhage on computed tomography scans of the head with clinical workflow integration
Authors: Arbabshirani Mohammad R. , Fornwalt Brandon K. , Mongelluzzo Gino J. , Suever Jonathan D. , Geise Brandon D. , Patel Aalpen A. , Moore Gregory J. 
Published: January 2018

AbstractIntracranial hemorrhage (ICH) requires prompt diagnosis to optimize patient outcomes. We hypothesized that machine learning algorithms could automatically analyze computed tomography (CT) of the head, prioritize radiology worklists and reduce time to diagnosis of ICH. 46,583 head CTs (~2 million images) acquired from 2007–2017 were collected from several facilities across Geisinger. A deep convolutional neural network was trained on 37,074 studies and subsequently evaluated on 9499 unseen studies. The predictive model was implemented prospectively for 3 months to re-prioritize “routine” head CT studies as “stat” on realtime radiology worklists if an ICH was detected. Time to diagnosis was compared between the re-prioritized “stat” and “routine” studies. A neuroradiologist blinded to the study reviewed false positive studies to determine whether the dictating radiologist overlooked ICH. The model achieved an area under the ROC curve of 0.846 (0.837–0.856). During implementation, 94 of 347 “routine” studies were re-prioritized to “stat”, and 60/94 had ICH identified by the radiologist. Five new cases of ICH were identified, and median time to diagnosis was significantly reduced (p < 0.0001) from 512 to 19 min. In particular, one outpatient with vague symptoms on anti-coagulation was found to have an ICH which was treated promptly with reversal of anticoagulation, resulting in a good clinical outcome. Of the 34 false positives, the blinded over-reader identified four probable ICH cases overlooked in original interpretation. In conclusion, an artificial intelligence algorithm can prioritize radiology worklists to reduce time to diagnosis of new outpatient ICH by 96% and may also identify subtle ICH overlooked by radiologists. This demonstrates the positive impact of advanced machine learning in radiology workflow optimization.