bluuebunny/crossref_metadata_2025_split huggingface dataset:
High cell densities favor lysogeny: induction of an H20 prophage is repressed by quorum sensing and enhances biofilm formation in Vibrio anguillarum
Authors: Tan Demeng , Hansen Mads Frederik , de Carvalho Luís Nunes , Røder Henriette Lyng , Burmølle Mette , Middelboe Mathias , Lo Svenningsen Sine 
Published: April 2020

Abstract
Temperate ϕH20-like phages are repeatedly identified at geographically distinct areas as free phage particles or as prophages of the fish pathogen Vibrio anguillarum. We studied mutants of a lysogenic isolate of V. anguillarum locked in the quorum-sensing regulatory modes of low (ΔvanT) and high (ΔvanO) cell densities by in-frame deletion of key regulators of the quorum-sensing pathway. Remarkably, we find that induction of the H20-like prophage is controlled by the quorum-sensing state of the host, with an eightfold increase in phage particles per cell in high-cell-density cultures of the quorum-sensing-deficient ΔvanT mutant. Comparative studies with prophage-free strains show that biofilm formation is promoted at low cell density and that the H20-like prophage stimulates this behavior. In contrast, the high-cell-density state is associated with reduced prophage induction, increased proteolytic activity, and repression of biofilm. The proteolytic activity may dually function to disperse the biofilm and as a quorum-sensing-mediated antiphage strategy. We demonstrate an intertwined regulation of phage-host interactions and biofilm formation, which is orchestrated by host quorum-sensing signaling, suggesting that increased lysogeny at high cell density is not solely a strategy for phages to piggy-back the successful bacterial hosts but is also a host strategy evolved to take control of the lysis-lysogeny switch to promote host fitness.
Highly efficient blue organic light-emitting diodes based on carbene-metal-amides
Authors: Conaghan Patrick J. , Matthews Campbell S. B. , Chotard Florian , Jones Saul T. E. , Greenham Neil C. , Bochmann Manfred , Credgington Dan , Romanov Alexander S. 
Published: April 2020

AbstractCarbene-metal-amides are soluble and thermally stable materials which have recently emerged as emitters in high-performance organic light-emitting diodes. Here we synthesise carbene-metal-amide photoemitters with CF3-substituted ligands to show sky-blue to deep-blue photoluminescence from charge-transfer excited states. We demonstrate that the emission colour can be adjusted from blue to yellow and observe that the relative energies of charge transfer and locally excited triplet states influence the performance of the deep-blue emission. High thermal stability and insensitivity to aggregation-induced luminescence quenching allow us to fabricate organic light-emitting diodes in both host-free and host-guest architectures. We report blue devices with a peak external quantum efficiency of 17.3% in a host-free emitting layer and 20.9% in a polar host. Our findings inform the molecular design of the next generation of stable blue carbene-metal-amide emitters.
Automatic diagnosis of the 12-lead ECG using a deep neural network
Authors: Ribeiro Antônio H. , Ribeiro Manoel Horta , Paixão Gabriela M. M. , Oliveira Derick M. , Gomes Paulo R. , Canazart Jéssica A. , Ferreira Milton P. S. , Andersson Carl R. , Macfarlane Peter W. , Meira Wagner , Schön Thomas B. , Ribeiro Antonio Luiz P. 
Published: April 2020

AbstractThe role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. Deep Neural Networks (DNNs) are models composed of stacked transformations that learn tasks by examples. This technology has recently achieved striking success in a variety of task and there are great expectations on how it might improve clinical practice. Here we present a DNN model trained in a dataset with more than 2 million labeled exams analyzed by the Telehealth Network of Minas Gerais and collected under the scope of the CODE (Clinical Outcomes in Digital Electrocardiology) study. The DNN outperform cardiology resident medical doctors in recognizing 6 types of abnormalities in 12-lead ECG recordings, with F1 scores above 80% and specificity over 99%. These results indicate ECG analysis based on DNNs, previously studied in a single-lead setup, generalizes well to 12-lead exams, taking the technology closer to the standard clinical practice.
Membrane mediated toppling mechanism of the folate energy coupling factor transporter
Authors: Faustino Ignacio , Abdizadeh Haleh , Souza Paulo C. T. , Jeucken Aike , Stanek Weronika K. , Guskov Albert , Slotboom Dirk J. , Marrink Siewert J. 
Published: April 2020

AbstractEnergy coupling factor (ECF) transporters are responsible for the uptake of micronutrients in bacteria and archaea. They consist of an integral membrane unit, the S-component, and a tripartite ECF module. It has been proposed that the S-component mediates the substrate transport by toppling over in the membrane when docking onto an ECF module. Here, we present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter. Simulations reveal a strong bending of the membrane around the ECF module that provides a driving force for toppling of the S-component. The stability of the toppled state depends on the presence of non-bilayer forming lipids, as confirmed by folate transport activity measurements. Together, our data provide evidence for a lipid-dependent toppling-based mechanism for the folate-specific ECF transporter, a mechanism that might apply to other ECF transporters.
Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy
Authors: Torii Satoru , Yamaguchi Hirofumi , Nakanishi Akira , Arakawa Satoko , Honda Shinya , Moriwaki Kenta , Nakano Hiroyasu , Shimizu Shigeomi 
Published: April 2020

AbstractAlternative autophagy is an autophagy-related protein 5 (Atg5)-independent type of macroautophagy. Unc51-like kinase 1 (Ulk1) is an essential initiator not only for Atg5-dependent canonical autophagy but also for alternative autophagy. However, the mechanism as to how Ulk1 differentially regulates both types of autophagy has remained unclear. In this study, we identify a phosphorylation site of Ulk1 at Ser746, which is phosphorylated during genotoxic stress-induced alternative autophagy. Phospho-Ulk1746 localizes exclusively on the Golgi and is required for alternative autophagy, but not canonical autophagy. We also identify receptor-interacting protein kinase 3 (RIPK3) as the kinase responsible for genotoxic stress-induced Ulk1746 phosphorylation, because RIPK3 interacts with and phosphorylates Ulk1 at Ser746, and loss of RIPK3 abolishes Ulk1746 phosphorylation. These findings indicate that RIPK3-dependent Ulk1746 phosphorylation on the Golgi plays a pivotal role in genotoxic stress-induced alternative autophagy.
Conserved in-ovo cranial ossification sequences of extant saurians allow estimation of embryonic dinosaur developmental stages
Authors: Chapelle Kimberley E. J. , Fernandez Vincent , Choiniere Jonah N. 
Published: April 2020

AbstractDinosaur embryos are among the rarest of fossils, yet they provide a unique window into the palaeobiology of these animals. Estimating the developmental stage of dinosaur embryos is hindered by the lack of a quantitative method for age determination, by the scarcity of material, and by the difficulty in visualizing that material. Here we present the results of a broad inquiry, using 3D reconstructions from X-ray computed tomography data, into cranial ossification sequences in extant saurian taxa and in well-preserved embryos of the early branching sauropodomorph dinosaur Massospondylus carinatus. Our findings support deep-time conservation of cranial ossification sequences in saurians including dinosaurs, allowing us to develop a new method for estimating the relative developmental percentage of embryos from that clade. We also observe null-generation teeth in the Massospondylus carinatus embryos which get resorbed or shed before hatching, similar to those of geckos. These lines of evidence allow us to confidently estimate that the Massospondylus carinatus embryos are only approximately 60% through their incubation period, much younger than previously hypothesized. The overall consistency of our results with those of living saurians indicates that they can be generalized to other extinct members of that lineage, and therefore our method provides an independent means of assessing the developmental stage of extinct, in-ovo saurians.
Direct evidence of Neanderthal fibre technology and its cognitive and behavioral implications
Authors: Hardy B. L. , Moncel M.-H. , Kerfant C. , Lebon M. , Bellot-Gurlet L. , Mélard N. 
Published: April 2020

AbstractNeanderthals are often considered as less technologically advanced than modern humans. However, we typically only find faunal remains or stone tools at Paleolithic sites. Perishable materials, comprising the vast majority of material culture items, are typically missing. Individual twisted fibres on stone tools from the Abri du Maras led to the hypothesis of Neanderthal string production in the past, but conclusive evidence was lacking. Here we show direct evidence of fibre technology in the form of a 3-ply cord fragment made from inner bark fibres on a stone tool recovered in situ from the same site. Twisted fibres provide the basis for clothing, rope, bags, nets, mats, boats, etc. which, once discovered, would have become an indispensable part of daily life. Understanding and use of twisted fibres implies the use of complex multi-component technology as well as a mathematical understanding of pairs, sets, and numbers. Added to recent evidence of birch bark tar, art, and shell beads, the idea that Neanderthals were cognitively inferior to modern humans is becoming increasingly untenable.
Nanofabrication of Isoporous Membranes for Cell Fractionation
Authors: Sabirova Ainur , Pisig Florencio , Rayapuram Naganand , Hirt Heribert , Nunes Suzana P. 
Published: April 2020

AbstractCell fractionations and other biological separations frequently require several steps. They could be much more effectively done by filtration, if isoporous membranes would be available with high pore density, and sharp pore size distribution in the micro- and nanoscale. We propose a combination of two scalable methods, photolithography and dry reactive ion etching, to fabricate a series of polyester membranes with isopores of size 0.7 to 50 μm and high pore density with a demonstrated total area of 38.5 cm2. The membranes have pore sizes in the micro- and submicro-range, and pore density 10-fold higher than track-etched analogues, which are the only commercially available isoporous polymeric films. Permeances of 220,000 L m−2 h−1bar−1 were measured with pore size 787 nm. The method does not require organic solvents and can be applied to many homopolymeric materials. The pore reduction from 2 to 0.7 μm was obtained by adding a step of chemical vapor deposition. The isoporous system was successfully demonstrated for the organelle fractionation of Arabidopsis homogenates and could be potentially extended to other biological fractionations.
Metabolomic and transcriptomic profiling reveals the alteration of energy metabolism in oyster larvae during initial shell formation and under experimental ocean acidification
Authors: Liu Zhaoqun , Zhang Yukun , Zhou Zhi , Zong Yanan , Zheng Yan , Liu Chang , Kong Ning , Gao Qiang , Wang Lingling , Song Linsheng 
Published: April 2020

AbstractMarine bivalves secrete calcified shells to protect their soft bodies from predation and damages, which is of great importance for their survival, and for the safety of the coastal ecosystem. In recent years, larval shell formation of marine bivalves has been severely affected by ocean acidification (OA), and previous study indicated that OA might affect such process by disrupting endogenous energy metabolism. Developmental stages from trochophore to D-shape larvae are extremely important for initial shell formation in oyster since a calcified shell was formed to cover the chitin one. In the present study, metabolomic and transcriptomic approaches were employed to investigate the energy metabolism of oyster larvae during initial shell (prodissoconch I, PDI shell) formation and under experimental OA treatment. Totally 230 chemical compounds were identified from the present dataset, most of which were highly expressed in the “middle” stage (early D-shape larvae) which was critical for PDI shell formation since a calcified shell was formed to cover the chitin one. Several compounds such as glucose, glutarylcarnitine (C5), β-hydroxyisovaleroylcarnitine, 5-methylthioadenosine (MTA), myristoleate (14:1n5) and palmitoleate (16:1n7) were identified, which were involved in energy metabolic processes including amino acid oxidation, glycolysis, pentose phosphate pathway and fatty acid metabolism. In addition, mRNA expressions of genes related to protein metabolism, glycolysis, lipid degradation, calcium transport and organic matrix formation activities were significantly down-regulated upon experimental OA. These results collectively suggested that formation of the initial shell in oyster larvae required endogenous energy coming from amino acid oxidation, glycolysis, pentose phosphate pathway and fatty acid metabolism. These metabolic activities could be severely inhibited by experimental OA, which might alter the allocation of endogenous energy. Insufficient endogenous energy supply then suppressed the mobilization of calcium and resulted in a failure or delay in PDI shell formation.
Synthesis, biological activity and molecular modeling study of novel 1,2,4-triazolo[4,3-b][1,2,4,5]tetrazines and 1,2,4-triazolo[4,3-b][1,2,4]triazines
Authors: El-Reedy Ahmed A. M. , Soliman N. K. 
Published: April 2020

AbstractDifferent novel 1,2,4-triazolo[4,3-b][1,2,4,5]tetrazines and 1,2,4-triazolo[4,3-b][1,2,4]triazines have been obtained from heterocyclization of 3-substituted-4-amino-5-substituted-amino-1,2,4-triazoles (3a-d) and 3-substituted-4-amino-5-hydrazino-1,2,4-triazoles (9a,b) with (α and β) bifunctional compounds like chloromethyl biphenyl-phosphanoxide, pyruvic acid, phenacyl bromide, diethyl oxalate, triethyl orthoformate, triethyl phosphite, fluorinated benzaldehydes, carbon disulfide and ethyl chloroformate under different experimental settings. Fourier transformer infrared analysis (FTIR), Proton nuclear magnetic resonance (1H NMR) and 13C nuclear magnetic resonance (13C NMR), as well as that of the mass spectral data, were used as the appropriate characterization techniques for the chemical structures of all newly synthesized compounds. The newly prepared compounds were examined as an anti-inflammatory, antibacterial agents (against E. coli (Escherichia coli) and P. aeruginosa (Pseudomonas aeruginosa) as examples for Gram-negative bacteria and S. aureus (Staphylococcus aureus) as examples for Gram-positive bacteria), as well as antifungal (against C. albicans (Candida albicans)) agents. The newly prepared compound showed high antibacterial, antifungal, and anti-inflammatory activities in comparing with the commercial antibiotics Indomethacin, Nalidixic acid, Imipenem, and Nystatin. Docking of the most active compounds was performed depending on the results of antibacterial screening and the anti-inflammatory assay.
Synthesis of mesoporous silica post-loaded by methyl eugenol as an environment-friendly slow-release bio pesticide
Authors: Chen Huayao , Chen Lishen , Shen Zhichuan , Zhou Hongjun , Hao Li , Xu Hua , Zhou Xinhua 
Published: April 2020

AbstractSalicylaldimine, furfuralimine and benzaldehyde imine were adopted to modify mesoporous silica (MCM) respectively denoted as Sal-MCM, Fur-MCM and Ben-MCM before loading methyl eugenol (Me) for pesticide delivery. Me was adsorbed by Schiff base mesoporous silica without destructing regular hexagonal pore structure verified by the characterization results. DSC result implied that Me in amorphous state which was distributed in the pores of the mesoporous silica. The loading content of Me-Sal-MCM, Me-Fur-MCM and Me-Ben-MCM 67.89%, 73.34% and 73.84% which was higher than Me-MCM without modification (67.35%).Because the electrostatic interaction and π-π interaction between Schiff base and Me strengthened the adsorption capacity of the carrier. And the electrostatic interaction played a more important role in interaction between Me and Schiff base modified mesoporous silica. As a result, Schiff base modified sustained release system also has significantly longer sustained release time with a sequence of Me-Sal-MCM > Me-Ben-MCM > Me-Fur-MCM in release speed in negative correlation with the electric potential sequence. The behaviors of their sustained release performance can be fitted by First order kinetic model before Schiff base modification. After modification, their sustained release behaviors were consistent with Korsmeyer-Peppas equation with non-Fickian diffusion mechanism indicating that main impact on the release process after modification was no longer mainly controlled by the difference of the concentration. Finally, the highest lure rate of the modified MCM (Me-Fur-MCM) equals to the 73% of the pure Me due to its highest BET surface area and strongest interaction with Me among the three Schiff base modified samples. Therefore, the environment-friendly slow-release bio pesticide with long service life was prepared to reduce the damage on the environment caused by pesticide.
Network Systems Pharmacology-Based Mechanism Study on the Beneficial Effects of Vitamin D against Psychosis in Alzheimer’s Disease
Authors: Fan Peihao , Qi Xiguang , Sweet Robert A. , Wang Lirong 
Published: April 2020

AbstractAlzheimer’s disease (AD) is a chronic neurodegenerative disease with significant financial costs and negative impacts on quality of life. Psychotic symptoms, i.e., the presence of delusions and/or hallucinations, is a frequent complication of AD. About 50% of AD patients will develop psychotic symptoms (AD with Psychosis, or AD + P) and these patients will experience an even more rapid cognitive decline than AD patients without psychosis (AD-P). In a previous analysis on medication records of 776 AD patients, we had shown that use of Vitamin D was associated with delayed time to psychosis in AD patients and Vitamin D was used more by AD-P than AD + P patients. To explore the potential molecular mechanism behind our findings, we applied systems pharmacology approaches to investigate the crosstalk between AD and psychosis. Specifically, we built protein-protein interaction (PPI) networks with proteins encoded by AD- and psychosis-related genes and Vitamin D-perturbed genes. Using network analysis we identified several high-impact genes, including NOTCH4, COMT, CACNA1C and DRD3 which are related to calcium homeostasis. The new findings highlight the key role of calcium-related signaling pathways in AD + P development and may provide a new direction and facilitate hypothesis generation for future drug development.
Looking to recognise: the pre-eminence of semantic over sensorimotor processing in human tool use
Authors: Federico Giovanni , Brandimonte Maria A. 
Published: April 2020

AbstractAlongside language and bipedal locomotion, tool use is a characterizing activity of human beings. Current theories in the field embrace two contrasting approaches: “manipulation-based” theories, which are anchored in the embodied-cognition view, explain tool use as deriving from past sensorimotor experiences, whereas “reasoning-based” theories suggest that people reason about object properties to solve everyday-life problems. Here, we present results from two eye-tracking experiments in which we manipulated the visuo-perceptual context (thematically consistent vs. inconsistent object-tool pairs) and the goal of the task (free observation or looking to recognise). We found that participants exhibited reversed tools’ visual-exploration patterns, focusing on the tool’s manipulation area under thematically consistent conditions and on its functional area under thematically inconsistent conditions. Crucially, looking at the tools with the aim of recognising them produced longer fixations on the tools’ functional areas irrespective of thematic consistency. In addition, tools (but not objects) were recognised faster in the thematically consistent conditions. These results strongly support reasoning-based theories of tool use, as they indicate that people primarily process semantic rather than sensorimotor information to interact with the environment in an agent’s consistent-with-goal way. Such a pre-eminence of semantic processing challenges the mainstream embodied-cognition view of human tool use.
Toxicology of Heavy Metals to Subsurface Lithofacies and Drillers during Drilling of Hydrocarbon Wells
Authors: Okoro Emmanuel E. , Okolie Amarachi G. , Sanni Samuel E. , Omeje Maxwell 
Published: April 2020

AbstractThis study investigates the toxicological effects of heavy metals on lithofacies of the subsurface in a drilled hydrocarbon well as well as, to the drilling crew and people in an environment. The pollution levels of selected heavy metals were considered alongside their ecological effects during dry and wet seasons. The health hazard potential of human exposures to the metals, were estimated in terms of intensity and time using the USEPA recommended model. The heavy metal concentration for each layer decreased across the lithofacies as follows; Layer 5> Layer 4> Layer 3> Layer 2> Layer 1. The average concentrations of the heavy metals present in the samples obtained from the formation zone, varied significantly and decreased in the order of Al> Zn> Ni> Pb> Cr> Cu> Cd> As> Hg. The highest concentration of Al, Cu, and Zn in this present study were within the maximum allowable limits whereas, those of As, Cd, Hg and Ni were all above their maximum allowable limits. Among the transition metals analysed, the maximum mean daily dose of Pb (9.18 × 10−6 mg/kg/d) and Cr (1.42 × 10−6 mg/kg/d) were confirmed susceptible to human carcinogens and environmental toxins. The estimated hazard quotient shows that the dermal pathway is the most likely route via which the drilling crew and people in the environment can get contaminated. The cancer risk values for the Pb (7.72 × 10−4), Cd (1.35 × 10−1), Ni (9.97 × 10−3), As (1.50 × 10−1) and Cr (3.16 × 10−3) are all above the acceptable values. The cancer risk contribution for each metal was in the order of As> Cd> Ni> Cr> Pb. Layer 5 had the maximum Geo-accumulation index for the heavy metals considered. This higher Geo-accumulation index noted at the depth in Layer 5 may be attributed to the effect of water basin with turbidity currents, deltas, and shallow marine sediment deposits with storm impacted conditions. Also, the pollution from lead (Pb) in the dry season was maximum with an Igeo value> 5 for all the lithofacies considered because of the low background concentration of the metal. During the wet season, the heavy metal pollution rate was moderate for Zn whereas, it was extremely polluted with respect to Pb. The ecological risk potential of Pb shows that the associated ecological risks range from 536 – 664 in the wet season (i.e. extremely strong) and 2810 – 3480 in dry season (extremely strong). The high level of Pb pollution found in the area at such shallow depth may be due to the sedimentary folds possibly caused by the full spectrum of metamorphic rocks and primary flow structures at shallow depths. This was used to identify the environmental sensitivities of the heavy metals during the dry and wet seasons.