bluuebunny/crossref_metadata_2025 huggingface dataset:
Pim1 kinase positively regulates myoblast behaviors and skeletal muscle regeneration
Authors: Liu Yuantong , Shang Yue , Yan Zihan , Li Hao , Wang Zhen , Liu Zhen , Li Zhenzhong
Published: October 2019

Adult skeletal muscle regeneration after injury depends on normal myoblast function. However, the intrinsic mechanisms for the control of myoblast behaviors are not well defined. Herein, we identified Pim1 kinase as a novel positive regulator of myoblast behaviors in vitro and muscle regeneration in vivo. Specifically, knockdown of Pim1 significantly restrains the proliferation and accelerates the apoptosis of myoblasts in vitro, indicating that Pim1 is critical for myoblast survival and amplification. Meanwhile, we found that Pim1 kinase is increased and translocated from cytoplasm into nucleus during myogenic differentiation. By using Pim1 kinase inhibitor, we proved that inhibition of Pim1 activity prevents myoblast differentiation and fusion, suggesting the necessity of Pim1 kinase activity for proper myogenesis. Mechanistic studies demonstrated that Pim1 kinase interacts with myogenic regulator MyoD and controls its transcriptional activity, inducing the expression of muscle-specific genes, which consequently promotes myogenic differentiation. Additionally, in skeletal muscle injury mouse model, deletion of Pim1 hinders the regeneration of muscle fibers and the recovery of muscle strength. Taken together, our study provides a potential target for the manipulation of myoblast behaviors in vitro and the myoblast-based therapeutics of skeletal muscle injury.
Artificial tethering of LC3 or p62 to organelles is not sufficient to trigger autophagy
Authors: Loos Friedemann , Xie Wei , Sica Valentina , Bravo-San Pedro José Manuel , Souquère Sylvie , Pierron Gérard , Lachkar Sylvie , Sauvat Allan , Petrazzuolo Adriana , Jimenez Ana Joaquina , Perez Franck , Maiuri Maria Chiara , Kepp Oliver , Kroemer Guido
Published: October 2019

The retention using selective hooks (RUSH) system allows to retain a target protein fused to green fluorescent protein (GFP) and a streptavidin-binding peptide (SBP) due to the interaction with a molar excess of streptavidin molecules (“hooks”) targeted to selected subcellular compartments. Supplementation of biotin competitively disrupts the interaction between the SBP moiety and streptavidin, liberating the chimeric target protein from its hooks, while addition of avidin causes the removal of biotin from the system and reestablishes the interaction. Based on this principle, we engineered two chimeric proteins involved in autophagy, namely microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B, best known as LC3) and sequestosome-1 (SQSTM1, best known as p62) to move them as SBP–GFP–LC3 and p62–SBP–GFP at will between the cytosol and two different organelles, the endoplasmic reticulum (ER) and the Golgi apparatus. Although both proteins were functional in thus far that SBP–GFP–LC3 and p62–SBP–GFP could recruit their endogenous binding partners, p62 and LC3, respectively, their enforced relocation to the ER or Golgi failed to induce organelle-specific autophagy. Hence, artificial tethering of LC3 or p62 to the surface of the ER and the Golgi is not sufficient to trigger autophagy.
Detection of spacer precursors formed in vivo during primed CRISPR adaptation
Authors: Shiriaeva Anna A. , Savitskaya Ekaterina , Datsenko Kirill A. , Vvedenskaya Irina O. , Fedorova Iana , Morozova Natalia , Metlitskaya Anastasia , Sabantsev Anton , Nickels Bryce E. , Severinov Konstantin , Semenova Ekaterina
Published: October 2019

Type I CRISPR-Cas loci provide prokaryotes with a nucleic-acid-based adaptive immunity against foreign DNA. Immunity involves adaptation, the integration of ~30-bp DNA fragments, termed prespacers, into the CRISPR array as spacers, and interference, the targeted degradation of DNA containing a protospacer. Interference-driven DNA degradation can be coupled with primed adaptation, in which spacers are acquired from DNA surrounding the targeted protospacer. Here we develop a method for strand-specific, high-throughput sequencing of DNA fragments, FragSeq, and apply this method to identify DNA fragments accumulated in Escherichia coli cells undergoing robust primed adaptation by a type I-E or type I-F CRISPR-Cas system. The detected fragments have sequences matching spacers acquired during primed adaptation and function as spacer precursors when introduced exogenously into cells by transformation. The identified prespacers contain a characteristic asymmetrical structure that we propose is a key determinant of integration into the CRISPR array in an orientation that confers immunity.
Cathode porosity is a missing key parameter to optimize lithium-sulfur battery energy density
Authors: Kang Ning , Lin Yuxiao , Yang Li , Lu Dongping , Xiao Jie , Qi Yue , Cai Mei
Published: October 2019

While high sulfur loading has been pursued as a key parameter to build realistic high-energy lithium-sulfur batteries, less attention has been paid to the cathode porosity, which is much higher in sulfur/carbon composite cathodes than in traditional lithium-ion battery electrodes. For high-energy lithium-sulfur batteries, a dense electrode with low porosity is desired to minimize electrolyte intake, parasitic weight, and cost. Here we report the profound impact on the discharge polarization, reversible capacity, and cell cycling life of lithium-sulfur batteries by decreasing cathode porosities from 70 to 40%. According to the developed mechanism-based analytical model, we demonstrate that sulfur utilization is limited by the solubility of lithium-polysulfides and further conversion from lithium-polysulfides to Li2S is limited by the electronically accessible surface area of the carbon matrix. Finally, we predict an optimized cathode porosity to maximize the cell level volumetric energy density without sacrificing the sulfur utilization.
Marine nitrogen fixers mediate a low latitude pathway for atmospheric CO2 drawdown
Authors: Buchanan Pearse J. , Chase Zanna , Matear Richard J. , Phipps Steven J. , Bindoff Nathaniel L.
Published: October 2019

Roughly a third (~30 ppm) of the carbon dioxide (CO2) that entered the ocean during ice ages is attributed to biological mechanisms. A leading hypothesis for the biological drawdown of CO2 is iron (Fe) fertilisation of the high latitudes, but modelling efforts attribute at most 10 ppm to this mechanism, leaving ~20 ppm unexplained. We show that an Fe-induced stimulation of dinitrogen (N2) fixation can induce a low latitude drawdown of 7–16 ppm CO2. This mechanism involves a closer coupling between N2 fixers and denitrifiers that alleviates widespread nitrate limitation. Consequently, phosphate utilisation and carbon export increase near upwelling zones, causing deoxygenation and deeper carbon injection. Furthermore, this low latitude mechanism reproduces the regional patterns of organic δ15N deposited in glacial sediments. The positive response of marine N2 fixation to dusty ice age conditions, first proposed twenty years ago, therefore compliments high latitude changes to amplify CO2 drawdown.
BRG1 attenuates colonic inflammation and tumorigenesis through autophagy-dependent oxidative stress sequestration
Authors: Liu Min , Sun Tongyu , Li Ni , Peng Junjie , Fu Da , Li Wei , Li Li , Gao Wei-Qiang
Published: October 2019

Autophagy is a central component of integrated stress responses that influences many inflammatory diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). While the core machinery is known, the molecular basis of the epigenetic regulation of autophagy and its role in colon inflammation remain largely undefined. Here, we report that BRG1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for the homeostatic maintenance of intestinal epithelial cells (IECs) to prevent the inflammation and tumorigenesis. BRG1 emerges as a key regulator that directly governs the transcription of Atg16l1, Ambra1, Atg7 and Wipi2, which are important for autophagosome biogenesis. Defective autophagy in BRG1-deficient IECs results in excess reactive oxygen species (ROS), which leads to the defects in barrier integrity. Together, our results establish that BRG1 may represent an autophagy checkpoint that is pathogenetically linked to colitis and is therefore likely a potential therapeutic target for disease intervention.
Non-reciprocal robotic metamaterials
Authors: Brandenbourger Martin , Locsin Xander , Lerner Edan , Coulais Corentin
Published: October 2019

Non-reciprocal transmission of motion is potentially highly beneficial to a wide range of applications, ranging from wave guiding to shock and vibration damping and energy harvesting. To date, large levels of non-reciprocity have been realized using broken spatial or temporal symmetries, yet mostly in the vicinity of resonances, bandgaps or using nonlinearities, thereby non-reciprocal transmission remains limited to narrow ranges of frequencies or input magnitudes and sensitive to attenuation. Here, we create a robotic mechanical metamaterials wherein we use local control loops to break reciprocity at the level of the interactions between the unit cells. We show theoretically and experimentally that first-of-their-kind spatially asymmetric standing waves at all frequencies and unidirectionally amplified propagating waves emerge. These findings realize the mechanical analogue of the non-Hermitian skin effect. They significantly advance the field of active metamaterials for non hermitian physics and open avenues to channel mechanical energy in unprecedented ways.
Reduced body sizes in climate-impacted Borneo moth assemblages are primarily explained by range shifts
Authors: Wu Chung-Huey , Holloway Jeremy D. , Hill Jane K. , Thomas Chris D. , Chen I-Ching , Ho Chuan-Kai
Published: October 2019

Both community composition changes due to species redistribution and within-species size shifts may alter body-size structures under climate warming. Here we assess the relative contribution of these processes in community-level body-size changes in tropical moth assemblages that moved uphill during a period of warming. Based on resurvey data for seven assemblages of geometrid moths (>8000 individuals) on Mt. Kinabalu, Borneo, in 1965 and 2007, we show significant wing-length reduction (mean shrinkage of 1.3% per species). Range shifts explain most size restructuring, due to uphill shifts of relatively small species, especially at high elevations. Overall, mean forewing length shrank by ca. 5%, much of which is accounted for by species range boundary shifts (3.9%), followed by within-boundary distribution changes (0.5%), and within-species size shrinkage (0.6%). We conclude that the effects of range shifting predominate, but considering species physiological responses is also important for understanding community size reorganization under climate warming.
Consumption of betel quid contributes to sensorineural hearing impairment through arecoline-induced oxidative stress
Authors: Chan Yen-Hui , Liu Tien-Chen , Liao Chun-Kang , Cheng Yen-Fu , Tsai Ching-Hui , Lu Ying-Chang , Hu Chin-Ju , Lin Hung-Ju , Lee Yungling Leo , Wu Chen-Chi , Hsu Chuan-Jen
Published: October 2019

Betel quid is one of the most widely used psychoactive substances, and is consumed by approximately 10% of the world’s population. In addition to its carcinogenicity, betel quid has also been reported to affect many organs, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. As betel quid contains several neurotoxic ingredients, we hypothesize that it also possesses ototoxicity and may lead to sensorineural hearing impairment (SNHI). In this study, we investigated the contribution of betel quid consumption to SNHI in a large clinical cohort, and validated the pathogenetic mechanisms inex vivotissue explants. We enrolled a total of 2364 volunteers, and determined their audiologic results based on Z-scores converted from their original frequency-specific hearing thresholds. Using generalized linear regression, we identified a positive correlation between betel quid consumption and the Z-scores across different frequencies. Subsequently, we explored the toxicity of arecoline, the main neuroactive component of betel quid, on tissue explants from murine cochleae. Arecoline reduced cell activity in the explant cultures and induced apoptosis in the hair cells, probably through the effects of oxidative stress. These findings have expanded the potential hazards of betel quid to common neurological disorders, and provide insights into preventive strategies against SNHI caused by neurotoxic substances.
Volcanic history in the Smythii basin based on SELENE radar observation
Authors: Ishiyama Ken , Kumamoto Atsushi
Published: October 2019

Elucidation of the subsurface structure in the Smythii basin on the moon is important for understanding lunar volcanic history. Two lava units (Units 1 and 2) cover this basin. The spatial subsurface structure below Unit 2 is unknown. We used SELENE/Lunar Radar Sounder data to identify four subsurface boundaries at 130, 190, 300, and 420 m depths. The radar is reflected at the paleo-regolith layer sandwiched among lava flows, which is supported by a simple radar reflection/transmission model. The spatial distribution of subsurface boundaries demonstrates the deposition of Unit 2 on the subsidence in Unit 1. A simple loading model explained the maximum depth of subsidence (~500 m) and indicated that lithospheric thickness in the Smythii basin was ~24 km at 3.95 Gya. The estimated growth rate of the lithosphere was ~60 km/Ga during 3.95 to 3.07 Gya. After the formation of the Smythii basin at ~4.11 Gya, Unit 1 and Unit 2 deposited with eruption rates of ~8.4 × 10−4 km3/yr by 3.95 Gya and ~7.5 × 10−6 km3/yr by 3.07 Gya respectively. The timing of decline in volcanic activity in the Smythii basin differs from that for the lunar nearside maria, indicating the diversity of volcanism in various lunar areas.
Tunable Magnetism of Organometallic Nanoclusters by Graphene Oxide On-Surface Chemistry
Authors: Sakurai Makoto , Koley Pradyot , Aono Masakazu
Published: October 2019

Assembly of interacting molecular spins is an attractive candidate for spintronic and quantum computing devices. Here, we report on-surface chemical assembly of aminoferrocene molecules on a graphene oxide (GO) sheet and their magnetic properties. On the GO surface, organometallic molecules having individual spins through charge transfer between the molecule and the sheet are arranged in nanoclusters having diameters of about 2 nm. The synthetic fine tuning of the reaction time enables to change the interspacing between the nanoclusters, keeping their size intact. Their magnetism changes from paramagnetic behavior to collective one gradually as the interspacing decreases. The creation of collective nature among weakly interacting molecular spins through their nanoscale arrangement on the GO surface opens a new avenue to molecular magnetism.
Galectin-3 orchestrates the histology of mesentery and protects liver during lupus-like syndrome induced by pristane
Authors: Lemos F. S. , Pereira J. X. , Carvalho V. F. , Bernardes E. S. , Chammas R. , Pereira T. M. , Carvalho R. S. , Luisetto R. , El-Cheikh M. C. , Calil-Elias S. , Oliveira F. L.
Published: October 2019

Galectin-3 (Gal-3) controls intercellular and cell-extracellular matrix interactions during immunological responses. In chronic inflammation, Gal-3 is associated with fibrotic events, regulates B cell differentiation and delays lupus progression. Gal-3 deficient mice (Lgals3−/−) have intense germinal center formation and atypical plasma cell generation correlated to high levels IgG, IgE, and IgA. Here, we used pristane (2,6,10,14-tetramethylpentadecane) to induce lupus-like syndrome in Lgals3−/− and Lgals3+/+ BALB/c mice. Mesentery and peritoneal cells were monitored because promptly react to pristane injected in the peritoneal cavity. For the first time, mesenteric tissues have been associated to the pathogenesis of experimental lupus-like syndrome. In Lgals3+/+ pristane-induced mice, mesentery was hallmarked by intense fibrogranulomatous reaction restricted to submesothelial regions and organized niches containing macrophages and B lymphocytes and plasma cells. In contrast, Lgals3−/− pristane-treated mice had diffuse mesenteric fibrosis affecting submesothelium and peripheral tissues, atypical M1/M2 macrophage polarization and significant DLL1+ cells expansion, suggesting possible involvement of Notch/Delta pathways in the disease. Early inflammatory reaction to pristane was characterized by significant disturbances on monocyte recruitment, macrophage differentiation and dendritic cell (DC) responses in the peritoneal cavity of pristane-induced Lgals3−/− mice. A correlative analysis showed that mesenteric damages in the absence of Gal-3 were directly associated with severe portal inflammation and hepatitis. In conclusion, it has suggested that Gal-3 orchestrates histological organization in the mesentery and prevents lupoid hepatitis in experimental lupus-like syndrome by controlling macrophage polarization, Notch signaling pathways and DC differentiation in mesenteric structures.
Organically-preserved multicellular eukaryote from the early Ediacaran Nyborg Formation, Arctic Norway
Authors: Agić Heda , Högström Anette E. S. , Moczydłowska Małgorzata , Jensen Sören , Palacios Teodoro , Meinhold Guido , Ebbestad Jan Ove R. , Taylor Wendy L. , Høyberget Magne
Published: October 2019

Eukaryotic multicellularity originated in the Mesoproterozoic Era and evolved multiple times since, yet early multicellular fossils are scarce until the terminal Neoproterozoic and often restricted to cases of exceptional preservation. Here we describe unusual organically-preserved fossils from mudrocks, that provide support for the presence of organisms with differentiated cells (potentially an epithelial layer) in the late Neoproterozoic.Cyathinema digermulensegen. et sp. nov. from the Nyborg Formation, Vestertana Group, Digermulen Peninsula in Arctic Norway, is a new carbonaceous organ-taxon which consists of stacked tubes with cup-shaped ends. It represents parts of a larger organism (multicellular eukaryote or a colony), likely with greater preservation potential than its other elements. Arrangement of open-ended tubes invites comparison with cells of an epithelial layer present in a variety of eukaryotic clades. This tissue may have benefitted the organism in: avoiding overgrowth, limiting fouling, reproduction, or water filtration.C.digermulenseshares characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Regardless of its precise affinity,C.digermulensewas a complex and likely benthic marine eukaryote exhibiting cellular differentiation, and a rare occurrence of early multicellularity outside of Konservat-Lagerstätten.
In vitro Antimicrobial Activity of Acne Drugs Against Skin-Associated Bacteria
Authors: Blaskovich Mark A. T. , Elliott Alysha G. , Kavanagh Angela M. , Ramu Soumya , Cooper Matthew A.
Published: October 2019

Acne is a common skin affliction that involves excess sebum production and modified lipid composition, duct blockage, colonization by bacteria, and inflammation. Acne drugs target one or more of these steps, with antibiotics commonly used to treat the microbial infection for moderate to severe cases. Whilst a number of other acne therapies are purported to possess antimicrobial activity, this has been poorly documented in many cases. We conducted a comparative analysis of the activity of common topical acne drugs against the principal etiological agent associated with acne: the aerotolerant anaerobic Gram-positive organism Propionibacterium acnes (recently renamed as Cutibacterium acnes). We also assessed their impact on other bacteria that could also be affected by topical treatments, including both antibiotic-sensitive and antibiotic-resistant strains, using broth microdilution assay conditions. Drugs designated specifically as antibiotics had the greatest potency, but lost activity against resistant strains. The non-antibiotic acne agents did possess widespread antimicrobial activity, including against resistant strains, but at substantially higher concentrations. Hence, the antimicrobial activity of non-antibiotic acne agents may provide protection against a background of increased drug-resistant bacteria.
Topological Indices of Proteins
Authors: Melnikov Dmitry , Niemi Antti J. , Sedrakyan Ara
Published: October 2019

Protein molecules can be approximated by discrete polygonal chains of amino acids. Standard topological tools can be applied to the smoothening of the polygons to introduce a topological classification of folded states of proteins, for example, using the self-linking number of the corresponding framed curves. In this paper we extend this classification to the discrete version, taking advantage of the “randomness” of such curves. Known definitions of the self-linking number apply to non-singular framings: for example, the Frenet framing cannot be used if the curve has inflection points. However, in the discrete proteins the special points are naturally resolved. Consequently, a separate integer topological characteristics can be introduced, which takes into account the intrinsic features of the special points. This works well for the proteins in our analysis, for which we compute integer topological indices associated with the singularities of the Frenet framing. We show how a version of the Calugareanu’s theorem is satisfied for the associated self-linking number of a discrete curve. Since the singularities of the Frenet framing correspond to the structural motifs of proteins, we propose topological indices as a technical tool for the description of the folding dynamics of proteins.
Epidemiological and time series analysis of haemorrhagic fever with renal syndrome from 2004 to 2017 in Shandong Province, China
Authors: Zhang Chao , Fu Xiao , Zhang Yuanying , Nie Cuifang , Li Liu , Cao Haijun , Wang Junmei , Wang Baojia , Yi Shuying , Ye Zhen
Published: October 2019

Shandong Province is an area of China with a high incidence of haemorrhagic fever with renal syndrome (HFRS); however, the general epidemic trend of HFRS in Shandong remains unclear. Therefore, we established a mathematical model to predict the incidence trend of HFRS and used Joinpoint regression analysis, a generalised additive model (GAM), and other methods to evaluate the data. Incidence data from the first half of 2018 were included in a range predicted by a modified sum autoregressive integrated moving average-support vector machine (ARIMA-SVM) combination model. The highest incidence of HFRS occurred in October and November, and the annual mortality rate decreased by 7.3% (p < 0.05) from 2004 to 2017. In cold months, the incidence of HFRS increased by 4%, −1%, and 0.8% for every unit increase in temperature, relative humidity, and rainfall, respectively; in warm months, this incidence changed by 2%, −3%, and 0% respectively. Overall, HFRS incidence and mortality in Shandong showed a downward trend over the past 10 years. In both cold and warm months, the effects of temperature, relative humidity, and rainfall on HFRS incidence varied. A modified ARIMA-SVM combination model could effectively predict the occurrence of HFRS.
Improvements on activated sludge settling and flocculation using biomass-based fly ash as activator
Authors: Chen Xiaoqian , Kong Fangong , Fu Yingjuan , Si Chuanling , Fatehi Pedram
Published: October 2019

Biomass-based fly ash and wastewater are undesired products of the pulping industry. Recently, the use of biomass-based fly ash as an adsorbent (i.e., a valued material) for constituents of wastewater effluents was reported. In this work, the settling performance and properties of activated sludge were studied in the presence of fly ash. Upon mixing, fly ash increased the zeta potential of the sludge from −31 mV to −28 mV, which was due to the release of cationic ions from fly ash in the sludge suspension. The sludge settling and its flocculation affinity were improved through the complexation of flocs and released cation ions from fly ash. The relationships between the protein/polysaccharide (PN/PS) ratio and the content of extracellular polymeric substances (EPS) as well as the ratio and the properties of the sludge flocs were determined. A correlation between the total loosely bound-EPS (LB-EPS) content and the effluent suspended solids (ESS) (Pearson’s coefficient, rp = 0.83) was observed. The performance of sludge flocculation and settling were much more closely correlated with LB-EPS than with tightly bound EPS (TB-EPS). Scanning electron microscopy (SEM) analysis of sludge flocs before and after EPS extraction showed that the sludge flocs contained a large number of microorganisms, mainly Bacillus and Cocci. The amount of LB-EPS had an adverse influence on bioflocculation, effluent clarification and sludge settling affinity. The sludge properties had a moderate relationship with the PN/PS ratio of LB-EPS. Also, no correlation could be established between the ratio and the TB-EPS content.
TCRpMHCmodels: Structural modelling of TCR-pMHC class I complexes
Authors: Jensen Kamilla Kjærgaard , Rantos Vasileios , Jappe Emma Christine , Olsen Tobias Hegelund , Jespersen Martin Closter , Jurtz Vanessa , Jessen Leon Eyrich , Lanzarotti Esteban , Mahajan Swapnil , Peters Bjoern , Nielsen Morten , Marcatili Paolo
Published: October 2019

The interaction between the class I major histocompatibility complex (MHC), the peptide presented by the MHC and the T-cell receptor (TCR) is a key determinant of the cellular immune response. Here, we present TCRpMHCmodels, a method for accurate structural modelling of the TCR-peptide-MHC (TCR-pMHC) complex. This TCR-pMHC modelling pipeline takes as input the amino acid sequence and generates models of the TCR-pMHC complex, with a median Cα RMSD of 2.31 Å. TCRpMHCmodels significantly outperforms TCRFlexDock, a specialised method for docking pMHC and TCR structures. TCRpMHCmodels is simple to use and the modelling pipeline takes, on average, only two minutes. Thanks to its ease of use and high modelling accuracy, we expect TCRpMHCmodels to provide insights into the underlying mechanisms of TCR and pMHC interactions and aid in the development of advanced T-cell-based immunotherapies and rational design of vaccines. The TCRpMHCmodels tool is available at http://www.cbs.dtu.dk/services/TCRpMHCmodels/.
Dynamical transitions during the collapse of inertial holes
Authors: Lu Jiakai , Corvalan Carlos M
Published: October 2019

At the center of a collapsing hole lies a singularity, a point of infinite curvature where the governing equations break down. It is a topic of fundamental physical interest to clarify the dynamics of fluids approaching such singularities. Here, we use scaling arguments supported by high-fidelity simulations to analyze the dynamics of an axisymmetric hole undergoing capillary collapse in a fluid sheet of small viscosity. We characterize the transitions between the different dynamical regimes —from the initial inviscid dynamics that dominate the collapse at early times to the final Stokes dynamics that dominate near the singularity— and demonstrate that the crossover hole radii for these transitions are related to the fluid viscosity by power-law relationships. The findings have practical implications for the integrity of perforated fluid films, such as bubble films and biological membranes, as well as fundamental implications for the physics of fluids converging to a singularity.
Minimization of energy transduction confers resistance to phosphine in the rice weevil, Sitophilus oryzae
Authors: Kim Kyeongnam , Yang Jeong Oh , Sung Jae-Yoon , Lee Ji-Young , Park Jeong Sun , Lee Heung-Sik , Lee Byung-Ho , Ren Yonglin , Lee Dong-Woo , Lee Sung-Eun
Published: October 2019

Infestation of phosphine (PH3) resistant insects threatens global grain reserves. PH3 fumigation controls rice weevil (Sitophilus oryzae) but not highly resistant insect pests. Here, we investigated naturally occurring strains of S. oryzae that were moderately resistant (MR), strongly resistant (SR), or susceptible (wild-type; WT) to PH3 using global proteome analysis and mitochondrial DNA sequencing. Both PH3 resistant (PH3–R) strains exhibited higher susceptibility to ethyl formate-mediated inhibition of cytochrome c oxidase than the WT strain, whereas the disinfectant PH3 concentration time of the SR strain was much longer than that of the MR strain. Unlike the MR strain, which showed altered expression levels of genes encoding metabolic enzymes involved in catabolic pathways that minimize metabolic burden, the SR strain showed changes in the mitochondrial respiratory chain. Our results suggest that the acquisition of strong PH3 resistance necessitates the avoidance of oxidative phosphorylation through the accumulation of a few non-synonymous mutations in mitochondrial genes encoding complex I subunits as well as nuclear genes encoding dihydrolipoamide dehydrogenase, concomitant with metabolic reprogramming, a recognized hallmark of cancer metabolism. Taken together, our data suggest that reprogrammed metabolism represents a survival strategy of SR insect pests for the compensation of minimized energy transduction under anoxic conditions. Therefore, understanding the resistance mechanism of PH3–R strains will support the development of new strategies to control insect pests.
Nestling carcasses from colonially breeding wading birds: patterns of access and energetic relevance for a vertebrate scavenger community
Authors: Gabel Wray , Frederick Peter , Zabala Jabi
Published: October 2019

Energy transfer is fundamental to ecosystem processes, affecting productivity and community structure. Large aggregations of colonially breeding birds are known as nutrient sources through deposition of feces, but also may deposit large quantities of energy in the form of dead nestlings. The magnitude and ecological relevance of this process to the scavenger community is poorly understood. We used trail cameras to monitor the fates of size-appropriate chicken carcasses in heron colonies in order to quantify the proportion of available fallen nestlings that were consumed by scavengers in the Everglades of Florida, USA. Overall, 85% of 160 carcasses were consumed, with Turkey Vultures (Cathartes aura, 47%) and American Alligators (Alligator mississippiensis, 29%) being the primary consumers. Probability of consumption by alligators or vultures was related to distance from nest to water, local nesting density, and colony type. Consumption probabilities of both scavengers in relation to habitat covariates suggested clear resource partitioning promoting coexistence. We estimate fallen nestlings throughout this ecosystem could support 16% of the alligator population and 147 adult Turkey Vultures during a nesting season. This work indicates that fallen nestlings can serve as an important source of energy for scavengers at colonial breeding aggregations, particularly in oligotrophic systems.
Timing of follow-up blood cultures for community-onset bacteremia
Authors: Lee Ching-Chi , Yang Chao-Yung , Hsieh Chih-Chia , Hong Ming-Yuan , Lee Chung-Hsun , Tang Hung-Jen , Ko Wen-Chien
Published: October 2019

Bacteremia is associated with high morbidity and mortality, but the utility and optimal timing of follow-up blood cultures (FUBCs) remain undefined. To assess the optimal timing of FUBCs related to appropriate antibiotic therapy (AAT), adults with community-onset bacteremia and FUBCs after bacteremia onset were retrospectively studied during the 6-year period in two hospitals. Based on the time gap between the initiation of AAT and FUBC sampling, 1,247 eligible patients were categorized as FUBCs prior to AAT (65 patients, 5.2%), 0–3 days (202, 16.2%), 3.1–6 days (470, 37.7%), 6.1–9 days (299, 24.0%), and ≥9 days (211, 16.9%) after AAT. The prognostic impact of the growth of the same bacteria in FUBCs on 30-day mortality was evidenced only in patients with FUBCs at 3.1–6 days after AAT (adjusted odds ratio [AOR], 3.75; P < 0.001), not in those with FUBCs prior to AAT (AOR, 2.86; P = 0.25), 0–3 days (AOR, 0.39; P = 0.08), 6.1–9 days (AOR, 2.19; P = 0.32), and ≥9 days (AOR, 0.41; P = 0.41) of AAT, after adjusting independent factors of 30-day mortality recognized by the multivariable regression in each category. Conclusively, persistent bacteremia in FUBCs added prognostic significance in the management of adults with community-onset bacteremia after 3.1–6 days of AAT.
DNA sequence-dependent chromatin architecture and nuclear hubs formation
Authors: Jabbari Kamel , Chakraborty Maharshi , Wiehe Thomas
Published: October 2019

In this study, by exploring chromatin conformation capture data, we show that the nuclear segregation of Topologically Associated Domains (TADs) is contributed by DNA sequence composition. GC-peaks and valleys of TADs strongly influence interchromosomal interactions and chromatin 3D structure. To gain insight on the compositional and functional constraints associated with chromatin interactions and TADs formation, we analysed intra-TAD and intra-loop GC variations. This led to the identification of clear GC-gradients, along which, the density of genes, super-enhancers, transcriptional activity, and CTCF binding sites occupancy co-vary non-randomly. Further, the analysis of DNA base composition of nucleolar aggregates and nuclear speckles showed strong sequence-dependant effects. We conjecture that dynamic DNA binding affinity and flexibility underlay the emergence of chromatin condensates, their growth is likely promoted in mechanically soft regions (GC-rich) of the lowest chromatin and nucleosome densities. As a practical perspective, the strong linear association between sequence composition and interchromosomal contacts can help define consensus chromatin interactions, which in turn may be used to study alternative states of chromatin architecture.
Stateful Three-Input Logic with Memristive Switches
Authors: Siemon A. , Drabinski R. , Schultis M. J. , Hu X. , Linn E. , Heittmann A. , Waser R. , Querlioz D. , Menzel S. , Friedman J. S.
Published: October 2019

Memristive switches are able to act as both storage and computing elements, which make them an excellent candidate for beyond-CMOS computing. In this paper, multi-input memristive switch logic is proposed, which enables the function X OR (Y NOR Z) to be performed in a single-step with three memristive switches. This ORNOR logic gate increases the capabilities of memristive switches, improving the overall system efficiency of a memristive switch-based computing architecture. Additionally, a computing system architecture and clocking scheme are proposed to further utilize memristive switching for computation. The system architecture is based on a design where multiple computational function blocks are interconnected and controlled by a master clock that synchronizes system data processing and transfer. The clocking steps to perform a full adder with the ORNOR gate are presented along with simulation results using a physics-based model. The full adder function block is integrated into the system architecture to realize a 64-bit full adder, which is also demonstrated through simulation.
Spatial Surface Charge Engineering for Electrochemical Electrodes
Authors: Xie Lingyun , Wang Peng , Qian Yinping , Rao Lujia , Yin Hongjie , Wang Xingyu , Chen Hedong , Zhou Guofu , Nötzel Richard
Published: October 2019

We introduce a novel concept for the design of functional surfaces of materials: Spatial surface charge engineering. We exploit the concept for an all-solid-state, epitaxial InN/InGaN-on-Si reference electrode to replace the inconvenient liquid-filled reference electrodes, such as Ag/AgCl. Reference electrodes are universal components of electrochemical sensors, ubiquitous in electrochemistry to set a constant potential. For subtle interrelation of structure design, surface morphology and the unique surface charge properties of InGaN, the reference electrode has less than 10 mV/decade sensitivity over a wide concentration range, evaluated for KCl aqueous solutions and less than 2 mV/hour long-time drift over 12 hours. Key is a nanoscale charge balanced surface for the right InGaN composition, InN amount and InGaN surface morphology, depending on growth conditions and layer thickness, which is underpinned by the surface potential measured by Kelvin probe force microscopy. When paired with the InN/InGaN quantum dot sensing electrode with super-Nernstian sensitivity, where only structure design and surface morphology are changed, this completes an all-InGaN-based electrochemical sensor with unprecedented performance.
Prion strain-dependent tropism is maintained between spleen and granuloma and relies on lymphofollicular structures
Authors: Al-Dybiat Iman , Moudjou Mohammed , Martin Davy , Reine Fabienne , Herzog Laetitia , Truchet Sandrine , Berthon Patricia , Laude Hubert , Rezaei Human , Andréoletti Olivier , Béringue Vincent , Sibille Pierre
Published: October 2019

In peripherally acquired prion diseases, prions move through several tissues of the infected host, notably in the lymphoid tissue, long before the occurrence of neuroinvasion. Accumulation can even be restricted to the lymphoid tissue without neuroinvasion and clinical disease. Several experimental observations indicated that the presence of differentiated follicular dendritic cells (FDCs) in the lymphoid structures and the strain type are critical determinants of prion extraneural replication. In this context, the report that granulomatous structures apparently devoid of FDCs could support prion replication raised the question of the requirements for prion lymphotropism. The report also raised the possibility that nonlymphoid tissue-tropic prions could actually target these inflammatory structures. To investigate these issues, we examined the capacity of closely related prions, albeit with opposite lymphotropism (or FDC dependency), for establishment in experimentally-induced granuloma in ovine PrP transgenic mice. We found a positive correlation between the prion capacity to accumulate in the lymphoid tissue and granuloma, regardless of the prion detection method used. Surprisingly, we also revealed that the accumulation of prions in granulomas involved lymphoid-like structures associated with the granulomas and containing cells that stain positive for PrP, Mfge-8 but not CD45 that strongly suggest FDCs. These results suggest that the FDC requirement for prion replication in lymphoid/inflammatory tissues may be strain-dependent.
Velocity-dependent friction enhances tribomechanical differences between monolayer and multilayer graphene
Authors: Ptak F. , Almeida C. M. , Prioli R.
Published: October 2019

The influence of sliding speed in the nanoscale friction forces between a silicon tip and monolayer and multilayer graphene were investigated with the use of an atomic force microscope. We found that the friction forces increase linearly with the logarithm of the sliding speed in a highly layer-dependent way. The increase in friction forces with velocity is amplified at the monolayer. The amplification of the friction forces with velocity results from the introduction of additional corrugation in the interaction potential driven by the tip movement. This effect can be interpreted as a manifestation of local thermally induced surface corrugations in nanoscale influencing the hopping dynamics of the atoms at the contact. These experimental observations were explained by modeling the friction forces with the thermally activated Prandtl-Tomlinson model. The model allowed determination of the interaction potential between tip and graphene, critical forces, and attempt frequencies of slip events. The latter was observed to be dominated by the effective contact stiffness and independent of the number of layers.
Raman Spectroscopy for Rapid Evaluation of Surgical Margins during Breast Cancer Lumpectomy
Authors: Zúñiga Willie C. , Jones Veronica , Anderson Sarah M. , Echevarria Alex , Miller Nathaniel L. , Stashko Connor , Schmolze Daniel , Cha Philip D. , Kothari Ragini , Fong Yuman , Storrie-Lombardi Michael C.
Published: October 2019

Failure to precisely distinguish malignant from healthy tissue has severe implications for breast cancer surgical outcomes. Clinical prognoses depend on precisely distinguishing healthy from malignant tissue during surgery. Laser Raman spectroscopy (LRS) has been previously shown to differentiate benign from malignant tissue in real time. However, the cost, assembly effort, and technical expertise needed for construction and implementation of the technique have prohibited widespread adoption. Recently, Raman spectrometers have been developed for non-medical uses and have become commercially available and affordable. Here we demonstrate that this current generation of Raman spectrometers can readily identify cancer in breast surgical specimens. We evaluated two commercially available, portable, near-infrared Raman systems operating at excitation wavelengths of either 785 nm or 1064 nm, collecting a total of 164 Raman spectra from cancerous, benign, and transitional regions of resected breast tissue from six patients undergoing mastectomy. The spectra were classified using standard multivariate statistical techniques. We identified a minimal set of spectral bands sufficient to reliably distinguish between healthy and malignant tissue using either the 1064 nm or 785 nm system. Our results indicate that current generation Raman spectrometers can be used as a rapid diagnostic technique distinguishing benign from malignant tissue during surgery.
Investigation of multimorbidity and prevalent disease combinations in older Irish adults using network analysis and association rules
Authors: Hernández Belinda , Reilly Richard B. , Kenny Rose Anne
Published: October 2019

Multimorbidity (the presence of multiple medical conditions) is well known to increase with age. People with multimorbidities often have higher physical and functional decline as well as increased mortality. Despite growing evidence that integrated and collaborative care improves many undesirable outcomes of multimorbidity, the majority of health systems are based around treating individual diseases. A pattern analysis of comorbidities using network graphs and a novel use of association rules was conducted to investigate disease associations on 6101 Irish adults aged 50+. The complex network of morbidities and differences in the prevalence and interactions of these morbidities by sex was also assessed. Gender specific differences in disease prevalence was found for 22/31 medical conditions included in this study. Females had a more complex network of disease associations than males with strong associations found between arthritis, osteoporosis and thyroid issues among others. To assess the strength of these associations we provide probabilities of being diagnosed with a comorbid condition given the presence of an index morbidity for 639 pairwise combinations. This information can be used to guide clinicians in deciding which comorbidities should be incorporated into comprehensive assessments in addition to anticipating likely future morbidities and thus developing prevention strategies.
Dysregulated liver lipid metabolism and innate immunity associated with hepatic steatosis in neonatal BBdp rats and NOD mice
Authors: Serrano D. , Crookshank J. A. , Morgan B. S. , Mueller R. W. , Paré M.-F. , Marandi L. , Poussier P. , Scott F. W.
Published: October 2019

In a previous study we reported that prediabetic rats have a unique gene signature that was apparent even in neonates. Several of the changes we observed, including enhanced expression of pro-inflammatory genes and dysregulated UPR and metabolism genes were first observed in the liver followed by the pancreas. In the present study we investigated further early changes in hepatic innate immunity and metabolism in two models of type 1 diabetes (T1D), the BBdp rat and NOD mouse. There was a striking increase in lipid deposits in liver, particularly in neonatal BBdp rats, with a less striking but significant increase in neonatal NOD mice in association with dysregulated expression of lipid metabolism genes. This was associated with a decreased number of extramedullary hematopoietic clusters as well as CD68+ macrophages in the liver of both models. In addition, PPARɣ and phosphorylated AMPKα protein were decreased in neonatal BBdp rats. BBdp rats displayed decreased expression of antimicrobial genes in neonates and decreased M2 genes at 30 days. This suggests hepatic steatosis could be a common early feature in development of T1D that impacts metabolic homeostasis and tolerogenic phenotype in the prediabetic liver.
Color preferences affect learning in zebrafish, Danio rerio
Authors: Roy Tamal , Suriyampola Piyumika S. , Flores Jennifer , López Melissa , Hickey Collin , Bhat Anuradha , Martins Emília P.
Published: October 2019

Animals may exhibit preference for colors that match their environment or the resources in the environment. These preferences may impact ability to learn associations with these colors and revert the associations when the reward contingency is modified. We used zebrafish Danio rerio from four populations to test if color preferences impact associative and reversal learning ability. First, we tested if preference for blue or green impact associative ability. We subjected individual fish through eight trials to associate a social stimulus with blue or green. Next, we tested if preference for red or green impact associative reversal learning ability. We trained fish in groups of three to associate a social stimulus with red or green over three trials, and reversed the reward contingency during the following session. Results showed that zebrafish preferred green over blue and domesticated fish chose green more than blue when there was a reward attached. Zebrafish also preferred red over green. Fish from one wild population learned with both colors and reversed learning only from green to red and not vice-versa. Fish from another population showed an overwhelming preference for red irrespective of what was rewarded. Domesticated fish did not show reversal learning ability.
Light-induced Nrf2−/− mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel
Authors: Wang Kai , Zheng Min , Lester Kaitlyn Lee , Han Zongchao
Published: October 2019

Elevated oxidative stress and associated reactive oxygen species (ROS) accumulation are hallmarks in the induction and progression of age-related macular degeneration (AMD). By exposing nuclear factor erythroid 2-related factor (Nrf2) knockout (Nrf2−/−) mice to mild white light, we were able to generate a new dry-AMD like murine model to the study. This animal model developed phenotypes of photoreceptor degeneration, retinal function impairment, ROS accumulation, and inflammation reaction in a relatively shorter time. In the treatment of this animal model we utilized an antioxidative and water soluble nanoparticle known as glycol chitosan coated cerium oxide nanoparticles (GCCNP). The delivery of GCCNP protected retina against progressive retinal oxidative damage. Further combination of GCCNP with alginate-gelatin based injectable hydrogel provided synergistic antioxidant effects and achieved a more rapid recovery of the retinal pigment epithelium and photoreceptor cells. This combined treatment technique has the potential to translate into a clinical intervention for the treatment of AMD.