bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for an effect of receptor density on ligand occupancy and agonist EC50
Authors: Jarvis Gavin E. , Thompson Andrew J. 
Published: December 2019

AbstractDrug-receptor interaction theory predicts that proportional receptor occupancy is a function of ligand concentration as defined by a ligand-receptor affinity constant, and is independent of receptor density. However, we previously observed that the EC50 of 5-HT reduced as the density of 5-HT3 receptors increased, suggesting an effect of receptor density on occupancy. The current study was designed to maximise variability in experimentally observed currents and confirm this apparent contradiction prospectively. Xenopus oocytes were injected with RNA encoding 5-HT3A receptors under conditions designed to achieve varying receptor expression levels and 5-HT-evoked currents measured using two electrode voltage clamp. Results from 99 oocytes showed that as the maximal peak current increased from 0.05 µA to 12.1 µA there was a 3.7-fold reduction in EC50. Since occupancy and conductance are directly related in this system, this indicates that for a given concentration of 5-HT, proportional occupancy increases with increased receptor density. We conclude that normalising data masks this correlation, and can result in reduced accuracy of pharmacological measurements. We propose a mechanistic explanation for our observations.
Cranial irradiation mediated spine loss is sex-specific and complement receptor-3 dependent in male mice
Authors: Hinkle Joshua J. , Olschowka John A. , Love Tanzy M. , Williams Jacqueline P. , O’Banion M. Kerry 
Published: December 2019

AbstractCranial irradiation is the main therapeutic treatment for primary and metastatic malignancies in the brain. However, cranial radiation therapy produces long-term impairment in memory, information processing, and attention that contribute to a decline in quality of life. The hippocampal neural network is fundamental for proper storage and retrieval of episodic and spatial memories, suggesting that hippocampal signaling dysfunction could be responsible for the progressive memory deficits observed following irradiation. Previous rodent studies demonstrated that irradiation induces significant loss in dendritic spine number, alters spine morphology, and is associated with behavioral task deficits. Additionally, the literature suggests a common mechanism in which synaptic elimination via microglial-mediated phagocytosis is complement dependent and associated with cognitive impairment in aging as well as disease. We demonstrate sexual dimorphisms in irradiation-mediated alterations of microglia activation markers and dendritic spine density. Further, we find that the significant dendritic spine loss observed in male mice following irradiation is microglia complement receptor 3 (CR3)-dependent. By identifying sex-dependent cellular and molecular factors underlying irradiation-mediated spine loss, therapies can be developed to counteract irradiation-induced cognitive decline and improve patient quality of life.
Morphology of planktonic zoeal stages of Palicus caronii (Decapoda, Brachyura), identified by DNA barcoding, provides novelties to Palicoidea larval systematics
Authors: Di Muzio Giorgia , Mussat Sartor Rocco , Nurra Nicola , Battuello Marco , Pessani Daniela , Cervella Piero , Cuesta Jose A. 
Published: December 2019

AbstractThe zoeal development of the brachyuran crab, Palicus caronii, comprises two zoeal stages and the morphology is described and illustrated in detail. The zoeae were collected in plankton samples from the Southern Ligurian Sea (Western Mediterranean). Although the morphology of the larval stages of this species was unknown, a combination of characters allowed the zoeae to initially be assigned to the Palicidae, based on the previous unique known first zoeal description of one species of this family. Later, the identification of the larvae as Palicus caronii was confirmed through molecular analysis. The morphological features of the zoeae that characterize the Palicidae and separate them from the Crossotonotidae are confirmed. Also, the larval development comprising only two zoeal stages observed in Palicus caronii, the peculiar and uncommon carapace surface setation, and the presence of anterodorsal and posterodorsal sensory dorsal organs suggest that these characters could be common to the Palicoidea.
In situ Microfluidic Cryofixation for Cryo Focused Ion Beam Milling and Cryo Electron Tomography
Authors: Fuest Marie , Schaffer Miroslava , Nocera Giovanni Marco , Galilea-Kleinsteuber Rodrigo I. , Messling Jan-Erik , Heymann Michael , Plitzko Jürgen M. , Burg Thomas P. 
Published: December 2019

AbstractWe present a microfluidic platform for studying structure-function relationships at the cellular level by connecting video rate live cell imaging with in situ microfluidic cryofixation and cryo-electron tomography of near natively preserved, unstained specimens. Correlative light and electron microscopy (CLEM) has been limited by the time required to transfer live cells from the light microscope to dedicated cryofixation instruments, such as a plunge freezer or high-pressure freezer. We recently demonstrated a microfluidic based approach that enables sample cryofixation directly in the light microscope with millisecond time resolution, a speed improvement of up to three orders of magnitude. Here we show that this cryofixation method can be combined with cryo-electron tomography (cryo-ET) by using Focused Ion Beam milling at cryogenic temperatures (cryo-FIB) to prepare frozen hydrated electron transparent sections. To make cryo-FIB sectioning of rapidly frozen microfluidic channels achievable, we developed a sacrificial layer technique to fabricate microfluidic devices with a PDMS bottom wall <5 µm thick. We demonstrate the complete workflow by rapidly cryo-freezing Caenorhabditis elegans roundworms L1 larvae during live imaging in the light microscope, followed by cryo-FIB milling and lift out to produce thin, electron transparent sections for cryo-ET imaging. Cryo-ET analysis of initial results show that the structural preservation of the cryofixed C. elegans was suitable for high resolution cryo-ET work. The combination of cryofixation during live imaging enabled by microfluidic cryofixation with the molecular resolution capabilities of cryo-ET offers an exciting avenue to further advance space-time correlative light and electron microscopy (st-CLEM) for investigation of biological processes at high resolution in four dimensions.
Potential chiral fluorescent molecular probes based on an α,β-unsaturated ketone for anion detection
Authors: Li Congshu , Liu Lixia , Pan Weitong , Chen Yanmei , Shang Xuefang , Wang Yingling , Wang Tianyun , Xu Xiufang 
Published: December 2019

AbstractA series of potential chiral compounds containing an α,β-unsaturated ketone was developed for anion detection. The interplay of compounds and biological momentous anions (Cl−, H2PO4−, I−, AcO−, HS−, F−, and Br−) was evaluated by UV-vis experiments, fluorescence experiments, and electrochemical tests. By comparison, compound 1 had the best selectivity and compound 5 had the strongest binding ability among the five compounds. And compound 5 had the highest sensitivity to H2PO4− among the measured anions, and it also can be applied to actual samples, the content of H2PO4− tested in the potassium dihydrogen phosphate fertilizer solution reached above 97.5% of the marked content, and the recovery rates were within the range of 98.5–99.1%, attesting that this method was reliable for the test of H2PO4− in fertilizer. Through HRMS titration, circular dichroism and optical rotation experiments, the probable interacted mechanism was proved that the interaction site was the C=C of the α,β-unsaturated ketone structure. In addition, the interacted mechanism was researched from the perspective of chirality. Furthermore, theoretical investigation analysis was introduced to reveal that the roles of molecular frontier orbitals in molecular interplay were determined. Therefore, this series of potential chiral compounds has potential application prospects in anion recognition.
Negative optokinetic afternystagmus in larval zebrafish demonstrates set-point adaptation
Authors: Lin Ting-Feng , Mohammadi Mohammad , Fathalla Ahmed M. , Pul Duygu , Lüthi Dennis , Romano Fausto , Straumann Dominik , Cullen Kathleen E. , Chacron Maurice J. , Huang Melody Ying-Yu 
Published: December 2019

AbstractMotor learning is essential to maintain accurate behavioral responses. We used a larval zebrafish model to study ocular motor learning behaviors. During a sustained period of optokinetic stimulation in 5-day-old wild-type zebrafish larvae the slow-phase eye velocity decreased over time. Then interestingly, a long-lasting and robust negative optokinetic afternystagmus (OKAN) was evoked upon light extinction. The slow-phase velocity, the quick-phase frequency, and the decay time constant of the negative OKAN were dependent on the stimulus duration and the adaptation to the preceding optokinetic stimulation. Based on these results, we propose a sensory adaptation process during continued optokinetic stimulation, which, when the stimulus is removed, leads to a negative OKAN as the result of a changed retinal slip velocity set point, and thus, a sensorimotor memory. The pronounced negative OKAN in larval zebrafish not only provides a practical solution to the hitherto unsolved problems of observing negative OKAN, but also, and most importantly, can be readily applied as a powerful model for studying sensorimotor learning and memory in vertebrates.
Frailty is Associated with an Increased Risk of Major Adverse Outcomes in Elderly Patients Following Surgical Treatment of Hip Fracture
Authors: Chen Chiu-Liang , Chen Chun-Min , Wang Chun-Yi , Ko Po-Wei , Chen Chung-Hwan , Hsieh Chen-Pu , Chiu Herng-Chia 
Published: December 2019

AbstractWe intended to explore the effect of level of frailty on, and relationship with, 1-, 3-, and 6-month postoperative emergency department visits, readmissions, and mortality. This is a prospective multicenter observational cohort study design. Patients aged 50 years or older treated for hip fracture (n = 245) were taken from Orthopedic wards in one medical center (n = 131) and one district hospital (n = 114) in Changhua County, Taiwan. Frailty was defined as measured by the validated Clinical Frailty Scale and categorized as robust, pre-frail, and frail. We used Kaplan-Meier analysis to estimate survival rates and Cox regression to estimate the risk of frailty associated with adverse outcomes. To examine the longitudinal associations between frailty and adverse outcome, the cross-lagged models were explored. Of the 245 patients, 55 (22.4%) were classified as frail, 113 (46.1%) as pre-frail, and 77 (31.4%) as robust. More cumulative events occurred for frail than for robust patients for each adverse outcome. Frailty has long-term effect on each adverse outcome after discharge, rather than the effect simultaneously. Targeting pre-frailty and frailty is essential for prevent adverse outcomes and improving the overall health of older adults after discharge for hip fracture.
A qPCR method for genome editing efficiency determination and single-cell clone screening in human cells
Authors: Li Bo , Ren Naixia , Yang Lele , Liu Junhao , Huang Qilai 
Published: December 2019

AbstractCRISPR/Cas9 technology has been widely used for targeted genome modification both in vivo and in vitro. However, an effective method for evaluating genome editing efficiency and screening single-cell clones for desired modification is still lacking. Here, we developed this real time PCR method based on the sensitivity of Taq DNA polymerase to nucleotide mismatch at primer 3′ end during initiating DNA replication. Applications to CRISPR gRNAs targeting EMX1, DYRK1A and HOXB13 genes in Lenti-X 293 T cells exhibited comprehensive advantages. Just in one-round qPCR analysis using genomic DNA from cells underwent CRISPR/Cas9 or BE4 treatments, the genome editing efficiency could be determined accurately and quickly, for indel, HDR as well as base editing. When applied to single-cell clone screening, the genotype of each cell colony could also be determined accurately. This method defined a rigorous and practical way in quantify genome editing events.
Quantum Mechanisms of Electron and Positron Acceleration through Nonlinear Compton Scatterings and Nonlinear Breit-Wheeler Processes in Coherent Photon Dominated Regime
Authors: Zhang Bo , Zhang Zhimeng , Deng Zhi-gang , Teng Jian , He Shu-kai , Hong Wei , Zhou Weimin , Gu Yuqiu 
Published: December 2019

AbstractElectric force is presently the only means in laboratory to accelerate charged particles to high energies, corresponding acceleration processes are classical and continuous. Here we report on how to accelerate electrons and positrons to high energies using ultra intense lasers (UIL) through two quantum processes, nonlinear Compton scattering and nonlinear Breit-Wheeler process. In the coherent photon dominated regime of these two processes, the former can effectively boost electrons/positrons and the latter can produce high energy electrons and positrons with low energy γ photons. The energy needed for such quantum acceleration (QA) is transferred from large numbers of coherent laser photons through the two quantum processes. QA also collimate the generated high energy electrons and positrons along the laser axis and the effective acceleration distance is of microscopic dimensions. Proof of principle QA experiment can be performed on 100 petawatt (PW) scale lasers which are in building or planning.
Modeling recovery of natural gas from hydrate reservoirs with carbon dioxide sequestration: Validation with Iġnik Sikumi field data
Authors: Palodkar Avinash V. , Jana Amiya K. 
Published: December 2019

AbstractFundamental understanding of guest gas replacement in hydrate reservoirs is crucial for the enhanced recovery of natural gas and carbon dioxide (CO2) sequestration. To gain physical insight into this exchange process, this work aims at developing and validating a clathrate hydrate model for gas replacement. Most of the practical concerns associated with naturally occurring gas hydrates, including hydrate formation and dissociation in interstitial pore space between distributed sand particles in the presence of salt ions and in irregular nanometer-sized pores of those particles, irregularity in size of particles and shape of their pores, interphase dynamics during hydrate formation and decay, and effect of surface tension, are addressed. An online parameter identification technique is devised for automatic tuning of model parameters in the field. This model is employed to predict the laboratory-scale data for methane hydrate formation and decomposition. Subsequently, the model is validated with the field data of the Prudhoe Bay Unit on the Alaska North Slope during 2011 and 2012. In this Iġnik Sikumi field experiment, mixed CO2 (i.e., CO2 + N2) is used as a replacement agent for natural gas recovery. It is observed that the proposed formulation secures a promising performance with a maximum absolute average relative deviation (AARD) of about 2.83% for CH4, which is even lower, 0.84% for CO2 and 1.67% for N2.
Finnish Parkinson’s disease study integrating protein-protein interaction network data with exome sequencing analysis
Authors: Siitonen Ari , Kytövuori Laura , Nalls Mike A. , Gibbs Raphael , Hernandez Dena G. , Ylikotila Pauli , Peltonen Markku , Singleton Andrew B. , Majamaa Kari 
Published: December 2019

AbstractVariants associated with Parkinson’s disease (PD) have generally a small effect size and, therefore, large sample sizes or targeted analyses are required to detect significant associations in a whole exome sequencing (WES) study. Here, we used protein-protein interaction (PPI) information on 36 genes with established or suggested associations with PD to target the analysis of the WES data. We performed an association analysis on WES data from 439 Finnish PD subjects and 855 controls, and included a Finnish population cohort as the replication dataset with 60 PD subjects and 8214 controls. Single variant association (SVA) test in the discovery dataset yielded 11 candidate variants in seven genes, but the associations were not significant in the replication cohort after correction for multiple testing. Polygenic risk score using variants rs2230288 and rs2291312, however, was associated to PD with odds ratio of 2.7 (95% confidence interval 1.4–5.2; p < 2.56e-03). Furthermore, an analysis of the PPI network revealed enriched clusters of biological processes among established and candidate genes, and these functional networks were visualized in the study. We identified novel candidate variants for PD using a gene prioritization based on PPI information, and described why these variants may be involved in the pathogenesis of PD.
Combined Ultrasound/Microwave Chemocatalytic Method for Selective Conversion of Cellulose into Lactic Acid
Authors: Tallarico Sofia , Costanzo Paola , Bonacci Sonia , Macario Anastasia , Di Gioia Maria Luisa , Nardi Monica , Procopio Antonio , Oliverio Manuela 
Published: December 2019

AbstractCellulose is the main component of lignocellulosic biomass. Its direct chemocatalytic conversion into lactic acid (LA), a powerful biobased chemical platform, represents an important, and more easily scalable alternative to the fermentative way. In this paper, we present the selective hydrothermal conversion of cellulose and simple sugars into LA, under mild reaction conditions in presence of ErCl3 grafted on the mesoporous silica (MCM-41) surface. High yields and selectivity were obtained for the conversion of sugars under microwave (MW) irradiation at a relatively low temperature (200 °C) and short reaction times (10 min) under microwave (MW) irradiation. Ultrasounds (US) pre-treatment was investigated to reduce the cellulose crystallinity, before the MW-assisted conversion, providing LA with a yield of 64% within 90 min at 220 °C below the subcritical water conditions with increased operational safety. We finally discuss the scalability of the process and the recyclability of the catalyst.
Mechanical feedback cooling assisted by optical cavity cooling of the thermal vibration of a microcantilever
Authors: Kawamura Y. 
Published: December 2019

AbstractThis study describes a new two-step process to cool the thermal vibration of microcantilevers. The process combines active mechanical feedback cooling and optical cavity cooling. A micro-Fabry–Perot interferometer, built in-house, is set atop a microcantilever to measure the vibration amplitude, the high optical power density of which induces cavity cooling in the optical cavity. Using a two-step cooling procedure, the equivalent temperature of the thermal vibration of a microcantilever is lowered from room temperature to the theoretical cooling limit of 0.063 K, a much lower temperature than that achieved via simple cavity cooling (18 K), and then by mechanical feedback cooling (0.135 K) obtained for the same type of microcantilevers in previous studies. This experimental demonstration showcases a new type of cooling process of the amplitude of thermal vibration for micro-mechanical resonators to a lower temperature and does not need additional cooling using a conventional cryogenic refrigerator.
Immunity to Influenza is dependent on MHC II polymorphism: study with 2 HLA transgenic strains
Authors: Luckey David , Weaver Eric A. , Osborne Douglas G. , Billadeau Daniel D. , Taneja Veena 
Published: December 2019

AbstractMajor histocompatibility complex II (MHC II) molecules are involved in antigen presentation and the development of a functional adaptive immune response. Evolutionary selection for MHC molecules that effectively clear infectious agents provides an advantage to humans. However, certain class II molecules are associated with autoimmune diseases. In this study we infected autoimmune-susceptible DRB1*0401.AEo and non-susceptible *0402.AEo mice with H1N1 influenza and determined clearance and protective immunity to H3N2 virus. *0401 mice generated a robust TLR-triggered immune response and cleared H1N1 influenza virus infection. After vaccination and challenge with H1N1, *0401 mice, when challenged with H3N2, generated cross-protective immunity to heterosubtypic H3N2 influenza strain whereas *0402 mice cleared the H1N1 infection but did not generate cross-protective immunity against the H3N2 influenza strain. The intracellular trafficking route of MHCII revealed that *0401 molecules traffic through the late endosome/lysosomes while *0402 molecules traffic into early endosomes. This suggested that trafficking of MHCII could affect the functional output of the innate immune response and clearance of viral infections. Also, DRB1*0401 mice live longer than HLA-DRB1*0402 mice. The study provides a potential hypothesis for evolutionary selection of *0401 molecule, even though it is associated with autoreactivity, which may be dependent on the availability of peptide repertoire of self-antigens.
Au-PDA@SiO2 core-shell nanospheres decorated rGO modified electrode for electrochemical sensing of cefotaxime
Authors: Khan M. Z. H. , Daizy M. , Tarafder C. , Liu X. 
Published: December 2019

AbstractIn this work, we have successfully synthesized core-shell structured Au-PDA@SiO2 nanospheres and decorated on reduced graphene oxide (rGO) modified glassy carbon electrode for the electrochemical detection of cefotaxime. The one-pot hydrothermal method was used to synthesis core-shell nanostructures by loading Au nanoparticles on polydopamine (PDA) coated SiO2 nanospheres. The as-prepared Au-PDA@SiO2 nanospheres were used to fabricate electrochemically reduced graphene oxide (rGO) modified glassy carbon electrode (Au-PDA@SiO2/rGO/GCE) for electrochemical determination of cefotaxime. Scanning electron microscopy, powder x-ray diffraction, transmission electron microscopy, and Fourier-transform infrared spectroscopy were used to confirm the structure and morphology of the as-prepared nanospheres. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were performed for electrochemical characterizations different modified electrodes. It was revealed that the nanocomposite modified electrodes exhibited excellent electrochemical performances for electrooxidation of target analytes and could achieve ultra-sensitive detections. A linear relationship was observed between peak currents and concentrations in the ranges of 1.0 × 10−9 to 5.0 × 10−8 M (R2 = 0.9877), and 1.0 × 10−7 to 5.0 × 10−6 M (R2 = 0.9821) for cefotaxime with a detection limit (S/N = 3) of 1.0 × 10−10 M. It can be deduced that the proposed sensor is suitable for the sensitive detection of cefotaxime in pharmaceutical samples.