bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Classification of White Blood Cell Leukemia with Improved Swarm Optimization of Deep Features
Authors: Sahlol Ahmed T. , Kollmannsberger Philip , Ewees Ahmed A.
Published: February 2020

White Blood Cell (WBC) Leukaemia is caused by excessive production of leukocytes in the bone marrow, and image-based detection of malignant WBCs is important for its detection. Convolutional Neural Networks (CNNs) present the current state-of-the-art for this type of image classification, but their computational cost for training and deployment can be high. We here present an improved hybrid approach for efficient classification of WBC Leukemia. We first extract features from WBC images using VGGNet, a powerful CNN architecture, pre-trained on ImageNet. The extracted features are then filtered using a statistically enhanced Salp Swarm Algorithm (SESSA). This bio-inspired optimization algorithm selects the most relevant features and removes highly correlated and noisy features. We applied the proposed approach to two public WBC Leukemia reference datasets and achieve both high accuracy and reduced computational complexity. The SESSA optimization selected only 1 K out of 25 K features extracted with VGGNet, while improving accuracy at the same time. The results are among the best achieved on these datasets and outperform several convolutional network models. We expect that the combination of CNN feature extraction and SESSA feature optimization could be useful for many other image classification tasks.
Modeling membrane nanotube morphology: the role of heterogeneity in composition and material properties
Authors: Alimohamadi Haleh , Ovryn Ben , Rangamani Padmini
Published: February 2020

Membrane nanotubes are dynamic structures that may connect cells over long distances. Nanotubes are typically thin cylindrical tubes, but they may occasionally have a beaded architecture along the tube. In this paper, we study the role of membrane mechanics in governing the architecture of these tubes and show that the formation of bead-like structures along the nanotubes can result from local heterogeneities in the membrane either due to protein aggregation or due to membrane composition. We present numerical results that predict how membrane properties, protein density, and local tension compete to create a phase space that governs the morphology of a nanotube. We also find that there exists a discontinuity in the energy that impedes two beads from fusing. These results suggest that the membrane-protein interaction, membrane composition, and membrane tension closely govern the tube radius, number of beads, and the bead morphology.
Gaze-in-wild: A dataset for studying eye and head coordination in everyday activities
Authors: Kothari Rakshit , Yang Zhizhuo , Kanan Christopher , Bailey Reynold , Pelz Jeff B. , Diaz Gabriel J.
Published: February 2020

The study of gaze behavior has primarily been constrained to controlled environments in which the head is fixed. Consequently, little effort has been invested in the development of algorithms for the categorization of gaze events (e.g. fixations, pursuits, saccade, gaze shifts) while the head is free, and thus contributes to the velocity signals upon which classification algorithms typically operate. Our approach was to collect a novel, naturalistic, and multimodal dataset of eye + head movements when subjects performed everyday tasks while wearing a mobile eye tracker equipped with an inertial measurement unit and a 3D stereo camera. This Gaze-in-the-Wild dataset (GW) includes eye + head rotational velocities (deg/s), infrared eye images and scene imagery (RGB + D). A portion was labelled by coders into gaze motion events with a mutual agreement of 0.74 sample based Cohen’s κ. This labelled data was used to train and evaluate two machine learning algorithms, Random Forest and a Recurrent Neural Network model, for gaze event classification. Assessment involved the application of established and novel event based performance metrics. Classifiers achieve ~87% human performance in detecting fixations and saccades but fall short (50%) on detecting pursuit movements. Moreover, pursuit classification is far worse in the absence of head movement information. A subsequent analysis of feature significance in our best performing model revealed that classification can be done using only the magnitudes of eye and head movements, potentially removing the need for calibration between the head and eye tracking systems. The GW dataset, trained classifiers and evaluation metrics will be made publicly available with the intention of facilitating growth in the emerging area of head-free gaze event classification.
Downregulation of peripheral PTGS2/COX-2 in response to valproate treatment in patients with epilepsy
Authors: Rawat Chitra , Kutum Rintu , Kukal Samiksha , Srivastava Ankit , Dahiya Ujjwal Ranjan , Kushwaha Suman , Sharma Sangeeta , Dash Debasis , Saso Luciano , Srivastava Achal K. , Kukreti Ritushree
Published: February 2020

Antiepileptic drug therapy has significant inter-patient variability in response towards it. The current study aims to understand this variability at the molecular level using microarray-based analysis of peripheral blood gene expression profiles of patients receiving valproate (VA) monotherapy. Only 10 unique genes were found to be differentially expressed in VA responders (n = 15) and 6 genes in the non-responders (n = 8) (fold-change >2, p < 0.05).PTGS2which encodes cyclooxygenase-2, COX-2, showed downregulation in the responders compared to the non-responders.PTGS2/COX-2 mRNA profiles in the two groups corresponded to their plasma profiles of the COX-2 product, prostaglandin E2(PGE2). Since COX-2 is believed to regulate P-glycoprotein (P-gp), a multidrug efflux transporter over-expressed at the blood-brain barrier (BBB) in drug-resistant epilepsy, the pathway connecting COX-2 and P-gp was further exploredin vitro. Investigation of the effect of VA upon the brain endothelial cells (hCMEC/D3) in hyperexcitatory conditions confirmed suppression of COX-2-dependent P-gp upregulation by VA. Our findings suggest that COX-2 downregulation by VA may suppress seizure-mediated P-gp upregulation at the BBB leading to enhanced drug delivery to the brain in the responders. Our work provides insight into the association of peripheralPTGS2/COX-2 expression with VA efficacy and the role of COX-2 as a potential therapeutic target for developing efficacious antiepileptic treatment.
Effective Attributes Quantification to Bridge Gap between Elastic Properties and Reservoir Parameters in Self-Resource Rocks
Authors: Abid Muhammad , Geng Jianhua
Published: February 2020

The successful production of unconventional resources such as shale gas is highly dependent on its two reservoir properties, organic matter and rock brittleness. High resolution spatially characterization of these two unconventional reservoir properties needs surface reflection seismic data. However, to delineate these two parameters on seismic scale is a challenging task because poor correlation is observed between these parameters and elastic properties of the rock. To encounter this adversity in current study we proposed effective attributes method in which organic shale reservoir properties are divided into their hard and soft elastic response. From the analysis of worldwide laboratory dataset, we find that hard and soft components have shown us much better linear correlation with P- and S- wave impedance. The proposed effective attributes, helped us to reduce the gap between unconventional reservoir properties and seismic characteristics. These attributes are the main controlling factor for rock elastic properties and exhibit information about hydrocarbon generation capacity and rock brittleness. A well data example from Sembar shale has also shown successful results for proposed effective attributes methodology. These attributes application on inverted P-wave impedance seismic data of employed organic shale reservoir have shown productive results to quantify its unconventional prospect on seismic scale. The approach used in this study can be confidently employed to assess unconventional reservoir potential in other parts of the world.
Correlative Study of Enhanced Excitonic Emission in ZnO Coated with Al Nanoparticles using Electron and Laser Excitation
Authors: Fiedler Saskia , Lem Laurent O. Lee Cheong , Ton-That Cuong , Schleuning Markus , Hoffmann Axel , Phillips Matthew R.
Published: February 2020

Recently, metal nanoparticle surface coatings have been found to significantly enhance the ultra-violet luminescence intensity from ZnO, providing a viable means to mitigate optical losses and improve LED performance. Although there is general agreement that resonantly excited Localized Surface Plasmons (LSPs) in metal nanoparticles can directly couple to excitons in the semiconductor increasing their spontaneous emission rate, the exact mechanisms involved in this phenomenon are currently not fully understood. In this work, LSP-exciton coupling in bulk and nanostructured ZnO coated with a 2 nm Al nanoparticle layer is investigated using correlative photoluminescence and depth-resolved cathodoluminescence and time-resolved photoluminescence spectroscopy. Temperature-resolved cathodoluminescence and photoluminescence measurements from 10 K to 250 K show free exciton (FX) emission enhancement factors up to 12x at 80 K, and reveal that the FX couple more efficiently to the LSPs compared to the localized donor-bound excitons. A strong polarization dependence between the LSPs and FX is observed where FX transitions are more strongly enhanced when polarized in the same direction as the electric field of the incident excitation, which is different for laser and electron beam sources. This result indicates that selective enhancement of the excitonic emission peaks in the ZnO coated with Al nanoparticles can be achieved by choosing the appropriate ZnO substrate orientation.
Record statistics of bursts signals the onset of acceleration towards failure
Authors: Kádár Viktória , Pál Gergő , Kun Ferenc
Published: February 2020

Forecasting the imminent catastrophic failure has a high importance for a large variety of systems from the collapse of engineering constructions, through the emergence of landslides and earthquakes, to volcanic eruptions. Failure forecast methods predict the lifetime of the system based on the time-to-failure power law of observables describing the final acceleration towards failure. We show that the statistics of records of the event series of breaking bursts, accompanying the failure process, provides a powerful tool to detect the onset of acceleration, as an early warning of the impending catastrophe. We focus on the fracture of heterogeneous materials using a fiber bundle model, which exhibits transitions between perfectly brittle, quasi-brittle, and ductile behaviors as the amount of disorder is increased. Analyzing the lifetime of record size bursts, we demonstrate that the acceleration starts at a characteristic record rank, below which record breaking slows down due to the dominance of disorder in fracturing, while above it stress redistribution gives rise to an enhanced triggering of bursts and acceleration of the dynamics. The emergence of this signal depends on the degree of disorder making both highly brittle fracture of low disorder materials, and ductile fracture of strongly disordered ones, unpredictable.
Integrative data modeling from lung and lymphatic cancer predicts functional roles for miR-34a and miR-16 in cell fate regulation
Authors: Gupta Shantanu , Silveira Daner A. , Barbé-Tuana Florencia M. , Mombach José Carlos M.
Published: February 2020

MiR-34a and miR-16 coordinately control cell cycle checkpoint in non-small cell lung cancer (NSCLC) cells. In cutaneous T-cell lymphoma (CTCL) cells miR-16 regulates a switch between apoptosis and senescence, however the role of miR-34a in this process is unclear. Both miRNAs share many common targets and experimental evidences suggest that they synergistically control the cell-fate regulation of NSCLC. In this work we investigate whether the coordinate action between miR-34a and miR-16 can explain experimental results in multiple cell lines of NSCLC and CTCL. For that we propose a Boolean model of the G1/S checkpoint regulation contemplating the regulatory influences of both miRNAs. Model validation was performed by comparisons with experimental information from the following cell lines: A549, H460, H1299, MyLa and MJ presenting excellent agreement. The model integrates in a single logical framework the mechanisms responsible for cell fate decision in NSCLC and CTCL cells. From the model analysis we suggest that miR-34a is the main controller of miR-16 activity in these cells. The model also allows to investigate perturbations of single or more molecules with the purpose to intervene in cell fate mechanisms of NSCLC and CTCL cells.
C-phycocyanin attenuates RANKL-induced osteoclastogenesis and bone resorption in vitro through inhibiting ROS levels, NFATc1 and NF-κB activation
Authors: AlQranei Mohammed S. , Aljohani Hanan , Majumdar Sunipa , Senbanjo Linda T. , Chellaiah Meenakshi A.
Published: February 2020

Excessive bone loss occurs in inflammatory disorders such as periodontitis and osteoporosis. The underlying mechanism is related to the differentiation of macrophages into multinucleated giant osteoclasts and their bone resorptive activity. C-Phycocyanin (C-PC) is a phycobiliprotein extracted from the blue-green algae, which has been shown to have various pharmacological effects. The role of C-PC on bone metabolism needs revelation. In this study, we determined the effectiveness of C-PC as an inhibitor of osteoclast differentiation, activity, and survival in vitro. We found that C-PC strongly inhibited the differentiation of macrophages to TRAP-positive osteoclasts, distinctive osteoclast specific podosomal organization, and dentine matrix resorption without any cytotoxicity. Also, it suppressed the expression of osteoclast specific markers, such as cathepsin K and integrin β3 at mRNA and protein levels. RANKL mediated signaling utilizes reactive oxygen species (ROS) for the differentiation of osteoclasts. C-PC attenuated RANKL stimulated ROS. Mechanistic studies indicate that C-PC has the potential to reduce osteoclast formation via blocking the degradation of cytosolic IκB-α and hence, the activation of downstream markers such as c-Fos and NFATc1. However, it does not have any effect on osteoblast-mediated bone formation in vitro. Collectively, our data suggest that C-PC may be utilized as a therapeutic agent that can target bone loss mediated by excessive osteoclastic bone resorption without affecting osteoblastic activity in bone.
Developing a faster way to identify biocontamination in the air of controlled environment rooms with HEPA filters: airborne particle counting
Authors: Figuerola-Tejerina Angels , Hernández-Aceituno Ana , Alemán-Vega Guadalupe , Orille-García César , Ruiz-Álvarez Miguel , Sandoval-Insausti Helena
Published: February 2020

Our aim was to assess whether airborne particle counting is an immediate indicator of biocontamination in controlled environment rooms with HEPA filters in a hospital. A prospective study was carried out in a tertiary care hospital between 2016 and 2018. The study was divided in two periods and the measurements were performed in different controlled environment rooms with HEPA filters. The Environmental Biosafety Criterion (EBC) was defined as the absence of fungal and bacterial contamination. In the training period, the area under the ROC curve (aROC) of airborne particle counting and EBC was calculated for each particle size as well as the cut-off points that optimize the combination of sensitivity and specificity in the association between them. aROC is created by plotting sensitivity against 1-specificity. In the testing period, the cut-off points previously selected were validated. 328 measurements were carried out in the training period and 301 in the testing period. In the training period, an association was found between airborne particle counting and EBC. An aROC = 0.760, 95% Confidence Interval (95% CI) 0.695–0.825 was observed for 0.3 µm particles; an aROC = 0.797 (95% CI 0.734–0.860) for 0.5 µm particles; and an aROC = 0.751 (95% CI 0.673–0.829) for 5 µm particles. The cut-off points that optimized the combination of sensitivity and specificity were 9.0 × 103 for 0.3 µm particles, 3.6 × 103 particles for 0.5 µm, and 3.2 × 102 particles for 5 µm. In the testing period, the previous cut-off points were validated. We conclude that airborne particle counting is a useful, immediate, and preliminary measure to identify the presence of biocontamination in controlled environment rooms with HEPA filters.
Optimisation of assessment of maximal rate of heart rate increase for tracking training-induced changes in endurance exercise performance
Authors: Nelson Maximillian J. , Bellenger Clint R. , Thomson Rebecca L. , Robertson Eileen Y. , Davison Kade , Olstad Daniela Schäfer , Buckley Jonathan D.
Published: February 2020

The maximal rate of heart rate (HR) increase (rHRI), a marker of HR acceleration during transition from rest to submaximal exercise, correlates with exercise performance. In this cohort study, whether rHRI tracked performance better when evaluated over shorter time-periods which include a greater proportion of HR acceleration and less steady-state HR was evaluated. rHRI and five-km treadmill running time-trial performance (5TTT) were assessed in 15 runners following one week of light training (LT), two weeks of heavy training (HT) and 10-day taper (T). rHRI was the first derivative maximum of a sigmoidal curve fit to one, two, three and four minutes of R-R data during transition from rest to running at 8 km/h (rHRI8 km/h), 10.5 km/h, 13 km/h and transition from 8 to 13 km/h (rHRI8–13km/h). 5TTT time increased from LT to HT (effect size [ES] 1.0, p < 0.001) then decreased from HT to T (ES −1.7, p < 0.001). 5TTT time was inversely related to rHRI8 km/h assessed over two (B = −5.54, p = 0.04) three (B = −5.34, p = 0.04) and four (B = −5.37, p = 0.04) minutes, and rHRI8–13km/h over one (B = −11.62, p = 0.006) and three (B = −11.44, p = 0.03) minutes. 5TTT correlated most consistently with rHRI8 km/h. rHRI8 km/h assessed over two to four minutes may be suitable for evaluating athlete responses to training.
No evidence for after-effects of noisy galvanic vestibular stimulation on motion perception
Authors: Keywan Aram , Badarna Hiba , Jahn Klaus , Wuehr Max
Published: February 2020

Noisy galvanic vestibular stimulation (nGVS) delivered at imperceptible intensities can improve vestibular function in health and disease. Here we evaluated whether nGVS effects on vestibular function are only present during active stimulation or may exhibit relevant post-stimulation after-effects. Initially, nGVS amplitudes that optimally improve posture were determined in 13 healthy subjects. Subsequently, effects of optimal nGVS amplitudes on vestibular roll-tilt direction recognition thresholds (DRT) were examined during active and sham nGVS. Ten of 13 subjects exhibited reduced DRTs during active nGVS compared to sham stimulation (p < 0.001). These 10 participants were then administered to 30 mins of active nGVS treatment while being allowed to move freely. Immediately post-treatment , DRTs were increased again (p = 0.044), reverting to baseline threshold levels (i.e. were comparable to the sham nGVS thresholds), and remained stable in a follow-up assessment after 30 min. After three weeks, participants returned for a follow-up experiment to control for learning effects, in which DRTs were measured during and immediately after 30 min application of sham nGVS. DRTs during both assessments did not differ from baseline level. These findings indicate that nGVS does not induce distinct post-stimulation effects on vestibular motion perception and favor the development of a wearable technology that continuously delivers nGVS to patients in order to enhance vestibular function.
Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning
Authors: Hara Shuichi , Kobayashi Masamune , Kuriiwa Fumi , Mizukami Hajime , Mukai Toshiji
Published: February 2020

Oxidative stress has been suggested to play a role in brain damage during carbon monoxide (CO) poisoning. Severe poisoning induced by CO at 3000 ppm, but not 1000 ppm, enhances hydroxyl radical (˙OH) production in the rat striatum, which might be mediated by NADPH oxidase (NOX) activation associated with Ras-related C3 botulinum toxin substrate (Rac) via cAMP signaling pathway activation. CO-induced ˙OH production was suppressed by antagonists of angiotensin II (AngII) type 1 receptor (AT1R) and type 2 receptor (AT2R) but not an antagonist of the Mas receptor. Suppression by an AT1R antagonist was unrelated to peroxisome proliferator-activated receptor γ. Angiotensin-converting enzyme inhibitors also suppressed CO-induced ˙OH production. Intrastriatal AngII at high concentrations enhanced ˙OH production. However, the enhancement of ˙OH production was resistant to inhibitors selective for NOX and Rac and to AT1R and AT2R antagonists. This indicates a different mechanism for ˙OH production induced by AngII than for that induced by CO poisoning. AT1R and AT2R antagonists had no significant effects on CO-induced cAMP production or ˙OH production induced by forskolin, which stimulates cAMP production. These findings suggest that the renin-angiotensin system might be involved in CO-induced ˙OH production in a manner independent of cAMP signaling pathways.
Reduced Resting-State Connectivity in the Precuneus is correlated with Apathy in Patients with Schizophrenia
Authors: Forlim Caroline Garcia , Klock Leonie , Bächle Johanna , Stoll Laura , Giemsa Patrick , Fuchs Marie , Schoofs Nikola , Montag Christiane , Gallinat Jürgen , Kühn Simone
Published: February 2020

A diagnosis of schizophrenia is associated with a heterogeneous psychopathology including positive and negative symptoms. The disconnection hypothesis, an early pathophysiological framework conceptualizes the diversity of symptoms as a result of disconnections in neural networks. In line with this hypothesis, previous neuroimaging studies of patients with schizophrenia reported alterations within the default mode network (DMN), the most prominent network at rest. The aim of the present study was to investigate the functional connectivity during rest in patients with schizophrenia and with healthy individuals and explore whether observed functional alterations are related to the psychopathology of patients. Therefore, functional magnetic resonance images at rest were recorded of 35 patients with schizophrenia and 41 healthy individuals. Independent component analysis (ICA) was used to extract resting state networks. Comparing ICA results between groups indicated alterations only within the network of the DMN. More explicitly, reduced connectivity in the precuneus was observed in patients with schizophrenia compared to healthy controls. Connectivity in this area was negatively correlated with the severity of negative symptoms, more specifically with the domain of apathy. Taken together, the current results provide further evidence for a role DMN alterations might play in schizophrenia and especially in negative symptoms such as apathy.
Conversion of chemical to mechanical energy by the nucleotide binding domains of ABCB1
Authors: Szöllősi Dániel , Chiba Peter , Szakacs Gergely , Stockner Thomas
Published: February 2020

P-glycoprotein (ABCB1) is an important component of barrier tissues that extrudes a wide range of chemically unrelated compounds. ABCB1 consists of two transmembrane domains forming the substrate binding and translocation domain, and of two cytoplasmic nucleotide binding domains (NBDs) that provide the energy by binding and hydrolyzing ATP. We analyzed the mechanistic and energetic properties of the NBD dimer via molecular dynamics simulations. We find that MgATP stabilizes the NBD dimer through strong attractive forces by serving as an interaction hub. The irreversible ATP hydrolysis step converts the chemical energy stored in the phosphate bonds of ATP into potential energy. Following ATP hydrolysis, interactions between the NBDs and the ATP hydrolysis products MgADP + Pi remain strong, mainly because Mg2+ forms stabilizing interactions with ADP and Pi. Despite these stabilizing interactions MgADP + Pi are unable to hold the dimer together, which becomes separated by avid interactions of MgADP + Pi with water. ATP binding to the open NBDs and ATP hydrolysis in the closed NBD dimer represent two steps of energy input, each leading to the formation of a high energy state. Relaxation from these high energy states occurs through conformational changes that push ABCB1 through the transport cycle.
Complex Evolutionary History of Mboumar, a Mariner Element Widely Represented in Ant Genomes
Authors: Sanllorente Olivia , Vela Jesús , Mora Pablo , Ruiz-Mena Areli , Torres María Isabel , Lorite Pedro , Palomeque Teresa
Published: February 2020

Mboumar-9 is an active mariner-transposable element previously isolated in the ant Messor bouvieri. In this work, a mariner-like element, Mboumar, isolated from 22 species of ants, is analyzed. These species belong to nine different subfamilies, including Leptanillinae, the most primitive ant subfamily, and Myrmicinae and Formicidae, the most derived ones. Consequently, Mboumar-like elements seem to be well-represented in ant genomes. The phylogenetic tree drawn for mariner elements is highly inconsistent with the phylogeny of host ants, with almost identical elements found in clearly distant species and, on the contrary, more variable elements in closely related species. The inconsistency between the two phylogenetic trees indicates that these transposable elements have evolved independently from the speciation events of the ants that host them. Besides, we found closer genetic relationships among elements than among their host ants. We also found potential coding copies with an uninterrupted open reading frame of 345 aa in 11 species. The putative transposase codified by them showed a high sequence identity with the active Mboumar-9 transposase. The results of selection tests suggest the intervention of purifying selection in the evolution of these elements. Overall, our study suggests a complex evolutionary history of the Mboumar-like mariner in ants, with important participation of horizontal transfer events. We also suggest that the evolutionary dynamics of Mboumar-like elements can be influenced by the genetic system of their host ants, which are eusocial insects with a haplodiploid genetic system.
Epitaxial Growth and Characterization of AlInN-Based Core-Shell Nanowire Light Emitting Diodes Operating in the Ultraviolet Spectrum
Authors: Velpula Ravi Teja , Jain Barsha , Philip Moab Rajan , Nguyen Hoang Duy , Wang Renjie , Nguyen Hieu Pham Trung
Published: February 2020

We report the demonstration of the first axial AlInN ultraviolet core-shell nanowire light-emitting diodes with highly stable emission in the ultraviolet wavelength range. During epitaxial growth of the AlInN layer, an AlInN shell is spontaneously formed, resulting in reduced nonradiative recombination on the nanowire surface. The AlInN nanowires exhibit a high internal quantum efficiency of ~52% at room temperature for emission at 295 nm. The peak emission wavelength can be varied from 290 nm to 355 nm by changing the growth conditions. Moreover, significantly strong transverse magnetic (TM) polarized emission is recorded, which is ~4 times stronger than the transverse electric (TE) polarized light at 295 nm. This study provides an alternative approach for the fabrication of new types of high-performance ultraviolet light emitters.
Barium Titanate Nanoparticles Sensitise Treatment-Resistant Breast Cancer Cells to the Antitumor Action of Tumour-Treating Fields
Authors: Yoon Yi Na , Lee Dae-Sik , Park Hyung Ju , Kim Jae-Sung
Published: February 2020

Although tumour-treating fields (TTFields) is a promising physical treatment modality based on disruption of dipole alignments and generation of dielectrophoretic forces during cytokinesis, not much is known about TTFields-responsive sensitisers. Here, we report a novel TTFields-responsive sensitiser, barium titanate nanoparticles (BTNPs), which exhibit cytocompatibility, with non-cytotoxic effects on breast cancer cells. BTNPs are characterised by high dielectric constant values and ferroelectric properties. Notably, we found that BTNPs sensitised TTFields-resistant breast cancer cells in response to TTFields. In addition, BTNPs accumulated in the cytoplasm of cancer cells in response to TTFields. Further, we showed that TTFields combined with BTNPs exhibited antitumor activity by modulating several cancer-related pathways in general, and the cell cycle-related apoptosis pathway in particular. Therefore, our data suggest that BTNPs increase the antitumor action of TTFields by an electric field-responsive cytosolic accumulation, establishing BTNP as a TTFields-responsive sensitiser.
Structure-antioxidant activity relationship of methoxy, phenolic hydroxyl, and carboxylic acid groups of phenolic acids
Authors: Chen Jinxiang , Yang Jing , Ma Lanlan , Li Jun , Shahzad Nasir , Kim Chan Kyung
Published: February 2020

The antioxidant activities of 18 typical phenolic acids were investigated using 2, 2′-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. Five thermodynamic parameters involving hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton-loss electron transfer (SPLET) mechanisms were calculated using density functional theory with the B3LYP/UB3LYP functional and 6–311++G (d, p) basis set and compared in the phenolic acids. Based on the same substituents on the benzene ring, -CH2COOH and -CH = CHCOOH can enhance the antioxidant activities of phenolic acids, compared with -COOH. Methoxyl (-OCH3) and phenolic hydroxyl (-OH) groups can also promote the antioxidant activities of phenolic acids. These results relate to the O-H bond dissociation enthalpy of the phenolic hydroxyl group in phenolic acids and the values of proton affinity and electron transfer enthalpy (ETE) involved in the electron donation ability of functional groups. In addition, we speculated that HAT, SET-PT, and SPLET mechanisms may occur in the DPPH reaction system. Whereas SPLET was the main reaction mechanism in the FRAP system, because, except for 4-hydroxyphenyl acid, the ETE values of the phenolic acids in water were consistent with the experimental results.
Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity
Authors: Ferraro Florencia , Corvo Ileana , Bergalli Lucia , Ilarraz Andrea , Cabrera Mauricio , Gil Jorge , Susuki Brian M. , Caffrey Conor R. , Timson David J. , Robert Xavier , Guillon Christophe , Freire Teresa , Álvarez Guzmán
Published: February 2020

Trematode infections such as schistosomiasis and fascioliasis cause significant morbidity in an estimated 250 million people worldwide and the associated agricultural losses are estimated at more than US$ 6 billion per year. Current chemotherapy is limited. Triosephosphate isomerase (TIM), an enzyme of the glycolytic pathway, has emerged as a useful drug target in many parasites, includingFasciola hepaticaTIM (FhTIM). We identified 21 novel compounds that selectively inhibit this enzyme. Using microscale thermophoresis we explored the interaction between target and compounds and identified a potent interaction between the sulfonyl-1,2,4-thiadiazole (compound187) andFhTIM, which showed an IC50of 5 µM and a Kdof 66 nM. In only 4 hours, this compound killed the juvenile form ofF. hepaticawith an IC50of 3 µM, better than the reference drug triclabendazole (TCZ). Interestingly, we discoveredin vitroinhibition ofFhTIM by TCZ, with an IC50of 7 µM suggesting a previously uncharacterized role ofFhTIM in the mechanism of action of this drug. Compound187was also active against various developmental stages ofSchistosoma mansoni. The low toxicityin vitroin different cell types and lack of acute toxicity in mice was demonstrated for this compound, as was demonstrated the efficacy of187in vivoinF. hepaticainfected mice. Finally, we obtained the first crystal structure ofFhTIM at 1.9 Å resolution which allows us using docking to suggest a mechanism of interaction between compound187and TIM. In conclusion, we describe a promising drug candidate to control neglected trematode infections in human and animal health.
Sonoelastographic evaluation of plantar fascia after shock wave therapy for recalcitrant plantar fasciitis: A 12-month longitudinal follow-up study
Authors: Wu Chueh-Hung , Lin Yun-Yi , Chen Wen-Shiang , Wang Tyng-Guey
Published: February 2020

Extracorporeal shockwave therapy (ESWT) is proposed to be effective in reducing pain and improving functional outcome in chronic plantar fasciitis. However, no long-term reports exist on the changes in plantar fascia (PF) elasticity after ESWT. We aimed to evaluate the changes in PF stiffness in patients with plantar fasciitis undergoing ESWT. The visual analogue scale (VAS, 0–100) was used for evaluating heel pain severity. B-mode sonography and strain sonoelastography were used for evaluating the PF thickness and stiffness. The sonoelastogram was analyzed using hue histogram analysis (value: 0–255, from stiffer to softer). All evaluations were recorded before ESWT, and 1 week, 1 month, 3 months, 6 months, and 12 months after ESWT. Repeated measures ANOVA was used to compare pain VAS, PF thickness, and PF hue value at different follow-up time-points. Twenty-two participants (8 men, 14 women) completed all measurements for 12 months. The VAS of heel pain, PF thickness, and PF hue values at pre-ESWT, and 1-week, 1-month, 3-month, 6-month, and 12-month evaluations after ESWT were 62.4 ± 4.2, 49.3 ± 5.8, 38.3 ± 5.7, 27.9 ± 5.3, 18.9 ± 4.7, and 13.2 ± 3.0 (p < 0.01 in all measurements post ESWT versus pre-ESWT); 5.57 ± 0.22 mm, 5.64 ± 0.18 mm, 5.45 ± 0.24 mm, 5.37 ± 0.20 mm, 5.08 ± 0.20 mm, and 4.62 ± 0.15 mm (p < 0.01 at 6-month; otherwise p > 0.05); and 24.5 ± 2.4, 35.2 ± 3.1, 31.0 ± 4.1, 30.5 ± 3.9, 21.4 ± 2.1, and 15.9 ± 1.6 (p < 0.01 at 1-week and 6-month; otherwise p > 0.05), respectively. In conclusion, the heel pain intensity and PF thickness reduced gradually over 12 months after ESWT. The PF stiffness decreased during the first week and increased thereafter; at the 12-month follow-up, stiffness was more than at pre-ESWT.
Cross-kingdom signalling regulates spore germination in the moss Physcomitrella patens
Authors: Vesty Eleanor F. , Whitbread Amy L. , Needs Sarah , Tanko Wesal , Jones Kirsty , Halliday Nigel , Ghaderiardakani Fatemeh , Liu Xiaoguang , Cámara Miguel , Coates Juliet C.
Published: February 2020

Plants live in close association with microorganisms that can have beneficial or detrimental effects. The activity of bacteria in association with flowering plants has been extensively analysed. Bacteria use quorum-sensing as a way of monitoring their population density and interacting with their environment. A key group of quorum sensing molecules in Gram-negative bacteria are the N-acylhomoserine lactones (AHLs), which are known to affect the growth and development of both flowering plants, including crops, and marine algae. Thus, AHLs have potentially important roles in agriculture and aquaculture. Nothing is known about the effects of AHLs on the earliest-diverging land plants, thus the evolution of AHL-mediated bacterial-plant/algal interactions is unknown. In this paper, we show that AHLs can affect spore germination in a representative of the earliest plants on land, the Bryophyte moss Physcomitrella patens. Furthermore, we demonstrate that sporophytes of some wild isolates of Physcomitrella patens are associated with AHL-producing bacteria.
Physiologic heart rate dependency of the PQ interval and its sex differences
Authors: Toman Ondřej , Hnatkova Katerina , Smetana Peter , Huster Katharina M. , Šišáková Martina , Barthel Petra , Novotný Tomáš , Schmidt Georg , Malik Marek
Published: February 2020

On standard electrocardiogram (ECG) PQ interval is known to be moderately heart rate dependent, but no physiologic details of this dependency have been established. At the same time, PQ dynamics is a clear candidate for non-invasive assessment of atrial abnormalities including the risk of atrial fibrillation. We studied PQ heart rate dependency in 599 healthy subjects (aged 33.5 ± 9.3 years, 288 females) in whom drug-free day-time 12-lead ECG Holters were available. Of these, 752,517 ECG samples were selected (1256 ± 244 per subject) to measure PQ and QT intervals and P wave durations. For each measured ECG sample, 5-minute history of preceding cardiac cycles was also obtained. Although less rate dependent than the QT intervals (36 ± 19% of linear slopes), PQ intervals were found to be dependent on underlying cycle length in a highly curvilinear fashion with the dependency significantly more curved in females compared to males. The PQ interval also responded to the heart rate changes with a delay which was highly sex dependent (95% adaptation in females and males after 114.9 ± 81.1 vs 65.4 ± 64.3 seconds, respectively, p < 0.00001). P wave duration was even less rate dependent than the PQ interval (9 ± 10% of linear QT/RR slopes). Rate corrected P wave duration was marginally but significantly shorter in females than in males (106.8 ± 8.4 vs 110.2 ± 7.9 ms, p < 0.00001). In addition to establishing physiologic standards, the study suggests that the curvatures and adaptation delay of the PQ/cycle-length dependency should be included in future non-invasive studies of atrial depolarizations.
Integrative proteomic and functional analyses provide novel insights into the action of the repurposed drug candidate nitroxoline in AsPC-1 cells
Authors: Veschi Serena , Ronci Maurizio , Lanuti Paola , De Lellis Laura , Florio Rosalba , Bologna Giuseppina , Scotti Luca , Carletti Erminia , Brugnoli Federica , Di Bella Maria Cristina , Bertagnolo Valeria , Marchisio Marco , Cama Alessandro
Published: February 2020

We recently identified nitroxoline as a repurposed drug candidate in pancreatic cancer (PC) showing a dose-dependent antiproliferative activity in different PC cell lines. This antibiotic is effective in several in vitro and animal cancer models. To date, the mechanisms of nitroxoline anticancer action are largely unknown. Using shotgun proteomics we identified 363 proteins affected by nitroxoline treatment in AsPC-1 pancreatic cancer cells, including 81 consistently deregulated at both 24- and 48-hour treatment. These proteins previously unknown to be affected by nitroxoline were mostly downregulated and interconnected in a single highly-enriched network of protein-protein interactions. Integrative proteomic and functional analyses revealed nitroxoline-induced downregulation of Na/K-ATPase pump and β-catenin, which associated with drastic impairment in cell growth, migration, invasion, increased ROS production and induction of DNA damage response. Remarkably, nitroxoline induced a previously unknown deregulation of molecules with a critical role in cell bioenergetics, which resulted in mitochondrial depolarization. Our study also suggests that deregulation of cytosolic iron homeostasis and of co-translational targeting to membrane contribute to nitroxoline anticancer action. This study broadens our understanding of the mechanisms of nitroxoline action, showing that the drug modulates multiple proteins crucial in cancer biology and previously unknown to be affected by nitroxoline.
Does sediment composition sort kinorhynch communities? An ecomorphological approach through geometric morphometrics
Authors: Cepeda Diego , Trigo Dolores , Pardos Fernando , Sánchez Nuria
Published: February 2020

Ecomorphology studies the relationship between organisms’ morphology and environment features. To better understand whether the shape of the body and the appendages involved in the movement is correlated to sediment composition in meiofaunal organisms, we study the evolved morphological adaptations to environment in selected taxa of the phylum Kinorhyncha: the allomalorhagid families Dracoderidae and Pycnophyidae, and the cyclorhagid genus Echinoderes. The selected taxa include the most diverse groups of Kinorhyncha worldwide, representing the 75.5% of the total phylum diversity. Widened, plump bodies and lateral terminal spines may be adaptive for species living in coarse, more heterogeneous sediments, as they could maintain a more powerful musculature to actively displace the sediment grains applying a greater force. Conversely, slender, vermiform bodies and lateral terminal spines would represent an adaptation of species inhabiting fine, more homogeneous sediments where there would not be much need to exert a high force to displace the sediment particles, and a more vermiform shape would even favour the burrowing of the animal through the smaller interstices. The studied kinorhynch taxa would also be adapted to the higher velocity of the sea-water and the intense erosion and transportation of heterogeneous sediments by possessing more robust bodies, avoiding getting laid off substratum under these conditions. These findings provide evolutionary evidence that body shape in the studied kinorhynch groups is adapted to environment.
Inhibition of cyclooxygenase-1 by nonsteroidal anti-inflammatory drugs demethylates MeR2 enhancer and promotes Mbnl1 transcription in myogenic cells
Authors: Huang Kun , Masuda Akio , Chen Guiying , Bushra Samira , Kamon Masayoshi , Araki Toshiyuki , Kinoshita Masanobu , Ohkawara Bisei , Ito Mikako , Ohno Kinji
Published: February 2020

Muscleblind-like 1 (MBNL1) is a ubiquitously expressed RNA-binding protein, which is highly expressed in skeletal muscle. Abnormally expanded CUG-repeats in the DMPK gene cause myotonic dystrophy type 1 (DM1) by sequestration of MBNL1 to nuclear RNA foci and by upregulation of another RNA-binding protein, CUG-binding protein 1 (CUGBP1). We previously reported that a nonsteroidal anti-inflammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. NSAIDs inhibit cyclooxygenase (COX), which is comprised of COX-1 and COX-2 isoforms. In this study, we screened 29 NSAIDs in C2C12 myoblasts, and found that 13 NSAIDs enhanced Mbnl1 expression, where COX-1-selective NSAIDs upregulated Mbnl1 more than COX-2-selective NSAIDs. Consistently, knockdown of COX-1, but not of COX-2, upregulated MBNL1 expression in C2C12 myoblasts and myotubes, as well as in myotubes differentiated from DM1 patient-derived induced pluripotent stem cells (iPSCs). Luciferase assay showed that COX-1-knockdown augmented the MeR2 enhancer activity. Furthermore, bisulfite sequencing analysis demonstrated that COX-1-knockdown suppressed methylation of MeR2. These results suggest that COX-1 inhibition upregulates Mbnl1 transcription through demethylation of the MeR2 enhancer. Taken together, our study provides new insights into the transcriptional regulation of Mbnl1 by the COX-1-mediated pathway.
Sweet potato viromes in eight different geographical regions in Korea and two different cultivars
Authors: Jo Yeonhwa , Kim Sang-Min , Choi Hoseong , Yang Jung Wook , Lee Bong Choon , Cho Won Kyong
Published: February 2020

The sweet potato in the family Convolvulaceae is a dicotyledonous perennial plant. Here, we conducted a comprehensive sweet potato virome study using 10 different libraries from eight regions in Korea and two different sweet potato cultivars by RNA-Sequencing. Comprehensive bioinformatics analyses revealed 10 different virus species infecting sweet potato. Moreover, we identified two novel viruses infecting sweet potato referred to as Sweet potato virus E (SPVE) in the genus Potyvirus and Sweet potato virus F (SPVF) in the genus Carlavirus. Of the identified viruses, Sweet potato feathery mottle virus (SPFMV) was the dominant virus followed by Sweet potato virus C (SPVC) and SPVE in Korea. We obtained a total of 30 viral genomes for eight viruses. Our phylogenetic analyses showed many potyvirus isolates are highly correlated with geographical regions. However, two isolates of SPFMV and a single isolate of Sweet potato virus G (SPVG) were genetically distant from other known isolates. The mutation rate was the highest in SPFMV followed by SPVC and SPVG. Two different sweet potato cultivars, Beni Haruka and Hogammi, were infected by seven and five viruses, respectively. Taken together, we provide a complete list of viruses infecting sweet potato in Korea and diagnostic methods.
Effects of Compound Sand Barrier for Habitat Restoration on Sediment Grain-size Distribution in Ulan Buh Desert
Authors: Pan Xia , Wang Zhenyi , Gao Yong
Published: February 2020

Wind erosion is a huge challenge for ecologists to stabilize sand dunes and to change them into stable productive ecosystems. In order to better understand its role in the process of ecological restoration, the sediment grain-size characteristics of compound sand barrier were evaluated through field experimental observation. The results indicated that the compound sand barrier was mainly composed of extremely fine sand and fine sand, and the fine sand and extremely fine sand in the inner side were higher than the east and west sides of the compound sand barrier. Due to the blocking effect of compound sand barrier, the Sorting Coefficient became better, the Skewness belonged to the positive deviation and the Kurtosis presented leptokurtosis distribution. Moreover, while the cumulative frequency distribution curve in the inner side became steeper, the slope increased and reached the top of the curve ahead of time. The effect of wind environment and vegetation coverage on the surface sediments showed that the average annual wind velocity and vegetation coverage was negatively correlated with the average grain-size, but positively correlated with the Sorting Coefficient. There was a significant correlation among the annual wind speed, vegetation coverage, average grain-size and Sorting Coefficient, which indicated that vegetation coverage and wind environment was the key factor leading to the difference of surface sediments in this area. Collectively, the establishment of compound sand barrier is one of the most effective methods of sand-fixing with engineering measure in the arid desert regions. Therefore, given the complexities of agricultural systems, stubble retention and black film covered during harvesting and incorporation of the stubble into soil in the next spring appears to be the best choice in the dry northern China where farmlands suffer serious wind erosion.