bluuebunny/crossref_metadata_2025 huggingface dataset:
An Open-Source Web Platform to Share Multisource, Multisensor Geospatial Data and Measurements of Ground Deformation in Mountain Areas
Authors: Cignetti Martina , Guenzi Diego , Ardizzone Francesca , Allasia Paolo , Giordan Daniele
Published: December 2019

Nowadays, the increasing demand to collect, manage and share archives of data supporting geo-hydrological processes investigations requires the development of spatial data infrastructure able to store geospatial data and ground deformation measurements, also considering multisource and heterogeneous data. We exploited the GeoNetwork open-source software to simultaneously organize in-situ measurements and radar sensor observations, collected in the framework of the HAMMER project study areas, all located in high mountain regions distributed in the Alpines, Apennines, Pyrenees and Andes mountain chains, mainly focusing on active landslides. Taking advantage of this free and internationally recognized platform based on standard protocols, we present a valuable instrument to manage data and metadata, both in-situ surface measurements, typically acquired at local scale for short periods (e.g., during emergency), and satellite observations, usually exploited for regional scale analysis of surface displacement. Using a dedicated web-interface, all the results derived by instrumental acquisitions and by processing of remote sensing images can be queried, analyzed and downloaded from both expert users and stakeholders. This leads to a useful instrument able to share various information within the scientific community, including the opportunity of reprocessing the raw data for other purposes and in other contexts.
A Novel Underwater Simultaneous Localization and Mapping Online Algorithm Based on Neural Network
Authors: Hou Guangchao , Shao Qi , Zou Bo , Dai Liwen , Zhang Zhe , Mu Zhehan , Zhang Yadong , Zhai Jingsheng
Published: December 2019

The navigation and localization of autonomous underwater vehicles (AUVs) in seawater are of the utmost importance for scientific research, petroleum engineering, search and rescue, and military missions concerning the special environment of seawater. However, there is still no general method for AUVs navigation and localization, especially in the featureless seabed. The reported approaches to solving AUVs navigation and localization problems employ an expensive inertial navigation system (INS), with cumulative errors and dead reckoning, and a high-cost long baseline (LBL) in a featureless subsea. In this study, a simultaneous localization and mapping (AMB-SLAM) online algorithm, based on acoustic and magnetic beacons, was proposed. The AMB-SLAM online algorithm is based on multiple randomly distributed beacons of low-frequency magnetic fields and a single fixed acoustic beacon for location and mapping. The experimental results show that the performance of the AMB-SLAM online algorithm has a high robustness. The proposed approach (the AMB-SLAM online algorithm) provides a low-complexity, low-cost, and high-precision online solution to the AUVs navigation and localization problem in featureless seawater environments. The AMB-SLAM online solution could enable AUVs to autonomously explore or autonomously intervene in featureless seawater environments, which would enable AUVs to accomplish fully autonomous survey missions.
Spoofing Detection of Civilian UAVs Using Visual Odometry
Authors: Varshosaz Masood , Afary Alireza , Mojaradi Barat , Saadatseresht Mohammad , Ghanbari Parmehr Ebadat
Published: December 2019

Spoofing of Unmanned Aerial Vehicles (UAV) is generally carried out through spoofing of the UAV’s Global Positioning System (GPS) receiver. This paper presents a vision-based UAV spoofing detection method that utilizes Visual Odometry (VO). This method is independent of the other complementary sensors and any knowledge or archived map and datasets. The proposed method is based on the comparison of relative sub-trajectory of the UAV from VO, with its absolute replica from GPS within a moving window along the flight path. The comparison is done using three dissimilarity measures including (1) Sum of Euclidian Distances between Corresponding Points (SEDCP), (2) angle distance and (3) taxicab distance between the Histogram of Oriented Displacements (HOD) of these sub-trajectories. This method can determine the time and location of UAV spoofing and bounds the drift error of VO. It can be used without any restriction in the usage environment and can be implemented in real-time applications. This method is evaluated on four UAV spoofing scenarios. The results indicate that this method is effective in the detection of UAV spoofing due to the Sophisticated Receiver-Based (SRB) GPS spoofing. This method can detect UAV spoofing in the long-range UAV flights when the changes in UAV flight direction is larger than 3° and in the incremental UAV spoofing with the redirection rate of 1°. Additionally, using SEDCP, the spoofing of the UAV, when there is no redirection and only the velocity of the UAV is changed, can be detected. The results show that SEDCP is more effective in the detection of UAV spoofing and fake GPS positions.
Geo-DMP: A DTN-Based Mobile Prototype for Geospatial Data Retrieval
Authors: Li Chao , Lu Huimei , Xiang Yong , Gao Rui
Published: December 2019

Geospatial information is gaining immense interest and importance as we enter the era of highly developed transportation and communication. Despite the proliferation of cellular network and WiFi, on some occasions, users still face barriers to accessing geospatial data. In this paper, we design and implement a distributed prototype system with a delay/disruption tolerant network (DTN), named Geo-DMP, for cooperatively and opportunistically sharing and exchanging named geospatial contents in a device-to-device fashion. First of all, we construct a lightweight “content agent” module to bridge the gap between the application layer and the underlying DTN protocol stack. Afterwards, to profile the mobility history of users in practical geospatial environments, we present a map segmentation scheme based on road network and administrative subdivision information. Subsequently, we associate the regional movement history information with the content retrieval process to devise a hierarchical and region-oriented DTN routing scheme for both requests and responses. Finally, we conduct extensive experiments with real-world trajectories and complete implementations on the emulation platform composed of virtual machines. The experiments corroborate that Geo-DMP has the capability of successfully retrieving geospatial contents for users for most of the time under mobile circumstances with episodic connectivity. Moreover, en-route caches can be efficiently exploited to provision contents from multiple sources with less network resource consumption and shorter user-perceived latencies.
Single-Molecule Long-Read Sequencing Reveals the Diversity of Full-Length Transcripts in Leaves of Gnetum (Gnetales)
Authors: Deng Nan , Hou Chen , Ma Fengfeng , Liu Caixia , Tian Yuxin
Published: December 2019

The limitations of RNA sequencing make it difficult to accurately predict alternative splicing (AS) and alternative polyadenylation (APA) events and long non-coding RNAs (lncRNAs), all of which reveal transcriptomic diversity and the complexity of gene regulation. Gnetum, a genus with ambiguous phylogenetic placement in seed plants, has a distinct stomatal structure and photosynthetic characteristics. In this study, a full-length transcriptome of Gnetum luofuense leaves at different developmental stages was sequenced with the latest PacBio Sequel platform. After correction by short reads generated by Illumina RNA-Seq, 80,496 full-length transcripts were obtained, of which 5269 reads were identified as isoforms of novel genes. Additionally, 1660 lncRNAs and 12,998 AS events were detected. In total, 5647 genes in the G. luofuense leaves had APA featured by at least one poly(A) site. Moreover, 67 and 30 genes from the bHLH gene family, which play an important role in stomatal development and photosynthesis, were identified from the G. luofuense genome and leaf transcripts, respectively. This leaf transcriptome supplements the reference genome of G. luofuense, and the AS events and lncRNAs detected provide valuable resources for future studies of investigating low photosynthetic capacity of Gnetum.
Editorial of Special Issue “Surface-Functionalized Nanoparticles as Drug Carriers”
Authors: Layek Buddhadev , Singh Jagdish
Published: December 2019

Safe and effective delivery of therapeutics at the target site is the key to successful therapy. Nanocarriers can offer significant advantages over conventional dosage forms. Over the decades, nanoparticles have been extensively used to increase bioavailability, improve solubility and stability, reduce toxicities, and facilitate the controlled release of therapeutics. Further, nanoparticles have often been surface-functionalized with a variety of ligands to enhance circulation half-life and increase target-specificity. Although nanotechnology has shown significant therapeutic benefits for multiple biomedical applications, limited nanoparticle-based formulations have progressed to clinical trials, and only a few have reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Surface-Functionalized Nanoparticles as Drug Carriers. We outline the scope of the special issue, summarize the results and conclusions of the nine articles published in this issue, and provide perspective on the application of surface-functionalized nanoparticles in the drug delivery field.
Bioactive Polyphenols Modulate Enzymes Involved in Grapevine Pathogenesis and Chitinase Activity at Increasing Complexity Levels
Authors: Filippi Antonio , Petrussa Elisa , Boscutti Francesco , Vuerich Marco , Vrhovsek Urska , Rabiei Zohreh , Braidot Enrico
Published: December 2019

The reduction of synthetic chemistry use in modern viticulture relies on either the biological control of microorganisms or the induction of pathogenesis-related proteins. In the present study, the effects of hydro-alcoholic plant extracts (PEs) (i.e., by-products of Vitis vinifera L., leaves of Olea europaea L. and Ailanthus altissima (Mill.) Swingle) were tested on purified enzymes activity involved in plant-pathogen interactions. The polyphenolic composition was assayed and analyzed to characterize the extract profiles. In addition, suspension cell cultures of grapevine were treated with PEs to study their modulation of chitinase activity. Application of grape marc’s PE enhanced chitinase activity at 4 g L−1. Additionally, foliar treatment of grape marc’s PE at two doses (4 g L−1 and 800 g L−1) on grapevine cuttings induced a concentration-dependent stimulation of chitinase activity. The obtained results showed that the application of bioactive compounds based on PEs, rich in phenolic compounds, was effective both at in vitro and ex/in vivo level. The overall effects of PEs on plant-pathogen interaction were further discussed by applying a multi-criteria decision analysis, showing that grape marc was the most effective extract.
Proteomics Analysis of Early Developmental Stages of Zebrafish Embryos
Authors: Purushothaman Kathiresan , Das Prem Prakash , Presslauer Christopher , Lim Teck Kwang , Johansen Steinar D. , Lin Qingsong , Babiak Igor
Published: December 2019

Zebrafish is a well-recognized organism for investigating vertebrate development and human diseases. However, the data on zebrafish proteome are scarce, particularly during embryogenesis. This is mostly due to the overwhelming abundance of egg yolk proteins, which tend to mask the detectable presence of less abundant proteins. We developed an efficient procedure to reduce the amount of yolk in zebrafish early embryos to improve the Liquid chromatography–tandem mass spectrometry (LC–MS)-based shotgun proteomics analysis. We demonstrated that the deyolking procedure resulted in a greater number of proteins being identified. This protocol resulted in approximately 2-fold increase in the number of proteins identified in deyolked samples at cleavage stages, and the number of identified proteins increased greatly by 3–4 times compared to non-deyolked samples in both oblong and bud stages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed a high number of functional proteins differentially accumulated in the deyolked versus non-deyolked samples. The most prominent enrichments after the deyolking procedure included processes, functions, and components related to cellular organization, cell cycle, control of replication and translation, and mitochondrial functions. This deyolking procedure improves both qualitative and quantitative proteome analyses and provides an innovative tool in molecular embryogenesis of polylecithal animals, such as fish, amphibians, reptiles, or birds.
S1P/S1P Receptor Signaling in Neuromuscolar Disorders
Authors: Meacci Elisabetta , Garcia-Gil Mercedes
Published: December 2019

The bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P), and the signaling pathways triggered by its binding to specific G protein-coupled receptors play a critical regulatory role in many pathophysiological processes, including skeletal muscle and nervous system degeneration. The signaling transduced by S1P binding appears to be much more complex than previously thought, with important implications for clinical applications and for personalized medicine. In particular, the understanding of S1P/S1P receptor signaling functions in specific compartmentalized locations of the cell is worthy of being better investigated, because in various circumstances it might be crucial for the development or/and the progression of neuromuscular diseases, such as Charcot–Marie–Tooth disease, myasthenia gravis, and Duchenne muscular dystrophy.
Phenolic Compounds with Antioxidant Properties from Canola Meal Extracts Inhibit Adipogenesis
Authors: Hussain Saira , Rehman Ata Ur , Luckett David J. , Blanchard Christopher L. , Obied Hassan K. , Strappe Padraig
Published: December 2019

The extraction of phenolic compounds from canola meal produces functional health products and renders the canola meal a more digestible animal feed. The extracted phenolics may have novel bioactivity worth investigation. In this study, several solvents were evaluated for their ability to extract phenolic compounds from canola meal: water (WE) and various 80% organic solvent/water mixtures of methanol (ME), acetone (AE), ethanol (EE), butanol (BE), chloroform (CE) and hexane (HE). The in vitro antioxidant and anti-obesity properties of various extracts were investigated. Anti-obesity properties were studied using adipogenic differentiation inhibition of a murine mesenchymal stem cell line (C3H10T1/2) and a pancreatic lipase inhibition assay. AE, ME, and BE showed significant (p < 0.05) adipogenesis and pancreatic lipase inhibitory activities and may have more pharmacological properties. AE down-regulated the gene expression of the major adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), correlating to phenolic content in a dose-dependent manner. The chemical characterization of AE revealed the presence of sinapic acid, ferulic acid, and kaempferol derivatives as main bioactive phenols.
Characterization of p53 Family Homologs in Evolutionary Remote Branches of Holozoa
Authors: Bartas Martin , Brázda Václav , Červeň Jiří , Pečinka Petr
Published: December 2019

The p53 family of transcription factors plays key roles in development, genome stability, senescence and tumor development, and p53 is the most important tumor suppressor protein in humans. Although intensively investigated for many years, its initial evolutionary history is not yet fully elucidated. Using bioinformatic and structure prediction methods on current databases containing newly-sequenced genomes and transcriptomes, we present a detailed characterization of p53 family homologs in remote members of the Holozoa group, in the unicellular clades Filasterea, Ichthyosporea and Corallochytrea. Moreover, we show that these newly characterized homologous sequences contain domains that can form structures with high similarity to the human p53 family DNA-binding domain, and some also show similarities to the oligomerization and SAM domains. The presence of these remote homologs demonstrates an ancient origin of the p53 protein family.
Ion-Based Cellular Signal Transmission, Principles of Minimum Information Loss, and Evolution by Natural Selection
Authors: Frieden B. Roy , Gatenby Robert
Published: December 2019

The Extreme Physical Information EPI principle states that maximum information transmission or, equivalently, a minimum information loss is a fundamental property of nature. Prior work has demonstrated the universal EPI principle allows derivation of nearly all physical laws. Here, we investigate whether EPI can similarly give rise to the fundamental law of life: Evolution. Living systems require information to survive and proliferate. Heritable information in the genome encodes the structure and function of cellular macromolecules but this information remains fixed over time. In contrast, a cell must rapidly and continuously access, analyze, and respond to a wide range of continuously changing spatial and temporal information in the environment. We propose these two information dynamics are linked because the genes encode the structure of the macromolecules that form information conduits necessary for the dynamical interactions with the external environment. However, because the genome does not have the capacity to precisely locate the time and location of external signals, we propose the cell membrane is the site at which most external information is received and processed. In our model, an external signal is detected by gates on transmembrane ion channel and transmitted into the cytoplasm through ions that flow along pre-existing concentration gradients when the gate opens. The resulting cytoplasmic ion “puff” is localized in both time and space, thus producing spatial and temporal information. Small, localized signals in the cytoplasm are “processed” through alterations in the function and location of peripheral membrane proteins. Larger perturbations produce prolonged or spatially extensive changes in cytoplasmic ion concentrations that can be transmitted to other organelles via ion flows along elements of the cytoskeleton. An evolutionary constraint to the ever-increasing acquisition of environmental information is the cost of doing so. One solution to this trade-off is the evolution of information conduits that minimize signal loss during transmission. Since the structures of these conduits are encoded in the genome, evolution of macromolecular conduits that minimize signal loss is linked to and, in fact, governed by a universal principle, termed extreme physical information (EPI). Mathematical analysis of information dynamics based on the flow of ions through membrane channels and along wire-like cytoskeleton macromolecules fulfills the EPI principle. Thus, the empirically derived model of evolution by natural selection, although uniquely applicable to living systems, is theoretically grounded in a universal principle that can also be used to derive the laws of physics. Finally, if minimization of signal loss is a mechanism to overcome energy constraints, the model predicts increasing information and associated complexity are closely linked to increased efficiency of energy production or improved substrate acquisition.
Correction: Sciacca, F. L., et al. Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome. Int. J. Mol. Sci. 2018, 19, 3675
Authors: Sciacca Francesca Luisa , Rizzo Ambra , Bedini Gloria , Capone Fioravante , Di Lazzaro Vincenzo , Nava Sara , Acerbi Francesco , Sebastiano Davide Rossi , Binelli Simona , Faragò Giuseppe , Gioppo Andrea , Grisoli Marina , Bruzzone Maria Grazia , Ferroli Paolo , Pantaleoni Chiara , Caputi Luigi , Gomez Jesus Vela , Parati Eugenio Agostino , Bersano Anna
Published: December 2019

The authors wish to make the corrections to this paper [1] [...]
Discovery of an Orally Effective Factor IX-Transferrin Fusion Protein for Hemophilia B
Authors: Xie Chen , Wang Zhijun , Su Yang , Wang Jeffrey , Shen Wei-Chiang
Published: December 2019

Hemophilia B is a severe blood clotting disorder caused by the deficiency of factor IX (FIX). FIX is not bioavailable when given orally due to poor stability and permeability in the gastrointestinal tract. The feasibility of fusing FIX with transferrin (Tf) to enhance the oral bioavailability of FIX is explored. Seven recombinant fusion proteins (rFIX-Tf) with different linkers were constructed and expressed in HEK293 cells and characterized by in vitro transcytosis and transferrin receptor (TfR) binding assay in Caco-2 cells and a one-stage clotting assay. The in vivo efficacy study was performed using a tail-bleeding model in hemophilia B mice. Fusion proteins rFIX-Tf/G2 and rFIX-Tf/SVSQ were most permeable and showed a specific binding ability to TfR in Caco-2 cells. Both proteins retained FIX activity in clotting generation. The in vivo efficacy study showed that both proteins by intravenous injection significantly reduced blood loss. Most significantly, rFIX-Tf/G2 demonstrated anti-bleeding activity when administered orally. Our results showed that the fusion protein technique with Tf could be potentially used for oral delivery of FIX and the linker between FIX and Tf in the fusion protein is crucial. rFIX-Tf/G2 appears to be the most promising fusion protein as potential oral therapeutics for hemophilia B.
Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences
Authors: Karasev Dmitry , Sobolev Boris , Lagunin Alexey , Filimonov Dmitry , Poroikov Vladimir
Published: December 2019

The affinity of different drug-like ligands to multiple protein targets reflects general chemical–biological interactions. Computational methods estimating such interactions analyze the available information about the structure of the targets, ligands, or both. Prediction of protein–ligand interactions based on pairwise sequence alignment provides reasonable accuracy if the ligands’ specificity well coincides with the phylogenic taxonomy of the proteins. Methods using multiple alignment require an accurate match of functionally significant residues. Such conditions may not be met in the case of diverged protein families. To overcome these limitations, we propose an approach based on the analysis of local sequence similarity within the set of analyzed proteins. The positional scores, calculated by sequence fragment comparisons, are used as input data for the Bayesian classifier. Our approach provides a prediction accuracy comparable or exceeding those of other methods. It was demonstrated on the popular Gold Standard test sets, presenting different sequence heterogeneity and varying from the group, including different protein families to the more specific groups. A reasonable prediction accuracy was also found for protein kinases, displaying weak relationships between sequence phylogeny and inhibitor specificity. Thus, our method can be applied to the broad area of protein–ligand interactions.
Hypoxia in the Initiation and Progression of Neuroblastoma Tumours
Authors: Huertas-Castaño Carlos , Gómez-Muñoz María A. , Pardal Ricardo , Vega Francisco M.
Published: December 2019

Neuroblastoma is the most frequent extracranial solid tumour in children, causing 10% of all paediatric oncology deaths. It arises in the embryonic neural crest due to an uncontrolled behaviour of sympathetic nervous system progenitors, giving rise to heterogeneous tumours. Low local or systemic tissue oxygen concentration has emerged as a cellular stimulus with important consequences for tumour initiation, evolution and progression. In neuroblastoma, several evidences point towards a role of hypoxia in tumour initiation during development, tumour cell differentiation, survival and metastatic spreading. However, the heterogeneous nature of the disease, its developmental origin and the lack of suitable experimental models have complicated a clear understanding of the effect of hypoxia in neuroblastoma tumour progression and the molecular mechanisms implicated. In this review, we have compiled available evidences to try to shed light onto this important field. In particular, we explore the effect of hypoxia in neuroblastoma cell transformation and differentiation. We also discuss the experimental models available and the emerging alternatives to study this problem, and we present hypoxia-related therapeutic avenues being explored in the field.
The Molecular Mechanisms Underlying Iron Deficiency Responses in Rice
Authors: Li Qian , Chen Lei , Yang An
Published: December 2019

Iron (Fe) is an essential element required for plant growth and development. Under Fe-deficientconditions, plants have developed two distinct strategies (designated as strategy I and II) to acquire Fe from soil. As a graminaceous species, rice is not a typical strategy II plant, as it not only synthesizes DMA (2’-deoxymugineic acid) in roots to chelate Fe3+ but also acquires Fe2+ through transporters OsIRT1 and OsIRT2. During the synthesis of DMA in rice, there are three sequential enzymatic reactions catalyzed by enzymes NAS (nicotianamine synthase), NAAT (nicotianamine aminotransferase), and DMAS (deoxymugineic acid synthase). Many transporters required for Fe uptake from the rhizosphere and internal translocation have also been identified in rice. In addition, the signaling networks composed of various transcription factors (such as IDEF1, IDEF2, and members of the bHLH (basic helix-loop-helix) family), phytohormones, and signaling molecules are demonstrated to regulate Fe uptake and translocation. This knowledge greatly contributes to our understanding of the molecular mechanisms underlying iron deficiency responses in rice.
Are Leukaemic Stem Cells Restricted to a Single Cell Lineage?
Authors: Brown Geoffrey , Sánchez Lucía , Sánchez-García Isidro
Published: December 2019

Cancer-stem-cell theory states that most, if not all, cancers arise from a stem/uncommitted cell. This theory revolutionised our view to reflect that cancer consists of a hierarchy of cells that mimic normal cell development. Elegant studies of twins who both developed acute lymphoblastic leukaemia in childhood revealed that at least two genomic insults are required for cancer to develop. These ‘hits’ do not appear to confer a growth advantage to cancer cells, nor do cancer cells appear to be better equipped to survive than normal cells. Cancer cells created by investigators by introducing specific genomic insults generally belong to one cell lineage. For example, transgenic mice in which the LIM-only 2 (LMO2, associated with human acute T-lymphoblastic leukaemia) and BCR-ABLp210 (associated with human chronic myeloid leukaemia) oncogenes were active solely within the haematopoietic stem-cell compartment developed T-lymphocyte and neutrophil lineage-restricted leukaemia, respectively. This recapitulated the human form of these diseases. This ‘hardwiring’ of lineage affiliation, either throughout leukaemic stem cell development or at a particular stage, is different to the behaviour of normal haematopoietic stem cells. While normal cells directly commit to a developmental pathway, they also remain versatile and can develop into a terminally differentiated cell that is not part of the initial lineage. Many cancer stem cells do not have this versatility, and this is an essential difference between normal and cancer stem cells. In this report, we review findings that support this notion.
Missing Link Between Molecular Aspects of Ventricular Arrhythmias and QRS Complex Morphology in Left Ventricular Hypertrophy
Authors: Bacharova Ljuba
Published: December 2019

The aim of this opinion paper is to point out the knowledge gap between evidence on the molecular level and clinical diagnostic possibilities in left ventricular hypertrophy (LVH) regarding the prediction of ventricular arrhythmias and monitoring the effect of therapy. LVH is defined as an increase in left ventricular size and is associated with increased occurrence of ventricular arrhythmia. Hypertrophic rebuilding of myocardium comprises interrelated processes on molecular, subcellular, cellular, tissue, and organ levels affecting electrogenesis, creating a substrate for triggering and maintaining arrhythmias. The knowledge of these processes serves as a basis for developing targeted therapy to prevent and treat arrhythmias. In the clinical practice, the method for recording electrical phenomena of the heart is electrocardiography. The recognized clinical electrocardiogram (ECG) predictors of ventricular arrhythmias are related to alterations in electrical impulse propagation, such as QRS complex duration, QT interval, early repolarization, late potentials, and fragmented QRS, and they are not specific for LVH. However, the simulation studies have shown that the QRS complex patterns documented in patients with LVH are also conditioned remarkably by the alterations in impulse propagation. These QRS complex patterns in LVH could be potentially recognized for predicting ventricular arrhythmia and for monitoring the effect of therapy.
Glucocorticoids Equally Stimulate Epithelial Na+ Transport in Male and Female Fetal Alveolar Cells
Authors: Laube Mandy , Riedel Diana , Ackermann Benjamin , Haase Melanie , H. Thome Ulrich
Published: December 2019

Preterm infants frequently suffer from respiratory distress syndrome (RDS), possibly due to lower expression of epithelial Na+ channels (ENaC). RDS incidence is sex-specific, affecting males almost twice as often. Despite the use of antenatal glucocorticoids (GCs), the sex difference persists. It is still controversial whether both sexes benefit equally from GCs. We previously showed that Na+ transport is higher in female compared with male fetal distal lung epithelial (FDLE) cells. Since GCs increase Na+ transport, we hypothesized that their stimulating effect might be sex-specific. We analyzed FDLE cells with Ussing chambers and RT-qPCR in the presence or absence of fetal serum. In serum-free medium, GCs increased the ENaC activity and mRNA expression, independent of sex. In contrast, GCs did not increase the Na+ transport in serum-supplemented media and abolished the otherwise observed sex difference. Inhibition of the GC receptor in the presence of serum did not equalize Na+ transport between male and female cells. The GC-induced surfactant protein mRNA expression was concentration and sex-specific. In conclusion, female and male FDLE cells exhibit no sex difference in response to GCs with regard to Na+ transport, and GR activity does not contribute to the higher Na+ transport in females.
Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells
Authors: Komarova Elena Y. , Marchenko Larisa V. , Zhakhov Alexander V. , Nikotina Alina D. , Aksenov Nikolay D. , Suezov Roman V. , Ischenko Alexander M. , Margulis Boris A. , Guzhova Irina V.
Published: December 2019

Cancer cells are known to contain high levels of the heat shock protein 70 kDa (Hsp70), which mediates increased cell proliferation, escape from programmed cell death, enhanced invasion, and metastasis. A part of Hsp70 molecules may release from cancer cells and affect the behavior of adjacent stromal cells. To explore the effects of Hsp70 on the status of monocytes/macrophages in the tumor locale, we incubated human carcinoma cells of three distinct lines with normal and reduced content of Hsp70 with THP1 monocytes. Using two methods, we showed that the cells with knock-down of Hsp70 released a lower amount of protein in the extracellular medium. Three cycles of the co-cultivation of cancer and monocytic cells led to the secretion of several cytokines typical of the tumor microenvironment (TME) and to pro-cancer activation of the monocytes/macrophages as established by elevation of F4/80 and arginase-1 markers. Unexpectedly, the efficacy of epithelial–mesenchymal transition and resistance of carcinoma cells to anticancer drugs after incubation with monocytic cells were more pronounced in cells with lower Hsp70, e.g., releasing less Hsp70 into the extracellular milieu. These data suggest that Hsp70 released from tumor cells into the TME is able, together with the development of an anti-cancer immune response, to limit the conversion of a considerable part of monocytic cells to the pro-tumor phenotype.
Folic Acid Decreases Astrocyte Apoptosis by Preventing Oxidative Stress-Induced Telomere Attrition
Authors: Li Wen , Ma Yue , Li Zhenshu , Lv Xin , Wang Xinyan , Zhou Dezheng , Luo Suhui , Wilson John X. , Huang Guowei
Published: December 2019

Astrocytes are the most widely distributed cells in the brain, and astrocyte apoptosis may play an important role in the pathogenesis of neurodegenerative diseases. Folate is required for the normal development of the nervous system, but its effect on astrocyte apoptosis is unclear. In this study, we hypothesized that folic acid (the therapeutic form of folate) decreases astrocyte apoptosis by preventing oxidative stress-induced telomere attrition. Primary cultures of astrocytes were incubated for 12 days with various concentrations of folic acid (0–40 μmol/L), then cell proliferation, apoptosis, intracellular folate concentration, intracellular homocysteine (Hcy) concentration, intracellular reactive oxygen species (ROS) levels, telomeric DNA oxidative damage, and telomere length were determined. The results showed that folic acid deficiency decreased intracellular folate, cell proliferation, and telomere length, whereas it increased Hcy concentration, ROS levels, telomeric DNA oxidative damage, and apoptosis. In contrast, folic acid dose-dependently increased intracellular folate, cell proliferation, and telomere length but it decreased Hcy concentration, ROS levels, telomeric DNA oxidative damage, and apoptosis. In conclusion, folic acid inhibited apoptosis in astrocytes. The underlying mechanism for this protective effect may be that folic acid decreased oxidative stress and thereby prevented telomeric DNA oxidative damage and telomere attrition.
Immune Functional Analysis of Chitin Deacetylase 3 from the Asian Citrus Psyllid Diaphorina citri
Authors: Yu Hai-Zhong , Li Ning-Yan , Li Bing , Toufeeq Shahzad , Xie Yan-Xin , Huang Yu-Ling , Du Yi-Ming , Zeng Xiang-Dong , Zhu Bo , Lu Zhan-Jun
Published: December 2019

Chitin deacetylase (CDA) is a chitin degradation enzyme that strictly catalyzes the deacetylation of chitin to form chitosan, which plays an important role in regulating growth and development, as well as the immune response. In this study, a chitin deacetylase 3 gene (CDA3) was identified with a complete open reading frame (ORF) of 1362 bp from the genome database of Diaphorina citri, encoding a protein of 453 amino acids. Spatiotemporal expression analysis suggested that D. citri CDA3 (DcCDA3) had the highest expression level in the integument and third-instar nymph stage. Furthermore, DcCDA3 expression level can be induced by 20-hydroxyecdysone (20E). Injection of Escherichia coli and Staphylococcus aureus induced the upregulation of DcCDA3 in the midgut, while DcCDA3 was downregulated in the fat body. After silencing DcCDA3 by RNA interference, there was no influence on the D. citri phenotype. In addition, bactericidal tests showed that recombinant DcCDA3 inhibited gram-positive bacteria, including S. aureus and Bacillus subtilis (B. subtilis). In conclusion, our results suggest that DcCDA3 might play an important role in the immune response of D. citri.
Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients
Authors: Boldrin Elisa , Nardo Giorgia , Zulato Elisabetta , Bonanno Laura , Polo Valentina , Frega Stefano , Pavan Alberto , Indraccolo Stefano , Saggioro Daniela
Published: December 2019

Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.
Unconventional Myosins: How Regulation Meets Function
Authors: Fili Natalia , Toseland Christopher P.
Published: December 2019

Unconventional myosins are multi-potent molecular motors that are assigned important roles in fundamental cellular processes. Depending on their mechano-enzymatic properties and structural features, myosins fulfil their roles by acting as cargo transporters along the actin cytoskeleton, molecular anchors or tension sensors. In order to perform such a wide range of roles and modes of action, myosins need to be under tight regulation in time and space. This is achieved at multiple levels through diverse regulatory mechanisms: the alternative splicing of various isoforms, the interaction with their binding partners, their phosphorylation, their applied load and the composition of their local environment, such as ions and lipids. This review summarizes our current knowledge of how unconventional myosins are regulated, how these regulatory mechanisms can adapt to the specific features of a myosin and how they can converge with each other in order to ensure the required tight control of their function.
Targeting Pseudomonas aeruginosa in the Sputum of Primary Ciliary Dyskinesia Patients with a Combinatorial Strategy Having Antibacterial and Anti-Virulence Potential
Authors: Maisetta Giuseppantonio , Grassi Lucia , Esin Semih , Kaya Esingül , Morelli Andrea , Puppi Dario , Piras Martina , Chiellini Federica , Pifferi Massimo , Batoni Giovanna
Published: December 2019

In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium.
Comparative Proteomic Analysis of Nodulated and Non-Nodulated Casuarina glauca Sieb. ex Spreng. Grown under Salinity Conditions Using Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS)
Authors: Graça Inês , Mendes Vera M. , Marques Isabel , Duro Nuno , da Costa Mário , Ramalho José C. , Pawlowski Katharina , Manadas Bruno , Pinto Ricardo Cândido P. , Ribeiro-Barros Ana I.
Published: December 2019

Casuarina glauca displays high levels of salt tolerance, but very little is known about how this tree adapts to saline conditions. To understand the molecular basis of C. glauca response to salt stress, we have analyzed the proteome from branchlets of plants nodulated by nitrogen-fixing Frankia Thr bacteria (NOD+) and non-nodulated plants supplied with KNO3 (KNO3+), exposed to 0, 200, 400, and 600 mM NaCl. Proteins were identified by Short Gel, Long Gradient Liquid Chromatography coupled to Tandem Mass Spectrometry and quantified by Sequential Window Acquisition of All Theoretical Mass Spectra -Mass Spectrometry. 600 proteins were identified and 357 quantified. Differentially Expressed Proteins (DEPs) were multifunctional and mainly involved in Carbohydrate Metabolism, Cellular Processes, and Environmental Information Processing. The number of DEPs increased gradually with stress severity: (i) from 7 (200 mM NaCl) to 40 (600 mM NaCl) in KNO3+; and (ii) from 6 (200 mM NaCl) to 23 (600 mM NaCl) in NOD+. Protein–protein interaction analysis identified different interacting proteins involved in general metabolic pathways as well as in the biosynthesis of secondary metabolites with different response networks related to salt stress. Salt tolerance in C. glauca is related to a moderate impact on the photosynthetic machinery (one of the first and most important stress targets) as well as to an enhancement of the antioxidant status that maintains cellular homeostasis.
Prediction of Crosswind Separation Velocity for Fan and Nacelle Systems Using Body Force Models: Part 2: Comparison of Crosswind Separation Velocity with and without Detailed Fan Stage Geometry
Authors: Minaker Quentin J. , Defoe Jeffrey J.
Published: December 2019

Modern aircraft engines must accommodate inflow distortions entering the engines as a consequence of modifying the size, shape, and placement of the engines and/or nacelle to increase propulsive efficiency and reduce aircraft weight and drag. It is important to be able to predict the interactions between the external flow and the fan early in the design process. This is challenging due to computational cost and limited access to detailed fan/engine geometry. In this, the second part of a two part paper, we apply the fan gas path and body force model design process from Part 1 to the problem of predicting flow separation over an engine nacelle lip caused by crosswind. The inputs to the design process are based on NASA Stage 67. A body force model using the detailed Stage 67 geometry is also used to enable assessment of the accuracy of the design process based approach. In uniform flow, the model produced by the design process recreates the spanwise loading distribution of Rotor 67 with a 7% RMS error. Both models are then employed to predict crosswind separation velocity. The two approaches are found to agree in their prediction of the crosswind separation velocity to within 5%.
Development of an Electrohydraulic Variable Buoyancy System
Authors: Falcão Carneiro João , Pinto João Bravo , Cruz Nuno A. , Gomes de Almeida Fernando
Published: December 2019

The growing needs in exploring ocean resources have been pushing the length and complexity of autonomous underwater vehicle (AUV) missions, leading to more stringent energy requirements. A promising approach to reduce the energy consumption of AUVs is to use variable buoyancy systems (VBSs) as a replacement or complement to thruster action, since VBSs only require energy consumption during limited periods of time to control the vehicle’s floatation. This paper presents the development of an electrohydraulic VBS to be included in an existing AUV for shallow depths of up to 100 m. The device’s preliminary mechanical design is presented, and a mathematical model of the device’s power consumption is developed, based on data provided by the manufacturer. Taking a standard mission profile as an example, a comparison between the energy consumed using thrusters and the designed VBS is presented and compared.
Reinforcement Learning for Efficient Network Penetration Testing
Authors: Ghanem Mohamed C. , Chen Thomas M.
Published: December 2019

Penetration testing (also known as pentesting or PT) is a common practice for actively assessing the defenses of a computer network by planning and executing all possible attacks to discover and exploit existing vulnerabilities. Current penetration testing methods are increasingly becoming non-standard, composite and resource-consuming despite the use of evolving tools. In this paper, we propose and evaluate an AI-based pentesting system which makes use of machine learning techniques, namely reinforcement learning (RL) to learn and reproduce average and complex pentesting activities. The proposed system is named Intelligent Automated Penetration Testing System (IAPTS) consisting of a module that integrates with industrial PT frameworks to enable them to capture information, learn from experience, and reproduce tests in future similar testing cases. IAPTS aims to save human resources while producing much-enhanced results in terms of time consumption, reliability and frequency of testing. IAPTS takes the approach of modeling PT environments and tasks as a partially observed Markov decision process (POMDP) problem which is solved by POMDP-solver. Although the scope of this paper is limited to network infrastructures PT planning and not the entire practice, the obtained results support the hypothesis that RL can enhance PT beyond the capabilities of any human PT expert in terms of time consumed, covered attacking vectors, accuracy and reliability of the outputs. In addition, this work tackles the complex problem of expertise capturing and re-use by allowing the IAPTS learning module to store and re-use PT policies in the same way that a human PT expert would learn but in a more efficient way.
Analytical Model for Air Flow into Cracked Concrete Structures for Super-Speed Tube Transport Systems
Authors: Devkota Prakash , Park Joonam
Published: December 2019

The super-speed tube transport (SSTT) system, which enables high-speed transportation in a partially vacuumed tube by minimizing the air resistance, is drawing attention as a next-generation transportation system. To evaluate the applicability of concrete as a material for the system, the effect of cracks on the airtightness of the system needs to be considered. This study aims to establish an analytical relationship between the cracks induced on a concrete tube structure and the system airtightness. An analytical model for the leakage rate through the concrete cracks is first applied to establish a differential equation, which can help determine the air flow rate into the concrete tube structure through the cracks. A mathematical formula for predicting the internal pressure changes over time in the concrete tube structure is then derived. The effect of crack development on the system airtightness is assessed through parametric analysis and a crack index for describing the extent of crack development is proposed by investigating the correlation with the system airtightness. Finally, assuming that the cracks due to external loadings are closely related to the displacement, the correlation between displacements and the airtightness of concrete tube structures is demonstrated through a set of experimental tests. As a result, the necessity of crack analysis for evaluation of the airtightness performance is emphasized.