bluuebunny/crossref_metadata_2025 huggingface dataset:
Hg Levels in Marine Porifera of Montecristo and Giglio Islands (Tuscan Archipelago, Italy)
Authors: Roveta Camilla , Pica Daniela , Calcinai Barbara , Girolametti Federico , Truzzi Cristina , Illuminati Silvia , Annibaldi Anna , Puce Stefania
Published: June 2020

Porifera are filter-feeding organisms known to bioaccumulate different contaminants in their tissues. The presence of mercury (Hg) has been reported in different Mediterranean species, mainly collected in the southern coast of France. In the present study, mercury concentrations in the tissue of the sponges of Montecristo and Giglio, two islands of Tuscany Archipelago National Park (TANP), are presented for the first time. Analyses of total mercury content were performed by Direct Mercury Analyzer. Statistical differences have been reported in the Hg concentrations of species collected in both islands, but they do not appear related to the anthropic impacts of the islands. Among the collected species, a high intra- and inter-variability have been recorded, with Cliona viridis showing the lowest concentration (0.0167–0.033 mg·kg−1 dry weight), and Chondrosia reniformis and Sarcotragus spinosulus the highest (0.57 ± 0.15 and 0.64 ± 0.01 mg·kg−1 dry weight, respectively). The variability of Hg measured did not allow us to identify sponges as bioindicators of toxic elements. Anyway, these results improve knowledge on the ecosystem of the TANP, underlining the species-specificity of metal concentrations for Porifera, and providing additional data to address the main input of the Marine Strategy guidelines to protect coasts, seas and oceans.
An Event-Driven Agent-Based Simulation Model for Industrial Processes
Authors: Iannino Vincenzo , Mocci Claudio , Vannocci Marco , Colla Valentina , Caputo Andrea , Ferraris Francesco
Published: June 2020

Process manufacturing industries are complex and dynamic systems composed of several processes, subject to many operations and unexpected events that can compromise overall system performance. Therefore, the use of technologies and methods that can transform traditional process industries into smart factories is necessary. In this paper, a smart industrial process based on intelligent software agents is presented with the aim of providing a technological solution to the specific needs of the process industry. An event-driven agent-based simulation model composed of eight reactive agents was designed to simulate and control the operations of a generic industrial process. The agents were modeled using the actor approach and the communication mechanism was based on the publish–subscribe paradigm. The overall system was tested in different scenarios, such as faults, changing operating conditions and off-spec productions. The proposed agent-based simulation model proved to be very efficient in promptly reacting to different dynamic scenarios and in suitably handling different situations. Furthermore, the usability and the practicality of the proposed software tool facilitate its deployment and customization to different production chains, and provide a practical example of the use of multi-agent systems and artificial intelligence in the context of industry 4.0.
Shear Lag Effect and Accordion Effect on Dynamic Characteristics of Composite Box Girder Bridge with Corrugated Steel Webs
Authors: Zhang Yuntai , Jiang Lizhong , Zhou Wangbao , Feng Yulin
Published: June 2020

This study proposed a dynamic characteristic analytical method (ANM) of a composite box girder bridge with corrugated steel web (CBGCSW) by completely considering the impact of shear lag effect and accordion effect of corrugated steel webs. Based on energy principles and variational principles, a vibration differential equation and the natural boundary conditions of a CBGCSW were developed. The analytical calculation formula for solving the vibration differential equation was then obtained. The results calculated using the ANM agreed well with previous experimental results, which validated the correctness of ANM. To demonstrate the superiority of the ANM, the vibration frequencies of several abstract CBGCSWs with varying ratios of span–width, obtained using the elementary beam theory (EBT) and the finite element method (FEM), were compared with those obtained by ANM. The efficacy of the ANM was verified and some meaningful conclusions were drawn which are helpful to relevant engineering design, such as the observation that a higher natural vibration frequency and smaller span–width ratio significantly magnified the shear lag effect of CBGCSW. The first five-order natural vibration frequencies of the CBGCSW were significantly lower than those of the composite box girder bridge with general steel web (CBGGSW), which indicates that the impact of the accordion effect is significant.
Identification of Surgical Plan for Syndesmotic Fixation Procedure Based on Finite Element Method
Authors: Goh Tae Sik , Lim Beop-Yong , Lee Jung Sub , Lee Chi-Seung
Published: June 2020

Syndesmosis injuries account for approximately 20% of ankle fractures that require surgery. Although multiple surgical options are available, all of them are based on metal screws. Serious complications that arise when applying metal screws include screw loosening or breakage. To prevent such complications, we applied a simulation method using a finite element (FE) analysis. We created a 3D FE model of an ankle joint and conducted an FE analysis focusing on syndesmosis in terms of the level, material, and diameter of the syndesmotic screw and the number of penetrated cortical bones. The magnitude and direction of the force applied to the tibia in the midstance state were considered for simulating the model. The maximum von-Mises stress and syndesmosis widening were analyzed in terms of different biomechanical parameters. We identified the characteristics of the most biomechanically stable syndesmotic screw and its fixation point on the basis of the two parameters. We demonstrated that the ideal syndesmotic screw fixation should be fixed at a level 20 to 25 mm above the ankle using a 4.5 mm titanium screw.
Electronic and Transport Properties of Epitaxial Graphene on SiC and 3C-SiC/Si: A Review
Authors: Pradeepkumar Aiswarya , Gaskill D. Kurt , Iacopi Francesca
Published: June 2020

The electronic and transport properties of epitaxial graphene are dominated by the interactions the material makes with its surroundings. Based on the transport properties of epitaxial graphene on SiC and 3C-SiC/Si substrates reported in the literature, we emphasize that the graphene interfaces formed between the active material and its environment are of paramount importance, and how interface modifications enable the fine-tuning of the transport properties of graphene. This review provides a renewed attention on the understanding and engineering of epitaxial graphene interfaces for integrated electronics and photonics applications.
Neuromorphic Robotic Platform with Visual Input, Processor and Actuator, Based on Spiking Neural Networks
Authors: Cheng Ran , Mirza Khalid B. , Nikolic Konstantin
Published: June 2020

This paper describes the design and modus of operation of a neuromorphic robotic platform based on SpiNNaker, and its implementation on the goalkeeper task. The robotic system utilises an address event representation (AER) type of camera (dynamic vision sensor (DVS)) to capture features of a moving ball, and a servo motor to position the goalkeeper to intercept the incoming ball. At the backbone of the system is a microcontroller (Arduino Due) which facilitates communication and control between different robot parts. A spiking neuronal network (SNN), which is running on SpiNNaker, predicts the location of arrival of the moving ball and decides where to place the goalkeeper. In our setup, the maximum data transmission speed of the closed-loop system is approximately 3000 packets per second for both uplink and downlink, and the robot can intercept balls whose speed is up to 1 m/s starting from the distance of about 0.8 m. The interception accuracy is up to 85%, the response latency is 6.5 ms and the maximum power consumption is 7.15 W. This is better than previous implementations based on PC. Here, a simplified version of an SNN has been developed for the ‘interception of a moving object’ task, for the purpose of demonstrating the platform, however a generalised SNN for this problem is a nontrivial problem. A demo video of the robot goalie is available on YouTube.
Antiarrhythmic Properties of Elsholtzia ciliata Essential Oil on Electrical Activity of the Isolated Rabbit Heart and Preferential Inhibition of Sodium Conductance
Authors: Mačianskienė Regina , Pudžiuvelytė Lauryna , Bernatonienė Jurga , Almanaitytė Mantė , Navalinskas Antanas , Treinys Rimantas , Andriulė Inga , Jurevičius Jonas
Published: June 2020

Elsholtzia ciliata essential oil (E. ciliata) has been developed in Lithuania and internationally patented as exerting antiarrhythmic properties. Here we demonstrate the pharmacological effects of this herbal preparation on cardiac electrical activity. We used cardiac surface ECG and a combination of microelectrode and optical mapping techniques to track the action potentials (APs) in the Langendorff-perfused rabbit heart model during atrial/endo-/epi-cardial pacing. Activation time, conduction velocity and AP duration (APD) maps were constructed. E. ciliata increased the QRS duration and shortened QT interval of ECG at concentrations of 0.01–0.1 μL/mL, whereas 0.3 μL/mL (0.03%) concentration resulted in marked strengthening of changes. In addition, the E. ciliata in a concentration dependent manner reduced the AP upstroke dV/dtmax and AP amplitude as well as APD. A marked attenuation of the AP dV/dtmax and a slowing spread of electrical signals suggest the impaired functioning of Na+-channels, and the effect was use-dependent. Importantly, all these changes were at least partially reversible. Our results indicate that E. ciliata modulates cardiac electrical activity preferentially inhibiting Na+ conductance, which may contribute to its effects as a natural antiarrhythmic medicine.
Metabolism of Soy Isoflavones by Intestinal Bacteria: Genome Analysis of an Adlercreutzia equolifaciens Strain That Does Not Produce Equol
Authors: Vázquez Lucía , Flórez Ana Belén , Redruello Begoña , Mayo Baltasar
Published: June 2020

Isoflavones are transformed in the gut into more estrogen-like compounds or into inactive molecules. However, neither the intestinal microbes nor the pathways leading to the synthesis of isoflavone-derived metabolites are fully known. In the present work, 73 fecal isolates from three women with an equol-producing phenotype were considered to harbor equol-related genes by qPCR. After typing, 57 different strains of different taxa were tested for their ability to act on the isoflavones daidzein and genistein. Strains producing small to moderate amounts of dihydrodaidzein and/or O-desmethylangolensin (O-DMA) from daidzein and dihydrogenistein from genistein were recorded. However, either alone or in several strain combinations, equol producers were not found, even though one of the strains, W18.34a (also known as IPLA37004), was identified as Adlercreutzia equolifaciens, a well-described equol-producing species. Analysis and comparison of A. equolifaciens W18.34a and A. equolifaciens DSM19450T (an equol producer bacterium) genome sequences suggested a deletion in the former involving a large part of the equol operon. Furthermore, genome comparison of A. equolifaciens and Asaccharobacter celatus (other equol-producing species) strains from databases indicated many of these also showed deletions within the equol operon. The present results contribute to our knowledge to the activity of gut bacteria on soy isoflavones.
The Citrus Flavonoid Hesperetin Has an Inadequate Anti-Arrhythmic Profile in the ΔKPQ NaV1.5 Mutant of the Long QT Type 3 Syndrome
Authors: Alvarez-Collazo Julio , López-Requena Alejandro , Alvarez Julio L. , Talavera Karel
Published: June 2020

Type 3 long QT syndromes (LQT3) are associated with arrhythmogenic gain-of-function mutations in the cardiac voltage-gated Na+ channel (hNaV1.5). The citrus flavanone hesperetin (HSP) was previously suggested as a template molecule to develop new anti-arrhythmic drugs, as it blocks slowly-inactivating currents carried by the LQT3-associated hNaV1.5 channel mutant R1623Q. Here we investigated whether HSP also has potentially beneficial effects on another LQT3 hNaV1.5 channel variant, the ΔKPQ, which is associated to lethal ventricular arrhythmias. We used whole-cell patch-clamp to record Na+ currents (INa) in HEK293T cells transiently expressing hNaV1.5 wild type or ΔKPQ mutant channels. HSP blocked peak INa and the late INa carried by ΔKPQ mutant channels with an effective concentration of ≈300 μM. This inhibition was largely voltage-independent and tonic. HSP decreased the rate of inactivation of ΔKPQ channels and, consequently, was relatively weak in reducing the intracellular Na+ load in this mutation. We conclude that, although HSP has potential value for the treatment of the R1623Q LQT3 variant, this compound is inadequate to treat the LQT3 associated to the ΔKPQ genetic variant. Our results underscore the precision medicine rationale of better understanding the basic pathophysiological and pharmacological mechanisms to provide phenotype- genotype-directed individualization of treatment.
False Myths versus Medical Facts: Ten Common Misconceptions Related to Dry Eye Disease
Authors: Giannaccare Giuseppe , Scorcia Vincenzo
Published: June 2020

Since the first definition of dry eye, rapid progress has been made in this field over the past decades that has guided profound changes in the definition, classification, diagnosis and management of the disease. Although dry eye is one of the most frequently encountered ocular conditions, various “old” misconceptions persist, in particular among comprehensive ophthalmologists not specialized in ocular surface diseases. These misconceptions hamper the correct diagnosis and the proper management of dry eye in the routine clinical practice. In the present review, we described the 10 most common misconceptions related to dry eye and provided an evidence-based guide for reconsidering them using the format “false myth versus medical fact”. These misconceptions concern the dry eye definition and classification (#1, #2, #3), disease physiopathology (#4), diagnosis (#5), symptoms (#6, #7) and treatment (#8, #9, #10). Nowadays, dry eye is still an under-recognized and evolving disease that poses significant clinical challenges to ophthalmologists. The two major reasons behind these challenges include the heterogeneity of the conditions that fall under the umbrella term of dry eye and the common discrepancy between signs and symptoms.
Detection of Cardiovascular CRP Protein Biomarker Using a Novel Nanofibrous Substrate
Authors: Macwan Isaac , Aphale Ashish , Bhagvath Prathamesh , Prasad Shalini , Patra Prabir
Published: June 2020

It is known that different diseases have characteristic biomarkers that are secreted very early on, even before the symptoms have developed. Before any kind of therapeutic approach can be used, it is necessary that such biomarkers be detected at a minimum concentration in the bodily fluids. Here, we report the fabrication of an interdigitated sensing device integrated with polyvinyl alcohol (PVA) nanofibers and carbon nanotubes (CNT) for the detection of an inflammatory biomarker, C-reactive protein (CRP). The limit of detection (LOD) was achieved in a range of 100 ng mL−1 and 1 fg mL−1 in both phosphate buffered saline (PBS) and human serum (hs). Furthermore, a significant change in the electrochemical impedance from 45% to 70% (hs) and 38% to 60% (PBS) over the loading range of CRP was achieved. The finite element analysis indicates that a non-redox charge transduction at the solid/liquid interface on the electrode surface is responsible for the enhanced sensitivity. Furthermore, the fabricated biosensor consists of a large electro-active surface area, along with better charge transfer characteristics that enabled improved specific binding with CRP. This was determined both experimentally and from the simulated electrochemical impedance of the PVA nanofiber patterned gold electrode.
Contribution of Dopamine Transporter Gene Methylation Status to Cannabis Dependency
Authors: Grzywacz Anna , Barczak Wojciech , Chmielowiec Jolanta , Chmielowiec Krzysztof , Suchanecka Aleksandra , Trybek Grzegorz , Masiak Jolanta , Jagielski Paweł , Grocholewicz Katarzyna , Rubiś Blazej
Published: June 2020

The susceptibility to cannabis dependency results from the influence of numerous factors such as social, genetic, as well as epigenetic factors. Many studies have attempted to discover a molecular basis for this disease. However, our study aimed at evaluating the connection between altered methylation of the dopamine transporter gene (DAT1) promoter CpG sites and cannabis dependency. In the cases of some DNA sequences, including the DAT1 gene region, their methylation status in blood cells may reflect a systemic modulation in the whole organism. Consequently, we isolated the DNA from the peripheral blood cells from a group of 201 cannabis-dependent patients and 285 controls who were healthy volunteers and who were matched for age and sex. The DNA was subjected to bisulfite conversion and sequencing. Our analysis revealed no statistical differences in the general methylation status of the DAT1 gene promoter CpG island between the patients and controls. Yet, the analysis of individual CpG sites where methylation occurred indicated significant differences. These sites are known to be bound by transcription factors (e.g., SP1, p53, PAX5, or GR), which, apart from other functions, were shown to play a role in the development of the nervous system. Therefore, DAT1 gene promoter methylation studies may provide important insight into the mechanism of cannabis dependency.
Increased Neural Reward Responsivity in Adolescents with ASD after Social Skills Intervention
Authors: Baker Elizabeth , Veytsman Elina , Martin Ann Marie , Blacher Jan , Stavropoulos Katherine K. M.
Published: June 2020

The reward system has been implicated as a potential neural mechanism underlying social-communication deficits in individuals with autism spectrum disorder (ASD). However, it remains unclear whether the neural reward system in ASD is sensitive to behavioral interventions. The current study measured the reward positivity (RewP) in response to social and nonsocial stimuli in seven adolescents with ASD before and after participation in the Program for the Education and Enrichment of Relational Skills (PEERS®) intervention. This study also included seven neurotypical adolescents who were tested at two time points but did not receive intervention. We examined the RewP across the course of a task by comparing brain activity during the first versus second half of trials to understand patterns of responsivity over time. Improvements in social skills and decreased social-communication impairments for teens with ASD were observed after PEERS®. Event-related potential (ERP) results suggested increased reward sensitivity during the first half of trials in the ASD group after intervention. Adolescents with ASD who exhibited less reward-related brain activity before intervention demonstrated the greatest behavioral benefits from the intervention. These findings have implications for how neuroscience can be used as an objective outcome measure before and after intervention in ASD.
Reduced Graphene Oxide/ZnIn2S4 Nanocomposite Photocatalyst with Enhanced Photocatalytic Performance for the Degradation of Naproxen under Visible Light Irradiation
Authors: Fu Kun , Pan Yishuai , Ding Chao , Shi Jun , Deng Huiping
Published: June 2020

The development of photocatalysts with visible light response is of great significance to cope with energy crisis and environmental remediation. In this study, a visible light-driven photocatalyst reduced graphene oxide/ZnIn2S4 (rGO/ZIS) was prepared by a facile one-pot hydrothermal method. The photocatalyst was used for the degradation of naproxen under visible light illumination and it exhibited remarkably degradation efficiency (nearly 99% within 60 min). The improved photocatalytic degradation performance can be attributed to the enhancement of light adsorption capacity and effective separation of photoinduced electron–hole pairs. The reactive species quenching experiments and EPR measurements demonstrated that superoxide radical (O2−) and hole (h+) play a dominant role in the photocatalytic degradation reactions. In addition, the degradation intermediates were identified and the degradation pathway was suggested.
Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives
Authors: Moore Gillian , Annett Stephanie , McClements Lana , Robson Tracy
Published: June 2020

Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, lung and adenoid cystic carcinoma. Moreover, upregulation of Notch receptors and ligands and aberrant Notch signalling is frequently observed in cancer. It is involved in cancer hallmarks including proliferation, survival, migration, angiogenesis, cancer stem cell renewal, metastasis and drug resistance. It is a key component of cell-to-cell interactions between cancer cells and cells of the tumour microenvironment, such as endothelial cells, immune cells and fibroblasts. Notch displays diverse crosstalk with many other oncogenic signalling pathways, and may drive acquired resistance to targeted therapies as well as resistance to standard chemo/radiation therapy. The past 10 years have seen the emergence of different classes of drugs therapeutically targeting Notch including receptor/ligand antibodies, gamma secretase inhibitors (GSI) and most recently, the development of Notch transcription complex inhibitors. It is an exciting time for Notch research with over 70 cancer clinical trials registered and the first-ever Phase III trial of a Notch GSI, nirogacestat, currently at the recruitment stage.
Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death
Authors: Battaglia Anna Martina , Chirillo Roberta , Aversa Ilenia , Sacco Alessandro , Costanzo Francesco , Biamonte Flavia
Published: June 2020

Ferroptosis is a new type of oxidative regulated cell death (RCD) driven by iron-dependent lipid peroxidation. As major sites of iron utilization and master regulators of oxidative metabolism, mitochondria are the main source of reactive oxygen species (ROS) and, thus, play a role in this type of RCD. Ferroptosis is, indeed, associated with severe damage in mitochondrial morphology, bioenergetics, and metabolism. Furthermore, dysregulation of mitochondrial metabolism is considered a biochemical feature of neurodegenerative diseases linked to ferroptosis. Whether mitochondrial dysfunction can, per se, initiate ferroptosis and whether mitochondrial function in ferroptosis is context-dependent are still under debate. Cancer cells accumulate high levels of iron and ROS to promote their metabolic activity and growth. Of note, cancer cell metabolic rewiring is often associated with acquired sensitivity to ferroptosis. This strongly suggests that ferroptosis may act as an adaptive response to metabolic imbalance and, thus, may constitute a new promising way to eradicate malignant cells. Here, we review the current literature on the role of mitochondria in ferroptosis, and we discuss opportunities to potentially use mitochondria-mediated ferroptosis as a new strategy for cancer therapy.
Mechanistic Involvement of Long Non-Coding RNAs in Oncotherapeutics Resistance in Triple-Negative Breast Cancer
Authors: Kansara Samarth , Pandey Vijay , Lobie Peter E. , Sethi Gautam , Garg Manoj , Pandey Amit Kumar
Published: June 2020

Triple-negative breast cancer (TNBC) is one of the most lethal forms of breast cancer (BC), with a significant disease burden worldwide. Chemoresistance and lack of targeted therapeutics are major hindrances to effective treatments in the clinic and are crucial causes of a worse prognosis and high rate of relapse/recurrence in patients diagnosed with TNBC. In the last decade, long non-coding RNAs (lncRNAs) have been found to perform a pivotal role in most cellular functions. The aberrant functional expression of lncRNAs plays an ever-increasing role in the progression of diverse malignancies, including TNBC. Therefore, lncRNAs have been recently studied as predictors and modifiers of chemoresistance. Our review discusses the potential involvement of lncRNAs in drug-resistant mechanisms commonly found in TNBC and highlights various therapeutic strategies to target lncRNAs in this malignancy.
Isoleucine 44 Hydrophobic Patch Controls Toxicity of Unanchored, Linear Ubiquitin Chains through NF-κB Signaling
Authors: Blount Jessica R. , Libohova Kozeta , Silva Gustavo M. , Todi Sokol V.
Published: June 2020

Ubiquitination is a post-translational modification that regulates cellular processes by altering the interactions of proteins to which ubiquitin, a small protein adduct, is conjugated. Ubiquitination yields various products, including mono- and poly-ubiquitinated substrates, as well as unanchored poly-ubiquitin chains whose accumulation is considered toxic. We previously showed that transgenic, unanchored poly-ubiquitin is not problematic in Drosophila melanogaster. In the fruit fly, free chains exist in various lengths and topologies and are degraded by the proteasome; they are also conjugated onto other proteins as one unit, eliminating them from the free ubiquitin chain pool. Here, to further explore the notion of unanchored chain toxicity, we examined when free poly-ubiquitin might become problematic. We found that unanchored chains can be highly toxic if they resemble linear poly-ubiquitin that cannot be modified into other topologies. These species upregulate NF-κB signaling, and modulation of the levels of NF-κB components reduces toxicity. In additional studies, we show that toxicity from untethered, linear chains is regulated by isoleucine 44, which anchors a key interaction site for ubiquitin. We conclude that free ubiquitin chains can be toxic, but only in uncommon circumstances, such as when the ability of cells to modify and regulate them is markedly restricted.
The Function of Mitochondrial Calcium Uniporter at the Whole-Cell and Single Mitochondrion Levels in WT, MICU1 KO, and MICU2 KO Cells
Authors: Shah Syed Islamuddin , Ullah Ghanim
Published: June 2020

Mitochondrial Ca2+ ([Ca2+]M) uptake through its Ca2+ uniporter (MCU) is central to many cell functions such as bioenergetics, spatiotemporal organization of Ca2+ signals, and apoptosis. MCU activity is regulated by several intrinsic proteins including MICU1, MICU2, and EMRE. While significant details about the role of MICU1, MICU2, and EMRE in MCU function have emerged recently, a key challenge for the future experiments is to investigate how these regulatory proteins modulate mitochondrial Ca2+ influx through MCU in intact cells under pathophysiological conditions. This is further complicated by the fact that several variables affecting MCU function change dynamically as cell functions. To overcome this void, we develop a data-driven model that closely replicates the behavior of MCU under a wide range of cytosolic Ca2+ ([Ca2+]C), [Ca2+]M, and mitochondrial membrane potential values in WT, MICU1 knockout (KO), and MICU2 KO cells at the single mitochondrion and whole-cell levels. The model is extended to investigate how MICU1 or MICU2 KO affect mitochondrial function. Moreover, we show how Ca2+ buffering proteins, the separation between mitochondrion and Ca2+-releasing stores, and the duration of opening of Ca2+-releasing channels affect mitochondrial function under different conditions. Finally, we demonstrate an easy extension of the model to single channel function of MCU.
Hepatogenic Potential and Liver Regeneration Effect of Human Liver-derived Mesenchymal-Like Stem Cells
Authors: Lee Jooyoung , Choi Jiwan , Kang Seoon , Kim Jiye , Lee Ryunjin , So Seongjun , Yoon Young-In , Kirchner Varvara A. , Song Gi-Won , Hwang Shin , Lee Sung-Gyu , Kang Eunju , Tak Eunyoung
Published: June 2020

Human liver-derived stem cells (hLD-SCs) have been proposed as a possible resource for stem cell therapy in patients with irreversible liver diseases. However, it is not known whether liver resident hLD-SCs can differentiate toward a hepatic fate better than mesenchymal stem cells (MSCs) obtained from other origins. In this study, we compared the differentiation ability and regeneration potency of hLD-SCs with those of human umbilical cord matrix-derived stem cells (hUC-MSCs) by inducing hepatic differentiation. Undifferentiated hLD-SCs expressed relatively high levels of endoderm-related markers (GATA4 and FOXA1). During directed hepatic differentiation supported by two small molecules (Fasudil and 5-azacytidine), hLD-SCs presented more advanced mitochondrial respiration compared to hUC-MSCs. Moreover, hLD-SCs featured higher numbers of hepatic progenitor cell markers on day 14 of differentiation (CPM and CD133) and matured into hepatocyte-like cells by day 7 through 21 with increased hepatocyte markers (ALB, HNF4A, and AFP). During in vivo cell transplantation, hLD-SCs migrated into the liver of ischemia-reperfusion injury-induced mice within 2 h and relieved liver injury. In the thioacetamide (TAA)-induced liver injury mouse model, transplanted hLD-SCs trafficked into the liver and spontaneously matured into hepatocyte-like cells within 14 days. These results collectively suggest that hLD-SCs hold greater hepatogenic potential, and hepatic differentiation-induced hLD-SCs may be a promising source of stem cells for liver regeneration.
Intratumoral versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?
Authors: Gascón Marta , Isla Dolores , Cruellas Mara , Gálvez Eva M. , Lastra Rodrigo , Ocáriz Maitane , Paño José Ramón , Ramírez Ariel , Sesma Andrea , Torres-Ramón Irene , Yubero Alfonso , Pardo Julián , Martínez-Lostao Luis
Published: June 2020

The molecular and cell determinants that modulate immune checkpoint (ICI) efficacy in lung cancer are still not well understood. However, there is a necessity to select those patients that will most benefit from these new treatments. Recent studies suggest the presence and/or the relative balance of specific lymphoid cells in the tumor microenvironment (TEM) including the T cell (activated, memory, and regulatory) and NK cell (CD56dim/bright) subsets, and correlate with a better response to ICI. The analyses of these cell subsets in peripheral blood, as a more accessible and homogeneous sample, might facilitate clinical decisions concerning fast prediction of ICI efficacy. Despite recent studies suggesting that lymphoid circulating cells might correlate with ICI efficacy and toxicity, more analyses and investigation are required to confirm if circulating lymphoid cells are a relevant picture of the lung TME and could be instrumental as ICI response biomarkers. This short review is aimed to discuss the recent advances in this fast-growing field.
The Barley S-Adenosylmethionine Synthetase 3 Gene HvSAMS3 Positively Regulates the Tolerance to Combined Drought and Salinity Stress in Tibetan Wild Barley
Authors: Ahmed Imrul Mosaddek , Nadira Umme Aktari , Qiu Cheng-Wei , Cao Fangbin , Chen Zhong-Hua , Vincze Eva , Wu Feibo
Published: June 2020

Drought and salinity are two of the most frequently co-occurring abiotic stresses. Despite recent advances in the elucidation of the effects of these stresses individually during the vegetative stage of plants, significant gaps exist in our understanding of the combined effects of these two frequently co-occurring stresses. Here, Tibetan wild barley XZ5 (drought tolerant), XZ16 (salt tolerant), and cultivated barley cv. CM72 (salt tolerant) were subjected to drought (D), salinity (S), or a combination of both treatments (D+S). Protein synthesis is one of the primary activities of the green part of the plant. Therefore, leaf tissue is an important parameter to evaluate drought and salinity stress conditions. Sixty differentially expressed proteins were identified by mass spectrometry (MALDI-TOF/TOF) and classified into 9 biological processes based on Gene Ontology annotation. Among them, 21 proteins were found to be expressed under drought or salinity alone; however, under D+S, 7 proteins, including S-adenosylmethionine synthetase 3 (SAMS3), were exclusively upregulated in drought-tolerant XZ5 but not in CM72. HvSAMS3 carries both N-terminal and central domains compared with Arabidopsis and activates the expression of several ethylene (ET)-responsive transcription factors. HvSAMS3 is mainly expressed in the roots and stems, and HvSAMS3 is a secretory protein located in the cell membrane and cytoplasm. Barley stripe mosaic virus-based virus-induced gene silencing (BSMV-VIGS) of HvSAMS3 in XZ5 severely compromised its tolerance to D+S and significantly reduced plant growth and K+ uptake. The reduced tolerance to the combined stress was associated with the inhibition of polyamines such as spermidine and spermine, polyamine oxidase, ethylene, biotin, and antioxidant enzyme activities. Furthermore, the exogenous application of ethylene and biotin improved the tolerance to D+S in BSMV-VIGS:HvSAMS3-inoculated plants. Our findings highlight the significance of HvSAMS3 in the tolerance to D+S in XZ5.
Cytokine Profile in Striated Muscle Laminopathies: New Promising Biomarkers for Disease Prediction
Authors: Cappelletti Cristina , Tramacere Irene , Cavalcante Paola , Schena Elisa , Politano Luisa , Carboni Nicola , Gambineri Alessandra , D’Amico Adele , Ruggiero Lucia , Ricci Giulia , Siciliano Gabriele , Boriani Giuseppe , Mongini Tiziana Enrica , Vercelli Liliana , Biagini Elena , Ziacchi Matteo , D’Apice Maria Rosaria , Lattanzi Giovanna , Mantegazza Renato , Maggi Lorenzo , Bernasconi Pia
Published: June 2020

Laminopathies are a wide and heterogeneous group of rare human diseases caused by mutations of the LMNA gene or related nuclear envelope genes. The variety of clinical phenotypes and the wide spectrum of histopathological changes among patients carrying an identical mutation in the LMNA gene make the prognostic process rather difficult, and classical genetic screens appear to have limited predictive value for disease development. The aim of this study was to evaluate whether a comprehensive profile of circulating cytokines may be a useful tool to differentiate and stratify disease subgroups, support clinical follow-ups and contribute to new therapeutic approaches. Serum levels of 51 pro- and anti-inflammatory molecules, including cytokines, chemokines and growth factors, were quantified by a Luminex multiple immune-assay in 53 patients with muscular laminopathy (Musc-LMNA), 10 with non-muscular laminopathy, 22 with other muscular disorders and in 35 healthy controls. Interleukin-17 (IL-17), granulocyte colony-stimulating factor (G-CSF) and transforming growth factor beta (TGF-β2) levels significantly discriminated Musc-LMNA from controls; interleukin-1β (IL-1β), interleukin-4 (IL-4) and interleukin-8 (IL-8) were differentially expressed in Musc-LMNA patients compared to those with non-muscular laminopathies, whereas IL-17 was significantly higher in Musc-LMNA patients with muscular and cardiac involvement. These findings support the hypothesis of a key role of the immune system in Musc-LMNA and emphasize the potential use of cytokines as biomarkers for these disorders.
Transcriptomic microRNA Profiling of Dendritic Cells in Response to Gut Microbiota-Secreted Vesicles
Authors: Díaz-Garrido Natalia , Bonnin Sarah , Riera Marta , Gíménez Rosa , Badia Josefa , Baldomà Laura
Published: June 2020

The interconnection between nutrients, metabolites and microbes is a key factor governing the healthy/pathological status of an individual. Thus, microbiota-based research is essential in order to better understand human health and nutrition. Gut bacteria release membrane vesicles (MVs) as an intercellular communication mechanism that allows the direct delivery of factors that prime the host’s innate immune system. We have previously shown that MVs from intestinal E. coli activate dendritic cells (DCs) in a strain-specific manner. To gain insights into the regulatory mechanisms involved, here, we have used an RNA deep sequencing approach to identify differentially expressed miRNAs (microRNAs) in DCs which are challenged by the MVs of the probiotic Nissle 1917 (EcN) or the commensal ECOR12. MicroRNAs are post-transcriptional regulatory mediators that permit the fine tuning of signaling pathways. This approach allowed the identification of a common set of miRNAs which are modulated by MVs from both strains and miRNAs which are differentially expressed in response to EcN or ECOR12 MVs. Based on the differential expression of the target genes and subsequent validation experiments, we correlated some of the selected miRNAs with the reported cytokine profile and specific T cell responses. As far as we know, this is the first study to analyze the regulation of miRNAs in DCs by MVs released by gut microbiota.
Methylation-Based Therapies for Colorectal Cancer
Authors: Cervena Klara , Siskova Anna , Buchler Tomas , Vodicka Pavel , Vymetalkova Veronika
Published: June 2020

Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been included in the classification of the CRC molecular subtype, and this points out their prognostic impact. As epigenetic modifications are reversible, they may represent relevant therapeutic targets. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), regulates gene expression. For many years, the deregulation of DNA methylation has been considered to play a substantial part in CRC etiology and evolution. Despite considerable advances in CRC treatment, patient therapy response persists as limited, and their profit from systemic therapies are often hampered by the introduction of chemoresistance. In addition, inter-individual changes in therapy response in CRC patients can arise from their specific (epi)genetic compositions. In this review article, we summarize the options of CRC treatment based on DNA methylation status for their predictive value. This review also includes the therapy outcomes based on the patient’s methylation status in CRC patients. In addition, the current challenge of research is to develop therapeutic inhibitors of DNMT. Based on the essential role of DNA methylation in CRC development, the application of DNMT inhibitors was recently proposed for the treatment of CRC patients, especially in patients with DNA hypermethylation.
Early Onset of Sex-Dependent Mitochondrial Deficits in the Cortex of 3xTg Alzheimer’s Mice
Authors: Djordjevic Jelena , Roy Chowdhury Subir , Snow Wanda M. , Perez Claudia , Cadonic Chris , Fernyhough Paul , Albensi Benedict C.
Published: June 2020

Alzheimer’s disease (AD) is a major public health concern worldwide. Advanced age and female sex are two of the most prominent risk factors for AD. AD is characterized by progressive neuronal loss, especially in the cortex and hippocampus, and mitochondrial dysfunction has been proposed to be an early event in the onset and progression of the disease. Our results showed early perturbations in mitochondrial function in 3xTg mouse brain, with the cortex being more susceptible to mitochondrial changes than the hippocampus. In the cortex of 3xTg females, decreased coupled and uncoupled respiration were evident early (at 2 months of age), while in males it appeared later at 6 months of age. We observed increased coupled respiration in the hippocampus of 2-month-old 3xTg females, but no changes were detected later in life. Changes in mitochondrial dynamics were indicated by decreased mitofusin (Mfn2) and increased dynamin related protein 1 (Drp1) (only in females) in the hippocampus and cortex of 3xTg mice. Our findings highlight the importance of controlling and accounting for sex, brain region, and age in studies examining brain bioenergetics using this common AD model in order to more accurately evaluate potential therapies and improve the sex-specific translatability of preclinical findings.
Iron (III) Oxide-Based Ceramic Material for Radiation Shielding
Authors: Mori Hiroyuki , Oku Yohei , Mannami Yudo , Kunisada Takahiro
Published: June 2020

We developed a new ceramic from raw material mainly composed of iron (III) oxide. The measured attenuation coefficient of the ceramic for high-energy gamma rays was in the range 0.268–0.355, which is approximately 40% of that of lead and twice that of concrete. The measured penetrating dose of the ceramic is half of that of concrete. Thus, the novel ceramic material named RASHIX may serve as a novel ceramic alternative for the wide variety of radiation shielding materials used in construction.
CivilEng: A New International Open Access Journal in Civil Engineering
Authors: Luongo Angelo
Published: June 2020

Civil Engineering is the oldest branch of engineering [...]
Precision Machining of Nimonic C 263 Super AlloyUsing WEDM
Authors: Mouralova Katerina , Benes Libor , Bednar Josef , Zahradnicek Radim , Prokes Tomas , Fiala Zdenek , Fries Jiri
Published: June 2020

Wire electrical discharge machining (WEDM) is an unconventional and very efficient technology for precision machining of the Nimonic C 263 super alloy, which is very widespread, especially in the energy, aerospace and automotive industries. Due to electrical discharge, defects in the form of cracks or burned cavities often occur on the machined surfaces, which negatively affect the correct functionality and service life of the manufactured components. To increase the efficiency of the machining of Nimonic C 263 using WEDM, in this study, extensive design of experiments was carried out, monitoring input factors in the form of machine parameters like Pulse off time, Gap voltage, Discharge current, Pulse on time and Wire feed, the output of which was comprehensive information about the behaviour of such machined surfaces, which allowed the optimization of the entire machining process. Thus, the optimization of the Cutting speed was performed in relation to the quality of the machined surface and the machining accuracy, as well as an analysis of the chemical composition of the machined surfaces and a detailed analysis of the lamella using a transmission electron microscope. A detailed study of the occurrence of surface or subsurface defects was also included. It was found that with the help of complex optimization tools, it is possible to significantly increase the efficiency of the machining of the Nimonic C 263 super alloy and achieve both financial savings in the form of shortened machine time and increasing the quality of machined surfaces.
Analysis of the Actual Contact Surface of Selected Aircraft Tires with the Airport Pavement as a Function of Pressure and Vertical Load
Authors: Wesołowski Mariusz , Blacha Krzysztof , Pietruszewski Paweł , Iwanowski Paweł
Published: June 2020

The contact surface of the wheel with the airport surface is important for the safety of flight operations in the ground manoeuvring area. The area of the contact surface, its shape and stress distribution at the pavement surface are the subject of many scientists’ considerations. However, there are only a few research studies which include pressure and vertical load directly and its influence on tire-pavement contact area. There are no research studies which take into account aircraft tires. This work is a piece of an extensive research project which aims to develop a device and a method for continuous measurement of the natural airport pavement’s load capacity. One of the work elements was to estimate the relationship between wheel pressure and wheel pressure on the surface, and the area of the contact surface. The results of the research are presented in this article. Global experience in this field is cited at the beginning of the article. Then, the theoretical basis for calculating the wheel with the road surface contact area was presented. Next, the author’s research views and measurement method are presented. Finally, the obtained test results and comments are shown. The tests were carried out for four types of tires. Two of them were airplane tires from the PZL M28 Skytruck/Bryza and Sukhoi Su-22 aircraft. Two more came from the airport ASFT (airport surface friction tester) friction tester-one smooth ASTM; the other smooth retreaded type T520. The tires were tested in a pressure range from 200 to 800 kPa. The range of vertical wheel load on the pavement was 3.23–25.93 kN for airplane tires, and 0.8–4.0 kN for friction tester tires. The tests proved a significant influence of the wheel pressure value and wheel pressure on the surface on the obtained contact surface area of the wheel with the surface. In addition, it was noted that the final shape and size of the contact surface is affected by factors other than wheel pressure, tire pressure and dimensions.
Biofunctionalization of Textile Materials. 3. Fabrication of Poly(lactide)-Potassium Iodide Composites with Antifungal Properties
Authors: Kudzin Marcin H. , Mrozińska Zdzisława
Published: June 2020

The paper presents a method of obtaining poly(lactide) (PLA) nonwoven fabrics with antifungal properties using potassium iodide as a nonwoven modifying agent. PLA nonwoven fabrics were obtained by the melt-blown technique and subsequently surface modified (PLA→PLA-SM-KI) by the dip-coating method. The analysis of these PLA-SM-KI (0.1%–2%) composites included Scanning Electron Microscopy (SEM), UV/VIS transmittance, FTIR spectrometry and air permeability. The nonwovens were subjected to microbial activity tests against Aspergillus niger fungal mold species, exhibiting substantial antifungal activity. The studies showed that PLA-KI hybrids containing 2% KI have appropriate mechanical properties, morphology and demanded antimicrobial properties to be further developed as a potential antimicrobial, biodegradable material.
Privacy Protection in Real Time HEVC Standard Using Chaotic System
Authors: Abu Taha Mohammed , Hamidouche Wassim , Sidaty Naty , Viitanen Marko , Vanne Jarno , El Assad Safwan , Deforges Olivier
Published: June 2020

Video protection and access control have gathered steam over recent years. However, the most common methods encrypt the whole video bit stream as unique data without taking into account the structure of the compressed video. These full encryption solutions are time and power consuming and, thus, are not aligned with the real-time applications. In this paper, we propose a Selective Encryption (SE) solution for Region of Interest (ROI) security based on the tile concept in High Efficiency Video Coding (HEVC) standards and selective encryption of all sensitive parts in videos. The SE solution depends on a chaos-based stream cipher that encrypts a set of HEVC syntax elements normatively, that is, the bit stream can be decoded with a standard HEVC decoder, and a secret key is only required for ROI decryption. The proposed ROI encryption solution relies on the independent tile concept in HEVC that splits the video frame into independent rectangular areas. Tiles are used to pull out the ROI from the background and only the tiles figuring the ROI are encrypted. In inter coding, the independence of tiles is guaranteed by limiting the motion vectors of non-ROI to use only the unencrypted tiles in the reference frames. Experimental results have shown that the encryption solution performs secure video encryption in a real time context, with a diminutive bit rate and complexity overheads.