bluuebunny/crossref_metadata_2025 huggingface dataset:
Methanol Electrolysis for Hydrogen Production Using Polymer Electrolyte Membrane: A Mini-Review
Authors: Pethaiah Sethu Sundar , Sadasivuni Kishor Kumar , Jayakumar Arunkumar , Ponnamma Deepalekshmi , Tiwary Chandra Sekhar , Sasikumar Gangadharan
Published: November 2020

Hydrogen (H2) has attained significant benefits as an energy carrier due to its gross calorific value (GCV) and inherently clean operation. Thus, hydrogen as a fuel can lead to global sustainability. Conventional H2 production is predominantly through fossil fuels, and electrolysis is now identified to be most promising for H2 generation. This review describes the recent state of the art and challenges on ultra-pure H2 production through methanol electrolysis that incorporate polymer electrolyte membrane (PEM). It also discusses about the methanol electrochemical reforming catalysts as well as the impact of this process via PEM. The efficiency of H2 production depends on the different components of the PEM fuel cells, which are bipolar plates, current collector, and membrane electrode assembly. The efficiency also changes with the nature and type of the fuel, fuel/oxygen ratio, pressure, temperature, humidity, cell potential, and interfacial electronic level interaction between the redox levels of electrolyte and band gap edges of the semiconductor membranes. Diverse operating conditions such as concentration of methanol, cell temperature, catalyst loading, membrane thickness, and cell voltage that affect the performance are critically addressed. Comparison of various methanol electrolyzer systems are performed to validate the significance of methanol economy to match the future sustainable energy demands.
Numerical Study on the Effects of Relative Diameters on the Performance of Small Modular Reactors Driven by Natural Circulation
Authors: Kim Young Jin , Lee Byung Jin , Yi Kunwoo , Choe Yoon Jae , Lee Min Chul
Published: November 2020

Most of the small modular reactors (SMRs) under development worldwide present the same components: an integral reactor vessel with a low-positioned core as the heat source and a high-positioned steam generator as the heat sink. Moreover, some SMRs are being designed to be driven by natural circulation during normal power generation. This work focused on such designs and on their performance, considering the changes generated by the geometric and hydraulic parameters of the system. Numerical simulations using mass, momentum, and energy equations that considered buoyancy forces were performed to determine the effects of various geometric and hydraulic parameters, such as diameters and flow resistances, on the reactor’s performance. It was found that nonuniform diameters promote velocity changes that affect the natural circulation flow rate. Moreover, the reactor’s temperature distribution depends on the steam generator tube pitch. Therefore, the hydraulic diameters of the reactor’s coolant passages should be maintained as uniform as possible to obtain a more uniform temperature distribution and a larger mass flow rate in SMRs.
Principal Component Analysis (PCA)-Supported Underfrequency Load Shedding Algorithm
Authors: Skrjanc Tadej , Mihalic Rafael , Rudez Urban
Published: November 2020

This research represents a conceptual shift in the process of introducing flexibility into power system frequency stability-related protection. The existing underfrequency load shedding (UFLS) solution, although robust and fast, has often proved to be incapable of adjusting to different operating conditions. It triggers upon detection of frequency threshold violations, and functions by interrupting the electricity supply to a certain number of consumers, both of which values are decided upon beforehand. Consequently, it often does not comply with its main purpose, i.e., bringing frequency decay to a halt. Instead, the power imbalance is often reversed, resulting in equally undesirable frequency overshoots. Researchers have sought a solution to this shortcoming either by increasing the amount of available information (by means of wide-area communication) or through complex changes to all involved protection relays. In this research, we retain the existing concept of UFLS that performs so well for fast-occurring frequency events. The flexible rebalancing of power is achieved by a small and specialized group of intelligent electronic devices (IEDs) with machine learning functionalities. These IEDs interrupt consumers only when the need to do so is detected with a high degree of certainty. Their small number assures the fine-tuning of power rebalancing and, at the same time, poses no serious threat to system stability in cases of malfunction.
The Genealogy of No-Self: Marguerite Yourcenar’s Koan of the Labyrinth
Authors: Janca-Aji Joyce
Published: November 2020

20th-century French author, Marguerite Yourcenar, prefaces the first volume of her autobiographical/genealogical trilogy, Dear Departed with a 13th-century Zen koan: What is your original face before your parents were born? In the context of the meticulously researched family history of her maternal line, Yourcenar examines the foundations and major resources of individual and collective self-writing in light of Buddhist discourses on the nature of self, while offering an incisive critique of and alternative to the function of genealogical inquiry.
Fault Detection with Crosshole and Reflection Geo-Radar for Underground Mine Safety
Authors: Kulich Jakob , Bleibinhaus Florian
Published: November 2020

Ground-penetrating radar and crosshole radar are applied in an underground marble mine for fault detection and to test if different geological bodies can be distinguished. Boreholes are often drilled in advance of mining to clarify the locations of ore bodies and gangues. Here, such boreholes were used for crosshole investigations to supplement optical borehole imaging. Four boreholes were drilled along a profile with increasing offsets from 5 to 25 m. The crosshole measurements were performed with 100 MHz antennas. Tomographic panels were created up to a depth of 28 m and were complemented by reflection mode ground-penetrating radar (GPR) measurements along a 25 m-long profile with 100 and 250 MHz antennas. The GPR imaging successfully delineates the fault and karstification zones with higher water content due to their strong dielectric permittivity contrast compared to the surrounding geology.
Trends of Late Presentation to Care in Patients with Chronic Hepatitis C during a 10-Year Period in Croatia
Authors: Papic Neven , Radmanic Leona , Dusek Davorka , Kurelac Ivan , Zidovec Lepej Snjezana , Vince Adriana
Published: November 2020

Late presentation to care is the major obstacle to receiving treatment for chronic hepatitis C (CHC). Our aim was to analyze the prevalence and trends of late presenters (LP) at first consultations in Croatia during a 10-year period. This retrospective cross-sectional study included all adult CHC patients (n = 854) entering specialist medical care at the University Hospital for Infectious Diseases Zagreb between 2009 and 2018. LP was defined as liver stiffness measurement ≥ 9.5 kPa or biopsy METAVIR F ≥ 3. During the study period, mean patients’ age increased from 37 to 52 years while HCV genotype distribution changed leading to the replacement of genotype 1b with 1a (g1b 32% to 21%; g1a 19% to 38%). A total of 320 (37.4%) were LP; they were older (47.5, IQR 40.5–57.6), and more commonly infected with g1b (34.1%) and g3 (42.5%). The prevalence of LP significantly increased from 31.9% in 2009 to 46.5% in 2018. Late presentation for care of CHC is increasing in Croatia suggesting a gap of diagnosing strategies in patients over 50 years.
Fruit Extract Mediated Green Synthesis of Metallic Nanoparticles: A New Avenue in Pomology Applications
Authors: Kumar Harsh , Bhardwaj Kanchan , Dhanjal Daljeet Singh , Nepovimova Eugenie , Șen Fatih , Regassa Hailemeleak , Singh Reena , Verma Rachna , Kumar Vinod , Kumar Dinesh , Bhatia Shashi Kant , Kuča Kamil
Published: November 2020

Fruit extracts have natural bioactive molecules that are known to possess significant therapeutic potential. Traditionally, metallic nanoparticles were synthesized via chemical methods, in which the chemical act as the reducing agent. Later, these traditional metallic nanoparticles emerged as the biological risk, which prompted researchers to explore an eco-friendly approach. There are different eco-friendly methods employed for synthesizing these metallic nanoparticles via the usage of microbes and plants, primarily via fruit extract. These explorations have paved the way for using fruit extracts for developing nanoparticles, as they eliminate the usage of reducing and stabilizing agents. Metallic nanoparticles have gained significant attention, and are used for diverse biological applications. The present review discusses the potential activities of phytochemicals, and it intends to summarize the different metallic nanoparticles synthesized using fruit extracts and their associated pharmacological activities like anti-cancerous, antimicrobial, antioxidant and catalytic efficiency.
Exposome and Immunity Training: How Pathogen Exposure Order Influences Innate Immune Cell Lineage Commitment and Function
Authors: Adams Kevin , Weber K. Scott , Johnson Steven M.
Published: November 2020

Immune memory is a defining characteristic of adaptive immunity, but recent work has shown that the activation of innate immunity can also improve responsiveness in subsequent exposures. This has been coined “trained immunity” and diverges with the perception that the innate immune system is primitive, non-specific, and reacts to novel and recurrent antigen exposures similarly. The “exposome” is the cumulative exposures (diet, exercise, environmental exposure, vaccination, genetics, etc.) an individual has experienced and provides a mechanism for the establishment of immune training or immunotolerance. It is becoming increasingly clear that trained immunity constitutes a delicate balance between the dose, duration, and order of exposures. Upon innate stimuli, trained immunity or tolerance is shaped by epigenetic and metabolic changes that alter hematopoietic stem cell lineage commitment and responses to infection. Due to the immunomodulatory role of the exposome, understanding innate immune training is critical for understanding why some individuals exhibit protective phenotypes while closely related individuals may experience immunotolerant effects (e.g., the order of exposure can result in completely divergent immune responses). Research on the exposome and trained immunity may be leveraged to identify key factors for improving vaccination development, altering inflammatory disease development, and introducing potential new prophylactic treatments, especially for diseases such as COVID-19, which is currently a major health issue for the world. Furthermore, continued exposome research may prevent many deleterious effects caused by immunotolerance that frequently result in host morbidity or mortality.
Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies
Authors: Bartuzi Damian , Kędzierska Ewa , Kaczor Agnieszka A. , Schmidhammer Helmut , Matosiuk Dariusz
Published: November 2020

Opioids are the drugs of choice in severe pain management. Unfortunately, their use involves serious, potentially lethal side effects. Therefore, efforts in opioid drug design turn toward safer and more effective mechanisms, including allosteric modulation. In this study, molecular dynamics simulations in silico and ‘writhing’ tests in vivo were used to characterize potential allosteric mechanism of two previously reported compounds. The results suggest that investigated compounds bind to μ opioid receptor in an allosteric site, augmenting action of morphine at subeffective doses, and exerting antinociceptive effect alone at higher doses. Detailed analysis of in silico calculations suggests that first of the compounds behaves more like allosteric agonist, while the second compound acts mainly as a positive allosteric modulator.
The Physiological MicroRNA Landscape in Nipple Aspirate Fluid: Differences and Similarities with Breast Tissue, Breast Milk, Plasma and Serum
Authors: Patuleia Susana I. S. , van Gils Carla H. , Oneto Cao Angie M. , Bakker Marije F. , van Diest Paul J. , van der Wall Elsken , Moelans Cathy B.
Published: November 2020

Background: MicroRNAs (miRNAs) target 60% of human messenger RNAs and can be detected in tissues and biofluids without loss of stability during sample processing, making them highly appraised upcoming biomarkers for evaluation of disease. However, reporting of the abundantly expressed miRNAs in healthy samples is often surpassed. Here, we characterized for the first time the physiological miRNA landscape in a biofluid of the healthy breast: nipple aspirate fluid (NAF), and compared NAF miRNA expression patterns with publically available miRNA expression profiles of healthy breast tissue, breast milk, plasma and serum. Methods: MiRNA RT-qPCR profiling of NAF (n = 41) and serum (n = 23) samples from two healthy female cohorts was performed using the TaqMan OpenArray Human Advanced MicroRNA 754-Panel. MiRNA quantification data based on non-targeted or multi-targeted profiling techniques for breast tissue, breast milk, plasma and serum were retrieved from the literature by means of a systematic search. MiRNAs from each individual study were orderly ranked between 1 and 50, combined into an overall ranking per sample type and compared. Results: NAF expressed 11 unique miRNAs and shared 21/50 miRNAs with breast tissue. Seven miRNAs were shared between the five sample types. Overlap between sample types varied between 42% and 62%. Highly ranked NAF miRNAs have established roles in breast carcinogenesis. Conclusion: This is the first study to characterize and compare the unique physiological NAF-derived miRNA landscape with the physiological expression pattern in breast tissue, breast milk, plasma and serum. Breast-specific sources did not mutually overlap more than with systemic sources. Given their established role in carcinogenesis, NAF miRNA assessment could be a valuable tool in breast tumor diagnostics.
Cell-Type-Specific Complement Profiling in the ABCA4−/− Mouse Model of Stargardt Disease
Authors: Jabri Yassin , Biber Josef , Diaz-Lezama Nundehui , Grosche Antje , Pauly Diana
Published: November 2020

Stargardt macular degeneration is an inherited retinal disease caused by mutations in the ATP-binding cassette subfamily A member 4 (ABCA4) gene. Here, we characterized the complement expression profile in ABCA4−/− retinae and aligned these findings with morphological markers of retinal degeneration. We found an enhanced retinal pigment epithelium (RPE) autofluorescence, cell loss in the inner retina of ABCA4−/− mice and demonstrated age-related differences in complement expression in various retinal cell types irrespective of the genotype. However, 24-week-old ABCA4−/− mice expressed more c3 in the RPE and fewer cfi transcripts in the microglia compared to controls. At the protein level, the decrease of complement inhibitors (complement factor I, CFI) in retinae, as well as an increased C3b/C3 ratio in the RPE/choroid and retinae of ABCA4−/−, mice was confirmed. We showed a corresponding increase of the C3d/C3 ratio in the serum of ABCA4−/− mice, while no changes were observed for CFI. Our findings suggest an overactive complement cascade in the ABCA4−/− retinae that possibly contributes to pathological alterations, including microglial activation and neurodegeneration. Overall, this underpins the importance of well-balanced complement homeostasis to maintain retinal integrity.
Targeting NF-κB-Inducing Kinase (NIK) in Immunity, Inflammation, and Cancer
Authors: Pflug Kathryn M. , Sitcheran Raquel
Published: November 2020

NF-κB-inducing kinase (NIK), the essential upstream kinase, which regulates activation of the noncanonical NF-κB pathway, has important roles in regulating immunity and inflammation. In addition, NIK is vital for maintaining cellular health through its control of fundamental cellular processes, including differentiation, growth, and cell survival. As such aberrant expression or regulation of NIK is associated with several disease states. For example, loss of NIK leads to severe immune defects, while the overexpression of NIK is observed in inflammatory diseases, metabolic disorders, and the development and progression of cancer. This review discusses recent studies investigating the therapeutic potential of NIK inhibitors in various diseases.
Natural Health Products (NHP’s) and Natural Compounds as Therapeutic Agents for the Treatment of Cancer; Mechanisms of Anti-Cancer Activity of Natural Compounds and Overall Trends
Authors: Scaria Benjamin , Sood Siddhartha , Raad Christopher , Khanafer Jana , Jayachandiran Rahul , Pupulin Alaina , Grewal Sahibjot , Okoko Michael , Arora Mansi , Miles Lauren , Pandey Siyaram
Published: November 2020

Most cancer therapeutics, such as tubulin-targeting chemotherapy drugs, cause cytotoxic, non-selective effects. These harmful side-effects drastically reduce the cancer patient’s quality of life. Recently, researchers have focused their efforts on studying natural health products (NHP’s) which have demonstrated the ability to selectively target cancer cells in cellular and animal models. However, the major hurdle of clinical validation remains. NHP’s warrant further clinical investigation as a therapeutic option since they exhibit low toxicity, while retaining a selective effect. Additionally, they can sensitize cancerous cells to chemotherapy, which enhances the efficacy of chemotherapeutic drugs, indicating that they can be utilized as supplemental therapy. An additional area for further research is the investigation of drug–drug interactions between NHP’s and chemotherapeutics. The objectives of this review are to report the most recent results from the field of anticancer NHP research, and to highlight the most recent advancements in possible supplemental therapeutic options.
Post-Translational Modifications of Cytochrome c in Cell Life and Disease
Authors: Guerra-Castellano Alejandra , Márquez Inmaculada , Pérez-Mejías Gonzalo , Díaz-Quintana Antonio , De la Rosa Miguel A. , Díaz-Moreno Irene
Published: November 2020

Mitochondria are the powerhouses of the cell, whilst their malfunction is related to several human pathologies, including neurodegenerative diseases, cardiovascular diseases, and various types of cancer. In mitochondrial metabolism, cytochrome c is a small soluble heme protein that acts as an essential redox carrier in the respiratory electron transport chain. However, cytochrome c is likewise an essential protein in the cytoplasm acting as an activator of programmed cell death. Such a dual role of cytochrome c in cell life and death is indeed fine-regulated by a wide variety of protein post-translational modifications. In this work, we show how these modifications can alter cytochrome c structure and functionality, thus emerging as a control mechanism of cell metabolism but also as a key element in development and prevention of pathologies.
A SINE-VNTR-Alu in the LRIG2 Promoter Is Associated with Gene Expression at the Locus
Authors: Hall Ashley , Moore Anni K. , Hernandez Dena G. , Billingsley Kimberley J. , Bubb Vivien J. , Quinn John P. ,   NABEC (North American Brain Expression Consortium)
Published: November 2020

The hominid SINE-VNTR-Alu (SVA) retrotransposons represent a repertoire of genomic variation which could have significant effects on genome function. A human-specific SVA in the promoter region of the gene leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2), which we termed SVA_LRIG2, is a common retrotransposon insertion polymorphism (RIP), defined as an element which is polymorphic for its presence or absence in the genome. We hypothesised that this RIP might be associated with differential levels of expression of LRIG2. The RIP genotype of SVA_LRIG2 was determined in a subset of frontal cortex DNA samples from the North American Brain Expression Consortium (NABEC) cohort and was imputed for a larger set of that cohort. Utilising available frontal cortex total RNA-seq and CpG methylation data for this cohort, we observed that increased allele dosage of SVA_LRIG2 was non-significantly associated with a decrease in transcription from the region and significantly associated with increased methylation of the CpG probe nearest to SVA_LRIG2, i.e., SVA_LRIG2 is a significant methylation quantitative trait loci (mQTL) at the LRIG2 locus. These data are consistent with SVA_LRIG2 being a transcriptional regulator, which in part may involve epigenetic modulation.
Loss of DIAPH3, a Formin Family Protein, Leads to Cytokinetic Failure Only under High Temperature Conditions in Mouse FM3A Cells
Authors: Kazama Hiroki , Kashiwaba Shu-ichiro , Ishii Sayaka , Yoshida Keiko , Yatsuo Yuta , Naraoka Takuma , Fukuoka Masashi , Murakami Yasufumi
Published: November 2020

Cell division is essential for the maintenance of life and involves chromosome segregation and subsequent cytokinesis. The processes are tightly regulated at both the spatial and temporal level by various genes, and failures in this regulation are associated with oncogenesis. Here, we investigated the gene responsible for defects in cell division by using murine temperature-sensitive (ts) mutant strains, tsFT101 and tsFT50 cells. The ts mutants normally grow in a low temperature environment (32 °C) but fail to divide in a high temperature environment (39 °C). Exome sequencing and over-expression analyses identified Diaph3, a member of the formin family, as the cause of the temperature sensitivity observed in tsFT101 and tsFT50 cells. Interestingly, Diaph3 knockout cells showed abnormality in cytokinesis at 39 °C, and the phenotype was rescued by re-expression of Diaph3 WT, but not Diaph1 and Diaph2, other members of the formin family. Furthermore, Diaph3 knockout cells cultured at 39 °C showed a significant increase in the level of acetylated α-tubulin, an index of stabilized microtubules, and the level was reduced by Diaph3 expression. These results suggest that Diaph3 is required for cytokinesis only under high temperature conditions. Therefore, our study provides a new insight into the mechanisms by which regulatory factors of cell division function in a temperature-dependent manner.
Development of a Method for Scaffold-Free Elastic Cartilage Creation
Authors: Enomura Masahiro , Murata Soichiro , Terado Yuri , Tanaka Maiko , Kobayashi Shinji , Oba Takayoshi , Kagimoto Shintaro , Yabuki Yuichiro , Morita Kenichi , Uemura Toshimasa , Maegawa Jiro , Taniguchi Hideki
Published: November 2020

Microtia is a congenital aplasia of the auricular cartilage. Conventionally, autologous costal cartilage grafts are collected and shaped for transplantation. However, in this method, excessive invasion occurs due to limitations in the costal cartilage collection. Due to deformation over time after transplantation of the shaped graft, problems with long-term morphological maintenance exist. Additionally, the lack of elasticity with costal cartilage grafts is worth mentioning, as costal cartilage is a type of hyaline cartilage. Medical plastic materials have been transplanted as alternatives to costal cartilage, but transplant rejection and deformation over time are inevitable. It is imperative to create tissues for transplantation using cells of biological origin. Hence, cartilage tissues were developed using a biodegradable scaffold material. However, such materials suffer from transplant rejection and biodegradation, causing the transplanted cartilage tissue to deform due to a lack of elasticity. To address this problem, we established a method for creating elastic cartilage tissue for transplantation with autologous cells without using scaffold materials. Chondrocyte progenitor cells were collected from perichondrial tissue of the ear cartilage. By using a multilayer culture and a three-dimensional rotating suspension culture vessel system, we succeeded in creating scaffold-free elastic cartilage from cartilage progenitor cells.
Characterization of Mesenchymal Stem Cell Differentiation within Miniaturized 3D Scaffolds through Advanced Microscopy Techniques
Authors: Parodi Valentina , Jacchetti Emanuela , Bresci Arianna , Talone Benedetta , Valensise Carlo M. , Osellame Roberto , Cerullo Giulio , Polli Dario , Raimondi Manuela T.
Published: November 2020

Three-dimensional culture systems and suitable substrates topographies demonstrated to drive stem cell fate in vitro by mechanical conditioning. For example, the Nichoid 3D scaffold remodels stem cells and shapes nuclei, thus promoting stem cell expansion and stemness maintenance. However, the mechanisms involved in force transmission and in biochemical signaling at the basis of fate determination are not yet clear. Among the available investigation systems, confocal fluorescence microscopy using fluorescent dyes enables the observation of cell function and shape at the subcellular scale in vital and fixed conditions. Contrarily, nonlinear optical microscopy techniques, which exploit multi-photon processes, allow to study cell behavior in vital and unlabeled conditions. We apply confocal fluorescence microscopy, coherent anti-Stokes Raman scattering (CARS), and second harmonic generation (SHG) microscopy to characterize the phenotypic expression of mesenchymal stem cells (MSCs) towards adipogenic and chondrogenic differentiation inside Nichoid scaffolds, in terms of nuclear morphology and specific phenotypic products, by comparing these techniques. We demonstrate that the Nichoid maintains a rounded nuclei during expansion and differentiation, promoting MSCs adipogenic differentiation while inhibiting chondrogenesis. We show that CARS and SHG techniques are suitable for specific estimation of the lipid and collagenous content, thus overcoming the limitations of using unspecific fluorescent probes.
Respiratory Burst Oxidase Homologs RBOHD and RBOHF as Key Modulating Components of Response in Turnip Mosaic Virus—Arabidopsis thaliana (L.) Heyhn System
Authors: Otulak-Kozieł Katarzyna , Kozieł Edmund , Bujarski Józef Julian , Frankowska-Łukawska Justyna , Torres Miguel Angel
Published: November 2020

Turnip mosaic virus (TuMV) is one of the most important plant viruses worldwide. It has a very wide host range infecting at least 318 species in over 43 families, such as Brassicaceae, Fabaceae, Asteraceae, or Chenopodiaceae from dicotyledons. Plant NADPH oxidases, the respiratory burst oxidase homologues (RBOHs), are a major source of reactive oxygen species (ROS) during plant–microbe interactions. The functions of RBOHs in different plant–pathogen interactions have been analyzed using knockout mutants, but little focus has been given to plant–virus responses. Therefore, in this work we tested the response after mechanical inoculation with TuMV in ArabidopsisrbohD and rbohF transposon knockout mutants and analyzed ultrastructural changes after TuMV inoculation. The development of the TuMV infection cycle was promoted in rbohD plants, suggesting that RbohD plays a role in the Arabidopsis resistance response to TuMV. rbohF and rbohD/F mutants display less TuMV accumulation and a lack of virus cytoplasmic inclusions were observed; these observations suggest that RbohF promotes viral replication and increases susceptibility to TuMV. rbohD/F displayed a reduction in H2O2 but enhanced resistance similarly to rbohF. This dominant effect of the rbohF mutation could indicate that RbohF acts as a susceptibility factor. Induction of hydrogen peroxide by TuMV was partially compromised in rbohD mutants whereas it was almost completely abolished in rbohD/F, indicating that these oxidases are responsible for most of the ROS produced in this interaction. The pattern of in situ H2O2 deposition after infection of the more resistant rbohF and rbohD/F genotypes suggests a putative role of these species on systemic signal transport. The ultrastructural localization and quantification of pathogenesis-related protein 1 (PR1) indicate that ROS produced by these oxidases also influence PR1 distribution in the TuMV-A.thaliana pathosystem. Our results revealed the highest activation of PR1 in rbohD and Col-0. Thus, our findings indicate a correlation between PR1 accumulation and susceptibility to TuMV. The specific localization of PR1 in the most resistant genotypes after TuMV inoculation may indicate a connection of PR1 induction with susceptibility, which may be characteristic for this pathosystem. Our results clearly indicate the importance of NADPH oxidases RbohD and RbohF in the regulation of the TuMV infection cycle in Arabidopsis. These findings may help provide a better understanding of the mechanisms modulating A.thaliana–TuMV interactions.
Purinergic Signaling in Endometriosis-Associated Pain
Authors: Trapero Carla , Martín-Satué Mireia
Published: November 2020

Endometriosis is an estrogen-dependent gynecological disease, with an associated chronic inflammatory component, characterized by the presence of endometrial tissue outside the uterine cavity. Its predominant symptom is pain, a condition notably altering the quality of life of women with the disease. This review is intended to exhaustively gather current knowledge on purinergic signaling in endometriosis-associated pain. Altered extracellular ATP hydrolysis, due to changes in ectonucleotidase activity, has been reported in endometriosis; the resulting accumulation of ATP in the endometriotic microenvironment points to sustained activation of nucleotide receptors (P2 receptors) capable of generating a persistent pain message. P2X3 receptor, expressed in sensory neurons, mediates nociceptive, neuropathic, and inflammatory pain, and is enrolled in endometriosis-related pain. Pharmacological inhibition of P2X3 receptor is under evaluation as a pain relief treatment for women with endometriosis. The role of other ATP receptors is also discussed here, e.g., P2X4 and P2X7 receptors, which are involved in inflammatory cell–nerve and microglia–nerve crosstalk, and therefore in inflammatory and neuropathic pain. Adenosine receptors (P1 receptors), by contrast, mainly play antinociceptive and anti-inflammatory roles. Purinome-targeted drugs, including nucleotide receptors and metabolizing enzymes, are potential non-hormonal therapeutic tools for the pharmacological management of endometriosis-related pain.
E3 Ubiquitin Ligase TRIP12: Regulation, Structure, and Physiopathological Functions
Authors: Brunet Manon , Vargas Claire , Larrieu Dorian , Torrisani Jérôme , Dufresne Marlène
Published: November 2020

The Thyroid hormone Receptor Interacting Protein 12 (TRIP12) protein belongs to the 28-member Homologous to the E6-AP C-Terminus (HECT) E3 ubiquitin ligase family. First described as an interactor of the thyroid hormone receptor, TRIP12’s biological importance was revealed by the embryonic lethality of a murine model bearing an inactivating mutation in the TRIP12 gene. Further studies showed the participation of TRIP12 in the regulation of major biological processes such as cell cycle progression, DNA damage repair, chromatin remodeling, and cell differentiation by an ubiquitination-mediated degradation of key protein substrates. Moreover, alterations of TRIP12 expression have been reported in cancers that can serve as predictive markers of therapeutic response. The TRIP12 gene is also referenced as a causative gene associated to intellectual disorders such as Clark–Baraitser syndrome and is clearly implicated in Autism Spectrum Disorder. The aim of the review is to provide an exhaustive and integrated overview of the different aspects of TRIP12 ranging from its regulation, molecular functions and physio-pathological implications.
Optimization of the Biocatalysis for D-DIBOA Synthesis Using a Quick and Sensitive New Spectrophotometric Quantification Method
Authors: Cabrera Gema , Linares Teresa , de la Calle Maria Elena , Cantero Domingo , Valle Antonio , Bolivar Jorge
Published: November 2020

D-DIBOA (4-hydroxy-(2H)-1,4-benzoxazin-3-(4H)-one) is an allelopathic-derived compound with interesting herbicidal, fungicidal, and insecticide properties whose production has been successfully achieved by biocatalysis using a genetically engineered Escherichia coli strain. However, improvement and scaling-up of this process are hampered by the current methodology for D-DIBOA quantification, which is based on high-performance liquid chromatographic (HPLC), a time-consuming technique that requires expensive equipment and the use of environmentally unsafe solvents. In this work, we established and validated a rapid, simple, and sensitive spectrophotometric method for the quantification of the D-DIBOA produced by whole-cell biocatalysis, with limits of detection and quantification of 0.0165 and 0.0501 µmol·mL−1 respectively. This analysis takes place in only a few seconds and can be carried out using 100 µL of the sample in a microtiter plate reader. We performed several whole-cell biocatalysis strategies to optimize the process by monitoring D-DIBOA production every hour to keep control of both precursor and D-DIBOA concentrations in the bioreactor. These experiments allowed increasing the D-DIBOA production from the previously reported 5.01 mM up to 7.17 mM (43% increase). This methodology will facilitate processes such as the optimization of the biocatalyst, the scaling up, and the downstream purification.
Emerging Strategies to Combat β-Lactamase Producing ESKAPE Pathogens
Authors: Vrancianu Corneliu Ovidiu , Gheorghe Irina , Dobre Elena-Georgiana , Barbu Ilda Czobor , Cristian Roxana Elena , Popa Marcela , Lee Sang Hee , Limban Carmen , Vlad Ilinca Margareta , Chifiriuc Mariana Carmen
Published: November 2020

Since the discovery of penicillin by Alexander Fleming in 1929 as a therapeutic agent against staphylococci, β-lactam antibiotics (BLAs) remained the most successful antibiotic classes against the majority of bacterial strains, reaching a percentage of 65% of all medical prescriptions. Unfortunately, the emergence and diversification of β-lactamases pose indefinite health issues, limiting the clinical effectiveness of all current BLAs. One solution is to develop β-lactamase inhibitors (BLIs) capable of restoring the activity of β-lactam drugs. In this review, we will briefly present the older and new BLAs classes, their mechanisms of action, and an update of the BLIs capable of restoring the activity of β-lactam drugs against ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. Subsequently, we will discuss several promising alternative approaches such as bacteriophages, antimicrobial peptides, nanoparticles, CRISPR (clustered regularly interspaced short palindromic repeats) cas technology, or vaccination developed to limit antimicrobial resistance in this endless fight against Gram-negative pathogens.
Astaxanthin Counteracts Vascular Calcification In Vitro Through an Early Up-Regulation of SOD2 Based on a Transcriptomic Approach
Authors: Chao Chia-Ter , Yeh Hsiang-Yuan , Tsai You-Tien , Yuan Tzu-Hang , Liao Min-Tser , Huang Jenq-Wen , Chen Huei-Wen
Published: November 2020

Vascular calcification (VC) is a critical contributor to the rising cardiovascular risk among at-risk populations such as those with diabetes or renal failure. The pathogenesis of VC involves an uprising of oxidative stress, for which antioxidants can be theoretically effective. However, astaxanthin, a potent antioxidant, has not been tested before for the purpose of managing VC. To answer this question, we tested the efficacy of astaxanthin against VC using the high phosphate (HP)-induced vascular smooth muscle cell (VSMC) calcification model. RNAs from treated groups underwent Affymetrix microarray screening, with intra-group consistency and inter-group differential expressions identified. Candidate hub genes were selected, followed by validation in experimental models and functional characterization. We showed that HP induced progressive calcification among treated VSMCs, while astaxanthin dose-responsively and time-dependently ameliorated calcification severities. Transcriptomic profiling revealed that 3491 genes exhibited significant early changes during VC progression, among which 26 potential hub genes were selected based on closeness ranking and biologic plausibility. SOD2 was validated in the VSMC model, shown to drive the deactivation of cellular senescence and enhance antioxidative defenses. Astaxanthin did not alter intracellular reactive oxygen species (ROS) levels without HP, but significantly lowered ROS production in HP-treated VSMCs. SOD2 knockdown prominently abolished the anti-calcification effect of astaxanthin on HP-treated VSMCs, lending support to our findings. In conclusion, we demonstrated for the first time that astaxanthin could be a potential candidate treatment for VC, through inducing the up-regulation of SOD2 early during calcification progression and potentially suppressing vascular senescence.
Exploring the Role of a Novel Peptide from Allomyrina dichotoma Larvae in Ameliorating Lipid Metabolism in Obesity
Authors: Bae Sung Mun , Fan Meiqi , Choi Young-Jin , Tang Yujiao , Jeong Gwanghui , Myung Kyungjae , Kim Byung-gyu , Kim Eun-Kyung
Published: November 2020

The aim of this study was to identify an anti-obesity peptide from Allomyrina dichotoma and investigate the lipid metabolic mechanism. Enzymatically hydrolyzed A. dichotoma larvae were further separated using tangential flow filtration and consecutive chromatographic processes. Finally, an anti-obesity peptide that showed the highest inhibitory effect on lipid accumulation was obtained, and the sequence was Glu-Ile-Ala-Gln-Asp-Phe-Lys-Thr-Asp-Leu (EIA10). EIA10 decreased lipid aggregation in vitro and significantly reduced the accumulation of body weight gain, liver weight, and adipose tissue weight in high-fat-fed mice. Compared with the control group, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in the high-fat diet (HFD) group increased significantly, and the content of high-density lipoprotein cholesterol (HDL) in the serum decreased significantly. On the contrary, the levels of TC, TG, and insulin in the EIA10 group decreased significantly, and the HDL content increased significantly compared with the HFD group. Additionally, EIA10 dramatically decreased mRNA and protein levels of transcription factors involved in lipid adipogenesis. Taken together, our results suggest that EIA10 could be a promising agent for the treatment and prevention of obesity.
Current Status and Application of Metformin for Prostate Cancer: A Comprehensive Review
Authors: Ahn Hyun Kyu , Lee Young Hwa , Koo Kyo Chul
Published: November 2020

Metformin, an oral biguanide used for first-line treatment of type 2 diabetes mellitus, has attracted attention for its anti-proliferative and anti-cancer effects in several solid tumors, including prostate cancer (PCa). Liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK) activation, inhibition of the mammalian target of rapamycin (mTOR) activity and protein synthesis, induction of apoptosis and autophagy by p53 and p21, and decreased blood insulin level have been suggested as direct anti-cancer mechanisms of metformin. Research has shown that PCa development and progression are associated with metabolic syndrome and its components. Therefore, reduction in the risk of PCa and improvement in survival in metformin users may be the results of the direct anti-cancer mechanisms of the drug or the secondary effects from improvement of metabolic syndrome. In contrast, some research has suggested that there is no association between metformin use and PCa incidence or survival. In this comprehensive review, we summarize updated evidence on the relationship between metformin use and oncological effects in patients with PCa. We also highlight ongoing clinical trials evaluating metformin as an adjuvant therapy in novel drug combinations in various disease settings.
Characterization of the Complete Mitochondrial Genomes from Two Nitidulid Pests with Phylogenetic Implications
Authors: Chen Xiaoxiao , Song Qing , Huang Min
Published: November 2020

The complete mitochondrial genomes of Xenostrongylusvariegatus and Epuraea sp. were sequenced and analyzed. The total genome lengths are 17,657 and 16,641 bp, with an A+T content of 77.2% and 76.4%, respectively. Each mitochondrial genome consists of 37 coding genes and a non-coding (AT-rich) region. All protein-coding genes (PCGs) start with the standard start codon, ATN, and end with complete stop codons, TAA and TAG, or an incomplete stop codon, T. All tRNAs can be folded into the typical clover-leaf secondary structure, with the exception of trnS1 in both species with a reduced dihydrouridine (DHU) arm. The AT-rich region has tandem repeats differing in both number and length. Genetic distance and Ka/Ks analyses show that nad6 has a higher variability and more rapid evolutionary rate than other PCGs. Both maximum likelihood and Bayesian inference phylogenetic analyses based on 13 PCGs and 2 ribosome DNAs (rDNAs) agree with the previous phylogenies in supporting the Nitidulidae monophyly and the sister-group relationship of Kateretidae + (Monotomidae + Nitidulidae).
Novel Biofuel Cell Using Hydrogen Generation of Photosynthesis
Authors: Iwahashi Akinari , Yamada Takuya , Matsuo Yasumitsu , Kawakami Hinako
Published: November 2020

Energies based on biomaterials attract a lot of interest as next-generation energy because biomaterials are environmentally friendly materials and abundant in nature. Fuel cells are also known as the clean and important next-generation source of energy. In the present study, to develop the fuel cell based on biomaterials, a novel biofuel cell, which consists of collagen electrolyte and the hydrogen fuel generated from photochemical system II (PSII) in photosynthesis, has been fabricated, and its property has been investigated. It was found that the PSII solution, in which PSII was extracted from the thylakoid membrane using a surfactant, generates hydrogen by the irradiation of light. The typical hydrogen-generating rate is approximately 7.41 × 1014 molecules/s for the light intensity of 0.5 mW/cm2 for the PSII solution of 5 mL. The biofuel cell using the PSII solution as the fuel exhibited approximately 0.12 mW/cm2. This result indicates that the fuel cell using the collagen electrolyte and the hydrogen fuel generated from PSII solution becomes the new type of biofuel cell and will lead to the development of the next-generation energy.
The Performance of Preloaded Bolts in Seismically Prequalified Steel Joints in a Fire Scenario
Authors: Tartaglia Roberto , D’Aniello Mario , Andreini Marco , La Mendola Saverio
Published: November 2020

Seismically pre-qualified beam-to-column joints guarantee large ductility in seismic scenarios thanks to the effectiveness of the design rules and technological requirements that are devoted to avoiding the failure of brittle components (i.e., bolts and welds). However, their performance under different severe actions like those induced by fire has not been properly investigated. Therefore, a parametric study based on finite element simulations has been carried out with the aim to verify the effectiveness of local details of seismically prequalified joints under fire. Finite element analyses were carried out on beam-to-column assemblies sub-structured from a reference archetype building accounting for both material and geometrical imperfections. The bolts’ internal actions were monitored in all the investigated specimens varying the applied vertical loads. The results show that the seismic design rules adopted to size the bolts are effective to resist the large increase in shear forces in the bolts occurring under fire. Thus, the investigated joints provide satisfactory ductility and rotation capacity at high temperature preventing the failure of bolts; further analysis could be conducted to investigated the fire performance of the investigated joints in a seismic scenario.
An Antibiotic-Releasing Bone Void Filling (ABVF) Putty for the Treatment of Osteomyelitis
Authors: Hasan Raquib , Wohlers Abbey , Shreffler Jacob , Mulinti Pranothi , Ostlie Hunter , Schaper Codi , Brooks Benjamin , Brooks Amanda
Published: November 2020

The number of total joint replacements (TJR) is on the rise with a corresponding increase in the number of infected TJR, which necessitates revision surgeries. Current treatments with either non-biodegradable, antibiotic-releasing polymethylmethacrylate (PMMA) based bone cement, or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection. Here, we report a biodegradable, easy-to-use “press-fitting” antibiotic-releasing bone void filling (ABVF) putty that not only provides efficient antibiotic release kinetics at the site of infection but also allows efficient osseointegration. The ABVF formulation was prepared using poly (D,L-lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), and polycaprolactone (PCL) as the polymer matrix, antibiotic vancomycin, and osseointegrating synthetic bone PRO OSTEON for bone-growth support. ABVF was homogenous, had a porous structure, was moldable, and showed putty-like mechanical properties. The ABVF putty released vancomycin for 6 weeks at therapeutic level. Furthermore, the released vancomycin showed in vitro antibacterial activity against Staphylococcus aureus for 6 weeks. Vancomycin was not toxic to osteoblasts. Finally, ABVF was biodegradable in vivo and showed an effective infection control with the treatment group showing significantly higher bone growth (p < 0.001) compared to the control group. The potential of infection treatment and osseointegration makes the ABVF putty a promising treatment option for osteomyelitis after TJR.
Bottom Contact Metal Oxide Interface Modification Improving the Efficiency of Organic Light Emitting Diodes
Authors: Pozov Sergey M. , Ioakeimidis Apostolos , Papadas Ioannis T. , Sun Chen , Chrusou Alexandra Z. , Bradley Donal D. C. , Choulis Stelios A.
Published: November 2020

The performance of solution-processed organic light emitting diodes (OLEDs) is often limited by non-uniform contacts. In this work, we introduce Ni-containing solution-processed metal oxide (MO) interfacial layers inserted between indium tin oxide (ITO) and poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) to improve the bottom electrode contact for OLEDs using the poly(p-phenylene vinylene) (PPV) derivative Super-Yellow (SY) as an emission layer. For ITO/Ni-containing MO/PEDOT:PSS bottom electrode structures we show enhanced wetting properties that result in an improved OLED device efficiency. Best performance is achieved using a Cu-Li co-doped spinel nickel cobaltite [(Cu-Li):NiCo2O4], for which the current efficiency and luminous efficacy of SY OLEDs increased, respectively, by 12% and 11% from the values obtained for standard devices without a Ni-containing MO interface modification between ITO and PEDOT:PSS. The enhanced performance was attributed to the improved morphology of PEDOT:PSS, which consequently increased the hole injection capability of the optimized ITO/(Cu-Li):NiCo2O4/PEDOT:PSS electrode.