bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Review and Meta-Analysis of Vesical Imaging-Reporting and Data System (VI-RADS) Inter-Observer Reliability: An Added Value for Muscle Invasive Bladder Cancer Detection
Authors: Del Giudice Francesco Del , Pecoraro Martina , Vargas Hebert Alberto , Cipollari Stefano , De Berardinis Ettore , Bicchetti Marco , Chung Benjamin I. , Catalano Carlo , Narumi Yoshifumi , Catto James W. F. , Panebianco Valeria
Published: October 2020

The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC). PubMed, Web of Science, Cochrane, and Embase were searched up until 30 July 2020. The Quality Appraisal of Diagnostic Reliability (QAREL) checklist was utilized to assess the quality of included studies and a pooled measure of inter-rater reliability (Cohen’s Kappa [κ] and/or Intraclass correlation coefficients (ICCs)) was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate the contribution of moderators to heterogeneity. In total, eight studies between 2018 and 2020, which evaluated a total of 1016 patients via 21 interpreting genitourinary (GU) radiologists, met inclusion criteria and were critically examined. No study was considered to be significantly flawed with publication bias. The pooled weighted mean κ estimate was 0.83 (95%CI: 0.78–0.88). Heterogeneity was present among the studies (Q = 185.92, d.f. = 7, p < 0.001; I2 = 92.7%). Meta-regression analyses showed that the relative % of MIBC diagnosis and cumulative reader’s experience to influence the estimated outcome (Coeff: 0.019, SE: 0.007; p= 0.003 and 0.036, SE: 0.009; p = 0.001). In the present study, we confirm excellent pooled inter-reader agreement of VI-RADS to discriminate NMIBC from MIBC underlying the importance that standardization and reproducibility of VI-RADS may confer to multiparametric magnetic resonance (mpMRI) for preoperative BCa staging.
Combination of CTec2 and GH5 or GH26 Endo-Mannanases for Effective Lignocellulosic Biomass Degradation
Authors: Malgas Samkelo , Pletschke Brett I.
Published: October 2020

Among endo-mannanases, glycoside hydrolase (GH) family 26 enzymes have been shown to be more catalytically active than GH5 enzymes on mannans. However, only GH5 endo-mannanases have been used for the formulation of enzyme cocktails. In this study, Bacillus sp.-derived GH5 and GH26 endo-mannanases were comparatively analysed biochemically for their synergistic action with a commercial cellulase blend, CTec2, during pre-treated lignocellulose degradation. Substrate specificity and thermo-stability studies on mannan substrates showed that GH26 endo-mannanase was more catalytically active and stable than GH5. GH26 also exhibited higher binding affinity for mannan than GH5, while GH5 showed more affinity for lignocellulosic substrates than GH26. Applying the endo-mannanases in combination with CTec2 for lignocellulose degradation led to synergism with a 1.3-fold increase in reducing sugar release compared to when CTec2 was used alone. This study showed that using the activity of endo-mannanases displayed with model substrates is a poor predictor of their activity and synergism on complex lignocelluloses.
Novel Push–Pull Dyes Derived from 1H-cyclopenta[b]naphthalene-1,3(2H)-dione as Versatile Photoinitiators for Photopolymerization and Their Related Applications: 3D Printing and Fabrication of Photocomposites
Authors: Sun Ke , Liu Shaohui , Pigot Corentin , Brunel Damien , Graff Bernadette , Nechab Malek , Gigmes Didier , Morlet-Savary Fabrice , Zhang Yijun , Xiao Pu , Dumur Frédéric , Lalevée Jacques
Published: October 2020

A series of eleven push–pull chromophores with specific structures have been designed for the free radical polymerization of acrylates, but also for the fabrication of photocomposites and 3D-printed structures. New photoinitiating systems comprising the different push–pull dyes showed excellent photochemical reactivities at 405 nm. Notably, polymerization reactions could be initiated with light-emitting diodes (LEDs) which constitute a unique opportunity to promote the free radical polymerization under mild conditions, i.e., low light intensity (e.g., sunlight) and under air. Photopolymerization is an active research field, and push–pull dyes have already been investigated for this purpose. Besides, it remains of crucial interest to investigate new reactive structures capable of efficiently initiating photopolymerization reactions. The plausible potential of these structures to act as efficient photoinitiators in vat photopolymerization (or 3D printing) and fabrication of photocomposites prompts us to select eleven new push–pull dyes to design multi-component photoinitiating systems activable with LEDs emitting at 405 nm. Precisely, a tertiary amine, i.e., ethyl dimethylaminobenzoate (EDB) used as an electron/hydrogen donor and an iodonium salt used as an electron acceptor were selected to behave as powerful co-initiators to construct three-component photoinitiating systems (PISs) with the different push–pull dyes. Among these new PISs, dye 8 and 9-based PISs could efficiently promote the free radical photopolymerization of acrylates upon exposure to a LED emitting at 405 nm also upon sunlight irradiation, highlighting their huge performance. Photoinitiating abilities could be explained on the basis of steady state photolysis experiments. Fluorescence measurements and electron spin resonance (ESR) spin-trapping experiments were also performed to obtain a deeper insight into the chemical mechanisms supporting the polymerization reaction and determine the way the initiating species, i.e., the radicals, are observed. Finally, two investigated dye-based PISs were applied to the fabrications of photocomposites. Three-dimensional patterns with excellent spatial resolutions were generated by the laser writing technique to identify the effects of photopolymerization of acrylates both in the absence and presence of fillers (silica). Interestingly, comparison between the 3D objects fabricated by the PISs/monomer systems and the PISs/monomer/filler photocomposites indicates that the newly designed photocomposites are suitable for practical applications.
High-Loaded Nickel Based Sol–Gel Catalysts for Methylcyclohexane Dehydrogenation
Authors: Gulyaeva Yuliya K. , Alekseeva (Bykova) Maria V. , Ermakov Dmitry Yu. , Bulavchenko Olga A. , Zaikina Olesya O. , Yakovlev Vadim A.
Published: October 2020

Application of liquid organic hydrogen carriers, such as “methylcyclohexane (MCH)–toluene” chemical couple, is one of the promising approaches for hydrogen storage and transportation. In the present study, copper-modified nickel catalysts with high metal loading of 75 wt% were synthesized via heterophase sol–gel technique, and investigated in the dehydrogenation of MCH. Two approaches towards the copper introduction were applied. The catalyst samples prepared via wetness impregnation of the nickel sol–gel catalyst are characterized by more effective Ni-Cu interaction compared to those where two metals were introduced simultaneously by the mixing of their solid precursors. As a result, the “impregnated” catalysts revealed higher selectivity towards toluene. The addition of copper up to 30 wt% of total metal content was shown to increase significantly toluene selectivity and yield without a noticeable decrease in MCH conversion. The catalyst with the active component including 80 wt% of Ni and 20 wt% of Cu demonstrated 96% and 89% toluene selectivity at 40% and 80% MCH conversion, respectively. Based on the obtained data, this non-noble catalytic system appears quite promising for the MCH dehydrogenation.
Dynasore Blocks Ferroptosis through Combined Modulation of Iron Uptake and Inhibition of Mitochondrial Respiration
Authors: Clemente Laura Prieto , Rabenau Malena , Tang Stephan , Stanka Josefina , Cors Eileen , Stroh Jenny , Culmsee Carsten , von Karstedt Silvia
Published: October 2020

Ferroptosis is a form of regulated necrosis characterized by a chain-reaction of detrimental membrane lipid peroxidation following collapse of glutathione peroxidase 4 (Gpx4) activity. This lipid peroxidation is catalyzed by labile ferric iron. Therefore, iron import mediated via transferrin receptors and both, enzymatic and non-enzymatic iron-dependent radical formation are crucial prerequisites for the execution of ferroptosis. Intriguingly, the dynamin inhibitor dynasore, which has been shown to block transferrin receptor endocytosis, can protect from ischemia/reperfusion injury as well as neuronal cell death following spinal cord injury. Yet, it is unknown how dynasore exerts these cell death-protective effects. Using small interfering RNA suppression, lipid reactive oxygen species (ROS), iron tracers and bona fide inducers of ferroptosis, we find that dynasore treatment in lung adenocarcinoma and neuronal cell lines strongly protects these from ferroptosis. Surprisingly, while the dynasore targets dynamin 1 and 2 promote extracellular iron uptake, their silencing was not sufficient to block ferroptosis suggesting that this route of extracellular iron uptake is dispensable for acute induction of ferroptosis and dynasore must have an additional off-target activity mediating full ferroptosis protection. Instead, in intact cells, dynasore inhibited mitochondrial respiration and thereby mitochondrial ROS production which can feed into detrimental lipid peroxidation and ferroptotic cell death in the presence of labile iron. In addition, in cell free systems, dynasore showed radical scavenger properties and acted as a broadly active antioxidant which is superior to N-acetylcysteine (NAC) in blocking ferroptosis. Thus, dynasore can function as a highly active inhibitor of ROS-driven types of cell death via combined modulation of the iron pool and inhibition of general ROS by simultaneously blocking two routes required for ROS and lipid-ROS driven cell death, respectively. These data have important implications for the interpretation of studies observing tissue-protective effects of this dynamin inhibitor as well as raise awareness that off-target ROS scavenging activities of small molecules used to interrogate the ferroptosis pathway should be taken into consideration.
Pseudomonas aeruginosa Planktonic- and Biofilm-Conditioned Media Elicit Discrete Metabolic Responses in Human Macrophages
Authors: Fuchs Amanda , Miller Isaac , Schiller Sage , Ammons Mary , Eilers Brian , Tripet Brian , Copié Valérie
Published: October 2020

Macrophages (MΦs) are prevalent innate immune cells, present throughout human bodily tissues where they orchestrate innate and adaptive immune responses to maintain cellular homeostasis. MΦs have the capacity to display a wide array of functional phenotypes due to different microenvironmental cues, particularly soluble bacterial secretory products. Recent evidence has emerged demonstrating that metabolism supports MΦ function and plasticity, in addition to energy and biomolecular precursor production. In this study, 1D 1H-NMR-based metabolomics was used to identify the metabolic pathways that are differentially altered following primary human monocyte-derived MΦ exposure to P. aeruginosa planktonic- and biofilm-conditioned media (PCM and BCM). Metabolic profiling of PCM- and BCM-exposed MΦs indicated a significant increase in glycolytic metabolism, purine biosynthesis, and inositol phosphate metabolism. In addition, these metabolic patterns suggested that BCM-exposed MΦs exhibit a hyperinflammatory metabolic profile with reduced glycerol metabolism and elevated catabolism of lactate and amino acids, relative to PCM-exposed MΦs. Altogether, our study reveals novel findings concerning the metabolic modulation of human MΦs after exposure to secretory microbial products and contributes additional knowledge to the field of immunometabolism in MΦs.
The Functional Role of microRNAs in the Pathogenesis of Tauopathy
Authors: Praticò Domenico
Published: October 2020

Tauopathies are neurodegenerative disorders which include Alzheimer’s disease, Pick’s disease, corticobasal degeneration, and progressive supranuclear palsy among others. Pathologically, they are characterized by the accumulation of highly phosphorylated and aggregated tau protein in different brain regions. Currently, the mechanisms responsible for their pathogenesis are not known, and for this reason, there is no cure. MicroRNAs (miRNAs) are abundantly present in the central nervous system where they act as master regulators of pathways considered important for tau post-translational modifications, metabolism, and clearance. Although in recent years, several miRNAs have been reported to be altered in tauopathy, we still do not know whether these changes contribute to the onset and progression of the disorder, or are secondary events following the development of tau neuropathology. Additionally, since miRNAs are relatively stable in biological fluids and their measurement is easy and non-invasive, these small molecules hold the potential to function as biomarkers for tauopathy. Herein, we showcase recent findings on the biological link between miRNAs and the pathogenesis of tauopathy, and present emerging evidence supporting their role as biomarkers and targets for novel therapies against them.
Learning from Fifteen Years of Genome-Wide Association Studies in Age-Related Macular Degeneration
Authors: Strunz Tobias , Kiel Christina , Sauerbeck Bastian L. , Weber Bernhard H. F.
Published: October 2020

Over the last 15 years, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic landscape of complex phenotypes. Nevertheless, causal interpretations of GWAS data are challenging but crucial to understand underlying mechanisms and pathologies. In this review, we explore to what extend the research community follows up on GWAS data. We have traced the scientific activities responding to the two largest GWAS conducted on age-related macular degeneration (AMD) so far. Altogether 703 articles were manually categorized according to their study type. This demonstrates that follow-up studies mainly involve “Review articles” (33%) or “Genetic association studies” (33%), while 19% of publications report on findings from experimental work. It is striking to note that only three of 16 AMD-associated loci described de novo in 2016 were examined in the four-year follow-up period after publication. A comparative analysis of five studies on gene expression regulation in AMD-associated loci revealed consistent gene candidates for 15 of these loci. Our random survey highlights the fact that functional follow-up studies on GWAS results are still in its early stages hampering a significant refinement of the vast association data and thus a more accurate insight into mechanisms and pathways.
Small-Molecule Chemical Knockdown of MuRF1 in Melanoma Bearing Mice Attenuates Tumor Cachexia Associated Myopathy
Authors: Adams Volker , Gußen Victoria , Zozulya Sergey , Cruz André , Moriscot Anselmo , Linke Axel , Labeit Siegfried
Published: October 2020

Patients with malignant tumors frequently suffer during disease progression from a syndrome referred to as cancer cachexia (CaCax): CaCax includes skeletal muscle atrophy and weakness, loss of bodyweight, and fat tissues. Currently, there are no FDA (Food and Drug Administration) approved treatments available for CaCax. Here, we studied skeletal muscle atrophy and dysfunction in a murine CaCax model by injecting B16F10 melanoma cells into mouse thighs and followed mice during melanoma outgrowth. Skeletal muscles developed progressive weakness as detected by wire hang tests (WHTs) during days 13–23. Individual muscles analyzed at day 24 had atrophy, mitochondrial dysfunction, augmented metabolic reactive oxygen species (ROS) stress, and a catabolically activated ubiquitin proteasome system (UPS), including upregulated MuRF1. Accordingly, we tested as an experimental intervention of recently identified small molecules, Myomed-205 and -946, that inhibit MuRF1 activity and MuRF1/MuRF2 expression. Results indicate that MuRF1 inhibitor fed attenuated induction of MuRF1 in tumor stressed muscles. In addition, the compounds augmented muscle performance in WHTs and attenuated muscle weight loss. Myomed-205 and -946 also rescued citrate synthase and complex-1 activities in tumor-stressed muscles, possibly suggesting that mitochondrial-metabolic and muscle wasting effects in this CaCax model are mechanistically connected. Inhibition of MuRF1 during tumor cachexia may represent a suitable strategy to attenuate skeletal muscle atrophy and dysfunction.
K+ Channel Tetramerization Domain 5 (KCTD5) Protein Regulates Cell Migration, Focal Adhesion Dynamics and Spreading through Modulation of Ca2+ Signaling and Rac1 Activity
Authors: Canales Jimena , Cruz Pablo , Díaz Nicolás , Riquelme Denise , Leiva-Salcedo Elías , Cerda Oscar
Published: October 2020

Cell migration is critical for several physiological and pathophysiological processes. It depends on the coordinated action of kinases, phosphatases, Rho-GTPases proteins, and Ca2+ signaling. Interestingly, ubiquitination events have emerged as regulatory elements of migration. Thus, the role of proteins involved in ubiquitination processes could be relevant to a complete understanding of pro-migratory mechanisms. KCTD5 is a member of Potassium Channel Tetramerization Domain (KCTD) proteins that have been proposed as a putative adaptor for Cullin3-E3 ubiquitin ligase and a novel regulatory protein of TRPM4 channels. Here, we study whether KCTD5 participates in cell migration-associated mechanisms, such as focal adhesion dynamics and cellular spreading. Our results show that KCTD5 CRISPR/Cas9- and shRNA-based depletion in B16-F10 cells promoted an increase in cell migration and cell spreading, and a decrease in the focal adhesion area, consistent with an increased focal adhesion disassembly rate. The expression of a dominant-negative mutant of Rho-GTPases Rac1 precluded the KCTD5 depletion-induced increase in cell spreading. Additionally, KCTD5 silencing decreased the serum-induced Ca2+ response, and the reversion of this with ionomycin abolished the KCTD5 knockdown-induced decrease in focal adhesion size. Together, these data suggest that KCTD5 acts as a regulator of cell migration by modulating cell spreading and focal adhesion dynamics through Rac1 activity and Ca2+ signaling, respectively.
Special Issue on “New Advances in Cyclic AMP Signalling”—An Editorial Overview
Authors: Yarwood Stephen John
Published: October 2020

The cyclic nucleotides 3′,5′-adenosine monophosphate (cyclic AMP) signalling system underlies the control of many biological events and disease processes in man. Cyclic AMP is synthesised by adenylate cyclase (AC) enzymes in order to activate effector proteins and it is then degraded by phosphodiesterase (PDE) enzymes. Research in recent years has identified a range of cell-type-specific cyclic AMP effector proteins, including protein kinase A (PKA), exchange factor directly activated by cyclic AMP (EPAC), cyclic AMP responsive ion channels (CICs), and the Popeye domain containing (POPDC) proteins, which participate in different signalling mechanisms. In addition, recent advances have revealed new mechanisms of action for cyclic AMP signalling, including new effectors and new levels of compartmentalization into nanodomains, involving AKAP proteins and targeted adenylate cyclase and phosphodiesterase enzymes. This Special Issue contains 21 papers that highlight advances in our current understanding of the biology of compartmentlised cyclic AMP signalling. This ranges from issues of pathogenesis and associated molecular pathways, functional assessment of novel nanodomains, to the development of novel tool molecules and new techniques for imaging cyclic AMP compartmentilisation. This editorial aims to summarise these papers within the wider context of cyclic AMP signalling.
Age-Dependent Maturation of iPSC-CMs Leads to the Enhanced Compartmentation of β2AR-cAMP Signalling
Authors: Hasan Alveera , Mohammadi Neda , Nawaz Aisha , Kodagoda Thusharika , Diakonov Ivan , Harding Sian E. , Gorelik Julia
Published: October 2020

The ability to differentiate induced-pluripotent stem cells into cardiomyocytes (iPSC-CMs) has opened up novel avenues for potential cardiac therapies. However, iPSC-CMs exhibit a range of somewhat immature functional properties. This study explored the development of the beta-adrenergic receptor (βAR) pathway, which is crucial in regulating contraction and signifying the health and maturity of myocytes. We explored the compartmentation of β2AR-signalling and phosphodiesterases (PDEs) in caveolae, as functional nanodomains supporting the mature phenotype. Förster Resonance Energy Transfer (FRET) microscopy was used to study the cyclic adenosine monophosphate (cAMP) levels in iPSC-CMs at day 30, 60, and 90 following βAR subtype-specific stimulation. Subsequently, the PDE2, PDE3, and PDE4 activity was investigated using specific inhibitors. Cells were treated with methyl-β-cyclodextrin (MβCD) to remove cholesterol as a method of decompartmentalising β2AR. As iPSC-CMs mature with a prolonged culture time, the caveolae density is increased, leading to a reduction in the overall cytoplasmic cAMP signal stimulated through β2AR (but not β1AR). Pan-phosphodiesterase inhibition or caveolae depletion leads to an increase in the β2AR-stimulated cytoplasmic cAMP. Moreover, with time in culture, the increase in the βAR-dependent cytoplasmic cAMP becomes more sensitive to cholesterol removal. The regulation of the β2AR response by PDE2 and 4 is similarly increased with the time in culture. We conclude that both the β2AR and PDEs are restricted to the caveolae nanodomains, and thereby exhibit a tighter spatial restriction over the cAMP signal in late-stage compared to early iPSC-CMs.
Understanding IGF-II Action through Insights into Receptor Binding and Activation
Authors: Blyth Andrew J. , Kirk Nicholas S. , Forbes Briony E.
Published: October 2020

The insulin-like growth factor (IGF) system regulates metabolic and mitogenic signaling through an intricate network of related receptors and hormones. IGF-II is one of several hormones within this system that primarily regulates mitogenic functions and is especially important during fetal growth and development. IGF-II is also found to be overexpressed in several cancer types, promoting growth and survival. It is also unique in the IGF system as it acts through both IGF-1R and insulin receptor isoform A (IR-A). Despite this, IGF-II is the least investigated ligand of the IGF system. This review will explore recent developments in IGF-II research including a structure of IGF-II bound to IGF-1R determined using cryo-electron microscopy (cryoEM). Comparisons are made with the structures of insulin and IGF-I bound to their cognate receptors. Finally discussed are outstanding questions in the mechanism of action of IGF-II with the goal of developing antagonists of IGF action in cancer.
Aberrant DNA Methylation of ABC Transporters in Cancer
Authors: Zappe Katja , Cichna-Markl Margit
Published: October 2020

ATP-binding cassette (ABC) transporters play a crucial role in multidrug resistance (MDR) of cancers. They function as efflux pumps, resulting in limited effectiveness or even failure of therapy. Increasing evidence suggests that ABC transporters are also involved in tumor initiation, progression, and metastasis. Tumors frequently show multiple genetic and epigenetic abnormalities, including changes in histone modification and DNA methylation. Alterations in the DNA methylation status of ABC transporters have been reported for a variety of cancer types. In this review, we outline the current knowledge of DNA methylation of ABC transporters in cancer. We give a brief introduction to structure, function, and gene regulation of ABC transporters that have already been investigated for their DNA methylation status in cancer. After giving an overview of the applied methodologies and the CpGs analyzed, we summarize and discuss the findings on aberrant DNA methylation of ABC transporters by cancer types. We conclude our review with the discussion of the potential to target aberrant DNA methylation of ABC transporters for cancer therapy.
LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response
Authors: Koos Björn , Moderegger Eva Lotta , Rump Katharina , Nowak Hartmuth , Willemsen Katrin , Holtkamp Caroline , Thon Patrick , Adamzik Michael , Rahmel Tim
Published: October 2020

Mitochondrial DNA (mtDNA) plays a vital role as a damage-associated molecular pattern in sepsis being able to shape the immune response. Since pathogen recognition receptors of innate immune cells are activated by demethylated DNA only, we set out to investigate the amount of DNA methyltransferase 1 (DNMT1) in mitochondria and the extent of mtDNA methylation in a human endotoxin model. Peripheral blood mononuclear cells of 20 healthy individuals were isolated from whole blood and stimulated with lipopolysaccharide (LPS) for 48 h. Subsequently, DNMT1 protein abundance was assessed in whole cells and a mitochondrial fraction. At the same time, methylation levels of mtDNA were quantified, and cytokine expression in the supernatant was measured. Despite increased cellular expression of DNMT1 after LPS stimulation, the degree of mtDNA methylation slightly decreased. Strikingly the mitochondrial protein abundance of DNMT1 was reduced by 50% in line with the lower degree of mtDNA methylation. Although only modest alterations were seen in the degree of mtDNA methylation, these strongly correlated with IL-6 and IL-10 expression. Our data may hint at a protein import problem for DNMT1 into the mitochondria under LPS stimulation and suggest a role of demethylated mtDNA in the regulation of the inflammatory immune response.
Role of the Cation-Chloride-Cotransporters in Cardiovascular Disease
Authors: Meor Azlan Nur Farah , Zhang Jinwei
Published: October 2020

The SLC12 family of cation-chloride-cotransporters (CCCs) is comprised of potassium chloride cotransporters (KCCs), which mediate Cl− extrusion and sodium-potassium chloride cotransporters (N[K]CCs), which mediate Cl− loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. The functions of CCCs influence a variety of physiological processes, many of which overlap with the pathophysiology of cardiovascular disease. Although not all of the cotransporters have been linked to Mendelian genetic disorders, recent studies have provided new insights into their functional role in vascular and renal cells in addition to their contribution to cardiovascular diseases. Particularly, an imbalance in potassium levels promotes the pathogenesis of atherosclerosis and disturbances in sodium homeostasis are one of the causes of hypertension. Recent findings suggest hypothalamic signaling as a key signaling pathway in the pathophysiology of hypertension. In this review, we summarize and discuss the role of CCCs in cardiovascular disease with particular emphasis on knowledge gained in recent years on NKCCs and KCCs.
The Role of Aryl-Hydrocarbon Receptor (AhR) in Osteoclast Differentiation and Function
Authors: Park Robin , Madhavaram Shreya , Ji Jong Dae
Published: October 2020

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mechanism of AhR signaling in regulating osteoclastogenesis is not widely understood. AhR, when binding with exogenous ligands (environmental pollutants such as polycylic aryl hydrocarbon (PAH), dioxins) or endogenous ligand indoxyl-sulfate (IS), has dual functions that are mediated by the nature of the binding ligand, binding time, and specific pathways of distinct ligands. In this review, AhR is discussed with a focus on (i) the role of AhR in osteoclast differentiation and function and (ii) the mechanisms of AhR signaling in inhibiting or promoting osteoclastogenesis. These findings facilitate an understanding of the role of AhR in the functional regulation of osteoclasts and in osteoclast-induced bone destructive conditions such as rheumatoid arthritis and cancer.
Associations between Pregnane X Receptor and Breast Cancer Growth and Progression
Authors: Creamer Bradley A. , Sloan Shelly N. B. , Dennis Jennifer F. , Rogers Robert , Spencer Sidney , McCuen Andrew , Persaud Purnadeo , Staudinger Jeff L.
Published: October 2020

Pregnane X receptor (PXR, NR1I2) is a member of the ligand-activated nuclear receptor superfamily. This receptor is promiscuous in its activation profile and is responsive to a broad array of both endobiotic and xenobiotic ligands. PXR is involved in pivotal cellular detoxification processes to include the regulation of genes that encode key drug-metabolizing cytochrome-P450 enzymes, oxidative stress response, as well as enzymes that drive steroid and bile acid metabolism. While PXR clearly has important regulatory roles in the liver and gastrointestinal tract, this nuclear receptor also has biological functions in breast tissue. In this review, we highlight current knowledge of PXR’s role in mammary tumor carcinogenesis. The elevated level of PXR expression in cancerous breast tissue suggests a likely interface between aberrant cell division and xeno-protection in cancer cells. Moreover, PXR itself exerts positive effect on the cell cycle, thereby predisposing tumor cells to unchecked proliferation. Activation of PXR also plays a key role in regulating apoptosis, as well as in acquired resistance to chemotherapeutic agents. The repressive role of PXR in regulating inflammatory mediators along with the existence of genetic polymorphisms within the sequence of the PXR gene may predispose individuals to developing breast cancer. Further investigations into the role that PXR plays in driving tumorigenesis are needed.
Role of the JAK/STAT Pathway in Cervical Cancer: Its Relationship with HPV E6/E7 Oncoproteins
Authors: Gutiérrez-Hoya Adriana , Soto-Cruz Isabel
Published: October 2020

The janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is associated with the regulation of essential cellular mechanisms, such as proliferation, invasion, survival, inflammation, and immunity. Aberrant JAK/STAT signaling contributes to cancer progression and metastatic development. STAT proteins play an essential role in the development of cervical cancer, and the inhibition of the JAK/STAT pathway may be essential for enhancing tumor cell death. Persistent activation of different STATs is present in a variety of cancers, including cervical cancer, and their overactivation may be associated with a poor prognosis and poor overall survival. The oncoproteins E6 and E7 play a critical role in the progression of cervical cancer and may mediate the activation of the JAK/STAT pathway. Inhibition of STAT proteins appears to show promise for establishing new targets in cancer treatment. The present review summarizes the knowledge about the participation of the different components of the JAK/STAT pathway and the participation of the human papillomavirus (HPV) associated with the process of cellular malignancy.
Cannabinoid-Induced Autophagy and Heme Oxygenase-1 Determine the Fate of Adipose Tissue-Derived Mesenchymal Stem Cells under Stressful Conditions
Authors: Bublitz Katharina , Böckmann Sabine , Peters Kirsten , Hinz Burkhard
Published: October 2020

The administration of adipose tissue-derived mesenchymal stem cells (ADMSCs) represents a promising therapeutic option after myocardial ischemia or myocardial infarction. However, their potential is reduced due to the high post-transplant cell mortality probably caused by oxidative stress and mitogen-deficient microenvironments. To identify protection strategies for ADMSCs, this study investigated the influence of the non-psychoactive phytocannabinoid cannabidiol (CBD) and the endocannabinoid analogue R(+)-methanandamide (MA) on the induction of heme oxygenase-1 (HO-1) and autophagy under serum-free conditions. At a concentration of 3 µM, CBD induced an upregulation of HO-1 mRNA and protein within 6 h, whereas for MA only a late and comparatively lower increase in the HO-1 protein could be detected after 48 h. In addition, both cannabinoids induced time- and concentration-dependent increases in LC3A/B-II protein, a marker of autophagy, and in metabolic activity. A participation of several cannabinoid-binding receptors in the effect on metabolic activity and HO-1 was excluded. Similarly, knockdown of HO-1 by siRNA or inhibition of HO-1 activity by tin protoporphyrin IX (SnPPIX) had no effect on CBD-induced autophagy and metabolic activity. On the other hand, the inhibition of autophagy by bafilomycin A1 led to a significant decrease in cannabinoid-induced metabolic activity and to an increase in apoptosis. Under these circumstances, a significant induction of HO-1 expression after 24 h could also be demonstrated for MA. Remarkably, inhibition of HO-1 by SnPPIX under conditions of autophagy deficit led to a significant reversal of apoptosis in cannabinoid-treated cells. In conclusion, the investigated cannabinoids increase metabolic viability of ADMSCs under serum-free conditions by inducing HO-1-independent autophagy but contribute to apoptosis under conditions of additional autophagy deficit via an HO-1-dependent pathway.
How Altered Ribosome Production Can Cause or Contribute to Human Disease: The Spectrum of Ribosomopathies
Authors: Venturi Giulia , Montanaro Lorenzo
Published: October 2020

A number of different defects in the process of ribosome production can lead to a diversified spectrum of disorders that are collectively identified as ribosomopathies. The specific factors involved may either play a role only in ribosome biogenesis or have additional extra-ribosomal functions, making it difficult to ascribe the pathogenesis of the disease specifically to an altered ribosome biogenesis, even if the latter is clearly affected. We reviewed the available literature in the field from this point of view with the aim of distinguishing, among ribosomopathies, the ones due to specific alterations in the process of ribosome production from those characterized by a multifactorial pathogenesis.
The Multi-Omics Architecture of Juvenile Idiopathic Arthritis
Authors: Hou Xiaoyuan , Qu Huiqi , Zhang Sipeng , Qi Xiaohui , Hakonarson Hakon , Xia Qianghua , Li Jin
Published: October 2020

Juvenile idiopathic arthritis (JIA) is highly heterogeneous in terms of etiology and clinical presentation with ambiguity in JIA classification. The advance of high-throughput omics technologies in recent years has gained us significant knowledge about the molecular mechanisms of JIA. Besides a minor proportion of JIA cases as monogenic, most JIA cases are polygenic disease caused by autoimmune mechanisms. A number of HLA alleles (including both HLA class I and class II genes), and 23 non-HLA genetic loci have been identified of association with different JIA subtypes. Omics technologies, i.e., transcriptome profiling and epigenomic analysis, contributed significant knowledge on the molecular mechanisms of JIA in addition to the genetic approach. New molecular knowledge on different JIA subtypes enables us to reconsider the JIA classification, but also highlights novel therapeutic targets to develop a cure for the devastating JIA.
Oncogenic and Tumor-Suppressive Functions of NOTCH Signaling in Glioma
Authors: Parmigiani Elena , Taylor Verdon , Giachino Claudio
Published: October 2020

Although the role of NOTCH signaling has been extensively studied in health and disease, many questions still remain unresolved. Being crucial for tissue homeostasis, NOTCH signaling is also implicated in multiple cancers by either promoting or suppressing tumor development. In this review we illustrate the context-dependent role of NOTCH signaling during tumorigenesis with a particular focus on gliomas, the most frequent and aggressive brain tumors in adults. For a long time, NOTCH has been considered an oncogene in glioma mainly by virtue of its neural stem cell-promoting activity. However, the recent identification of NOTCH-inactivating mutations in some glioma patients has challenged this notion, prompting a re-examination of the function of NOTCH in brain tumor subtypes. We discuss recent findings that might help to reconcile the controversial role of NOTCH signaling in this disease, and pose outstanding questions that still remain to be addressed.
Photoluminescence of Layered Semiconductor Materials for Emission-Color Conversion of Blue Micro Light-Emitting Diode (µLED)
Authors: Tsuboi Yuma , Urakami Noriyuki , Hashimoto Yoshio
Published: October 2020

A micro light-emitting diode (μLED) is a key device for the future of advanced information. Owing to expand its application widely, the concept of the emission-color conversion using layered semiconductors as a color converter is proposed. In addition, it is demonstrated that layered semiconductors were transferred directly onto μLED chips, and the emission-color conversion is realized. The layered GaS1−xSex alloy, whose energy bandgap can be controlled by tuning the S and Se compositions, was selected as a color converter. The photoluminescence (PL) measurements using a blue LED as an excitation source revealed that GaS0.65Se0.35 and GaSe can show green and red luminescence with center energies of 2.34 and 1.94 eV, respectively. The emission color of gallium nitride (GaN)-based blue μLEDs covered with GaS0.65Se0.35 and GaSe thin films were clearly converted to green and red, respectively. Furthermore, the emission color could be controlled by changing the film thickness. Thus, these results suggest the possibility of emission-color conversion of blue μLED chips utilizing layered materials.
Microstructure Evolution and Mechanical Behavior of Mo–Si–N Films
Authors: Liu Yu-Cheng , Liang Bing-Hao , Huang Chi-Ruei , Wu Fan-Bean
Published: October 2020

The molybdenum silicon nitride (Mo–Si–N) films were deposited by a radio frequency (RF) magnetron reactive dual-gun co-sputtering technique with process control on input power and gas ratio. Composition variation, microstructure evolution, and related mechanical and tribological behavior of the Mo–Si–N coatings were investigated. The N2/(Ar + N2) flow ratios were controlled at 10/20 and 5/20 levels with the tuning of input power on the Si target at 0, 100, and 150 W. As the silicon contents increased from 0 to 33.7 at.%, the film microstructure evolved from a crystalline structure with Mo2N and MoN phases to an amorphous feature with the Si3N4 phase. The analysis of selected area electron diffraction patterns in TEM also indicated an amorphous feature of the Mo–Si–N films when Si content reached 20 at.% and beyond. The hardness and Young’s modulus changed from 16.5 to 26.9 and 208 to 273 GPa according to their microstructure features. The highest hardness and modulus were attributed to nanocrystalline Mo2N and MoN with Si solid-solution. The crystalline Mo–Si–N films showed a smooth tribological track and less wear failure was found. In contrast, the wear track with severe failures were observed for Mo–N and amorphous Mo–Si–N coatings due to their lower hardness. The ratios of H/E and H3/E2 were intensively discussed and correlated to the wear behavior of the Mo–Si–N coatings.
A Review of Polysaccharide-Zinc Oxide Nanocomposites as Safe Coating for Fruits Preservation
Authors: Anugrah Daru Seto Bagus , Alexander Hugo , Pramitasari Rianita , Hudiyanti Dwi , Sagita Christyowati Primi
Published: October 2020

Safe coating formulated from biopolymer can be an alternative for better packaging for fruits. Among biopolymers used for safe coating, polysaccharides attracted more attention due to its biocompatibility and edibility. However, polysaccharide-based materials have weaknesses such as low water barrier and mechanical properties which result in lower capability on preserving the coated fruits. Hence, the incorporation of nanoparticles (NPs) such as zinc oxide (ZnO) is expected to increase the ability of polysaccharide-based coating for the enhancement of fruit shelf life. In this review paper, the basic information and the latest updates on the incorporation of ZnO NPs into the polysaccharide-based safe coating for fruit are presented. Various research has investigated polysaccharide-ZnO nanocomposite safe coating to prolong the shelf life of fruits. The polysaccharides used include chitosan, alginate, carrageenan, cellulose, and pectin. Overall, polysaccharide-ZnO nanocomposites can improve the shelf life of fruits by reducing weight loss, maintaining firmness, reducing the ripening process, reducing respiration, reducing the oxidation process, and inhibiting microbial growth. Finally, the challenges and potential of ZnO NPs as an active agent in the safe coating application are also discussed.
State Estimation and Localization Based on Sensor Fusion for Autonomous Robots in Indoor Environment
Authors: Doumbia Mamadou , Cheng Xu
Published: October 2020

Currently, almost all robot state estimation and localization systems are based on the Kalman filter (KF) and its derived methods, in particular the unscented Kalman filter (UKF). When applying the UKF alone, the estimate of the state is not sufficiently precise. In this paper, a new hierarchical infrared navigational algorithm hybridization (HIRNAH) system is developed to provide better state estimation and localization for mobile robots. Two navigation subsystems (inertial navigation system (INS) and, using a novel infrared navigation algorithm (NIRNA), Odom-NIRNA) and an RPLIDAR-A3 scanner cooperation to build HIRNAH. The robot pose (position and orientation) errors are estimated by a system filtering module (SFM) and used to smooth the robot’s final poses. A prototype (two rotary encoders, one smartphone-based robot sensing model and one RPLIDAR-A3 scanner) has been built and mounted on a four-wheeled mobile robot (4-WMR). Simulation results have motivated real-life experiments, and obtained results are compared to some existent research (hardware and control technology navigation (HCTNav), rapid exploring random tree (RRT) and in stand-alone mode (INS)) for performance measurements. The experimental results confirm that HIRNAH presents a more accurate estimation and a lower mean square error (MSE) of the robot’s state than those calculated by the previously cited HCTNav, RRT and INS.
Characterization of Pure Face-Shear Strain in Piezoelectric α-Tellurium Dioxide (α-TeO2)
Authors: Boivin Guillaume , Bélanger Pierre , Zednik Ricardo J.
Published: October 2020

Paratellurite, also known as α-tellurium dioxide, is a ceramic that is primarily employed for its interesting optical properties. However, this material’s crystal structure belongs to the 422 symmetry class that allows a unique piezoelectric behavior to manifest itself: deformation in pure face-shear. This means that crystal symmetry necessitates the piezoelectric tensor to have only a single non-zero coefficient, d123 = d14: such unique behavior has the potential to enable novel gyroscopic sensors and high-precision torsional microelectromechanical systems (MEMS) actuators, as pure face-shear can be used to induce pure torsion. Although α-TeO2 is one of the few known materials belonging to this symmetry class, considerable uncertainty in its single piezoelectric coefficient exists, with the few reported literature values ranging from 6.13 to 14.58 pC/N; this large uncertainty results from the difficulty in using conventional piezoelectric characterization techniques on paratellurite, limiting measurements to indirect methods. The novel applications that would be enabled by the adoption of this extraordinary material are frustrated by this lack of confidence in the literature. We therefore leverage, for the first time, a first-principles analytical physical model with electrochemical impedance spectroscopy (EIS) to determine, directly, the lone piezoelectric coefficient d123 = d14 = 7.92 pC/N.
Correction: Oleas, N.H., et al. Muddy Boots Beget Wisdom: Implications for Rare or Endangered Plant Species Distribution Models. Diversity, 2019, 11, 10
Authors: Oleas Nora H. , Feeley Kenneth J. , Fajardo Javier , Meerow Alan W. , Gebelein Jennifer , Francisco-Ortega Javier
Published: October 2020

An error on our paper [...]
Rapid Detection of Methicillin-Resistant Staphylococcus aureus Directly from Blood for the Diagnosis of Bloodstream Infections: A Mini-Review
Authors: Buonomini Anna Rita , Riva Elisabetta , Di Bonaventura Giovanni , Gherardi Giovanni
Published: October 2020

Staphylococcus aureus represents a major human pathogen able to cause a number of infections, especially bloodstream infections (BSI). Clinical use of methicillin has led to the emergence of methicillin-resistant S. aureus (MRSA) and MRSA-BSI have been reported to be associated with high morbidity and mortality. Clinical diagnosis of BSI is based on the results from blood culture that, although considered the gold standard method, is time-consuming. For this reason, rapid diagnostic tests to identify the presence of methicillin-susceptible S. aureus (MSSA) and MRSA isolates directly in blood cultures are being used with increasing frequency to rapidly commence targeted antimicrobial therapy, also in the light of antimicrobial stewardship efforts. Here, we review and report the most common rapid non-molecular and molecular methods currently available to detect the presence of MRSA directly from blood.
Postnatal Outcome and Associated Anomalies of Prenatally Diagnosed Right Aortic Arch with Concomitant Right Ductal Arch: A Systematic Review and Meta-Analysis
Authors: Cavoretto Paolo Ivo , Sotiriadis Alexandros , Girardelli Serena , Spinillo Silvia , Candiani Massimo , Amodeo Silvia , Farina Antonio , Fesslova Vlasta
Published: October 2020

Right aortic arch presents a reported incidence of 0.1% of the general population; the aim of our study was to evaluate the risk of associated intracardiac (ICA), extracardiac (ECA), or chromosomal abnormalities in fetuses with right aortic arch (RAA) and concomitant right ductal arch (RDA). A systematic review of the literature selected 18 studies including 60 cases of RAA/RDA. A meta-analysis with a random effect model calculated for each outcome the pooled crude proportion of associated abnormal outcomes in cases of RAA/RDA and the pooled proportions and odds ratios in RAA with LDA or RDA. Quality assessment of the included studies was achieved using the NIH quality assessment tool for case series studies. RAA/RDA presents risk of associated conotruncal CHDs of about 30% and risk of 22q11 microdeletion in the region of 1%. Two-thirds of 22q11 microdeletions had concomitant thymic hypoplasia and no other chromosomal defects were described. Risks for ICA, ECA, 22q11 microdeletion, and aberrant left subclavian artery are not substantially different in RAA with right or left arterial duct. RAA increases the risk of associated cardiac defects regardless of laterality of the ductal arch. In isolated RDA/RAA cases, absolute risks of extracardiac associated problems or surgery are rather low, we would therefore recommend reassurance, particularly when the thymus and karyotype are normal.