bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dichotomous Role of Inflammation in the CNS: A Mitochondrial Point of View
Authors: Vezzani Bianca , Carinci Marianna , Patergnani Simone , Pasquin Matteo P. , Guarino Annunziata , Aziz Nimra , Pinton Paolo , Simonato Michele , Giorgi Carlotta
Published: October 2020

Innate immune response is one of our primary defenses against pathogens infection, although, if dysregulated, it represents the leading cause of chronic tissue inflammation. This dualism is even more present in the central nervous system, where neuroinflammation is both important for the activation of reparatory mechanisms and, at the same time, leads to the release of detrimental factors that induce neurons loss. Key players in modulating the neuroinflammatory response are mitochondria. Indeed, they are responsible for a variety of cell mechanisms that control tissue homeostasis, such as autophagy, apoptosis, energy production, and also inflammation. Accordingly, it is widely recognized that mitochondria exert a pivotal role in the development of neurodegenerative diseases, such as multiple sclerosis, Parkinson’s and Alzheimer’s diseases, as well as in acute brain damage, such in ischemic stroke and epileptic seizures. In this review, we will describe the role of mitochondria molecular signaling in regulating neuroinflammation in central nervous system (CNS) diseases, by focusing on pattern recognition receptors (PRRs) signaling, reactive oxygen species (ROS) production, and mitophagy, giving a hint on the possible therapeutic approaches targeting mitochondrial pathways involved in inflammation.
Comparative Analysis of Cx31 and Cx43 in Differentiation-Competent Rodent Keratinocytes
Authors: Au Akina , Shao Qing , White Kyra K. , Lucaciu Sergiu A. , Esseltine Jessica L. , Barr Kevin , Laird Dale W.
Published: October 2020

When considering connexin expression and regulation, the epidermis of the skin is one of the most complex tissues found in mammals even though it largely contains a single cell type, the keratinocyte. In the rodent epidermis, up to 9 connexin family members have been detected at the mRNA level. Many of these connexins are temporally and spatially regulated in coordination with keratinocyte progenitor cell differentiation and migration from the stratum basale to form the stratum spinosum and stratum granulosum layers before finally forming the stratum corneum. Cx43 is the principal connexin found in basal keratinocytes and to a lesser degree found in keratinocytes that have begun to differentiate where Cx26, Cx30 and Cx31 become prevalent. Here we show that the CRISPR-Cas9 ablation of Cx43 reduces overall gap junction coupling in monolayer cultures of rat epidermal keratinocytes (REKs) and dysregulates the differentiation of REKs when grown in organotypic cultures. Natively found in differentiated keratinocytes, Cx31 readily assembles into gap junctions when expressed in REKs where it can extensively co-assemble into the same gap junctions with co-expressed Cx30. Time-lapse imaging indicated that many Cx31 gap junctions are mobile within the plasma membrane undergoing both fusion and fission events. Finally, the persistence of pre-existing Cx31 gap junctions in the presence of the protein trafficking blocker, brefeldin A, is longer than that found for Cx43 gap junctions indicating that it has a distinctly different life expectancy in REKs. Collectively, this study highlights the importance of Cx43 in rodent keratinocyte differentiation and suggests that Cx31 acquires life-cycle properties that are distinct from Cx43.
Preventive Effect of Muscone against Cisplatin Nephrotoxicity in LLC-PK1 Cells
Authors: Phung Hung Manh , Lee Sullim , Hwang Ji Hye , Kang Ki Sung
Published: October 2020

Cisplatin, one of the most common antitumor agents, is widely applied to treat various cancerous diseases and is included in the World Health Organization Model List of Essential Medicines. Cisplatin therapy is used to treat 10–20% of all cancerous cases, and its cure rate is especially high in testicular cancer (over 90%). However, a major side effect of this anticancer drug is nephrotoxicity, limiting treatment effect and reducing the quality of life in cancer patients. Muscone, an odoriferous constituent of musk, was confirmed to inhibit cisplatin-induced LLC-PK1 kidney proximal tubule cell death in a dose-dependent manner. In term of renal protective mechanism, muscone inhibited cisplatin oxidative toxicity by decreasing reactive oxygen species (ROS) level and stimulating HO-1 expression. Muscone also exerted anti-inflammation effect through inhibition of p38 phosphorylation. Furthermore, muscone mitigated cisplatin-induced apoptosis in LLC-PK1 cells via both intrinsic and extrinsic pathways by inhibiting pro-apoptotic protein Bax expression, and cleaved caspase-3, 7, and 8; and increase of anti-apoptotic protein Bcl-2 level. In addition, the anti-apoptotic effect of muscone also was enhanced by preventing p53 expression and its phosphorylation. Our study showed that muscone may be a potential protective agent against cisplatin-induced nephrotoxicity.
Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression
Authors: Ming Zizhen , Lim Su Yin , Rizos Helen
Published: October 2020

Genetic alterations in the INK4a/ARF (or CDKN2A) locus have been reported in many cancer types, including melanoma; head and neck squamous cell carcinomas; lung, breast, and pancreatic cancers. In melanoma, loss of function CDKN2A alterations have been identified in approximately 50% of primary melanomas, in over 75% of metastatic melanomas, and in the germline of 40% of families with a predisposition to cutaneous melanoma. The CDKN2A locus encodes two critical tumor suppressor proteins, the cyclin-dependent kinase inhibitor p16INK4a and the p53 regulator p14ARF. The majority of CDKN2A alterations in melanoma selectively target p16INK4a or affect the coding sequence of both p16INK4a and p14ARF. There is also a subset of less common somatic and germline INK4a/ARF alterations that affect p14ARF, while not altering the syntenic p16INK4a coding regions. In this review, we describe the frequency and types of somatic alterations affecting the CDKN2A locus in melanoma and germline CDKN2A alterations in familial melanoma, and their functional consequences in melanoma development. We discuss the clinical implications of CDKN2A inactivating alterations and their influence on treatment response and resistance.
Nonhistone Proteins HMGB1 and HMGB2 Differentially Modulate the Response of Human Embryonic Stem Cells and the Progenitor Cells to the Anticancer Drug Etoposide
Authors: Bagherpoor Alireza Jian , Kučírek Martin , Fedr Radek , Sani Soodabeh Abbasi , Štros Michal
Published: October 2020

HMGB1 and HMGB2 proteins are abundantly expressed in human embryonic stem cells(hESCs) and hESC-derived progenitor cells (neuroectodermal cells, hNECs), though their functionalroles in pluripotency and the mechanisms underlying their dierentiation in response to the anticancerdrug etoposide remain to be elucidated. Here, we show that HMGB1 and/or HMGB2 knockdown(KD) by shRNA in hESCs did not aect the cell stemness/pluripotency regardless of etoposidetreatments, while in hESC-derived neuroectodermal cells, treatment resulted in dierential eects oncell survival and the generation of rosette structures. The objective of this work was to determinewhether HMGB1/2 proteins could modulate the sensitivity of hESCs and hESC-derived progenitorcells (hNECs) to etoposide. We observed that HMGB1 KD knockdown (KD) and, to a lesser extent,HMGB2 KD enhanced the sensitivity of hESCs to etoposide. Enhanced accumulation of 53BP1 ontelomeres was detected by confocal microscopy in both untreated and etoposide-treated HMGB1KD hESCs and hNECs, indicating that the loss of HMGB1 could destabilize telomeres. On the otherhand, decreased accumulation of 53BP1 on telomeres in etoposide-treated HMGB2 KD hESCs(but not in HMGB2 KD hNECs) suggested that the loss of HMGB2 promoted the stability of telomeres.Etoposide treatment of hESCs resulted in a significant enhancement of telomerase activity, withthe highest increase observed in the HMGB2 KD cells. Interestingly, no changes in telomerase activitywere found in etoposide-treated control hNECs, but HMGB2 KD (unlike HMGB1 KD) markedlydecreased telomerase activity in these cells. Changes in telomerase activity in the etoposide-treatedHMGB2 KD hESCs or hNECs coincided with the appearance of DNA damage markers and couldalready be observed before the onset of apoptosis. Collectively, we have demonstrated that HMGB1or HMGB2 dierentially modulate the impact of etoposide treatment on human embryonic stem cellsand their progenitor cells, suggesting possible strategies for the enhancement of the ecacy of thisanticancer drug.
Suppression of Inflammation Delays Hair Cell Regeneration and Functional Recovery Following Lateral Line Damage in Zebrafish Larvae
Authors: Zhang Ru , Liu Xiaopeng , Li Yajuan , Wang Ming , Chen Lin , Hu Bing
Published: October 2020

Cochlear hair cells in human beings cannot regenerate after loss; however, those in fish and other lower species can. Recently, the role of inflammation in hair cell regeneration has been attracting the attention of scientists. In the present study, we investigated how suppression of inflammatory factors affects hair cell regeneration and the functional recovery of regenerated hair cells in zebrafish. We killed hair cells in the lateral line of zebrafish larvae with CuSO4 to induce an inflammatory response and coapplied BRS-28, an anti-inflammatory agent to suppress the inflammation. The recovery of the hair cell number and rheotaxis was slower when CuSO4 and BRS-28 were coapplied than when CuSO4 was applied alone. The recovery of hair cell count lagged behind that of the calcium imaging signal during the regeneration. The calcium imaging signal in the neuromasts in the inflammation-inhibited group was weaker than that in the noninflammation-inhibited group at the early stage of regeneration, although it returned to normal at the late stage. Our study demonstrates that suppressing inflammation by BRS-28 delays hair cell regeneration and functional recovery when hair cells are damaged. We suspect that BRS-28 inhibits pro-inflammatory factors and thereby reduces the migration of macrophages to delay the regeneration of hair cells.
Engineering and Preclinical Evaluation of Western Reserve Oncolytic Vaccinia Virus Expressing A167Y Mutant Herpes Simplex Virus Thymidine Kinase
Authors: Islam S. M. Bakhtiar UL , Hong Young Mi , Ornella Mefotse saha Cyrelle , Ngabire Daniel , Jang Hyunjung , Cho Euna , Kim Eung-Kyun , Hale Jessye Jin Joo , Kim Cy Hyun , Ahn Soon Cheol , Cho Mong , Hwang Tae-Ho
Published: October 2020

Viral replication of thymidine kinase deleted (tk−) vaccinia virus (VV) is attenuated in resting normal cells, enabling cancer selectivity, however, replication potency of VV-tk− appears to be diminished in cancer cells. Previously, we found that wild-type herpes simplex virus (HSV)-tk (HSV-tk) disappeared in most of the recombinant VV after multiple screenings, and only a few recombinant VV containing naturally mutated HSV-tk remained stable. In this study, VV-tk of western reserve (WR) VV was replaced by A167Y mutated HSV-tk (HSV-tk418m), to alter nucleoside selectivity from broad spectrum to purine exclusive selectivity. WOTS-418 remained stable after numerous passages. WOTS-418 replication was significantly attenuated in normal cells, but cytotoxicity was almost similar to that of wild type WR VV in cancer cells. WOTS-418 showed no lethality following a 5 × 108 PFU intranasal injection, contrasting WR VV, which showed 100% lethality at 1 × 105 PFU. Additionally, ganciclovir (GCV) but not BvdU inhibited WOTS-418 replication, confirming specificity to purine nucleoside analogs. The potency of WOTS-418 replication inhibition by GCV was > 10-fold higher than that of our previous truncated HSV-tk recombinant OTS-412. Overall, WOTS-418 demonstrated robust oncolytic efficacy and pharmacological safety which may delegate it as a candidate for future clinical use in OV therapy.
The Untapped Area Potential for Photovoltaic Power in the European Union
Authors: Jäger-Waldau Arnulf
Published: October 2020

The political goal of the European Union is to transform into a prosperous, modern, competitive and climate-neutral economy by 2050. To accelerate this transition, the European Commission has presented a European Green Deal in 2019. The aim is to reduce up to 55% the greenhouse gas emissions by 2030. The paper looks at the role photovoltaic electricity generation can play to achieve this and whether the required areas for the installation of the photovoltaicaic power needed are available. Following a review of the existing literature, the paper concludes that better use of the technology that has been largely neglected so far coupled with dual-use options would generate much more PV capacity than required to achieve a neutral economy.
Unconventional Transport Properties of Reduced Tungsten Oxide WO2.9
Authors: Shengelaya Alexander , Mattina Fabio La , Conder Kazimierz
Published: October 2020

The temperature and magnetic field dependence of resistivity in WO2.9 was investigated. The variation of resistivity with temperature displayed unusual features, such as a broad maximum around 230 K and a logarithmic increase of resistivity below 16 K. In the temperature range 16–230 K, we observed metallic-like behavior with a positive temperature coefficient. The combined analysis of resistivity and magnetoresistance (MR) data shows that these unusual transport properties of WO2.9 can be understood by considering the (bi)polaronic nature of charge carriers. In contrast to magnetization data, superconducting transition below Tc = 80 K was not detected in resistivity measurements, indicating that the superconductivity is localized in small regions that do not percolate. We found a strong increase in positive MR below 80 K. This effect is similar to that observed in underdoped cuprates, where the substantial increase of MR is attributed to superconducting fluctuations in small clusters. Therefore, the temperature dependence of MR indicates the presence of non-percolating superconducting clusters in WO2.9 below 80 K in agreement with magnetization data.
Short-Range Transportation Using Unmanned Aerial Vehicles (UAVs) during Disasters in Japan
Authors: Yakushiji Koki , Fujita Hiroshi , Murata Mikio , Hiroi Naoki , Hamabe Yuuichi , Yakushiji Fumiatsu
Published: October 2020

Larger types of small unmanned aerial vehicles (UAVs) are beginning to be used in the United States and Europe for commercial transportation. Additionally, some blood product transport systems have been commercialized in Rwanda and other countries and used in pandemic operations for the coronavirus disease 2019 (COVID-19) in infected areas. Conversely, implementing goods transportation for commercial purposes in Japan has been difficult, especially in urban areas, due to national legislation. This study examined UAV-assisted transportation in Japan, a natural disaster hotspot, with a focus on the potential uses of UAVs in situations where traffic blockages make ground transportation impossible. UAVs were used to transport 17 kg of medical supplies belonging to a disaster medical assistance team (DMAT), along with 100 emergency meals. We also transported insulin under controlled-temperature conditions, as well as many other emergency supplies. Using UAVs to transport emergency supplies could be an effective approach when dealing with disasters. This paper summarizes the effectiveness of this approach for medical care and disaster response activities. We present a method for using drones to bridge the gap between medical and firefighting personnel, such as DMAT personnel, who are engaged in life-saving activities at the time of a disaster, and those who are unable to transport necessary goods by land using terrestrial vehicles due to traffic interruptions.
Emergence of Organisms
Authors: Roli Andrea , Kauffman Stuart A.
Published: October 2020

Since early cybernetics studies by Wiener, Pask, and Ashby, the properties of living systems are subject to deep investigations. The goals of this endeavour are both understanding and building: abstract models and general principles are sought for describing organisms, their dynamics and their ability to produce adaptive behavior. This research has achieved prominent results in fields such as artificial intelligence and artificial life. For example, today we have robots capable of exploring hostile environments with high level of self-sufficiency, planning capabilities and able to learn. Nevertheless, the discrepancy between the emergence and evolution of life and artificial systems is still huge. In this paper, we identify the fundamental elements that characterize the evolution of the biosphere and open-ended evolution, and we illustrate their implications for the evolution of artificial systems. Subsequently, we discuss the most relevant issues and questions that this viewpoint poses both for biological and artificial systems.
“Can East Asian Students Think?”: Orientalism, Critical Thinking, and the Decolonial Project
Authors: Moosavi Leon
Published: October 2020

Amidst the increasing calls for the decolonisation of universities, this article interrogates the representation of East Asian students in Western academia. It is argued that East Asian students are often imagined in Orientalist ways, as can be evidenced by evaluating the depiction of East Asian students in academic publications. More specifically, it is suggested that common perceptions of East Asian students as lacking in critical thinking may unwittingly reinforce stereotypes that are rooted in historic narratives which depict East Asians as inferior to (white) Westerners. This article also explores the way in which East Asian academics and students may also subscribe to these Orientalist perceptions. Finally, this article offers a refutation of the stereotype that East Asian students struggle with critical thinking and it suggests that being more reflexive about the way that we imagine ethnic minority students should be a key component of our efforts to decolonise the university.
Cross-Shelf Transport Through the Interaction among a Coastal Jet, a Topographic Wave, and Tides
Authors: Huntley Helga S. , McMahon Charles W. , Kuehl Joseph J. , Kirwan A. D.
Published: October 2020

Shelf break flows are often characterized by along-isobath jets with cross-shelf currents associated with tides and waves guided by variable topography. Here, we address the question: Can a superposition of such flows produce significant aperiodic cross-shelf transport? To answer this question, we use a barotropic analytic model for the jet based on a similarity solution of the shallow water equations over variable topography, a wave disturbance determined by the topography, and a diurnal tidal disturbance. We use standard Lagrangian methods to assess the cross-shelf transport, presenting the results, however, in a Eulerian frame, so as to be amenable to oceanographic observations. The relative roles of the different flow components in cross-shelf transport are assessed through an extensive parameter study. We find that a superposition of all three flow components can indeed produce consequential background aperiodic transport. An application of the model using recent observations from the Texas Shelf demonstrates that a combination of these background mechanisms can produce significant transport under realistic conditions.
Cytokinesis-Block Micronucleus Cytome Assay Evolution into a More Comprehensive Method to Measure Chromosomal Instability
Authors: Fenech Michael
Published: October 2020

This review describes the cytokinesis-block micronucleus (CBMN) cytome assay and its evolution into a molecular cytogenetic method of chromosomal instability (CIN). Micronuclei (MNi) originate from whole chromosomes or chromosome fragments that fail to segregate to the poles of the cell during mitosis. These lagging chromosomes are excluded from the daughter nuclei and are enveloped in their own membrane to form MNi. The CBMN assay was developed to allow MNi to be scored exclusively in once-divided binucleated cells, which enables accurate measurement of chromosome breakage or loss without confounding by non-dividing cells that cannot express MNi. The CBMN assay can be applied to cell lines in vitro and cells such as lymphocytes that can be stimulated to divide ex vivo. In the CBMN assay, other CIN biomarkers such as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) are also measured. Use of centromere, telomere, and chromosome painting probes provides further insights into the mechanisms through which MNi, NPBs and NBUDs originate. Measurement of MNi is also important because entrapment within a micronucleus may cause chromosomes to shatter and, after nuclear reintegration, become rearranged. Additionally, leakage of DNA from MNi can stimulate inflammation via the cyclic GMP-AMP Synthase—Stimulator of Interferon Genes (cGAS-STING) DNA sensing mechanism of the innate immune system.
PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells
Authors: Cantonero Carlos , Salido Ginés M. , Rosado Juan A. , Redondo Pedro C.
Published: October 2020

Progesterone receptor membrane component 1 (PGRMC1) has been shown to regulate some cancer hallmarks. Progesterone (P4) evokes intracellular calcium (Ca2+) changes in the triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and BT-20) and in other breast cancer cell lines like the luminal MCF7 cells. PGRMC1 expression is elevated in MDA-MB-231 and MCF7 cells as compared to non-tumoral MCF10A cell line, and PGRMC1 silencing enhances P4-evoked Ca2+ mobilization. Here, we found a new P4-dependent Ca2+ mobilization pathway in MDA-MB-231 cells and other triple-negative breast cancer cells, as well as in MCF7 cells that involved Stromal interaction molecule 2 (STIM2), Calcium release-activated calcium channel protein 1 (Orai1), and Transient Receptor Potential Channel 1 (TRPC1). Stromal interaction molecule 1 (STIM1) was not involved in this novel Ca2+ pathway, as evidenced by using siRNA STIM1. PGRMC1 silencing reduced the negative effect of P4 on cell proliferation and cell death in MDA-MB-231 cells. In line with the latter observation, Nuclear Factor of Activated T-Cells 1 (NFAT1) nuclear accumulation due to P4 incubation for 48 h was enhanced in cells transfected with the small hairpin siRNA against PGRMC1 (shPGRMC1). These results provide evidence for a novel P4-evoked Ca2+ entry pathway that is downregulated by PGRMC1.
Photoperiod Affects Leptin Action on the Choroid Plexus in Ewes Challenged with Lipopolysaccharide—Study on the mRNA Level
Authors: Szczepkowska Aleksandra , Kowalewska Marta , Krawczyńska Agata , Herman Andrzej P. , Skipor Janina
Published: October 2020

The ovine choroid plexus (ChP) expresses the long isoform of the leptin receptor, which makes this structure a potential target for leptin action. In sheep, leptin concentration in plasma is higher during long days (LD) than short days (SD). This study evaluates the influence a of photoperiod on leptin impact on the gene expression of Toll-like receptor 4 (TLR4), proinflammatory cytokines (IL1B, IL6), their receptors (IL1R1, IL1R2, ILRN, IL6R, IL6ST) and inflammasome components necessary for pro-IL-1β activation (NLRP3, PYCARD, CASP1), chemokine (CCL2), leptin receptor isoforms (LEPRa, LEPRb) and a suppressor of cytokine signalling (SOCS3) in the ChP of ewes treated or not with lipopolysaccharide (LPS). Studies were conducted on adult female sheep divided into four groups (n = 6 in each): control, leptin (20 μg/kg), LPS (400 ng/kg), and LPS and leptin injected under SD and LD photoperiods. The leptin alone did not affect the gene expression but in co-treatment with LPS increased (p < 0.05) IL1B but only during SD, and SOCS3, IL1R2, IL1RN, IL6ST and CCL2 only during LD, and decreased (p < 0.05) the IL1R1 expression only during SD photoperiod. This indicates that the immunomodulatory action of leptin on the ChP is manifested only under the LPS challenge and is photoperiodically dependent.
Synthesis of Hantzsch Adducts as Cholinesterases and Calcium Flux inhibitors, Antioxidants and Neuroprotectives
Authors: Pachón Angona Irene , Martin Helene , Daniel Solene , Moraleda Ignacio , Bonet Alexandre , Wnorowski Artur , Maj Maciej , Jozwiak Krzysztof , Iriepa Isabel , Refouvelet Bernard , Marco-Contelles José , Ismaili Lhassane
Published: October 2020

We report herein the design, synthesis, biological evaluation, and molecular modelling of new inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), able to block Ca+2 channels also showing antioxidant and neuroprotective activities. The new MTDL, dialkyl 2,6-dimethyl-4-(4-((5-aminoalkyl)oxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate 3a-p, have been obtained via Hantzsch reaction from appropriate and commercially available precursors. Pertinent biological analysis has prompted us to identify MTDL 3h [dimethyl-4-(4-((5-(4-benzylpiperidin-1-yl)pentyl)oxy)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate] as an attractive inhibitor of AChE (1.8 μM) and BuChE (2 μM), Ca+2 channel antagonist (47.72% at 10 μM), and antioxidant (2.54 TE) agent, showing significant neuroprotection 28.68% and 38.29% against H2O2, and O/R, respectively, at 0.3 μM, thus being considered a hit-compound for further investigation in our search for anti-Alzheimer’s disease agents.
The 90th Birthday of Professor Raphael Mechoulam, a Top Cannabinoid Scientist and Pioneer
Authors: Pertwee Roger G.
Published: October 2020

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NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells
Authors: Garrido Maritza P. , Torres Ignacio , Avila Alba , Chnaiderman Jonás , Valenzuela-Valderrama Manuel , Aramburo José , Oróstica Lorena , Durán-Jara Eduardo , Lobos-Gonzalez Lorena , Romero Carmen
Published: October 2020

Nerve Growth Factor (NGF) and its high-affinity receptor tropomyosin receptor kinase A (TRKA) increase their expression during the progression of epithelial ovarian cancer (EOC), promoting cell proliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial growth factor (VEGF). The expression of these proteins is controlled by microRNAs (miRs), such as miR-145, whose dysregulation has been related to cancer. The aims of this work were to evaluate in EOC cells whether NGF/TRKA decreases miR-145 levels, and the effect of miR-145 upregulation. The levels of miR-145-5p were assessed by qPCR in ovarian biopsies and ovarian cell lines (human ovarian surface epithelial cells (HOSE), A2780 and SKOV3) stimulated with NGF. Overexpression of miR-145 in ovarian cells was used to evaluate cell proliferation, migration, invasion, c-MYC and VEGF protein levels, as well as tumor formation and metastasis in vivo. In EOC samples, miR-145-5p levels were lower than in epithelial ovarian tumors. Overexpression of miR-145 decreased cell proliferation, migration and invasion of EOC cells, changes that were concomitant with the decrease in c-MYC and VEGF protein levels. We observed decreased tumor formation and suppressed metastasis behavior in mice injected with EOC cells that overexpressed miR-145. As expected, ovarian cell lines stimulated with NGF diminished miR-145-5p transcription and abundance. These results suggest that the tumoral effects of NGF/TRKA depend on the regulation of miR-145-5p levels in EOC cells, and that its upregulation could be used as a possible therapeutic strategy for EOC.
Roles of ABCC1 and ABCC4 in Proliferation and Migration of Breast Cancer Cell Lines
Authors: Low Floren G. , Shabir Kiran , Brown James E. , Bill Roslyn M. , Rothnie Alice J.
Published: October 2020

ABCC1 and ABCC4 utilize energy from ATP hydrolysis to transport many different molecules, including drugs, out of the cell and, as such, have been implicated in causing drug resistance. However recently, because of their ability to transport signaling molecules and inflammatory mediators, it has been proposed that ABCC1 and ABCC4 may play a role in the hallmarks of cancer development and progression, independent of their drug efflux capabilities. Breast cancer is the most common cancer affecting women. In this study, the aim was to investigate whether ABCC1 or ABCC4 play a role in the proliferation or migration of breast cancer cell lines MCF-7 (luminal-type, receptor-positive) and MDA-MB-231 (basal-type, triple-negative). The effects of small molecule inhibitors or siRNA-mediated knockdown of ABCC1 or ABCCC4 were measured. Colony formation assays were used to assess the clonogenic capacity, MTT assays to measure the proliferation, and scratch assays and Transwell assays to monitor the cellular migration. The results showed a role for ABCC1 in cellular proliferation, whilst ABCC4 appeared to be more important for cellular migration. ELISA studies implicated cAMP and/or sphingosine-1-phosphate efflux in the mechanism by which these transporters mediate their effects. However, this needs to be investigated further, as it is key to understand the mechanisms before they can be considered as targets for treatment.
Adenosine Triphosphate Accumulated Following Cerebral Ischemia Induces Neutrophil Extracellular Trap Formation
Authors: Kim Seung-Woo , Davaanyam Dashdulam , Seol Song-I , Lee Hye-Kyung , Lee Hahnbie , Lee Ja-Kyeong
Published: October 2020

In ischemic stroke, neutrophils infiltrate damaged brain tissue immediately following the ischemic insult and aggravate inflammation via various mechanisms which include neutrophil extracellular traps (NETs) formation. In the present study, we showed that adenosine triphosphate (ATP), a DAMP molecule, accumulates in the brain and induces NETosis in brain parenchyma and in circulating neutrophils (PMNs) isolated from a murine model of stroke induced by middle cerebral artery occlusion (MCAO). Expression of peptidylarginine deiminase-4 (PAD4), which induces citrullination of histones H3 (CitH3) and initiates NETosis, was significantly enhanced in brain parenchyma and blood PMNs following MCAO. ATP or BzATP (a prototypic P2X7R agonist) significantly enhanced the inductions of PAD4 and CitH3 in a P2X7R-dependent manner and intracellular Ca2+ influx, PKCα activation, and NADPH oxidase-dependent reactive oxygen species (ROS) production play critical roles in this ATP-P2X7R-mediated NETosis. In our MCAO animal model, NETosis was markedly suppressed by treatment with apyrase, an enzyme hydrolyzing ATP, but enhanced by co-treatment of BzATP, confirming ATP-P2X7R-mediated NETosis. Since ATP not only induced NETosis but was also extruded after NETosis, our results indicate that ATP accumulated in the ischemic brain induces NETosis, mediating a cross-talk linking NETosis with neuronal damage that might aggravate inflammation and brain damage.
Head and Neck Paragangliomas—A Genetic Overview
Authors: Majewska Anna , Budny Bartłomiej , Ziemnicka Katarzyna , Ruchała Marek , Wierzbicka Małgorzata
Published: October 2020

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to consolidate knowledge concerning PGL mutations, familial occurrence, and the practical application of this information. Available scientific databases were searched using the keywords head and neck paraganglioma and genetics, and 274 articles in PubMed and 1183 in ScienceDirect were found. From these articles, those concerning genetic changes in HNPGLs were selected. The aim of this review is to describe the known genetic changes and their practical applications. We found that the etiology of the tumors in question is based on genetic changes in the form of either germinal or somatic mutations. 40% of PCC and PGL have a predisposing germline mutation (including VHL, SDHB, SDHD, RET, NF1, THEM127, MAX, SDHC, SDHA, SDHAF2, HIF2A, HRAS, KIF1B, PHD2, and FH). Approximately 25–30% of cases are due to somatic mutations, such as RET, VHL, NF1, MAX, and HIF2A. The tumors were divided into three main clusters by the Cancer Genome Atlas (TCGA); namely, the pseudohypoxia group, the Wnt signaling group, and the kinase signaling group. The review also discusses genetic syndromes, epigenetic changes, and new testing technologies such as next-generation sequencing (NGS).
Applications of Nanomaterials for Theranostics of Melanoma
Authors: Jin Guanqiao , Cheah Pohlee , Qu Jing , Liu Lijuan , Zhao Yongfeng
Published: October 2020

Melanoma is an aggressive form of skin cancer with a very high mortality rate. Early diagnosis of the disease, the utilization of more potent pharmacological agents, and more effective drug delivery systems are essential to achieve an optimal treatment plan. The applications of nanotechnology to improve therapeutic efficacy and early diagnosis for melanoma treatment have received great interest among researchers and clinicians. In this review, we summarize the recent progress of utilizing various nanomaterials for theranostics of melanoma. The key importance of using nanomaterials for theranostics of melanoma is to improve efficacy and reduce side effects, ensuring safe implementation in clinical use. As opposed to conventional in vitro diagnostic methods, in vivo medical imaging technologies have the advantages of being a type of non-invasive, real-time monitoring. Several common nanoparticles, including ultrasmall superparamagnetic iron oxide nanoparticles, silica nanoparticles, and carbon-based nanoparticles, have been applied to deliver chemotherapeutic agents for the theranostics of melanoma. The application of nanomaterials for theranostics in molecular imaging (MRI, PET, US, OI, etc.) plays an important role in targeting drug delivery of melanoma, by monitoring the distribution site of the molecular imaging probe and the therapeutic drug in the body in real-time. Hence, it is worthwhile to anticipate the approval of these nanomaterials for theranostics in molecular imaging by the US Food and Drug Administration in clinical trials.
Hmg1 Gene Mutation Prevalence in Triazole-Resistant Aspergillus fumigatus Clinical Isolates
Authors: Resendiz-Sharpe Agustin , Hokken Margriet W.J. , Mercier Toine , Merckx Rita , Verhagen Kamiel , Dewitte Lisa , Melchers Willem J.G. , Verweij Paul E. , Maertens Johan , Lagrou Katrien
Published: October 2020

Recently, mutations in the 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase-encoding gene (hmg1), a gene involved in ergosterol production, were associated with triazole-resistance in Aspergillus fumigatus. In this study, we determined the prevalence and characteristics of hmg1 mutations in a collection of clinical triazole-resistant A. fumigatus isolates collected during 2001–2019 from two international mycology reference centers: the Belgian National Reference Center for Mycosis and the Center of Expertise in Mycology Radboudumc/CWZ. Clinical isolates with and without cyp51A gene mutations and randomly selected wild-type (WT) controls were included. Isolates were characterized by in vitro susceptibility testing, cyp51A and hmg1 sequencing, and short tandem repeat typing. Available clinical records were analyzed for previous triazole exposure. In 23 isolates (24%) of the 95 triazole-resistant A. fumigatus isolates, hmg1 gene mutations were observed; including 5/23 (22%) isolates without cyp51A gene mutations and 18/72 (25%) with cyp51A mutations. Four previously described hmg1 gene mutations (E105K, G307R/D, G466V, and S541G) and two novel mutations (W273S and L304P) were found; 4/23 (17%) in the sterol-sensing-domain region. No triazole-antifungal exposure was reported in 75% (9/12) of patients harboring an isolate with hmg1 gene mutations. Three of 39 WT isolates (8%) contained a hmg1 gene mutation; E105K (2-isolates) and S541G. Hmg1 gene mutations were predominantly found in A. fumigatus with cyp51A mutations with voriconazole MICs ≥ 8 mg/L.
Histomorphometric, Immunohistochemical, Ultrastructural Characterization of a Nano-Hydroxyapatite/Beta-Tricalcium Phosphate Composite and a Bone Xenograft in Sub-Critical Size Bone Defect in Rat Calvaria
Authors: da Silva Brum Igor , Frigo Lucio , Lana Devita Renan , da Silva Pires Jorge Luís , Hugo Vieira de Oliveira Victor , Rosa Nascimento Ana Lucia , de Carvalho Jorge José
Published: October 2020

Nowadays, we can observe a worldwide trend towards the development of synthetic biomaterials. Several studies have been conducted to better understand the cellular mechanisms involved in the processes of inflammation and bone healing related to living tissues. The aim of this study was to evaluate tissue behaviors of two different types of biomaterials: synthetic nano-hydroxyapatite/beta-tricalcium phosphate composite and bone xenograft in sub-critical bone defects in rat calvaria. Twenty-four rats underwent experimental surgery in which two 3 mm defects in each cavity were tested. Rats were divided into two groups: Group 1 used xenogen hydroxyapatite (Bio Oss™); Group 2 used synthetic nano-hydroxyapatite/beta-tricalcium phosphate (Blue Bone™). Sixty days after surgery, calvaria bone defects were filled with biomaterial, animals were euthanized, and tissues were stained with Masson’s trichrome and periodic acid–Schiff (PAS) techniques, immune-labeled with anti-TNF-α and anti-MMP-9, and electron microscopy analyses were also performed. Histomorphometric analysis indicated a greater presence of protein matrix in Group 2, in addition to higher levels of TNF-α and MMP-9. Ultrastructural analysis showed that biomaterial fibroblasts were associated with the tissue regeneration stage. Paired statistical data indicated that Blue Bone™ can improve bone formation/remodeling when compared to biomaterials of xenogenous origin.
The Use of Ultra-Small Fe3O4 Magnetic Nanoparticles for Hydrothermal Synthesis of Fe3+-Doped Titanate Nanotubes
Authors: Marć Maciej , Najder-Kozdrowska Lidia , Guskos Nikos , Żołnierkiewicz Grzegorz , Montero Ana Maria , Dudek Mirosław Roman
Published: October 2020

A method of the hydrothermal synthesis of Fe3+-doped titanate nanotubes (TNT) is reported in which the ultra-small Fe3O4 nanoparticles are used as the sources of Fe3+ ions. The magnetic nanoparticles with a diameter of about 2 nm are added during the washing stage of the hydrothermal procedure. During washing, they gradually degrade and at the same time, the titanate product is transformed into nanotubes. The obtained nanotubes were characterized by structural and magnetic measurements. It was found that, depending on the value of the external magnetic field, they may show the property of room temperature ferromagnetism, paramagnetism or they may be diamagnetic. It was also shown that the modified TNTs have greater photocatalytic activity compared to unmodified TNTs.
Eliashberg Theory of a Multiband Non-Phononic Spin Glass Superconductor
Authors: Ummarino Giovanni Alberto
Published: October 2020

I solved the Eliashberg equations for a multiband non-phononic s± wave spin-glass superconductor, calculating the temperature dependence of the gaps and of superfluid density. Their behaviors were revealed to be unusual: showing non-monotonic temperature dependence and reentrant superconductivity. By considering particular input parameters values that could describe the iron pnictide EuFe2(As1−xPx)2, a rich and complex phase diagram arises, with two different ranges of temperature in which superconductivity appears.
Union of Sets of Lengths of Numerical Semigroups
Authors: García-García J. I. , Marín-Aragón D. , Vigneron-Tenorio A.
Published: October 2020

Let S=⟨a1,…,ap⟩ be a numerical semigroup, let s∈S and let Z(s) be its set of factorizations. The set of lengths is denoted by L(s)={L(x1,⋯,xp)∣(x1,⋯,xp)∈Z(s)}, where L(x1,⋯,xp)=x1+⋯+xp. The following sets can then be defined: W(n)={s∈S∣∃x∈Z(s)suchthatL(x)=n}, ν(n)=⋃s∈W(n)L(s)={l1<l2<⋯<lr} and Δν(n)={l2−l1,…,lr−lr−1}. In this paper, we prove that the function Δν:N→P(N) is almost periodic with period lcm(a1,ap).
The Impact of Teamwork on an Organization’s Performance: A Cooperative Game’s Approach
Authors: Askari Gholamreza , Asghri Nader , Gordji Madjid Eshaghi , Asgari Heshmatolah , Filipe José António , Azar Adel
Published: October 2020

In this article, we study the impact of teamwork on an organization’s performance, considering a cooperative game’s framework. To promote teamwork culture, performance indexes were considered both individually and collectively, and by comparing the scores that every employee earned individually and collectively, their differences became obvious. In this approach, a cooperative game’s model was used in order to improve the organization’s performance. The proposed model, in addition to evaluating the organization and employee’s activities, implemented all payments, including overtime pay, rewards, etc., fairly and along with increasing performance and satisfaction. The cooperative approach created effective communications between employees and authorities and enhanced their motivation for teamwork. Moreover, results could be used for decisions related to employees (such as promotion, transition, firing, and secondment), analysis of training requirements, employees’ development, and research and plan valuation. Our findings show that the collaborative coefficient (CC) is a key factor in increasing productivity and improving the efficiency of an organization in the long run. The collaborative coefficient is a new concept in teamwork that has rarely been considered in scientific research.
A New Continuous-Discrete Fuzzy Model and Its Application in Finance
Authors: Long Hoang Viet , Jebreen Haifa Bin , Chalco-Cano Y.
Published: October 2020

In this paper, we propose a fuzzy differential-difference equation for modeling of mixed continuous-discrete phenomena. In the special case, we present the general solution of linear fuzzy differential-difference equations. The dynamical process in the intervals is presented by the corresponding fuzzy differential equation and with impulsive jumps in some points. We illustrate the applicability of the model to study the time value of money.
Predictive Value of HPV, p53, and p16 in the Post-Treatment Evolution of Malignant Tumors of the Oropharynx and Retromolar Trigone–Oropharynx Junction
Authors: Cobzeanu Bogdan Mihail , Cobzeanu Mihail Dan , Moscalu Mihaela , Palade Octavian Dragos , Rădulescu Luminița , Negru Dragoș , Moisii Liliana Gheorghe , Cobzeanu Luiza Maria , Ungureanu Loredana Beatrice , Vonica Patricia , Matei Daniela Viorelia , Rusu Daniela Carmen , Volovaț Constantin , Costan Victor Vlad
Published: October 2020

Background and objectives: Knowledge of the interactions and influences of infectious, genetic, and environmental factors on the evolution and treatment response of malignant tumors is essential for improving the management of the disease and increasing patient survival. The objective of this study was to establish the contribution of human papillomavirus (HPV), as well as p53 and p16 tumor markers, alongside associated factors (smoking and alcohol consumption), in the progression of malignancies located in the oropharynx and at the retromolar trigone–oropharyngeal junction. Materials and Methods: We performed a prospective study including 50 patients with malignant tumors of the oropharynx and retromolar trigone–oropharyngeal junction. In all patients, the presence and type of HPV were determined, as well as the status of the tumor markers p53 and p16. The associated risk factors, biopsy results, treatment method, and post-treatment evolution were all documented. Statistical analyses were performed to evaluate the correlations between the determining factors and their influence on the post-treatment evolution. An overall increased survival rate was found in HPV(+) patients. Results: Our study outlined the prevalence of different high-risk subtypes of HPV from the ones presented by other studies, suggesting a possible geographic variation. Correlations between the p53 and p16 statuses and patient survival could be established. The association of smoking and alcohol consumption strongly correlated with an unfavorable evolution. Conclusions: Awareness of the differences in the post-treatment evolution of the patients in relation to the presence of the factors determined in our study could change the future management of such cases for ensuring improved treatment outcomes.
Joining of Metal to Ceramic Plate Using Super-Spread Wetting
Authors: Yeon Jaebong , Yamamoto Michiru , Ni Peiyuan , Nakamoto Masashi , Tanaka Toshihiro
Published: October 2020

Ceramic-metal composites with novel performance are desirable materials; however, differences in their properties result in difficulties in joining. In this study, the joining of metal to ceramic is investigated. We recently succeeded in causing super-spread wetting on the surface fine crevice structures of metal surfaces produced by both laser irradiation and reduction-sintering of oxide powders. In this work, joining copper onto an Al2O3 plate was achieved by taking advantage of super-spread wetting. Fe2O3 powder was first sintered under reducing conditions to produce a microstructure which can cause super-spread wetting of liquid metal on an Al2O3 plate. A powder-based surface fine crevice structure of metallic iron with high porosity was well-formed due to the bonding of the reduced metallic iron particles. This structure was joined on an Al2O3 plate with no cracking by the formation of an FeAl2O4 layer buffering the mismatch gap between the thermal expansion coefficients of iron and Al2O3. We successfully achieved metalizing of the Al2O3 surface with copper without interfacial cracks using super-spread wetting of liquid copper through the sintered metallic iron layer on the Al2O3 plate. Then, laser irradiation was conducted on the surface of the copper-metalized Al2O3 plate. A laser-irradiated surface fine crevice structure was successfully created on the copper-metalized Al2O3 plate. Moreover, it was confirmed that the super-spread wetting of liquid tin occurred on the laser-irradiated surface fine crevice structure, finally accomplishing the joining of a copper block and the copper-metalized Al2O3.
Multimodal Navigation Systems for Users with Visual Impairments—A Review and Analysis
Authors: Kuriakose Bineeth , Shrestha Raju , Sandnes Frode Eika
Published: October 2020

Multimodal interaction refers to situations where users are provided with multiple modes for interacting with systems. Researchers are working on multimodality solutions in several domains. The focus of this paper is within the domain of navigation systems for supporting users with visual impairments. Although several literature reviews have covered this domain, none have gone through the research synthesis of multimodal navigation systems. This paper provides a review and analysis of multimodal navigation solutions aimed at people with visual impairments. This review also puts forward recommendations for effective multimodal navigation systems. Moreover, this review also presents the challenges faced during the design, implementation and use of multimodal navigation systems. We call for more research to better understand the users’ evolving modality preferences during navigation.