bluuebunny/crossref_metadata_2025 huggingface dataset:
Moss-Derived Human Recombinant GAA Provides an Optimized Enzyme Uptake in Differentiated Human Muscle Cells of Pompe Disease
Authors: Hintze Stefan , Limmer Sarah , Dabrowska-Schlepp Paulina , Berg Birgit , Krieghoff Nicola , Busch Andreas , Schaaf Andreas , Meinke Peter , Schoser Benedikt
Published: April 2020

Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of lysosomal acid alpha-glucosidase (GAA). The result of the GAA deficiency is a ubiquitous lysosomal and non-lysosomal accumulation of glycogen. The most affected tissues are heart, skeletal muscle, liver, and the nervous system. Replacement therapy with the currently approved enzyme relies on M6P-mediated endocytosis. However, therapeutic outcomes still leave room for improvement, especially with regard to skeletal muscles. We tested the uptake, activity, and effect on glucose metabolism of a non-phosphorylated recombinant human GAA produced in moss (moss-GAA). Three variants of moss-GAA differing in glycosylation pattern have been analyzed: two with terminal mannose residues in a paucimannosidic (Man3) or high-mannose (Man 5) configuration and one with terminal N-acetylglucosamine residues (GnGn). Compared to alglucosidase alfa the moss-GAA GnGn variant showed increased uptake in differentiated myotubes. Moreover, incubation of immortalized muscle cells of Gaa−/− mice with moss-GAA GnGn led to similarly efficient clearance of accumulated glycogen as with alglucosidase alfa. These initial data suggest that M6P-residues might not always be necessary for the cellular uptake in enzyme replacement therapy (ERT) and indicate the potential of moss-GAA GnGn as novel alternative drug for targeting skeletal muscle in Pompe patients.
Patches and Blebs: A Comparative Study of the Composition and Biophysical Properties of Two Plasma Membrane Preparations from CHO Cells
Authors: Monasterio Bingen G. , Jiménez-Rojo Noemi , García-Arribas Aritz B. , Riezman Howard , Goñi Félix M. , Alonso Alicia
Published: April 2020

This study was aimed at preparing and characterizing plasma membranes (PM) from Chinese Hamster Ovary (CHO) cells. Two methods of PM preparation were applied, one based on adhering cells to a poly-lysine-coated surface, followed by hypotonic lysis and removal of intracellular components, so that PM patches remain adhered to each other, and a second one consisting of bleb induction in cells, followed by separation of giant plasma membrane vesicles (GPMV). Both methods gave rise to PM in sufficient amounts to allow biophysical and biochemical characterization. Laurdan generalized polarization was used to measure molecular order in membranes, PM preparations were clearly more ordered than the average cell membranes (GP ≈0.450 vs. ≈0.20 respectively). Atomic force microscopy was used in the force spectroscopy mode to measure breakthrough forces of PM, both PM preparations provided values in the 4–6 nN range, while the corresponding value for whole cell lipid extracts was ≈2 nN. Lipidomic analysis of the PM preparations revealed that, as compared to the average cell membranes, PM were enriched in phospholipids containing 30–32 C atoms in their acyl chains but were relatively poor in those containing 34–40 C atoms. PM contained more saturated and less polyunsaturated fatty acids than the average cell membranes. Blebs (GPMV) and patches were very similar in their lipid composition, except that blebs contained four-fold the amount of cholesterol of patches (≈23 vs. ≈6 mol% total membrane lipids) while the average cell lipids contained 3 mol%. The differences in lipid composition are in agreement with the observed variations in physical properties between PM and whole cell membranes.
Reply to Comments: Using the Cardio-Ankle Vascular Index (CAVI) or the Mathematical Correction Form (CAVI0) in Clinical Practice
Authors: Spronck Bart , Jurko Alexander , Mestanik Michal , Avolio Alberto P. , Tonhajzerova Ingrid
Published: April 2020

We read with great interest Alizargar et al [...]
Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death
Authors: Park Hyun Kyung , Han Bo Ram , Park Woo Hyun
Published: April 2020

Arsenic trioxide (ATO; As2O3) has anti-cancer effects in various solid tumors as well as hematological malignancy. Valproic acid (VPA), which is known to be a histone deacetylase inhibitor, has also anti-cancer properties in several cancer cells including lung cancer cells. Combined treatment of ATO and VPA (ATO/VPA) could synergistically enhance anti-cancer effects and reduce ATO toxicity ATO. In this study, the combined anti-cancer effects of ATO and VPA (ATO/VPA) was investigated in NCI-H460 and NCI-H1299 lung cancer cells in vitro and in vivo. A combination of 3 μM ATO and 3 mM VPA (ATO/VPA) strongly inhibited the growths of both lung cancer cell types. DNA flow cytometry indicated that ATO/VPA significantly induced G2/M-phase arrest in both cell lines. In addition, ATO/VPA strongly increased the percentages of sub-G1 cells and annexin V-FITC positive cells in both cells. However, lactate dehydrogenase (LDH) release from cells was not increased in ATO/VPA-treated cells. In addition, ATO/VPA increased apoptosis in both cell types, accompanied by loss of mitochondrial membrane potential (MMP, ∆Ψm), activation of caspases, and cleavage of anti-poly ADP ribose polymerase-1. Moreover, a pan-caspase inhibitor, Z-VAD, significantly reduced apoptotic cell death induced by ATO/VPA. In the xenograft model, ATO/VPA synergistically inhibited growth of NCI-H460-derived xenograft tumors. In conclusion, the combination of ATO/VPA effectively inhibited the growth of lung cancer cells through G2/M-phase arrest and apoptotic cell death, and had a synergistic antitumor effect in vivo.
Salicylic Acid Signalling in Plants
Authors: Janda Tibor , Szalai Gabriella , Pál Magda
Published: April 2020

Ten articles published in the “Special Issue: Salicylic Acid Signalling in Plants” are summarized, in order to get a global picture about the mode of action of salicylic acid in plants, and about its interaction with other stress-signalling routes. Its ecological aspects and possible practical use are also discussed.
Therapeutic Effects of Human Amniotic Epithelial Stem Cells in a Transgenic Mouse Model of Alzheimer’s Disease
Authors: Kim Ka , Suh Yoo-Hun , Chang Keun-A
Published: April 2020

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized clinically by cognitive decline and pathologically by the development of amyloid plaques. AD is the most common cause of dementia among older people. However, there is currently no cure for AD. In this study, we aimed to elucidate the therapeutic effects of human amniotic epithelial stem cells (hAESCs) in a transgenic mouse model of AD. Tg2576 transgenic (Tg) mice underwent behavioral tests, namely the Morris water maze and Y-maze tests, to assess their cognitive function. In the Morris water maze test, hAESC-treated Tg mice exhibited significantly shorter escape latencies than vehicle-treated Tg mice. In the Y-maze test, hAESC-treated Tg mice exhibited significantly higher rate of spontaneous alteration than vehicle-treated Tg mice, while the total number of arm entries did not differ between the groups. Furthermore, Congo red staining revealed that hAESCs injection reduced the number of amyloid plaques present in the brains of Tg mice. Finally, beta-secretase (BACE) activity was significantly decreased in Tg mice at 60 min after hAESCs injection. In this study, we found that intracerebral injection of hAESCs alleviated cognitive impairment in a Tg2576 mouse model of AD. Our results indicate that hAESCs injection reduced amyloid plaques caused by reduced BACE activity. These results indicate that hAESCs may be a useful therapeutic agent for the treatment of AD-related memory impairment.
Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases
Authors: Ghosh Arnab , Shcherbik Natalia
Published: April 2020

Cardiovascular diseases (CVDs) are a group of disorders that affect the heart and blood vessels. Due to their multifactorial nature and wide variation, CVDs are the leading cause of death worldwide. Understanding the molecular alterations leading to the development of heart and vessel pathologies is crucial for successfully treating and preventing CVDs. One of the causative factors of CVD etiology and progression is acute oxidative stress, a toxic condition characterized by elevated intracellular levels of reactive oxygen species (ROS). Left unabated, ROS can damage virtually any cellular component and affect essential biological processes, including protein synthesis. Defective or insufficient protein translation results in production of faulty protein products and disturbances of protein homeostasis, thus promoting pathologies. The relationships between translational dysregulation, ROS, and cardiovascular disorders will be examined in this review.
Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers
Authors: Mukai Shoichiro , Yamasaki Koji , Fujii Masato , Nagai Takahiro , Terada Naoki , Kataoka Hiroaki , Kamoto Toshiyuki
Published: April 2020

Unlike in normal epithelium, dysregulated overactivation of various proteases have been reported in cancers. Degradation of pericancerous extracellular matrix leading to cancer cell invasion by matrix metalloproteases is well known evidence. On the other hand, several cell-surface proteases, including type II transmembrane serine proteases (TTSPs), also induce progression through activation of growth factors, protease activating receptors and other proteases. Hepatocyte growth factor (HGF) known as a multifunctional growth factor that upregulates cancer cell motility, invasiveness, proliferative, and anti-apoptotic activities through phosphorylation of MET (a specific receptor of HGF). HGF secreted as inactive zymogen (pro-HGF) from cancer associated stromal fibroblasts, and the proteolytic activation by several TTSPs including matriptase and hepsin is required. The activation is strictly regulated by HGF activator inhibitors (HAIs) in physiological condition. However, downregulation is frequently observed in cancers. Indeed, overactivation of MET by upregulation of matriptase and hepsin accompanied by the downregulation of HAIs in urological cancers (prostate cancer, renal cell carcinoma, and bladder cancer) are also reported, a phenomenon observed in cancer cells with malignant phenotype, and correlated with poor prognosis. In this review, we summarized current reports focusing on TTSPs, HAIs, and MET signaling axis in urological cancers.
Sex-Dependent Effects of Developmental Lead Exposure in Wistar Rats: Evidence from Behavioral and Molecular Correlates
Authors: Tartaglione Anna Maria , Serafini Melania Maria , Raggi Andrea , Iacoponi Francesca , Zianni Elisa , Scalfari Alessandro , Minghetti Luisa , Ricceri Laura , Cubadda Francesco , Calamandrei Gemma , Viviani Barbara
Published: April 2020

Lead (Pb) exposure in early life affects brain development resulting in cognitive and behavioral deficits. Epidemiologic and experimental evidence of sex as an effect modifier of developmental Pb exposure is emerging. In the present study, we investigated Pb effects on behavior and mechanisms of neuroplasticity in the hippocampus and potential sex differences. To this aim, dams were exposed, from one month pre-mating to offspring weaning, to Pb via drinking water at 5 mg/kg body weight per day. In the offspring of both sexes, the longitudinal assessment of motor, emotional, and cognitive end points was performed. We also evaluated the expression and synaptic distribution of N-methyl-D-Aspartate receptor (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits at post-natal day (pnd) 23 and 70 in the hippocampus. Neonatal motor patterns and explorative behavior in offspring were affected in both sexes. Pb effects in emotional response and memory retention were observed in adult females only, preceded by increased levels of GluN2A and GluA1 subunits at the post-synapse at pnd 23. These data suggest that Pb exposure during development affects glutamatergic receptors distribution at the post-synaptic spine in females. These effects may contribute to alterations in selected behavioral domains.
Evaluation of Salivary Cytokines and Vitamin D Levels in Periodontopathic Patients
Authors: Costantini Erica , Sinjari Bruna , Piscopo Francesca , Porreca Annamaria , Reale Marcella , Caputi Sergio , Murmura Giovanna
Published: April 2020

Periodontal disease (PD) is an inflammatory condition of the tissues supporting the teeth, which is widespread among the adult population. Evidence shows a relationship between PD and vitamin D levels, which is involved in the regulation of bone metabolism, mineral homeostasis, and inflammatory response. This study aimed to perform a simultaneous evaluation of inflammatory mediators and vitamin D levels in saliva in periodontopathic patients to better understand their role in periodontal disease. In this observational study, clinical periodontal parameter examination was performed for each patient. Moreover, the saliva levels of 25(OH)D3, TGFβ, IL-35, IL-17A, and MMP9 were evaluated using an ELISA assay. An increase in TGFβ, IL-35, MMP9, and IL-17A salivary levels and a reduction in 25(OH)D3 levels were observed in periodontopathic patients with respect to the healthy controls. The present study revealed significant positive correlation between cytokines and highly negative correlation between 25(OH)D3 and salivary cytokine levels. Further studies are needed to better understand if salivary cytokines and vitamin D evaluation may represent a new approach for detection and prevention of progressive diseases, such as PD.
Matrix Metalloproteinases: How Much Can They Do?
Authors: Ågren Magnus S. , auf dem Keller Ulrich
Published: April 2020

Zinc-dependent matrix metalloproteinases (MMPs) belong to metzincins that comprise not only 23 human MMPs but also other metalloproteinases, such as 21 human ADAMs (a disintegrin and metalloproteinase domain) and 19 secreted ADAMTSs (a disintegrin and metalloproteinase thrombospondin domain). The many setbacks from the clinical trials of broad-spectrum MMP inhibitors for cancer indications in the late 1990s emphasized the extreme complexity of the participation of these proteolytic enzymes in biology. This editorial mini-review summarizes the Special Issue, which includes four review articles and 10 original articles that highlight the versatile roles of MMPs, ADAMs, and ADAMTSs, in normal physiology as well as in neoplastic and destructive processes in tissue. In addition, we briefly discuss the unambiguous involvement of MMPs in wound healing.
Genetic Interactions of Histone Modification Machinery Set1 and PAF1C with the Recombination Complex Rec114-Mer2-Mei4 in the Formation of Meiotic DNA Double-Strand Breaks
Authors: Zhang Ying , Suzuki Takuya , Li Ke , Gothwal Santosh K. , Shinohara Miki , Shinohara Akira
Published: April 2020

Homologous recombination is essential for chromosome segregation during meiosis I. Meiotic recombination is initiated by the introduction of double-strand breaks (DSBs) at specific genomic locations called hotspots, which are catalyzed by Spo11 and its partners. DSB hotspots during meiosis are marked with Set1-mediated histone H3K4 methylation. The Spo11 partner complex, Rec114-Mer2-Mei4, essential for the DSB formation, localizes to the chromosome axes. For efficient DSB formation, a hotspot with histone H3K4 methylation on the chromatin loops is tethered to the chromosome axis through the H3K4 methylation reader protein, Spp1, on the axes, which interacts with Mer2. In this study, we found genetic interaction of mutants in a histone modification protein complex called PAF1C with the REC114 and MER2 in the DSB formation in budding yeast Saccharomyces cerevisiae. Namely, the paf1c mutations rtf1 and cdc73 showed synthetic defects in meiotic DSB formation only when combined with a wild-type-like tagged allele of either the REC114 or MER2. The synthetic defect of the tagged REC114 allele in the DSB formation was seen also with the set1, but not with spp1 deletion. These results suggest a novel role of histone modification machinery in DSB formation during meiosis, which is independent of Spp1-mediated loop-axis tethering.
Target of Rapamycin (TOR) Negatively Regulates Ethylene Signals in Arabidopsis
Authors: Zhuo Fengping , Xiong Fangjie , Deng Kexuan , Li Zhengguo , Ren Maozhi
Published: April 2020

Target of rapamycin (TOR) acts as a master regulator in coordination of cell growth with energy and nutrient availability. Despite the increased appreciation of the essential role of the TOR complex in interaction with phytohormone signaling, little is known about its function on ethylene signaling. Here, through expression analysis, genetic and biochemical approaches, we reveal that TOR functions in the regulation of ethylene signals. Transcriptional analysis indicates that TOR inhibition by AZD8055 upregulated senescence- and ethylene-related genes expression. Furthermore, ethylene insensitive mutants like etr1-1, ein2-5 and ein3 eil1, showed more hyposensitivity to AZD8055 than that of WT in hypocotyl growth inhibition. Similarly, blocking ethylene signals by ethylene action inhibitor Ag+ or biosynthesis inhibitor aminoethoxyvinylglycine (AVG) largely rescued hypocotyl growth even in presence of AZD8055. In addition, we also demonstrated that Type 2A phosphatase-associated protein of 46 kDa (TAP46), a downstream component of TOR signaling, physically interacts with 1-aminocy-clopropane-1-carboxylate (ACC) synthase ACS2 and ACS6. Arabidopsis overexpressing ACS2 or ACS6 showed more hypersensitivity to AZD8055 than WT in hypocotyl growth inhibition. Moreover, ACS2/ACS6 protein was accumulated under TOR suppression, implying TOR modulates ACC synthase protein levels. Taken together, our results indicate that TOR participates in negatively modulating ethylene signals and the molecular mechanism is likely involved in the regulation of ethylene biosynthesis by affecting ACSs in transcription and protein levels.
Modified DNA Aptamers for C-Reactive Protein and Lactate Dehydrogenase-5 with Sub-Nanomolar Affinities
Authors: Minagawa Hirotaka , Kataoka Yuka , Fujita Hiroto , Kuwahara Masayasu , Horii Katsunori , Shiratori Ikuo , Waga Iwao
Published: April 2020

Human C-reactive protein (CRP) and lactate dehydrogenase are important markers in clinical laboratory testing—the former is used to detect in vivo inflammation, and the latter is used to detect cell necrosis and tissue destruction. We developed aptamers that bind to human CRP and human lactate dehydrogenase-5 (LDH-5) with high affinities (dissociation constants of 6.2 pM and 235 pM, respectively), applying the systematic evolution of ligands by exponential enrichment (SELEX) method, and by using a modified DNA library containing the following base-appended base modifications: analog adenine derivative at the fifth position of uracil (Uad), analog guanine derivative at the fifth position of uracil (Ugu), and analog adenine derivative at the seventh position of adenine (Aad). A potential application of these aptamers as sensor elements includes high-sensitivity target detection in point-of-care testing.
Vascular Calcification—New Insights into Its Mechanism
Authors: Lee Sun Joo , Lee In-Kyu , Jeon Jae-Han
Published: April 2020

Vascular calcification (VC), which is categorized by intimal and medial calcification, depending on the site(s) involved within the vessel, is closely related to cardiovascular disease. Specifically, medial calcification is prevalent in certain medical situations, including chronic kidney disease and diabetes. The past few decades have seen extensive research into VC, revealing that the mechanism of VC is not merely a consequence of a high-phosphorous and -calcium milieu, but also occurs via delicate and well-organized biologic processes, including an imbalance between osteochondrogenic signaling and anticalcific events. In addition to traditionally established osteogenic signaling, dysfunctional calcium homeostasis is prerequisite in the development of VC. Moreover, loss of defensive mechanisms, by microorganelle dysfunction, including hyper-fragmented mitochondria, mitochondrial oxidative stress, defective autophagy or mitophagy, and endoplasmic reticulum (ER) stress, may all contribute to VC. To facilitate the understanding of vascular calcification, across any number of bioscientific disciplines, we provide this review of a detailed updated molecular mechanism of VC. This encompasses a vascular smooth muscle phenotypic of osteogenic differentiation, and multiple signaling pathways of VC induction, including the roles of inflammation and cellular microorganelle genesis.
Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy
Authors: Kim Sun Jeong , Oh Hae Won , Chang Jong Wook , Kim Sang Jun
Published: April 2020

The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy.
A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization
Authors: Kiel Christina , Berber Patricia , Karlstetter Marcus , Aslanidis Alexander , Strunz Tobias , Langmann Thomas , Grassmann Felix , Weber Bernhard H.F.
Published: April 2020

Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.
New Insights on the Effect of TNF Alpha Blockade by Gene Silencing in Noise-Induced Hearing Loss
Authors: Rodrigues Janaína C. , Bachi André L. L. , Silva Gleiciele A. V. , Rossi Marcelo , do Amaral Jonatas B. , Lezirovitz Karina , de Brito Rubens
Published: April 2020

Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor α (TNFα) was involved in this context. The effect of Tnfα gene silencing on the expression profile related to the TNFα metabolic pathway in an experimental model of noise-induced hearing loss had not previously been studied. Methods: Single ears of Wistar rats were pretreated with Tnfα small interfering RNA (siRNA) by trans-tympanic administration 24 h before they were exposed to white noise (120 dBSPL for three hours). After 24 h of noise exposure, we analyzed the electrophysiological threshold and the amplitude of waves I, II, III, and IV in the auditory brain response click. In addition, qRT-PCR was performed to evaluate the TNFα metabolic pathway in the ears submitted or not to gene silencing. Results: Preservation of the electrophysiological threshold and the amplitude of waves was observed in the ears submitted to gene silencing compared to the ears not treated. Increased anti-apoptotic gene expression and decreased pro-apoptotic gene expression were found in the treated ears. Conclusion: Our results allow us to suggest that the blockade of TNFα by gene silencing was useful to prevent noise-induced hearing loss.
Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses
Authors: Shin Seung-Heon , Ye Mi-Kyung , Lee Dong-Won , Chae Mi-Hyun , Han Ba-Da
Published: April 2020

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells’ (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with Alternaria alternata, Aspergillus fumigatus, Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. Alternaria, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-κB, AP-1, and MAPK pathway. NECM induced IL-5, IFN-γ, and TNF-α production from PBMCs, without increasing ILC2 expression. Alternaria and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.
Potential Roles of Long Noncoding RNAs as Therapeutic Targets in Renal Fibrosis
Authors: Jung Hyun Jin , Kim Hyun-Ju , Park Kwan-Kyu
Published: April 2020

Many studies have made clear that most of the genome is transcribed into noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which can affect different cell features. LncRNAs are long heterogeneous RNAs that regulate gene expression and a variety of signaling pathways involved in cellular homeostasis and development. Several studies have demonstrated that lncRNA is an important class of regulatory molecule that can be targeted to change cellular physiology and function. The expression or dysfunction of lncRNAs is closely related to various hereditary, autoimmune, and metabolic diseases, and tumors. Specifically, recent work has shown that lncRNAs have an important role in kidney pathogenesis. The effective roles of lncRNAs have been recognized in renal ischemia, injury, inflammation, fibrosis, glomerular diseases, renal transplantation, and renal-cell carcinoma. The present review focuses on the emerging role and function of lncRNAs in the pathogenesis of kidney inflammation and fibrosis as novel essential regulators. Although lncRNAs are important players in the initiation and progression of many pathological processes, their role in renal fibrosis remains unclear. This review summarizes the current understanding of lncRNAs in the pathogenesis of kidney fibrosis and elucidates the potential role of these novel regulatory molecules as therapeutic targets for the clinical treatment of kidney inflammation and fibrosis.
Melatonin Non-Linearly Modulates Bull Spermatozoa Motility and Physiology in Capacitating and Non-Capacitating Conditions
Authors: Fernández-Alegre Estela , Álvarez-Fernández Indira , Domínguez Juan Carlos , Casao Adriana , Martínez-Pastor Felipe
Published: April 2020

Bull spermatozoa physiology may be modulated by melatonin. We washed ejaculated spermatozoa free of melatonin and incubated them (4 h, 38 °C) with 0-pM, 1-pM, 100-pM, 10-nM and 1-µM melatonin in TALP-HEPES (non-capacitating) and TALP-HEPES-heparin (capacitating). This range of concentrations encompassed the effects mediated by melatonin receptors (pM), intracellular targets (nM–µM) or antioxidant activity (µM). Treatment effects were assessed as motility changes by computer-assisted sperm analysis (CASA) of motility and physiological changes by flow cytometry. Melatonin effects were more evident in capacitating conditions, with 100 pM reducing motility and velocity (VCL) while increasing a “slow” subpopulation. All concentrations decreased apoptotic spermatozoa and stimulated mitochondrial activity in viable spermatozoa, with 100 pM–1 µM increasing acrosomal damage, 10 nM–1 µM increasing intracellular calcium and 1 pM reducing the response to a calcium-ionophore challenge. In non-capacitating media, 1 µM increased hyperactivation-related variables and decreased apoptotic spermatozoa; 100 pM–1 µM increased membrane disorders (related to capacitation); all concentrations decreased mitochondrial ROS production. Melatonin concentrations had a modal effect on bull spermatozoa, suggesting a capacitation-modulating role and protective effect at physiological concentrations (pM). Some effects may be of practical use, considering artificial reproductive techniques.
The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism
Authors: Gavrilov Dimitar K. , Piazza Amy L. , Pino Gisele , Turgeon Coleman , Matern Dietrich , Oglesbee Devin , Raymond Kimiyo , Tortorelli Silvia , Rinaldo Piero
Published: April 2020

The expansion of the recommend uniform screening panel to include more than 50 primary and secondary target conditions has resulted in a substantial increase of false positive results. As an alternative to subjective manipulation of cutoff values and overutilization of molecular testing, here we describe the performance outcome of an algorithm for disorders of methionine, cobalamin, and propionate metabolism that includes: (1) first tier screening inclusive of the broadest available spectrum of markers measured by tandem mass spectrometry; (2) integration of all results into a score of likelihood of disease for each target condition calculated by post-analytical interpretive tools created byCollaborative Laboratory Integrated Reports (CLIR), a multivariate pattern recognition software; and (3) further evaluation of abnormal scores by a second tier test measuring homocysteine, methylmalonic acid, and methylcitric acid. This approach can consistently reduce false positive rates to a <0.01% level, which is the threshold of precision newborn screening. We postulate that broader adoption of this algorithm could lead to substantial savings in health care expenditures. More importantly, it could prevent the stress and anxiety experienced by many families when faced with an abnormal newborn screening result that is later resolved as a false positive outcome.
Technology Development of Fast-Response Aerodynamic Pressure Probes
Authors: Gaetani Paolo , Persico Giacomo
Published: April 2020

This paper presents and discusses the recent developments on the Fast-Response Aerodynamic Pressure Probe (FRAPP) technology at the Laboratorio di Fluidodinamica delle Macchine (LFM) of the Politecnico di Milano. First, the different geometries developed and tested at LFM are presented and critically discussed: the paper refers to single-sensor or two-sensor probes applied as virtual 2D or 3D probes for phase-resolved measurements. The static calibration of the sensors inserted inside the head of the probes is discussed, also taking into account for the temperature field of application: in this context, a novel calibration procedure is discussed and the new manufacturing process is presented. The dynamic calibration is reconsidered in view of the 15-years’ experience, including the extension to probes operating at different temperature and pressure levels with respect to calibration. As for the probe aerodynamics, the calibration coefficients are discussed and the most reliable set here is evidenced. A novel procedure for the quantification of the measurement uncertainty, recently developed and based on the Montecarlo methodology, is introduced and discussed in the paper.
Iron Oxide Nanoparticles: An Alternative for Positive Contrast in Magnetic Resonance Imaging
Authors: Fernández-Barahona Irene , Muñoz-Hernando María , Ruiz-Cabello Jesus , Herranz Fernando , Pellico Juan
Published: April 2020

Iron oxide nanoparticles have been extensively utilised as negative (T2) contrast agents in magnetic resonance imaging. In the past few years, researchers have also exploited their application as positive (T1) contrast agents to overcome the limitation of traditional Gd3+ contrast agents. To provide T1 contrast, these particles must present certain physicochemical properties with control over the size, morphology and surface of the particles. In this review, we summarise the reported T1 iron oxide nanoparticles and critically revise their properties, synthetic protocols and application, not only in MRI but also in multimodal imaging. In addition, we briefly summarise the most important nanoparticulate Gd and Mn agents to evaluate whether T1 iron oxide nanoparticles can reach Gd/Mn contrast capabilities.
Diversity and Global Distribution of Viruses of the Western Honey Bee, Apis mellifera
Authors: Beaurepaire Alexis , Piot Niels , Doublet Vincent , Antunez Karina , Campbell Ewan , Chantawannakul Panuwan , Chejanovsky Nor , Gajda Anna , Heerman Matthew , Panziera Delphine , Smagghe Guy , Yañez Orlando , de Miranda Joachim R. , Dalmon Anne
Published: April 2020

In the past centuries, viruses have benefited from globalization to spread across the globe, infecting new host species and populations. A growing number of viruses have been documented in the western honey bee, Apis mellifera. Several of these contribute significantly to honey bee colony losses. This review synthetizes the knowledge of the diversity and distribution of honey-bee-infecting viruses, including recent data from high-throughput sequencing (HTS). After presenting the diversity of viruses and their corresponding symptoms, we surveyed the scientific literature for the prevalence of these pathogens across the globe. The geographical distribution shows that the most prevalent viruses (deformed wing virus, sacbrood virus, black queen cell virus and acute paralysis complex) are also the most widely distributed. We discuss the ecological drivers that influence the distribution of these pathogens in worldwide honey bee populations. Besides the natural transmission routes and the resulting temporal dynamics, global trade contributes to their dissemination. As recent evidence shows that these viruses are often multihost pathogens, their spread is a risk for both the beekeeping industry and the pollination services provided by managed and wild pollinators.
Human Gender Classification Using Transfer Learning via Pareto Frontier CNN Networks
Authors: Islam Md. Mahbubul , Tasnim Nusrat , Baek Joong-Hwan
Published: April 2020

Human gender is deemed as a prime demographic trait due to its various usage in the practical domain. Human gender classification in an unconstrained environment is a sophisticated task due to large variations in the image scenarios. Due to the multifariousness of internet images, the classification accuracy suffers from traditional machine learning methods. The aim of this research is to streamline the gender classification process using the transfer learning concept. This research proposes a framework that performs automatic gender classification in unconstrained internet images deploying Pareto frontier deep learning networks; GoogleNet, SqueezeNet, and ResNet50. We analyze the experiment with three different Pareto frontier Convolutional Neural Network (CNN) models pre-trained on ImageNet. The massive experiments demonstrate that the performance of the Pareto frontier CNN networks is remarkable in the unconstrained internet image dataset as well as in the frontal images that pave the way to developing an automatic gender classification system.
The Role of Non-Cognitive Factors in the SAT Remains Unclear: A Commentary on Hannon (2019)
Authors: Conway Andrew R. A. , Hao Han
Published: April 2020

In the current issue of the Journal of Intelligence, Hannon (2019) reports a novel and intriguing pattern of results that could be interpreted as evidence that the SAT is biased against Hispanic students. Specifically, Hannon’s analyses suggest that non-cognitive factors, such as test anxiety, contribute to SAT performance and the impact of test anxiety on the SAT is stronger among Hispanic students than European-American students. Importantly, this pattern of results was observed after controlling for individual differences in cognitive abilities. We argue that there are multiple issues with Hannon’s investigation and interpretation. For instance, Hannon did not include an adequate number or variety of measures of cognitive ability. In addition, the measure of test anxiety was a retrospective self-report survey on evaluated anxiety rather than a direct measure of situational test anxiety associated with the SAT. Based on these and other observations, we conclude that Hannon’s current results do not provide sufficient evidence to suggest that non-cognitive factors play a significant role in the SAT or that they impact European-American and Hispanic students differently.
A Numerical Analysis of the Temporal and Spatial Temperature Development during the Ultrasonic Spot Welding of Fibre-Reinforced Thermoplastics
Authors: Tutunjian Shahan , Dannemann Martin , Modler Niels , Kucher Michael , Fellermayer Albert
Published: April 2020

The ultrasonic spot welding of fibre-reinforced thermoplastic laminates has received great interest from researchers, mainly in the fields of aerospace and automotive industries. It offers an efficient solution to join large thermoplastic composite parts through the spot welding approach with a high level of automation. In this paper, the temporal and spatial development of the temperature in an ultrasonic weld spot between two fibre-reinforced thermoplastic laminates was modelled. During the ultrasonic welding of thermoplastic composite laminates without energy directors a sudden temperature jump in the weld spot is usually observed. The temperature increase occurs rapidly up to the decomposition of the thermoplastic matrix and causes the degradation of the weld spot. To understand the temperature distribution within the weld spot and to calculate its temporal development, the thermal problem was analysed using a two-dimensional explicit finite difference method. To evaluate the models, the calculated time traces of the temperature in the weld spot were compared with the experimentally obtained values under comparable conditions.
Biological Aspects of Juveniles of the Common Stingray, Dasyatis pastinaca (Linnaeus, 1758) (Elasmobranchii, Dasyatidae), from the Central Mediterranean Sea
Authors: Tiralongo Francesco , Messina Giuseppina , Lombardo Bianca Maria
Published: April 2020

Data on the biology of Dasyatis pastinaca are absent from the Ionian Sea and only a few studies were conducted in the Mediterranean Sea. Some biological and ecological aspects of D. pastinaca were investigated between November 2019 and February 2020 in the central Mediterranean Sea. In particular, we investigated several morphologic, population and ecological aspects of the species. The analysis of the stomach contents showed that D. pastinaca is a generalist carnivorous, mainly feeding on small crustaceans and polychaetes. The Levin’s index value (Bi) was 0.85. The sex ratio showed no significant differences from 1:1 ratio. Females were larger than males, but no statistical differences were found in disc width-weight and total length-disc width relationships between sexes. Most of the specimens caught were juveniles and inhabit shallow sandy bottoms.
“Are You Planning to Follow Your Route?” The Effect of Route Exchange on Decision Making, Trust, and Safety
Authors: Aylward Katie , Weber Reto , Man Yemao , Lundh Monica , MacKinnon Scott N.
Published: April 2020

The Sea Traffic Management (STM) Validation project is a European based initiative which focuses on connecting and updating the maritime world in real time, with efficient information exchange. The purpose of this paper is to evaluate two functions developed during the project: a ship to ship route exchange (S2SREX) function and rendezvous (RDV) information layer, collectively referred to as S2SREX/RDV. S2SREX displays the route segment consisting of the next seven waypoints of the monitored route of a collaborating ship and the RDV layer that predicts a meeting point. S2SREX/RDV provides supplementary information to data acquired by existing navigation systems and is intended to improve situational awareness and safety through a more comprehensive understanding of the surrounding traffic. Chalmers University of Technology and Solent University completed an experiment using twenty-four experienced navigators in bridge simulators. Six traffic scenarios were developed by subject matter experts and tested with and without S2SREX/RDV functionalities. Qualitative data were collected using post-test questionnaires and group debriefs to evaluate the participants’ perceptions of S2SREX/RDV in the various traffic scenarios, and quantitative data were collected to assess the ship distances and behavior in relation to the International Regulations for Preventing Collisions at Sea (COLREGs). The results revealed that participants generally trusted the S2SREX/RDV information, and most used S2SREX/RDV for decision support. The quantitative assessment revealed that the COLREGs were breached more often when S2SREX/RDV was used. Experimental findings are discussed in relation to safety, trust, reliance, situational awareness, and human-automation interaction constructs.
Relative Efficiency of Canadian Banks: A Three-Stage Network Bootstrap DEA
Authors: Dia Mohamed , Golmohammadi Amirmohsen , Takouda Pawoumodom M.
Published: April 2020

In this study, we focus on how banks can enhance their efficiency in the utilization of resources to ensure their economic sustainability. We propose a novel three-stage (production, investment, and revenue generation) network Data Envelopment Analysis (DEA) with bootstrapping to evaluate the performance of the six big Canadian banks for the period 2000–2017, amid the 2007 financial crisis and the increasing competition level due to new technologies. We identify the best practices in each stage that can be used as benchmarks by other banks to improve their economic sustainability. Our results indicate that the 2007 financial crisis resulted in lower efficiencies in the performance of Canadian banks. This decline was not substantial for the production and investment stages when the revenue generation stage received the greatest hit. In addition, we observed that the individual banks did not have consistent performance in the different stages. Finally, we compared our model with the black box DEA model and concluded that the network DEA provides more insightful and accurate results in terms of banks’ efficiencies.
Dynamic Spillovers between Gulf Cooperation Council’s Stocks, VIX, Oil and Gold Volatility Indices
Authors: Alqahtani Abdullah , Chevallier Julien
Published: April 2020

This paper analyzes the conditional correlations between the stock market returns of countries that are members of the Gulf Cooperation Council (GCC). The innovative aspects of the paper consist of focusing on three volatility indices: the oil (OVX), gold (GVZ), and S&P500 (VIX) markets (considered in log-difference). We use weekly data and resort to DCC-GARCH modeling. The novelty of the paper consists in revealing that: (i) GCC stock market returns are negatively correlated with each of the volatility measures, and the correlations are stronger during crisis periods; (ii) GCC stock returns are mostly correlated with oil shocks; and (iii) Saudi Arabia and Qatar are the most responsive to all shocks among the GCC countries, while Bahrain correlates weakly to shocks in oil, gold, and VIX. The most striking results feature extra sensitivity of Saudi Arabia and Qatar in terms of volatility indices, which should be the foremost concern of policymakers and banking analysts.
Oil Price, Oil Price Implied Volatility (OVX) and Illiquidity Premiums in the US: (A)symmetry and the Impact of Macroeconomic Factors
Authors: Essa Mohammad Sharik , Giouvris Evangelos
Published: April 2020

We examine the impact of oil price and oil price volatility on US illiquidity premiums (return on illiquid-minus-liquid stocks), using the US Oil Fund options implied volatility OVX index. We use daily data from 2007 to 2018, taking into account the structural break in June 2009 and controlling for macroeconomic factors. Both OLS and VAR models indicate that oil price has a significantly positive impact and OVX has a significantly negative impact on premiums, for the full sample and post-crisis period. These relationships are potentially driven by investor sentiments and market liquidity. Oil price has a negative impact on premiums during the crisis period. Using an autoregressive distribution lag model and an error correction model, we analyse long- and short-run elasticities. We find that oil price has a significantly positive impact on premiums both in the long- and short-run, for the full sample and post-crisis period. OVX only has a significantly negative impact in the short-run for the full sample. The reverting mechanism to establish long-run equilibrium is effective for the full sample and post-crisis period. Illiquidity premiums do not show any asymmetric responses to oil price changes but we do find evidence of asymmetric response to OVX changes.