bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanostructured Magnéli-Phase W18O49 Thin Films for Photoelectrochemical Water Splitting
Authors: Mohamedkhair A. K. , Drmosh Q. A. , Qamar Mohammad , Yamani Z. H.
Published: May 2020

Converting water into hydrogen through the photo-electrochemical (PEC) process is one of the most exciting approaches in this field, and there is a quest to design or search for new electro-photo-catalytic materials. In this work, simple steps for fabrication and transformation of metallic tungsten thin film into the photo-active Magnéli-phase (W18O49) of tungsten oxide thin film is demonstrated. The post-annealing temperature has a significant impact on the phase evolution of tungsten film into W18O49. The film thickness of W18O49 is controlled by controlling the sputtering time (or deposition time) of W film. The PEC performance of the as-prepared electrodes is evaluated by monitoring the water oxidation reaction under visible radiation. The PEC findings reveal a correlation between PEC performance and phase, morphology, and thickness of the film. The as-derived W18O49 can efficiently catalyze the water oxidation reaction at neutral solution pH, generating 0.6 and 1.4 mA cm−1 photo-current at 0.6 and 0.8 V vs. Saturated calomel electrode (SCE), respectively, in addition to excellent stability. The electrical conductivity and the charge transfer kinetics are investigated employing the electrochemical impedance spectroscopic (EIS) technique.
Comparative Study of ZnO Thin Films Doped with Transition Metals (Cu and Co) for Methylene Blue Photodegradation under Visible Irradiation
Authors: Vallejo William , Cantillo Alvaro , Salazar Briggitte , Diaz-Uribe Carlos , Ramos Wilkendry , Romero Eduard , Hurtado Mikel
Published: May 2020

We synthesized and characterized both Co-doped ZnO (ZnO:Co) and Cu-doped ZnO (ZnO:Cu) thin films. The catalysts’ synthesis was carried out by the sol–gel method while the doctor blade technique was used for thin film deposition. The physicochemical characterization of the catalysts was carried out by Raman spectroscopy, scanning electron microscopy (SEM), X-ray diffraction, and diffuse reflectance measurements. The photocatalytic activity was studied under visible irradiation in aqueous solution, and kinetic parameters were determined by pseudo-first-order fitting. The Raman spectra results evinced the doping process and suggested the formation of heterojunctions for both dopants. The structural diffraction patterns indicated that the catalysts were polycrystalline and demonstrated the presence of a ZnO wurtzite crystalline phase. The SEM analysis showed that the morphological properties changed significantly, the micro-aggregates disappeared, and agglomeration was reduced after modification of ZnO. The ZnO optical bandgap (3.22 eV) reduced after the doping process, these being ZnO:Co (2.39 eV) and ZnO:Co (3.01 eV). Finally, the kinetic results of methylene blue photodegradation reached 62.6% for ZnO:Co thin films and 42.5% for ZnO:Cu thin films.
Creatine Kinase and Progression Rate in Amyotrophic Lateral Sclerosis
Authors: Ceccanti Marco , Pozzilli Valeria , Cambieri Chiara , Libonati Laura , Onesti Emanuela , Frasca Vittorio , Fiorini Ilenia , Petrucci Antonio , Garibaldi Matteo , Palma Eleonora , Bendotti Caterina , Fabbrizio Paola , Trolese Maria Chiara , Nardo Giovanni , Inghilleri Maurizio
Published: May 2020

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no recognized clinical prognostic factor. Creatinine kinase (CK) increase in these patients is already described with conflicting results on prognosis and survival. In 126 ALS patients who were fast or slow disease progressors, CK levels were assayed for 16 months every 4 months in an observational case-control cohort study with prospective data collection conducted in Italy. CK was also measured at baseline in 88 CIDP patients with secondary axonal damage and in two mouse strains (129SvHSD and C57-BL) carrying the same SOD1G93A transgene expression but showing a fast (129Sv-SOD1G93A) and slow (C57-SOD1G93A) ALS progression rate. Higher CK was found in ALS slow progressors compared to fast progressors in T1, T2, T3, and T4, with a correlation with Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores. Higher CK was found in spinal compared to bulbar-onset patients. Transgenic and non-transgenic C57BL mice showed higher CK levels compared to 129SvHSD strain. At baseline mean CK was higher in ALS compared to CIDP. CK can predict the disease progression, with slow progressors associated with higher levels and fast progressors to lower levels, in both ALS patients and mice. CK is higher in ALS patients compared to patients with CIDP with secondary axonal damage; the higher levels of CK in slow progressors patients, but also in C57BL transgenic and non-transgenic mice designs CK as a predisposing factor for disease rate progression.
Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure
Authors: Nielsen Marlene Christina , Hvidbjerg Gantzel Rasmus , Clària Joan , Trebicka Jonel , Møller Holger Jon , Grønbæk Henning
Published: May 2020

Macrophages facilitate essential homeostatic functions e.g., endocytosis, phagocytosis, and signaling during inflammation, and express a variety of scavenger receptors including CD163 and CD206, which are upregulated in response to inflammation. In healthy individuals, soluble forms of CD163 and CD206 are constitutively shed from macrophages, however, during inflammation pathogen- and damage-associated stimuli induce this shedding. Activation of resident liver macrophages viz. Kupffer cells is part of the inflammatory cascade occurring in acute and chronic liver diseases. We here review the existing literature on sCD163 and sCD206 function and shedding, and potential as biomarkers in acute and chronic liver diseases with a particular focus on Acute-on-Chronic Liver Failure (ACLF). In multiple studies sCD163 and sCD206 are elevated in relation to liver disease severity and established as reliable predictors of morbidity and mortality. However, differences in expression- and shedding-stimuli for CD163 and CD206 may explain dissimilarities in prognostic utility in patients with acute decompensation of cirrhosis and ACLF.
Two Birds with One Stone: NFAT1-MDM2 Dual Inhibitors for Cancer Therapy
Authors: Wang Wei , Zafar Atif , Rajaei Mehrdad , Zhang Ruiwen
Published: May 2020

The tumor suppressor p53 is believed to be the mostly studied molecule in modern biomedical research. Although p53 interacts with hundreds of molecules to exert its biological functions, there are only a few modulators regulating its expression and function, with murine double minute 2 (MDM2) playing a key role in this regard. MDM2 also contributes to malignant transformation and cancer development through p53-dependent and -independent mechanisms. There is an increasing interest in developing MDM2 inhibitors for cancer prevention and therapy. We recently demonstrated that the nuclear factor of activated T cells 1 (NFAT1) activates MDM2 expression. NFAT1 regulates several cellular functions in cancer cells, such as cell proliferation, migration, invasion, angiogenesis, and drug resistance. Both NFAT isoforms and MDM2 are activated and overexpressed in several cancer subtypes. In addition, a positive correlation exists between NFAT1 and MDM2 in tumor tissues. Our recent clinical study has demonstrated that high expression levels of NFAT1 and MDM2 are independent predictors of a poor prognosis in patients with hepatocellular carcinoma. Thus, inhibition of the NFAT1-MDM2 pathway appears to be a novel potential therapeutic strategy for cancer. In this review, we summarize the potential oncogenic roles of MDM2 and NFAT1 in cancer cells and discuss the efforts of discovery and the development of several newly identified MDM2 and NFAT1 inhibitors, focusing on their potent in vitro and in vivo anticancer activities. This review also highlights strategies and future directions, including the need to focus on the development of more specific and effective NFAT1-MDM2 dual inhibitors for cancer therapy.
Mitochondria in Health and Diseases
Authors: Javadov Sabzali , Kozlov Andrey V. , Camara Amadou K. S.
Published: May 2020

Mitochondria are subcellular organelles evolved by endosymbiosis of bacteria with eukaryotic cells characteristics. They are the main source of ATP in the cell and play a pivotal role in cell life and cell death. Mitochondria are engaged in the pathogenesis of human diseases and aging directly or indirectly through a broad range of signaling pathways. However, despite an increased interest in mitochondria over the past decades, the mechanisms of mitochondria-mediated cell/organ dysfunction in response to pathological stimuli remain unknown. The Special Issue, “Mitochondria in Health and Diseases,” organized by Cells includes 24 review and original articles that highlight the latest achievements in elucidating the role of mitochondria under physiological (healthy) conditions and, in various cell/animal models of human diseases and, in patients. Altogether, the Special Issue summarizes and discusses different aspects of mitochondrial metabolism and function that open new avenues in understanding mitochondrial biology.
Group 2 Innate Lymphoid Cells and the House Dust Mite-Induced Asthma Mouse Model
Authors: Yasuda Yuichiro , Nagano Tatsuya , Kobayashi Kazuyuki , Nishimura Yoshihiro
Published: May 2020

Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis of asthma. Recently, in addition to acquired immunity, innate immunity has also been thought to be involved in asthma. Among innate immune cells, group 2 innate lymphoid cells (ILC2s) have been considered to be crucial for eosinophilic airway inflammation by releasing T helper 2 cytokines. Moreover, house dust mites (HDMs) belonging to group 1 act on airway epithelial cells not only as allergens but also as cysteine proteases. The production of interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP) from airway epithelial cells was induced by the protease activity of HDMs. These cytokines activate ILC2s, and activated ILC2s produce IL-5, IL-9, IL-13, and amphiregulin. Hence, the HDM-induced asthma mouse model greatly contributes to understanding asthma pathogenesis. In this review, we highlight the relationship between ILC2s and the HDM in the asthma mouse model to help researchers and clinicians not only choose a proper asthma mouse model but also to understand the molecular mechanisms underlying HDM-induced asthma.
Functional Characterisation of the Autophagy ATG12~5/16 Complex in Dictyostelium discoideum
Authors: Karow Malte , Fischer Sarah , Meßling Susanne , Konertz Roman , Riehl Jana , Xiong Qiuhong , Rijal Ramesh , Wagle Prerana , S. Clemen Christoph , Eichinger Ludwig
Published: May 2020

Macroautophagy, a highly conserved and complex intracellular degradative pathway, involves more than 20 core autophagy (ATG) proteins, among them the hexameric ATG12~5/16 complex, which is part of the essential ubiquitin-like conjugation systems in autophagy. Dictyostelium discoideum atg5 single, atg5/12 double, and atg5/12/16 triple gene knock-out mutant strains displayed similar defects in the conjugation of ATG8 to phosphatidylethanolamine, development, and cell viability upon nitrogen starvation. This implies that ATG5, 12 and 16 act as a functional unit in canonical autophagy. Macropinocytosis of TRITC dextran and phagocytosis of yeast were significantly decreased in ATG5¯ and ATG5¯/12¯ and even further in ATG5¯/12¯/16¯ cells. In contrast, plaque growth on Klebsiella aerogenes was about twice as fast for ATG5¯ and ATG5¯/12¯/16¯ cells in comparison to AX2, but strongly decreased for ATG5¯/12¯ cells. Along this line, phagocytic uptake of Escherichia coli was significantly reduced in ATG5¯/12¯ cells, while no difference in uptake, but a strong increase in membrane association of E. coli, was seen for ATG5¯ and ATG5¯/12¯/16¯ cells. Proteasomal activity was also disturbed in a complex fashion, consistent with an inhibitory activity of ATG16 in the absence of ATG5 and/or ATG12. Our results confirm the essential function of the ATG12~5/16 complex in canonical autophagy, and furthermore are consistent with autophagy-independent functions of the complex and its individual components. They also strongly support the placement of autophagy upstream of the ubiquitin-proteasome system (UPS), as a fully functional UPS depends on autophagy.
Innovative Visualization and Quantification of Extracellular Vesicles Interaction with and Incorporation in Target Cells in 3D Microenvironments
Authors: Ragni Enrico , Palombella Silvia , Lopa Silvia , Talò Giuseppe , Perucca Orfei Carlotta , De Luca Paola , Moretti Matteo , de Girolamo Laura
Published: May 2020

Extracellular vesicles (EVs) showed therapeutic properties in several applications, many in regenerative medicine. A clear example is in the treatment of osteoarthritis (OA), where adipose-derived mesenchymal stem cells (ASCs)-EVs were able to promote regeneration and reduce inflammation in both synovia and cartilage. A still obscure issue is the effective ability of EVs to be internalized by target cells, rather than simply bound to the extracellular matrix (ECM) or plasma membrane, since the current detection or imaging technologies cannot fully decipher it due to technical limitations. In the present study, human articular chondrocytes (ACHs) and fibroblast-like synoviocytes (FLSs) isolated from the same OA patients were cocultured in 2D as well as in 3D conditions with fluorescently labeled ASC-EVs, and analyzed by flow cytometry or confocal microscopy, respectively. In contrast with conventional 2D, in 3D cultures, confocal microscopy allowed a clear detection of the tridimensional morphology of the cells and thus an accurate discrimination of EV interaction with the external and/or internal cell environment. In both 2D and 3D conditions, FLSs were more efficient in interacting with ASC-EVs and 3D imaging demonstrated a faster uptake process. The removal of the hyaluronic acid component from the ECM of both cell types reduced their interaction with ASC-EVs only in the 2D system, showing that 2D and 3D conditions can yield different outcomes when investigating events where ECM plays a key role. These results indicate that studying EVs binding and uptake both in 2D and 3D guarantees a more precise and complementary characterization of the molecular mechanisms involved in the process. The implementation of this strategy can become a valuable tool not only for basic research, but also for release assays and potency prediction for clinical EV batches.
Hinge and Transmembrane Domains of Chimeric Antigen Receptor Regulate Receptor Expression and Signaling Threshold
Authors: Fujiwara Kento , Tsunei Ayaka , Kusabuka Hotaka , Ogaki Erika , Tachibana Masashi , Okada Naoki
Published: May 2020

Chimeric antigen receptor (CAR)-T cells have demonstrated significant clinical potential; however, their strong antitumor activity may cause severe adverse effects. To ensure efficacy and safe CAR-T cell therapy, it is important to understand CAR’s structure–activity relationship. To clarify the role of hinge and transmembrane domains in CAR and CAR-T cell function, we generated different chimeras and analyzed their expression levels and antigen-specific activity on CAR-T cells. First, we created a basic CAR with hinge, transmembrane, and signal transduction domains derived from CD3ζ, then we generated six CAR variants whose hinge or hinge/transmembrane domains originated from CD4, CD8α, and CD28. CAR expression level and stability on the T cell were greatly affected by transmembrane rather than hinge domain. Antigen-specific functions of most CAR-T cells depended on their CAR expression levels. However, CARs with a CD8α- or CD28-derived hinge domain showed significant differences in CAR-T cell function, despite their equal expression levels. These results suggest that CAR signaling intensity into T cells was affected not only by CAR expression level, but also by the hinge domain. Our discoveries indicate that the hinge domain regulates the CAR signaling threshold and the transmembrane domain regulates the amount of CAR signaling via control of CAR expression level.
Truncated Pneumolysin from Streptococcus pneumoniae as a TLR4-Antagonizing New Drug for Chronic Inflammatory Conditions
Authors: Chang Shun-Fu , Chen Cheng-Nan , Lin Jung-Chung , Wang Hsin-Ell , Mori Shigetarou , Li Jia-Je , Yen Chia-Kuang , Hsu Ching-Yun , Fung Chang-Phone , Chong Pele Choi-Sing , Leng Chih-Hsiang , Ding Yi-Jun , Chang Feng-Yee , Siu L. Kristopher
Published: May 2020

Microbial proteins have recently been found to have more benefits in clinical disease treatment because of their better-developed strategy and properties than traditional medicine. In this study, we investigated the effectiveness of a truncated peptide synthesized from the C-terminal sequence of pneumolysin, i.e., C70PLY4, in Streptococcus pneumoniae, in treating chronic inflammatory conditions. It has been shown that C70PLY4 significantly blocks the transendothelial migration of neutrophils and attenuates the formation of atherosclerotic plaque and the secretion of soluble forms of the intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule 1 (VCAM-1), and E-selectin in high-fat-diet/streptozotocin-induced inflammatory rats. The mechanism and the docking simulation analysis further indicated that C70PLY4 might serve as a Toll-like receptor 4 (TLR4) antagonist by competing for the binding site of MD2, an indispensable protein for lipopolysaccharide (LPS)–TLR4 interaction signaling, on the TLR4 structure. Moreover, compared to the full-length PLY, C70PLY4 seems to have no cytotoxicity in human vascular endothelial cells. Our study elucidated a possible therapeutic efficacy of C70PLY4 in reducing chronic inflammatory conditions and clarified the underlying mechanism. Thus, our findings identify a new drug candidate that, by blocking TLR4 activity, could be an effective treatment for patients with chronic inflammatory diseases.
TFEB Modulates p21/WAF1/CIP1 during the DNA Damage Response
Authors: Pisonero-Vaquero Sandra , Soldati Chiara , Cesana Marcella , Ballabio Andrea , Medina Diego Luis
Published: May 2020

The MiT/TFE family of transcription factors (MITF, TFE3, and TFEB), which control transcriptional programs for autophagy and lysosome biogenesis have emerged as regulators of energy metabolism in cancer. Thus, their activation increases lysosomal catabolic function to sustain cancer cell growth and survival in stress conditions. Here, we found that TFEB depletion dramatically reduces basal expression levels of the cyclin-dependent kinase (CDK) inhibitor p21/WAF1 in various cell types. Conversely, TFEB overexpression increases p21 in a p53-dependent manner. Furthermore, induction of DNA damage using doxorubicin induces TFEB-mediated activation of p21, delays G2/M phase arrest, and promotes cell survival. Pharmacological inhibition of p21, instead, abrogates TFEB-mediated protection during the DNA damage response. Together, our findings uncover a novel and direct role of TFEB in the regulation of p21 expression in both steady-state conditions and during the induction of DNA-damage response (DDR). Our observations might open novel therapeutic strategies to promote cancer cell death by targeting the TFEB-p21 pathway in the presence of genotoxic agents.
Genome-Wide Transcriptomic Analysis Identifies Pathways Regulated by Sterculic Acid in Retinal Pigmented Epithelium Cells
Authors: Pariente Ana , Pérez-Sala Álvaro , Ochoa Rodrigo , Peláez Rafael , Larráyoz Ignacio M.
Published: May 2020

In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is a cyclopropene fatty acid with numerous biological activities, generally attributed to its Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently of SCD inhibition, may be mediating anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD), but the mechanisms involved are poorly understood. In order to provide insights into those mechanisms, genome-wide transcriptomic analyses were carried out in mRPE cells exposed to SA for 24 h. Integrative functional enrichment analysis of genome-wide expression data provided biological insight about the protective mechanisms induced by SA. On the one hand, pivotal genes related to fatty acid biosynthesis, steroid biosynthesis, cell death, actin-cytoskeleton reorganization and extracellular matrix-receptor interaction were significantly downregulated by exposition to SA. On the other hand, genes related to fatty acid degradation and beta-oxidation were significantly upregulated. In conclusion, SA administration to RPE cells regulates crucial pathways related to cell proliferation, inflammation and cell death that may be of interest for the treatment of ocular diseases.
Increasing the Duration of Light Physical Activity Ameliorates Insulin Resistance Syndrome in Metabolically Healthy Obese Adults
Authors: Al-Rashed Fatema , Alghaith Abdulwahab , Azim Rafaat , AlMekhled Dawood , Thomas Reeby , Sindhu Sardar , Ahmad Rasheed
Published: May 2020

Obesity is a well-known risk factor for insulin resistance syndrome (IRS). Nevertheless, limited data are available regarding the effects of physical activity (PA) intensity on the ability to modulate IRS. The study aim was to investigate the beneficial effects of the longer duration of light PA vs. a single bout of the acute moderate or vigorous PA for improvement in IRS indicators. Sixty metabolically healthy obese (MHO) participants, 30 males and 30 females, with body mass index (BMI) of ≥30 were enrolled in this study. PA levels were measured using an accelerometer, and the expression of monocytic surface markers was analyzed using flow cytometry. Plasma cytokines’ secretion was determined by enzyme-linked immunosorbent assay (ELISA). Univariate regression analysis evaluated the actigraphy-assessed PA measures, inflammatory cytokines, and insulin resistance. The longer duration of PA was found to be associated with the homeostatic model assessment of insulin resistance (HOMA-IR), a lower lipid profile, and the expression of inflammatory cytokines by monocytes. Even though, higher intensities of PA were found to be associated with lower body fat percentage, only the light intensity PA was found to be beneficial as it associated with the improved insulin sensitivity and lower expression of inflammatory markers. In conclusion, maintaining the longer duration of low-intensity PA throughout the day could be more beneficial for reducing inflammation and improving insulin resistance. This study supports a more feasible approach model to gain beneficial lifestyle changes for the prevention of IRS in metabolically healthy adults with obesity.
MMTR/Dmap1 Sets the Stage for Early Lineage Commitment of Embryonic Stem Cells by Crosstalk with PcG Proteins
Authors: Lee Young Jin , Son Seung Han , Lim Chang Su , Kim Min Young , Lee Si Woo , Lee Sangwon , Jeon Jinseon , Ha Dae Hyun , Jung Na Rae , Han Su Youne , Do Byung-Rok , Na Insung , Uversky Vladimir N. , Kim Chul Geun
Published: May 2020

Chromatin remodeling, including histone modification, chromatin (un)folding, and nucleosome remodeling, is a significant transcriptional regulation mechanism. By these epigenetic modifications, transcription factors and their regulators are recruited to the promoters of target genes, and thus gene expression is controlled through either transcriptional activation or repression. The Mat1-mediated transcriptional repressor (MMTR)/DNA methyltransferase 1 (DNMT1)-associated protein (Dmap1) is a transcription corepressor involved in chromatin remodeling, cell cycle regulation, DNA double-strand break repair, and tumor suppression. The Tip60-p400 complex proteins, including MMTR/Dmap1, interact with the oncogene Myc in embryonic stem cells (ESCs). These proteins interplay with the stem cell-related proteome networks and regulate gene expressions. However, the detailed mechanisms of their functions are unknown. Here, we show that MMTR/Dmap1, along with other Tip60-p400 complex proteins, bind the promoters of differentiation commitment genes in mouse ESCs. Hence, MMTR/Dmap1 controls gene expression alterations during differentiation. Furthermore, we propose a novel mechanism of MMTR/Dmap1 function in early stage lineage commitment of mouse ESCs by crosstalk with the polycomb group (PcG) proteins. The complex controls histone mark bivalency and transcriptional poising of commitment genes. Taken together, our comprehensive findings will help better understand the MMTR/Dmap1-mediated transcriptional regulation in ESCs and other cell types.
Super-Resolution Localisation of Nuclear PI(4)P and Identification of Its Interacting Proteome
Authors: Fáberová Veronika , Kalasová Ilona , Krausová Alžběta , Hozák Pavel
Published: May 2020

Phosphoinositides are glycerol-based phospholipids, and they play essential roles in cellular signalling, membrane and cytoskeletal dynamics, cell movement, and the modulation of ion channels and transporters. Phosphoinositides are also associated with fundamental nuclear processes through their nuclear protein-binding partners, even though membranes do not exist inside of the nucleus. Phosphatidylinositol 4-phosphate (PI(4)P) is one of the most abundant cellular phosphoinositides; however, its functions in the nucleus are still poorly understood. In this study, we describe PI(4)P localisation in the cell nucleus by super-resolution light and electron microscopy, and employ immunoprecipitation with a specific anti-PI(4)P antibody and subsequent mass spectrometry analysis to determine PI(4)P’s interaction partners. We show that PI(4)P is present at the nuclear envelope, in nuclear lamina, in nuclear speckles and in nucleoli and also forms multiple small foci in the nucleoplasm. Nuclear PI(4)P undergoes re-localisation to the cytoplasm during cell division; it does not localise to chromosomes, nucleolar organising regions or mitotic interchromatin granules. When PI(4)P and PI(4,5)P2 are compared, they have different nuclear localisations during interphase and mitosis, pointing to their functional differences in the cell nucleus. Mass spectrometry identified hundreds of proteins, including 12 potentially novel PI(4)P interactors, most of them functioning in vital nuclear processes such as pre-mRNA splicing, transcription or nuclear transport, thus extending the current knowledge of PI(4)P’s interaction partners. Based on these data, we propose that PI(4)P also plays a role in essential nuclear processes as a part of protein–lipid complexes. Altogether, these observations provide a novel insight into the role of PI(4)P in nuclear functions and provide a direction for further investigation.
The Connection of Azole Fungicides with Xeno-Sensing Nuclear Receptors, Drug Metabolism and Hepatotoxicity
Authors: Marx-Stoelting Philip , Knebel Constanze , Braeuning Albert
Published: May 2020

Azole fungicides, especially triazole compounds, are widely used in agriculture and as pharmaceuticals. For a considerable number of agricultural azole fungicides, the liver has been identified as the main target organ of toxicity. A number of previous studies points towards an important role of nuclear receptors such as the constitutive androstane receptor (CAR), the pregnane-X-receptor (PXR), or the aryl hydrocarbon receptor (AHR), within the molecular pathways leading to hepatotoxicity of these compounds. Nuclear receptor-mediated hepatic effects may comprise rather adaptive changes such as the induction of drug-metabolizing enzymes, to hepatocellular hypertrophy, histopathologically detectable fatty acid changes, proliferation of hepatocytes, and the promotion of liver tumors. Here, we present a comprehensive review of the current knowledge of the interaction of major agricultural azole-class fungicides with the three nuclear receptors CAR, PXR, and AHR in vivo and in vitro. Nuclear receptor activation profiles of the azoles are presented and related to histopathological findings from classic toxicity studies. Important issues such as species differences and multi-receptor agonism and the consequences for data interpretation and risk assessment are discussed.
Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain
Authors: Cao Tuoxin , Matyas Jessica J. , Renn Cynthia L. , Faden Alan I. , Dorsey Susan G. , Wu Junfang
Published: May 2020

Brain-derived neurotrophic factor (BDNF), a major focus for regenerative therapeutics, has been lauded for its pro-survival characteristics and involvement in both development and recovery of function within the central nervous system (CNS). However, studies of tyrosine receptor kinase B (TrkB), a major receptor for BDNF, indicate that certain effects of the TrkB receptor in response to disease or injury may be maladaptive. More specifically, imbalance among TrkB receptor isoforms appears to contribute to aberrant signaling and hyperpathic pain. A truncated isoform of the receptor, TrkB.T1, lacks the intracellular kinase domain of the full length receptor and is up-regulated in multiple CNS injury models. Such up-regulation is associated with hyperpathic pain, and TrkB.T1 inhibition reduces neuropathic pain in various experimental paradigms. Deletion of TrkB.T1 also limits astrocyte changes in vitro, including proliferation, migration, and activation. Mechanistically, TrkB.T1 is believed to act through release of intracellular calcium in astrocytes, as well as through interactions with neurotrophins, leading to cell cycle activation. Together, these studies support a potential role for astrocytic TrkB.T1 in hyperpathic pain and suggest that targeted strategies directed at this receptor may have therapeutic potential.
TNF-α Pretreatment Improves the Survival and Function of Transplanted Human Neural Progenitor Cells Following Hypoxic-Ischemic Brain Injury
Authors: Kim Miri , Jung Kwangsoo , Ko Younhee , Kim Il-Sun , Hwang Kyujin , Jang Jae-Hyung , Shin Jeong Eun , Park Kook In
Published: May 2020

Neural progenitor cells (NPCs) therapy offers great promise in hypoxic-ischemic (HI) brain injury. However, the poor survival of implanted NPCs in the HI host environment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that is induced in response to a variety of pathological processes including inflammation and immunity. On the other hand, TNF-α has protective effects on cell apoptosis and death and affects the differentiation, proliferation, and survival of neural stem/progenitor cells in the brain. The present study investigated whether TNF-α pretreatment on human NPCs (hNPCs) enhances the effectiveness of cell transplantation therapy under ischemic brain. Fetal brain tissue-derived hNPCs were pretreated with TNF-α before being used in vitro experiments or transplantation. TNF-α significantly increased expression of cIAP2, and the use of short hairpin RNA-mediated knockdown of cIAP2 demonstrated that cIAP2 protected hNPCs against HI-induced cytotoxicity. In addition, pretreatment of hNPCs with TNF-α mediated neuroprotection by altering microglia polarization via increased expression of CX3CL1 and by enhancing expression of neurotrophic factors. Furthermore, transplantation of TNF-α-treated hNPCs reduced infarct volume and improved neurological functions in comparison with non-pretreated hNPCs or vehicle. These findings show that TNF-α pretreatment, which protects hNPCs from HI-injured brain-induced apoptosis and increases neuroprotection, is a simple and safe approach to improve the survival of transplanted hNPCs and the therapeutic efficacy of hNPCs in HI brain injury.
Differences in the Corrosive Spalling Behavior of Alumina-Rich Castables: Microstructural and Crystallographic Considerations of Alumina and Calcium Aluminate Matrices
Authors: Loison Lise , Sassi Mouna , Tonnesen Thorsten , De Bilbao Emmanuel , Telle Rainer , Poirier Jacques
Published: May 2020

The energy transition from the incineration and gasification of fossil fuels to the incineration and gasification of biomass refractory linings is being held up by a severe corrosion issue, caused by high alkali contents and the wide variety of biomass sources. Incinerators optimized for fossil fuels are commonly lined with mullite, Al2O3-Cr or SiC-based refractory products; however, those materials are not always suitable for the use of organic fuels. Hibonite (CaO·6Al2O3)-based refractory products have shown promising performance because of their high resistance against alkali attacks. Indeed, previous works have shown that the reaction between calcium hexa-aluminate and an alkali does not lead to the strong volume expansion observed with other mineral phases, such as corundum or andalusite. The present work aims to describe the reactions kinetics occurring between hibonite-based raw materials and biomass ashes. Therefore, the three main oxides contained in an average biomass, namely, CaO, SiO2 and K2O, were selected to examine the high temperature reactions with a calcium hexa-aluminate matrix. The resulting phase composition and microstructure were compared with the performance of an alumina matrix through, respectively, X-ray diffraction (XRD) analysis and scanning electron microscopy (SEM). The post-mortem observations show a higher extent of reaction for the alumina than for the calcium hexa-aluminate. Moreover, the microstructure of the alumina matrix suffered a strong chemical spalling, while the calcium hexa-aluminate microstructure remained undamaged after the corrosion.
Oxidative Repair of Pyrimidine Cyclobutane Dimers by Nitrate Radicals (NO3•): A Kinetic and Computational Study
Authors: Haddad Tomas , Nathanael Joses , White Jonathan , Wille Uta
Published: May 2020

Pyrimidine cyclobutane dimers are hazardous DNA lesions formed upon exposure of DNA to UV light, which can be repaired through oxidative electron transfer (ET). Laser flash photolysis and computational studies were performed to explore the role of configuration and constitution at the cyclobutane ring on the oxidative repair process, using the nitrate radical (NO3•) as oxidant. The rate coefficients of 8–280 × 107 M−1 s−1 in acetonitrile revealed a very high reactivity of the cyclobutane dimers of N,N’-dimethylated uracil (DMU), thymine (DMT), and 6-methyluracil (DMU6-Me) towards NO3•, which likely proceeds via ET at N(1) as a major pathway. The overall rate of NO3• consumption was determined by (i) the redox potential, which was lower for the syn- than for the anti-configured dimers, and (ii) the accessibility of the reaction site for NO3•. In the trans dimers, both N(1) atoms could be approached from above and below the molecular plane, whereas in the cis dimers, only the convex side was readily accessible for NO3•. The higher reactivity of the DMT dimers compared with isomeric DMU dimers was due to the electron-donating methyl groups on the cyclobutane ring, which increased their susceptibility to oxidation. On the other hand, the approach of NO3• to the dimers of DMU6-Me was hindered by the methyl substituents adjacent to N(1), making these dimers the least reactive in this series.
Optical Chemosensors and Biosensors
Authors: Giannetti Ambra , Bocková Markéta
Published: May 2020

The field of chemo- and biosensors, ranging from biomedical/clinical applications to environmental applications and food analyses, has been growing in the last two decades [...]
A Sensitive Impedimetric Sensor Based on Biosourced Polyphosphine Films for the Detection of Lead Ions
Authors: Chabbah Taha , Abderrazak Houyem , Souissi Radhia , Saint-Martin Patrice , Casabianca Herve , Chatti Saber , Mercier Regis , Rassas Ilhem , Errachid Abdelhamid , Hammami Mohamed , Jaffrezic-Renault Nicole
Published: May 2020

In this work, impedimetric sensors were developed for the detection of the four WFD heavy metals Pb2+, Cd2+, Hg2+ and Ni2+, by the modification of a gold electrode with four partially biosourced polyphosphine polymers. These polymers were obtained with satisfactory yields by polycondensation of the bis(4-fluorophenyl)(4-methylphenyl)phosphine sulfide and the bis(4-fluorophenyl)(4-methylphenyl)phosphine oxide using isosorbide or bisphenol A. The chemical structures and number-average molecular weights of the resulting polymers were determined by NMR spectroscopy (1H, 19F, and 31P) and by size exclusion chromatography. Glass transition temperatures varied between 184 and 202 °C depending on the composition of polymers. The bio-based poly(etherphosphine) oxide modified sensor showed better analytical performance than petrochemical based oxide for the detection of Pb2+. A detection limit of 10−10 g/L or 0.5 pM, which is 104 times lower than that of the anodic stripping voltammetric and the potentiometric sensors. A reversibility is obtained through rinsing of the impedimetric sensor with an EDTA solution.
Parental Educational Attainment and Social Environment of Urban Public Schools in the U.S.: Blacks’ Diminished Returns
Authors: Boyce Shanika , Bazargan Mohsen , Caldwell Cleopatra H. , Zimmerman Marc A. , Assari Shervin
Published: May 2020

Background: Recent research has documented marginalization-related diminished returns (MDRs) of socioeconomic status (SES), defined as weaker effects of SES indicators, such as parental educational attainment, on securing tangible outcomes for the members of socially marginalized (e.g., racial and ethnic minority) groups, compared to privileged social groups (e.g., non-Hispanic Whites). Aims: To explore race/ethnic differences between non-Hispanic Blacks vs. non-Hispanic Whites who attend urban public schools on the effect of parental education on lower school environmental risk among American high schoolers. Methods: For this cross-sectional study, we borrowed the Education Longitudinal Study (ELS-2002) baseline data, a nationally representative study that enrolled 1706 10th grade youths who were attending urban public schools. From this number, 805 (47.2%) were non-Hispanic Black and 901 (52.8%) were non-Hispanic White youths. The dependent variable was the level of school social environmental risk measured using 18 items as self-reported, and was treated as a continuous variable. The independent variable was parental educational attainment, treated as a continuous measure. Gender, region, and parental marital status were the covariates. Race/ethnicity was the moderating variable. Linear regressions were applied to perform our data analysis. Results: Black students were found to attend schools with higher levels of social environmental risk. Youths with parents with a higher educational attainment were found to attend schools with a lower social environmental risk. We found a significant interaction between race (non-Hispanic Black vs. non-Hispanic White) and parental educational attainment on the level of school social environmental risk, suggesting that the protective effect of high parental education on reducing the school social environmental risk was smaller for non-Hispanic Black than for non-Hispanic White youths. Conclusions: Although high parental educational attainment is protective against social environmental risk for American youths, this protective effect is weaker for non-Hispanic Black than non-Hispanic White youths. The diminished returns of parental education in reducing school social environmental risk may explain why the effects of parental education on educational outcomes are smaller for non-Hispanic Black than non-Hispanic White youths (i.e., MDRs). The social environment indirectly generates racial youth educational disparities through deteriorating non-Hispanic Black youth educational outcomes across all SES levels. To prevent the confounding effects of private, suburban, rural, and Catholic schools, we limited this analysis to public urban schools. More research is needed on other settings.
Parental Attachment Patterns in Mothers of Children with Anxiety Disorder
Authors: Karayağız Şaban , Aktan Timuçin , Karayağız Lider Zeynep
Published: May 2020

Anxiety disorder on of the most common illnesses in the context of psychiatry. Potential causes include genetic and environmental factors, as well as the parental attachment of the individuals. The purpose of this study is to examine the relationship between parental attachment style and anxiety disorders for a group of children and their parents. Study data were collected from the mothers (N = 40) of children with an anxiety disorder who visited a child psychiatry outpatient clinic at a city hospital and a private institution in Kayseri (Turkey) in 2018. For the control group, 40 mothers of children without any mental illness were also included in the study. The purposive sampling method was used in the selection of the participants for both groups (experimental and control). Sociodemographic data sheet and parental bonding instrument (PBI) were utilized as the data collection instruments. Then, data were analyzed based on the descriptive analysis methodology that included mean scores, standard deviation, p-value, t-experimental, two-way ANOVA and Pearson correlation experiments by using SPSS v.22. The findings revealed that the mothers of the participants with a college degree in the experimental group had fewer perceptions of protection (t = 2.38, p < 0.01), but more perception of care from their mothers than fathers (t =−2.28, p < 0.05). In addition, although the perceived care of parents was found lower than the participants in the control group, the participants in both groups evaluated their parents analogously for overprotection. Findings showed that the mothers in the experimental group predominantly described their parents as neglecting.
Peptide-Based Formulation from Lactic Acid Bacteria Impairs the Pathogen Growth in Ananas Comosus (Pineapple)
Authors: Tenea Gabriela N. , Olmedo Daniela , Ortega Clara
Published: May 2020

Worldwide, street vending commerce has grown exponentially, representing in some countries, including Ecuador, a significant proportion of food consumed by the urban population. Pineapple is one of the common fruits sold as ready-to-eat slices by ambulant vendors in the street or on public transport at risk of contamination by various microorganisms. Previously, we selected Lactobacillus plantarum UTNCys5-4 and Lactococcus lactis subsp. lactis Gt28 strains producing peptides with high capacity to inhibit pathogen growth in vitro. In this study, the effect of different edited formulations containing a mixture of Cys5-4/Gt28 peptides was evaluated in vitro and ex vitro against a pathogenic cocktail containing E. coli (2), Salmonella (2) and Shigella (1). The growth of bacterial cocktail co-inoculated with cell-free supernatant containing peptides (formulation T1) and precipitated peptides (formulation T6), in a ratio of Cys5-4/Gt28:1:1 (v/v), results in a decrease of total cell viability with 1.85 and 1.2 log CFU/mL orders of magnitude at 6 h of incubation. About the same decrease (1.9 log CFU/g) was observed when pineapple slices artificially inoculated with the pathogenic cocktail were coated with T1 formulation, indicating the capacity to diminish simultaneous pathogens in situ, thus demonstrating its great biological control and protection. However, the E. coli cell counts reduced by 2.08 log CFU/g while Salmonella and Shigella cell counts reduced by 1.43 and 1.91 log CFU/g, respectively, at 5 days of refrigeration. In the untreated pineapple slices, the total cell density was maintained during storage, suggesting the adaptation of the pathogens to the fruit matrix. The peptide-based formulation exerted a bacteriolytic mode of action inducing pathogenic cell death. The results indicate that coating pineapple slices with peptide-based formulation is a promising approach to protect them from further contamination by microbial spoilage as well as an alternative to increase the food safety.
Amphiphilic Poly(vinyl Alcohol) Copolymers Designed for Optical Sensor Applications—Synthesis and Properties
Authors: Lazarova Katerina , Bozhilova Silvia , Novakov Christo , Christova Darinka , Babeva Tsvetanka
Published: May 2020

A possible approach for enhancement of Poly(vinyl alcohol) (PVA) humidity-sensing performance using hydrophobically modified PVA copolymers is studied. Series of poly(vinylalcohol-co-vinylacetal)s (PVA–Ac) of acetal content in the range 18%–28% are synthesized by partial acetalization of hydroxyl groups of PVA with acetaldehyde and thin films are deposited by spin-coating using silicon substrates and glass substrates covered with Au–Pd thin film with thickness of 30 nm. Sensing properties are probed through reflectance measurements at relative humidity (RH) in the range 5%–95% RH. The influence of film thickness, post-deposition annealing temperature, and substrate type/configuration on hysteresis, sensitivity, and accuracy/resolution of humidity sensing is studied for partially acetalized PVA copolymer films, and comparison with neat PVA is made. Enhancement of sensing behavior through preparation of polymer–silica hybrids is demonstrated. The possibility of color sensing is discussed.
Biomimetic Coatings Obtained by Combinatorial Laser Technologies
Authors: Axente Emanuel , Elena Sima Livia , Sima Felix
Published: May 2020

The modification of implant devices with biocompatible coatings has become necessary as a consequence of premature loosening of prosthesis. This is caused mainly by chronic inflammation or allergies that are triggered by implant wear, production of abrasion particles, and/or release of metallic ions from the implantable device surface. Specific to the implant tissue destination, it could require coatings with specific features in order to provide optimal osseointegration. Pulsed laser deposition (PLD) became a well-known physical vapor deposition technology that has been successfully applied to a large variety of biocompatible inorganic coatings for biomedical prosthetic applications. Matrix assisted pulsed laser evaporation (MAPLE) is a PLD-derived technology used for depositions of thin organic material coatings. In an attempt to surpass solvent related difficulties, when different solvents are used for blending various organic materials, combinatorial MAPLE was proposed to grow thin hybrid coatings, assembled in a gradient of composition. We review herein the evolution of the laser technological process and capabilities of growing thin bio-coatings with emphasis on blended or multilayered biomimetic combinations. These can be used either as implant surfaces with enhanced bioactivity for accelerating orthopedic integration and tissue regeneration or combinatorial bio-platforms for cancer research.