bluuebunny/crossref_metadata_2025 huggingface dataset:
Waterpipe Tobacco Smoke Inhalation Triggers Thrombogenicity, Cardiac Inflammation and Oxidative Stress in Mice: Effects of Flavouring
Authors: Nemmar Abderrahim , Al-Salam Suhail , Beegam Sumaya , Yuvaraju Priya , Zaaba Nur Elena , Yasin Javed , Ali Badreldin H.
Published: February 2020

The consumption of water-pipe smoking (WPS) has been promoted by the use of flavoured tobacco. However, little is known about the impact of flavouring on the cardiovascular toxicity induced by WPS inhalation. Here, we compared the cardiovascular effects and underlying mechanism of actions of plain (P) (unflavoured) versus apple-flavoured (AF) WPS (30 minutes/day, 5 days/week for 1 month) in mice. Control mice were exposed to air. Both P- and AF-WPS inhalation induced an increase in systolic blood pressure, thrombogenicity and plasma concentration of fibrinogen and von Willebrand factor. In heart homogenates, AF-WPS inhalation caused an increase of 8-isoprostane and a decrease in the levels of reduced glutathione (GSH) and superoxide dismutase (SOD). Nevertheless, P-WPS decreased only the activity of SOD. The concentrations of tumour necrosis factor α and interleukin 1β were increased only in heart homogenates of mice exposed to AF-WPS. Although both P- and AF-WPS increased the concentration of troponin I in heart homogenates and induced DNA damage, the concentration of cleaved caspase 3 was only increased in mice exposed to AF-WPS. Immunohistochemical analysis of the hearts showed that both P- and AF- WPS inhalation decreased the expression of SOD. Moreover, the expression of nuclear factor erythroid-derived 2-like 2 at nuclear level in the heart was higher in both AF-WPS and P-WPS compared with control group, and the effect observed in AF-WPS group was more significant than that seen in P-WPS group. Likewise, the concentration of heme oxygenase-1 was significantly increased in both P-WPS and AF-WPS groups compared with control group, and the effect seen in AF-group was higher than that observed in P-WPS group. In conclusion, our findings showed that both P- and AF-WPS induce thrombogenicity and cardiac injury, and that this toxicity is potentiated by the presence of flavouring.
Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing
Authors: Mazini Loubna , Rochette Luc , Admou Brahim , Amal Said , Malka Gabriel
Published: February 2020

Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.
High-Density Lipoprotein (HDL) Inhibits Serum Amyloid A (SAA)-Induced Vascular and Renal Dysfunctions in Apolipoprotein E-Deficient Mice
Authors: Cai Xiaoping , Ahmad Gulfam , Hossain Farjaneh , Liu Yuyang , Wang XiaoSuo , Dennis Joanne , Freedman Ben , Witting Paul K.
Published: February 2020

Serum amyloid A (SAA) promotes endothelial inflammation and dysfunction that is associated with cardiovascular disease and renal pathologies. SAA is an apoprotein for high-density lipoprotein (HDL) and its sequestration to HDL diminishes SAA bioactivity. Herein we investigated the effect of co-supplementing HDL on SAA-mediated changes to vascular and renal function in apolipoprotein E-deficient (ApoE−/−) mice in the absence of a high-fat diet. Male ApoE−/− mice received recombinant human SAA or vehicle (control) by intraperitoneal (i.p.) injection every three days for two weeks with or without freshly isolated human HDL supplemented by intravenous (i.v.) injection in the two weeks preceding SAA stimulation. Aorta and kidney were harvested 4 or 18 weeks after commencement of treatment. At 4 weeks after commencement of treatment, SAA increased aortic vascular cell adhesion molecule (VCAM)-1 expression and F2-isoprostane level and decreased cyclic guanosine monophosphate (cGMP), consistent with SAA stimulating endothelial dysfunction and promoting atherosclerosis. SAA also stimulated renal injury and inflammation that manifested as increased urinary protein, kidney injury molecule (KIM)-1, and renal tissue cytokine/chemokine levels as well as increased protein tyrosine chlorination and P38 MAPkinase activation and decreased in Bowman’s space, confirming that SAA elicited a pro-inflammatory phenotype in the kidney. At 18 weeks, vascular lesions increased significantly in the cohort of ApoE−/− mice treated with SAA alone. By contrast, pretreatment of mice with HDL decreased SAA pro-inflammatory activity, inhibited SAA enhancement of aortic lesion size and renal function, and prevented changes to glomerular Bowman’s space. Taken together, these data indicate that supplemented HDL reduces SAA-mediated endothelial and renal dysfunction in an atherosclerosis-prone mouse model.
Doxorubicin Inhibits Phosphatidylserine Decarboxylase and Modifies Mitochondrial Membrane Composition in HeLa Cells
Authors: Bellance Nadège , Furt Fabienne , Melser Su , Lalou Claude , Thoraval Didier , Maneta-Peyret Lilly , Lacombe Didier , Moreau Patrick , Rossignol Rodrigue
Published: February 2020

Doxorubicin (DXR) is a drug widely used in chemotherapy. Its mode of action is based on its intercalation properties, involving the inhibition of topoisomerase II. However, few studies have reported the mitochondrial effects of DXR while investigating cardiac toxicity induced by the treatment, mostly in pediatric cases. Here, we demonstrate that DXR alters the mitochondrial membrane composition associated with bioenergetic impairment and cell death in human cancer cells. The remodeling of the mitochondrial membrane was explained by phosphatidylserine decarboxylase (PSD) inhibition by DXR. PSD catalyzes phosphatidylethanolamine (PE) synthesis from phosphatidylserine (PS), and DXR altered the PS/PE ratio in the mitochondrial membrane. Moreover, we observed that DXR localized to the mitochondrial compartment and drug uptake was rapid. Evaluation of other topoisomerase II inhibitors did not show any impact on the mitochondrial membrane composition, indicating that the DXR effect was specific. Therefore, our findings revealed a side molecular target for DXR and PSD, potentially involved in DXR anti-cancer properties and the associated toxicity.
A Wheat WRKY Transcription Factor TaWRKY46 Enhances Tolerance to Osmotic Stress in transgenic Arabidopsis Plants
Authors: Li Xiaorui , Tang Yan , Zhou Chunju , Zhang Lixin , Lv Jinyin
Published: February 2020

WRKY transcription factors play central roles in developmental processes and stress responses of wheat. Most WRKY proteins of the same group (Group III) have a similar function in abiotic stress responses in plants. TaWRKY46, a member of Group III, was up-regulated by PEG treatment. TaWRKY46-GFP fusion proteins localize to the nucleus in wheat mesophyll protoplasts. Overexpression of TaWRKY46 enhanced osmotic stress tolerance in transgenic Arabidopsis thaliana plants, which was mainly demonstrated by transgenic Arabidopsis plants forming higher germination rate and longer root length on 1/2 Murashige and Skoog (MS) medium containing mannitol. Furthermore, the expression of several stress-related genes (P5CS1, RD29B, DREB2A, ABF3, CBF2, and CBF3) was significantly increased in TaWRKY46-overexpressing transgenic Arabidopsis plants after mannitol treatment. Taken together, these findings proposed that TaWRKY46 possesses vital functions in improving drought tolerance through ABA-dependent and ABA-independent pathways when plants are exposed to adverse osmotic conditions. TaWRKY46 can be taken as a candidate gene for transgenic breeding against osmotic stress in wheat. It can further complement and improve the information of the WRKY family members of Group III.
Overexpression of Grapevine VvIAA18 Gene Enhanced Salt Tolerance in Tobacco
Authors: Li Wei , Dang Changxi , Ye Yuxiu , Wang Zunxin , Hu Laibao , Zhang Fan , Zhang Yang , Qian Xingzhi , Shi Jiabin , Guo Yanyun , Zhou Qing , Wang Tailin , Chen Xinhong , Wang Feibing
Published: February 2020

In plants, auxin/indoleacetic acid (Aux/IAA) proteins are transcriptional regulators that regulate developmental process and responses to phytohormones and stress treatments. However, the regulatory functions of the Vitis vinifera L. (grapevine) Aux/IAA transcription factor gene VvIAA18 have not been reported. In this study, the VvIAA18 gene was successfully cloned from grapevine. Subcellular localization analysis in onion epidermal cells indicated that VvIAA18 was localized to the nucleus. Expression analysis in yeast showed that the full length of VvIAA18 exhibited transcriptional activation. Salt tolerance in transgenic tobacco plants and Escherichia. coli was significantly enhanced by VvIAA18 overexpression. Real-time quantitative PCR analysis showed that overexpression of VvIAA18 up-regulated the salt stress-responsive genes, including pyrroline-5-carboxylate synthase (NtP5CS), late embryogenesis abundant protein (NtLEA5), superoxide dismutase (NtSOD), and peroxidase (NtPOD) genes, under salt stress. Enzymatic analyses found that the transgenic plants had higher SOD and POD activities under salt stress. Meanwhile, component analysis showed that the content of proline in transgenic plants increased significantly, while the content of hydrogen peroxide (H2O2) and malondialdehyde (MDA) decreased significantly. Based on the above results, the VvIAA18 gene is related to improving the salt tolerance of transgenic tobacco plants. The VvIAA18 gene has the potential to be applied to enhance plant tolerance to abiotic stress.
Direct Interaction between Calmodulin and the Grb7 RA-PH Domain
Authors: Watson Gabrielle M. , Wilce Jacqueline A.
Published: February 2020

Grb7 is a signalling adapter protein that engages activated receptor tyrosine kinases at cellular membranes to effect downstream pathways of cell migration, proliferation and survival. Grb7’s cellular location was shown to be regulated by the small calcium binding protein calmodulin (CaM). While evidence for a Grb7/CaM interaction is compelling, a direct interaction between CaM and purified Grb7 has not been demonstrated and quantitated. In this study we sought to determine this, and prepared pure full-length Grb7, as well as its RA-PH and SH2 subdomains, and tested for CaM binding using surface plasmon resonance. We report a direct interaction between full-length Grb7 and CaM that occurs in a calcium dependent manner. While no binding was observed to the SH2 domain alone, we observed a high micromolar affinity interaction between the Grb7 RA-PH domain and CaM, suggesting that the Grb7/CaM interaction is mediated through this region of Grb7. Together, our data support the model of a CaM interaction with Grb7 via its RA-PH domain.
Genomic Prediction for Grain Yield and Yield-Related Traits in Chinese Winter Wheat
Authors: Ali Mohsin , Zhang Yong , Rasheed Awais , Wang Jiankang , Zhang Luyan
Published: February 2020

Genomic selection (GS) is a strategy to predict the genetic merits of individuals using genome-wide markers. However, GS prediction accuracy is affected by many factors, including missing rate and minor allele frequency (MAF) of genotypic data, GS models, trait features, etc. In this study, we used one wheat population to investigate prediction accuracies of various GS models on yield and yield-related traits from various quality control (QC) scenarios, missing genotype imputation, and genome-wide association studies (GWAS)-derived markers. Missing rate and MAF of single nucleotide polymorphism (SNP) markers were two major factors in QC. Five missing rate levels (0%, 20%, 40%, 60%, and 80%) and three MAF levels (0%, 5%, and 10%) were considered and the five-fold cross validation was used to estimate the prediction accuracy. The results indicated that a moderate missing rate level (20% to 40%) and MAF (5%) threshold provided better prediction accuracy. Under this QC scenario, prediction accuracies were further calculated for imputed and GWAS-derived markers. It was observed that the accuracies of the six traits were related to their heritability and genetic architecture, as well as the GS prediction model. Moore–Penrose generalized inverse (GenInv), ridge regression (RidgeReg), and random forest (RForest) resulted in higher prediction accuracies than other GS models across traits. Imputation of missing genotypic data had marginal effect on prediction accuracy, while GWAS-derived markers improved the prediction accuracy in most cases. These results demonstrate that QC on missing rate and MAF had positive impact on the predictability of GS models. We failed to identify one single combination of QC scenarios that could outperform the others for all traits and GS models. However, the balance between marker number and marker quality is important for the deployment of GS in wheat breeding. GWAS is able to select markers which are mostly related to traits, and therefore can be used to improve the prediction accuracy of GS.
Inheritance and Molecular Characterization of a Novel Mutated AHAS Gene Responsible for the Resistance of AHAS-Inhibiting Herbicides in Rapeseed (Brassica napus L.)
Authors: Huang Qianxin , Lv Jinyang , Sun Yanyan , Wang Hongmei , Guo Yuan , Qu Gaoping , Hu Shengwu
Published: February 2020

The use of herbicides is an effective and economic way to control weeds, but their availability for rapeseed is limited due to the shortage of herbicide-resistant cultivars in China. The single-point mutation in the acetohydroxyacid synthase (AHAS) gene can lead to AHAS-inhibiting herbicide resistance. In this study, the inheritance and molecular characterization of the tribenuron-methyl (TBM)-resistant rapeseed (Brassica napus L.) mutant, K5, are performed. Results indicated that TBM-resistance of K5 was controlled by one dominant allele at a single nuclear gene locus. The novel substitution of cytosine with thymine at position 544 in BnAHAS1 was identified in K5, leading to the alteration of proline with serine at position 182 in BnAHAS1. The TBM-resistance of K5 was approximately 100 times that of its wild-type ZS9, and K5 also showed cross-resistance to bensufuron-methyl and monosulfuron-ester sodium. The BnAHAS1544T transgenic Arabidopsis exhibited higher TBM-resistance than that of its wild-type, which confirmed that BnAHAS1544T was responsible for the herbicide resistance of K5. Simultaneously, an allele-specific marker was developed to quickly distinguish the heterozygous and homozygous mutated alleles BnAHAS1544T. In addition, a method for the fast screening of TBM-resistant plants at the cotyledon stage was developed. Our research identified and molecularly characterized one novel mutative AHAS allele in B. napus and laid a foundation for developing herbicide-resistant rapeseed cultivars.
Iron Overload Mimicking Conditions Skews Bone Marrow Dendritic Cells Differentiation into MHCIIlowCD11c+CD11b+F4/80+ Cells
Authors: Verna Giulio , Liso Marina , De Santis Stefania , Dicarlo Manuela , Cavalcanti Elisabetta , Crovace Alberto , Sila Annamaria , Campiglia Pietro , Santino Angelo , Lippolis Antonio , Serino Grazia , Fasano Alessio , Chieppa Marcello
Published: February 2020

Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c+MHCIIhi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, cells cultured in iron-enriched conditions show increased ARG1 and PU.1, and decreased IRF8 expression.
Expression and In Vitro Function of Anti-Breast Cancer Llama-Based Single Domain Antibody VHH Expressed in Tobacco Plants
Authors: Park Se Ra , Lee Jeong-Hwan , Kim Kibum , Kim Taek Min , Lee Seung Ho , Choo Young-Kug , Kim Kyung Soo , Ko Kisung
Published: February 2020

Overexpression of human epidermal growth factor receptor type 2 (HER2) is considered as a prognostic factor of breast cancer, which is positively associated with recurrence when cancer metastasizes to the lymph nodes. Here, we expressed the single variable domain on a heavy chain (VHH) form of anti-HER2 camelid single domain antibody in tobacco plants and compared its in vitro anticancer activities with the anti-HER2 full size antibody. The gene expression cassette containing anti-HER2 camelid single domain antibody VHH fused to human IgG Fc region with KDEL endoplasmic reticulum (ER) (VHH-FcK) was transferred into the tobacco plant via the Agrobacterium-mediated transformation. The transformants were screened with polymerase chain reaction and Western blot analyses. Enzyme-linked immunosorbent assay (ELISA) confirmed the binding of the purified anti-HER2 VHH-FcK to the HER2-positive breast cancer cell line, SK-BR-3. Migration assay results confirmed anticancer activity of the plant-derived anticancer camelid single chain antibody. Taken together, we confirmed the possibility of using anti-HER2 VHH-FcK as a therapeutic anticancer agent, which can be expressed and assembled and purified from a plant expression system as an alternative antibody production system.
Tinkering Cis Motifs Jigsaw Puzzle Led to Root-Specific Drought-Inducible Novel Synthetic Promoters
Authors: Jameel Aysha , Noman Muhammad , Liu Weican , Ahmad Naveed , Wang Fawei , Li Xiaowei , Li Haiyan
Published: February 2020

Following an in-depth transcriptomics-based approach, we first screened out and analyzed (in silico) cis motifs in a group of 63 drought-inducible genes (in soybean). Six novel synthetic promoters (SynP14-SynP19) were designed by concatenating 11 cis motifs, ABF, ABRE, ABRE-Like, CBF, E2F-VARIANT, G-box, GCC-Box, MYB1, MYB4, RAV1-A, and RAV1-B (in multiple copies and various combination) with a minimal 35s core promoter and a 222 bp synthetic intron sequence. In order to validate their drought-inducibility and root-specificity, the designed synthetic assemblies were transformed in soybean hairy roots to drive GUS gene using pCAMBIA3301. Through GUS histochemical assay (after a 72 h 6% PEG6000 treatment), we noticed higher glucuronidase activity in transgenic hairy roots harboring SynP15, SynP16, and SynP18. Further screening through GUS fluorometric assay flaunted SynP16 as the most appropriate combination of efficient drought-responsive cis motifs. Afterwards, we stably transformed SynP15, SynP16, and SynP18 in Arabidopsis and carried out GUS staining as well as fluorometric assays of the transgenic plants treated with simulated drought stress. Consistently, SynP16 retained higher transcriptional activity in Arabidopsis roots in response to drought. Thus the root-specific drought-inducible synthetic promoters designed using stimulus-specific cis motifs in a definite fashion could be exploited in developing drought tolerance in soybean and other crops as well. Moreover, the rationale of design extends our knowledge of trial-and-error based cis engineering to construct synthetic promoters for transcriptional upgradation against other stresses.
Zinc Finger Proteins in the Human Fungal Pathogen Cryptococcus neoformans
Authors: Li Yuan-Hong , Liu Tong-Bao
Published: February 2020

Zinc is one of the essential trace elements in eukaryotes and it is a critical structural component of a large number of proteins. Zinc finger proteins (ZNFs) are zinc-finger domain-containing proteins stabilized by bound zinc ions and they form the most abundant proteins, serving extraordinarily diverse biological functions. In recent years, many ZNFs have been identified and characterized in the human fungal pathogen Cryptococcus neoformans, a fungal pathogen causing fatal meningitis mainly in immunocompromised individuals. It has been shown that ZNFs play important roles in the morphological development, differentiation, and virulence of C. neoformans. In this review, we, first, briefly introduce the ZNFs and their classification. Then, we explain the identification and classification of the ZNFs in C. neoformans. Next, we focus on the biological role of the ZNFs functionally characterized so far in the sexual reproduction, virulence factor production, ion homeostasis, pathogenesis, and stress resistance in C. neoformans. We also discuss the perspectives on future function studies of ZNFs in C. neoformans.
The Major Cat Allergen Fel d 1 Binds Steroid and Fatty Acid Semiochemicals: A Combined In Silico and In Vitro Study
Authors: Bienboire-Frosini Cécile , Durairaj Rajesh , Pelosi Paolo , Pageat Patrick
Published: February 2020

The major cat allergen Fel d 1 is a tetrameric glycoprotein of the secretoglobin superfamily. Structural aspects and allergenic properties of this protein have been investigated, but its physiological function remains unclear. Fel d 1 is assumed to bind lipids and steroids like the mouse androgen-binding protein, which is involved in chemical communication, either as a semiochemical carrier or a semiochemical itself. This study focused on the binding activity of a recombinant model of Fel d 1 (rFel d 1) towards semiochemical analogs, i.e., fatty acids and steroids, using both in silico calculations and fluorescence measurements. In silico analyses were first adopted to model the interactions of potential ligands, which were then tested in binding assays using the fluorescent reporter N-phenyl-1-naphthylamine. Good ligands were fatty acids, such as the lauric, oleic, linoleic, and myristic fatty acids, as well as steroids like androstenone, pregnenolone, and progesterone, that were predicted by in silico molecular models to bind into the central and surface cavities of rFel d 1, respectively. The lowest dissociation constants were shown by lauric acid (2.6 µM) and androstenone (2.4 µM). The specific affinity of rFel d 1 to semiochemicals supports a function of the protein in cat’s chemical communication, and highlights a putative role of secretoglobins in protein semiochemistry.
Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction
Authors: Leong Huey Sze , Philp Morgan , Simone Martin , Witting Paul Kenneth , Fu Shanlin
Published: February 2020

Increasing reports of neurological and psychiatric complications due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the precise mechanism of SC toxicity is unclear. This paucity of understanding highlights the need to investigate the in-vitro toxicity and mechanistic pathways of three SCs: butylone, pentylone, and 3,4-Methylenedioxypyrovalerone (MDPV). Human neuronal cells of SH-SY5Y were cultured in supplemented DMEM/F12 media and differentiated to a neuronal phenotype using retinoic acid (10 μM) and 12-O-tetradecanoylphorbol-13-acetate (81 nM). Trypan blue and lactate dehydrogenase assays were utilized to assess the neurotoxicity potential and potency of these three SCs. To investigate the underlying neurotoxicity mechanisms, measurements included markers of oxidative stress, mitochondrial bioenergetics, and intracellular calcium (Ca2+), and cell death pathways were evaluated at two doses (EC15 and EC40), for each drug tested. Following 24 h of treatment, all three SCs exhibited a dose-dependent neurotoxicity, characterized by a significant (p < 0.0001 vs. control) production of reactive oxygen species, decreased mitochondrial bioenergetics, and increased intracellular Ca2+ concentrations. The activation of caspases 3 and 7 implicated the orchestration of mitochondrial-mediated neurotoxicity mechanisms for these SCs. Identifying novel therapeutic agents to enhance an altered mitochondrial function may help in the treatment of acute-neurological complications arising from the illicit use of these SCs.
The ER Unfolded Protein Response Effector, ATF6, Reduces Cardiac Fibrosis and Decreases Activation of Cardiac Fibroblasts
Authors: Stauffer Winston T. , Blackwood Erik A. , Azizi Khalid , Kaufman Randal J. , Glembotski Christopher C.
Published: February 2020

Activating transcription factor-6 α (ATF6) is one of the three main sensors and effectors of the endoplasmic reticulum (ER) stress response and, as such, it is critical for protecting the heart and other tissues from a variety of environmental insults and disease states. In the heart, ATF6 has been shown to protect cardiac myocytes. However, its roles in other cell types in the heart are unknown. Here we show that ATF6 decreases the activation of cardiac fibroblasts in response to the cytokine, transforming growth factor β (TGFβ), which can induce fibroblast trans-differentiation into a myofibroblast phenotype through signaling via the TGFβ–Smad pathway. ATF6 activation suppressed fibroblast contraction and the induction of α smooth muscle actin (αSMA). Conversely, fibroblasts were hyperactivated when ATF6 was silenced or deleted. ATF6 thus represents a novel inhibitor of the TGFβ–Smad axis of cardiac fibroblast activation.
Correlation between Antibodies to Bacterial Lipopolysaccharides and Barrier Proteins in Sera Positive for ASCA and ANCA
Authors: Vojdani Aristo , Vojdani Elroy , Herbert Martha , Kharrazian Datis
Published: February 2020

Individuals with intestinal barrier dysfunction are more prone to autoimmunity. Lipopolysaccharides (LPS) from gut bacteria have been shown to play a role in systemic inflammation, leading to the opening of the gut and blood-brain barrier (BBB). This study aims to measure antibodies against LPS and barrier proteins in samples positive for anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) and compare them with these same antibodies in controls to determine whether a correlation between LPS and barrier proteins could be found. We obtained 94 ASCA- and 94 ANCA-positive blood samples, as well as 188 blood samples from healthy controls. Samples were assessed for antibodies to LPS, zonulin+occludin, S100B, and aquaporin-4 (AQP4). Results show significant elevation in antibodies in about 30% of ASCA- and ANCA-positive sera and demonstrate positive linear relationships between these antibodies. The findings suggest that individuals positive for ASCA and ANCA have increased odds of developing intestinal and BBB permeability compared to healthy subjects. The levels of LPS antibodies in both ASCA- and ANCA-positive and negative specimens showed from low and moderate to high correlation with antibodies to barrier proteins. This study shows that LPS, by damaging the gut and BBBs, contribute to the extra-intestinal manifestation of IBD. We conclude that IBD patients should be screened for LPS antibodies in an effort to detect or prevent possible barrier damage at the earliest stage possible to abrogate disease symptoms in IBS and associated disorders.
Numerical Investigation into Freak Wave Effects on Deepwater Pipeline Installation
Authors: Xu Pu , Du Zhixin , Gong Shunfeng
Published: February 2020

Freak waves are an extreme marine environment factor in offshore structure design and become a potential risk, particularly for laying oil-gas pipelines in deep waters. The objective of this study was to reveal the freak wave effects on dynamic behaviors of offshore pipelines for deepwater installation. Thus, a dedicated finite element model (FEM) for deepwater pipeline installation by the S-lay method was developed with special consideration of freak waves. The FEM also took pipelay vessel motions, pipe–stinger roller interactions, and the cyclic contacts between the pipeline and seabed soil into account. Real vessel and stinger data from an actual engineering project in the South China Sea were collected to obtain an accurate simulation. Moreover, an effective superposition approach of combined transient wave trains and random wave trains was introduced, and various types of freak wave trains were simulated. Extensive numerical analyses of a 12 inch gas pipeline being installed into a water depth of 1500 m were implemented under various freak wave conditions. The noticeable influences of freak waves on the pipeline and seabed responses were identified, which provides significant awareness of offshore pipelines for deepwater installation design and field operation monitoring.
Diethyl pyrrole-2,5-dicarboxylate
Authors: Aitken R. Alan , Bloomfield Charles , McGeachie Liam J. R. , Slawin Alexandra M. Z.
Published: February 2020

The title compound was obtained in moderate yield by a new and unexpected base-induced ring contraction from a 1,4-thiazine precursor. Its X-ray structure showing hydrogen bonded dimers was compared with those of other crystallographically characterised 2-acylpyrroles.
Impact on Stability by the Use of Memory in Traub-Type Schemes
Authors: Chicharro Francisco I. , Cordero Alicia , Garrido Neus , Torregrosa Juan R.
Published: February 2020

In this work, two Traub-type methods with memory are introduced using accelerating parameters. To obtain schemes with memory, after the inclusion of these parameters in Traub’s method, they have been designed using linear approximations or the Newton’s interpolation polynomials. In both cases, the parameters use information from the current and the previous iterations, so they define a method with memory. Moreover, they achieve higher order of convergence than Traub’s scheme without any additional functional evaluations. The real dynamical analysis verifies that the proposed methods with memory not only converge faster, but they are also more stable than the original scheme. The methods selected by means of this analysis can be applied for solving nonlinear problems with a wider set of initial estimations than their original partners. This fact also involves a lower number of iterations in the process.
Electrolyte-Dependent Supercapacitor Performance on Nitrogen-Doped Porous Bio-Carbon from Gelatin
Authors: Deng Jie , Li Jing , Song Shuang , Zhou Yanping , Li Luming
Published: February 2020

The carbon supercapacitance strongly relies upon the electrolyte’s nature, but the clear-cut structure–performance nexus remains elusive. Herein, a series of bio-carbons with gradually varied pore structure and surface chemistry are derived using a new salt template protocol (with eco-benign KNO3 as the template, activator, and porogen, and cheap gelatin as the carbon precursor), and are used as model systems to probe the dependence of the electrochemical mechanism of such nanocarbons on two typical electrolytes (KOH and EMIBF4). By only adjusting the KNO3 dosage, two pivotal figures of merit of biochar—multiscale porosity and surface functionalization—were finely modulated to construct electric double layers. Electrochemical data clarify that the combined porosity and doping effects all contribute to enhanced supercapacitance, but with only one of the two factors playing the leading role in different electrolytes. Kinetic analysis corroborates the fact that ample heteroatom doping can effectively compensate capacitance by intensive surface redox insertion in KOH, while a suitable pore size dispersion plays a preponderant part in self-amplifying the ion partitioning, and thus dictating a good charge separation in EMIBF4. A quasi-quantitative model of performance–structure relevance in EMIBF4 is judiciously conjectured to hint at a superb ion–pore-size compatibility, in which the bi- and mono-layer ion confinement coupling in integrated single and double ion-sized pores is found to be more useful for curbing notorious over-screening effects and for changing the coordination number, Coulombic ordering, and phase conformation of EMIBF4 in several nm-sized nanopores. This unique energy storage fashion in ion-matching pores promotes the energy density of optimal samples to a novel level of 88.3 Wh kg−1 at 1 kW kg−1, which rivals the overwhelming majority of the reported carbon materials. In short, the comparison case study here reveals a valuable correlation of carbon’s figure of merit and electrolyte type, which may act as a vital rudder to design electrolyte-contingent state-of-the-art supercapacitor materials.
Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View
Authors: Valenzuela Rodrigo , Videla Luis A.
Published: February 2020

Nonalcoholic fatty liver disease (NAFLD) is present in approximately 25% of the population worldwide. It is characterized by the accumulation of triacylglycerol in the liver, which can progress to steatohepatitis with different degrees of fibrosis, stages that lack approved pharmacological therapies and represent an indication for liver transplantation with consistently increasing frequency. In view that hepatic steatosis is a reversible condition, effective strategies preventing disease progression were addressed using combinations of natural products in the preclinical high-fat diet (HFD) protocol (60% of fat for 12 weeks). Among them, eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:5n-3, DHA), DHA and extra virgin olive oil (EVOO), or EPA plus hydroxytyrosol (HT) attained 66% to 83% diminution in HFD-induced steatosis, with the concomitant inhibition of the proinflammatory state associated with steatosis. These supplementations trigger different molecular mechanisms that modify antioxidant, antisteatotic, and anti-inflammatory responses, and in the case of DHA and HT co-administration, prevent NAFLD. It is concluded that future studies in NAFLD patients using combined supplementations such as DHA plus HT are warranted to prevent liver steatosis, thus avoiding its progression into more unmanageable stages of the disease.
Association of Neck Circumference with Anthropometric Indicators and Body Composition Measured by DXA in Young Spanish Adults
Authors: Téllez María José Arias , Acosta Francisco M. , Sanchez-Delgado Guillermo , Martinez-Tellez Borja , Muñoz-Hernández Victoria , Martinez-Avila Wendy D. , Henriksson Pontus , Ruiz Jonatan R.
Published: February 2020

Background: Due to a clinical and public health interest of neck circumference (NC), a better understanding of this simple anthropometric measurement, as a valid marker of body composition is necessary. Methods: A total of 119 young healthy adults participated in this study. NC was measured over the thyroid cartilage and perpendicular to the longitudinal axis of the neck. Body weight, height, waist circumference (WC), and hip circumference were measured. A Dual X-ray absorptiometry (DXA) scan was used to determine fat mass, lean mass, and visceral adipose tissue (VAT). Additionally, body mass index (BMI) and triponderal mass index (TMI), the waist to hip and waist to height ratios, and the fat mass and lean mass indexes (FMI and LMI, respectively) were calculated. Results: NC was positively associated in women (W) and men (M), with BMI (rW = 0.70 and rM = 0.84, respectively), TMI (rW = 0.63 and rM = 0.80, respectively), WC (rW = 0.75 and rM = 0.86, respectively), VAT (rW = 0.74 and rM = 0.82, respectively), Waist/hip (rW = 0.51 and rM = 0.67, respectively), Waist/height (rW = 0.68 and rM = 0.83, respectively) and FMI (rW = 0.61 and rM = 0.81, respectively). The association between NC and indicators of body composition was however weaker than that observed by BMI, TMI, WC and Waist/height in both women and men. It is of note that in women, NC was associated with FMI, VAT and LMI independently of BMI. In men, adding NC to anthropometric variables did not improve the prediction of body composition, while slight improvements were observed in women. Conclusions: Taken together, the present study provides no indication for NC as a useful proxy of body composition parameters in young adults, yet future studies should explore its usefulness as a measure to use in combination with BMI, especially in women.
Hazard Warning Systems to Improve Young Distracted Drivers’ Hazard Perception Skills
Authors: Arslanyilmaz Abdurrahman
Published: February 2020

Texting while driving has been shown to impair driving performance with the greatest probability of leading to an accident. This is a great concern with young and inexperienced drivers, who are reported to be the most prolific users of texting while driving and are disproportionately involved in car crashes as compared to their experienced and older counterparts. Hazard Warning Systems (HWSs) have been researched to reduce distracted driving and improve driving performance. The first purpose of this study is to showcase a game-based, multi-player, online simulated training (GMOST) application with an integrated HWS. The second is to examine whether such an HWS integrated into the GMOST improves young and inexperienced drivers’ hazard perception skills, as measured by hazard reaction time (HRT) and horizontal road scanning (HS). A total of 22 high school students from a private school participated in this study. To determine the effects of HWS, a 2 × 2 ANOVA and a 2 × 2 MANOVA were run. The results of this study suggest that the GMOST with integrated HWS leads to earlier detection and reaction to hazards as well as wider HS by novice drivers. Therefore, this study reports that HWSs improve novice distracted drivers’ hazard perception skills. Accordingly, a wide-spread use of the GMOST-like training applications by novice drivers would be a proactive approach to lower accident rates caused by texting while driving.
The N-glycosylation of Equine Tetherin Affects Antiviral Activity by Regulating Its Subcellular Localization
Authors: Bai Bowen , Wang Xue-Feng , Zhang Mengmeng , Na Lei , Zhang Xiangmin , Zhang Haili , Yang Zhibiao , Wang Xiaojun
Published: February 2020

Tetherin is an interferon-inducible type II transmembrane glycoprotein which inhibits the release of viruses, including retroviruses, through a “physical tethering” model. However, the role that the glycosylation of tetherin plays in its antiviral activity remains controversial. In this study, we found that mutation of N-glycosylation sites resulted in an attenuation of the antiviral activity of equine tetherin (eqTHN), as well as a reduction in the expression of eqTHN at the plasma membrane (PM). In addition, eqTHN N-glycosylation mutants colocalize obviously with ER, CD63, LAMP1 and endosomes, while WT eqTHN do not. Furthermore, we also found that N-glycosylation impacts the transport of eqTHN in the cell not by affecting the endocytosis, but rather by influencing the anterograde trafficking of the protein. These results suggest that the N-glycosylation of eqTHN is important for the antiviral activity of the protein through regulating its normal subcellular localization. This finding will enhance our understanding of the function of this important restriction factor.
Visualizing Sacbrood Virus of Honey Bees via Transformation and Coupling with Enhanced Green Fluorescent Protein
Authors: Jin Lang , Mehmood Shahid , Zhang Giikailang , Song Yuwei , Su Songkun , Huang Shaokang , Huang Heliang , Zhang Yakun , Geng Haiyang , Huang Wei-Fone
Published: February 2020

Sacbrood virus (SBV) of honey bees is a picornavirus in the genus Iflavirus. Given its relatively small and simple genome structure, single positive-strand RNA with only one ORF, cloning the full genomic sequence is not difficult. However, adding nonsynonymous mutations to the bee iflavirus clone is difficult because of the lack of information about the viral protein processes. Furthermore, the addition of a reporter gene to the clones has never been accomplished. In preliminary trials, we found that the site between 3′ untranslated region (UTR) and poly(A) can retain added sequences. We added enhanced green fluorescent protein (EGFP) expression at this site, creating a SBV clone with an expression tag that does not affect virus genes. An intergenic region internal ribosome entry site (IRES) from Black queen cell virus (BQCV) was inserted to initiate EGFP expression. The SBV-IRES-EGFP clone successfully infected Apis cerana and Apis mellifera, and in A. cerana larvae, it was isolated and passaged using oral inoculation. The inoculated larvae had higher mortality and the dead larvae showed sacbrood symptoms. The added IRES-EGFP remained in the clone through multiple passages and expressed the expected EGFP in all infected bees. We demonstrated the ability to add gene sequences in the site between 3′-UTR and poly(A) in SBV and the potential to do so in other bee iflaviruses; however, further investigations of the mechanisms are needed. A clone with a desired protein expression reporter will be a valuable tool in bee virus studies.
An Oleanolic Acid Derivative Inhibits Hemagglutinin-Mediated Entry of Influenza A Virus
Authors: Ye Mengdie , Liao Yixian , Wu Li , Qi Wenbao , Choudhry Namrta , Liu Yahong , Chen Weisan , Song Gaopeng , Chen Jianxin
Published: February 2020

Influenza A viruses (IAV) have been a major public health threat worldwide, and options for antiviral therapy become increasingly limited with the emergence of drug-resisting virus strains. New and effective anti-IAV drugs, especially for highly pathogenic influenza, with different modes of action, are urgently needed. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. In this study, we show that OA-10, a newly synthesized triterpene out of 11 oleanane-type derivatives, exhibited significant antiviral activity against four different subtypes of IAV (H1N1, H5N1, H9N2 and H3N2) replications in A549 cell cultures with EC50 ranging from 6.7 to 19.6 μM and a negligible cytotoxicity (CC50 > 640 μM). It inhibited acid-induced hemolysis in a dose-dependent manner, with an IC50 of 26 µM, and had a weak inhibition on the adsorption of H5 HA to chicken erythrocytes at higher concentrations (≥40 µM). Surface plasmon resonance (SPR) analysis showed that OA-10 interacted with HA in a dose-dependent manner with the equilibrium dissociation constants (KD) of the interaction of 2.98 × 10−12 M. Computer-aided molecular docking analysis suggested that OA-10 might bind to the cavity in HA stem region which is known to undergo significant rearrangement during membrane fusion. Our results demonstrate that OA-10 inhibits H5N1 IAV replication mainly by blocking the conformational changes of HA2 subunit required for virus fusion with endosomal membrane. These findings suggest that OA-10 could serve as a lead for further development of novel virus entry inhibitors to prevent and treat IAV infections.
A Novel Role for PX, a Structural Protein of Fowl Adenovirus Serotype 4 (FAdV4), as an Apoptosis-Inducer in Leghorn Male Hepatocellular Cell
Authors: Zhao Mingliang , Duan Xueyan , Wang Yongqiang , Gao Li , Cao Hong , Li Xiaoqi , Zheng Shijun J.
Published: February 2020

Hydropericardium-Hepatitis Syndrome (HHS) caused by Fowl Adenovirus Serotype 4 (FAdV4) infection is a severe threat to the poultry industry worldwide, especially in China since 2015. Recent studies show that FAdV4 induces liver injury through apoptosis. However, the underlying molecular mechanism is still unclear. We report here that FAdV4 infection caused apoptosis in Leghorn male hepatocellular (LMH) cells and that PX, a structural protein of FAdV4, acted as a major viral factor inducing apoptosis. Furthermore, the nuclear localization of PX is determined by the R/K regions of PX and required for PX-induced apoptosis. Moreover, alanines 11 and 129 of PX are crucial to PX-induced apoptosis. Inhibition of FAdV4-induced apoptosis by caspase inhibitors retarded viral replication, suggesting that PX serves as a virulence factor for FAdV4 infection, which may further our understandings of the pathogenesis of FAdV4 infection.
Hepatitis C Virus Vaccine: Challenges and Prospects
Authors: Duncan Joshua D. , Urbanowicz Richard A. , Tarr Alexander W. , Ball Jonathan K.
Published: February 2020

The hepatitis C virus (HCV) causes both acute and chronic infection and continues to be a global problem despite advances in antiviral therapeutics. Current treatments fail to prevent reinfection and remain expensive, limiting their use to developed countries, and the asymptomatic nature of acute infection can result in individuals not receiving treatment and unknowingly spreading HCV. A prophylactic vaccine is therefore needed to control this virus. Thirty years since the discovery of HCV, there have been major gains in understanding the molecular biology and elucidating the immunological mechanisms that underpin spontaneous viral clearance, aiding rational vaccine design. This review discusses the challenges facing HCV vaccine design and the most recent and promising candidates being investigated.
African Swine Fever in Mongolia: Course of the Epidemic and Applied Control Measures
Authors: Heilmann Martin , Lkhagvasuren Amarsanaa , Adyasuren Tuvshinbayar , Khishgee Bodisaikhan , Bold Bayartungalag , Ankhanbaatar Ulaankhuu , Fusheng Guo , Raizman Eran , Dietze Klaas
Published: February 2020

African swine fever (ASF) is spreading rapidly in Asia and was confirmed in Mongolia on 10 January 2019. Following the outbreak confirmation, a state emergency committee was established with representation from municipal authorities and other relevant authorities including the General Authority for Veterinary Services, National Emergency Management Agency, General Agency for Specialized Inspection, and the Ministry of Environment and Tourism. The committee provided recommendations and coordinated closely with the State Central Veterinary Laboratory to ensure quick outbreak investigation and response. In addition to outbreak investigations, sampling took place at farms and food premises and suggests a link between the outbreaks and swill feeding practices among backyard pig farmers. Upon government request, the Food and Agriculture Organization of the United Nations (FAO) deployed an expert team to assist in identifying risk factors for the disease spread and provide recommendations as how to improve disease prevention and response. Following the control measures from the involved agencies, the epidemic was successfully controlled and declared over on 11 April 2019. In total, the epidemic affected 83 pig farming households and led to a total of 2862 dead or culled pigs in eleven districts of seven provinces in Mongolia.