bluuebunny/crossref_metadata_2025 huggingface dataset:
Valuing Acute Health Risks of Air Pollution in the Jinchuan Mining Area, China: A Choice Experiment with Perceived Exposure and Hazardousness as Co-Determinants
Authors: Li Zhengtao
Published: November 2019

This paper analyzes the choice of illness-cure combinations to estimate people’s willingness to pay (WTP) for the reduction of acute health risks correlated with air pollution caused by mining and smelting in the Jinchuan mining area, China. To improve explaining the power of choice experiment (CE), a random parameter logit model (RPL) was employed and extended by considering rank ordered choice sets and non-linear effects of health risk perception on choice behaviors. The results of this study indicated that the ordered RPL approach produced better results than the unordered alternative after comparing different modeling techniques. Perceived health risk, illness attributes, and the residents’ external characteristics: income, education, age, family health experience, work environment and proximity to pollution source are important determinants of the Jinchuan people’s choice mode for avoiding acute health risks caused by air pollution. Taking all acute illnesses investigated together, the mean Jinchuan household WTP for reducing acute health risk caused by air pollution is 146.69 RMB (abbreviation of Chinese yuan) per year (US$23.38, 0.31% of average yearly household income). On the basis of our findings, we conclude that virtually Jinchuan residents perceive air pollution as a serious health risk. To assist the residents to take appropriate preventive action, the local government should develop counseling and educational campaigns and institutionalize disclosure of air quality conditions.
The Impacts of Green Innovation Input and Channel Service in a Dual-Channel Value Chain
Authors: Li Qiuxiang , Chen Xingli , Huang Yimin , Gui Huangbao , Liu Shengyang
Published: November 2019

This paper constructs a dual-channel value chain composed of one altruistic manufacturer and one altruistic retailer, where the manufacturer makes green innovation input for green products and sells its green products to its customers through both the direct channel and the traditional channel, the retailer provides channel service for customers and sells green products through the traditional channel. We consider two scenarios in which the manufacturer and the retailer make decentralized and centralized decisions, respectively. We develop two dynamic game models for the two scenarios and analyze the dynamic behaviors of the two dynamic game models using bifurcation diagram, LLE (largest Lyapunov exponent) and attraction of basin, etc. We find that the stability region in decentralized decision model is greater than that of centralized decision, and narrow with increase of service value, green innovation input. In the decentralized decision model, the stability of the system decreases with the altruistic behavior increasing. With the price adjustment speed increasing, the dual-channel green value chain system enters into chaotic state through flip bifurcation or N-S bifurcation. In the stable state, the manufacturer and the retailer can obtain the maximum utility with the appropriate value of green innovation input. In the chaotic state, the utilities of the manufacturer and retailer are greatly affected and significantly reduced. This study will provide good guidance for sustainable development decision-making of dual-channel green value chain.
Dynamic 3D Simulation of Flood Risk Based on the Integration of Spatio-Temporal GIS and Hydrodynamic Models
Authors: Wu Yongxing , Peng Fei , Peng Yang , Kong Xiaoyang , Liang Heming , Li Qi
Published: November 2019

Dynamic visual simulation of flood risk is crucial for scientific and intelligent emergency management of flood disasters, in which data quality, availability, visualization, and interoperability are important. Here, a seamless integration of a spatio-temporal Geographic Information System (GIS) with one-dimensional (1D) and two-dimensional (2D) hydrodynamic models is achieved for data flow, calculation processes, operation flow, and system functions. Oblique photography-based three-dimensional (3D) modeling technology is used to quickly build a 3D model of the study area (including the hydraulic engineering facilities). A multisource spatio-temporal data platform for dynamically simulating flood risk was built based on the digital earth platform. Using the spatio-temporal computation framework, a dynamic visual simulation and decision support system for flood risk management was developed for the Xiashan Reservoir. The integration method proposed here was verified using flood simulation calculations, dynamic visual simulations, and downstream river channel and dam-break flood simulations. The results show that the proposed methods greatly improve the efficiency of flood risk simulation and decision support. The methods and system put forward in this study can be applied to flood risk simulations and practical management.
Roles of Transposable Elements in the Different Layers of Gene Expression Regulation
Authors: Drongitis Denise , Aniello Francesco , Fucci Laura , Donizetti Aldo
Published: November 2019

The biology of transposable elements (TEs) is a fascinating and complex field of investigation. TEs represent a substantial fraction of many eukaryotic genomes and can influence many aspects of DNA function that range from the evolution of genetic information to duplication, stability, and gene expression. Their ability to move inside the genome has been largely recognized as a double-edged sword, as both useful and deleterious effects can result. A fundamental role has been played by the evolution of the molecular processes needed to properly control the expression of TEs. Today, we are far removed from the original reductive vision of TEs as “junk DNA”, and are more convinced that TEs represent an essential element in the regulation of gene expression. In this review, we summarize some of the more recent findings, mainly in the animal kingdom, concerning the active roles that TEs play at every level of gene expression regulation, including chromatin modification, splicing, and protein translation.
RAF Kinase Inhibitor Protein in Myeloid Leukemogenesis
Authors: Zebisch Armin , Caraffini Veronica , Sill Heinz
Published: November 2019

RAF kinase inhibitor protein (RKIP) is an essential regulator of intracellular signaling. A somatic loss of RKIP expression is a frequent event in solid human cancers, and a role of RKIP as metastasis-suppressor is widely accepted nowadays. Recently, RKIP loss has been described in acute myeloid leukemia (AML) and a series of other myeloid neoplasias (MNs). Functional in vitro and in vivo experiments revealed that RKIP is an essential player within the development of these liquid tumors; however, the respective role of RKIP seems to be complex and multi-faceted. In this review, we will summarize the current knowledge about RKIP in myeloid leukemogenesis. We will initially describe its involvement in physiologic hematopoiesis, and will then proceed to discuss its role in the development of AML and other MNs. Finally, we will discuss potential therapeutic implications arising thereof.
Rapid Regulation of Human Mesenchymal Stem Cell Proliferation Using Inducible Caspase-9 Suicide Gene for Safe Cell-Based Therapy
Authors: Tsujimura Mari , Kusamori Kosuke , Nishikawa Makiya
Published: November 2019

The regulation of transplanted cell proliferation and function is important to achieve safe cell-based therapies. We previously reported that the proliferation and function of transplanted cells, which expressed the herpes simplex virus thymidine kinase (HSVtk) suicide gene, could be controlled by ganciclovir (GCV) administration. However, there are some concerns regarding the use of GCV. It is reported that the inducible caspase-9 (iC9) gene, a human caspase-9-derived genetically engineered suicide gene, rapidly induces cell apoptosis in the presence of apoptosis inducers, such as AP20187. In this study, we used a combination of the iC9 gene and AP20187 to achieve rapid regulation of transplanted cell proliferation. Cells from the human mesenchymal stem cell line UE7T-13 were transfected with the iC9 gene to obtain UE7T-13/iC9 cells. AP20187 significantly reduced the number of UE7T-13/iC9 cells within 24 h in a concentration-dependent manner. This reduction was much faster than the reduction of HSVtk-expressing UE7T-13 cells induced by GCV addition. Subcutaneous AP20187 administration rapidly reduced the luminescence signal from NanoLuc luciferase (Nluc)-expressing UE7T-13/iC9 cells transplanted into mice. These results indicate that the combined use of the iC9 gene and AP20187 is effective in rapidly regulating transplanted cell proliferation.
Perfluorooctanoate in Aqueous Urea Solutions: Micelle Formation, Structure, and Microenvironment
Authors: Kancharla Samhitha , Canales Emmanuel , Alexandridis Paschalis
Published: November 2019

Fluorinated surfactants are used in a wide range of applications that involve aqueous solvents incorporating various additives. The presence of organic compounds such as urea is expected to affect the self-assembly of fluorinated surfactants, however, very little is known about this. We investigated the effect of urea on the micellization in water of the common fluorinated surfactant ammonium perfluorooctanoate (APFO), and on the structure and microenvironment of the micelles that APFO forms. Addition of urea to aqueous APFO solution decreased the critical micellization concentration (CMC) and increased the counterion dissociation. The observed increase in surface area per APFO headgroup and decrease in packing density at the micelle surface suggest the localization of urea at the micelle surface in a manner that reduces headgroup repulsions. Micropolarity data further support this picture. The results presented here indicate that significant differences exist between urea effects on fluorinated surfactant and on hydrocarbon surfactant micellization in aqueous solution. For example, the CMC of sodium dodecyl sulfate (SDS) increased with urea addition, while the increase in surface area per headgroup and packing density of SDS with urea addition are much lower than those observed for APFO. This study informs fluorinated surfactant fate and transport in the environment, and also applications involving aqueous media in which urea or similar additives are present.
Defining Signatures of Arm-Wise Copy Number Change and Their Associated Drivers in Kidney Cancers
Authors: Benstead-Hume Graeme , Wooller Sarah K. , Downs Jessica A , Pearl Frances M. G.
Published: November 2019

Using pan-cancer data from The Cancer Genome Atlas (TCGA), we investigated how patterns in copy number alterations in cancer cells vary both by tissue type and as a function of genetic alteration. We find that patterns in both chromosomal ploidy and individual arm copy number are dependent on tumour type. We highlight for example, the significant losses in chromosome arm 3p and the gain of ploidy in 5q in kidney clear cell renal cell carcinoma tissue samples. We find that specific gene mutations are associated with genome-wide copy number changes. Using signatures derived from non-negative factorisation, we also find gene mutations that are associated with particular patterns of ploidy change. Finally, utilising a set of machine learning classifiers, we successfully predicted the presence of mutated genes in a sample using arm-wise copy number patterns as features. This demonstrates that mutations in specific genes are correlated and may lead to specific patterns of ploidy loss and gain across chromosome arms. Using these same classifiers, we highlight which arms are most predictive of commonly mutated genes in kidney renal clear cell carcinoma (KIRC).
Androgen-Regulated microRNAs (AndroMiRs) as Novel Players in Adipogenesis
Authors: Jansen Julia , Greither Thomas , Behre Hermann M.
Published: November 2019

The development, homeostasis, or increase of the adipose tissue is driven by the induction of the adipogenic differentiation (adipogenesis) of undifferentiated mesenchymal stem cells (MSCs). Adipogenesis can be inhibited by androgen stimulation of these MSCs resulting in the transcription initiation or repression of androgen receptor (AR) regulated genes. AR not only regulates the transcription of protein-coding genes but also the transcription of several non-coding microRNAs involved in the posttranscriptional gene regulation (herein designated as AndroMiRs). As microRNAs are largely involved in differentiation processes such as adipogenesis, the involvement of AndroMiRs in the androgen-mediated inhibition of adipogenesis is likely, however, not yet intensively studied. In this review, existing knowledge about adipogenesis-related microRNAs and AndroMiRs is summarized, and putative cross-links are drawn, which are still prone to experimental validation.
Exploring the Interface between Inflammatory and Therapeutic Glucocorticoid Induced Bone and Muscle Loss
Authors: Webster Justine M. , Fenton Chloe G. , Langen Ramon , Hardy Rowan S.
Published: November 2019

Due to their potent immunomodulatory anti-inflammatory properties, synthetic glucocorticoids (GCs) are widely utilized in the treatment of chronic inflammatory disease. In this review, we examine our current understanding of how chronic inflammation and commonly used therapeutic GCs interact to regulate bone and muscle metabolism. Whilst both inflammation and therapeutic GCs directly promote systemic osteoporosis and muscle wasting, the mechanisms whereby they achieve this are distinct. Importantly, their interactions in vivo are greatly complicated secondary to the directly opposing actions of GCs on a wide array of pro-inflammatory signalling pathways that underpin catabolic and anti-anabolic metabolism. Several clinical studies have attempted to address the net effects of therapeutic glucocorticoids on inflammatory bone loss and muscle wasting using a range of approaches. These have yielded a wide array of results further complicated by the nature of inflammatory disease, underlying the disease management and regimen of GC therapy. Here, we report the latest findings related to these pathway interactions and explore the latest insights from murine models of disease aimed at modelling these processes and delineating the contribution of pre-receptor steroid metabolism. Understanding these processes remains paramount in the effective management of patients with chronic inflammatory disease.
Sickle Cell Trait Induces Oxidative Damage on Plasmodium falciparum Proteome at Erythrocyte Stages
Authors: Díaz-Castillo Alber , Contreras-Puentes Neyder , Alvear-Sedán Ciro , Moneriz-Pretell Carlos , Rodríguez-Cavallo Erika , Mendez-Cuadro Darío
Published: November 2019

The presence of hemoglobin A-S (HbAS) in erythrocytes has been related to the high production of reactive oxygen species (ROS) and an increased in intracellular oxidative stress that affects the progress of Plasmodium erythrocytic cycle life and attenuates its serious clinical symptoms. Nevertheless, oxidative effects on P. falciparum proteome across the intraerythrocytic cycle in the presence of HbAS traits have not been described yet. Here, an immune dot-blot assay was used to quantify the carbonyl index (C.I) on P. falciparum 3D7 proteome at the different asexual erythrocytic stages. Protein carbonylation on parasites cultivated in erythrocytes from two donors with HbAS increased 5.34 ± 1.42 folds at the ring stage compared to control grown in hemoglobin A-A (HbAA) red blood cells. Whereas at trophozoites and schizonts stages were augmented 2.80 ± 0.52 and 3.05 ± 0.75 folds, respectively. Besides proteins involved in processes of the stress response, recognition and invasion were identified from schizonts carbonylated bands by combining SDS-PAGE with MALDI-TOF-TOF analysis. Our results reinforce the hypothesis that such oxidative modifications do not appear to happen randomly, and the sickle cell trait affects mainly a small fraction of parasite proteins particularly sensitive to ROS.
Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway
Authors: Jin Sun Woo , Pham Hoa Thi , Choi Jae Ho , Lee Gi Ho , Han Eun Hee , Cho Young Ho , Chung Young Chul , Kim Young Ho , Jeong Hye Gwang
Published: November 2019

Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular function including systemic blood pressure and vascular inflammation in vascular endothelium. In this study hypothesized that Impressic acid (IPA), a component isolated from Acanthopanax koreanum, acts as an enhancer of eNOS activity and NO production. IPA treatment induced eNOS phosphorylation and NO production, which was correlated with eNOS phosphorylation via the activation of JNK1/2, p38 MAPK, AMPK, and CaMKII. In addition, the induction of eNOS phosphorylation by IPA was attenuated by pharmacological inhibitor of MAPKs, AMPK, and CaMKII. Finally, IPA treatment prevented the adhesion of TNF-α-induced monocytes to endothelial cells and suppressed the TNF-α-stimulated ICAM-1 expression via activation of NF-κB, while treatment with L-NAME, the NOS inhibitor, reversed the inhibitory effect of IPA on TNF-α-induced ICAM-1 expression via activation of NF-κB. Taken together, these findings show that IPA protects against TNF-α-induced vascular endothelium dysfunction through attenuation of the NF-κB pathway by activating eNOS/NO pathway in endothelial cells.
Impact of Paraburkholderia phytofirmans PsJN on Grapevine Phenolic Metabolism
Authors: Miotto-Vilanova Lidiane , Courteaux Barbara , Padilla Rosa , Rabenoelina Fanja , Jacquard Cédric , Clément Christophe , Comte Gilles , Lavire Céline , Ait Barka Essaïd , Kerzaon Isabelle , Sanchez Lisa
Published: November 2019

Phenolic compounds are implied in plant-microorganisms interaction and may be induced in response to plant growth-promoting rhizobacteria (PGPRs). Among PGPR, the beneficial bacterium Paraburkholderia phytofirmans PsJN was previously described to stimulate the growth of plants and to induce a better adaptation to both abiotic and biotic stresses. This study aimed to investigate the impact of PsJN on grapevine secondary metabolism. For this purpose, gene expression (qRT-PCR) and profiling of plant secondary metabolites (UHPLC-UV/DAD-MS QTOF) from both grapevine root and leaves were compared between non-bacterized and PsJN-bacterized grapevine plantlets. Our results showed that PsJN induced locally (roots) and systemically (leaves) an overexpression of PAL and STS and specifically in leaves the overexpression of all the genes implied in phenylpropanoid and flavonoid pathways. Moreover, the metabolomic approach revealed that relative amounts of 32 and 17 compounds in roots and leaves, respectively, were significantly modified by PsJN. Once identified to be accumulated in response to PsJN by the metabolomic approach, antifungal properties of purified molecules were validated in vitro for their antifungal effect on Botrytis cinerea spore germination. Taking together, our findings on the impact of PsJN on phenolic metabolism allowed us to identify a supplementary biocontrol mechanism developed by this PGPR to induce plant resistance against pathogens.
The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma
Authors: Takabatake Kiyofumi , Shimo Tsuyoshi , Murakami Jun , Anqi Chang , Kawai Hotaka , Yoshida Saori , Wathone Oo May , Haruka Omori , Sukegawa Shintaro , Tsujigiwa Hidetsugu , Nakano Keisuke , Nagatsuka Hitoshi
Published: November 2019

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of SHH expression appear to correlate with cancer progression. However, the role of SHH in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is still unclear. No studies have compared the expression of SHH in different subtypes of OSCC and focused on the relationship between the tumor parenchyma and stroma. In this study, we analyzed SHH and expression of its receptor, Patched-1 (PTCH), in the TME of different subtypes of OSCC. Fifteen endophytic-type cases (ED type) and 15 exophytic-type cases (EX type) of OSCC were used. H&E staining, immunohistochemistry (IHC), double IHC, and double-fluorescent IHC were performed on these samples. ED-type parenchyma more strongly expressed both SHH and PTCH than EX-type parenchyma. In OSCC stroma, CD31-positive cancer blood vessels, CD68- and CD11b-positive macrophages, and α-smooth muscle actin-positive cancer-associated fibroblasts partially expressed PTCH. On the other hand, in EX-type stroma, almost no double-positive cells were observed. These results suggest that autocrine effects of SHH induce cancer invasion, and paracrine effects of SHH govern parenchyma-stromal interactions of OSCC. The role of the SHH pathway is to promote growth and invasion.
A Stress-Associated Protein, PtSAP13, From Populus trichocarpa Provides Tolerance to Salt Stress
Authors: Li Jianbo , Sun Pei , Xia Yongxiu , Zheng Guangshun , Sun Jingshuang , Jia Huixia
Published: November 2019

The growth and production of poplars are usually affected by unfavorable environmental conditions such as soil salinization. Thus, enhancing salt tolerance of poplars will promote their better adaptation to environmental stresses and improve their biomass production. Stress-associated proteins (SAPs) are a novel class of A20/AN1 zinc finger proteins that have been shown to confer plants’ tolerance to multiple abiotic stresses. However, the precise functions of SAP genes in poplars are still largely unknown. Here, the expression profiles of Populus trichocarpa SAPs in response to salt stress revealed that PtSAP13 with two AN1 domains was up-regulated dramatically during salt treatment. The β-glucuronidase (GUS) staining showed that PtSAP13 was accumulated dominantly in leaf and root, and the GUS signal was increased under salt condition. The Arabidopsis transgenic plants overexpressing PtSAP13 exhibited higher seed germination and better growth than wild-type (WT) plants under salt stress, demonstrating that overexpression of PtSAP13 increased salt tolerance. Higher activities of antioxidant enzymes were found in PtSAP13-overexpressing plants than in WT plants under salt stress. Transcriptome analysis revealed that some stress-related genes, including Glutathione peroxidase 8, NADP-malic enzyme 2, Response to ABA and Salt 1, WRKYs, Glutathione S-Transferase, and MYBs, were induced by salt in transgenic plants. Moreover, the pathways of flavonoid biosynthesis and metabolic processes, regulation of response to stress, response to ethylene, dioxygenase activity, glucosyltransferase activity, monooxygenase activity, and oxidoreductase activity were specially enriched in transgenic plants under salt condition. Taken together, our results demonstrate that PtSAP13 enhances salt tolerance through up-regulating the expression of stress-related genes and mediating multiple biological pathways.
Genome-Wide Identification and Characterization of ABC Transporters in Nine Rosaceae Species Identifying MdABCG28 as a Possible Cytokinin Transporter linked to Dwarfing
Authors: Feng Yi , Sun Qiran , Zhang Guifen , Wu Ting , Zhang Xinzhong , Xu Xuefeng , Han Zhenhai , Wang Yi
Published: November 2019

ATP-binding cassette (ABC) transporters constitute a large, diverse, and ubiquitous superfamily that is involved in a broad range of processes. The completion of genome sequencing provides an opportunity to understand the phylogenetic history of the ABC transporter superfamily among Rosaceae species. This study identified a total of 1323 ABC transporter genes from nine Rosaceae genomes: 191 from Malus domestica, 174 from Pyrus communis, 138 from Prunus persica, 118 from Prunus avium, 141 from Prunus dulcis, 122 from Fragaria vesca, 98 from Rubus occidentalis, 162 from Prunus mume, and 179 from Rosa chinensis. Their chemical characterization, phylogenetic analysis, chromosomal localization, gene structure, gene duplication, and tissue-specific expression were studied. Their subcellular localization, transmembrane structures, and protein motifs were predicted. All the ABC transporter genes were grouped into eight subfamilies on the basis of their phylogenetic relationships and structural features. Furthermore, cis-element and expression analysis of 10 potential phytohormone transporters in MdABCG subfamily genes were also performed. Loss of the W-box in the promoter region of MdABCG28 was found to reduce the gene expression level and was linked to the dwarfing phenotype in apple rootstocks. MdABCG28 overexpression promoted shoot growth of atabcg14 mutants in Arabidopsis.
Fluorescent Protein-Based Indicators for Functional Super-Resolution Imaging of Biomolecular Activities in Living Cells
Authors: Lu Kai , Vu Cong Quang , Matsuda Tomoki , Nagai Takeharu
Published: November 2019

Super-resolution light microscopy (SRM) offers a unique opportunity for diffraction-unlimited imaging of biomolecular activities in living cells. To realize such potential, genetically encoded indicators were developed recently from fluorescent proteins (FPs) that exhibit phototransformation behaviors including photoactivation, photoconversion, and photoswitching, etc. Super-resolution observations of biomolecule interactions and biochemical activities have been demonstrated by exploiting the principles of bimolecular fluorescence complementation (BiFC), points accumulation for imaging nanoscale topography (PAINT), and fluorescence fluctuation increase by contact (FLINC), etc. To improve functional nanoscopy with the technology of genetically encoded indicators, it is essential to fully decipher the photo-induced chemistry of FPs and opt for innovative indicator designs that utilize not only fluorescence intensity but also multi-parametric readouts such as phototransformation kinetics. In parallel, technical improvements to both the microscopy optics and image analysis pipeline are promising avenues to increase the sensitivity and versatility of functional SRM.
The Effect of Schisandra chinensis Baillon on Cross-Talk between Oxidative Stress, Endoplasmic Reticulum Stress, and Mitochondrial Signaling Pathway in Testes of Varicocele-Induced SD Rat
Authors: Karna Keshab Kumar , Choi Bo Ram , Kim Min-Ji , Kim Hye Kyung , Park Jong Kwan
Published: November 2019

Schisandra chinensis Baillon (SC) has been utilized for its antioxidants and anti-inflammatory activities in a broad variety of medical applications. However; SC uses for improving fertility in males and related disorders with proper scientific validation remain obscure. The present study aimed to investigate the effects of SC on varicocele (VC)-induced testicular dysfunction and the potential molecular mechanism associated with VC-induced germ cell apoptosis. The male Sprague–Dawley rats were equally divided into four groups consisting of 10 rats in a normal control group (CTR), a control group administered SC 200 mg/kg (SC 200), a varicocele-induced control group (VC), and a varicocele-induced group administered SC 200 mg/kg (VC + SC 200). Rats were administrated 200 mg/kg SC once daily for 28 days after induction of varicocele rats and sham controls. At the end of the treatment period, body and reproductive organ weight, sperm parameters, histopathological damages, proinflammatory cytokines, apoptosis markers, biomarkers of oxidative stress, endoplasmic reticulum (ER) stress, and steroidogenic acute regulatory protein (StAR) were evaluated. The effects of SC extract on human sperm motility were also analyzed. SC treatment reduces VC-induced testicular dysfunction by significantly increasing testicular weight, sperm count and sperm motility, serum testosterone level, Johnsen score, spermatogenic cell density, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase level, and steroidogenic acute regulatory protein (StAR) level. Furthermore, the effects of SC on malondialdehyde (MDA) level, reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, apoptotic index, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, Glucose-regulated protein-78 (Grp 78), phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α), cleaved caspase 3, and Bax:Bcl2 in VC-induced rats were significantly decreased. Treatment with SC extracts also increased sperm motility in human sperm. Our findings suggest that the SC ameliorate testicular dysfunction in VC-induced rats via crosstalk between oxidative stress, ER stress, and mitochondrial-mediated testicular germ cell apoptosis signaling pathways. SC promotes spermatogenesis by upregulating abnormal sex hormones and decreasing proinflammatory cytokines (interleukin-6; TNF-α).
S100 Calcium Binding Protein A9 Represses Angiogenic Activity and Aggravates Osteonecrosis of the Femoral Head
Authors: Wu Re-Wen , Lian Wei-Shiung , Kuo Chung-Wen , Chen Yu-Shan , Ko Jih-Yang , Wang Feng-Sheng
Published: November 2019

Ischemic damage aggravation of femoral head collapse is a prominent pathologic feature of osteonecrosis of the femoral head (ONFH). In this regard, S100 calcium binding protein A9 (S100A9) is known to deteriorate joint integrity, however, little is understood about which role S100A9 may play in ONFH. In this study, a proteomics analysis has revealed a decrease in the serum S100A9 level in patients with ONFH upon hyperbaric oxygen therapy. Serum S100A9 levels, along with serum vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), and tartrate-resistant acid phosphatase 5b levels were increased in patients with ONFH, whereas serum osteocalcin levels were decreased as compared to healthy controls. Serum S100A9 levels were increased with the Ficat and Arlet stages of ONFH and correlated with the patients with a history of being on glucocorticoid medication and alcohol consumption. Osteonecrotic tissue showed hypovasculature histopathology together with weak immunostaining for vessel marker CD31 and von Willrbrand factor (vWF) as compared to femoral head fracture specimens. Thrombosed vessels, fibrotic tissue, osteocytes, and inflammatory cells displayed strong S100A9 immunoreactivity in osteonecrotic lesion. In vitro, ONFH serum and S100A9 inhibited the tube formation of vessel endothelial cells and vessel outgrowth of rat aortic rings, whereas the antibody blockade of S100A9 improved angiogenic activities. Taken together, increased S100A9 levels are relevant to the development of ONFH. S100A9 appears to provoke avascular damage, ultimately accelerating femoral head deterioration through reducing angiogenesis. This study provides insight into the molecular mechanism underlying the development of ONFH. Here, analysis also highlights that serum S100A9 is a sensitive biochemical indicator of ONFH.
VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer
Authors: Papachristos Apostolos , Kemos Polychronis , Katsila Theodora , Panoilia Eirini , Patrinos George P. , Kalofonos Haralabos , Sivolapenko Gregory B.
Published: November 2019

Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intracellular signaling pathways involved in the pathogenesis of mCRC as an attempt to find predictors of clinical outcome. Forty-six patients treated with first-line bevacizumab-based chemotherapy were included in this study with a 5 year follow up. Genomic DNA was isolated from whole blood for the analysis of VEGF-A (rs2010963, 1570360, rs699947), ICAM-1 (rs5498, rs1799969) SNPs and from tumor tissue for the detection of genomic variants in KRAS, NRAS, BRAF genes. PCR and next generation sequencing were used for the analysis. The endpoints of the study were progression-free survival (PFS) and overall survival (OS). The VEGF-A rs699947 A/A allele was associated with increased PFS (p = 0.006) and OS (p = 0.043). The ICAM-1 rs1799969 G/A allele was associated with prolonged OS (p = 0.036). Finally, BRAF wild type was associated with increased OS (p = 0.027). We identified VEGF-A and ICAM-1 variants in angiogenesis and other major intracellular signaling pathways, such as BRAF, that can predict clinical outcome upon bevacizumab administration. These identified biomarkers could be used to select patients with mCRC who may achieve long-term responses and benefit from bevacizumab-based therapies.
Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?
Authors: Iglesia Rebeca Piatniczka , Fernandes Camila Felix de Lima , Coelho Bárbara Paranhos , Prado Mariana Brandão , Melo Escobar Maria Isabel , Almeida Gustavo Henrique Doná Rodrigues , Lopes Marilene Hohmuth
Published: November 2019

Heat shock proteins (HSPs) are evolutionary conserved proteins that work as molecular chaperones and perform broad and crucial roles in proteostasis, an important process to preserve the integrity of proteins in different cell types, in health and disease. Their function in cancer is an important aspect to be considered for a better understanding of disease development and progression. Glioblastoma (GBM) is the most frequent and lethal brain cancer, with no effective therapies. In recent years, HSPs have been considered as possible targets for GBM therapy due their importance in different mechanisms that govern GBM malignance. In this review, we address current evidence on the role of several HSPs in the biology of GBMs, and how these molecules have been considered in different treatments in the context of this disease, including their activities in glioblastoma stem-like cells (GSCs), a small subpopulation able to drive GBM growth. Additionally, we highlight recent works that approach other classes of chaperones, such as histone and mitochondrial chaperones, as important molecules for GBM aggressiveness. Herein, we provide new insights into how HSPs and their partners play pivotal roles in GBM biology and may open new therapeutic avenues for GBM based on proteostasis machinery.
Behavioral Impairments and Oxidative Stress in the Brain, Muscle, and Gill Caused by Chronic Exposure of C70 Nanoparticles on Adult Zebrafish
Authors: Sarasamma Sreeja , Audira Gilbert , Samikannu Prabu , Juniardi Stevhen , Siregar Petrus , Hao Erwei , Chen Jung-Ren , Hsiao Chung-Der
Published: November 2019

There is an imperative need to develop efficient whole-animal-based testing assays to determine the potential toxicity of engineered nanomaterials. While previous studies have demonstrated toxicity in lung and skin cells after C70 nanoparticles (NPs) exposure, the potential detrimental role of C70 NPs in neurobehavior is largely unaddressed. Here, we evaluated the chronic effects of C70 NPs exposure on behavior and alterations in biochemical responses in adult zebrafish. Two different exposure doses were used for this experiment: low dose (0.5 ppm) and high dose (1.5 ppm). Behavioral tests were performed after two weeks of exposure of C70 NPs. We found decreased locomotion, exploration, mirror biting, social interaction, and shoaling activities, as well as anxiety elevation and circadian rhythm locomotor activity impairment after ~2 weeks in the C70 NP-exposed fish. The results of biochemical assays reveal that following exposure of zebrafish to 1.5 ppm of C70 NPs, the activity of superoxide dismutase (SOD) in the brain and muscle tissues increased significantly. In addition, the concentration of reactive oxygen species (ROS) also increased from 2.95 ± 0.12 U/ug to 8.46 ± 0.25 U/ug and from 0.90 ± 0.03 U/ug to 3.53 ± 0.64 U/ug in the muscle and brain tissues, respectively. Furthermore, an increased level of cortisol was also observed in muscle and brain tissues, ranging from 17.95 ± 0.90 pg/ug to 23.95 ± 0.66 pg/ug and from 3.47 ± 0.13 pg/ug to 4.91 ± 0.51 pg/ug, respectively. Increment of Hif1-α level was also observed in both tissues. The elevation was ranging from 11.65 ± 0.54 pg/ug to 18.45 ± 1.00 pg/ug in the muscle tissue and from 4.26 ± 0.11 pg/ug to 6.86 ± 0.37 pg/ug in the brain tissue. Moreover, the content of DNA damage and inflammatory markers such as ssDNA, TNF-α, and IL-1β were also increased substantially in the brain tissues. Significant changes in several biomarker levels, including catalase and malondialdehyde (MDA), were also observed in the gill tissues. Finally, we used a neurophenomic approach with a particular focus on environmental influences, which can also be easily adapted for other aquatic fish species, to assess the toxicity of metal and carbon-based nanoparticles. In summary, this is the first study to illustrate the adult zebrafish toxicity and the alterations in several neurobehavior parameters after zebrafish exposure to environmentally relevant amounts of C70 NPs.
The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology
Authors: Hyttinen Juha M. T. , Kannan Ram , Felszeghy Szabolcs , Niittykoski Minna , Salminen Antero , Kaarniranta Kai
Published: November 2019

Age-related macular degeneration (AMD) is a mounting cause of loss of sight in the elderly in the developed countries, a trend enhanced by the continual ageing of the population. AMD is a multifactorial and only partly understood, malady. Unfortunately, there is no effective treatment for most AMD patients. It is known that oxidative stress (OS) damages the retinal pigment epithelium (RPE) and contributes to the progression of AMD. We review here the potential importance of two OS-related cellular systems in relation to AMD. First, the nuclear factor erythroid 2-related factor 2 (NFE2L2; NRF2)-mediated OS response signalling pathway is important in the prevention of oxidative damage and a failure of this system could be critical in the development of AMD. Second, epithelial-to-mesenchymal transition (EMT) represents a change in the cellular phenotype, which ultimately leads to the fibrosis encountered in RPE, a characteristic of AMD. Many of the pathways triggering EMT are promoted by OS. The possible interconnections between these two signalling routes are discussed here. From a broader perspective, the control of NFE2L2 and EMT as ways of preventing OS-derived cellular damage could be potentially valuable in the therapy of AMD.
An Intrusion Detection System Based on a Simplified Residual Network
Authors: Xiao Yuelei , Xiao Xing
Published: November 2019

Residual networks (ResNets) are prone to over-fitting for low-dimensional and small-scale datasets. And the existing intrusion detection systems (IDSs) fail to provide better performance, especially for remote-to-local (R2L) and user-to-root (U2R) attacks. To overcome these problems, a simplified residual network (S-ResNet) is proposed in this paper, which consists of several cascaded, simplified residual blocks. Compared with the original residual block, the simplified residual block deletes a weight layer and two batch normalization (BN) layers, adds a pooling layer, and replaces the rectified linear unit (ReLU) function with the parametric rectified linear unit (PReLU) function. Based on the S-ResNet, a novel IDS was proposed in this paper, which includes a data preprocessing module, a random oversampling module, a S-Resnet layer, a full connection layer and a Softmax layer. The experimental results on the NSL-KDD dataset show that the IDS based on the S-ResNet has a higher accuracy, recall and F1-score than the equal scale ResNet-based IDS, especially for R2L and U2R attacks. And the former has faster convergence velocity than the latter. It proves that the S-ResNet reduces the complexity of the network and effectively prevents over-fitting; thus, it is more suitable for low-dimensional and small-scale datasets than ResNet. Furthermore, the experimental results on the NSL-KDD datasets also show that the IDS based on the S-ResNet achieves better performance in terms of accuracy and recall compared to the existing IDSs, especially for R2L and U2R attacks.
The Competitive Mating of Irradiated Brown Marmorated Stink Bugs, Halyomorpha halys, for the Sterile Insect Technique
Authors: Suckling David , Cristofaro Massimo , Roselli Gerardo , Levy Mary , Cemmi Alessia , Mazzoni Valerio , Stringer Lloyd , Zeni Valeria , Ioriatti Claudio , Anfora Gianfranco
Published: November 2019

The sterility of eggs and nymphs from gamma-irradiated male Halyomorpha halys was investigated to determine the potential for the sterile insect technique (SIT). Males irradiated at 0, 16, 24 and 32 Gy were placed with untreated virgin females, and egg sterility was determined, showing 54.3% at 16 Gy. The percentage of sterility from irradiation was 26 percent lower than previous results from the USA and the variance was very high. Competitive overflooding ratio trials between irradiated virgin males and fertile virgin males at a 5:1 ratio resulted in the expected egg sterility, indicating competitive performance by irradiated males. By July and August, older, irradiated overwintered males were significantly less competitive than similar, non-irradiated males. There is a need to revisit the irradiation delivery method to achieve proper precision around the paternal dose required for an expected >80% egg sterility and subsequent ~99% endpoint sterility estimated at adult emergence in the F1 phase. These results suggest that the mating competitiveness and competency of males after irradiation at 16 Gy is not limiting to the sterile insect technique for suppression. A wild harvest of overwintering males using the aggregation pheromone, followed by irradiation and male release, might replace rearing. Mass-collected, sterilized bugs could be transported from an area of high H. halys density and shipped for release to enable suppression or eradication elsewhere. This concept is under development but further work is needed now to understand the difference in results between the US and Italian irradiators and increase the reliability of dosimetry.
Olfactory Learning in the Stingless Bee Melipona eburnea Friese (Apidae: Meliponini)
Authors: Amaya-Márquez Marisol , Tusso Sergio , Hernández Juan , Jiménez Juan Darío , Wells Harrington , I. Abramson Charles
Published: November 2019

Olfactory learning and floral scents are co-adaptive traits in the plant–pollinator relationship. However, how scent relates to cognition and learning in the diverse group of Neotropical stingless bees is largely unknown. Here we evaluated the ability of Melipona eburnea to be conditioned to scent using the proboscis extension reflex (PER) protocol. Stingless bees did not show PER while harnessed but were able to be PER conditioned to scent when free-to-move in a mini-cage (fmPER). We evaluated the effect of: 1) unconditioned stimulus (US) reward, and 2) previous scent–reward associations on olfactory learning performance. When using unscented-US, PER-responses were low on day 1, but using scented-US reward the olfactory PER-response increased on day 1. On day 2 PER performance greatly increased in bees that previously had experienced the same odor and reward combination, while bees that experienced a different odor on day 2 showed poor olfactory learning. Bees showed higher olfactory PER conditioning to guava than to mango odor. The effect of the unconditioned stimulus reward was not a significant factor in the model on day 2. This indicates that olfactory learning performance can increase via either taste receptors or accumulated experience with the same odor. Our results have application in agriculture and pollination ecology.
Trends in Guideline-Driven Revascularization in Diabetic Patients with Multivessel Coronary Heart Disease
Authors: Rumana Umme , Kones Richard , Taheer Montather O. , Elsayed Mohamed , Johnson Craig W.
Published: November 2019

In diabetes patients with chronic ≥3 vessel disease, coronary artery bypass grafting (CABG) holds a class I recommendation in the American College of Cardiology and American Heart Association (ACC/AHA) 2011 guidelines, and this classification has not changed to date. Much of the literature has focused upon whether CABG or percutaneous coronary intervention (PCI) produces better outcomes; there is a paucity of data comparing the odds of receiving these procedures. A secondary analysis was conducted in a de-identified database comprised of 30,482 patients satisfying the entry criteria. Odds of occurrence (CABG, PCI) were determined as the binary dependent variable in period 1, (17 October 2009 through 31 December 2011), and period 2 (1 January 2013 through 16 March 2015), before and after the 2011 guidelines, while controlling for gender, ethnicity/race, and ischemic heart disease as covariates. The odds of performing CABG rather than PCI in period 2 were not statistically significantly different than in period 1 (p = 0.400). The logistic regression model chi-square statistic was statistically significant, with χ2 (7) = 308.850, p < 0.0001. The Wald statistic showed that ethnicity/race (African American, Caucasian, Hispanic and Other), gender, and heart disease contributed significantly to the prediction model with p < 0.05, but ethnicity ‘Unknown’ did not. The odds of CABG versus PCI in period 2 were 0.98 times those in period 1 95% confidence interval (CI) = (0.925, 1.032), statistically controlling for covariates. There was no significant rise in the odds of undergoing a CABG among this dataset of high-risk patients with diabetes and multivessel coronary heart disease. Modern practice has evolved regarding patient choice and additional variables that impact the final revascularization method employed. The degree to which odds of occurrence of procedures are a reliable surrogate for provider compliance with guidelines remains uncertain.