bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress Testing the Capacity of Health Systems to Manage Climate Change-Related Shocks and Stresses
Authors: Ebi Kristie L. , Berry Peter , Hayes Katie , Boyer Christopher , Sellers Samuel , Enright Paddy M. , Hess Jeremy J.
Published: October 2018

Vulnerability and adaptation assessments can provide valuable input to foster climate-resilient health systems. However, these assessments often do not explore the potential health risks of climate change far outside the range of recent experience with extreme weather events and other climate-related hazards. Climate and health stress tests are designed to increase the capacity of health systems and related sectors to manage potentially disruptive climate-related shocks and stresses. Stress tests focus on hypothetical scenarios, during which it would be difficult for the health system to maintain its essential function of providing services to protect population health. The stress test explores approaches to effectively manage acute and chronic climate-related events and conditions that could directly impact health systems, and climate-related events in non-health sectors that can indirectly impact health outcomes and/or health system function. We provide detailed methods and guidance for conducting climate and health stress tests, centering on three primary activities: (1) preparing and scoping the stress test; (2) successfully conducting the stress test; and (3) communicating the results to key stakeholders to facilitate policy and programmatic reforms.
Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses
Authors: Gunnarsson Lars-Gunnar , Bodin Lennart
Published: October 2018

Objectives: We conducted a systematic literature review to identify studies fulfilling good scientific epidemiological standards for use in meta-analyses of occupational risk factors for amyotrophic lateral sclerosis (ALS). Methods: We identified 79 original publications on associations between work and ALS. The MOOSE (Meta-analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) guidelines were used to ensure high scientific quality, and reliable protocols were applied to classify the articles. Thirty-seven articles fulfilled good scientific standards, while 42 were methodologically deficient and thus were excluded from our meta-analyses. Results: The weighted relative risks for the various occupational exposures were respectively; 1.29 (95% confidence interval (CI): 0.97–1.72; six articles) for heavy physical work, 3.98 (95% CI: 2.04–7.77; three articles) for professional sports, 1.45 (95% CI: 1.07–1.96; six articles) for metals, 1.19 (95% CI: 1.07–1.33; 10 articles) for chemicals, 1.18 (95% CI: 1.07–1.31; 16 articles) for electromagnetic fields or working with electricity, and 1.18 (95% CI: 1.05–1.34; four articles) for working as a nurse or physician. Conclusions: Meta-analyses based only on epidemiologic publications of good scientific quality show that the risk of ALS is statistically significantly elevated for occupational exposures to excessive physical work, chemicals (especially pesticides), metals (especially lead), and possibly also to electromagnetic fields and health care work. These results are not explained by publication bias.
Effect of Subsidies and Tax Deductions on Promoting the Construction of Long-Life Quality Houses in Japan
Authors: Matsumoto Ken’ichi , Yamamoto Yuki , Ohya Nao
Published: October 2018

Securing a quantity of houses for citizens has been the priority of housing policies in Japan. However, these policies shifted from quantity to quality in the 21st century, including the promotion of “long-life quality housing (LLQH)”, which contributes to a sustainable and healthy society for the residential sector. Since then, various policies have been introduced at the national and prefectural (local) levels to promote the construction of LLQH. Using panel data for 47 prefectures across seven years, this study aims to analyze the factors that Japanese households choose when constructing LLQH. Although various research on LLQH and similar housing exists, this study is the first attempt to empirically explore the factors that promote LLQH. We found that policy measures covering only LLQH were generally effective in promoting the construction of LLQH, and these policy measures were more effective than those covering both LLQH and other types of housing. National-level measures tended to be effective, whereas prefectural-level measures were not. Furthermore, although the effects of individual measures differed, the overall effects of policy measures were confirmed. In conclusion, providing economic incentives had a positive effect on promoting LLQH, and such measures were successful in achieving the intended purpose.
Ethanol and Methanol Burn Risks in the Home Environment
Authors: Log Torgrim , Moi Asgjerd Litlere
Published: October 2018

Biofuel heaters and fireplaces have in recent years been introduced for indoor and outdoor use. Due to their simplicity, they are usually equipped with few or no safety features. Worldwide, incidents resulting in major skin burn injury and long hospitalization periods have occurred when using such biofuel units. The present study analyses the characteristics of the liquids ethanol and methanol to get a scientific background for understanding related accidents. The comparably heavy vapors, especially from ethanol, may generate a pillow of combustible gas in the vicinity of the unit, particularly in quiescent indoor air conditions. It is also revealed that these fuels represent a potential severe risk, since the equilibrium vapor pressures are close to the stoichiometric fuel–air composition at normal room temperatures. Selected incidents were reviewed to understand the mechanisms involved when severe burns were received by the users. It turns out that the most severe incidents were related to refilling operations and included ignition of the fuel container vapor phase. When ignited, the container gas phase expansion propelled burning fuel from the bottle or container onto the user or other persons in the vicinity. Similar incidents involving refilling methanol for chemistry demonstrations and ethanol for endodontic (dentistry) treatment were also studied and it was shown that these accidents followed similar accident mechanisms. It may be concluded that the main contributors to burn risk are the near-stoichiometric vapor pressure of these liquids at room temperature and the close proximity of the fuel container to burning fuel. Research needs and possible technical barriers are suggested to reduce this risk for the future.
Co-Evolution of Intrinsically Disordered Proteins with Folded Partners Witnessed by Evolutionary Couplings
Authors: Pancsa Rita , Zsolyomi Fruzsina , Tompa Peter
Published: October 2018

Although improved strategies for the detection and analysis of evolutionary couplings (ECs) between protein residues already enable the prediction of protein structures and interactions, they are mostly restricted to conserved and well-folded proteins. Whereas intrinsically disordered proteins (IDPs) are central to cellular interaction networks, due to the lack of strict structural constraints, they undergo faster evolutionary changes than folded domains. This makes the reliable identification and alignment of IDP homologs difficult, which led to IDPs being omitted in most large-scale residue co-variation analyses. By preforming a dedicated analysis of phylogenetically widespread bacterial IDP–partner interactions, here we demonstrate that partner binding imposes constraints on IDP sequences that manifest in detectable interprotein ECs. These ECs were not detected for interactions mediated by short motifs, rather for those with larger IDP–partner interfaces. Most identified coupled residue pairs reside close (<10 Å) to each other on the interface, with a third of them forming multiple direct atomic contacts. EC-carrying interfaces of IDPs are enriched in negatively charged residues, and the EC residues of both IDPs and partners preferentially reside in helices. Our analysis brings hope that IDP–partner interactions difficult to study could soon be successfully dissected through residue co-variation analysis.
Gold Nanorods for Light-Based Lung Cancer Theranostics
Authors: Knights Oscar B. , McLaughlan James R.
Published: October 2018

Gold nanorods (AuNRs) have the potential to be used in photoacoustic (PA) imaging and plasmonic photothermal therapy (PPTT) due to their unique optical properties, biocompatibility, controlled synthesis, and tuneable surface plasmon resonances (SPRs). Conventionally, continuous-wave (CW) lasers are used in PPTT partly due to their small size and low cost. However, if pulsed-wave (PW) lasers could be used to destroy tissue then combined theranostic applications, such as PA-guided PPTT, would be possible using the same laser system and AuNRs. In this study, we present the effects of AuNR size on PA response, PW-PPTT efficacy, and PA imaging in a tissue-mimicking phantom, as a necessary step in the development of AuNRs towards clinical use. At equivalent NP/mL, the PA signal intensity scaled with AuNR size, indicating that overall mass has an effect on PA response, and reinforcing the importance of efficient tumour targeting. Under PW illumination, all AuNRs showed toxicity at a laser fluence below the maximum permissible exposure to skin, with a maximum of 80% cell-death exhibited by the smallest AuNRs, strengthening the feasibility of PW-PPTT. The theranostic potential of PW lasers combined with AuNRs has been demonstrated for application in the lung.
Integrated Analysis of Transcriptomic and Proteomics Data Reveals the Induction Effects of Rotenoid Biosynthesis of Mirabilis himalaica Caused by UV-B Radiation
Authors: Gu Li , Zheng Weilie , Li Mingjie , Quan Hong , Wang Jianming , Wang Fengji , Huang Wei , Wu Yunfang , Lan Xiaozhong , Zhang Zhongyi
Published: October 2018

Mirabilis himalaica (Edgew.) Heimerl is one of the most important genuine medicinal plants in Tibet, in which the special plateau habitat has been associated with its excellent medicinal quality and efficacy. However, the mechanisms by which environmental factors affect biosynthesis of secondary metabolic components remain unclear in this species. In this study, RNA sequencing and iTRAQ (isobaric Tags for Relative and Absolute Quantification) techniques were used to investigate the critical molecular “events” of rotenoid biosynthesis responding to UV-B radiation, a typical plateau ecological factor presented in native environment-grown M. himalaica plants. A total of 3641 differentially expressed genes (DEGs) and 106 differentially expressed proteins (DEPs) were identified in M. himalaica between UV-B treatment and control check (CK). Comprehensive analysis of protein and transcript data sets resulted in 14 and 7 DEGs from the plant hormone signal transduction and phosphatidylinositol signaling system pathways, respectively, being significantly enriched. The result showed that the plant hormone signal transduction and phosphatidylinositol signaling system might be the key metabolic strategy of UV-B radiation to improve the biosynthesis of rotenoid in M. himalaica. At same time, most of the DEGs were associated with auxin and calcium signaling, inferring that they might drive the downstream transmission of these signal transduction pathways. Regarding those pathways, two chalcone synthase enzymes, which play key roles in the biosynthesis of rotenoid that were thought as the representative medicinal component of M. himalaica, were significantly upregulated in UV-B radiation. This study provides a theoretical basis for further exploration of the adaptation mechanism of M. himalaica to UV-B radiation, and references for cultivation standardization.
Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia
Authors: Stuani Lucille , Riols Fabien , Millard Pierre , Sabatier Marie , Batut Aurélie , Saland Estelle , Viars Fanny , Tonini Laure , Zaghdoudi Sonia , Linares Laetitia K. , Portais Jean-Charles , Sarry Jean-Emmanuel , Bertrand-Michel Justine
Published: October 2018

Background: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells. Moreover, two key metabolic enzymes, isocitrate dehydrogenases (IDH1/2), are mutated in more than 15% of AML patient, reinforcing the interest in studying metabolic reprogramming, in particular in this subgroup of patients. Methods: Using a multi-omics approach combining proteomics, lipidomics, and isotopic profiling of [U-13C] glucose and [U-13C] glutamine cultures with more classical biochemical analyses, we studied the impact of the IDH1 R132H mutation in AML cells on lipid biosynthesis. Results: Global proteomic and lipidomic approaches showed a dysregulation of lipid metabolism, especially an increase of phosphatidylinositol, sphingolipids (especially few species of ceramide, sphingosine, and sphinganine), free cholesterol and monounsaturated fatty acids in IDH1 mutant cells. Isotopic profiling of fatty acids revealed that higher lipid anabolism in IDH1 mutant cells corroborated with an increase in lipogenesis fluxes. Conclusions: This integrative approach was efficient to gain insight into metabolism and dynamics of lipid species in leukemic cells. Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production.
IL-18 and S100A12 Are Upregulated in Experimental Central Retinal Vein Occlusion
Authors: Cehofski Lasse Jørgensen , Kruse Anders , Kirkeby Svend , Alsing Alexander Nørgård , Ellegaard Nielsen Jonas , Kojima Kentaro , Honoré Bent , Vorum Henrik
Published: October 2018

Retinal vein occlusion (RVO) is a common retinal vascular disease. RVO may be complicated by pronounced ischemia that often leads to severe loss of visual function. The present work aimed at studying the retinal proteome of RVO complicated by ischemia. In six Danish Landrace pigs RVO was induced with argon laser in the right eye of each animal. As four retinal veins were occluded, the RVO best corresponded to a central retinal vein occlusion (CRVO). Left control eyes received a similar laser treatment without inducing occlusion. RVO and retinal ischemia were verified by angiography. The retinas were collected 15 days after RVO for proteomic analysis. RVO resulted in a downregulation of proteins involved in visual perception, including rhodopsin, transducin alpha chain, and peripherin-2. RVO also caused a downregulation of proteins involved in neurotransmitter transport, including glutamate decarboxylase 1 (GAD1), glutamate decarboxylase 2 (GAD2), and complexins 2–4. RVO lead to increased contents of proteins involved in inflammation, including interleukin-18 (IL-18), S100A12, and annexin A1 (ANXA1). Immunohistochemistry revealed a general retinal upregulation of IL-18 and ANXA1 while S100A12 was highly abundant in retinal ganglion cells in RVO. IL-18 and S100A12 are likely to be driving forces in the inflammatory response of RVO complicated by ischemia. Our findings also suggest that RVO results in compromised neurotransmission and a downregulation of proteins involved in visual perception.
Protective Effects of Kaempferitrin on Advanced Glycation End Products Induce Mesangial Cell Apoptosis and Oxidative Stress
Authors: Jiang Wenxian , Wang Rongshen , Liu Di , Zuo Min , Zhao Chunzhen , Zhang Tianliang , Li Wanzhong
Published: October 2018

Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) both play important roles in diabetic nephropathy (DN). Previous studies have identified glomerular mesangial cells (GMCs) injury as a key early risk factor in the development of DN. Kaempferitrin (KM) is a potent antioxidant with hypoglycemic action. Although KM is known to protect against AGE-induced damage in GMCs, the effects and the mechanisms by which they occur are poorly understood. In this study, cultured rat GMCs were exposed to AGE-induced oxidative stress (OS) to model DN in vitro. Reactive oxygen species (ROS) was analyzed by 2′,7′-dichlorofluorescin diacetate (DCFH-DA). Superoxide dismutase (SOD) and malondialdehyde (MDA) were studied using commercial kits. Mitochondrial membrane potential (Δψm) was measured by rhodamine 123. Hoechst 33258 and annexin V and propidium iodide (PI) double staining were performed to observe the apoptosis states in GMCs, whereas apoptosis and protective mechanism in AGE-induced GMCs were investigated by Western blot. The data revealed that KM effectively increased SOD activity, decreased MDA levels, suppressed ROS generation, and protected against OS in AGE-induced GMCs. Treatment with KM also inhibited the expression of collagen IV and transforming growth factor-β1 (TGF-β1), improved mitochondrial membrane potential recovery, and suppressed the mitochondrial/cytochrome c-mediated apoptosis pathway through the expression of anti-apoptotic factors in GMCs in vitro. These findings suggest that KM may be a new potential agent in the treatment of DN in future.
SREBP-1c-Dependent Metabolic Remodeling of White Adipose Tissue by Caloric Restriction
Authors: Kobayashi Masaki , Fujii Namiki , Narita Takumi , Higami Yoshikazu
Published: October 2018

Caloric restriction (CR) delays the onset of many age-related pathophysiological changes and extends lifespan. White adipose tissue (WAT) is not only a major tissue for energy storage, but also an endocrine tissue that secretes various adipokines. Recent reports have demonstrated that alterations in the characteristics of WAT can impact whole-body metabolism and lifespan. Hence, we hypothesized that functional alterations in WAT may play important roles in the beneficial effects of CR. Previously, using microarray analysis of WAT from CR rats, we found that CR enhances fatty acid (FA) biosynthesis, and identified sterol regulatory element-binding protein 1c (SREBP-1c), a master regulator of FA synthesis, as a mediator of CR. These findings were validated by showing that CR failed to upregulate factors involved in FA biosynthesis and to extend longevity in SREBP-1c knockout mice. Furthermore, we revealed that SREBP-1c is implicated in CR-associated mitochondrial activation through the upregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. Notably, these CR-associated phenotypes were observed only in WAT. We conclude that CR induces SREBP-1c-dependent metabolic remodeling, including the enhancement of FA biosynthesis and mitochondrial activation, via PGC-1α in WAT, resulting in beneficial effects.
Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model
Authors: Takitani Kimitaka , Kishi Kanta , Miyazaki Hiroshi , Koh Maki , Tamaki Hirofumi , Inoue Akiko , Tamai Hiroshi
Published: October 2018

Cholestasis is defined as a reduction of bile secretion caused by a dysfunction of bile formation. Insufficient bile secretion into the intestine undermines the formation of micelles, which may result in the reduced absorption of lipids and fat-soluble vitamins. Here, we investigated the retinol homeostasis and the alterations of retinol metabolism-related genes, including β-carotene 15,15′ monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), cytochrome P450 26A1 (CYP26A1), and retinoic acid receptors (RAR) β, in a α-naphthyl isothiocyanate (ANIT)-induced cholestasis rat model. Moreover, we examined the expression of the farnesoid X receptor (FXR) target genes. Our results showed that plasma retinol levels were decreased in ANIT rats compared to control rats. On the contrary, hepatic retinol levels were not different between the two groups. The expression of FXR target genes in the liver and intestine of cholestasis model rats was repressed. The BCMO expression was decreased in the liver and increased in the intestine of ANIT rats compared to control rats. Finally, the hepatic expression of LRAT, RARβ, and ALDH1A1 in cholestatic rats was decreased compared to the control rats, while the CYP26A1 expression of the liver was not altered. The increased expression of intestinal BCMO in cholestasis model rats might compensate for decreased circulatory retinol levels. The BCMO expression might be regulated in a tissue-specific manner to maintain the homeostasis of retinol.
Genome-Wide Identification and Characterization of Pectin Methylesterase Inhibitor Genes in Brassica oleracea
Authors: Liu Tingting , Yu Hui , Xiong Xingpeng , Yu Youjian , Yue Xiaoyan , Liu Jinlong , Cao Jiashu
Published: October 2018

The activities of pectin methylesterases (PMEs) are regulated by pectin methylesterase inhibitors (PMEIs), which consequently control the pectin methylesterification status. However, the role of PMEI genes in Brassica oleracea, an economically important vegetable crop, is poorly understood. In this study, 95 B. oleracea PMEI (BoPMEI) genes were identified. A total of 77 syntenic ortholog pairs and 10 tandemly duplicated clusters were detected, suggesting that the expansion of BoPMEI genes was mainly attributed to whole-genome triplication (WGT) and tandem duplication (TD). During diploidization after WGT, BoPMEI genes were preferentially retained in accordance with the gene balance hypothesis. Most homologous gene pairs experienced purifying selection with ω (Ka/Ks) ratios lower than 1 in evolution. Five stamen-specific BoPMEI genes were identified by expression pattern analysis. By combining the analyses of expression and evolution, we speculated that nonfunctionalization, subfunctionalization, neofunctionalization, and functional conservation can occur in the long evolutionary process. This work provides insights into the characterization of PMEI genes in B. oleracea and contributes to the further functional studies of BoPMEI genes.
The Role of PPAR-δ in Metabolism, Inflammation, and Cancer: Many Characters of a Critical Transcription Factor
Authors: Liu Yi , Colby Jennifer K. , Zuo Xiangsheng , Jaoude Jonathan , Wei Daoyan , Shureiqi Imad
Published: October 2018

Peroxisome proliferator-activated receptor-delta (PPAR-δ), one of three members of the PPAR group in the nuclear receptor superfamily, is a ligand-activated transcription factor. PPAR-δ regulates important cellular metabolic functions that contribute to maintaining energy balance. PPAR-δ is especially important in regulating fatty acid uptake, transport, and β-oxidation as well as insulin secretion and sensitivity. These salutary PPAR-δ functions in normal cells are thought to protect against metabolic-syndrome-related diseases, such as obesity, dyslipidemia, insulin resistance/type 2 diabetes, hepatosteatosis, and atherosclerosis. Given the high clinical burden these diseases pose, highly selective synthetic activating ligands of PPAR-δ were developed as potential preventive/therapeutic agents. Some of these compounds showed some efficacy in clinical trials focused on metabolic-syndrome-related conditions. However, the clinical development of PPAR-δ agonists was halted because various lines of evidence demonstrated that cancer cells upregulated PPAR-δ expression/activity as a defense mechanism against nutritional deprivation and energy stresses, improving their survival and promoting cancer progression. This review discusses the complex relationship between PPAR-δ in health and disease and highlights our current knowledge regarding the different roles that PPAR-δ plays in metabolism, inflammation, and cancer.
The Pathophysiology of Gestational Diabetes Mellitus
Authors: Plows Jasmine F , Stanley Joanna L , Baker Philip N , Reynolds Clare M , Vickers Mark H
Published: October 2018

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.
Interactive Roles for AMPK and Glycogen from Cellular Energy Sensing to Exercise Metabolism
Authors: Janzen Natalie R. , Whitfield Jamie , Hoffman Nolan J.
Published: October 2018

The AMP-activated protein kinase (AMPK) is a heterotrimeric complex with central roles in cellular energy sensing and the regulation of metabolism and exercise adaptations. AMPK regulatory β subunits contain a conserved carbohydrate-binding module (CBM) that binds glycogen, the major tissue storage form of glucose. Research over the past two decades has revealed that the regulation of AMPK is impacted by glycogen availability, and glycogen storage dynamics are concurrently regulated by AMPK activity. This growing body of research has uncovered new evidence of physical and functional interactive roles for AMPK and glycogen ranging from cellular energy sensing to the regulation of whole-body metabolism and exercise-induced adaptations. In this review, we discuss recent advancements in the understanding of molecular, cellular, and physiological processes impacted by AMPK-glycogen interactions. In addition, we appraise how novel research technologies and experimental models will continue to expand the repertoire of biological processes known to be regulated by AMPK and glycogen. These multidisciplinary research advances will aid the discovery of novel pathways and regulatory mechanisms that are central to the AMPK signaling network, beneficial effects of exercise and maintenance of metabolic homeostasis in health and disease.
iTRAQ-Based Quantitative Proteome Revealed Metabolic Changes in Winter Turnip Rape (Brassica rapa L.) under Cold Stress
Authors: Xu Yaozhao , Zeng Xiucun , Wu Jian , Zhang Fenqin , Li Caixia , Jiang Jinjin , Wang Youping , Sun Wancang
Published: October 2018

Winter turnip rape (Brassica rapa L.) is a large-scale winter-only oil crop cultivated in Northwest China. However, its cold-resistant molecular mechanism remains inadequate. Studying the cold adaptation mechanisms of winter turnip rape based on the proteomic technique of isobaric tags for relative and absolute quantification (iTRAQ) offers a solution to this problem. Under cold stress (−4 °C for eight hours), 51 and 94 differently accumulated proteins (DAPs) in Longyou 7 (cold-tolerant) and Tianyou 4 (cold-sensitive) were identified, respectively. These DAPs were classified into 38 gene ontology (GO) term categories, such as metabolic process, cellular process, catalytic activity, and binding. The 142 DAPs identified between the two cold-stressed cultivars were classified into 40 GO terms, including cellular process, metabolic process, cell, catalytic activity, and binding. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the DAPs participated in 10 pathways. The abundance of most protein functions in ribosomes, carbon metabolism, photosynthesis, and energy metabolism including the citrate cycle, pentose phosphate pathway, and glyoxylate and dicarboxylate metabolism decreased, and the proteins that participate in photosynthesis–antenna and isoflavonoid biosynthesis increased in cold-stressed Longyou 7 compared with those in cold-stressed Tianyou 4. The expression pattern of genes encoding the 10 significant DAPs was consistent with the iTRAQ data. This study provides new information on the proteomic differences between the leaves of Longyou 7 and Tianyou 4 plants and explains the possible molecular mechanisms of cold-stress adaptation in B. rapa.
Oleandrin and Its Derivative Odoroside A, Both Cardiac Glycosides, Exhibit Anticancer Effects by Inhibiting Invasion via Suppressing the STAT-3 Signaling Pathway
Authors: Ko Young , Rugira Trojan , Jin Hana , Park Sang , Kim Hye
Published: October 2018

The cardiac glycosides oleandrin and odoroside A, polyphenolic monomer compounds extracted from Nerium oleander, have been found to have antitumor effects on various tumors at low doses. However, the mechanisms of anticancer effects of oleandrin and odoroside A are not well known. Therefore, in this study, we aimed to investigate the anticancer effects of oleandrin and odoroside A and their associated mechanisms in highly metastatic MDA-MB-231 breast cancer cells and radiotherapy-resistant (RT-R) MDA-MB-231 cells. Our results showed that oleandrin and odoroside A dose-dependently decreased the colony formation and the invasion of both cell lines at nanomolar ranges. Furthermore, oleandrin (50 nM) and odoroside A (100 nM) reduced octamer-binding transcription factor 3/4 (OCT3/4) and β-catenin levels and matrix metalloproteinase-9 (MMP-9) activity. Finally, we found that phospho-STAT-3 levels were increased in MDA-MB-231 and RT-R-MDA-MB-231, but not in endothelial cells (ECs), and that the levels were significantly decreased by oleandrin (50 nM) and odoroside A (100 nM). Inhibition of phospho-signal transducer and activator of transcription (STAT)-3 significantly reduced OCT3/4 and β-catenin levels and MMP-9 activity, ultimately resulting in reduced invasion. These results suggest that the anticancer effects of oleandrin and odoroside A might be due to the inhibition of invasion through of phospho-STAT-3-mediated pathways that are involved in the regulation of invasion-related molecules.
ImplicPBDD: A New Approach to Extract Proper Implications Set from High-Dimension Formal Contexts Using a Binary Decision Diagram †
Authors: Santos Phillip G. , Ruas Pedro Henrique B. , Neves Julio C. V. , Silva Paula R. , Dias Sérgio M. , Zárate Luis E. , Song Mark A. J.
Published: October 2018

Formal concept analysis (FCA) is largely applied in different areas. However, in some FCA applications the volume of information that needs to be processed can become unfeasible. Thus, the demand for new approaches and algorithms that enable processing large amounts of information is increasing substantially. This article presents a new algorithm for extracting proper implications from high-dimensional contexts. The proposed algorithm, called ImplicPBDD, was based on the PropIm algorithm, and uses a data structure called binary decision diagram (BDD) to simplify the representation of the formal context and enhance the extraction of proper implications. In order to analyze the performance of the ImplicPBDD algorithm, we performed tests using synthetic contexts varying the number of objects, attributes and context density. The experiments show that ImplicPBDD has a better performance—up to 80% faster—than its original algorithm, regardless of the number of attributes, objects and densities.
A Semi-Empirical Method for the Estimation of the Hydration Number of Mn(II)-Complexes
Authors: Peters Joop A. , Geraldes Carlos F. G. C.
Published: October 2018

A semi-empirical equation to estimate the hydration number of Mn(II) complexes was derived from a database of 49 previously published 1H longitudinal Nuclear Magnetic Relaxation Dispersion profiles. This equation has the longitudinal 1H relaxivity and the molecular weight of the Mn(II) complex under consideration as parameters.
Changes in the Ground Reaction Force, Lower-Limb Muscle Activity, and Joint Angles in Athletes with Unilateral Ankle Dorsiflexion Restriction During A Rebound-Jump Task
Authors: Kondo Hitoshi
Published: October 2018

Background: This study compared differences between a control group and a group with unilateral ankle dorsiflexion restriction in the ground reaction force (GRF), angles of the lower limbs joints, and muscular activity during a rebound-jump task in athletes who continue to perform sports activities with unilateral ankle dorsiflexion restriction. Methods: The athletes were divided into the following two groups: The dorsiflexion group included those with a difference of ≥7° between bilateral ankle dorsiflexion angles (DF), and the control group included those with a difference of <7° between the two ankles (C). An ankle foot orthosis was attached to subjects in group C to apply a restriction on the right-angle dorsiflexion angle. The percentage of maximum voluntary contraction (%MVC) of the legs musculature, components of the GRF, and the hip and knee joint angles during the rebound-jump task were compared between groups DF and C. Results: Group DF showed increased %MVC of the quadriceps muscle, decreased upward component of the GRF, decreased hip flexion, and increased knee eversion angles. Conclusions: This study highlighted that athletes with ankle dorsiflexion restriction had significantly larger knee eversion angles in the rebound-jump task. The reduced hip flexion was likely caused by the restricted ankle dorsiflexion and compensated by the observed increase in quadriceps muscle activation when performing the jump.
Nonlinear Model Predictive Control Using Robust Fixed Point Transformation-Based Phenomena for Controlling Tumor Growth
Authors: Czakó Bence , Kovács Levente
Published: October 2018

In this paper a novel control strategy is introduced in order to create optimal dosage profiles for individualized cancer treatment. This approach uses Nonlinear Model Predictive Control to construct optimal dosage protocols in conjunction with Robust Fixed Point Transformations which hinders the negative effect of inherent model uncertainties and measurement disturbances. The results are validated by extensive simulation on the proposed control algorithm from which conclusions were drawn.
A New Concept of Fixed Point in Metric and Normed Interval Spaces
Authors: Wu Hsien-Chung
Published: October 2018

The main aim of this paper is to propose the concept of so-called near fixed point and establish many types of near fixed point theorems in the set of all bounded and closed intervals in R . The concept of null set will be proposed in order to interpret the additive inverse element in the set of all bounded closed intervals. Based on the null set, the concepts of metric interval space and normed interval space are proposed, which are not the conventional metric and normed spaces. The concept of near fixed point is also defined based on the null set. In this case, we shall establish many types of near fixed point theorems in the metric and normed interval spaces.
Metrics for Single-Edged Graphs over a Fixed Set of Vertices
Authors: Chen Ray-Ming
Published: October 2018

Graphs have powerful representations of all kinds of theoretical or experimental mathematical objects. A technique to measure the distance between graphs has become an important issue. In this article, we show how to define distance functions measuring the distance between graphs with directed edges over a fixed set of named and unnamed vertices, respectively. Furthermore, we show how to implement these distance functions via computational matrix operations.
Components from the Leaves and Twigs of Mangrove Lumnitzera racemosa with Anti-Angiogenic and Anti-Inflammatory Effects
Authors: Yu Szu-Yin , Wang Shih-Wei , Hwang Tsong-Long , Wei Bai-Luh , Su Chien-Jung , Chang Fang-Rong , Cheng Yuan-Bin
Published: October 2018

One new neolignan, racelactone A (1), together with seven known compounds (2−8) were isolated from the methanolic extract of the leaves and twigs of Lumnitzera racemosa. The structure of racelactone A (1) was determined on the basis of the mass and NMR spectroscopic data interpretation. With respect to bioactivity, compound 1 displayed an anti-angiogenic effect by suppressing tube formation. Furthermore, compounds 1, 4, and 5 showed significant anti-inflammatory effects with IC50 values of 4.95 ± 0.89, 1.95 ± 0.40, and 2.57 ± 0.23 μM, respectively. The plausible biosynthesis pathway of racelactone A (1) was proposed.
Bioactive Compounds from Marine-Derived Aspergillus, Penicillium, Talaromyces and Trichoderma Species
Authors: Nicoletti Rosario , Vinale Francesco
Published: October 2018

The impact of bioactive compounds from natural sources on human life, particularly in pharmacology and biotechnology, has challenged the scientific community to explore new environmental contexts and the associated microbial diversity. [...]
Critical Distance Default Values for Structural Steels and a Simple Formulation to Estimate the Apparent Fracture Toughness in U-Notched Conditions
Authors: Cicero Sergio , Fuentes Juan Diego , Procopio Isabela , Madrazo Virginia , González Pablo
Published: October 2018

The structural integrity assessment of components containing notch-type defects has been the subject of extensive research in the last few decades. The assumption that notches behave as cracks is generally too conservative, making it necessary to develop assessment methodologies that consider the specific nature of notches, providing accurate safe predictions of failure loads or defect sizes. Among the different theories or models that have been developed to address this issue the Theory of Critical Distances (TCD) is one of the most widely applied and extended. This theory is actually a group of methodologies that have in common the use of the material toughness and a length parameter that depends on the material (the critical distance; L). This length parameter requires calibration in those situations where there is a certain non-linear behavior on the micro or the macro scale. This calibration process constitutes the main practical barrier for an extensive use of the TCD in structural steels. The main purpose of this paper is to provide, through a set of proposed default values, a simple methodology to accurately estimate both the critical distance of structural steels and the corresponding apparent fracture toughness predictions derived from the TCD.
Evidence That Parietal Lobe Fatty Acids May Be More Profoundly Affected in Moderate Alzheimer’s Disease (AD) Pathology Than in Severe AD Pathology
Authors: Nasaruddin Muhammad L. , Pan Xiaobei , McGuinness Bernadette , Passmore Peter , Kehoe Patrick G. , Hölscher Christian , Graham Stewart F. , Green Brian D.
Published: October 2018

Brain is a lipid-rich tissue, and fatty acids (FAs) play a crucial role in brain function, including neuronal cell growth and development. This study used GC-MS to survey all detectable FAs in the human parietal cortex (Brodmann area 7). These FAs were accurately quantified in 27 cognitively normal age-matched controls, 16 cases of moderate Alzheimer’s disease (AD), 30 severe AD, and 14 dementia with Lewy bodies (DLB). A total of 24 FA species were identified. Multiple comparison procedures, using stepdown permutation tests, noted higher levels of 13 FAs but the majority of changes were in moderate AD and DLB, rather than severe AD. Subjects with moderate AD and DLB pathology exhibited significantly higher levels of a number of FAs (13 FAs and 12 FAs, respectively). These included nervonic, lignoceric, cis-13,16-docosadienoic, arachidonic, cis-11,14,17-eicosatrienoic, erucic, behenic, α-linolenic, stearic, oleic, cis-10-heptanoic, and palmitic acids. The similarities between moderate AD and DLB were quite striking—arachidic acid was the only FA which was higher in moderate AD than control, and was not similarly affected in DLB. Furthermore, there were no significant differences between moderate AD and DLB. The associations between each FA and a number of variables, including diagnosis, age, gender, Aβ plaque load, tau load, and frontal tissue pH, were also investigated. To conclude, the development of AD or DLB pathology affects brain FA composition but, intriguingly, moderate AD neuropathology impacts this to a much greater extent. Post-mortem delay is a potential confounding factor, but the findings here suggest that there could be a more dynamic metabolic response in the earlier stages of the disease pathology.
AlGaN/GaN High Electron Mobility Transistors on Semi-Insulating Ammono-GaN Substrates with Regrown Ohmic Contacts
Authors: Wojtasiak Wojciech , Góralczyk Marcin , Gryglewski Daniel , Zając Marcin , Kucharski Robert , Prystawko Paweł , Piotrowska Anna , Ekielski Marek , Kamińska Eliana , Taube Andrzej , Wzorek Marek
Published: October 2018

AlGaN/GaN high electron mobility transistors on semi-insulating bulk ammonothermal GaN have been investigated. By application of regrown ohmic contacts, the problem with obtaining low resistance ohmic contacts to low-dislocation high electron mobility transistor (HEMT) structures was solved. The maximum output current was about 1 A/mm and contact resistances was in the range of 0.3–0.6 Ω ·mm. Good microwave performance was obtained due to the absence of parasitic elements such as high access resistance.
Controls on Barite Crystal Morphology during Abiotic Precipitation
Authors: Widanagamage Inoka H. , Waldron Allison R. , Glamoclija Mihaela
Published: October 2018

Barite (BaSO4) is a stable and widely distributed mineral in Earth’s crust. As such, barite has the potential to preserve specific geochemical and morphological characteristics representative of conditions at the time of its formation, which could be useful for interpretations of Earth’s ancient rocks and paleoenvironments. In this study, we used variations in saturation index, solution temperature, solution chemistry, presence of organics, and Mg2+ and Ca2+ ions to investigate variations in barite crystal morphology. Through 42 experiments, we simulated poorly understood, low temperature spring settings similar to Zodletone Spring in Anadarko Basin, Oklahoma. Using SEM/EDS, we identified barite rosettes, rounded barite, euhedral/square-shaped barite, and elliptical barite as the crystal morphologies that directly reflect different formational settings. The X-ray diffraction (XRD) patterns revealed different crystallographic characters of the four distinct barite crystal morphologies; in particular, the samples that precipitated from supersaturated SrSO4 solution exhibited double peaks at 43° 2-Theta, which matched barite with strontium substitution as barite might have incorporated strontium in its structure. Barite crystals that formed in the presence of organics in the initial solution exhibited a double peak at 33° 2-Theta, which was absent in other samples. Confocal Raman microscopy indicated that all of the samples had typical barium sulfate bands, with a few differences in bands between the samples; for example, the 638 cm−1 band showed splitting or a double band between different samples. The samples that precipitated from solution with organics had organic compounds from the experimental solution included in their composition. In both cases, C–H stretches from 2800 cm−1 to 3000 cm−1 were present as well as bands from 1350 cm−1 to 1500 cm−1, which are typical of organic compounds. Based on our experiments, the variation in barite crystal morphologies reflected changes in initial solution chemistry (or environmental settings).
Medicinal Plants Used for the Traditional Management of Diabetes in the Eastern Cape, South Africa: Pharmacology and Toxicology
Authors: Odeyemi Samuel , Bradley Graeme
Published: October 2018

The use of medicinal plants for the management of diabetes mellitus is on the rise in the developing countries, including South Africa. There is increasing scientific evidence that supports the claims by the traditional healers. In this review, we compare the families of previously reported anti-diabetic plants in the Eastern Cape by rating the anti-diabetic activity, mode of action and also highlight their therapeutic potentials based on the available evidence on their pharmacology and toxicity. Forty-five plants mentioned in ethnobotanical surveys were subjected to a comprehensive literature search in the available electronic databases such as PubMed, ScienceDirect, Google Scholar and Elsevier, by using “plant name” and “family” as the keywords for the primary searches to determine the plants that have been scientifically investigated for anti-diabetic activity. The search returned 25 families with Asteraceae highly reported, followed by Asphodelaceae and Alliaceae. Most of the plants have been studied for their anti-diabetic potentials in vivo and/or in vitro, with most of the plants having a higher percentage of insulin release and inhibition against carbohydrate digesting enzymes as compared with insulin mimetic and peripheral glucose uptake. Almost all the investigated plants also inhibit oxidative stress as part of their hypoglycemic activity with less toxicity. However, the isolation of their bioactive molecules is still lacking. This review provides a resource to enable thorough assessments of the therapeutic profiles of available medicinal plants used for the management of diabetes in the Eastern Cape, South Africa. Further studies such as the identification of the active ingredients of potent plants still need to be carried out; this may lead to new molecules in drug discovery and development.
Bioformation of Volatile and Nonvolatile Metabolites by Saccharomycopsis fibuligera KJJ81 Cultivated under Different Conditions—Carbon Sources and Cultivation Times
Authors: Lee Sang Mi , Jung Ji Hye , Seo Jeong-Ah , Kim Young-Suk
Published: October 2018

Saccharomycopsis fibuligera KJJ81 isolated from nuruk is an amylolytic yeast that is widely used as a microbial starter in various fermented foods. Volatile and nonvolatile metabolites of S. fibuligera KJJ81 were investigated according to different carbon sources and cultivation times using a nontargeted metabolomic approach. Partial-least-squares discriminant analysis was applied to determine the major metabolites, which were found to be closely related to the clustering and discrimination of S. fibuligera KJJ81 samples. Some volatile metabolites derived from phenylalanine, such as 2-phenylethanol, 2-phenylethyl acetate, and ethyl phenylacetate, were predominantly found in cultivation medium containing glucose (YPD medium). In addition, the level of 2-phenylethanol increased continuously with the cultivation time. In terms of nonvolatile metabolites, carbohydrates (mannose, arabitol, and mannitol), fatty acids (palmitic acid and stearic acid), organic acids (oxalic acid and succinic acid), and amino acids (isoleucine, serine, alanine, glutamic acid, glycine, proline, phenylalanine, and threonine) were the main contributors to S. fibuligera KJJ81 samples cultivated in YPD medium according to cultivation time. These results show that the formation of volatile and nonvolatile metabolites of S. fibuligera KJJ81 can be significantly affected by both the carbon sources and the cultivation time.