bluuebunny/crossref_metadata_2025 huggingface dataset:
Concentration of Organotin and Booster Biocides in Sediments of Seagrass Area from Sungai Pulai Estuary, South of Johor, Malaysia
Authors: Mukhtar Aqilah , Mohamat-Yusuff Ferdaus , Zulkifli Syaizwan Zahmir , Harino Hiroya , Ismail Ahmad , Inoue Koji
Published: February 2019

Antifouling compounds are widely used in paints applied on ship hulls to prevent attachment of fouling organisms. However, a certain amount of these chemicals could leach from the painted surface, enter seawater, and pose deleterious effects on various marine biotas. The present study aimed to determine the concentration of organotin (OT) compounds and booster biocides in sediments collected from the seagrass area of Sungai Pulai estuary, Malaysia. The sediment samples were collected from three points on the seagrass bed, brought back to the laboratory, extracted using standard extraction procedure, and the analytes were analysed using gas chromatography-mass spectrometry (GC-MS) method. The results showed that tributyltin (TBT) concentrations in sediments were within the range of 8.1 ± 0.4 to 10.6 ± 0.5 µg/kg, whereas the values of triphenyltin (TPT) were between 17.1 ± 0.9 and 19.4 ± 1.0 µg/kg. The range of concentration of booster biocides, namely diuron, dichlofluanid chlorothalonil, Irgarol 1051, M1, and Sea-Nine 211, were from <0.1 to 22.9 ± 1.1, 48.7 ± 2.4 to 800 ± 40, <0.1 to 6.2 ± 0.3, <0.1 to 1.4 ± 0.1, 44 ± 2.2 to 877 ± 44, and 9.1 ± 0.5 to 170 ± 8.5 µg/kg, respectively. The concentration of organotin was much lower than the previous study conducted in southern Johor. Meanwhile, the increased concentration of booster biocides proves the use of these compounds as antifouling paints in shipping systems nowadays.
Effect of Microwave Drying on the Drying Characteristics, Color, Microstructure, and Thermal Properties of Trabzon Persimmon
Authors: Çelen Soner
Published: February 2019

In this study, changes in the drying kinetics, color change, and the energy consumption for microwave energy were investigated for Trabzon persimmon. In addition to that, the microstructure of the persimmon was also investigated by considering its thermal changes. It is important to be aware of the purpose of the drying process for determining the drying system. Results of this research showed that 460 W for 7 mm slice thickness depending on energy consumption, 600 W for 5 mm slice thickness depending on drying time, and 600 W depending on color changes were found as suitable drying processes depending on drying conditions. The effective diffusion values varied between 2.97 × 10−8 m2 s−1 and 4.63 × 10−6 m2 s−1. The activation energy values for 5 mm, 7 mm and 9 mm slice thickness were estimated as 32.82, 18.64, and 12.80 W g−1, respectively. The drying time and energy consumption decreased, whereas drying rate increased with an increase in the microwave energy. The number of pores increased compared to structure of fresh sample, and the pores got to be larger for 5 mm slice thickness as the power level increased. Results showed that the applied microwave energy had an important effect on the heating of the material and the change in the microstructure.
Identification of Potential Genes Responsible for Thermotolerance in Wheat under High Temperature Stress
Authors: Su Peipei , Jiang Cai , Qin Hao , Hu Rui , Feng Jialu , Chang Junli , Yang Guangxiao , He Guangyuan
Published: February 2019

Wheat, a major worldwide staple food crop, is relatively sensitive to a changing environment, including high temperature. The comprehensive mechanism of heat stress response at the molecular level and exploitation of candidate tolerant genes are far from enough. Using transcriptome data, we analyzed the gene expression profiles of wheat under heat stress. A total of 1705 and 17 commonly differential expressed genes (DEGs) were identified in wheat grain and flag leaf, respectively, through transcriptome analysis. Gene Ontology (GO) and pathway enrichment were also applied to illustrate the functions and metabolic pathways of DEGs involved in thermotolerance of wheat grain and flag leaf. Furthermore, our data suggest that there may be a more complex molecular mechanism or tighter regulatory network in flag leaf than in grain under heat stress over time, as less commonly DEGs, more discrete expression profiles of genes (principle component analysis) and less similar pathway response were observed in flag leaf. In addition, we found that transcriptional regulation of zeatin, brassinosteroid and flavonoid biosynthesis pathways may play an important role in wheat’s heat tolerance. The expression changes of some genes were validated using quantitative real-time polymerase chain reaction and three potential genes involved in the flavonoid biosynthesis process were identified.
Rehabilitative Support for Persons with Dementia and Their Families to Acquire Self-Management Attitude and Improve Social Cognition and Sense of Cognitive Empathy
Authors: Maki Yohko , Hattori Hideyuki
Published: February 2019

People with dementia are often inevitably confronted with various difficulties with social interaction and communication, which is a core problem that can be improved with rehabilitative support, thus improving their quality of life. The authors propose rehabilitative support using communication via activities; co-beneficial relationship-based rehabilitation, which emphasizes the following 3 points: support for people with dementia to improve social reserves, which is the ability to overcome the decline in social cognition; support for family members for improving cognitive empathy, which is the ability to analyze the background of others’ behaviors and speech; and the involvement of the practitioner to supervise and empower them. The process of intervention is as follows: (1) selecting activities for collaboration; (2) sharing information on their current situation including declined abilities; (3) enhancing cognitive empathy through dementia education; (4) designing the intervention measures together; and (5) practice and feedback. Living with dementia involves a continuous process of coping with various challenges in daily living, however, the process of effectively managing these challenges is one of the ways to improve the quality of life of people with dementia and their family members.
A Proposal for Afro-Hispanic Peoples and Culture as General Studies Course in African Universities
Authors: Uchechukwu Purity Ada
Published: February 2019

After centuries of denial, suppression and marginalization, the contributions of Afro-Hispanics/Latinos to the arts, culture, and the Spanish spoken in the Americas is gradually gaining recognition as Afro-descendants pursue their quest for visibility and space in Spanish America. Hand in hand with this development is the young generation of Afro-Latinos who, are proud to identify with the black race. Ironically, the young African student has very little knowledge of the presence and actual situation of Afro-descendants in Spanish-speaking America. This is because many African universities still follow the old colonial system which excludes knowledge of the presence and cultures of the once enslaved Africans in the Spanish speaking world. Thus, while Afro-descendants are fighting for visibility and recognition in Spanish America, they remain almost invisible in the African continent. The aim of this paper is to propose a curriculum, Afro-Hispanic Peoples and Culture, as a general studies course in African universities. Such a curriculum would create in Africa the much-needed visibility and contributions of Afro-descendants in Spanish-speaking America, and also foster collaborative works between young African academics and their counterparts in the Americas.
Shirley Jackson’s “The Lottery” and Holocaust Literature
Authors: Robinson Michael
Published: February 2019

Shirley Jackson’s “The Lottery” has been notorious since its first publication in 1948, but rarely, if ever, has it been read in light of its immediate historical context. This essay draws on literature, philosophy, and anthropology from the period to argue that Jackson’s story, which scholars have traditionally read through the lens of gender studies, invokes the themes of Holocaust literature. To support this argument, the essay explores imaginative Holocaust literature from the period by David Rousset, whose Holocaust memoir The Other Kingdom appeared in English translation in 1946, anthropological discourse from the period on scapegoating and European anti-Semitism, and critical discourse on the Holocaust and anti-Semitism from the period by Hannah Arendt and Theodor Adorno. The analysis finds that, in representing the phenomena of scapegoating and death selection in a small town in the US, Jackson’s story belongs to an abstract discourse on Holocaust-related themes and topics that was actively produced at midcentury, as evidenced partly by Rousset’s influential memoir. A master of the horror genre, Jackson could have drawn on her own experience of anti-Semitism, along with her known interest in the study of folklore, to contribute this chilling representation of the personal experience of death selection to a discourse on Holocaust-related themes. As this article shows, the abstract discourse Jackson’s story joined is marked by skepticism about or disinterest in ethnic difference and anthropological concepts. Due to the fact that this article features comparative analysis of Holocaust literature, a sub-topic is the debate among scholars concerning the ethics of literary representation of the Shoah and of analysis of Holocaust memoir. Jackson’s story and its context invoke perennially important questions about identity and representation in discourse about the Shoah and anti-Semitism.
An Examination of Twitter Data to Identify Risky Sexual Practices Among Youth and Young Adults in Botswana
Authors: Cornelius Judith , Kennedy Anna , Wesslen Ryan
Published: February 2019

Botswana has the third highest rate of HIV infection, as well as one of the highest mobile phone density rates in the world. The rate of mobile cell phone adoption has increased three-fold over the past 10 years. Due to HIV infection rates, youth and young adults are the primary target for prevention efforts. One way to improve prevention efforts is to examine how risk reduction messages are disseminated on social media platforms such as Twitter. Thus, to identify key words related to safer sex practices and HIV prevention, we examined three months of Twitter data in Botswana. 1 December 2015, was our kick off date, and we ended data collection on 29 February 2016. To gather the tweets, we searched for HIV-related terms in English and in Setswana. From the 140,240 tweets collected from 251 unique users, 576 contained HIV-related terms. A representative sample of 25 active Twitter users comprised individuals, one government site and 2 organizations. Data revealed that tweets related to HIV prevention and AIDS did not occur more frequently during the month of December when compared to January and February (t = 3.62, p > 0.05). There was no significant difference between the numbers of HIV related tweets that occurred from 1 December 2015 to 29 February 2016 (F = 32.1, p > 0.05). The tweets occurred primarily during the morning and evening hours and on Tuesdays followed by Thursdays and Fridays. The least number of tweets occurred on Sunday. The highest number of followers was associated with the Botswana government Twitter site. Twitter analytics was found to be useful in providing insight into information being tweeted regarding risky sexual behaviors.
Environmental and Genetic Factors in Autism Spectrum Disorders: Special Emphasis on Data from Arabian Studies
Authors: Almandil Noor B. , Alkuroud Deem N. , AbdulAzeez Sayed , AlSulaiman Abdulla , Elaissari Abdelhamid , Borgio J. Francis
Published: February 2019

One of the most common neurodevelopmental disorders worldwide is autism spectrum disorder (ASD), which is characterized by language delay, impaired communication interactions, and repetitive patterns of behavior caused by environmental and genetic factors. This review aims to provide a comprehensive survey of recently published literature on ASD and especially novel insights into excitatory synaptic transmission. Even though numerous genes have been discovered that play roles in ASD, a good understanding of the pathophysiologic process of ASD is still lacking. The protein–protein interactions between the products of NLGN, SHANK, and NRXN synaptic genes indicate that the dysfunction in synaptic plasticity could be one reason for the development of ASD. Designing more accurate diagnostic tests for the early diagnosis of ASD would improve treatment strategies and could enhance the appropriate monitoring of prognosis. This comprehensive review describes the psychotropic and antiepileptic drugs that are currently available as effective pharmacological treatments and provides in-depth knowledge on the concepts related to clinical, diagnostic, therapeutic, and genetic perspectives of ASD. An increase in the prevalence of ASD in Gulf Cooperation Council countries is also addressed in the review. Further, the review emphasizes the need for international networking and multidimensional studies to design novel and effective treatment strategies.
Associations between Green Building Design Strategies and Community Health Resilience to Extreme Heat Events: A Systematic Review of the Evidence
Authors: Houghton Adele , Castillo-Salgado Carlos
Published: February 2019

This project examined evidence linking green building design strategies with the potential to enhance community resilience to extreme heat events. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method for a systematic review, it assessed the strength of the evidence supporting the potential for Leadership in Energy and Environmental Design (LEED®) credit requirements to reduce the adverse effects of extreme heat events and/or enhance a building’s passive survivability (i.e., the ability to continue to function during utility outages) during those events. The PRISMA Flow Diagram resulted in the selection of 12 LEED for New Construction (LEED NC) credits for inclusion in the review. Following a preliminary scan of evidence supporting public health co-benefits of the LEED for Neighborhood Development rating system, queries were submitted in PubMed using National Library of Medicine Medical Subject Headings Terms. Queries identified links between LEED credit requirements and risk of exposure to extreme heat, environmental determinants of health, co-benefits to public health outcomes, and co-benefits to built environment outcomes. Public health co-benefits included reducing the risk of vulnerability to heat stress and reducing heat-related morbidity and mortality. The results lay the groundwork for collaboration across the public health, civil society, climate change, and green building sectors.
Comparison of Quality of Life and Work Ability of Taxi and Motorcycle Taxi Drivers: Evidence from Brazil
Authors: Machado Sanchez Hugo , Gouveia de Morais Sanchez Eliane , Alves Barbosa Maria , Celeno Porto Celmo , Silva Approbato Mario
Published: February 2019

Urban transport drivers, specifically taxi and motorcycle taxi drivers, are exposed to particular environmental, societal, and health situations related to their occupation. To compare work capacity and quality of life of taxi and motorcycle taxi drivers, and correlate quality of life and work ability, a cross-sectional descriptive study was conducted among 232 motorcycle taxi drivers and 60 male taxi drivers in urban cities of Brazil. Three instruments were used for evaluation: a questionnaire on sociodemographic and occupational issues, the Work Capacity Index (WCI), and the WHOQOL-bref (World Health Organization Quality of Life–Bref). Taxi drivers presented better evaluation scores in the physical and psychological domains and general quality of life (QOL) (p < 0.01), and better self-perceived work ability (lower physical and mental demands, fewer diagnosed diseases, less incapacity for professional practice, p < 0.001). In addition, there was a positive relationship between QOL and WCI (p = 0.001). Motorcycle taxi drivers had worse self-perceived QOL and of work ability, and there was a positive correlation between QOL and work ability.
Pre-Pregnancy Weight and Symptoms of Attention Deficit Hyperactivity Disorder and Executive Functioning Behaviors in Preschool Children
Authors: Fuemmeler Bernard F. , Zucker Nancy , Sheng Yaou , Sanchez Carmen E. , Maguire Rachel , Murphy Susan K. , Kollins Scott H. , Hoyo Cathrine
Published: February 2019

This study examines pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG) in relation to early childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and related executive self-regulation behaviors. The analyses sample (n = 331) included a subsample of participants from a birth cohort recruited from prenatal clinics and hospital facilities from April 2005 to June 2011 in Durham, North Carolina. Pre-pregnancy BMI was calculated from weight at the last menstrual period and height was extracted from medical records. Gestational weight gain was calculated from pre-pregnancy weight and weight measured at the time of delivery. ADHD symptoms and executive self-regulation behaviors were assessed by maternal report (mean age = 3 years). Multivariable regression methods with inverse probability weighting (IPW) were used to evaluate associations accounting for sample selection bias and confounding. Pre-pregnancy BMI at levels ≥35 was positively associated with higher ADHD symptoms and worse executive self-regulation behaviors (inhibitory control and attention). Compared to adequate GWG, less than adequate GWG was related to more ADHD hyperactive-impulsive symptoms, whereas greater than adequate GWG was related to more problematic behaviors related to working memory and planning. The findings support a link between maternal weight and child neurodevelopment. Continued research that help identify biological mechanisms are needed.
Contamination, Sources, and Health Risks Associated with Soil PAHs in Rebuilt Land from a Coking Plant, Beijing, China
Authors: Cao Wei , Yin Liqin , Zhang Dan , Wang Yingying , Yuan Jing , Zhu Yi , Dou Junfeng
Published: February 2019

This study investigated the polycyclic aromatic hydrocarbon (PAH) pollution in the reconstructed land of an abandoned industrial site: a coking plant in Beijing. To meet the needs of urban development, many factories have had to be relocated from city centers, and abandoned industrial sites often need to be transformed into residential land or urban green space through a series of restoration measures. It is necessary to study the level of residual pollutants and potential risks associated with industrial reconstructed land. The concentration of 16 PAHs in the study area ranged from 314.7 to 1618.3 µg/kg, and the average concentration was still at a medium pollution level; the concentration of PAHs in the original coking workshop had the highest levels (1350.5 µg/kg). The PAHs in the soil were mainly low-ring aromatics, especially naphthalene and phenanthrene. The isomer method and principal component analysis indicated that PAHs in the topsoil were the result of coal and biomass combustion. The seven carcinogenic PAHs were the main contributors to the total toxicity equivalence. The genetic toxicity of benzo[a]pyrene was relatively low, and the results were related to the concentration level. There were potential carcinogenic risks for people of varying ages in this residential area. In total, gender differences were small, and the comprehensive lifetime cancer risk level was still acceptable. For the remaining plots at the study site, the daily intake of PAHs by construction workers was between 0.74–2.31 ng/kg bw/day, which requires further evaluation about ignored area occupational exposure to environmental pollutants.
Association between Heavy Metals, Bisphenol A, Volatile Organic Compounds and Phthalates and Metabolic Syndrome
Authors: Shim Yun Hwa , Ock Jung Won , Kim Yoon-Ji , Kim Youngki , Kim Se Yeong , Kang Dongmug
Published: February 2019

The incidence of metabolic syndrome (MetS), which causes heart disease and stroke, has increased significantly worldwide. Although many studies have revealed the relationship between heavy metals (cadmium, mercury, and lead), the sum of metabolites of di(2-ethylhexyl) phthalate (DEHP), and MetS, the results remain inconsistent. No study has reported the association between various volatile organic compounds (VOCs) and phthalate metabolites with MetS. This cross-sectional study of a representative sample of adult South Koreans aimed to evaluate the relationship between heavy metals, VOC metabolites, phthalate metabolites, bisphenol A and MetS after adjusting for demographic variables. Data from the Korean National Environmental Health Survey II (2012–2014) (n = 5251) were used in the analysis. Multiple logistic regression analysis was performed for MetS with log-transformed hazardous material quartiles after covariate adjustment. Urine muconic acid (MuA) and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) levels were significantly associated with MetS after adjusting for confounders (odds ratio: 1.34 and 1.39, respectively). Urine MuA and MEHHP levels were significantly associated with MetS. Because of the rarity of this study, which investigated the relationship between each VOC and phthalate metabolite with MetS and the strict definition of all indirect measures of MetS components, further research is needed.
Perception of Climate Change in Shrimp-Farming Communities in Bangladesh: A Critical Assessment
Authors: Kais Shaikh Mohammad , Islam Md Saidul
Published: February 2019

Local contexts as well as levels of exposure play a substantial role in defining a community’s perception of climate and environmental vulnerabilities. In order to assess a community’s adaptation strategies, understanding of how different groups in that community comprehend climate change is crucial. Public risk perception is important as it can induce or confine political, economic, and social actions dealing with particular hazards. Climate change adaptation is a well-established policy discourse in Bangladesh that has made its people more or less aware of it. Similarly, shrimp-farming communities in southwestern Bangladesh understand environmental and climate change in their own ways. In order to understand how the shrimp-farming communities in coastal Bangladesh perceive current climate instabilities, we conducted a qualitative study in shrimp-farming villages in coastal Bangladesh where about 80% of commercial shrimp of the country is cultivated. We compared farmers’ perceptions of local climate change with existing scientific knowledge and found remarkable similarities. Our assessment shows that at least two factors are critical for this outcome: coastal people’s exposure to and experience of frequent climate extremes; and a radical approach to defining climate regimes in Bangladesh by various stakeholders and the media, depicting anthropogenic global warming as a certainty for the country. Thus, a convergence of scientific construct and sociocultural construct construes the level of awareness of the general public about climate change.
The Moderating Role of Self-Control and Financial Strain in the Relation between Exposure to the Food Environment and Obesity: The GLOBE Study
Authors: Mackenbach Joreintje D. , Beenackers Marielle A. , Noordzij J. Mark , Oude Groeniger Joost , Lakerveld Jeroen , van Lenthe Frank J.
Published: February 2019

Low self-control and financial strain may limit individuals’ capacity to resist temptations in the local food environment. We investigated the moderating role of self-control and financial strain in the relation between the food environment and higher body weight. We used data from 2812 Dutch adults who participated in the population-based GLOBE study in 2014. Participants’ home addresses and the location of food retailers in 2013 were mapped using GIS. The density of fast food retailers and the totality of food retailers in Euclidean buffers of 250, 400 and 800 m around the home were linked to body mass index and overweight status. A higher density of fast food outlets (B (95% confidence interval (CI)) = −0.04 (−0.07; −0.01)) and the totality of food outlets (B (95% CI) = −0.01 (−0.01; −0.00)) were associated with a lower body mass index. Stratification showed that associations were strongest for those experiencing low self-control or great financial strain. For example, every additional fast food outlet was associated with a 0.17 point lower BMI in those with great financial strain, while not significantly associated with BMI in those with no financial strain. In conclusion, we did find support for a moderating role of self-control and financial strain, but associations between the food environment and weight status were not in the expected direction.
Measuring the Environmental Efficiency and Technology Gap of PM2.5 in China’s Ten City Groups: An Empirical Analysis Using the EBM Meta-Frontier Model
Authors: Cheng Shixiong , Xie Jiahui , Xiao De , Zhang Yun
Published: February 2019

Since air pollution is an important factor hindering China’s economic development, China has passed a series of bills to control air pollution. However, we still lack an understanding of the status of environmental efficiency in regard to air pollution, especially PM2.5 (diameter of fine particulate matter less than 2.5 μm) pollution. Using panel data on ten major Chinese city groups from 2004 to 2016, we first estimate the environmental efficiency of PM2.5 by epsilon-based measure (EBM) meta-frontier model. The results show that there are large differences in PM2.5 environmental efficiency between cities and city groups. The cities with the highest environmental efficiency are the most economically developed cities and the city group with the highest environmental efficiency is mainly the eastern city group. Then, we use the meta-frontier Malmquist EBM model to measure the meta-frontier Malmquist total factor productivity index (MMPI) in each city group. The results indicate that, overall, China’s environmental total factor productivity declined by 3.68% and 3.49% when considering or not the influence of outside sources, respectively. Finally, we decompose the MMPI into four indexes, namely, the efficiency change (EC) index, the best practice gap change (BPC) index, the pure technological catch-up (PTCU) index, and the frontier catch-up (FCU) index. We find that the trend of the MMPI is consistent with those of the BPC and PTCU indexes, which indicates that the innovation effect of the BPC and PTCU indexes are the main driving forces for productivity growth. The EC and FCU effect are the main forces hindering productivity growth.
Small Molecule Inhibitors Specifically Targeting the Type III Secretion System of Xanthomonas oryzae on Rice
Authors: Tao Hui , Fan Su-Su , Jiang Shan , Xiang Xuwen , Yan Xiaojing , Zhang Lian-Hui , Cui Zi-Ning
Published: February 2019

The initiative strategy for the development of novel anti-microbial agents usually uses the virulence factors of bacteria as a target, without affecting their growth and survival. The type III secretion system (T3SS), one of the essential virulence factors in most Gram-negative pathogenic bacteria because of its highly conserved construct, has been regarded as an effective target that developed new anti-microbial drugs. Xanthomonas oryzae pv. oryzae (Xoo) causes leaf blight diseases and is one of the most important pathogens on rice. To find potential anti-virulence agents against this pathogen, a number of natural compounds were screened for their effects on the T3SS of Xoo. Three of 34 compounds significantly inhibited the promoter activity of the harpin gene, hpa1, and were further checked for their impact on bacterial growth and on the hypersensitive response (HR) caused by Xoo on non-host tobacco plants. The results indicated that treatment of Xoo with CZ-1, CZ-4 and CZ-9 resulted in an obviously attenuated HR without affecting bacterial growth and survival. Moreover, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that the expression of the Xoo T3SS was suppressed by treatment with the three inhibitors. The mRNA levels of representative genes in the hypersensitive response and pathogenicity (hrp) cluster, as well as the regulatory genes hrpG and hrpX, were reduced. Finally, the in vivo test demonstrated that the compounds could reduce the disease symptoms of Xoo on the rice cultivar (Oryza sativa) IR24.
Role of p90RSK in Kidney and Other Diseases
Authors: Lin Ling , White Samantha A. , Hu Kebin
Published: February 2019

The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases consisting of 4 RSK isoforms (RSK1-4), of which RSK1 is also designated as p90RSK. p90RSK plays an important role in the Ras-mitogen-activated protein kinase (MAPK) signalling cascade and is the direct downstream effector of Ras-extracellular signal-regulated kinase (ERK1/2) signalling. ERK1/2 activation directly phosphorylates and activates p90RSK, which, in turn, activates various signalling events through selection of different phosphorylation substrates. Upregulation of p90RSK has been reported in numerous human diseases. p90RSK plays an important role in the regulation of diverse cellular processes. Thus, aberrant activation of p90RSK plays a critical role in the pathogenesis of organ dysfunction and damage. In this review, we focus on the current understanding of p90RSK functions and roles in the development and progression of kidney diseases. Roles of p90RSK, as well as other RSKs, in cardiovascular disorders and cancers are also discussed.
Role of Histamine H3 Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma
Authors: Lanzi Cecilia , Lucarini Laura , Durante Mariaconcetta , Sgambellone Silvia , Pini Alessandro , Catarinicchia Stefano , Łażewska Dorota , Kieć-Kononowicz Katarzyna , Stark Holger , Masini Emanuela
Published: February 2019

Intraocular pressure (IOP) has a tendency to fluctuate throughout the day, reaching its peak in the early morning in healthy subjects or glaucoma patients. Likewise, histamine tone also fluctuates over time, being lower at nighttime. Numerous studies have demonstrated a correlation between short-term IOP fluctuation and glaucoma progression; however, it has not yet been determined whether histamine plays a role in IOP fluctuations. The aim of this research was to establish the distribution of the histamine receptor proteins and respective mRNAs in the eye by western blot, immunohistochemistry and RT-PCR in New Zealand rabbits. Furthermore, we used a transient ocular hypertension (OHT) model induced by injection of 50 µL of 5% hypertonic saline into the vitreous and a stable OHT model (100 µL 0.1% carbomer in the anterior chamber) to address the potential IOP-lowering ability of H3 receptor (H3R) antagonists (ciproxifan, DL76 and GSK189254). IOPs were performed with a Tono-Pen at baseline and 60, 120 and 240 min post treatment after transient OHT induction and, every day for 12 days in the stable OHT model. All histamine receptor subtypes were localized in the rabbit retina and ciliary body/trabecular meshwork. All the treatments lowered IOP in a dose-dependent fashion between 0.3% and 1%. More specifically, the effects were maximal with ciproxifan at 60 min post-dose (IOP60 change = −18.84 ± 4.85 mmHg, at 1%), remained stable until 120 min (IOP120 change = −16.38 ± 3.8 mmHg, at 1%) and decayed thereafter to reach baseline values at 240 min. These effects were highly specific and dependent on histamine release as pre-treatment with imetit (H3R agonist, 1%) or pyrilamine (H1R antagonist, 1%) largely blocked ciproxifan-mediated effects. Color Doppler ultrasound examination was performed to evaluate changes in ophtalmic artery resistivity index (RI) before and after repeated dosing with DL 76, GSK189254, ciproxifan and timolol. Chronic treatments with H3R antagonists and timolol improved the vascular performance of ophthalmic arteries and reduced retinal ganglion cell death. Oxidative stress was also reduced and measured 8-Hydroxy-2′-deoxyguanosine (8OHdG) expression, and by dihidroethydium (DHE) staining. These results demonstrated that the histamine system participates in IOP regulation and that H3R antagonists could represent a future promising therapy for glaucoma. Further studies should be focused on the long-term IOP circadian fluctuations.
Enhancement of Functionality and Therapeutic Efficacy of Cell-Based Therapy Using Mesenchymal Stem Cells for Cardiovascular Disease
Authors: Yun Chul Won , Lee Sang Hun
Published: February 2019

Cardiovascular disease usually triggers coronary heart disease, stroke, and ischemic diseases, thus promoting the development of functional failure. Mesenchymal stem cells (MSCs) are cells that can be isolated from various human tissues, with multipotent and immunomodulatory characteristics to help damaged tissue repair and avoidance of immune responses. Much research has proved the feasibility, safety, and efficiency of MSC-based therapy for cardiovascular disease. Despite the fact that the precise mechanism of MSCs remains unclear, their therapeutic capability to treat ischemic diseases has been tested in phase I/II clinical trials. MSCs have the potential to become an effective therapeutic strategy for the treatment of ischemic and non-ischemic cardiovascular disorders. The molecular mechanism underlying the efficacy of MSCs in promoting engraftment and accelerating the functional recovery of injury sites is still unclear. It is hypothesized that the mechanisms of paracrine effects for the cardiac repair, optimization of the niche for cell survival, and cardiac remodeling by inflammatory control are involved in the interaction between MSCs and the damaged myocardial environment. This review focuses on recent experimental and clinical findings related to cardiovascular disease. We focus on MSCs, highlighting their roles in cardiovascular disease repair, differentiation, and MSC niche, and discuss their therapeutic efficacy and the current status of MSC-based cardiovascular disease therapies.
Modulation of Obesity and Insulin Resistance by the Redox Enzyme and Adaptor Protein p66Shc
Authors: Ciciliot Stefano , Fadini Gian Paolo
Published: February 2019

Initially reported as a longevity-related protein, the 66 kDa isoform of the mammalian Shc1 locus has been implicated in several metabolic pathways, being able to act both as an adaptor protein and as a redox enzyme capable of generating reactive oxygen species (ROS) when it localizes to the mitochondrion. Ablation of p66Shc has been shown to be protective against obesity and the insurgence of insulin resistance, but not all the studies available in the literature agree on these points. This review will focus in particular on the role of p66Shc in the modulation of glucose homeostasis, obesity, body temperature, and respiration/energy expenditure. In view of the obesity and diabetes epidemic, p66Shc may represent a promising therapeutic target with enormous implications for human health.
The Modulatory Effect of Gender and Cytomegalovirus-Seropositivity on Circulating Inflammatory Factors and Cognitive Performance in Elderly Individuals
Authors: Di Benedetto Svetlana , Gaetjen Marcel , Müller Ludmila
Published: February 2019

Aging is characterized by a chronic increase in the systemic levels of inflammatory cytokines even in ostensibly healthy individuals. The drivers of age-related increase in systemic inflammation are unclear but one potential contributor may be a persistent infection with Cytomegalovirus (CMV). In this study, we characterized the inflammatory status of 161 older participants recruited to undergo a six-month training intervention. We investigated the influence of gender and CMV-seropositivity on the main inflammatory and anti-inflammatory circulating biomarkers, such as cytokines, receptor antagonist, soluble receptor, immune cells, and relevant metabolic markers. We found that both gender and CMV-seropositivity modulate circulating peripheral biomarkers, and that CMV-infection modifies associations among the latter. Moreover, we observed an interaction between CMV-serostatus and gender associations with cognitive abilities: gender differences in fluid intelligence (Gf) and working memory (WM) were noted only in CMV-negative individuals. Finally, we found that in the CMV-seronegative participants Gf, episodic memory (EM), and WM correlated negatively with pro-inflammatory tumor necrosis factor (TNF); and EM correlated positively with anti-inflammatory interleukin (IL)-10. In CMV-seropositive individuals EM and Gf correlated negatively with pro-inflammatory IL-6, while EM, Gf, and WM correlated negatively with anti-inflammatory IL-1RA. We conclude that both CMV-serostatus and gender may modulate neuroimmune factors, cognitive performance and the relationship between the two domains and should therefore be considered in comparative and interventional studies with elderly people.
Targeting the Iron-Response Elements of the mRNAs for the Alzheimer’s Amyloid Precursor Protein and Ferritin to Treat Acute Lead and Manganese Neurotoxicity
Authors: Rogers Jack T. , Xia Ning , Wong Angela , Bakshi Rachit , Cahill Catherine M.
Published: February 2019

The therapeutic value of inhibiting translation of the amyloid precursor protein (APP) offers the possibility to reduce neurotoxic amyloid formation, particularly in cases of familial Alzheimer’s disease (AD) caused by APP gene duplications (Dup–APP) and in aging Down syndrome individuals. APP mRNA translation inhibitors such as the anticholinesterase phenserine, and high throughput screened molecules, selectively inhibited the uniquely folded iron-response element (IRE) sequences in the 5’untranslated region (5’UTR) of APP mRNA and this class of drug continues to be tested in a clinical trial as an anti-amyloid treatment for AD. By contrast, in younger age groups, APP expression is not associated with amyloidosis, instead it acts solely as a neuroprotectant while facilitating cellular ferroportin-dependent iron efflux. We have reported that the environmental metallotoxins Lead (Pb) and manganese (Mn) cause neuronal death by interfering with IRE dependent translation of APP and ferritin. The loss of these iron homeostatic neuroprotectants thereby caused an embargo of iron (Fe) export from neurons as associated with excess unstored intracellular iron and the formation of toxic reactive oxidative species (ROS). We propose that APP 5’UTR directed translation activators can be employed therapeutically to protect neurons exposed to high acute Pb and/or Mn exposure. Certainly, high potency APP translation activators, exemplified by the Food and Drug Administration (FDA) pre-approved M1 muscarinic agonist AF102B and high throughput-screened APP 5’UTR translation activators, are available for drug development to treat acute toxicity caused by Pb/Mn exposure to neurons. We conclude that APP translation activators can be predicted to prevent acute metal toxicity to neurons by a mechanism related to the 5’UTR specific yohimbine which binds and targets the canonical IRE RNA stem loop as an H-ferritin translation activator.
Discovery of Novel Acetylcholinesterase Inhibitors as Potential Candidates for the Treatment of Alzheimer’s Disease
Authors: Son Minky , Park Chanin , Rampogu Shailima , Zeb Amir , Lee Keun Woo
Published: February 2019

Acetylcholinesterase (AChE) catalyzes the hydrolysis of neurotransmitter acetylcholine to acetate and choline in a synaptic cleft. Deficits in cholinergic neurotransmitters are linked closely with the progression of Alzheimer’s disease (AD), which is a neurodegenerative disorder characterized by memory impairment, and a disordered cognitive function. Since the previously approved AChE inhibitors, donepezil (Aricept), galantamine (Reminyl), and rivastigmine (Exelon), have side effects and several studies are being carried out out to develop novel AD drugs, we have applied a three-dimensional quantitative structure−activity relationship (3D QSAR) and structure-based pharmacophore modeling methodologies to identify potential candidate inhibitors against AChE. Herein, 3D QSAR and structure-based pharmacophore models were built from known inhibitors and crystal structures of human AChE in complex with donepezil, galantamine, huperzine A, and huprine W, respectively. The generated models were used as 3D queries to screen new scaffolds from various chemical databases. The hit compounds obtained from the virtual screening were subjected to an assessment of drug-like properties, followed by molecular docking. The final hit compounds were selected based on binding modes and molecular interactions in the active site of the enzyme. Furthermore, molecular dynamics simulations for AChE in complex with the final hits were performed to evaluate that they maintained stable interactions with the active site residues. The binding free energies of the final hits were also calculated using molecular mechanics/Poisson-Boltzmann surface area method. Taken together, we proposed that these hits can be promising candidates for anti-AD drugs.
The Oncogenic Activity of miR-29b-1-5p Induces the Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma
Authors: Kurihara-Shimomura Miyako , Sasahira Tomonori , Shimomura Hiroyuki , Nakashima Chie , Kirita Tadaaki
Published: February 2019

Background: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. Methods: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. Results: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. Conclusions: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells.
A Systematic Review of the Short-Term Health Effects of Air Pollution in Persons Living with Coronary Heart Disease
Authors: Warburton Darren E. R. , Bredin Shannon S. D. , Shellington Erin M. , Cole Christie , de Faye Amanda , Harris Jennifer , Kim David D. , Abelsohn Alan
Published: February 2019

Persons living with chronic medical conditions (such as coronary artery disease (CAD)) are thought to be at increased risk when exposed to air pollution. This systematic review critically evaluated the short-term health effects of air pollution in persons living with CAD. Original research articles were retrieved systematically through searching electronic databases (e.g., Medical Literature Analysis and Retrieval System Online (MEDLINE)), cross-referencing, and the authors’ knowledge. From 2884 individual citations, 26 eligible articles were identified. The majority of the investigations (18 of 22 (82%)) revealed a negative relationship between air pollutants and cardiac function or overall health. Heart rate variability (HRV) was the primary cardiovascular outcome measure, with 10 out of 13 studies reporting at least one index of HRV being significantly affected by air pollutants. However, there was some inconsistency in the relationship between HRV and air pollutants, mediated (at least in part) by the confounding effects of beta-blocker medications. In conclusion, there is strong evidence that air pollution can have adverse effects on cardiovascular function in persons living with CAD. All persons living with CAD should be educated on how to monitor air quality, should recognize the potential risks of excessive exposure to air pollution, and be aware of strategies to mitigate these risks. Persons living with CAD should minimize their exposure to air pollution by limiting outdoor physical activity participation when the forecast air quality health index indicates increased air pollution (i.e., an increased risk).
Residual Lattice Strain and Phase Distribution in Ti-6Al-4V Produced by Electron Beam Melting
Authors: Maimaitiyili Tuerdi , Woracek Robin , Neikter Magnus , Boin Mirko , Wimpory Robert , Pederson Robert , Strobl Markus , Drakopoulos Michael , Schäfer Norbert , Bjerkén Christina
Published: February 2019

Residual stress/strain and microstructure used in additively manufactured material are strongly dependent on process parameter combination. With the aim to better understand and correlate process parameters used in electron beam melting (EBM) of Ti-6Al-4V with resulting phase distributions and residual stress/strains, extensive experimental work has been performed. A large number of polycrystalline Ti-6Al-4V specimens were produced with different optimized EBM process parameter combinations. These specimens were post-sequentially studied by using high-energy X-ray and neutron diffraction. In addition, visible light microscopy, scanning electron microscopy (SEM) and electron backscattered diffraction (EBSD) studies were performed and linked to the other findings. Results show that the influence of scan speed and offset focus on resulting residual strain in a fully dense sample was not significant. In contrast to some previous literature, a uniform α- and β-Ti phase distribution was found in all investigated specimens. Furthermore, no strong strain variations along the build direction with respect to the deposition were found. The magnitude of strain in α and β phase show some variations both in the build plane and along the build direction, which seemed to correlate with the size of the primary β grains. However, no relation was found between measured residual strains in α and β phase. Large primary β grains and texture appear to have a strong effect on X-ray based stress results with relatively small beam size, therefore it is suggested to use a large beam for representative bulk measurements and also to consider the prior β grain size in experimental planning, as well as for mathematical modelling.