bluuebunny/crossref_metadata_2025 huggingface dataset:
Elasticity Analysis of Fossil Energy Sources for Sustainable Economies: A Case of Gasoline Consumption in Turkey
Authors: Mikayilov Jeyhun I. , Mukhtarov Shahriyar , Dinçer Hasan , Yüksel Serhat , Aydın Rıdvan
Published: February 2020

The current paper investigates the gasoline demand relationship in the case of Turkey, utilizing different econometric techniques and using quarterly data spanning from 2000Q1 to 2019Q1. The estimation results revealed that income and gasoline price are the main drivers of consumption. The found long-run income, price and auto stock elasticities are 0.25, −0.27 and −0.80, respectively. In addition, it is concluded that in the short-run, gasoline demand does not respond to changes in income, price and car stock. The estimation results also showed that the contribution of commercial and public car stock on gasoline demand is higher than that for private auto stock. Based on the finding of the study it is concluded that to achieve the optimal use of gasoline in line with providing high quality transport services, firstly, policies before the 2012 period can be followed. Secondly, channels such as pricing mechanism and taxation policies can be used in this framework.
Attitudes and Opinions of Social Media Users Towards Smart Meters’ Rollout in Turkey
Authors: Chawla Yash , Kowalska-Pyzalska Anna , Oralhan Burcu
Published: February 2020

Increasing the efficiency of electricity transmission is nearing the top of the agenda in many countries around the world. Turkey, the world’s most newly industrialized country, is no different. Modernizing the current transmission grids to smart grids (SG) and the national rollout of smart meters (SM), are some of the measures taken by the government to meet the growing demand for electricity. Consumer acceptance and engagement are among the most important elements for the success of SG and SM, however, there have not been much studies done among Turkish electricity consumers. This purpose of this study is to fill this void, by detailing the attitudes, awareness and expectations among Turkish citizens regarding SM and listing recommendations for energy companies based on the findings. Through an online questionnaire, responses from 504 social media users were collected and analyzed. Results show that the consumers are open towards the acceptance of SM, but there is a need to raise awareness and knowledge through proper communication channels. The study has also revealed that a range of conventional and digital channels need to be actively used in order to enhance consumer willingness to accept SM. Increasing social interactions regarding SM is one of the key recommendations detailed by the authors.
Remote Sensing Technology Applications in Forestry and REDD+
Authors: Calders Kim , Jonckheere Inge , Nightingale Joanne , Vastaranta Mikko
Published: February 2020

Advances in close-range and remote sensing technologies drive innovations in forest resource assessments and monitoring at varying scales. Data acquired with airborne and spaceborne platforms provide us with higher spatial resolution, more frequent coverage and increased spectral information. Recent developments in ground-based sensors have advanced three dimensional (3D) measurements, low-cost permanent systems and community-based monitoring of forests. The REDD+ mechanism has moved the remote sensing community in advancing and developing forest geospatial products which can be used by countries for the international reporting and national forest monitoring. However, there still is an urgent need to better understand the options and limitations of remote and close-range sensing techniques in the field of degradation and forest change assessment. This Special Issue contains 12 studies that provided insight into new advances in the field of remote sensing for forest management and REDD+. This includes developments into algorithm development using satellite data; synthetic aperture radar (SAR); airborne and terrestrial LiDAR; as well as forest reference emissions level (FREL) frameworks.
The Genome-Wide Analysis of RALF-Like Genes in Strawberry (Wild and Cultivated) and Five Other Plant Species (Rosaceae)
Authors: Zhang Hong , Jing Xiaotong , Chen Ying , Liu Zhe , Xin Yuting , Qiao Yushan
Published: February 2020

The rapid alkalinization factor (RALF) gene family is essential for the plant growth and development. However, there is little known about these genes among Rosaceae species. Here, we identify 124 RALF-like genes from seven Rosaceae species, and 39 genes from Arabidopsis, totally 163 genes, divided into four clades according to the phylogenetic analysis, which includes 45 mature RALF genes from Rosaceae species. The YISY motif and RRXL cleavage site are typical features of true RALF genes, but some variants were detected in our study, such as YISP, YIST, NISY, YINY, YIGY, YVGY, FIGY, YIAY, and RRVM. Motif1 is widely distributed among all the clades. According to screening of cis-regulatory elements, GO annotation, expression sequence tags (EST), RNA-seq, and RT-qPCR, we reported that 24 RALF genes coding mature proteins related to tissue development, fungal infection, and hormone response. Purifying selection may play an important role in the evolutionary process of RALF-like genes among Rosaceae species according to the result from ka/ks. The tandem duplication event just occurs in four gene pairs (Fv-RALF9 and Fv-RALF10, Md-RALF7 and Md-RALF8, Pm-RALF2 and Pm-RALF8, and Pp-RALF11 and Pp-RALF14) from four Rosaceae species. Our research provides a wide overview of RALF-like genes in seven Rosaceae species involved in identification, classification, structure, expression, and evolution analysis.
How Should Forests Be Characterized in Regard to Human Health? Evidence from Existing Literature
Authors: Bach Pagès Albert , Peñuelas Josep , Clarà Jana , Llusià Joan , Campillo i López Ferran , Maneja Roser
Published: February 2020

The potential of forests as a source of health has been addressed by the scientific community and is now being considered in national forest strategies, management plans and policies. Studies identifying the mechanisms by which forest characteristics may induce these effects on human health are nevertheless scarce. This systematic review of literature on forests and human health with real-life human exposure was conducted to assess the extent to which forests have been studied and described in detail and the extent to which relationships between forest variables and health effects have been reported. The analysis underlines the lack of forest descriptions in 19.35% of the 62 studies selected for review as well as the high heterogeneity of forest variables’ description. Patterns among the articles could not be identified correlating the broader forest variable (forest type) and the most studied health variables identified (blood pressure, pulse rate or/and cortisol levels). These findings, together with previous ex situ researches, suggest the need to ameliorate and incorporate more accurate descriptions of forest variables within human health studies to provide data for forest management and the potential use of these habitats for preventive medicine and clinical practice guidelines.
Per-Cooling (Using Cooling Systems during Physical Exercise) Enhances Physical and Cognitive Performances in Hot Environments. A Narrative Review
Authors: Douzi Wafa , Dupuy Olivier , Theurot Dimitri , Smolander Juhani , Dugué Benoit
Published: February 2020

There are many important sport events that are organized in environments with a very hot ambient temperature (Summer Olympics, FIFA World Cup, Tour de France, etc.) and in hot locations (e.g., Qatar). Additionally, in the context of global warming and heat wave periods, athletes are often subjected to hot ambient temperatures. It is known that exercising in the heat induces disturbances that may provoke premature fatigue and negatively affects overall performance in both endurance and high intensity exercises. Deterioration in several cognitive functions may also occur, and individuals may be at risk for heat illnesses. To train, perform, work and recover and in a safe and effective way, cooling strategies have been proposed and have been routinely applied before, during and after exercise. However, there is a limited understanding of the influences of per-cooling on performance, and it is the subject of the present review. This work examines the influences of per-cooling of different areas of the body on performance in terms of intense short-term exercises (“anaerobic” exercises), endurance exercises (“aerobic” exercises), and cognitive functioning and provides detailed strategies that can be applied when individuals train and/or perform in high ambient temperatures.
Physical Activity in Older Adults: An Investigation in a Metropolitan Area of Southern Italy
Authors: Gallè Francesca , Sabella Elita Anna , Da Molin Giovanna , Parisi Eduardo Alfonso , Liguori Giorgio , Montagna Maria Teresa , De Giglio Osvalda , Tondini Luca , Orsi Giovanni Battista , Napoli Christian
Published: February 2020

Physical activity (PA) and exercise are fundamental to maintaining health in older adults. World Health Organization guidelines state that older adults should practice at least 150 min/week of moderate/vigorous intensity PA to obtain health benefits. We assessed PA levels among older adults in southern Italy and evaluated possible associated determinants. The study was carried out between September and November 2019 in the metropolitan area of Bari. We collected information from participants over 65 years using a self-administered questionnaire. We investigated associations between sociodemographic characteristics, health conditions, and inactivity/PA levels. A total of 383 individuals completed the questionnaire. Mean body mass index indicated that 45.4% of participants were overweight. Mean time spent in PA was 476.2 ± 297.8 min/week, with women reporting lower levels than men (370.8 ± 210 vs. 555.2 ± 334.3 min/week, p = 0.08). Weekly sitting time was positively related to age. Attending religious or recreational activities was related to moderate PA. Educational level was positively associated with PA while dog ownership represented an obstacle to achieving recommended PA levels in our population. Participants generally met the recommended levels of PA, especially men; the educational level was the main determinant. Interventions aimed at promoting PA among older adults with lower education levels and women are needed in this setting.
Food Behaviors, Health, and Bean Nutrition Awareness among Low-Income Men: A Pilot Study
Authors: Heer Michelle M. , Winham Donna M.
Published: February 2020

Bean consumption is known to lower blood cholesterol and postprandial blood glucose. With higher chronic disease risk, low-income men could theoretically benefit from increased bean intakes. The study objective was to explore low-income men’s food behaviors, bean health benefit awareness, and bean consumption practices and preferences. Seventy-one low-income men aged 18–65 years (µ 41 ± 12.7; 53% white, 16% black, 31% Hispanic) completed a survey on health risks, food behaviors, bean health knowledge, attitudes toward dry and canned beans, and bean preferences. Eighty-seven percent had one or more health risk factors of physical inactivity, smoking, or obesity. Most men compared food prices, and thought about healthy food choices for their families, but few planned meals or read nutrition facts labels. White men had significantly higher bean health benefit knowledge than black or Hispanic men (p < 0.01). Most men liked the taste of beans, disagreed dry beans took too long to prepare, and 79% ate them at least 2–3 times per month. Forty-nine percent agreed beans caused intestinal gas. Improving men’s awareness of the health benefits of beans as well as leveraging existing positive attitudes may be useful approaches to increase bean consumption among low-income and minority male populations.
Women’s Health and Well-Being in the United Nations Sustainable Development Goals: A Narrative Review of Achievements and Gaps in the Gulf States
Authors: Daher-Nashif Suhad , Bawadi Hiba
Published: February 2020

Background: In 2014, United Nations member states proposed a set of sustainable development goals (SDGs) to help further the millennium development goals that they had proposed in New York in 2000. Of these 13 SDGs, Goal 3 (i.e., SDG 3) was titled “Good Health and Well-Being.” This goal highlighted women’s health and well-being via two key objectives. The first, SDG 3.1, aimed to reduce maternal mortality rates (MMR) and the second, SDG 3.7, aimed to ensure access to sexual and reproductive health care services. Drawing on all the latest reports, which have been released by Gulf Cooperation Council states (GCC), this paper sheds light on GCC states’ work on women’s wellbeing through SDG 3. Aim: the paper aims to review GCC states’ work on women’s wellbeing in SDG3, which achievements they obtained, which tools they used and which gaps still exist. The paper aims to explain the socio-cultural background behind these achievements, tools, and gaps. Methodology: For the purpose of this study, we used narrative review approach through which we reviewed reports from 2017 and 2018 on SDGs published online by the Ministry of Development and Planning of each GCC state, and latest reports of the WHO on the same states. Findings: the study found similarities and differences between different GCC states, which in turn reveals gaps and areas that are not meeting women’s needs. The findings show that MMR in GCC countries has declined by nearly half. The main strategies they adopted to address SDG 3.1 included awareness campaigns, improving access to healthcare systems and training professionals. The tools used to meet SDG 3.7 included training health professionals and raising awareness of consanguinity. The study reveals several gaps, such as a lack of discussion around challenges and barriers, and a lack of linkage between an SDG and the targets contained within it. Conclusion: The paper concludes that there is a much greater emphasis on reducing MMR, compared to providing access to sexual and reproductive healthcare. This difference is due to different socio-cultural framing of each of these two issues.
Application of Threshold Regression Analysis to Study the Impact of Clean Energy Development on China’s Carbon Productivity
Authors: Han Dongri , Li Tuochen , Feng Shaosong , Shi Ziyi
Published: February 2020

Facing the pressures of international carbon emission reduction, the transformation into a low-carbon economy has become a common issue of all countries. The core of developing a low-carbon economy is to increase carbon productivity, which can be measured as the economic benefits of unit carbon emissions. Therefore, using province-level panel data in China from 2009 to 2017, we analyze the carbon productivity level of each region, and empirically investigate the threshold effect of clean energy development on carbon productivity under different technological innovation levels. The results show that the carbon productivity is rising, and China’s economic development pattern has been shifting towards low-carbon and sustainable development. Furthermore, the driving force of clean energy development on carbon productivity is not monotonously increasing (decreasing) but is a “double threshold effect” of technological innovation capability. Finally, based on the research conclusions and realistic requirements of China’s low-carbon economic transformation, this paper proposes improving carbon productivity from the aspects of innovation capability improvement and institutional guarantee.
Prevalence and Relationships among Physical Activity Policy, Environment, and Practices in Licensed Childcare Centers from a Manager and Staff Perspective
Authors: McConnell-Nzunga Jennifer , Mâsse Louise C. , Buckler E. Jean , Carson Valerie , Faulkner Guy E. , Lau Erica Y. , McKay Heather A. , Temple Viviene A. , Wolfenden Luke , Naylor Patti-Jean
Published: February 2020

Physical activity (PA) is critical to early childhood health and development, and childcare is a key setting for establishing physically active play. In British Columbia (BC), a provincial standard for active play in childcare was enacted, identified here as the Active Play (AP) standard. Pragmatic constraints limit real-world data collection for evaluating policy impact. We explored whether information about policies, practices, and the environment varied when it was collected from managers or staff. Surveys were distributed to BC childcare centers before AP standard enactment to ascertain current PA and fundamental movement skill policies and practices. The full sample (n = 1037 from 625 facilities) and a subsample of paired managers and staff (n = 261 centers) were used to explore agreement across managers and staff in reported prevalence and relationships among indicators. The policy prevalence and relationships for active play and outdoor play variables were relatively similar for manager and staff data, although the matched data had modest agreement and less than optimal intraclass correlations. The prevalence of manager-reported PA policies ranged from 47% for screen-time limits to 77% for fundamental movement skill activities. The manager and staff data highlighted indoor and outdoor space as a primary factor in AP standard adherence. With reliance on sampling staff unfeasible, it appears that the manager data may adequately describe the policies and practices of childcare providers with some notable issues.
The Use of Stents in Children with Nasolacrimal Duct Obstruction Requiring Surgical Intervention: A Systematic Review
Authors: Tai Evelyn Li Min , Kueh Yee Cheng , Abdullah Baharudin
Published: February 2020

Nasolacrimal duct obstruction (NLDO) is the most common cause of childhood epiphora. It is managed conservatively in the first year of life, after which surgical treatment is classically based on a stepwise paradigm of probing, intubation, and dacryocystorhinostomy. This systematic review aims to present the current role of intubation in the management of children with NLDO requiring surgical intervention. A search for English-language articles from the electronic databases PubMed, SCOPUS, and the COCHRANE library was conducted over a period of five months in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook. The following keywords were used to aid retrieval: stents, children, lacrimal intubation, endoscopic dacryocystorhinostomy, external dacryocystorhinostomy, NLDO, dacryocystitis, congenital, acquired. The primary outcome was defined as the success of the intervention, determined by resolution of symptoms and patency of the lacrimal anatomy confirmed by the fluorescein dye disappearance test or syringing. Secondary outcomes included the presence of complications. A total of 144 articles were identified; of these, 35 fulfilled the study criteria. The majority of the included studies involved lacrimal intubation alone, followed by intubation as an adjunctive procedure to balloon dacryoplasty and dacryocystorhinostomy. The overall success rate of these procedures ranged from 41.1% to 100%. Post-operative complications were reported in 65.7% of the included studies. Lacrimal intubation was most commonly performed as a primary procedure in children with NLDO, with high success rates. The main complication was stent dislodgement. There is lack of evidence regarding the benefit of intubation over probing as primary treatment of congenital NLDO. In the absence of high-quality evidence, the decision of whether to perform lacrimal intubation in children with NLDO requiring surgical intervention depends on clinical judgement and other low-level evidence, such as observational non-randomised trials.
Using Smart Sensors to Monitor Physical Activity and Technical–Tactical Actions in Junior Tennis Players
Authors: Giménez-Egido José María , Ortega Enrique , Verdu-Conesa Isidro , Cejudo Antonio , Torres-Luque Gema
Published: February 2020

The use of smart devices to obtain real-time data has notably increased in the context of training. These technological tools provide data which monitor the external load and technical–tactical actions related to psychological and physical health in junior tennis players. The purpose of this paper is to monitor technical–tactical actions and physical activity during a current tennis competition in the Green stage using a Zepp Tennis Smart Sensor 2. The participants were 20 junior tennis players (under 10 years of age), with an average age of 9.46 years. The total number of strokes (n= 21,477) during 75 matches was analyzed. The study variables were the following aspects: (a) number of strokes, (b) ball impact in the sweet spot; (c) racket speed; (d) ball spin; (e) calories burned; and (f) match time. The current system of competition, based on knockout, does not meet the World Health Organization’s recommendations for daily physical activity time. Players mainly used flat forehands with a lack of variability in technical–tactical actions which did not meet the current learning opportunity criteria of comprehensive methodologies. The competition system in under-11 tennis should be adapted to the players’ characteristics by improving the variability and quantity of practice.
Contamination Level, Ecological Risk, and Source Identification of Heavy Metals in the Hyporheic Zone of the Weihe River, China
Authors: Ahamad Muhammad Irfan , Song Jinxi , Sun Haotian , Wang Xinxin , Mehmood Muhammad Sajid , Sajid Muhammad , Su Ping , Khan Asif Jamal
Published: February 2020

The sediment pollution caused by different metals has attracted a great deal of attention because of the toxicity, persistence, and bio-accumulation. This study focuses on heavy metals in the hyporheic sediment of the Weihe River, China. Contamination levels of metals were examined by using “geo-accumulation index, enrichment factor, and contamination factor” while ecological risk of metals were determined by “potential ecological risk and risk index”. The pollutant accumulation of metals ranked as follows: “manganese (Mn)   >   chromium (Cr)   >   zinc (Zn)   > copper (Cu)   >   nickel (Ni)   >   arsenic (As)   >   lead (Pb)”. The geo-accumulation index identified arsenic as class 1 (uncontaminated to moderate contamination), whereas Cu, Cr, Ni, Zn, Pb, and Mn were classified as class 0 (uncontaminated). According to the enrichment factor, arsenic originated through anthropogenic activities and Cr, Ni, Cu, Zn, and Pb were mainly controlled by natural sources. The contamination factor elucidated that sediments were moderately polluted by (As, Cr, Cu, Zn, Mn, and Pb), whereas Ni slightly contaminated the sediments of the Weihe River. All metals posed a low ecological risk in the study area. The risk index revealed that contribution of arsenic (53.43 %) was higher than half of the total risk.
Full-Length Transcriptome Assembly of Italian Ryegrass Root Integrated with RNA-Seq to Identify Genes in Response to Plant Cadmium Stress
Authors: Hu Zhaoyang , Zhang Yufei , He Yue , Cao Qingqing , Zhang Ting , Lou Laiqing , Cai Qingsheng
Published: February 2020

Cadmium (Cd) is a toxic heavy metal element. It is relatively easily absorbed by plants and enters the food chain, resulting in human exposure to Cd. Italian ryegrass (Lolium multiflorum Lam.), an important forage cultivated widely in temperate regions worldwide, has the potential to be used in phytoremediation. However, genes regulating Cd translocation and accumulation in this species are not fully understood. Here, we optimized PacBio ISO-seq and integrated it with RNA-seq to construct a de novo full-length transcriptomic database for an un-sequenced autotetraploid species. With the database, we identified 2367 differentially expressed genes (DEGs) and profiled the molecular regulatory pathways of Italian ryegrass with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis in response to Cd stress. Overexpression of a DEG LmAUX1 in Arabidopsis thaliana significantly enhanced plant Cd concentration. We also unveiled the complexity of alternative splicing (AS) with a genome-free strategy. We reconstructed full-length UniTransModels using the reference transcriptome, and 29.76% of full-length models had more than one isoform. Taken together, the results enhanced our understanding of the genetic diversity and complexity of Italian ryegrass under Cd stress and provided valuable genetic resources for its gene identification and molecular breeding.
Current Biomedical Use of Copper Chelation Therapy
Authors: Baldari Silvia , Di Rocco Giuliana , Toietta Gabriele
Published: February 2020

Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.
Gene Expression Signature Predictive of Neuroendocrine Transformation in Prostate Adenocarcinoma
Authors: Ostano Paola , Mello-Grand Maurizia , Sesia Debora , Gregnanin Ilaria , Peraldo-Neia Caterina , Guana Francesca , Jachetti Elena , Farsetti Antonella , Chiorino Giovanna
Published: February 2020

Neuroendocrine prostate cancer (NEPC) can arise de novo, but much more commonly occurs as a consequence of a selective pressure from androgen deprivation therapy or androgen receptor antagonists used for prostate cancer (PCa) treatment. The process is known as neuroendocrine transdifferentiation. There is little molecular characterization of NEPCs and consequently there is no standard treatment for this kind of tumors, characterized by highly metastases rates and poor survival. For this purpose, we profiled 54 PCa samples with more than 10-years follow-up for gene and miRNA expression. We divided samples into two groups (NE-like vs. AdenoPCa), according to their clinical and molecular features. NE-like tumors were characterized by a neuroendocrine fingerprint made of known neuroendocrine markers and novel molecules, including long non-coding RNAs and components of the estrogen receptor signaling. A gene expression signature able to predict NEPC was built and tested on independently published datasets. This study identified molecular features (protein-coding, long non-coding, and microRNAs), at the time of surgery, that may anticipate the NE transformation process of prostate adenocarcinoma. Our results may contribute to improving the diagnosis and treatment of this subgroup of tumors for which traditional therapy regimens do not show beneficial effects.
Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators
Authors: Wang Hong , Ahn Kwang Seok , Alharbi Sulaiman Ali , Shair Omar H. M. , Arfuso Frank , Sethi Gautam , Chinnathambi Arunachalam , Tang Feng Ru
Published: February 2020

The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20 Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1β, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.
Dbp5/DDX19 between Translational Readthrough and Nonsense Mediated Decay
Authors: Beißel Christian , Grosse Sebastian , Krebber Heike
Published: February 2020

The DEAD-box protein Dbp5 (human DDX19) remodels RNA-protein complexes. Dbp5 functions in ribonucleoprotein export and translation termination. Termination occurs, when the ribosome has reached a stop codon through the Dbp5 mediated delivery of the eukaryotic termination factor eRF1. eRF1 contacts eRF3 upon dissociation of Dbp5, resulting in polypeptide chain release and subsequent ribosomal subunit splitting. Mutations in DBP5 lead to stop codon readthrough, because the eRF1 and eRF3 interaction is not controlled and occurs prematurely. This identifies Dbp5/DDX19 as a possible potent drug target for nonsense suppression therapy. Neurodegenerative diseases and cancer are caused in many cases by the loss of a gene product, because its mRNA contained a premature termination codon (PTC) and is thus eliminated through the nonsense mediated decay (NMD) pathway, which is described in the second half of this review. We discuss translation termination and NMD in the light of Dbp5/DDX19 and subsequently speculate on reducing Dbp5/DDX19 activity to allow readthrough of the PTC and production of a full-length protein to detract the RNA from NMD as a possible treatment for diseases.
Effect of Cholesterol on the Organic Cation Transporter OCTN1 (SLC22A4)
Authors: Pochini Lorena , Pappacoda Gilda , Galluccio Michele , Pastore Francesco , Scalise Mariafrancesca , Indiveri Cesare
Published: February 2020

The effect of cholesterol was investigated on the OCTN1 transport activity measured as [14C]-tetraethylamonium or [3H]-acetylcholine uptake in proteoliposomes reconstituted with native transporter extracted from HeLa cells or the human recombinant OCTN1 over-expressed in E. coli. Removal of cholesterol from the native transporter by MβCD before reconstitution led to impairment of transport activity. A similar activity impairment was observed after treatment of proteoliposomes harboring the recombinant (cholesterol-free) protein by MβCD, suggesting that the lipid mixture used for reconstitution contained some cholesterol. An enzymatic assay revealed the presence of 10 µg cholesterol/mg total lipids corresponding to 1% cholesterol in the phospholipid mixture used for the proteoliposome preparation. On the other way around, the activity of the recombinant OCTN1 was stimulated by adding the cholesterol analogue, CHS to the proteoliposome preparation. Optimal transport activity was detected in the presence of 83 µg CHS/ mg total lipids for both [14C]-tetraethylamonium or [3H]-acetylcholine uptake. Kinetic analysis of transport demonstrated that the stimulation of transport activity by CHS consisted in an increase of the Vmax of transport with no changes of the Km. Altogether, the data suggests a direct interaction of cholesterol with the protein. A further support to this interpretation was given by a docking analysis indicating the interaction of cholesterol with some protein sites corresponding to CARC-CRAC motifs. The observed direct interaction of cholesterol with OCTN1 points to a possible direct influence of cholesterol on tumor cells or on acetylcholine transport in neuronal and non-neuronal cells via OCTN1.
Evaluation of the Use of Formalin-Fixed and Paraffin-Embedded Archive Gastric Tissues for Microbiota Characterization Using Next-Generation Sequencing
Authors: Pinto-Ribeiro Ines , Ferreira Rui M. , Pereira-Marques Joana , Pinto Vanessa , Macedo Guilherme , Carneiro Fátima , Figueiredo Ceu
Published: February 2020

Large numbers of well-characterized clinical samples are fundamental to establish relevant associations between the microbiota and disease. Formalin-fixed and paraffin-embedded (FFPE) tissues are routinely used and are widely available clinical materials. Since current approaches to study the microbiota are based on next-generation sequencing (NGS) targeting the bacterial 16S rRNA gene, our aim was to evaluate the feasibility of FFPE gastric tissues for NGS-based microbiota characterization. Analysis of sequencing data revealed the presence of bacteria in the paraffin control. After the subtraction of the operational taxonomic units (OTUs) present in the paraffin control to the FFPE tissue sample dataset, we evaluated the microbiota profiles between paired FFPE and frozen gastric tissues, and between different times of archiving. Compared with frozen gastric tissues, we detected a lower number of OTUs in the microbiota of paired FFPE tissues, regardless of the time of archiving. No major differences in microbial diversity were identified, but taxonomic variation in the relative abundance of phyla and orders was observed between the two preservation methods. This variation was also evident in each case and throughout the times of FFPE archiving. The use of FFPE tissues for NGS-based microbiota characterization should be considered carefully, as biases can be introduced by the embedding process and the time of tissue archiving.
Plasma Membrane Ca2+ Permeable Mechanosensitive Channel OsDMT1 Is Involved in Regulation of Plant Architecture and Ion Homeostasis in Rice
Authors: Liang Jiayan , He Yan , Zhang Qiuxin , Wang Wenyi , Zhang Zemin
Published: February 2020

Plant architecture is an important factor for crop production. Plant height, tiller pattern, and panicle morphology are decisive factors for high grain yield in rice. Here, we isolated and characterized a T-DNA insertion rice mutant Osdmt1 (Oryza sativa dwarf and multi-tillering1) that exhibited a severe dwarf phenotype and multi-tillering. Molecular cloning revealed that DMT1 encodes a plasma membrane protein that was identified as a putative Ca2+ permeable mechanosensitive channel. The transcript expression level was significantly higher in the dmt1 mutant compared to wild type (WT). Additionally, the dmt1 homozygous mutant displayed a stronger phenotype than that of the WT and heterozygous seedlings after gibberellic acid (GA) treatment. RNA-seq and iTRAQ-based proteome analyses were performed between the dmt1 mutant and WT. The transcriptome profile revealed that several genes involved in GA and strigolactone (SL) biosyntheses were altered in the dmt1 mutant. Ca2+ and other ion concentrations were significantly enhanced in the dmt1 mutant, suggesting that DMT1 contributes to the accumulation of several ions in rice. Moreover, several EF-hand Ca2+ sensors, including CMLs (CaM-like proteins) and CDPKs (calcium-dependent protein kinases), displayed markedly altered transcript expression and protein levels in the dmt1 mutant. Overall, these findings aid in the elucidation of the multiply regulatory roles of OsDMT1/OsMCA1 in rice.
The Role Played by Wnt/β-Catenin Signaling Pathway in Acute Lymphoblastic Leukemia
Authors: Chiarini Francesca , Paganelli Francesca , Martelli Alberto M. , Evangelisti Camilla
Published: February 2020

Acute lymphoblastic leukemia (ALL) is an aggressive hematologic neoplastic disorder that arises from the clonal expansion of transformed T-cell or B-cell precursors. Thanks to progress in chemotherapy protocols, ALL outcome has significantly improved. However, drug-resistance remains an unresolved issue in the treatment of ALL and toxic effects limit dose escalation of current chemotherapeutics. Therefore, the identification of novel targeted therapies to support conventional chemotherapy is required. The Wnt/β-catenin pathway is a conserved signaling axis involved in several physiological processes such as development, differentiation, and adult tissue homeostasis. As a result, deregulation of this cascade is closely related to initiation and progression of various types of cancers, including hematological malignancies. In particular, deregulation of this signaling network is involved in the transformation of healthy HSCs in leukemic stem cells (LSCs), as well as cancer cell multi-drug-resistance. This review highlights the recent findings on the role of Wnt/β-catenin in hematopoietic malignancies and provides information on the current status of Wnt/β-catenin inhibitors with respect to their therapeutic potential in the treatment of ALL.
The Effect of 3′-Hydroxy-3,4,5,4′-Tetramethoxy -stilbene, the Metabolite of the Resveratrol Analogue DMU-212, on the Motility and Proliferation of Ovarian Cancer Cells
Authors: Nowicki Andrzej , Skupin-Mrugalska Paulina , Jozkowiak Malgorzata , Wierzchowski Marcin , Rucinski Marcin , Ramlau Piotr , Krajka-Kuzniak Violetta , Jodynis-Liebert Jadwiga , Piotrowska-Kempisty Hanna
Published: February 2020

Targeting tumor cell motility and proliferation is an extremely important challenge in the prevention of metastasis and improving the effectiveness of cancer treatment. We recently published data revealing that DMU-214, the metabolite of firmly cytotoxic resveratrol analogue DMU-212, exerted significantly higher biological activity than the parent compound in ovarian cancer cells. The aim of the present study was to assess the molecular mechanism of the potential anti-migration and anti-proliferative effect of DMU-214 in ovarian cancer cell line SKOV-3. We showed that DMU-214 reduced the migratory capacity of SKOV-3 cells. The microarray analysis indicated ontology groups of genes involved in processes of negative regulation of cell motility and proliferation. Furthermore, we found DMU-214 triggered changes in expression of several migration- and proliferation-related genes (SMAD7, THBS1, IGFBP3, KLF4, Il6, ILA, SOX4, IL15, SRF, RGCC, GPR56) and proteins (GPR56, RGCC, SRF, SMAD7, THBS1), which have been shown to interact to each other to reduce cell proliferation and motility. Our study showed for the first time that DMU-214 displayed anti-migratory and anti-proliferative activity in SKOV-3 ovarian cancer cells. On the basis of whole transcriptome analysis of these cells, we provide new insight into the role of DMU-214 in inhibition of processes related to metastasis.
Adaptation of Mitochondrial Substrate Flux in a Mouse Model of Nonalcoholic Fatty Liver Disease
Authors: Staňková Pavla , Kučera Otto , Peterová Eva , Lotková Halka , Maseko Tumisang Edward , Nožičková Kateřina , Červinková Zuzana
Published: February 2020

Maladaptation of mitochondrial oxidative flux seems to be a considerable feature of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to induce NAFLD in mice fed a Western-style diet (WD) and to evaluate liver mitochondrial functions. Experiments were performed on male C57BL/6J mice fed with a control diet or a WD for 24 weeks. Histological changes in liver and adipose tissue as well as hepatic expression of fibrotic and inflammatory genes and proteins were evaluated. The mitochondrial respiration was assessed by high-resolution respirometry. Oxidative stress was evaluated by measuring lipoperoxidation, glutathione, and reactive oxygen species level. Feeding mice a WD induced adipose tissue inflammation and massive liver steatosis accompanied by mild inflammation and fibrosis. We found decreased succinate-activated mitochondrial respiration and decreased succinate dehydrogenase (SDH) activity in the mice fed a WD. The oxidative flux with other substrates was not affected. We observed increased ketogenic capacity, but no impact on the capacity for fatty acid oxidation. We did not confirm the presence of oxidative stress. Mitochondria in this stage of the disease are adapted to increased substrate flux. However, inhibition of SDH can lead to the accumulation of succinate, an important signaling molecule associated with inflammation, fibrosis, and carcinogenesis.
Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity
Authors: Lee Shannon , Rauch Jens , Kolch Walter
Published: February 2020

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Here, we focus on the role of MAPK pathways in modulating drug sensitivity and resistance in cancer. We briefly discuss new findings in the extracellular signaling-regulated kinase (ERK) pathway, but mainly focus on the mechanisms how stress activated MAPK pathways, such as p38 MAPK and the Jun N-terminal kinases (JNK), impact the response of cancer cells to chemotherapies and targeted therapies. In this context, we also discuss the role of metabolic and epigenetic aberrations and new therapeutic opportunities arising from these changes.
Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish
Authors: Endo Yuka , Muraki Kyoji , Fuse Yuji , Kobayashi Makoto
Published: February 2020

Various dietary phytochemicals seem to display antioxidant activity through the NF-E2-related factor 2 (Nrf2) pathway. However, few studies have demonstrated its antioxidant effect and Nrf2 dependency at the animal level. We constructed a zebrafish-based assay system to analyze the in vivo antioxidant activity of phytochemicals and examined the activity of 10 phytochemicals derived from spices, using this system as a pilot study. Hydrogen peroxide and arsenite were used as oxidative stressors, and Nrf2 dependency was genetically analyzed using an Nrf2-mutant zebrafish line. The activities of curcumin, diallyl trisulfide and quercetin were involved in the reduction of hydrogen peroxide toxicity, while those of cinnamaldehyde, isoeugenol and 6-(methylsulfinyl)hexyl isothiocyanate were involved in the reduction of arsenite toxicity. The antioxidant activities of these phytochemicals were all Nrf2 dependent, with the exception of cinnamaldehyde, which showed strong antioxidant effects even in Nrf2-mutant zebrafish. In summary, we succeeded in constructing an assay system to evaluate the in vivo antioxidant activity of various phytochemicals using zebrafish larvae. Using this system, we found that each spice-derived phytochemical has its own specific property and mechanism of antioxidant action.
Functional Analysis Reveals the Regulatory Role of PpTST1 Encoding Tonoplast Sugar Transporter in Sugar Accumulation of Peach Fruit
Authors: Peng Qian , Wang Lu , Ogutu Collins , Liu Jingjing , Liu Li , Mollah Md. Dulal Ali , Han Yuepeng
Published: February 2020

Sugar content is related to fruit sweetness, and the complex mechanisms underlying fruit sugar accumulation still remain elusive. Here, we report a peach PpTST1 gene encoding tonoplast sugar transporter that is located in the quantitative trait loci (QTL) interval on Chr5 controlling fruit sucrose content. One derived Cleaved Amplified Polymorphic Sequence (dCAPS) marker was developed based on a nonsynonymous G/T variant in the third exon of PpTST1. Genotyping of peach cultivars with the dCAPS marker revealed a significant difference in fruit sugar content among genotypes. PpTST1 is located in the tonoplast, and substitution of glutamine by histidine caused by the G/T variation has no impact on subcellular location. The expression profile of PpTST1 exhibited a consistency with the sugar accumulation pattern, and its transient silencing significantly inhibited sugar accumulation in peach fruits. All of these results demonstrated the role of PpTST1 in regulating sugar accumulation in peach fruit. In addition, cis-elements for binding of MYB and WRKY transcript factors were found in the promoter sequence of PpTST1, suggesting a gene regulatory network of fruit sugar accumulation. Our results are not only helpful for understanding the mechanisms underlying fruit sugar accumulation, but will also be useful for the genetic improvement of fruit sweetness in peach breeding programs.
The Epigenetics of the Endocannabinoid System
Authors: Meccariello Rosaria , Santoro Antonietta , D'Angelo Stefania , Morrone Rossella , Fasano Silvia , Viggiano Andrea , Pierantoni Riccardo
Published: February 2020

The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries. The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment. Lifestyle and environmental factors can exert long-term effects on gene expression without any change in the nucleotide sequence of DNA, affecting health maintenance and influencing both disease load and resistance. This potentially reversible “epigenetic” modulation of gene expression occurs through the chemical modification of DNA and histone protein tails or the specific production of regulatory non-coding RNA (ncRNA). Recent findings demonstrate the epigenetic modulation of the ES in biological tissues; in the same way, endocannabinoids, phytocannabinoids, and cannabinoid receptor agonists and antagonists induce widespread or gene-specific epigenetic changes with the possibility of trans-generational epigenetic inheritance in the offspring explained by the transmission of deregulated epigenetic marks in the gametes. Therefore, this review provides an update on the epigenetics of the ES, with particular attention on the emerging role in reproduction and fertility.
Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases
Authors: Novellino Fabiana , Saccà Valeria , Donato Annalidia , Zaffino Paolo , Spadea Maria Francesca , Vismara Marco , Arcidiacono Biagio , Malara Natalia , Presta Ivan , Donato Giuseppe
Published: February 2020

The intricate relationships between innate immunity and brain diseases raise increased interest across the wide spectrum of neurodegenerative and neuropsychiatric disorders. Barriers, such as the blood–brain barrier, and innate immunity cells such as microglia, astrocytes, macrophages, and mast cells are involved in triggering disease events in these groups, through the action of many different cytokines. Chronic inflammation can lead to dysfunctions in large-scale brain networks. Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are associated with a substrate of dysregulated immune responses that impair the central nervous system balance. Recent evidence suggests that similar phenomena are involved in psychiatric diseases, such as depression, schizophrenia, autism spectrum disorders, and post-traumatic stress disorder. The present review summarizes and discusses the main evidence linking the innate immunological response in neurodegenerative and psychiatric diseases, thus providing insights into how the responses of innate immunity represent a common denominator between diseases belonging to the neurological and psychiatric sphere. Improved knowledge of such immunological aspects could provide the framework for the future development of new diagnostic and therapeutic approaches.