bluuebunny/crossref_metadata_2025 huggingface dataset:
GCKR rs780094 Polymorphism as A Genetic Variant Involved in Physical Exercise
Authors: Espinosa-Salinas Isabel , de la Iglesia Rocio , Colmenarejo Gonzalo , Molina Susana , Reglero Guillermo , Martinez J. Alfredo , Loria-Kohen Viviana , Ramirez de Molina Ana
Published: July 2019

Exercise performance is influenced by genetics. However, there is a lack of knowledge about the role played by genetic variability in the frequency of physical exercise practice. The objective was to identify genetic variants that modulate the commitment of people to perform physical exercise and to detect those subjects with a lower frequency practice. A total of 451 subjects were genotyped for 64 genetic variants related to inflammation, circadian rhythms, vascular function as well as energy, lipid and carbohydrate metabolism. Physical exercise frequency question and a Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ) were used to qualitatively and quantitatively measure the average amount of physical exercise. Dietary intake and energy expenditure due to physical activity were also studied. Differences between genotypes were analyzed using linear and logistic models adjusted for Bonferroni. A significant association between GCKR rs780094 and the times the individuals performed physical exercise was observed (p = 0.004). The carriers of the minor allele showed a greater frequency of physical exercise in comparison to the major homozygous genotype carriers (OR: 1.86, 95% CI: 1.36–2.56). The analysis of the GCKR rs780094 variant suggests a possible association with the subjects that present lower frequency of physical exercise. Nevertheless, future studies are needed to confirm these findings.
Groundwater Quality Assessment Using Fuzzy-AHP in An Giang Province of Vietnam
Authors: Minh Huynh , Avtar Ram , Kumar Pankaj , Tran Dat , Ty Tran , Behera Hari , Kurasaki Masaaki
Published: July 2019

Along with rapid population growth in Vietnam, there is an increasing dependence on groundwater for various activities. An Giang province is known to be one of the agricultural intensification areas of The Vietnamese Mekong Delta (VMD). This study aimed to evaluate the spatiotemporal variation of groundwater quality for a period of ten years from 2009 to 2018 in An Giang. The weighted groundwater quality index (GWQI) was developed based on the fuzzy analytic hierarchy process (Fuzzy-AHP) for assigning weighted parameters. The results show that that shallow wells in the Northeast and Southeast regions of An Giang were mostly categorized under “bad water” quality with high arsenic (As) concentration over the years partly due to huge amounts of sediment deposition in monsoon season. Overall, the reason for the poor groundwater quality in An Giang was the combined effect of both natural and human activities. On the other hand, we detected high values of GWQI links with high As concentration in areas where people extract more groundwater for irrigation. Temporal variation of GWQI suggested that groundwater quality at eight wells has improved from 2009 to 2018 in the wet season as compared to the dry season. The reason behind the improvement of groundwater quality during wet season was the decrease in river discharge, which causes less deposition of suspended solids near the flood plains. Moreover, the filling of unused wells can reduce the movement of pollutants from unused wells to groundwater aquifers. Although there was not sufficient evidence to show the relationship between As and sediment concentration, the temporal reduction trend in river discharge and suspended solids was detected in An Giang. The understanding of groundwater quality can help policymakers protect and manage limited water resources in the long-term.
Implementation of a Surgical Liaison Service for Elderly Patients: A Single Unit Experience
Authors: Bennett Jessica , Fung Dave , Hodson Rachel , Agarwal Anil
Published: July 2019

Older people over the age of 65 years are recognized as higher risk surgical candidates and it is therefore recommended that their care should be coordinated through a multidisciplinary team (MDT) approach involving senior geriatricians, anaesthetists and surgeons. As one of only a handful of hospitals to implement a liaison service for elderly surgical patients we have seen both quantitative and qualitative improvements in the care delivered. Both co-ordination and continuity of care has improved and overall staff feel that the service forms an integral part of caring for the older surgical patient. Currently only 1% of UK hospitals are meeting targets for implementation of liaison services for their elderly surgical patients. Our surgical liaison service offers consultant led care for older people and is valued amongst users. We would like to share our experiences in the service setup, provision and its subsequent impact on patient care.
Developing and Evaluating Management Services for Collective Memory ‡
Authors: Koukoulis Konstantinos , Koukopoulos Dimitrios
Published: July 2019

Collective memory is vital for people as it gives them the sense of belonging to a community. In particular, refugee population groups feel the need to maintain contact with their routes through collective memory, due to the abolishment of the physical connection to their homeland. However, people’s memories fade over time and stories are lost. In such a context a crucial question arises: Is it feasible to design and create a crowdsourcing collective memory management system for the benefit of such social groups preserving memory for next generations? In this work, we present a system that is able to collect and manage refugee stories disseminating them to the public. In order to stress the strength of the proposed system, we have created an evaluation methodology that assesses such a system in terms of system services and system stakeholders’ real impact. We chose to deal with the collective memory of refugee groups coming from Asia Minor to Greece at the end of the first quarter of the twentieth century. Evaluation results reveal that such a system positively affects personal and social impact factors. Furthermore, a preliminary results analysis suggests specific interactions among the examined personal and social impact factors. We believe that the proposed system facilitates the needs of collective memory management and the assessment scheme could be adapted in the creation and evaluation of collective memory management systems.
Conservation of Cultural Heritage: Issues along the Thapathali-Teku stretch of the Bagmati River in Kathmandu, Nepal
Authors: Tamrakar Anita , Parajuli Rishi Ram
Published: July 2019

The Bagmati, an auspicious and sacred river, is adorned with Ghat, Dharmashalas, Pati, Sattals, Temples, Brahmanaal etc. at various stretches within the valley for the facilitations of the devotees from the daily ritual bath to the last right of cremation. The Bagmati has been associated with the peoples of the Kathmandu valley, making it a highly significant cultural space of their devoutness. Authorities fail to recognize the significance of the site in terms of time, lack of proper policies, management plan, resources for safeguarding and conservation; several issues and challenges arise regarding the conservation of the site. Apart from technical issues such as material originality, financial issues, environmental issues, degradation of river water quality, development pressure and encroachment have ruined the site. This paper presents the significance of the 19th century cultural heritage sites along the Bagmati River from Thapathali to Teku Dobhan, which has not been prioritized for safeguarding. This also addresses the restoration, reconstruction, conservation and preparation of the management plan. In order to safeguard the past legacy of this site for the future generations, the holistic approach of conservation has to be opted for.
Changes in Acetylene Reduction Activities and nifH Genes Associated with Field-Grown Sweet Potatoes with Different Nursery Farmers and Cultivars
Authors: Itoh Kazuhito , Ohashi Keisuke , Yakai Nao , Adachi Fumihiko , Hayashi Shohei
Published: July 2019

Sweet potato cultivars obtained from different nursery farmers were cultivated in an experimental field from seedling-stage to harvest, and the acetylene reduction activity (ARA) of different parts of the plant as well as the nifH genes associated with the sweet potatoes were examined. The relationship between these parameters and the plant weights, nitrogen contents, and natural abundance of 15N was also considered. The highest ARA was detected in the tubers and in September. Fragments of a single type of nitrogenase reductase gene (nifH) were amplified, and most of them had similarities with those of Enterobacteriaceae in γ-Proteobacteria. In sweet potatoes from one nursery farm, Dickeya nifH was predominantly detected in all of the cultivars throughout cultivation. In sweet potatoes from another farm, on the other hand, a transition to Klebsiella and Phytobacter nifH was observed after the seedling stage. The N2-fixing ability contributed to plant growth, and competition occurred between autochthonous and allochthonous bacterial communities in sweet potatoes.
Correlates of Work-Study Conflict among International Students in Australia: A Multivariate Analysis
Authors: Thamrin Yahya , Pisaniello Dino , Guerin Cally , Rothmore Paul
Published: July 2019

International students represent an increasingly large segment of the Australian workforce. Most international students are working while studying, but there is a scarcity of quantitative data regarding potential work–study conflicts. Data from an online survey were analyzed with multivariate statistical methods to clarify the risk factors associated with perceived work–study conflicts in an Australian university. More than 66% of students felt that working demands interfered with their study. Negative impacts included tiredness and timetable clashes. Statistically significant correlates of work–study conflict were a perception of unfair wages and a lack of confidence in discussing occupational health and safety issues with employers. Underpayment may signify other vulnerabilities, such as unsafe working conditions. As many universities seek to increase their international student enrolments, these are important factors to consider for student retention. To mitigate this potential negative influence on study, universities should provide education and training related to international students’ rights and responsibilities in the workplace.
The Current Research Landscape of the Application of Artificial Intelligence in Managing Cerebrovascular and Heart Diseases: A Bibliometric and Content Analysis
Authors: Tran Bach Xuan , Latkin Carl A. , Vu Giang Thu , Nguyen Huong Lan Thi , Nghiem Son , Tan Ming-Xuan , Lim Zhi-Kai , Ho Cyrus S.H. , Ho Roger C.M.
Published: July 2019

The applications of artificial intelligence (AI) in aiding clinical decision-making and management of stroke and heart diseases have become increasingly common in recent years, thanks in part to technological advancements and the heightened interest of the research and medical community. This study aims to provide a comprehensive picture of global trends and developments of AI applications relating to stroke and heart diseases, identifying research gaps and suggesting future directions for research and policy-making. A novel analysis approach that combined bibliometrics analysis with a more complex analysis of abstract content using exploratory factor analysis and Latent Dirichlet allocation, which uncovered emerging research domains and topics, was adopted. Data were extracted from the Web of Science database. Results showed topics with the most compelling growth to be AI for big data analysis, robotic prosthesis, robotics-assisted stroke rehabilitation, and minimally invasive surgery. The study also found an emerging landscape of research that was centered on population-specific and early detection of stroke and heart disease. Application of AI in health behavior tracking and improvement as well as the use of robotics in medical diagnostics and prognostication have also been found to attract significant research attention. In light of these findings, it is suggested that the currently under-researched issues of data management, AI model reliability, as well as validation of its clinical utility, need to be further explored in future research and policy decisions to maximize the benefits of AI applications in stroke and heart diseases.
The Association between Mobile Phone Use and Severe Traffic Injuries: A Case-Control Study from Saudi Arabia
Authors: Alghnam Suliman , Towhari Jawaher , Alkelya Mohamed , Alsaif Ahmad , Alrowaily Mohamed , Alrabeeah Fawaz , Albabtain Ibrahim
Published: July 2019

Road traffic injury (RTI) is the third leading cause of death in Saudi Arabia. Using a mobile phone when driving is associated with distracted driving, which may result in RTIs. Because of limited empirical data, we investigated the association between mobile phone use and RTI in injured patients and community controls in Riyadh. Cases were patients admitted to King Abdulaziz Medical City (KAMC) between October 2016 and March 2018 due to RTIs. During admission, mobile phone use at the time of the accident was investigated. The controls were drivers observed at various locations citywide. A logistic regression model was constructed to estimate the association between mobile phone use while driving and sustaining RTIs. We included 318 cases and 1700 controls. For the cases, using a mobile phone was associated with higher severity and prevalence of disability. In addition, using a mobile phone while driving is associated with 44% higher odds of incurring a severe RTI (p = 0.04). Mobile phone use while driving is prevalent in Riyadh and pose a significant threat of disability. In addition, the low prevalence of seatbelt use is alarming and requires significant improvement. Prevention programs may use these findings to educate the public and policymakers and to advocate for increased visibility of enforcement to reduce RTIs and improve population health.
What Are Investors Afraid of? Finding the Big Bad Wolf
Authors: Alemanni Barbara , Uberti Pierpaolo
Published: July 2019

The aim of financial institutions and regulators is to find an effective way to measure the risk profile of different segments of investors. Both economists and psychologists developed several methodologies to elicit and assess individual risk attitude, but these are not perfect and show several drawbacks when used in practice. Thanks to a unique database of around 15,000 investors, this paper combines survey-based evidence with revealed preferences based upon observed asset allocation. This paper confirms some results known in the literature like the gender and age differences in risk-taking. Moreover, the behavioral clustering approach used for the analysis is useful in an inferential framework. The segments built starting from the questionnaire permit to “forecast” the individual risk attitude that is described by the individual choices in terms of asset allocation. Loss aversion per se is a relevant variable in explaining financial risk-taking.
Development of an Indoor Space Semantic Model and Its Implementation as an IndoorGML Extension
Authors: Maheshwari Nishith , Srivastava Srishti , Rajan Krishnan Sundara
Published: July 2019

Geospatial data capture and handling of indoor spaces is increasing over the years and has had a varied history of data sources ranging from architectural and building drawings to indoor data acquisition approaches. While these have been more data format and information driven primarily for the physical representation of spaces, it is important to note that many applications look for the semantic information to be made available. This paper proposes a space classification model leading to an ontology for indoor spaces that accounts for both the semantic and geometric characteristics of the spaces. Further, a Space semantic model is defined, based on this ontology, which can then be used appropriately in multiple applications. To demonstrate the utility of the model, we also present an extension to the IndoorGML data standard with a set of proposed classes that can help capture both the syntactic and semantic components of the model. It is expected that these proposed classes can be appropriately harnessed for use in diverse applications ranging from indoor data visualization to more user customised building evacuation path planning with a semantic overtone.
Poly(2,6-Dimethyl-1,4-Phenylene Oxide)-Based Hydroxide Exchange Separator Membranes for Zinc–Air Battery
Authors: Abbasi Ali , Hosseini Soraya , Somwangthanaroj Anongnat , Mohamad Ahmad Azmin , Kheawhom Soorathep
Published: July 2019

Rechargeable zinc–air batteries are deemed as the most feasible alternative to replace lithium–ion batteries in various applications. Among battery components, separators play a crucial role in the commercial realization of rechargeable zinc–air batteries, especially from the viewpoint of preventing zincate (Zn(OH)42−) ion crossover from the zinc anode to the air cathode. In this study, a new hydroxide exchange membrane for zinc–air batteries was synthesized using poly (2,6-dimethyl-1,4-phenylene oxide) (PPO) as the base polymer. PPO was quaternized using three tertiary amines, including trimethylamine (TMA), 1-methylpyrolidine (MPY), and 1-methylimidazole (MIM), and casted into separator films. The successful synthesis process was confirmed by proton nuclear magnetic resonance and Fourier-transform infrared spectroscopy, while their thermal stability was examined using thermogravimetric analysis. Besides, their water/electrolyte absorption capacity and dimensional change, induced by the electrolyte uptake, were studied. Ionic conductivity of PPO–TMA, PPO–MPY, and PPO–MIM was determined using electrochemical impedance spectroscopy to be 0.17, 0.16, and 0.003 mS/cm, respectively. Zincate crossover evaluation tests revealed very low zincate diffusion coefficient of 1.13 × 10−8, and 0.28 × 10−8 cm2/min for PPO–TMA, and PPO–MPY, respectively. Moreover, galvanostatic discharge performance of the primary batteries assembled using PPO–TMA and PPO–MPY as initial battery tests showed a high specific discharge capacity and specific power of ~800 mAh/gZn and 1000 mWh/gZn, respectively. Low zincate crossover and high discharge capacity of these separator membranes makes them potential materials to be used in zinc–air batteries.
Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure
Authors: Chen Lin , Simões Alyne , Chen Zujian , Zhao Yan , Wu Xinming , Dai Yang , DiPietro Luisa A. , Zhou Xiaofeng
Published: July 2019

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.
The Latest Studies on Lotus (Nelumbo nucifera)-an Emerging Horticultural Model Plant
Authors: Lin Zhongyuan , Zhang Cheng , Cao Dingding , Damaris Rebecca Njeri , Yang Pingfang
Published: July 2019

Lotus (Nelumbo nucifera) is a perennial aquatic basal eudicot belonging to a small family Nelumbonaceace, which contains only one genus with two species. It is an important horticultural plant, with its uses ranging from ornamental, nutritional to medicinal values, and has been widely used, especially in Southeast Asia. Recently, the lotus obtained a lot of attention from the scientific community. An increasing number of research papers focusing on it have been published, which have shed light on the mysteries of this species. Here, we comprehensively reviewed the latest advancement of studies on the lotus, including phylogeny, genomics and the molecular mechanisms underlying its unique properties, its economic important traits, and so on. Meanwhile, current limitations in the research of the lotus were addressed, and the potential prospective were proposed as well. We believe that the lotus will be an important model plant in horticulture with the generation of germplasm suitable for laboratory operation and the establishment of a regeneration and transformation system.
Partial Failure of Proteostasis Systems Counteracting TDP-43 Aggregates in Neurodegenerative Diseases
Authors: Cascella Roberta , Fani Giulia , Bigi Alessandra , Chiti Fabrizio , Cecchi Cristina
Published: July 2019

Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are progressive and fatal neurodegenerative disorders showing mislocalization and cytosolic accumulation of TDP-43 inclusions in the central nervous system. The decrease in the efficiency of the clearance systems in aging, as well as the presence of genetic mutations of proteins associated with cellular proteostasis in the familial forms of TDP-43 proteinopathies, suggest that a failure of these protein degradation systems is a key factor in the aetiology of TDP-43 associated disorders. Here we show that the internalization of human pre-formed TDP-43 aggregates in the murine neuroblastoma N2a cells promptly resulted in their ubiquitination and hyperphosphorylation by endogenous machineries, mimicking the post-translational modifications observed in patients. Moreover, our data identify mitochondria as the main responsible sites for the alteration of calcium homeostasis induced by TDP-43 aggregates, which, in turn, stimulates an increase in reactive oxygen species and, finally, caspase activation. The inhibition of TDP-43 proteostasis in the presence of selective inhibitors against the proteasome and macroautophagy systems revealed that these two systems are both severely involved in TDP-43 accumulation and have a strong influence on each other in neurodegenerative disorders associated with TDP-43.
Association between Lysosomal Dysfunction and Obesity-Related Pathology: A Key Knowledge to Prevent Metabolic Syndrome
Authors: Mizunoe Yuhei , Kobayashi Masaki , Tagawa Ryoma , Nakagawa Yoshimi , Shimano Hitoshi , Higami Yoshikazu
Published: July 2019

Obesity causes various health problems, such as type 2 diabetes, non-alcoholic fatty liver disease, and cardio- and cerebrovascular diseases. Metabolic organs, particularly white adipose tissue (WAT) and liver, are deeply involved in obesity. WAT contains many adipocytes with energy storage capacity and secretes adipokines depending on the obesity state, while liver plays pivotal roles in glucose and lipid metabolism. This review outlines and underscores the relationship between obesity and lysosomal functions, including lysosome biogenesis, maturation and activity of lysosomal proteases in WAT and liver. It has been revealed that obesity-induced abnormalities of lysosomal proteases contribute to inflammation and cellular senescence in adipocytes. Previous reports have demonstrated obesity-induced ectopic lipid accumulation in liver is associated with abnormality of lysosomal proteases as well as other lysosomal enzymes. These studies demonstrate that lysosomal dysfunction in WAT and liver underlies part of the obesity-related pathology, raising the possibility that strategies to modulate lysosomal function may be effective in preventing or treating the metabolic syndrome.
Gene–Environment Interactions on Body Fat Distribution
Authors: Li Xiang , Qi Lu
Published: July 2019

The prevalence of obesity has been increasing markedly in the U.S. and worldwide in the past decades; and notably, the obese populations are signified by not only the overall elevated adiposity but also particularly harmful accumulation of body fat in the central region of the body, namely, abdominal obesity. The profound shift from “traditional” to “obesogenic” environments, principally featured by the abundance of palatable, energy-dense diet, reduced physical activity, and prolonged sedentary time, promotes the obesity epidemics and detrimental body fat distribution. Recent advances in genomics studies shed light on the genetic basis of obesity and body fat distribution. In addition, growing evidence from investigations in large cohorts and clinical trials has lent support to interactions between genetic variations and environmental factors, e.g., diet and lifestyle factors, in relation to obesity and body fat distribution. This review summarizes the recent discoveries from observational studies and randomized clinical trials on the gene–environment interactions on obesity and body fat distribution.
Extracellular Vesicle-Induced Differentiation of Neural Stem Progenitor Cells
Authors: Stronati Eleonora , Conti Roberta , Cacci Emanuele , Cardarelli Silvia , Biagioni Stefano , Poiana Giancarlo
Published: July 2019

Neural stem progenitor cells (NSPCs) from E13.5 mouse embryos can be maintained in culture under proliferating conditions. Upon growth-factor removal, they may differentiate toward either neuronal or glial phenotypes or both. Exosomes are small extracellular vesicles that are part of the cell secretome; they may contain and deliver both proteins and genetic material and thus play a role in cell–cell communication, guide axonal growth, modulate synaptic activity and regulate peripheral nerve regeneration. In this work, we were interested in determining whether NSPCs and their progeny can produce and secrete extracellular vesicles (EVs) and if their content can affect cell differentiation. Our results indicate that cultured NSPCs produce and secrete EVs both under proliferating conditions and after differentiation. Treatment of proliferating NSPCs with EVs derived from differentiated NSPCs triggers cell differentiation in a dose-dependent manner, as demonstrated by glial- and neuronal-marker expression.
Role of the Monocyte–Macrophage System in Normal Pregnancy and Preeclampsia
Authors: Vishnyakova Polina , Elchaninov Andrey , Fatkhudinov Timur , Sukhikh Gennady
Published: July 2019

The proper functioning of the monocyte–macrophage system, an important unit of innate immunity, ensures the normal course of pregnancy. In this review, we present the current data on the origin of the monocyte–macrophage system and its functioning in the female reproductive system during the ovarian cycle, and over the course of both normal and complicated pregnancy. Preeclampsia is a crucial gestation disorder characterized by pronounced inflammation in the maternal body that affects the work of the monocyte–macrophage system. The effects of inflammation at preeclampsia manifest in changes in monocyte counts and their subset composition, and changes in placental macrophage counts and their polarization. Here we summarize the recent data on this issue for both the maternal organism and the fetus. The influence of estrogen on macrophages and their altered levels in preeclampsia are also discussed.
Fluorescence Enhancement Effect of TiO2 Nanoparticles and Application for Photodynamic Diagnosis
Authors: Kanehira Koki , Yano Yukiko , Hasumi Hisashi , Fukuhara Hideo , Inoue Keiji , Hanazaki Kazuhiro , Yao Masahiro
Published: July 2019

Photodynamic diagnosis (PDD) can improve diagnostic accuracy by using PDD agents such as 5-aminolevulinic acid (ALA). However, the weakness and photobleaching of fluorescence of PDD agents may lead to insufficient fluorescence visibility for the detection of cancer during resection operations. We focused on the “fluorescence enhancement effect” resulting from the addition of polyethylene glycol-modified titanium dioxide nanoparticles (TiO2-PEG NPs) to address these problems. The results showed that the combined administration of TiO2-PEG NPs and ALA could enhance and prolong fluorescence in bladder cancer cells, similar to in the mixture alone. It was suggested that the fluorescence enhancement was related to the accumulation of TiO2-PEG NPs in cells via endocytosis, causing the light scattering and enhancement of fluorescence. This fluorescence enhancement effect could be applicable for PDD.
Cell Autonomous Dysfunction and Insulin Resistance in Pancreatic α Cells
Authors: Honzawa Norikiyo , Fujimoto Kei , Kitamura Tadahiro
Published: July 2019

To date, type 2 diabetes is considered to be a “bi-hormonal disorder” rather than an “insulin-centric disorder,” suggesting that glucagon is as important as insulin. Although glucagon increases hepatic glucose production and blood glucose levels, paradoxical glucagon hypersecretion is observed in diabetes. Recently, insulin resistance in pancreatic α cells has been proposed to be associated with glucagon dysregulation. Moreover, cell autonomous dysfunction of α cells is involved in the etiology of diabetes. In this review, we summarize the current knowledge about the physiological and pathological roles of glucagon.
Co-Inhibition of the DNA Damage Response and CHK1 Enhances Apoptosis of Neuroblastoma Cells
Authors: Ando Kiyohiro , Nakamura Yohko , Nagase Hiroki , Nakagawara Akira , Koshinaga Tsugumichi , Wada Satoshi , Makishima Makoto
Published: July 2019

Checkpoint kinase 1 (CHK1) is a central mediator of the DNA damage response (DDR) at the S and G2/M cell cycle checkpoints, and plays a crucial role in preserving genomic integrity. CHK1 overexpression is thought to contribute to cancer aggressiveness, and several selective inhibitors of this kinase are in clinical development for various cancers, including neuroblastoma (NB). Here, we examined the sensitivity of MYCN-amplified NB cell lines to the CHK1 inhibitor PF-477736 and explored mechanisms to increase its efficacy. PF-477736 treatment of two sensitive NB cell lines, SMS-SAN and CHP134, increased the expression of two pro-apoptotic proteins, BAX and PUMA, providing a mechanism for the effect of the CHK1 inhibitor. In contrast, in NB-39-nu and SK-N-BE cell lines, PF-477736 induced DNA double-strand breaks and activated the ataxia telangiectasia mutated serine/threonine kinase (ATM)-p53-p21 axis of the DDR pathway, which rendered the cells relatively insensitive to the antiproliferative effects of the CHK1 inhibitor. Interestingly, combined treatment with PF-477736 and the ATM inhibitor Ku55933 overcame the insensitivity of NB-39-nu and SK-N-BE cells to CHK1 inhibition and induced mitotic cell death. Similarly, co-treatment with PF-477736 and NU7441, a pharmacological inhibitor of DNA-PK, which is also essential for the DDR pathway, rendered the cells sensitive to CHK1 inhibition. Taken together, our results suggest that synthetic lethality between inhibitors of CHK1 and the DDR drives G2/M checkpoint abrogation and could be a novel potential therapeutic strategy for NB.
Comparative Analysis of the Characteristics of Triterpenoid Transcriptome from Different Strains of Wolfiporia cocos
Authors: Zeng Guiping , Li Zhong , Zhao Zhi
Published: July 2019

The dried sclerotia of Wolfiporia cocos (Schwein.) Ryvarden & Gilb., a traditional Chinese medicine, has triterpenoid as its main active component. Breeding high-yield triterpenoid in W. cocos is an important research topic at present. We screened out two monosporal strains from the same W. cocos 5.78, high-yielding DZAC-Wp-H-29 (H) and low-yielding DZAC-Wp-L-123 (L), and cultured mycelia for 17 days, 34 days, and 51 days, respectively. Transcriptome analysis results showed that triterpenoid synthesis is closely related to gene expression in triterpenoid synthesis pathways (hydroxymethyl glutaryl-CoA reductase (HMGCR), farnesyl diphosphate synthase (FDPS), 4-hydroxybenzoate polyprenyltransferase (COQ2), C-8 sterol isomerase (ERG2), sterol O-acyltransferase (ACAT), tyrosine aminotransferase (TAT), torulene dioxygenase (CAO2), and sterol-4alpha-carboxylate 3-dehydrogenase (erg26)), and is limited by the expression of enzyme M20 combined with domain protein peptide (Pm20d2), aryl-alcohol dehydrogenase (norA), ISWI chromatin-remodeling complex ATPase ISW2, GroES-like protein (adh), cytochrome P450 (ftmP450-1), and unknown proteins unigene0001029 and unigene0011374. In addition, maintaining high triterpenoid accumulation in W. cocos may require a stable membrane structure, so the accumulation ability may be related to the high synthesis ability of sterols. The low accumulation of triterpenoid in W. cocos may be due to the products of key enzymes increasing flow to other pathways.
Expression of HERV Genes as Possible Biomarker and Target in Neurodegenerative Diseases
Authors: Dolei Antonina , Ibba Gabriele , Piu Claudia , Serra Caterina
Published: July 2019

Human endogenous retroviruses (HERVs) are genetic parasites, in-between genetics and environment. Few HERVs retain some coding capability. Sometimes, the host has the advantage of some HERV genes; conversely, HERVs may contribute to pathogenesis. The expression of HERVs depends on several factors, and is regulated epigenetically by stimuli such as inflammation, viral and microbial infections, etc. Increased expression of HERVs occurs in physiological and pathological conditions, in one or more body sites. Several diseases have been attributed to one or more HERVs, particularly neurological diseases. The key problem is to differentiate the expression of a HERV as cause or effect of a disease. To be used as a biomarker, a correlation between the expression of a certain HERV and the disease onset and/or behavior must be found. The greater challenge is to establish a pathogenic role. The criteria defining causal connections between HERVs and diseases include the development of animal models, and disease modulation in humans, by anti-HERV therapeutic antibody. So far, statistically significant correlations between HERVs and diseases have been achieved for HERV-W and multiple sclerosis; disease reproduction in transgenic animals was achieved for HERV-W and multiple sclerosis, and for HERV-K and amyotrophic lateral sclerosis. Clinical trials for both diseases are in progress.
Physiological and Transcriptomic Changes during the Early Phases of Adventitious Root Formation in Mulberry Stem Hardwood Cuttings
Authors: Shang Chunqiong , Yang Honglei , Ma Sang , Shen Qiudi , Liu Li , Hou Chengxiang , Cao Xu , Cheng Jialing
Published: July 2019

The initiation and induction of root primordia are of great importance for adventitious root (AR) formation in cutting propagation of horticultural and forestry crops. However, the underlying mechanisms orchestrating these early phases of AR formation remain largely unexplored. Here, we investigated the physiological and transcriptomic changes during the early AR phases in mulberry stem hardwood cuttings. The results showed that the concentrations of soluble proteins increased, whereas concentrations of soluble sugars and starch were decreased. Indole-3-acetic acid (IAA) and zeatin had a rapid transit peak at 6 h after planting (hAP) and declined thereafter. The activities of peroxidase and catalase persistently increased and indole-3-acetic acid oxidase was maintained at a higher stable level from 0 hAP, while the activities of polyphenol oxidase fluctuated with soluble phenolics and IAA levels. The comparative transcriptome identified 4276 common genes that were differentially regulated at −6, 0 and 54 hAP. They were separated into five clusters with distinct biological functions such as defense response and photosynthesis. Considerable common genes were assigned to pathways of sugar metabolism, mitogen-activated protein kinase, and circadian rhythm. The gene co-expression network analysis revealed three major co-expressed modules involved in stress responses, hormone signaling, energy metabolism, starch metabolism, and circadian rhythm. These findings demonstrate the positive effect of auxin on AR induction, and uncovered the crucial roles of stress responses, hormone signaling and circadian rhythm in coordinating the physiological changes during the early phases of AR formation in mulberry stem hardwood cuttings.
Editorial of Special Issue “The Interplay of Microbiome and Immune Response in Health and Diseases”
Authors: Amedei Amedeo , Barceló-Coblijn Gwendolyn
Published: July 2019

Increasing data suggests and supports the idea that the gut microbiota (GM) modulates different host pathways, playing a crucial role in human physiology and consequently impacting in the development of some pathologic conditions [...]
Estrogen Deficiency Potentiates Thioacetamide-Induced Hepatic Fibrosis in Sprague-Dawley Rats
Authors: Lee Yong Hee , Son Ji Yeon , Kim Kyeong Seok , Park Yoo Jung , Kim Hae Ri , Park Jae Hyeon , Kim Kyu-Bong , Lee Kwang Youl , Kang Keon Wook , Kim In Su , Kacew Sam , Lee Byung Mu , Kim Hyung Sik
Published: July 2019

Hepatic fibrosis is characterized by persistent deposition of extracellular matrix proteins and occurs in chronic liver diseases. The aim of the present study is to investigate whether estrogen deficiency (ED) potentiates hepatic fibrosis in a thioacetamide (TAA)-treated rat model. Fibrosis was induced via intraperitoneal injection (i.p.) of TAA (150 mg/kg/day) for four weeks in ovariectomized (OVX) female, sham-operated female, or male rats. In TAA-treated OVX rats, the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased compared to those in TAA-treated sham-operated OVX rats or TAA-treated male rats. Furthermore, α-smooth muscle actin (α-SMA) expression was significantly increased compared to that in TAA-treated sham-operated rats. This was accompanied by the appearance of fibrosis biomarkers including vimentin, collagen-I, and hydroxyproline, in the liver of TAA-treated OVX rats. In addition, ED markedly reduced total glutathione (GSH) levels, as well as catalase (CAT) and superoxide dismutase (SOD) activity in TAA-treated OVX rats. In contrast, hepatic malondialdehyde (MDA) levels were elevated in TAA-treated OVX rats. Apoptosis significantly increased in TAA-treated OVX rats, as reflected by elevated p53, Bcl-2, and cleaved caspase 3 levels. Significant increases in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were exhibited in TAA-treated OVX rats, and this further aggravated fibrosis through the transforming growth factor-β (TGF-β)/Smad pathway. Our data suggest that ED potentiates TAA-induced oxidative damage in the liver, suggesting that ED may enhance the severity of hepatic fibrosis in menopausal women.
Theoretical Studies of Nickel-Dependent Enzymes
Authors: Siegbahn Per E. M. , Chen Shi-Lu , Liao Rong-Zhen
Published: July 2019

The advancements of quantum chemical methods and computer power allow detailed mechanistic investigations of metalloenzymes. In particular, both quantum chemical cluster and combined QM/MM approaches have been used, which have been proven to successfully complement experimental studies. This review starts with a brief introduction of nickel-dependent enzymes and then summarizes theoretical studies on the reaction mechanisms of these enzymes, including NiFe hydrogenase, methyl-coenzyme M reductase, nickel CO dehydrogenase, acetyl CoA synthase, acireductone dioxygenase, quercetin 2,4-dioxygenase, urease, lactate racemase, and superoxide dismutase.
Vulnerable Plaque, Characteristics, Detection, and Potential Therapies
Authors: Hafiane Anouar
Published: July 2019

Plaque development and rupture are hallmarks of atherosclerotic vascular disease. Despite current therapeutic developments, there is an unmet necessity in the prevention of atherosclerotic vascular disease. It remains a challenge to determine at an early stage if atherosclerotic plaque will become unstable and vulnerable. The arrival of molecular imaging is receiving more attention, considering it allows for a better understanding of the biology of human plaque and vulnerabilities. Various plaque therapies with common goals have been tested in high-risk patients with cardiovascular disease. In this work, the process of plaque instability, along with current technologies for sensing and predicting high-risk plaques, is debated. Updates on potential novel therapeutic approaches are also summarized.
Prevalence of Asthma and COPD and Blood Eosinophil Count in a Middle-Aged Belgian Population
Authors: Wijnant Sara R. A. , Lahousse Lies , De Buyzere Marc L. , Brusselle Guy G. , Rietzschel Ernst R.
Published: July 2019

Various phenotypes exist in asthma and Chronic Obstructive Pulmonary Disease (COPD). These are important to identify in order to guide treatment decisions. We aim to investigate the prevalence and clinical characteristics of obstructive airway diseases in the middle-aged population. We estimated the prevalence of COPD and/or asthma in the Asklepios cohort study (Belgium), using information from the third European Community Respiratory Health Survey (ECRHS3), medical records, and spirometry. Respiratory symptoms, respiratory medication, and current disease status distinguished clinical from sub-clinical cases. In addition, we compared the blood eosinophil count/µL (median [IQR]) between cases and controls. Of the 2221 participants (mean age 56.1 ± 5.9 years; 48.7% males), 138 (6.2%) participants had clinical current asthma, 22 (1.0%) participants had sub-clinical ever asthma, 102 (4.6%) had sub-clinical spirometry-defined COPD, 104 (4.6%) participants had clinical spirometry-confirmed COPD, and 11 (0.5%) had asthma and COPD overlap (ACO). Clinical current asthma (160.0 [110.0–250.0]), sub-clinical ever asthma (170.0 [110.0–230.0]), and clinical COPD (160.0 [110.0–220.0])—but less sub-clinical COPD (140.0 [90.0–210.0])—had higher eosinophil counts, compared to controls (130.0 [80.0–200.0]). We conclude that obstructive airway diseases are prevalent in the middle-aged Asklepios cohort. Moreover, the systemic eosinophil count is increased in clinical COPD cases, and in asthma cases regardless of clinical remission.
Interannual and Seasonal Changes in the Benthic Algae Flora of Coral Reef in Xiaodong Hai (Hainan Island, China)
Authors: Titlyanov Eduard A. , Titlyanova Tamara V. , Scriptsova Anna V. , Ren Yuxiao , Li Xiubao , Huang Hui
Published: July 2019

Intensive algal sampling conducted in 2016–2019 in the Xiaodong Hai locality (Hainan Island, South China Sea), yielded a total of 198 benthic macroalgal species and their taxonomic forms (54% reds, 20% browns and 26% greens) and 20 species of Cyanobacteria. The largest number of species belonged to the families Rhodomelaceae, Ceramiaceae and Corallinaceae (Rhodophyta); Sargassaceae and Dictyotaceae (Phaeophyceae); Cladophoraceae and Caulerpaceae (Chlorophyta). The majority (79%) of species inhabiting only the tropics or subtropics were previously recorded and 21% of the species were also inhabiting temperate latitudes. Cosmopolitan algae inhabiting from the tropics to Arctic or Antarctic waters amounted to 14%. The level of maximum similarity of macroalgal species diversity in different years was on average more than 70%, interannual species specificity was observed only in the group of dominating species in algal turf communities. The seasonal variability of floras was manifested in a significant decrease in species diversity from the dry season to the rainy and in the change of dominant species in algal turf communities.
Multigene Genetic-Programming-Based Models for Initial Dilution of Laterally Confined Vertical Buoyant Jets
Authors: Yan Xiaohui , Mohammadian Abdolmajid
Published: July 2019

A new approach based on the multigene genetic-programming (MGGP) technique is proposed to predict initial dilution of vertical buoyant jets subjected to lateral confinement. The models are trained and tested using experimental data, and the good matches demonstrate the generalization and predictive capabilities of the evolved MGGP-based models. The best Pareto-optimal MGGP-based model is also compared with the model evolved using a single-gene genetic-programming (SGGP) algorithm and an existing regression-based empirical equation. The comparisons reveal the superiority of the MGGP-based model. This study confirms that the MGGP technique is promising in evolving an explicit, accurate, and compact model, and the developed models can be employed to estimate effectively and efficiently the dilution properties of a laterally confined vertical buoyant jet.
Modelling Bacteria-Inspired Dynamics with Networks of Interacting Chemicals
Authors: Bánsági Tamás , Taylor Annette
Published: July 2019

One approach to understanding how life-like properties emerge involves building synthetic cellular systems that mimic certain dynamical features of living cells such as bacteria. Here, we developed a model of a reaction network in a cellular system inspired by the ability of bacteria to form a biofilm in response to increasing cell density. Our aim was to determine the role of chemical feedback in the dynamics. The feedback was applied through the enzymatic rate dependence on pH, as pH is an important parameter that controls the rates of processes in cells. We found that a switch in pH can be used to drive base-catalyzed gelation or precipitation of a substance in the external solution. A critical density of cells was required for gelation that was essentially independent of the pH-driven feedback. However, the cell pH reached a higher maximum as a result of the appearance of pH oscillations with feedback. Thus, we conclude that while feedback may not play a vital role in some density-dependent behavior in cellular systems, it nevertheless can be exploited to activate internally regulated cell processes at low cell densities.
Engineering Properties of Engineered Cementitious Composite and Multi-Response Optimization Using PCA-Based Taguchi Method
Authors: Zhong Junfei , Shi Jun , Shen Jiyang , Zhou Guangchun , Wang Zonglin
Published: July 2019

The engineered cementitious composite (ECC) mixtures were prepared with Portland cement, ground fly ash, silica sand, and polyvinyl alcohol (PVA) fibers. Accordingly, four mix design factors with five levels each were designed using the Taguchi method. The engineering properties of ECC (flow expansion, compressive strength, flexural strength, charge passed, and maximum freeze–thaw cycle) were evaluated, and the single-response optimizations were conducted separately. Unlike other studies assigning a relative weighting parameter to each response, the principal component analysis (PCA) was innovatively introduced to optimize the ECC’s multiple responses so that the single principal performance was obtained from the most objective perspective. Furthermore, the weighting parameters for utility concept were determined by the PCA. Thereafter, an optimum mix formulation was estimated using the PCA-based Taguchi method and the updated utility concept, which provided the most desired balance of these engineering properties. Finally, the contribution of each mix design factor to the principal performance of ECC was examined, and the estimated mix formulation was verified via an additional experiment.