bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-Temporal Comprehensive Measurements of Chinese Citizens’ Health Levels and Associated Influencing Factors
Authors: Lu Chenyu , Jin Shulei , Tang Xianglong , Lu Chengpeng , Li Hengji , Pang Jiaxing
Published: July 2020

Health is the basis of a good life and a guarantee of a high quality of life. Furthermore, it is a symbol of social development and progress. How to further improve the health levels of citizens and reduce regional differences in citizens’ health status has become a research topic of great interest that is attracting attention globally. This study takes 31 provinces (municipalities and autonomous regions) of China as the research object. Through using GIS (Geographic Information System) technology, the entropy method, spatial autocorrelation, stepwise regression, and other quantitative analysis methods, measurement models and index systems are developed in order to perform an analysis of the spatio-temporal comprehensive measurements of Chinese citizens’ health levels. Furthermore, the associated influencing factors are analyzed. It has important theoretical and practical significance. The conclusions are as follows: (1) Between 2002 and 2018, the overall health levels of Chinese citizens have generally exhibited an upward trend. Moreover, for most provinces, the health levels of their citizens have improved dramatically, although some provinces, such as Tianjin and Henan, showed a fluctuating downward trend, suggesting that the health levels of citizens in these regions displayed a tendency to deteriorate. (2) The health levels of citizens from China’s various provinces showed clear spatial distribution characteristics of clustering, as well as an obvious spatial dependence and spatial heterogeneity. As time goes by, the degree of spatial clustering with regard to citizens’ health levels tends to weaken. The health levels of Chinese citizens have developed a certain temporal stability, the overall health status of Chinese citizens shows a spatial differentiation of a northeast–southwest distribution pattern. (3) The average years of education and urbanization rate have a significant positive effect on the improvement of citizens’ health levels. The increase of average years of education and urbanization rate can promote the per capita income, which certainly could help improve citizens’ health status. The Engel coefficient, urban–rural income ratio, and amount of wastewater discharge all pose a significant negative effect on the improvement of citizens’ health levels, these three factors have played important roles in hindering the improvements of citizen health.
A Frequency Pattern Mining Model Based on Deep Neural Network for Real-Time Classification of Heart Conditions
Authors: Yoo Hyun , Han Soyoung , Chung Kyungyong
Published: July 2020

Recently, a massive amount of big data of bioinformation is collected by sensor-based IoT devices. The collected data are also classified into different types of health big data in various techniques. A personalized analysis technique is a basis for judging the risk factors of personal cardiovascular disorders in real-time. The objective of this paper is to provide the model for the personalized heart condition classification in combination with the fast and effective preprocessing technique and deep neural network in order to process the real-time accumulated biosensor input data. The model can be useful to learn input data and develop an approximation function, and it can help users recognize risk situations. For the analysis of the pulse frequency, a fast Fourier transform is applied in preprocessing work. With the use of the frequency-by-frequency ratio data of the extracted power spectrum, data reduction is performed. To analyze the meanings of preprocessed data, a neural network algorithm is applied. In particular, a deep neural network is used to analyze and evaluate linear data. A deep neural network can make multiple layers and can establish an operation model of nodes with the use of gradient descent. The completed model was trained by classifying the ECG signals collected in advance into normal, control, and noise groups. Thereafter, the ECG signal input in real time through the trained deep neural network system was classified into normal, control, and noise. To evaluate the performance of the proposed model, this study utilized a ratio of data operation cost reduction and F-measure. As a result, with the use of fast Fourier transform and cumulative frequency percentage, the size of ECG reduced to 1:32. According to the analysis on the F-measure of the deep neural network, the model had 83.83% accuracy. Given the results, the modified deep neural network technique can reduce the size of big data in terms of computing work, and it is an effective system to reduce operation time.
Mental Health Patients’ Expectations about the Non-Medical Care They Receive in Primary Care: A Cross-Sectional Descriptive Study
Authors: Coronado-Vázquez Valle , Museros-Sos Dolores , Oliván-Blázquez Bárbara , Magallón-Botaya Rosa , Gómez-Salgado Juan , Sánchez-Calavera María Antonia , Masluk Bárbara , Gil-de-Gómez María Josefa , Rodríguez-Eguizábal Eva
Published: July 2020

A health system’s responsiveness is the result of patient expectations for the non-medical care they receive. The objective of this study was to assess mental patients’ responsiveness to the health system in primary care, as related to the domains of dignity, autonomy, confidentiality, and communication. Data were collected from 215 people over the age of 18 with mental disorders, using the Multi-Country Survey Study (MCSS) developed by the World Health Organization. Of them, 95% reported a good experience regarding the dignity, confidentiality, communication, and autonomy domains. Regarding responsiveness, patients valued the dignity domain as the most important one (25.1%). Among the patients who experienced poor confidentiality, five out of seven earned less than 900 euros per month (Χ2 = 10.8, p = 0.004). Among those who experienced good autonomy, 85 out of 156 belonged to the working social class (90.4%), and among those who valued it as poor (16.1%), the highest proportion was for middle class people (Χ2 = 13.1, p = 0.028). The two students and 87.5% of retirees experienced this dimension as good, and most patients who valued it as poor were unemployed (43.5%) (Χ2 = 13.0, p = 0.011). Patients with a household income higher than 900 euros more frequently valued responsiveness as good, regarding those domains related to communication, with OR = 3.84, 95% CI = 1.05–14.09, and confidentiality, with OR = 10.48, 95% CI = 1.94–56.59. To conclude, as regards responsiveness in primary care, the dignity domain always obtained the best scores by people with mental disorders. Low economic income is related to a poor assessment of confidentiality. Working class patients, students, and retirees value autonomy as good.
Tuberculosis Skin Test Screening in the National Tuberculosis Program of Trinidad and Tobago
Authors: Chattu Vijay Kumar , Sakhamuri Sateesh , Motilal Shastri , Pounder Liam J. , Persad Vasishma Kanita , Pierre Neelmani , Persad Shivannie , Pooran Nikesha , Pottinger Akua Mosi
Published: July 2020

Globally, a quarter of the population is infected with tuberculosis (TB), caused by Mycobacterium tuberculosis. About 5–10% of latent TB infections (LTBI) progress to active disease during the lifetime. Prevention of TB and treating LTBI is a critical component of the World Health Organization’s (WHO) End TB Strategy. This study aims to examine the screening practices for prevention and treatment employed by the National Tuberculosis Program of Trinidad and Tobago in comparison to the WHO’s standard guidelines. A cross-sectional retrospective study was conducted from the TB registers (2018–2019) for persons aged 18 years and above with recorded tuberculin skin test reactions (TST). Bivariate comparisons for categorical variables were made using Chi-square or Fisher’s exact test. Binary logistic regression was used for exploring predictors of TST positivity with adjustment for demographic confounders in multivariable models. Of the total 1972 eligible entries studied, 384 (19.4%) individuals were tested positive with TST. TB contact screening (aOR 2.49; 95% CI 1.65, 3.75) and Bacillus Calmette–Guerin (BCG) vaccination status (aOR 1.66; 95% CI, 1.24 to 2.22) were associated with a positive TST reaction, whereas, preplacement screening failed to show such association when compared to those screened as suspect cases. The findings suggest that TB contact screening and positive BCG vaccination status are associated with TST positivity independent of age and gender.
The Availability and Accumulation of Heavy Metals in Greenhouse Soils Associated with Intensive Fertilizer Application
Authors: Wei Binggan , Yu Jiangping , Cao Zhiqiang , Meng Min , Yang Linsheng , Chen Qing
Published: July 2020

In China, greenhouse agriculture, which provides abundant vegetable products for human consumption, has been rapidly developed in recent decades. Heavy metal accumulation in greenhouse soil and products obtained have received increasing attention. Therefore, the availability and accumulation of cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn) and their association with soil pH, soil organic matter (SOM), inorganic nitrogen (IN), total nitrogen (TN), available phosphorus (AP), and planting year (PY) in greenhouse soils were analyzed. The results showed that the mean concentrations of available Cd, Cu, Ni, Pb, and Zn were 17.25 μg/kg, 2.89, 0.18, 0.36, and 5.33 mg/kg, respectively, while their suggested levels in China are 0.6, 100, 100, 120, and 250 mg/kg. Cd, Cu, and Zn might be mainly originated from fertilizer application. A lower soil pH significantly increased the available Cu, Ni, and Zn concentrations and reduced Cd, Cu, Ni, and Zn accumulation. A higher AP significantly increased the proportions of available Cu, Ni, and Zn and elevated Cd, Cu, and Zn accumulation. There was a strong positive correlation between Cd, Pb, and Zn availability and TN, while IN was negatively related to the availability and accumulation of Cu and Zn. It was concluded that chemical fertilizer application increased the availability of Cu, Ni, Pb, and Zn and the accumulation of Cd, Cu, and Zn. Manure application clearly elevated the accumulation and availability of Cd and Zn in greenhouse soil.
Bayesian Network-Based Risk Analysis of Chemical Plant Explosion Accidents
Authors: Lu Yunmeng , Wang Tiantian , Liu Tiezhong
Published: July 2020

The chemical industry has made great contributions to the national economy, but frequent chemical plant explosion accidents (CPEAs) have also caused heavy property losses and casualties, as the CPEA is the result of interaction of many related risk factors, leading to uncertainty in the evolution of the accident. To systematically excavate and analyze the underlying causes of accidents, this paper first integrates emergency elements in the frame of orbit intersection theory and proposes 14 nodes to represent the evolution path of the accident. Then, combined with historical data and expert experience, a Bayesian network (BN) model of CPEAs was established. Through scenario analysis and sensitivity analysis, the interaction between factors and the impact of the factors on accident consequences was evaluated. It is found that the direct factors have the most obvious influence on the accident consequences, and the unsafe conditions contribute more than the unsafe behaviors. Furthermore, considering the factor chain, the management factors, especially safety education and training, are the key link of the accident that affects unsafe behaviors and unsafe conditions. Moreover, effective government emergency response has played a more prominent role in controlling environmental pollution. In addition, the complex network relationship between elements is presented in a sensitivity index matrix, and we extracted three important risk transmission paths from it. The research provides support for enterprises to formulate comprehensive safety production management strategies and control key factors in the risk transmission path to reduce CPEA risks.
Drivers’ Visual Attention Characteristics under Different Cognitive Workloads: An On-Road Driving Behavior Study
Authors: Ma Yanli , Qi Shouming , Zhang Yaping , Lian Guan , Lu Weixin , Chan Ching-Yao
Published: July 2020

In this study, an on-road driving experiment was designed to investigate the visual attention fixation and transition characteristics of drivers when they are under different cognitive workloads. First, visual attention was macroscopically analyzed through the entropy method. Second, the Markov glance one- and two-step transition probability matrices were constructed, which can study the visual transition characteristics under different conditions from a microscopic perspective. Results indicate that the fixation entropy value of male drivers is 23.08% higher than that of female drivers. Under the normal driving state, drivers’ fixation on in-vehicle systems is not continuous and usually shifts to the front and left areas quickly after such fixation. When under cognitive workload, drivers’ vision transition is concentrated only in the front and right areas. In mild cognitive workload, drivers’ sight trajectory is mainly focused on the distant front area. As the workload level increases, the transition trajectory shifts to the junction near the front and far sides. The current study finds that the difference between an on-road test and a driving simulation is that during the on-road driving process, drivers are twice as attentive to the front area than to the driving simulator. The research provides practical guidance for the improvement of traffic safety.
Tobacco Quit Intentions and Behaviors among Cigar Smokers in the United States in Response to COVID-19
Authors: Kowitt Sarah D. , Cornacchione Ross Jennifer , Jarman Kristen L. , Kistler Christine E. , Lazard Allison J. , Ranney Leah M. , Sheeran Paschal , Thrasher James F. , Goldstein Adam O.
Published: July 2020

Combustible tobacco users appear to be at greater risk for serious complications from COVID-19. This study examined cigar smokers’ perceived risk of COVID-19, quit intentions, and behaviors during the current pandemic. We conducted an online study between 23 April 2020 to 7 May 2020, as part of an ongoing study examining perceptions of different health effects of cigars. All participants used cigars in the past 30 days (n = 777). Three-quarters of the sample (76.0%) perceived they had a higher risk of complications from COVID-19 compared to non-smokers. The majority of participants (70.8%) intended to quit in the next six months due to COVID-19, and almost half of the sample (46.5%) reported making a quit attempt since the start of the COVID-19 pandemic. Far more participants reported increasing their tobacco use since COVID-19 started (40.9%) vs. decreasing their tobacco use (17.8%). Black or African American participants, participants who reported using a quitline, and participants with higher COVID-19 risk perceptions had higher intentions to quit using tobacco due to COVID-19, and higher odds of making a quit attempt since COVID-19 started. More research is needed to understand how tobacco users are perceiving COVID-19 risks and changing their tobacco use behaviors.
School and Family Environment is Positively Associated with Extracurricular Physical Activity Practice among 8 to 16 Years Old School Boys and Girls
Authors: Romero-Blanco Cristina , Dorado-Suárez Alberto , Jiménez-Zazo Fabio , Castro-Lemus Nuria , Aznar Susana
Published: July 2020

Extracurricular physical activity in children and adolescents can help achieve compliance with the World Health Organization (WHO) recommendations for physical activity. The purpose of this study was to evaluate factors in school and family environments of children and adolescents in Spain that could be related to the practice of extracurricular physical activity. Multistage random cluster sampling was conducted to include 128 schools with the participation of 10,096 students between the ages of 7 and 16. Participants completed the survey of sports habits designed by the National Sports Council. The results revealed a higher participation in extracurricular sports activities among boys (OR: 1.67 (1.5–1.9)) and students in primary education (up to 12 years old) (OR: 1.8 (1.7–2.0)). Likewise, a statistically significant relationship (p < 0.005) was observed between families where another family member practiced sports and lower number of screen time hours, improved academic performance, and better self-perceived health. Participation of children and adolescents in extracurricular sports activities seems to be associated with their immediate environment. It is therefore essential to emphasize the importance of establishing physical activity habits from an early age in family and school environments.
Migrant Women’s Access to Sexual and Reproductive Health Services in Malaysia: A Qualitative Study
Authors: Loganathan Tharani , Chan Zhie X. , de Smalen Allard W. , Pocock Nicola S.
Published: July 2020

Providing sexual and reproductive health (SRH) services to migrant workers is key to fulfilling sustainable developmental goals. This study aims to explore key informants’ views on the provision of SRH services for migrant women in Malaysia, exploring the provision of SRH education, contraception, abortion, antenatal and delivery, as well as the management of gender-based violence. In-depth interviews of 44 stakeholders were conducted from July 2018 to July 2019. Data were thematically analysed. Migrant workers that fall pregnant are unable to work legally and are subject to deportation. Despite this, we found that insufficient SRH information and contraceptive access are provided, as these are seen to encourage promiscuity. Pregnancy, rather than sexually transmitted infection prevention, is a core concern among migrant women, the latter of which is not adequately addressed by private providers. Abortions are often seen as the only option for pregnant migrants. Unsafe abortions occur which are linked to financial constraints and cultural disapproval, despite surgical abortions being legal in Malaysia. Pregnant migrants often delay care-seeking, and this may explain poor obstetric outcomes. Although health facilities for gender-based violence are available, non-citizen women face additional barriers in terms of discrimination and scrutiny by authorities. Migrant women face extremely limited options for SRH services in Malaysia and these should be expanded.
Compliance to Recommendations and Mental Health Consequences among Elderly in Sweden during the Initial Phase of the COVID-19 Pandemic—A Cross Sectional Online Survey
Authors: Gustavsson Johanna , Beckman Linda
Published: July 2020

Background (1): In the wake of COVID-19, elderly people have been labelled a risk group. As the pandemic is a new crisis in Sweden, we have no knowledge on how this group perceives the information and recommendations being provided. Complying with these recommendations entails physical distancing and, for some, isolation at home. Methods (2): From 16 April to 15 May 2020, we conducted an online survey targeting people aged 70 and older in Sweden (n = 1854). Results (3): A vast majority of the participants find the information and recommendations clear and reliable. Half of the participants report staying at home all the time, and up to half report decreased mental health in terms of, e.g., feeling depressed, having sleeping problems and that isolation makes them feel bad. However, elderly people are not a homogenous group, and there are gender and demographic differences. (4) Conclusion: At this point, we do not know the full extent of the ongoing pandemic, either in terms of duration or in terms of losses. The Swedish model for action on COVID-19 has not included a lock down. However, elderly people seem to comply with recommendations and practice social distancing to a high degree. This might lead to decreased mental health and long-term effects.
Biophysical Characterization of Cancer-Related Carbonic Anhydrase IX
Authors: Koruza Katarina , Murray A. Briana , Mahon Brian P. , Hopkins Jesse B. , Knecht Wolfgang , McKenna Robert , Fisher S. Zoë
Published: July 2020

Upregulation of carbonic anhydrase IX (CA IX) is associated with several aggressive forms of cancer and promotes metastasis. CA IX is normally constitutively expressed at low levels in selective tissues associated with the gastrointestinal tract, but is significantly upregulated upon hypoxia in cancer. CA IX is a multi-domain protein, consisting of a cytoplasmic region, a single-spanning transmembrane helix, an extracellular CA catalytic domain, and a proteoglycan-like (PG) domain. Considering the important role of CA IX in cancer progression and the presence of the unique PG domain, little information about the PG domain is known. Here, we report biophysical characterization studies to further our knowledge of CA IX. We report the 1.5 Å resolution crystal structure of the wild-type catalytic domain of CA IX as well as small angle X-ray scattering and mass spectrometry of the entire extracellular region. We used matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry to characterize the spontaneous degradation of the CA IX PG domain and confirm that it is only the CA IX catalytic domain that forms crystals. Small angle X-ray scattering analysis of the intact protein indicates that the PG domain is not randomly distributed and adopts a compact distribution of shapes in solution. The observed dynamics of the extracellular domain of CA IX could have physiological relevance, including observed cleavage and shedding of the PG domain.
Predicting In Vitro Neurotoxicity Induced by Nanoparticles Using Machine Learning
Authors: Furxhi Irini , Murphy Finbarr
Published: July 2020

The practice of non-testing approaches in nanoparticles hazard assessment is necessary to identify and classify potential risks in a cost effective and timely manner. Machine learning techniques have been applied in the field of nanotoxicology with encouraging results. A neurotoxicity classification model for diverse nanoparticles is presented in this study. A data set created from multiple literature sources consisting of nanoparticles physicochemical properties, exposure conditions and in vitro characteristics is compiled to predict cell viability. Pre-processing techniques were applied such as normalization methods and two supervised instance methods, a synthetic minority over-sampling technique to address biased predictions and production of subsamples via bootstrapping. The classification model was developed using random forest and goodness-of-fit with additional robustness and predictability metrics were used to evaluate the performance. Information gain analysis identified the exposure dose and duration, toxicological assay, cell type, and zeta potential as the five most important attributes to predict neurotoxicity in vitro. This is the first tissue-specific machine learning tool for neurotoxicity prediction caused by nanoparticles in in vitro systems. The model performs better than non-tissue specific models.
The Role of microRNAs in Organismal and Skin Aging
Authors: Gerasymchuk Marta , Cherkasova Viktoriia , Kovalchuk Olga , Kovalchuk Igor
Published: July 2020

The aging process starts directly after birth and lasts for the entire lifespan; it manifests itself with a decline in an organism’s ability to adapt and is linked to the development of age-related diseases that eventually lead to premature death. This review aims to explore how microRNAs (miRNAs) are involved in skin functioning and aging. Recent evidence has suggested that miRNAs regulate all aspects of cutaneous biogenesis, functionality, and aging. It has been noted that some miRNAs were down-regulated in long-lived individuals, such as let-7, miR-17, and miR-34 (known as longevity-related miRNAs). They are conserved in humans and presumably promote lifespan prolongation; conversely, they are up-regulated in age-related diseases, like cancers. The analysis of the age-associated cutaneous miRNAs revealed the increased expression of miR-130, miR-138, and miR-181a/b in keratinocytes during replicative senescence. These miRNAs affected cell proliferation pathways via targeting the p63 and Sirtuin 1 mRNAs. Notably, miR-181a was also implicated in skin immunosenescence, represented by the Langerhans cells. Dermal fibroblasts also expressed increased the levels of the biomarkers of aging that affect telomere maintenance and all phases of the cellular life cycle, such as let-7, miR-23a-3p, 34a-5p, miR-125a, miR-181a-5p, and miR-221/222-3p. Among them, the miR-34 family, stimulated by ultraviolet B irradiation, deteriorates collagen in the extracellular matrix due to the activation of the matrix metalloproteinases and thereby potentiates wrinkle formation. In addition to the pro-aging effects of miRNAs, the plausible antiaging activity of miR-146a that antagonized the UVA-induced inhibition of proliferation and suppressed aging-related genes (e.g., p21WAF-1, p16, and p53) through targeting Smad4 has also been noticed. Nevertheless, the role of miRNAs in skin aging is still not fully elucidated and needs to be further discovered and explained.
Inorganic Phosphate in the Pathogenesis of Pregnancy-Related Complications
Authors: Correia-Branco Ana , Rincon Monica P. , Pereira Leonardo M. , Wallingford Mary C.
Published: July 2020

Inorganic phosphate (Pi) is an essential nutrient that fulfills critical roles in human health. It enables skeletal ossification, supports cellular structure and organelle function, and serves key biochemical roles in energetics and molecular signaling. Pi homeostasis is modulated through diet, intestinal uptake, renal reabsorption, and mobilization of stores in bone and extracellular compartments. Disrupted Pi homeostasis is associated with phosphate wasting, mineral and bone disorders, and vascular calcification. Mechanisms of Pi homeostasis in pregnancy remain incompletely understood. The study presented herein examined biological fluid Pi characteristics over the course of gestation. Correlations with gestation age, pregnancy number, preterm birth, preeclampsia, diabetes mellitus, and placental calcification were evaluated during the last trimester. The results support that maternal urinary Pi levels increased during the third trimester of pregnancy. Reduced levels were observed with previous pregnancy. Amniotic fluid Pi levels decreased with gestation while low second trimester levels associated with preterm birth. No significant difference in urinary Pi levels was observed between preeclampsia and controls (8.50 ± 2.74 vs. 11.52 ± 2.90 mmol/L). Moreover, increased maternal urinary Pi was associated with preexisting diabetes mellitus in preeclampsia. Potential confounding factors in this study are maternal age at delivery and body mass index (BMI)—information which we do not have access to for this cohort. In conclusion, Pi levels provide clinical information regarding the pathogenesis of pregnancy-related complications, supporting that phosphate should be examined more closely and in larger populations.
Metabolic Response of the Yeast Candida utilis During Enrichment in Selenium
Authors: Kieliszek Marek , Bierla Katarzyna , Jiménez-Lamana Javier , Kot Anna Maria , Alcántara-Durán Jaime , Piwowarek Kamil , Błażejak Stanisław , Szpunar Joanna
Published: July 2020

Selenium (Se) was found to inhibit the growth of the yeast Candida utilis ATCC 9950. Cells cultured in 30 mg selenite/L supplemented medium could bind 1368 µg Se/g of dry weight in their structures. Increased accumulation of trehalose and glycogen was observed, which indicated cell response to stress conditions. The activity of antioxidative enzymes (glutathione peroxidase, glutathione reductase, thioredoxin reductase, and glutathione S-transferase) was significantly higher than that of the control without Se addition. Most Se was bound to water-insoluble protein fraction; in addition, the yeast produced 20–30 nm Se nanoparticles (SeNPs). Part of Se was metabolized to selenomethionine (10%) and selenocysteine (20%). The HPLC-ESI-Orbitrap MS analysis showed the presence of five Se compounds combined with glutathione in the yeast. The obtained results form the basis for further research on the mechanisms of Se metabolism in yeast cells.
ORAI2 Down-Regulation Potentiates SOCE and Decreases Aβ42 Accumulation in Human Neuroglioma Cells
Authors: Scremin Elena , Agostini Mario , Leparulo Alessandro , Pozzan Tullio , Greotti Elisa , Fasolato Cristina
Published: July 2020

Senile plaques, the hallmarks of Alzheimer’s Disease (AD), are generated by the deposition of amyloid-beta (Aβ), the proteolytic product of amyloid precursor protein (APP), by β and γ-secretase. A large body of evidence points towards a role for Ca2+ imbalances in the pathophysiology of both sporadic and familial forms of AD (FAD). A reduction in store-operated Ca2+ entry (SOCE) is shared by numerous FAD-linked mutations, and SOCE is involved in Aβ accumulation in different model cells. In neurons, both the role and components of SOCE remain quite obscure, whereas in astrocytes, SOCE controls their Ca2+-based excitability and communication to neurons. Glial cells are also directly involved in Aβ production and clearance. Here, we focus on the role of ORAI2, a key SOCE component, in modulating SOCE in the human neuroglioma cell line H4. We show that ORAI2 overexpression reduces both SOCE level and stores Ca2+ content, while ORAI2 downregulation significantly increases SOCE amplitude without affecting store Ca2+ handling. In Aβ-secreting H4-APPswe cells, SOCE inhibition by BTP2 and SOCE augmentation by ORAI2 downregulation respectively increases and decreases Aβ42 accumulation. Based on these findings, we suggest ORAI2 downregulation as a potential tool to rescue defective SOCE in AD, while preventing plaque formation.
Halophytic Hordeum brevisubulatum HbHAK1 Facilitates Potassium Retention and Contributes to Salt Tolerance
Authors: Zhang Haiwen , Xiao Wen , Yu Wenwen , Jiang Ying , Li Ruifen
Published: July 2020

Potassium retention under saline conditions has emerged as an important determinant for salt tolerance in plants. Halophytic Hordeum brevisubulatum evolves better strategies to retain K+ to improve high-salt tolerance. Hence, uncovering K+-efficient uptake under salt stress is vital for understanding K+ homeostasis. HAK/KUP/KT transporters play important roles in promoting K+ uptake during multiple stresses. Here, we obtained nine salt-induced HAK/KUP/KT members in H. brevisubulatum with different expression patterns compared with H. vulgare through transcriptomic analysis. One member HbHAK1 showed high-affinity K+ transporter activity in athak5 to cope with low-K+ or salt stresses. The expression of HbHAK1 in yeast Cy162 strains exhibited strong activities in K+ uptake under extremely low external K+ conditions and reducing Na+ toxicity to maintain the survival of yeast cells under high-salt-stress. Comparing with the sequence of barley HvHAK1, we found that C170 and R342 in a conserved domain played pivotal roles in K+ selectivity under extremely low-K+ conditions (10 μM) and that A13 was responsible for the salt tolerance. Our findings revealed the mechanism of HbHAK1 for K+ accumulation and the significant natural adaptive sites for HAK1 activity, highlighting the potential value for crops to promote K+-uptake under stresses.
VEGF-A in Cardiomyocytes and Heart Diseases
Authors: Braile Mariantonia , Marcella Simone , Cristinziano Leonardo , Galdiero Maria Rosaria , Modestino Luca , Ferrara Anne Lise , Varricchi Gilda , Marone Giancarlo , Loffredo Stefania
Published: July 2020

The vascular endothelial growth factor (VEGF), a homodimeric vasoactive glycoprotein, is the key mediator of angiogenesis. Angiogenesis, the formation of new blood vessels, is responsible for a wide variety of physio/pathological processes, including cardiovascular diseases (CVD). Cardiomyocytes (CM), the main cell type present in the heart, are the source and target of VEGF-A and express its receptors, VEGFR1 and VEGFR2, on their cell surface. The relationship between VEGF-A and the heart is double-sided. On the one hand, VEGF-A activates CM, inducing morphogenesis, contractility and wound healing. On the other hand, VEGF-A is produced by CM during inflammation, mechanical stress and cytokine stimulation. Moreover, high concentrations of VEGF-A have been found in patients affected by different CVD, and are often correlated with an unfavorable prognosis and disease severity. In this review, we summarized the current knowledge about the expression and effects of VEGF-A on CM and the role of VEGF-A in CVD, which are the most important cause of disability and premature death worldwide. Based on clinical studies on angiogenesis therapy conducted to date, it is possible to think that the control of angiogenesis and VEGF-A can lead to better quality and span of life of patients with heart disease.
Peroxisome Proliferator-Activated Receptor Beta/Delta Agonist Suppresses Inflammation and Promotes Neovascularization
Authors: Tobita Yutaro , Arima Takeshi , Nakano Yuji , Uchiyama Masaaki , Shimizu Akira , Takahashi Hiroshi
Published: July 2020

The effects of peroxisome proliferator-activated receptor (PPAR)β/δ ophthalmic solution were investigated in a rat corneal alkali burn model. After alkali injury, GW501516 (PPARβ/δ agonist) or vehicle ophthalmic solution was topically instilled onto the rat’s cornea twice a day until day 7. Pathological findings were evaluated, and real-time reverse transcription polymerase chain reaction was performed. GW501516 strongly suppressed infiltration of neutrophils and pan-macrophages, and reduced the mRNA expression of interleukin-6, interleukin-1β, tumor necrosis factor alpha, and nuclear factor-kappa B. On the other hand, GW501516 promoted infiltration of M2 macrophages, infiltration of vascular endothelial cells associated with neovascularization in the wounded area, and expression of vascular endothelial growth factor A mRNA. However, 7-day administration of GW501516 did not promote neovascularization in uninjured normal corneas. Thus, the PPARβ/δ ligand suppressed inflammation and promoted neovascularization in the corneal wound healing process. These results will help to elucidate the role of PPARβ/δ in the field of ophthalmology.
Discrimination between G/C Binding Sites by Olivomycin A Is Determined by Kinetics of the Drug-DNA Interaction
Authors: Beniaminov Artemy D. , Chashchina Galina V. , Livshits Mikhail A. , Kechko Olga I. , Mitkevich Vladimir A. , Mamaeva Olga K. , Tevyashova Anna N. , Shtil Alexander A. , Shchyolkina Anna K. , Kaluzhny Dmitry N.
Published: July 2020

Olivomycin A (OA) exerts its cytotoxic potency due to binding to the minor groove of the G/C-rich DNA and interfering with replication and transcription. Screening of the complete set of tetranucleotide G/C sites by electrophoretic mobility gel shift assay (EMSA) revealed that the sites containing central GC or GG dinucleotides were able to bind OA, whereas the sites with the central CG dinucleotide were not. However, studies of equilibrium OA binding in solution by fluorescence, circular dichroism and isothermal titration calorimetry failed to confirm the sequence preference of OA, indicating instead a similar type of complex and comparable affinity of OA to all G/C binding sites. This discrepancy was resolved by kinetics analysis of the drug–DNA interaction: the dissociation rate significantly differed between SGCS, SGGS and SCGS sites (S stands for G or C), thereby explaining the disintegration of the complexes during EMSA. The functional relevance of the revealed differential kinetics of OA–DNA interaction was demonstrated in an in vitro transcription assay. These findings emphasize the crucial role of kinetics in the mechanism of OA action and provide an important approach to the screening of new drug candidates.
Transcriptional Inhibition of Sp-IAG by Crustacean Female Sex Hormone in the Mud Crab, Scylla paramamosain
Authors: Jiang Qingling , Lu Bei , Wang Guizhong , Ye Haihui
Published: July 2020

In crustaceans, the regulation of sex differentiation is mediated by insulin-like androgenic hormone (IAG) and crustacean female sex hormone (CFSH). CFSH is reported to inhibit IAG gene (Sp-IAG) expression in the mud crab Scylla paramamosain, but the regulatory mechanism is not well understood. A 2674 bp 5′ flanking Sp-IAG contains many potential transcription factor binding sites. In this study, analysis of serially deleted 5′ flanking Sp-IAG and site-directed mutation (SDM) of transcription factor binding sites of the same gene showed that the promoter activity of reporter vectors with Sox-5-binding site, signal transducers and activators of transcription (STAT)-binding site and activator protein 1 (AP-1)-binding site were significantly higher than that of vectors without these regions, suggesting that they were involved in transcriptional regulation of Sp-IAG expression. The expression analysis of these transcription factor showed that there was no difference in the level of mRNA in Sox-5 and AP-1 in androgenic gland treated with recombinant CFSH, but expression of Sp-STAT was significantly reduced, suggesting that CFSH regulates the expression of Sp-STAT, inhibiting its function to regulate Sp-IAG. Further experiment revealed that RNAi mediated Sp-STAT gene knockdown reduced the expression of Sp-IAG. These results suggested that Sp-CFSH regulates Sp-IAG by inhibiting STAT. This is a pioneering finding on the transcriptional mechanism of IAG gene in crustaceans.
Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)
Authors: Rios-Fuller Tiffany J. , Mahe Melanie , Walters Beth , Abbadi Dounia , Pérez-Baos Sandra , Gadi Abhilash , Andrews John J. , Katsara Olga , Vincent C. Theresa , Schneider Robert J.
Published: July 2020

Non-communicable diseases (NCDs) are medical conditions that, by definition, are non-infectious and non-transmissible among people. Much of current NCDs are generally due to genetic, behavioral, and metabolic risk factors that often include excessive alcohol consumption, smoking, obesity, and untreated elevated blood pressure, and share many common signal transduction pathways. Alterations in cell and physiological signaling and transcriptional control pathways have been well studied in several human NCDs, but these same pathways also regulate expression and function of the protein synthetic machinery and mRNA translation which have been less well investigated. Alterations in expression of specific translation factors, and disruption of canonical mRNA translational regulation, both contribute to the pathology of many NCDs. The two most common pathological alterations that contribute to NCDs discussed in this review will be the regulation of eukaryotic initiation factor 2 (eIF2) by the integrated stress response (ISR) and the mammalian target of rapamycin complex 1 (mTORC1) pathways. Both pathways integrally connect mRNA translation activity to external and internal physiological stimuli. Here, we review the role of ISR control of eIF2 activity and mTORC1 control of cap-mediated mRNA translation in some common NCDs, including Alzheimer’s disease, Parkinson’s disease, stroke, diabetes mellitus, liver cirrhosis, chronic obstructive pulmonary disease (COPD), and cardiac diseases. Our goal is to provide insights that further the understanding as to the important role of translational regulation in the pathogenesis of these diseases.
The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia
Authors: Wahlund Martina , Sinha Indranil , Broliden Kristina , Saghafian-Hedengren Shanie , Nilsson Anna , Berggren Anna
Published: July 2020

Infection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy children. Here, we examined whether gene-expression profiling was feasible in children with FN who were undergoing cancer treatment. The blood transcriptome of the children (n = 63) was investigated at time of FN diagnosed as viral, bacterial, co-infection or unknown etiology, respectively, and compared to control samples derived from 12 of the patients following the FN episode. RNA sequencing was successful in 43 (68%) of the FN episodes. Only two genes were significantly differentially expressed in the bacterial versus the control group. Significantly up-regulated genes in patients with the other three etiologies versus the control group were enriched with cellular processes related to proliferation and cellular stress response, with no clear enrichment with innate responses to pathogens. Among the significantly down-regulated genes, a few clustered into pathways connected to responses to infection. In the present study of children during cancer treatment, the blood transcriptome was not suitable for determining the etiology of FN because of too few circulating immune cells for reliable gene expression analysis.
HIV Associated Risk Factors for Ischemic Stroke and Future Perspectives
Authors: Ismael Saifudeen , Moshahid Khan Mohammad , Kumar Prashant , Kodidela Sunitha , Mirzahosseini Golnoush , Kumar Santhosh , Ishrat Tauheed
Published: July 2020

Although retroviral therapy (ART) has changed the HIV infection from a fatal event to a chronic disease, treated HIV patients demonstrate high prevalence of HIV associated comorbidities including cardio/cerebrovascular diseases. The incidence of stroke in HIV infected subjects is three times higher than that of uninfected controls. Several clinical and postmortem studies have documented the higher incidence of ischemic stroke in HIV infected patients. The etiology of stroke in HIV infected patients remains unknown; however, several factors such as coagulopathies, opportunistic infections, vascular abnormalities, atherosclerosis and diabetes can contribute to the pathogenesis of stroke. In addition, chronic administration of ART contributes to the increased risk of stroke in HIV infected patients. Concurrently, experimental studies in murine model of ischemic stroke demonstrated that HIV infection worsens stroke outcome, increases blood brain barrier permeability and increases neuroinflammation. Additionally, residual HIV viral proteins, such as Trans-Activator of Transcription, glycoprotein 120 and Negative regulatory factor, contribute to the pathogenesis. This review presents comprehensive information detailing the risk factors contributing to ischemic stroke in HIV infected patients. It also outlines experimental evidence demonstrating the impact of HIV infection on stroke outcomes, in addition to possible novel therapeutic approaches to improve these outcomes.
Virtual Screening of C. Sativa Constituents for the Identification of Selective Ligands for Cannabinoid Receptor 2
Authors: Mizera Mikołaj , Latek Dorota , Cielecka-Piontek Judyta
Published: July 2020

The selective targeting of the cannabinoid receptor 2 (CB2) is crucial for the development of peripheral system-acting cannabinoid analgesics. This work aimed at computer-assisted identification of prospective CB2-selective compounds among the constituents of Cannabis Sativa. The molecular structures and corresponding binding affinities to CB1 and CB2 receptors were collected from ChEMBL. The molecular structures of Cannabis Sativa constituents were collected from a phytochemical database. The collected records were curated and applied for the development of quantitative structure-activity relationship (QSAR) models with a machine learning approach. The validated models predicted the affinities of Cannabis Sativa constituents. Four structures of CB2 were acquired from the Protein Data Bank (PDB) and the discriminatory ability of CB2-selective ligands and two sets of decoys were tested. We succeeded in developing the QSAR model by achieving Q2 5-CV > 0.62. The QSAR models helped to identify three prospective CB2-selective molecules that are dissimilar to already tested compounds. In a complementary structure-based virtual screening study that used available PDB structures of CB2, the agonist-bound, Cryogenic Electron Microscopy structure of CB2 showed the best statistical performance in discriminating between CB2-active and non-active ligands. The same structure also performed best in discriminating between CB2-selective ligands from non-selective ligands.
Temporal and Spatial Expression Analysis of Shoot-Regeneration Regulatory Genes during the Adventitious Shoot Formation in Hypocotyl and Cotyledon Explants of Tomato (CV. Micro-Tom)
Authors: Lee Myoung Hui , Lee Jiyoung , Jie Eun Yee , Choi Seung Hee , Jiang Lingmin , Ahn Woo Seok , Kim Cha Young , Kim Suk Weon
Published: July 2020

Enhancing the competence for plant regeneration in tissue culture studies is an important issue not only for efficient genetic transformation of commercial crops but also for the reproducibility of scientific reports. In this study, we investigated optimization of several tissue culture conditions including plant growth regulators, types and ages of explants, culture densities, and plant position in order to improve the competence of adventitious shoot formation of the tomato (Solanum lycopersicum cv. Micro-Tom). In addition, we examined the differential expression of D-type cyclin (CYCD3-1) and several shoot regeneration regulatory genes from hypocotyl and cotyledon explants of tomato during shoot organogenesis. A treatment of 1 mg L−1 Zeatin and 0.1 mg L−1 Indole-3-acetic acid (IAA) in Murashige and Skoog (MS) medium containing 3% sucrose was optimal for adventitious shoot formation from hypocotyl and cotyledon explants. The younger explants exhibited more shoot formation regardless of explant types. Additionally, those closest to the shoot apical meristem produced more shoots compared to the other regions in the hypocotyl and the cotyledon explants. Gene expression of CYCD3-1, SHOOT MERISTEMLESS (STM), and cytokinin dependent WUSCHEL (WUS) was significantly higher in younger explants than in older ones. Furthermore, an increase in CYCD3-1, STM, and WUS expression was evident at the distal part of hypocotyls and the proximal part of cotyledons compared to other regions. These differential gene expression profiles exhibited good agreement with the results of shoot formation obtained from diverse explants of tomato. These results suggest that temporal and spatial gene expression of shoot regeneration regulatory genes plays an important role in enhancing the competence and the reproducibility of adventitious shoot formation from tomato explants.