bluuebunny/crossref_metadata_2025 huggingface dataset:
HPLC-DAD-MS and Antioxidant Profile of Fractions from Amontillado Sherry Wine Obtained Using High-Speed Counter-Current Chromatography
Authors: Schwarz Mónica , Weber Fabian , Durán-Guerrero Enrique , Castro Remedios , Rodríguez-Dodero María del Carmen , García-Moreno Maria Valme , Winterhalter Peter , Guillén-Sánchez Dominico
Published: January 2021

In the present work, the polyphenolic profile of a complex matrix such as Amontillado sherry has been processed by means of high-speed counter-current chromatography (HSCCC) and characterized by HPLC-DAD-MS. An Amberlite XAD-7 column was used to obtain the wine extract, and three different biphasic solvent systems were applied for HSCCC separation: MTBE (methyl tert-butyl ether)/n-butanol/acetonitrile/water (1.1/3/1.1/5+0.1% trifluoroacetic acid), MTBE/n-butanol/acetonitrile/water (2/2/1/5), and hexane/ethyl acetate/ethanol/water (1/5/1/5). As a result, 42 phenolic compounds and furanic derivatives have been identified by means of HPLC-DAD-MS, with 11 of them being identified for the first time in Sherry wines: 3-feruloylquinic acid, isovanillin, ethyl vanillate, furoic acid, dihydro-p-coumaric acid, 6-O-feruloylglucose, ethyl gallate, hydroxytyrosol, methyl protocatechuate, homoveratric acid and veratraldehyde. In addition, the antioxidant capacity (ABTS) of the obtained fractions was determined, revealing higher values in those fractions in which compounds such as gallic acid, protocatechuic acid, protocatechualdehyde, trans-caftaric acid, syringic acid, isovanillin or tyrosol, among others, were present. This is the first time that HSCCC has been used to characterize the phenolic composition of Sherry wines.
Thaumatin-Like Protein (Pru av 2) Is a Cherry Allergen That Triggers Percutaneous Sensitization in Mice
Authors: Izumi Eri , Hidaka Shota , Hiroi Ayako , Kinugasa Serina , Yano Erika , Zaima Nobuhiro , Moriyama Tatsuya
Published: January 2021

Numerous recent studies have suggested that food allergens enter the skin and predispose individuals to food allergies through the production of IgE antibodies in the body. Cherries are a popular fruit eaten worldwide. However, cherries are an allergenic food and percutaneous sensitization with cherry allergens through the perioral region may occur while ingesting cherries. The identity of the cherry protein that triggers percutaneous sensitization in humans or animal models remains unknown. In this study, the backs of BALB/c mice were shaved and crude cherry extracts containing sodium dodecyl sulfate were applied to the skin. Thereafter, the cherry-specific IgE and IgG1 antibodies generated and secreted in response to the epidermal application were measured using an enzyme-linked immunosorbent assay or immunoblotting. Skin exposure to cherry extracts elevated cherry-specific IgG1 levels. Application of fractionated and purified cherry proteins (antigen candidates for percutaneous sensitization) that bound to the IgG1 antibodies led to the identification of a thaumatin-like protein (Pru av 2). This molecule is known as the major cherry allergen that affects humans. In conclusion, our study identified Pru av 2 as a cherry allergen that triggers percutaneous sensitization in mice for the first time.
Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity
Authors: Rimpelová Silvie , Zimmermann Tomáš , Drašar Pavel B. , Dolenský Bohumil , Bejček Jiří , Kmoníčková Eva , Cihlářová Petra , Gurská Soňa , Kuklíková Lucie , Hajdůch Marián , Ruml Tomáš , Opletal Lubomír , Džubák Petr , Jurášek Michal
Published: January 2021

Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na+/K+-ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na+/K+-ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na+/K+-ATPase inhibition, but also as novel cancer therapeutics.
Factors Affecting Health-Promoting Behaviors in Patients with Cardiovascular Disease
Authors: Park Hwan-Cheol , Oh Jihyun
Published: January 2021

Cardiovascular disease is the leading cause of death globally and the second most common cause of death in South Korea. Health-promoting behaviors recommended for patients with cardiovascular disease include control of diet, physical activity, cessation of smoking, medication adherence, and adherence to medical recommendations. This study aimed to determine the relationship between depression, anxiety, perception of health status, and health-promoting behavior in patients from South Korea who have suffered from cardiovascular disease. The study population comprised 161 patients at the cardiovascular center at H Hospital who were diagnosed with cardiovascular disease. Descriptive statistics and stepwise multiple regression were employed to analyze the data. Negative correlations existed between depression, perception of health status, and health-promoting behavior. By contrast, a positive correlation existed between the perception of health status and health-promoting behavior. The main factors affecting health-promoting behaviors were alcohol consumption, duration of diagnosis, perception of health status, and depression. These variables explained 15.8% of the variance. To prevent adverse cardiac events, patients who suffer from cardiovascular disease should be assessed as soon as possible to identify psychiatric symptoms, thereby developing a potential intervention aimed at decreasing negative illness consequences.
Cybersecurity and the Digital-Health: The Challenge of This Millennium
Authors: Giansanti Daniele
Published: January 2021

The problem of computer security is as old as computers themselves and dates back decades [...]
Thermoacoustic Instability Considerations for High Hydrogen Combustion in Lean Premixed Gas Turbine Combustors: A Review
Authors: Beita Jadeed , Talibi Midhat , Sadasivuni Suresh , Balachandran Ramanarayanan
Published: January 2021

Hydrogen is receiving increasing attention as a versatile energy vector to help accelerate the transition to a decarbonised energy future. Gas turbines will continue to play a critical role in providing grid stability and resilience in future low-carbon power systems; however, it is recognised that this role is contingent upon achieving increased thermal efficiencies and the ability to operate on carbon-neutral fuels such as hydrogen. An important consideration in the development of gas turbine combustors capable of operating with pure hydrogen or hydrogen-enriched natural gas are the significant changes in thermoacoustic instability characteristics associated with burning these fuels. This article provides a review of the effects of burning hydrogen on combustion dynamics with focus on swirl-stabilised lean-premixed combustors. Experimental and numerical evidence suggests hydrogen can have either a stabilising or destabilising impact on the dynamic state of a combustor through its influence particularly on flame structure and flame position. Other operational considerations such as the effect of elevated pressure and piloting on combustion dynamics as well as recent developments in micromix burner technology for 100% hydrogen combustion have also been discussed. The insights provided in this review will aid the development of instability mitigation strategies for high hydrogen combustion.
A Comparison of Cut Points for Measuring Risk Factors for Adolescent Substance Use and Antisocial Behaviors in the U.S. and Colombia
Authors: Brown Eric C. , Montero-Zamora Pablo , Cardozo-Macías Francisco , Reyes-Rodríguez María Fernanda , Briney John S. , Mejía-Trujillo Juliana , Pérez-Gómez Augusto
Published: January 2021

As the identification and targeting of salient risk factors for adolescent substance use become more widely used globally, an essential question arises as to whether U.S.-based cut points in the distributions of these risk factors that identify “high” risk can be used validly in other countries as well. This study examined proportions of youth at “high” risk using different empirically derived cut points in the distributions of 18 measured risk factors. Data were obtained from large-scale samples of adolescents in Colombia and the United States. Results indicated that significant (p < 0.05) differences in the proportions of “high” risk youth were found in 38.9% of risk factors for 6th graders, 61.1% for 8th graders, and 66.6% for 10th graders. Colombian-based cut points for determining the proportion of Colombian youth at “high” risk were preferable to U.S.-based cut points in almost all comparisons that exhibited a significant difference. Our findings suggest that observed differences were related to the type of risk factor (e.g., drug specific vs. non-drug specific). Findings from this study demonstrate the need for collecting large-scale national data on risk factors for adolescent substance use and developing country-specific cut points based on the distributions of these measures to avoid misidentification of youth at “high” risk.
Public Knowledge, Attitudes, and Practices toward Seasonal Influenza Vaccine in Saudi Arabia: A Cross-Sectional Study
Authors: Sales Ibrahim A. , Syed Wajid , Almutairi Majed F. , Al Ruthia Yazed
Published: January 2021

Objectives: Increasing national influenza vaccination rates continues to be a challenge for Saudi Arabia. Therefore, the purpose of this study was to explore the Saudi public perceptions toward seasonal influenza vaccination and their association with the rate of vaccination. Methods: Individuals aged 15 years and older were surveyed about their knowledge, attitudes, and practices toward the seasonal influenza vaccine using a previously developed and validated 19-item online questionnaire. The impact of the participants’ perceptions toward the seasonal influenza vaccine on their past influenza vaccination history was assessed using multiple linear regressions. Results: The rate of regular vaccination among the 790 surveyed participants was 12.65%, and those who were aged <24 years had the highest rate (57%). The vast majority of the participants with chronic diseases (>90%) reported irregular vaccination histories against seasonal influenza. Participants who believed that the influenza vaccine is safe (β = 3.27; 95% CI: 2.067 to 5.171; p <0.001), efficacious (β = 2.87; 95% CI: 1.834 to 4.498; p <0.001), should be given during a specific time in the year (β = 1.821; 95% CI: 1.188 to 2.789; p = 0.0059), and were aware of their need to get vaccinated against the seasonal influenza (β = 2.781; 95% CI: 1.254 to 6.188; p = 0.0119) were more likely to have received the vaccine. Conclusion: The findings of this study suggest that the rate of seasonal influenza vaccination is low among the Saudi population, which necessitates the launching of public awareness campaigns about the importance of the seasonal influenza vaccine.
Multidrug-Resistant Listeria Species Shows Abundance in Environmental Waters of a Key District Municipality in South Africa
Authors: Mpondo Liyabona , Ebomah Kingsley Ehi , Okoh Anthony Ifeanyi
Published: January 2021

The prevalence of bacteria with multidrug-resistance (MDR) is a significant threat to public health globally. Listeria spp. are naturally ubiquitous, with L. monocytogenes particularly being ranked as important foodborne disease-causing microorganisms. This study aimed to evaluate the incidence and determine the antimicrobial resistance (AMR) profiles of multidrug-resistant Listeria spp. (MDRL) isolated from different environmental samples (river and irrigation water) in the Sarah Baartman District Municipality (SBDM), Eastern Cape Province (ECP), South Africa. Molecular identification and characterization were carried out using polymerase chain reaction (PCR) and isolates that exhibited phenotypic resistance were further screened for relevant antimicrobial-resistant genes (ARGs). Findings revealed a total of 124 presumptive Listeria isolates; 69 were molecularly confirmed Listeria species. Out of the confirmed species, 41 isolates (59%) were classified as L. monocytogenes while 9 (13%) were classified as L. welshimeri. All Listeria spp. exhibited phenotypic resistance against ampicillin, penicillin, and trimethoprim-sulphamethoxazole and further screening revealed ARGs in the following proportions: sulI (71%), blaTEM (66%), tetA (63%), and blaCIT (33%). Results confirmed the occurrence of ARGs among Listeria inhabiting surface waters of ECP. The present study indicates that the river water samples collected from SBDM are highly contaminated with MDRL, hence, constituting a potential health risk.
A Mixed-Methods Systematic Review of the Impacts of Coronavirus on Society and Culture
Authors: Yu Yeon Jung , Park Young Su , Keller Alison , Noh Jin-Won , Cha Jiho
Published: January 2021

Little is understood of the social and cultural effects of coronaviruses such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS-CoV). This systematic review aims to synthesize existing findings (both qualitative and quantitative) that focus on the social and cultural impacts of coronaviruses in order to gain a better understanding of the COVID-19 pandemic. Utilizing a predetermined search strategy, we searched CINAHL, PsycINFO, PubMed, and Web of Science to identify existing (qualitative, quantitative, and mixed-methods) studies pertaining to the coronavirus infections and their intersection with societies and cultures. A narrative synthesis approach was applied to summarize and interpret findings of the study. Stemming from SARS outbreak in 2003, qualitative and quantitative findings (twelve adopted quantitative methods and eight exclusively used qualitative methods) were organized under five topical domains: governance, crisis communication and public knowledge, stigma and discrimination, social compliance of preventive measures, and the social experience of health workers. The selected studies suggest that current societies are not equipped for effective coronavirus response and control. This mixed-methods systematic review demonstrates that the effects of coronaviruses on a society can be debilitating.
Psychometric Properties of the Climate Change Worry Scale
Authors: Stewart Alan E.
Published: January 2021

Climate change worry involves primarily verbal-linguistic thoughts about the changes that may occur in the climate system and the possible effects of these changes. Such worry is one of several possible psychological responses (e.g., fear, anxiety, depression, and trauma) to climate change. Within this article, the psychometric development of the ten-item Climate Change Worry Scale (CCWS) is detailed in three studies. The scale was developed to assess proximal worry about climate change rather than social or global impacts. Study 1 provided evidence that the CCWS items were internally consistent, constituted a single factor, and that the facture structure of the items was invariant for men and women. The results from Study 1 also indicated a good fit with a Rasch model of the items. Study 2 affirmed the internal consistency of the CCWS items and indicated that peoples’ responses to the measure were temporally stable over a two-week test–retest interval (r = 0.91). Study 3 provided support for the convergent and divergent validity of the CCWS through its pattern of correlations with several established clinical and weather-related measures. The limitations of the studies and the possible uses of the CCWS were discussed. The current work represents a starting point.
Associations of Residential Brownness and Greenness with Fasting Glucose in Young Healthy Adults Living in the Desert
Authors: Olvera-Alvarez Hector A. , Browning Matthew H. E. M. , Neophytou Andreas M. , Bratman Gregory N.
Published: January 2021

Evolutionary psychology theories propose that contact with green, natural environments may benefit physical health, but little comparable evidence exists for brown, natural environments, such as the desert. In this study, we examined the association between “brownness” and “greenness” with fasting glucose among young residents of El Paso, Texas. We defined brownness as the surface not covered by vegetation or impervious land within Euclidian buffers around participants’ homes. Fasting glucose along with demographic and behavioral data were obtained from the Nurse Engagement and Wellness Study (n = 517). We found that residential proximity to brownness was not associated with fasting glucose when modeled independently. In contrast, we found that residential greenness was associated with decreased levels of fasting glucose, despite the relatively low levels of greenness within the predominantly desert environment of El Paso. A difference between the top and bottom greenness exposure quartiles within a 250 m buffer was associated with a 3.5 mg/dL decrease in fasting glucose levels (95% confidence interval: −6.2, −0.8). Our results suggest that within the understudied context of the desert, green vegetation may be health promoting to a degree that is similar to other, non-desert locations in the world that have higher baselines levels of green.
How Does Urban Farming Benefit Participants’ Health? A Case Study of Allotments and Experience Farms in Tokyo
Authors: Harada Kentaro , Hino Kimihiro , Iida Akiko , Yamazaki Takahiro , Usui Hiroyuki , Asami Yasushi , Yokohari Makoto
Published: January 2021

In Japan, the world’s most rapidly aging country, urban farming is attracting attention as an infrastructure for health activities. In Tokyo, urban residents generally participate in two types of farming programs: allotments and experience farms. The availability of regular interaction among participants distinguishes these two programs. We quantitatively examined the difference in changes in self-reported health status between participants in these two types of urban farming. We obtained retrospective cross-sectional data from questionnaire surveys of 783 urban farming participants and 1254 nonparticipants and analyzed the data using ordinal logistic regressions. As a result, compared with nonparticipants, participants in both types of urban farming reported significantly improved self-rated health (SRH) and mental health (MH). After controlling for changes in their physical activity (PA), although participants in allotments did not report significant improvement in SRH and MH, those in experience farms did, suggesting that their health improvement was not only caused by an increase in PA but also by social interaction among participants. From the perspective of health promotion, public support is needed not only for the municipality’s allotments but also for the experience farms operated by the farmers themselves.
Social Capital and Psychological Well-Being of Chinese Immigrants in Japan
Authors: Gong Shun , Xu Peng , Wang Senhu
Published: January 2021

Social capital in immigrants has drawn considerable attention from social scientists. Previous studies have paid attention to how immigrants’ bonding social capital (defined as social networks with co-ethnic residents) and bridging social capital (defined as social networks with native residents) are associated with their economic achievement. However, little attention has been paid to immigrants’ different social capital’s effects on psychological well-being. Drawing data from Chinese immigrants in Japan, we examined how these Chinese immigrants assimilated into Japanese society and how their bonding and bridging social capital related to their psychological well-being. The results show that bonding social capital directly affected immigrants’ psychological well-being, whereas bridging social capital indirectly improved their psychological well-being by improving economic status. This study contributes to previous literature on how immigrants’ different social capital is related to their psychological well-being.
“Freedom to Breathe”: Youth Participatory Action Research (YPAR) to Investigate Air Pollution Inequities in Richmond, CA
Authors: Nolan James E. S. , Coker Eric S. , Ward Bailey R. , Williamson Yahna A. , Harley Kim G.
Published: January 2021

Air pollution is a major contributor to human morbidity and mortality, potentially exacerbated by COVID-19, and a threat to planetary health. Participatory research, with a structural violence framework, illuminates exposure inequities and refines mitigation strategies. Home to profitable oil and shipping industries, several census tracts in Richmond, CA are among the most heavily impacted by aggregate burdens statewide. Formally trained researchers from the Center for Environmental Research and Children’s Health (CERCH) partnered with the RYSE youth justice center to conduct youth participatory action research on air quality justice. Staff engaged five youth researchers in: (1) collaborative research using a network of passive air monitors to quantify neighborhood disparities in nitrogen dioxide (NO2) and sulfur dioxide (SO2), noise pollution and community risk factors; (2) training in environmental health literacy and professional development; and (3) interpretation of findings, community outreach and advocacy. Inequities in ambient NO2, but not SO2, were observed. Census tracts with higher Black populations had the highest NO2. Proximity to railroads and major roadways were associated with higher NO2. Greenspace was associated with lower NO2, suggesting investment may be conducive to improved air quality, among many additional benefits. Youth improved in measures of empowerment, and advanced community education via workshops, Photovoice, video, and ”zines”.
Brazil’s Actions and Reactions in the Fight against COVID-19 from January to March 2020
Authors: Szylovec Ana , Umbelino-Walker Isis , Cain Brittany Nicole , Ng Hoi Tung , Flahault Antoine , Rozanova Liudmila
Published: January 2021

The outbreak of the novel coronavirus SARS-CoV-2 and the disease it causes, COVID-19, which emerged in 2019, was identified by the World Health Organization as a public health emergency of international concern. Brazil actively responded to contain the virus. This case study aims to examine Brazil’s response to COVID-19 by investigating the country’s actions and reflecting upon the outcomes throughout January and March 2020. The data collection strategy included gathering data from the country’s intergovernmental organization’s official website, epidemiological bulletins, and news reports, guided by intersectoral and interdisciplinary themes. Although the highest incidence rates were in the most rich and populated region in Brazil, it was the poorest region that had the highest case fatality rate. Nevertheless, Brazil took several non-pharmaceutical measures to control and mitigate the spread of the virus. However, the strategy seems to have failed to consider regional and social inequalities. The actions of the health minister were undermined by a conflicting discourse between the minister and the president. The outbreak of COVID-19 added an extra burden on the country’s healthcare system and the existing economic crises; exacerbated the inherent social, political, and economic challenges; and exposed the country’s contradictions.
Optimal Pricing Decisions for a Low-Carbon Supply Chain Considering Fairness Concern under Carbon Quota Policy
Authors: Zou Hao , Qin Jin , Dai Bo
Published: January 2021

This research investigates the effect of fairness concerns on a sustainable low-carbon supply chain (LCSC) with a carbon quota policy, in which a manufacturer is in charge of manufacturing low-carbon products and sells them to a retailer. The demand is affected by price and the carbon emission reduction rate. The optimal decisions of pricing and carbon emission reduction rate are analyzed under four decision models: (i) centralized decision, (ii) decentralized decision without fairness concern, (iii) decentralized decision with manufacturer’s fairness concern, (iv) decentralized decision with retailer’s fairness concern. The results indicate that the profits in the centralized LCSC are higher than those in the decentralized LCSC with fairness concern. If a manufacturer pays close attention to fairness, the fairness concern coefficient will reduce the carbon emission reduction rate and the profit of the LCSC and increase the wholesale price and the retail price of the product. If a retailer pays close attention to fairness, and the preference of consumers for a low-carbon product is low, the fairness concern coefficient of the retailer increases the total profit of the LCSC and decreases the carbon emission reduction rate and retail price of the product. Otherwise, if the preference of consumers for a low-carbon product is great, the fairness concern coefficient of the retailer would lead to a lower retail price compared with the retail price in the centralized decision and decrease the total profit of the LCSC.
Perinatal Outcomes in a Population of Diabetic and Obese Pregnant Women—The Results of the Polish National Survey
Authors: Wojtyla Cezary , Stanirowski Pawel , Gutaj Pawel , Ciebiera Michal , Wojtyla Andrzej
Published: January 2021

Obesity and diabetes increase the risk of complications during gestation and at delivery. The aim of this study was to compare the perinatal outcomes in the populations of diabetic and obese Polish women, based on the results of a national survey performed in years 2012 and 2017, as well as to determine the risk factors of the gestational diabetes mellitus (GDM). Questionnaires from 6276 women were collected. Obese women constituted 5.5% and 7.5% of study population in years 2012 and 2017, respectively. Among women whose pregnancies were complicated by diabetes mellitus, GDM constituted the most common type of glucose intolerance during both time periods (2012: 89% vs. 2017: 85.6%). In the group of obese women an insignificant increase in the rate of induced deliveries was noted (2012: 9.9% vs. 2017: 11.7%), whereas the fetal birth-weight decreased significantly (2012: 3565 g vs. 2017: 3405 g, p < 0.05). In the group of diabetic pregnant women the percentage of cesarean sections, labour inductions and fetal birth defects was characterized by an insignificant upward trend. Risk of GDM was significantly increased in women aged over 35 years—(2012: OR 1.9 (95% CI: 1.1–2.9) and 2017: OR = 2.1 (95% CI: 1.5–2.9), p < 0.05—, as well as in overweight women—2012: OR 1.8 (95% CI: 1.2–2.7) and 2017: OR 2.6 (95% CI: 1.9–3.4), p < 0.05—during both analysed time periods. Based on the study results, it is necessary to develop population-based programmes to prevent obesity and to introduce and enforce the rules of appropriate screening for glucose tolerance disorders during pregnancy.
Genome-Wide Association Study on Total Starch, Amylose and Amylopectin in Barley Grain Reveals Novel Putative Alleles
Authors: Li Mengdi , Geng La , Xie Shanggeng , Wu Dezhi , Ye Lingzhen , Zhang Guoping
Published: January 2021

The content and composition of starch in cereal grains are closely related to yield. Few studies have been done on the identification of the genes or loci associated with these traits in barley. This study was conducted to identify the genes or loci controlling starch traits in barley grains, including total starch (TS), amylose (AC) and amylopectin (AP) contents. A large genotypic variation was found in all examined starch traits. GWAS analysis detected 13, 2, 10 QTLs for TS, AC and AP, respectively, and 5 of them were commonly shared by AP and TS content. qTS-3.1, qAC-6.2 and qAP-5.1 may explain the largest variation of TS, AC and AP, respectively. Four putative candidate genes, i.e., HORVU6Hr1G087920, HORVU5Hr1G011230, HORVU5Hr1G011270 and HORVU5Hr1G011280, showed the high expression in the developing barley grains when starch accumulates rapidly. The examined 100 barley accessions could be divided into two groups based on the polymorphism of the marker S5H_29297679, with 93 accessions having allele GG and seven accessions having AA. Moreover, significantly positive correlation was found between the number of favorable alleles of the identified QTLs and TS, AC, AP content. In conclusion, the identified loci or genes in this study could be useful for genetic improvement of grains starch in barley.
Genetic Restrictive Cardiomyopathy: Causes and Consequences—An Integrative Approach
Authors: Cimiotti Diana , Budde Heidi , Hassoun Roua , Jaquet Kornelia
Published: January 2021

The sarcomere as the smallest contractile unit is prone to alterations in its functional, structural and associated proteins. Sarcomeric dysfunction leads to heart failure or cardiomyopathies like hypertrophic (HCM) or restrictive cardiomyopathy (RCM) etc. Genetic based RCM, a very rare but severe disease with a high mortality rate, might be induced by mutations in genes of non-sarcomeric, sarcomeric and sarcomere associated proteins. In this review, we discuss the functional effects in correlation to the phenotype and present an integrated model for the development of genetic RCM.
Synthesis and Characterization of Mesoporous Mg- and Sr-Doped Nanoparticles for Moxifloxacin Drug Delivery in Promising Tissue Engineering Applications
Authors: Pouroutzidou Georgia K. , Liverani Liliana , Theocharidou Anna , Tsamesidis Ioannis , Lazaridou Maria , Christodoulou Evi , Beketova Anastasia , Pappa Christina , Triantafyllidis Konstantinos S. , Anastasiou Antonios D. , Papadopoulou Lambrini , Bikiaris Dimitrios N. , Boccaccini Aldo R. , Kontonasaki Eleana
Published: January 2021

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol–gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.
Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions
Authors: Protasoni Margherita , Zeviani Massimo
Published: January 2021

Mitochondria are ubiquitous intracellular organelles found in almost all eukaryotes and involved in various aspects of cellular life, with a primary role in energy production. The interest in this organelle has grown stronger with the discovery of their link to various pathologies, including cancer, aging and neurodegenerative diseases. Indeed, dysfunctional mitochondria cannot provide the required energy to tissues with a high-energy demand, such as heart, brain and muscles, leading to a large spectrum of clinical phenotypes. Mitochondrial defects are at the origin of a group of clinically heterogeneous pathologies, called mitochondrial diseases, with an incidence of 1 in 5000 live births. Primary mitochondrial diseases are associated with genetic mutations both in nuclear and mitochondrial DNA (mtDNA), affecting genes involved in every aspect of the organelle function. As a consequence, it is difficult to find a common cause for mitochondrial diseases and, subsequently, to offer a precise clinical definition of the pathology. Moreover, the complexity of this condition makes it challenging to identify possible therapies or drug targets.
Molecular Aspects of Senescence and Organismal Ageing—DNA Damage Response, Telomeres, Inflammation and Chromatin
Authors: Sławińska Natalia , Krupa Renata
Published: January 2021

Cells can become senescent in response to stress. Senescence is a process characterised by a stable proliferative arrest. Sometimes it can be beneficial—for example, it can suppress tumour development or take part in tissue repair. On the other hand, studies show that it is also involved in the ageing process. DNA damage response (DDR) is triggered by DNA damage or telomere shortening during cell division. When left unresolved, it may lead to the activation of senescence. Senescent cells secrete certain proteins in larger quantities. This phenomenon is referred to as senescence-associated secretory phenotype (SASP). SASP can induce senescence in other cells; evidence suggests that overabundance of senescent cells contributes to ageing. SASP proteins include proinflammatory cytokines and metalloproteinases, which degrade the extracellular matrix. Shortening of telomeres is another feature associated with organismal ageing. Older organisms have shorter telomeres. Restoring telomerase activity in mice not only slowed but also partially reversed the symptoms of ageing. Changes in chromatin structure during senescence include heterochromatin formation or decondensation and loss of H1 histones. During organismal ageing, cells can experience heterochromatin loss, DNA demethylation and global histone loss. Cellular and organismal ageing are both complex processes with many aspects that are often related. The purpose of this review is to bring some of these aspects forward and provide details regarding them.
Development of A Continuous Fluorescence-Based Assay for N-Terminal Acetyltransferase D
Authors: Ho Yi-Hsun , Chen Lan , Huang Rong
Published: January 2021

N-terminal acetylation catalyzed by N-terminal acetyltransferases (NATs) has various biological functions in protein regulation. N-terminal acetyltransferase D (NatD) is one of the most specific NAT with only histone H4 and H2A proteins as the known substrates. Dysregulation of NatD has been implicated in colorectal and lung cancer progression, implying its therapeutic potential in cancers. However, there is no reported inhibitor for NatD yet. To facilitate the discovery of small-molecule NatD inhibitors, we report the development of a fluorescence-based acetyltransferase assay in 384-well high-throughput screening (HTS) format through monitoring the formation of coenzyme A. The fluorescent signal is generated from the adduct in the reaction between coenzyme A and fluorescent probe ThioGlo4. The assay exhibited a Z′-factor of 0.77 and a coefficient of variation of 6%, indicating it is a robust assay for HTS. A pilot screen of 1280 pharmacologically active compounds and subsequent validation identified two hits, confirming the application of this fluorescence assay in HTS.
Extracellular Vesicle-Mediated Purinergic Signaling Contributes to Host Microenvironment Plasticity and Metastasis in Triple Negative Breast Cancer
Authors: Duan Suzann , Nordmeier Senny , Byrnes Aidan E. , Buxton Iain L. O.
Published: January 2021

Metastasis accounts for over 90% of cancer-related deaths, yet the mechanisms guiding this process remain unclear. Secreted nucleoside diphosphate kinase A and B (NDPK) support breast cancer metastasis. Proteomic evidence confirms their presence in breast cancer-derived extracellular vesicles (EVs). We investigated the role of EV-associated NDPK in modulating the host microenvironment in favor of pre-metastatic niche formation. We measured NDPK expression and activity in EVs isolated from triple-negative breast cancer (MDA-MB-231) and non-tumorigenic mammary epithelial (HME1) cells using flow cytometry, western blot, and ATP assay. We evaluated the effects of EV-associated NDPK on endothelial cell migration, vascular remodeling, and metastasis. We further assessed MDA-MB-231 EV-induced proteomic changes in support of pre-metastatic lung niche formation. NDPK-B expression and phosphotransferase activity were enriched in MDA-MB-231 EVs that promote vascular endothelial cell migration and disrupt monolayer integrity. MDA-MB-231 EV-treated mice demonstrate pulmonary vascular leakage and enhanced experimental lung metastasis, whereas treatment with an NDPK inhibitor or a P2Y1 purinoreceptor antagonist blunts these effects. We identified perturbations to the purinergic signaling pathway in experimental lungs, lending evidence to support a role for EV-associated NDPK-B in lung pre-metastatic niche formation and metastatic outgrowth. These studies prompt further evaluation of NDPK-mediated EV signaling using targeted genetic silencing approaches.
The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy
Authors: Tolomeo Manlio , Cascio Antonio
Published: January 2021

Signal transducer and activator of transcription (STAT) 3 is one of the most complex regulators of transcription. Constitutive activation of STAT3 has been reported in many types of tumors and depends on mechanisms such as hyperactivation of receptors for pro-oncogenic cytokines and growth factors, loss of negative regulation, and excessive cytokine stimulation. In contrast, somatic STAT3 mutations are less frequent in cancer. Several oncogenic targets of STAT3 have been recently identified such as c-myc, c-Jun, PLK-1, Pim1/2, Bcl-2, VEGF, bFGF, and Cten, and inhibitors of STAT3 have been developed for cancer prevention and treatment. However, despite the oncogenic role of STAT3 having been widely demonstrated, an increasing amount of data indicate that STAT3 functions are multifaced and not easy to classify. In fact, the specific cellular role of STAT3 seems to be determined by the integration of multiple signals, by the oncogenic environment, and by the alternative splicing into two distinct isoforms, STAT3α and STAT3β. On the basis of these different conditions, STAT3 can act both as a potent tumor promoter or tumor suppressor factor. This implies that the therapies based on STAT3 modulators should be performed considering the pleiotropic functions of this transcription factor and tailored to the specific tumor type.
Structural Insights into Ankyrin Repeat-Containing Proteins and Their Influence in Ubiquitylation
Authors: Kane Emma I. , Spratt Donald E.
Published: January 2021

Ankyrin repeat (AR) domains are considered the most abundant repeat motif found in eukaryotic proteins. AR domains are predominantly known to mediate specific protein–protein interactions (PPIs) without necessarily recognizing specific primary sequences, nor requiring strict conformity within its own primary sequence. This promiscuity allows for one AR domain to recognize and bind to a variety of intracellular substrates, suggesting that AR-containing proteins may be involved in a wide array of functions. Many AR-containing proteins serve a critical role in biological processes including the ubiquitylation signaling pathway (USP). There is also strong evidence that AR-containing protein malfunction are associated with several neurological diseases and disorders. In this review, the structure and mechanism of key AR-containing proteins are discussed to suggest and/or identify how each protein utilizes their AR domains to support ubiquitylation and the cascading pathways that follow upon substrate modification.
2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with Staphylococcus aureus Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms
Authors: Oliveira Diana , Borges Anabela , Ruiz Reinaldo Molina , Negrín Zenaida Rodríguez , Distinto Simona , Borges Fernanda , Simões Manuel
Published: January 2021

Quorum sensing (QS) plays an essential role in the production of virulence factors, in biofilm formation and antimicrobial resistance. Consequently, inhibiting QS is being considered a promising target for antipathogenic/anti-virulence therapies. This study aims to screen 2-nitrovinylfuran derivatives structurally related to Furvina (a broad-spectrum antibiotic already used for therapeutic purposes) for their effects on QS and in biofilm prevention/control. Furvina and four 2-nitrovinylfuran derivatives (compounds 1–4) were tested to assess the ability to interfere with QS of Staphylococcus aureus using bioreporter strains (S. aureus ALC1742 and ALC1743). The activity of Furvina and the most promising quorum-sensing inhibitor (QSI) was evaluated in biofilm prevention and in biofilm control (combined with fusidic acid). The biofilms were further characterized in terms of biofilm mass, viability and membrane integrity. Compound 2 caused the most significant QS inhibition with reductions between 60% and 80%. Molecular docking simulations indicate that this compound interacts preferentially with the protein hydrophobic cleft in the LytTR domain of AgrA pocket. Metabolic inactivations of 40% for S. aureus ALC1742 and 20% for S. aureus ALC1743 were reached. A 24 h-old biofilm formed in the presence of the QSI increased the metabolic inactivation by fusidic acid to 80%, for both strains. The overall results highlight the effects of compound 2 as well as the potential of combining QSI with in-use antibiotics for the management of skin and soft tissues infections.
Molecular Mechanisms of Glucocorticoid-Induced Insulin Resistance
Authors: Beaupere Carine , Liboz Alexandrine , Fève Bruno , Blondeau Bertrand , Guillemain Ghislaine
Published: January 2021

Glucocorticoids (GCs) are steroids secreted by the adrenal cortex under the hypothalamic-pituitary-adrenal axis control, one of the major neuro-endocrine systems of the organism. These hormones are involved in tissue repair, immune stability, and metabolic processes, such as the regulation of carbohydrate, lipid, and protein metabolism. Globally, GCs are presented as ‘flight and fight’ hormones and, in that purpose, they are catabolic hormones required to mobilize storage to provide energy for the organism. If acute GC secretion allows fast metabolic adaptations to respond to danger, stress, or metabolic imbalance, long-term GC exposure arising from treatment or Cushing’s syndrome, progressively leads to insulin resistance and, in fine, cardiometabolic disorders. In this review, we briefly summarize the pharmacological actions of GC and metabolic dysregulations observed in patients exposed to an excess of GCs. Next, we describe in detail the molecular mechanisms underlying GC-induced insulin resistance in adipose tissue, liver, muscle, and to a lesser extent in gut, bone, and brain, mainly identified by numerous studies performed in animal models. Finally, we present the paradoxical effects of GCs on beta cell mass and insulin secretion by the pancreas with a specific focus on the direct and indirect (through insulin-sensitive organs) effects of GCs. Overall, a better knowledge of the specific action of GCs on several organs and their molecular targets may help foster the understanding of GCs’ side effects and design new drugs that possess therapeutic benefits without metabolic adverse effects.
Are Bioactive Molecules from Seaweeds a Novel and Challenging Option for the Prevention of HPV Infection and Cervical Cancer Therapy?—A Review
Authors: Moga Marius Alexandru , Dima Lorena , Balan Andreea , Blidaru Alexandru , Dimienescu Oana Gabriela , Podasca Cezar , Toma Sebastian
Published: January 2021

Cervical cancer represents one of the leading causes of cancer-related death in women all over the world. The infection with human papilloma virus (HPV) is one of the major risk factors for the development of premalignant lesions, which will progress to cervical cancer. Seaweeds are marine organisms with increased contents of bioactive compounds, which are described as potential anti-HPV and anti-cervical cancer agents. Our study aims to bring together all the results of the previous studies, conducted in order to highlight the potency of bioactive molecules from seaweeds, as anti-HPV and anti-cervical agents. This paper is a review of the English literature published between January 2010 and August 2020. We performed a systematic study in the Google Academic and PubMed databases using the key words “HPV infection”, “anticancer”, “seaweeds”, “cervical cancer” and “carcinogenesis process”, aiming to evaluate the effects of different bioactive molecules from marine algae on cervical cancer cell lines and on HPV-infected cells. Only original studies were considered for our research. None of the papers was excluded due to language usage or affiliation. Recent discoveries pointed out that sulfated polysaccharides, such as dextran sulfate heparan or cellulose sulfate, blocked the ability of HPV to infect cells, and inhibited the carcinogenesis process. Carrageenans inhibited the virions of HPV from binding the cellular wall. Fucoidan induced the growth inhibition of HeLa cervical cells in vitro. Heterofucans exhibited antiproliferative effects on cancer cell lines. Terpenoids from brown algae are also promising agents with anti-cervical cancer activity. Considering all the results of the previous studies, we observed that great amounts of bioactive molecules from seaweeds could treat both unapparent HPV infection and clinical visible disease. Furthermore, these molecules were very efficient in the treatment of invasive cervical carcinomas. In these conditions, we consider seaweeds extracts as a novel and challenging therapeutic strategy, and we hope that our study paves the way for further clinical trials in the field.