bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prevalence and Risk Factors of Type 2 Diabetes Mellitus (DMT2) in a Semi-Urban Saudi Population
Authors: Al Mansour Mohammed Abdullah
Published: December 2019

(1) Background: Diabetes mellitus is a common health problem in Saudi Arabia, causing a huge burden for individuals, families, and communities. The objectives of the current study were to determine the prevalence and risk factors of type 2 diabetes mellitus among a semi-urban population of Saudi Arabia. (2) Research methods: The research design was cross-sectional, and the research was conducted in five primary health care centers (PHCC) in Majmaah, Saudi Arabia. The sample size was calculated as 353. A pre-tested questionnaire was used to collect data after obtaining ethical approval. Blood samples were taken to assess glucose levels and other variables. SPSS version 21 was used to analyze data. (3) Results: The prevalence of type 2 diabetes mellitus was 34.6%. The disease was more prevalent among the older respondents compared with the younger age groups (44.6% versus 15.6%). We found that females acquire the disease at a slightly higher rate than males (34.9% versus 34.2%), but this difference is not statistically significant. The sociodemographic risk factors of the disease were as follows: old age (44%), business and private occupation (38.5%), divorced or widowed (56.3%), and low income (42.4%). The health behaviors factors were as follows: overweight or obese status (42.3%), high triglycerides (TG) (43.4%), low high-density lipoprotein (HDL) (37.3%), and high total cholesterol (23.7%). There was a statistically significant difference in these risk factors between patients with and without diabetes. (4) Conclusion: The prevalence of type 2 diabetes mellitus among the semi-urban population of Saudi Arabia is high. The disease is more prevalent among elderly respondents and is associated with obesity, high TG, low HDL, and high total cholesterol.
Cause Analysis of Unsafe Behaviors in Hazardous Chemical Accidents: Combined with HFACs and Bayesian Network
Authors: Li Xiaowei , Liu Tiezhong , Liu Yongkui
Published: December 2019

Hazardous chemical accidents (HCAs) seriously endanger public life, property, and health. Human and organizational factors are important causes of many kinds of accidents. In order to systematically explore the influencing factors of unsafe behaviors in HCAs in China, the method of human factors analysis and classification system based on the Bayesian network (BN-HFACs) was introduced. According to the 39 investigation reports of HCAs in China, the origin Bayesian network (BN) was obtained and the failure sensitivity of every node in BN was calculated. The results have shown that hazardous material environment (1.63) and mechanical equipment (0.49) in the level of preconditions of unsafe behavior have the same direction failure effect with operation error, while there is no factor has the same direction failure effect with operation violate. Some factors in organization influence and unsafe supervision, such as organization climate (0.34), operation guidance (0.37), planned operation (0.22), and legal supervision (0.19), are also important reasons for operational errors, while resource management (0.12), hidden investigation (0.18) and legal supervision (0.13) have an impact on operation violates. Moreover, there are still close relationships between other hierarchical elements, such as the operation guidance effect on the hazardous material environment (6.60), and the organizational climate has the most obvious impact on other factors at the level of organizational factors. Based on the above research conclusions, suggestions for individual, enterprise, and government were put forward, respectively, and the limitations of this study were also clarified.
Care Farming Program for Family Health: A Pilot Study with Mothers and Children
Authors: Lee A-Young , Kim Seon Ok , Gim Gyung Mee , Kim Dae Sik , Park Sin-Ae
Published: December 2019

We designed a pilot study to develop a family interaction model-integrated a care farming program with mother-child pairs as the participants. In this pilot study, we aimed to assess the effects of the care farming program on communication skills and psychological health in families. Sixteen mother-child pairs in Sejong, South Korea participated in this study. The families participated in a care farming program once a week for six weeks (90 min per session) between May and July 2018. The care farming program was developed based on parenting education skills, strengths-based cognitive behavioral therapy, and the emotional intelligence model; the result was a family interaction model intended to improve communication and psychological health among mothers and children. The program consisted of gardening activities such as making a garden plot, planting transplants, harvesting, and cooking the harvested crops. Upon completion of the six-session program, we evaluated communication with the Parent-Children Communication Inventory, depression with the Beck Depression Inventory, and resilience with the Connor–Davidson Resilience Scale among the mothers. We also evaluated emotional intelligence among the children with the Emotional Intelligence Scale. According to post-intervention results, mothers showed significantly increased resilience, improved communication skills with their child, and decreased depression, while children showed significantly improved emotional intelligence (p < 0.05). Despite the study’s limitation in establishing causality between the care farming program and the observed effects on family health, the care farming program clearly contributed to the observed improvements of mother-child communication skills, mothers’ psychological health, and children’s emotional intelligence, which in turn improved overall family health.
Smoking Cessation and Vaping Cessation Attempts among Cigarette Smokers and E-Cigarette Users in Central and Eastern Europe
Authors: Jankowski Mateusz , Lawson Joshua Allan , Shpakou Andrei , Poznański Michał , Zielonka Tadeusz Maria , Klimatckaia Ludmila , Loginovich Yelena , Rachel Marta , Gereová Justína , Minarowski Łukasz , Naumau Ihar , Kornicki Kamil , Pepłowska Paulina , Kovalevskiy Valeriy , Raskiliene Asta , Bielewicz Krzysztof , Krištúfková Zuzana , Mróz Robert , Majek Paulina , Skoczyński Szymon , Zejda Jan Eugeniusz , Brożek Grzegorz Marek
Published: December 2019

Our aim is to assess the smoking cessation and vaping cessation activity, including quit attempts and willingness to quit among university students in Central and Eastern Europe, as well as to investigate personal characteristics associated with smoking cessation and vaping cessation attempts. Data were collected by questionnaire which included 46 questions on cigarette and e-cigarette use. Questionnaires were obtained from 14,352 university students (aged 20.9 ± 2.4 years; cooperation rate of 72.2%). For the purposes of this analysis, only data from exclusive cigarette smokers (n = 1716), exclusive e-cigarette users (n = 129), and dual users (216) were included. Of all cigarette smokers, 51.6% had previously tried to quit smoking and 51.5% declared a willingness to quit cigarette smoking in the near future. Among all e-cigarette users only 13.9% had ever tried to quit using the e-cigarette and 25.2% declared a willingness to give up using e-cigarette in the near future. The majority of the group did not use pharmacotherapy to quit cigarette (87.5%) or e-cigarette (88.9%) use. Our results indicate that while most university students have some desire to quit conventional smoking, those who use e-cigarettes do not have the same desire.
Tempo-Spatial Variation of Vegetation Coverage and Influencing Factors of Large-Scale Mining Areas in Eastern Inner Mongolia, China
Authors: Fang Aman , Dong Jihong , Cao Zhiguo , Zhang Feng , Li Yongfeng
Published: December 2019

Vegetation in eastern Inner Mongolia grasslands plays an important role in preventing desertification, but mineral exploration has negative effects on the vegetation of these regions. In this study, the changing trend types of vegetation in eastern Inner Mongolia were analyzed using the normalized difference vegetation index (NDVI) time series from the Global Inventory Modeling and Mapping Studies (GIMMS) NDVI 3g dataset from 1982 to 2015. Meanwhile, changing trend and influencing factors of 25 large-scale mining areas before and after mining were explored with the methods of trend line, residual calculation, and correlation analysis. The vegetation coverage towards increasing in eastern Inner Mongolia decreased in the order of Tongliao > Hinggan League > Chifeng > Hulunbuir > Xilingol over the past 34 years. Vegetation showed a decreasing tendency in 40% mining areas, but an increasing tendency in 60% mining areas after mining. Vegetation change in Shengli No. 1 had a significant correlation with precipitation and human activities after mining. Except Shengli No. 1, an obvious correlation was found between vegetation change and precipitation in 45.83% mining areas after mining. Human activities had significant positive effects on vegetation growth in 25% mining areas. Significant negative effects of human activities were found in 8.34% mining areas, causing the vegetation degradation. However, there were 20.83% mining areas with vegetation changes not affected by precipitation and human activities.
Absenteeism during Menstruation among Nursing Students in Spain
Authors: Fernández-Martínez Elia , Onieva-Zafra María Dolores , Abreu-Sánchez Ana , Fernández-Muñóz Juan José , Parra-Fernández María Laura
Published: December 2019

Absenteeism can clearly have a negative impact on academic performance among university students. Certain experiences or symptoms such as menstrual pain are very common in women and can lead to absenteeism. The current study was aimed at examining the presence of menstrual experiences or symptoms and their impact upon absenteeism among healthy (illness-free) female university nursing students in Spain. A total of 299 students participated in this research, which was a descriptive cross-sectional, observational study. An ad hoc online questionnaire was used based on sociodemographic and gynecological data, together with the noted menstrual experiences; the most prevalent of which were bloating, which affected 87.3% of students; dysmenorrhea and irritability, which affected 76.3%; and fatigue, which affected 70.6%. Students with dysmenorrhea had a 6.95 higher (odds ratio (OR) 6.95; 95% confidence interval (CI) 3.39–14.25) odds of absenteeism; in those who reported dizziness, the odds of absenteeism was 4.82 times higher (OR 4.82; 1.76–13.23); in those who manifested nausea and vomiting, the percentage of absenteeism was 3.51 higher (OR 3.51; 95% CI 1.51–8.15); in those who presented sleep alterations, the odds were 2.95 higher (OR 2.95; 95% CI 1.39–6.25); and for those who felt depressed the odds were 2.18 times higher (OR 2.18; 95% CI 1.21–3.94) Absenteeism was found to be more likely in women with dysmenorrhea. However, in addition, higher odds of absenteeism were also found in women with nausea and vomiting, dizziness, sleep disorders, and those who feel depressed. These menstrual experiences can be considered a relevant problem among young women, leading to absenteeism, and a negative influence on academic performance. It is essential to raise awareness of the socioeconomic impact of absenteeism and establish new strategies for improving menstrual experiences.
Combined Interventions to Reduce Burnout Complaints and Promote Return to Work: A Systematic Review of Effectiveness and Mediators of Change
Authors: Pijpker Roald , Vaandrager Lenneke , Veen Esther J. , Koelen Maria A.
Published: December 2019

Burnout has adverse effects on the health and work-related outcomes of employees. Nevertheless, little is known about effective ways of reducing burnout complaints and facilitating full return to work, which defines rehabilitation. This study consists of a systematic review of the effects of combined interventions (i.e., both person-directed and organization-directed). It also includes the identification and description of mediators of change, thereby explaining how combined interventions do or do not work. Seven electronic databases were searched for English peer-reviewed publications: the Psychology and Behavioral Sciences Collection; PsycARTICLES; Web of Science; Scopus; SocINDEX; PubMed; and PsycINFO, using various combinations of search terms (e.g., burnout AND intervention). Out of 4110 abstracts published before 29 September, 2019, 10 studies (reporting the effects of nine combined interventions) fulfilled the inclusion criteria, which were defined using PICOS criteria (participants, interventions, comparators, outcomes and study design). Although the risk of bias of the included studies is high, all combined interventions were effective in facilitating rehabilitation. Results suggest that involving employees in decision-making and enhance their job control and social support, while eliminating stressors, explain the effectiveness of the intentions. With caution, workplace health promotion practitioners are encouraged to use these findings to tackle burnout among employees.
Adolescent Body Dissatisfaction in Contrasting Socioeconomic Milieus, Coming from a French and Luxembourgish Context
Authors: Regnier Faustine , Le Bihan Etienne , Tichit Christine , Baumann Michèle
Published: December 2019

Purpose: To analyze the relationships between body mass index (BMI), ideal body, current declared body shape, and gap between ideal and declared body shape, and the associations that these have with social and cultural factors among 329 adolescents (11 to 15 years i.e., at two stages of adolescence, the early and late adolescence), attending an international school in Luxembourg, and 281 from Paris. Methods: A cross-sectional survey was conducted using an online questionnaire. Missing data were addressed using the data augmentation method in a Bayesian framework. Results: For both sets, higher the BMI and bigger their current body shape (CBS), the slimmer their ideal body shape, especially for those who perceive a link between body shape and beauty. For girls, slimness is a shared ideal; for boys, older they are, more they want a muscular body shape. Most students want slimmer bodies, but in affluent or intermediate social milieu students in relations to identification to personalities such as celebrities, while students from modest milieus, this is expressed in relation to success in love. In addition, they declared that their “talk diet with friends” were associated with large gap between ideal and declared body shape. Conclusions: A social control norm was revealed involving a displacement of values affecting body weight and health in the late stage of adolescence to early adolescence, especially for boys.
Providing Students with Adequate School Drinking Water Access in an Era of Aging Infrastructure: A Mixed Methods Investigation
Authors: Kenney Erica L. , Daly James G. , Lee Rebekka M. , Mozaffarian Rebecca S. , Walsh Katherine , Carter Jill , Gortmaker Steven L.
Published: December 2019

Ensuring students’ access to safe drinking water at school is essential. However, many schools struggle with aging infrastructure and subsequent water safety problems and have turned to bottled water delivery systems. Little is known about whether such systems are feasible and effective in providing adequate student water access. This study was a mixed-methods investigation among six schools in an urban district in the U.S. with two types of water delivery systems: (1) tap water infrastructure, with updated water fountains and bottle fillers, and (2) bottled water coolers. We measured students’ water consumption and collected qualitative data from students and teachers about their perceptions of school drinking water. Student water consumption was low—between 2.0 (SD: 1.4) ounces per student and 2.4 (SD: 1.1) ounces per student during lunch. Students and teachers reported substantial operational hurdles for relying on bottled water as a school’s primary source of drinking water, including difficulties in stocking, cleaning, and maintaining the units. While students and teachers perceived newer bottle filler units positively, they also reported a distrust of tap water. Bottled water delivery systems may not be effective long-term solutions for providing adequate school drinking water access and robust efforts are needed to restore trust in tap water.
Emergencies in Long-Term Care Services for the Elderly in Korea: A Mixed-Methods Study
Authors: Kim Soon Ok , Bae Sun Hee
Published: December 2019

This mixed-methods study explored ways to enhance the emergency response abilities of workers in long-term care services for the elderly. Based on different service types, we identify emergency situations and the response abilities of workers in long-term care services. Results indicated that there are more emergency situations in care facilities than in home care services. However, 71.3% of respondents in facilities said emergency response abilities were low compared to 44.2% of workers in home care services. Qualitative research identified six categories and 16 themes based on emotions experienced during emergencies and the challenges in determining solutions. The study confirms that there is a difference in emergency incidences and the coping abilities of workers in facilities and home services with high emergency incidence rates. Developing and applying guidelines for emergency response management by service type is recommended.
The Association between Chronotype and Dietary Pattern among Adults: A Scoping Review
Authors: Mazri Fatin Hanani , Manaf Zahara Abdul , Shahar Suzana , Mat Ludin Arimi Fitri
Published: December 2019

Chronotype reflects an individual’s preferred time of the day for an activity/rest cycle and individuals can be classified as a morning, intermediate, or evening type. A growing number of studies have examined the relationship between chronotype and general health. This review aimed to map current evidence of the association between chronotype and dietary intake among the adult population. A systematic search was conducted across five databases: EBSCO Host, Medline & Ovid, Pubmed, Scopus, and The Cochrane Library. The inclusion criteria were adult subjects (more than 18 years old), and included an assessment of (i) chronotype, (ii) dietary behaviour/nutrient intake/food group intake, and (iii) an analysis of the association between chronotype and dietary behaviour/nutrient intake/food group intake. A total of 36 studies were included in the review. This review incorporated studies from various study designs, however, the majority of these studies were based on a cross-sectional design (n = 29). Dietary outcomes were categorized into three main groups, namely dietary behaviour, nutrient intake, and specific food group intake. This scoping review demonstrates that evening-type individuals are mostly engaged with unhealthy dietary habits related to obesity and were thus hampered in the case of weight loss interventions. Hence, this review has identified several dietary aspects that can be addressed in the development of a personalised chrono-nutrition weight loss intervention.
Magnesium Alginate in Gastro-Esophageal Reflux: A Randomized Multicenter Cross-Over Study in Infants
Authors: Baldassarre Maria Elisabetta , Di Mauro Antonio , Pignatelli Maria Cristina , Fanelli Margherita , Salvatore Silvia , Di Nardo Giovanni , Chiaro Andrea , Pensabene Licia , Laforgia Nicola
Published: December 2019

The aims of this study were to evaluate the efficacy of magnesium alginate in decreasing functional regurgitation symptoms in infants, and to assess the cost–benefit ratio of magnesium alginate compared to a thickened formula. A multicenter perspective cross-over study was conducted in formula-fed infants with persisting regurgitation, randomly assigned to receive two weeks of a magnesium-alginate-based formulation followed by two weeks of thickened formula, or vice-versa. Infants, exclusively breast-fed, were followed up for two weeks while receiving magnesium alginate. Symptoms of gastroesophageal reflux (GER) were evaluated through the Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R). Direct cost of treatments was also calculated. Seventy-two infants completed the study. We found a significant reduction of I-GERQ-R scores over time (F = 55.387; p < 0.001) in all groups with no difference between the sequences of administration (F = 0.268; p = 0.848) in formula-fed infants and between exclusively breast-fed and formula-fed infants receiving magnesium alginate (t = 1.55; p = 0.126). The mean cost savings per infant was € 4.60 (±11.2) in formula-fed infants treated with magnesium alginate compared to thickened formula (t = 2.91, p < 0.0005). Conclusions were that the magnesium-alginate formulation reduces GER symptoms both in formula-fed and breast-fed infants. In formula-fed infants, clinical efficacy is similar to thickened formulas with a slightly lower cost of treatment.
The State of Mapillary: An Exploratory Analysis
Authors: Ma Dawei , Fan Hongchao , Li Wenwen , Ding Xuan
Published: December 2019

As the world’s largest crowdsourcing-based street view platform, Mapillary has received considerable attention in both research and practical applications. By February 2019, more than 20,000 users worldwide contributed approximately 6.3 million kilometers of streetscape sequences. In this study, we attempted to get a deep insight into the Mapillary project through an exploratory analysis from the perspective of contributors, including the development of users, the spatiotemporal analysis of active users, the contribution modes (walking, cycling, and driving), and the devices used to contribute. It shows that inequality exists in the distribution of contributed users, similar to that in other volunteered geographic information (VGI) projects. However, the inequality in Mapillary contribution is less than in OpenStreetMap (OSM). Compared to OSM, the other main difference is that the data collection demonstrated obvious seasonal variation because contributions to OSM can be accomplished on a computer, whereas images have to be captured on the streets for Mapillary, and this is considerably affected by seasonal weather.
The Ubiquitin Proteasome System in Ischemic and Dilated Cardiomyopathy
Authors: Spänig Sabine , Kellermann Kristina , Dieterlen Maja-Theresa , Noack Thilo , Lehmann Sven , Borger Michael A. , Garbade Jens , Barac Yaron D. , Emrich Fabian
Published: December 2019

Dilated (DCM) and ischemic cardiomyopathies (ICM) are associated with cardiac remodeling, where the ubiquitin–proteasome system (UPS) holds a central role. Little is known about the UPS and its alterations in patients suffering from DCM or ICM. The aim of this study is to characterize the UPS activity in human heart tissue from cardiomyopathy patients. Myocardial tissue from ICM (n = 23), DCM (n = 28), and control (n = 14) patients were used to quantify ubiquitinylated proteins, E3-ubiquitin-ligases muscle-atrophy-F-box (MAFbx)/atrogin-1, muscle-RING-finger-1 (MuRF1), and eukaryotic-translation-initiation-factor-4E (eIF4E), by Western blot. Furthermore, the proteasomal chymotrypsin-like and trypsin-like peptidase activities were determined fluorometrically. Enzyme activity of NAD(P)H oxidase was assessed as an index of reactive oxygen species production. The chymotrypsin- (p = 0.71) and caspase-like proteasomal activity (p = 0.93) was similar between the groups. Trypsin-like proteasomal activity was lower in ICM (0.78 ± 0.11 µU/mg) compared to DCM (1.06 ± 0.08 µU/mg) and control (1.00 ± 0.06 µU/mg; p = 0.06) samples. Decreased ubiquitin expression in both cardiomyopathy groups (ICM vs. control: p < 0.001; DCM vs. control: p < 0.001), as well as less ubiquitin-positive deposits in ICM-damaged tissue (ICM: 4.19% ± 0.60%, control: 6.28% ± 0.40%, p = 0.022), were detected. E3-ligase MuRF1 protein expression (p = 0.62), NADPH-oxidase activity (p = 0.63), and AIF-positive cells (p = 0.50). Statistical trends were detected for reduced MAFbx protein expression in the DCM-group (p = 0.07). Different levels of UPS components, E3 ligases, and UPS activation markers were observed in myocardial tissue from patients affected by DCM and ICM, suggesting differential involvement of the UPS in the underlying pathologies.
Cardiac Extracellular Vesicles (EVs) Released in the Presence or Absence of Inflammatory Cues Support Angiogenesis in Different Manners
Authors: Beez Christien Madlen , Schneider Maria , Haag Marion , Pappritz Kathleen , Van Linthout Sophie , Sittinger Michael , Seifert Martina
Published: December 2019

Cells release extracellular vesicles (EVs) to communicate in a paracrine manner with other cells, and thereby influence processes, such as angiogenesis. The conditioned medium of human cardiac-derived adherent proliferating (CardAP) cells was recently shown to enhance angiogenesis. To elucidate whether their released EVs are involved, we isolated them by differential centrifugation from the conditioned medium derived either in the presence or absence of a pro-inflammatory cytokine cocktail. Murine recipient cells internalized CardAP-EVs as determined by an intracellular detection of human proteins, such as CD63, by a novel flow cytometry method for studying EV–cell interaction. Moreover, endothelial cells treated for 24 h with either unstimulated or cytokine stimulated CardAP-EVs exhibited a higher tube formation capability on Matrigel. Interestingly, unstimulated CardAP-EVs caused endothelial cells to release significantly more vascular endothelial growth factor and interleukin (IL)-6, while cytokine stimulated CardAP-EVs significantly enhanced the release of IL-6 and IL-8. By nCounter® miRNA expression assay (NanoString Technologies) we identified microRNA 302d-3p to be enhanced in unstimulated CardAP-EVs compared to their cytokine stimulated counterparts, which was verified by quantitative polymerase chain reaction. This study demonstrates that both CardAP-EVs are pro-angiogenic by inducing different factors from endothelial cells. This would allow to select potent targets for a safe and efficient therapeutic application.
The Terrestrial Carnivorous Plant Utricularia reniformis Sheds Light on Environmental and Life-Form Genome Plasticity
Authors: Silva Saura R. , Moraes Ana Paula , Penha Helen A. , Julião Maria H. M. , Domingues Douglas S. , Michael Todd P. , Miranda Vitor F. O. , Varani Alessandro M.
Published: December 2019

Utricularia belongs to Lentibulariaceae, a widespread family of carnivorous plants that possess ultra-small and highly dynamic nuclear genomes. It has been shown that the Lentibulariaceae genomes have been shaped by transposable elements expansion and loss, and multiple rounds of whole-genome duplications (WGD), making the family a platform for evolutionary and comparative genomics studies. To explore the evolution of Utricularia, we estimated the chromosome number and genome size, as well as sequenced the terrestrial bladderwort Utricularia reniformis (2n = 40, 1C = 317.1-Mpb). Here, we report a high quality 304 Mb draft genome, with a scaffold NG50 of 466-Kb, a BUSCO completeness of 87.8%, and 42,582 predicted genes. Compared to the smaller and aquatic U. gibba genome (101 Mb) that has a 32% repetitive sequence, the U. reniformis genome is highly repetitive (56%). The structural differences between the two genomes are the result of distinct fractionation and rearrangements after WGD, and massive proliferation of LTR-retrotransposons. Moreover, GO enrichment analyses suggest an ongoing gene birth–death–innovation process occurring among the tandem duplicated genes, shaping the evolution of carnivory-associated functions. We also identified unique patterns of developmentally related genes that support the terrestrial life-form and body plan of U. reniformis. Collectively, our results provided additional insights into the evolution of the plastic and specialized Lentibulariaceae genomes.
Tetrahydroquinoline-Isoxazole/Isoxazoline Hybrid Compounds as Potential Cholinesterases Inhibitors: Synthesis, Enzyme Inhibition Assays, and Molecular Modeling Studies
Authors: Rodríguez Núñez Yeray A. , Gutíerrez Margarita , Alzate-Morales Jans , Adasme-Carreño Francisco , Güiza Fausto M. , Bernal Cristian C. , Bohórquez Arnold R. Romero
Published: December 2019

A series of 44 hybrid compounds that included in their structure tetrahydroquinoline (THQ) and isoxazole/isoxazoline moieties were synthesized through the 1,3-dipolar cycloaddition reaction (1,3-DC) from the corresponding N-allyl/propargyl THQs, previously obtained via cationic Povarov reaction. In vitro cholinergic enzymes inhibition potential of all compounds was tested. Enzyme inhibition assays showed that some hybrids exhibited significant potency to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Especially, the hybrid compound 5n presented the more effective inhibition against AChE (4.24 µM) with an acceptable selectivity index versus BChE (SI: 5.19), while compound 6aa exhibited the greatest inhibition activity on BChE (3.97 µM) and a significant selectivity index against AChE (SI: 0.04). Kinetic studies were carried out for compounds with greater inhibitory activity of cholinesterases. Structure–activity relationships of the molecular hybrids were analyzed, through computational models using a molecular cross-docking algorithm and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding free energy approach, which indicated a good correlation between the experimental inhibition values and the predicted free binding energy.
Insight into Nephrocan Function in Mouse Endoderm Patterning
Authors: Addeo Martina , Buonaiuto Silvia , Guerriero Ilaria , Amendola Elena , Visconte Feliciano , Marino Antonio , De Angelis Maria Teresa , Russo Filomena , Roberto Luca , Marotta Pina , Russo Nicola Antonino , Iervolino Anna , Amodio Federica , De Felice Mario , Lucci Valeria , Falco Geppino
Published: December 2019

Endoderm-derived organs as liver and pancreas are potential targets for regenerative therapies, and thus, there is great interest in understanding the pathways that regulate the induction and specification of this germ layer. Currently, the knowledge of molecular mechanisms that guide the in vivo endoderm specification is restricted by the lack of early endoderm specific markers. Nephrocan (Nepn) is a gene whose expression characterizes the early stages of murine endoderm specification (E7.5–11.5) and encodes a secreted N-glycosylated protein. In the present study, we report the identification of a new transcript variant that is generated through alternative splicing. The new variant was found to have differential and tissue specific expression in the adult mouse. In order to better understand Nepn role during endoderm specification, we generated Nepn knock-out (KO) mice. Nepn−/− mice were born at Mendelian ratios and displayed no evident phenotype compared to WT mice. In addition, we produced nullizygous mouse embryonic stem cell (mESC) line lacking Nepn by applying (CRISPR)/CRISPR-associated systems 9 (Cas9) and employed a differentiation protocol toward endoderm lineage. Our in vitro results revealed that Nepn loss affects the endoderm differentiation impairing the expression of posterior foregut-associated markers.
The Interaction between 30b-5p miRNA and MBNL1 mRNA is Involved in Vascular Smooth Muscle Cell Differentiation in Patients with Coronary Atherosclerosis
Authors: Woo Chin Cheng , Liu Wenting , Lin Xiao Yun , Dorajoo Rajkumar , Lee Kee Wah , Richards A Mark , Lee Chuen Neng , Wongsurawat Thidathip , Nookaew Intawat , Sorokin Vitaly
Published: December 2019

Vascular smooth muscle cells (VSMCs) in the arterial wall have diverse functions. In pathological states, the interplay between transcripts and microRNAs (miRNAs) leads to phenotypic changes. Understanding the regulatory role of miRNAs and their target genes may reveal how VSMCs modulate the pathogenesis of coronary artery disease. Laser capture microdissection was performed on aortic wall tissues obtained from coronary artery bypass graft patients with and without recent acute myocardial infarction (MI). The mSMRT-qPCR miRNA assay platform (MiRXES, Singapore) was used to profile miRNA. The miRNA data were co-analyzed with significant mRNA transcripts. TargetScan 7.1 was applied to evaluate miRNA–mRNA interactions. The miRNA profiles of 29 patients (16 MI and 13 non-MI) were evaluated. Thirteen VSMC-related miRNAs were differentially expressed between the MI and non-MI groups. Analysis revealed seven miRNA-targeted mRNAs related to muscular tissue differentiation and proliferation. TargetScan revealed that among the VSMC-related transcripts, MBNL1 had a recognition site that matched the hsa-miR-30b-5p target seed sequence. In addition to predicted analysis, our experiment in vitro with human VSMC culture confirmed that hsa-miR-30b-5p negatively correlated with MBNL1. Our data showed that overexpression of hsa-miR-30b-5p led to downregulation of MBNL1 in VSMCs. This process influences VSMC proliferation and might be involved in VSMC differentiation.
Telomerase Does Not Improve DNA Repair in Mitochondria upon Stress but Increases MnSOD Protein under Serum-Free Conditions
Authors: Martens Alexander , Schmid Bianca , Akintola Olasubomi , Saretzki Gabriele
Published: December 2019

Telomerase is best known for its function in maintaining telomeres but has also multiple additional, non-canonical functions. One of these functions is the decrease of oxidative stress and DNA damage due to localisation of the telomerase protein TERT into mitochondria under oxidative stress. However, the exact molecular mechanisms behind these protective effects are still not well understood. We had shown previously that overexpression of human telomerase reverse transcriptase (hTERT) in human fibroblasts results in a decrease of mitochondrial DNA (mtDNA) damage after oxidative stress. MtDNA damage caused by oxidative stress is removed via the base excision repair (BER) pathway. Therefore we aimed to analyse whether telomerase is able to improve this pathway. We applied different types of DNA damaging agents such as irradiation, arsenite treatment (NaAsO2) and treatment with hydrogen peroxide (H2O2). Using a PCR-based assay to evaluate mtDNA damage, we demonstrate that overexpression of hTERT in MRC-5 fibroblasts protects mtDNA from H2O2 and NaAsO2 induced damage, compared with their isogenic telomerase-negative counterparts. However, overexpression of hTERT did not seem to increase repair of mtDNA after oxidative stress, but promoted increased levels of manganese superoxide dismutase (MnSOD) and forkhead-box-protein O3 (FoxO3a) proteins during incubation in serum free medium as well as under oxidative stress, while no differences were found in protein levels of catalase. Together, our results suggest that rather than interfering with mitochondrial DNA repair mechanisms, such as BER, telomerase seems to increase antioxidant defence mechanisms to prevent mtDNA damage and to increase cellular resistance to oxidative stress. However, the result has to be reproduced in additional cellular systems in order to generalise our findings.
Oral Administration of Lactobacillus Casei Expressing Flagellin A Protein Confers Effective Protection against Aeromonas Veronii in Common Carp, Cyprinus Carpio
Authors: Tian Jia-Xin , Kang Yuan-Huan , Chu Guo-Sheng , Liu Hong-Jian , Kong Yi-Di , Zhao Lin-Hui , Kong Yu-Xin , Shan Xiao-Feng , Wang Gui-Qin
Published: December 2019

Aeromonas veronii is a pathogen capable of infecting humans, livestock and aquatic animals, resulting in serious economic losses. In this study, two recombinant Lactobacillus casei expressing flagellin A (FlaA) of A. veronii, Lc-pPG-1-FlaA (surface-displayed) and Lc-pPG-2-FlaA (secretory) were constructed. The immune responses in fish administered with recombinant L. casei were evaluated. The two recombinant L. casei were orally administered to common carp, which stimulated high serum IgM and induced higher ACP, AKP, SOD and LYZ activity. Using qRT-PCR, the expression of IL-10, IL-8, IL-1β, TNF-α and IFN-γ in the tissue of fish immunized with recombinant L. casei was significantly (p < 0.05) upregulated, which indicated that recombinant L. casei could activate the innate immune system to trigger the cell immune response and inflammatory response. Furthermore, recombinant L. casei was able to survive the intestinal environment and colonize in intestine mucosal. The study showed that after being challenged by A. veronii, fish administered with Lc-pPG-1-FlaA (70%) and Lc-pPG-2-FlaA (50%) had higher survival rates compared to Lc-pPG and PBS, indicating that recombinant L. casei might prevent A. veronii infection by activating the immune system to trigger immune responses. We demonstrated that flagellin as an antigen of vaccine, is acceptable for preventing A. veronii infection in fish. The recombinant L. casei expressing FlaA may be a novel mucosal vaccine for treating and controlling A. veronii.
Proteomic Changes during MCMV Infection Revealed by iTRAQ Quantitative Proteomic Analysis in Maize
Authors: Dang Mingqing , Cheng Qi , Hu Ya , Wu Jianxiang , Zhou Xueping , Qian Yajuan
Published: December 2019

Maize chlorotic mottle virus (MCMV) has been occurring frequently worldwide and causes severe yield losses in maize (Zea mays). To better investigate the destructive effects of MCMV infection on maize plants, isobaric tagging for relative and absolute quantitation (iTRAQ)-based comparative proteomic analysis was performed on MCMV infected maize cv. B73. A total of 972 differentially abundant proteins (DAPs), including 661 proteins with increased abundance and 311 proteins with reduced abundance, were identified in response to MCMV infection. Functional annotations of DAPs and measurement of photosynthetic activity revealed that photosynthesis was decreased, while the abundance of ribosomal proteins, proteins related to stress responses, oxidation-reduction and redox homeostasis was altered significantly during MCMV infection. Two DAPs, disulfide isomerases like protein ZmPDIL-1 and peroxiredoxin family protein ZmPrx5, were further analyzed for their roles during MCMV infection through cucumber mosaic virus-based virus-induced gene silencing (CMV-VIGS). The accumulation of MCMV was suppressed in ZmPDIL-1-silenced or ZmPrx5-silenced B73 maize, suggesting ZmPDIL-1 and ZmPrx5 might enhance host susceptibility to MCMV infection.
Epigenetic Regulation in Etiology of Type 1 Diabetes Mellitus
Authors: Cerna Marie
Published: December 2019

Type 1 diabetes mellitus (T1DM) is caused by an autoimmune destruction of the pancreatic β-cells, a process in which autoreactive T cells play a pivotal role, and it is characterized by islet autoantibodies. Consequent hyperglycemia is requiring lifelong insulin replacement therapy. T1DM is caused by the interaction of multiple environmental and genetic factors. The integrations of environments and genes occur via epigenetic regulations of the genome, which allow adaptation of organism to changing life conditions by alternation of gene expression. T1DM has increased several-fold over the past half century. Such a short time indicates involvement of environment factors and excludes genetic changes. This review summarizes the most current knowledge of epigenetic changes in that process leading to autoimmune diabetes mellitus.
Comparative Analysis and Expression Patterns of the PLP_deC Genes in Dendrobium officinale
Authors: Zhang Lei , Jiao Chunyan , Cao Yunpeng , Cheng Xi , Wang Jian , Jin Qing , Cai Yongping
Published: December 2019

Studies have shown that the type II pyridoxal phosphate-dependent decarboxylase (PLP_deC) genes produce secondary metabolites and flavor volatiles in plants, and TDC (tryptophan decarboxylase), a member of the PLP_deC family, plays an important role in the biosynthesis of terpenoid indole alkaloids (TIAs). In this study, we identified eight PLP_deC genes in Dendrobium officinale (D. officinale) and six in Phalaenopsis equestris (P. equestris), and their structures, physicochemical properties, response elements, evolutionary relationships, and expression patterns were preliminarily predicted and analyzed. The results showed that PLP_deC genes play important roles in D. officinale and respond to different exogenous hormone treatments; additionally, the results support the selection of appropriate candidates for further functional characterization of PLP_deC genes in D. officinale.
Self-Assembly in Ganglioside‒Phospholipid Systems: The Co-Existence of Vesicles, Micelles, and Discs
Authors: Mojumdar Enamul Haque , Grey Carl , Sparr Emma
Published: December 2019

Ganglioside lipids have been associated with several physiological processes, including cell signaling. They have also been associated with amyloid aggregation in Parkinson’s and Alzheimer’s disease. In biological systems, gangliosides are present in a mix with other lipid species, and the structure and properties of these mixtures strongly depend on the proportions of the different components. Here, we study self-assembly in model mixtures composed of ganglioside GM1 and a zwitterionic phospholipid, 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC). We characterize the structure and molecular dynamics using a range of complementary techniques, including cryo-TEM, polarization transfer solid state NMR, diffusion NMR, small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and calorimetry. The main findings are: (1) The lipid acyl chains are more rigid in mixtures containing both lipid species compared to systems that only contain one of the lipids. (2) The system containing DOPC with 10 mol % GM1 contains both vesicles and micelles. (3) At higher GM1 concentrations, the sample is more heterogenous and also contains small disc-like or rod-like structures. Such a co-existence of structures can have a strong impact on the overall properties of the lipid system, including transport, solubilization, and partitioning, which can be crucial to the understanding of the role of gangliosides in biological systems.
iQSP: A Sequence-Based Tool for the Prediction and Analysis of Quorum Sensing Peptides Using Informative Physicochemical Properties
Authors: Charoenkwan Phasit , Schaduangrat Nalini , Nantasenamat Chanin , Piacham Theeraphon , Shoombuatong Watshara
Published: December 2019

Understanding of quorum-sensing peptides (QSPs) in their functional mechanism plays an essential role in finding new opportunities to combat bacterial infections by designing drugs. With the avalanche of the newly available peptide sequences in the post-genomic age, it is highly desirable to develop a computational model for efficient, rapid and high-throughput QSP identification purely based on the peptide sequence information alone. Although, few methods have been developed for predicting QSPs, their prediction accuracy and interpretability still requires further improvements. Thus, in this work, we proposed an accurate sequence-based predictor (called iQSP) and a set of interpretable rules (called IR-QSP) for predicting and analyzing QSPs. In iQSP, we utilized a powerful support vector machine (SVM) cooperating with 18 informative features from physicochemical properties (PCPs). Rigorous independent validation test showed that iQSP achieved maximum accuracy and MCC of 93.00% and 0.86, respectively. Furthermore, a set of interpretable rules IR-QSP was extracted by using random forest model and the 18 informative PCPs. Finally, for the convenience of experimental scientists, the iQSP web server was established and made freely available online. It is anticipated that iQSP will become a useful tool or at least as a complementary existing method for predicting and analyzing QSPs.
MicroRNA-204 Deficiency in Human Aortic Valves Elevates Valvular Osteogenic Activity
Authors: Song Rui , Zhai Yufeng , Ao Lihua , Fullerton David A. , Meng Xianzhong
Published: December 2019

Aortic valve interstitial cells (AVICs) play a major role in valvular calcification associated with calcific aortic valve disease (CAVD). Although AVICs from diseased valves display a pro-osteogenic phenotype, the underlying mechanism causing this remains unclear. MicroRNA-204 (miR-204) is a negative regulator of osteoblast differentiation. We sought to analyze miR-204 expression in diseased human aortic valves and determine the role of this miR in AVIC osteogenic activity associated with CAVD pathobiology. In situ hybridization and PCR analysis revealed miR-204 deficiency in diseased valves and in AVICs from diseased valves. MiR-204 mimic suppressed alkaline phosphatase (ALP) expression and calcium deposition in AVICs from diseased valves. MiR-204 antagomir enhanced ALP expression in AVICs from normal valves through induction of Runx2 and Osx, and expression of miR-204 antagomir in mouse aortic valves promoted calcium deposition through up-regulation of Runx2 and Osx. Further, miR-204 mimic suppressed the osteogenic responses to TGF-β1 in AVICs of normal valves. In conclusion, miR-204 deficiency contributes to the mechanism underlying elevated osteogenic activity in diseased aortic valves, and miR-204 is capable of reversing the pro-osteogenic phenotype of AVICs of diseased valves and suppressing AVIC osteogenic response to stimulation. Exogenous miR-204 may have therapeutic potential for inhibiting valvular calcification associated with CAVD progression.
De-Esterified Homogalacturonan Enrichment of the Cell Wall Region Adjoining the Preprophase Cortical Cytoplasmic Zone in Some Protodermal Cell Types of Three Land Plants
Authors: Giannoutsou Eleni , Galatis Basil , Apostolakos Panagiotis
Published: December 2019

The distribution of highly de-esterified homogalacturonans (HGs) in dividing protodermal cells of the monocotyledon Zea mays, the dicotyledon Vigna sinensis, and the fern Asplenium nidus was investigated in order to examine whether the cell wall region adjoining the preprophase band (PPB) is locally diversified. Application of immunofluorescence revealed that de-esterified HGs were accumulated selectively in the cell wall adjacent to the PPB in: (a) symmetrically dividing cells of stomatal rows of Z. mays, (b) the asymmetrically dividing protodermal cells of Z. mays, (c) the symmetrically dividing guard cell mother cells (GMCs) of Z. mays and V. sinensis, and (d) the symmetrically dividing protodermal cells of A. nidus. A common feature of the above cell types is that the cell division plane is defined by extrinsic cues. The presented data suggest that the PPB cortical zone-plasmalemma and the adjacent cell wall region function in a coordinated fashion in the determination/accomplishment of the cell division plane, behaving as a continuum. The de-esterified HGs, among other possible functions, might be involved in the perception and the transduction of the extrinsic cues determining cell division plane in the examined cells.