bluuebunny/crossref_metadata_2025 huggingface dataset:
Life Cycle Assessment of Bioethanol Production: A Review of Feedstock, Technology and Methodology
Authors: Soleymani Angili Tahereh , Grzesik Katarzyna , Rödl Anne , Kaltschmitt Martin
Published: May 2021

So far, a lot of efforts have been put in life cycle assessments (LCA) of bioethanol production. There are many works that have assessed bioethanol production in different points of view to illustrate the environmental impacts. This study reviewed former LCA studies on bioethanol produced from various biomass resources by considering the effect of methodological components, technical pathways and feedstock provision on the result of LCA studies. The review evaluated 48 papers published 2002–2021 with a focus on studies that included a complete set of environmental impact categories. However, due to lack of harmony among studies, comparing the LCA results was challenging but the review indicated that the final results of studies are influenced by LCA methodological components, such as system boundary, functional unit, etc. Around 80% of the reviewed papers show the reduction in global warming potential, while contrary results have been found about increasing acidification, eutrophication and photochemical oxidant formation impact categories because of the feedstock provision. Regarding technical aspects, results from the review revealed that most of the studies considered the pre-treatment as a crucial step in bioconversion processes. Despite several LCA studies of bioethanol production, there is still low attention given to uncertainty analysis in the publications.
The Effects of Informational Feedback on the Energy Consumption of Online Services: Some Evidence for the European Union
Authors: García-Muñiz Ana Salomé , Vicente María Rosalía
Published: May 2021

Information and Communication Technologies (ICT) have scarcely been considered in studies on green consumption. Likewise, little attention has been paid to the effects of informational feedback on household energy ICT-related consumption. This paper aims to fill these gaps in the literature. Using microdata from a representative sample of the European Union population, this paper analyzes, in a novel way, whether the provision of information about the energy consumed by online services would make internet users change to a greener ICT consumption behavior. To assess this issue, Heckman type selection models are estimated. The results show that people’s concerns about environmental problems, their environmental activism and self-perceived efficacy as consumers are directly related to the influence that information provision exerts. We also find that frequent internet users and those with better digital skills are more willing to change their online behavior if given information on energy consumption.
The Effect of RME-1-Butanol Blends on Combustion, Performance and Emission of a Direct Injection Diesel Engine
Authors: Tutak Wojciech , Jamrozik Arkadiusz , Grab-Rogaliński Karol
Published: May 2021

The main objective of this study was assessment of the performance, emissions and combustion characteristics of a diesel engine using RME–1-butanol blends. In assessing the combustion process, great importance was placed on evaluating the stability of this process. Not only were the typical COVIMEP indicators assessed, but also the non-burnability of the characteristic combustion stages: ignition delay, time of 50% heat release and the end of combustion. The evaluation of the combustion process based on the analysis of heat release. The tests carried out on a 1-cylinder diesel engine operating at a constant load. Research and evaluation of the combustion process of a mixture of RME and 1-butanol carried out for the entire range of shares of both fuels up to 90% of 1-butanol energetic fraction. The participation of butanol in combustion process with RME increased the in-cylinder peak pressure and the heat release rate. With the increase in the share of butanol there was noted a decrease in specific energy consumption and an increase in engine efficiency. The share of butanol improved the combustion stability. There was also an increase in NOx emissions and decrease in CO and soot emissions. The engine can be power by blend up to 80% energy share of butanol.
Towards the Development of Digital Manufacturing Ecosystems for Sustainable Performance: Learning from the Past Two Decades of Research
Authors: Shahatha Al-Mashhadani Abdulrazak F. , Qureshi Muhammad Imran , Hishan Sanil S. , Md Saad Mohd Shamsuri , Vaicondam Yamunah , Khan Nohman
Published: May 2021

Although the Internet of Things (IoT), advanced manufacturing technologies, and cloud manufacturing contribute to developing a digital manufacturing ecosystem that enhances energy efficiency and resource utilization, manufacturing processes are vulnerable to timely production and delivery. The digital manufacturing systems in Industrial Revolution 4.0 (IR 4.0) minimized the human-technology interactions to foster productivity and material flow. However, there is scarce research to gauge the efficiency of these digital technologies in the entire manufacturing process; also, little is known about the collaborative efforts among countries to achieve sustainable manufacturing performance through the digitalization of the production process. Thus, this systematic review aimed to highlight the effectiveness of the digital manufacturing systems for sustainable product development and the collaborative research on the subject. We selected 52 research articles for this review by following the 2015 Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) statement. The literature classifications were developed using text frequency algorithms in VOSviewer (Centre for Science and Technology Studies, Leiden University, The Netherlands) Results exposed literature from 2005 to 2020 can be categorized into four major research streams: digital transformation, digital manufacturing ecosystem, performance management, and sustainability. The study’s findings revealed that the manufacturing processes are moving towards the IoT, digital devices, and smart factories that are entirely dependent on digital technologies. The digital manufacturing ecosystem is dependent on the availability of digital technologies to all stakeholders. The study concluded that digital technologies are improving manufacturing efficiency and process effectiveness. However, this requires infrastructure that primarily available in developed countries; thus, the digital transformation in underdeveloped regions is deliberate and requires more collaborative research.
The Significance of the Adaptive Thermal Comfort Practice over the Structure Retrofits to Sustain Indoor Thermal Comfort
Authors: Albatayneh Aiman , Jaradat Mustafa , AlKhatib Mhd Bashar , Abdallah Ramez , Juaidi Adel , Manzano-Agugliaro Francisco
Published: May 2021

Any building’s design should sustain thermal comfort for occupants and promote less energy usage during its lifetime using accurate building retrofits to convert existing buildings into low-energy buildings so that the heating and cooling loads can be minimized. Regarding the methodology adopted in this research, an energy model of an educational building located at the German Jordanian University in Jordan was constructed utilizing DesignBuilder computer software. In addition, it was calibrated utilizing real energy consumption data for a 12-month simulation of energy performance. Subsequently, a computerized evaluation of the roles of building envelope retrofits or the adaptive thermal comfort limits in the reduction of the overall building energy consumption was analyzed. The results of the study show that the current building’s external wall insulation, roof insulation, glazing, windows, and external shading devices are relatively energy-efficient but with high cost, resulting in significant financial losses, even though they achieved noticeable energy savings. For instance, equipping the building’s ventilation system with an economizer culminated in the highest financial profit, contributing to an annual energy savings of 155 MWh. On the other hand, in an occupant-centered approach, applying the adaptive thermal comfort model in wider ranges by adding 1 °C, 2 °C, and 3 °C to the existing operating temperatures would save a significant amount of energy with the least cost (while maintaining indoor thermal comfort), taking over any retrofit option. Using different adaptive thermal comfort scenarios (1 °C, 2 °C, and 3 °C) led to significant savings of around 5%, 12%, and 21%, respectively. However, using different retrofits techniques proved to be costly, with minimum energy savings compared to the adaptive approach.
Genome Expression Dynamics Reveal the Parasitism Regulatory Landscape of the Root-Knot Nematode Meloidogyne incognita and a Promoter Motif Associated with Effector Genes
Authors: Da Rocha Martine , Bournaud Caroline , Dazenière Julie , Thorpe Peter , Bailly-Bechet Marc , Pellegrin Clément , Péré Arthur , Grynberg Priscila , Perfus-Barbeoch Laetitia , Eves-van den Akker Sebastian , Danchin Etienne G. J.
Published: May 2021

Root-knot nematodes (genus Meloidogyne) are the major contributor to crop losses caused by nematodes. These nematodes secrete effector proteins into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effector genes. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands, providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus, and we name it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode and identify a new set of candidate effector genes that will guide future functional analyses.
Special Issue: A Tale of Genes and Genomes
Authors: Ventura Mario , Antonacci Francesca
Published: May 2021

Variability is the source on which selective pressure acts, allowing genome evolution and adaptation [...]
Genotypic Diversity among Angolan Children with Sickle Cell Anemia
Authors: Delgadinho Mariana , Ginete Catarina , Santos Brígida , Miranda Armandina , Brito Miguel
Published: May 2021

Background. Sickle cell anemia (SCA) is an inherited blood disorder that affects over 300,000 newborns worldwide every year, being particularly prevalent in Sub-Saharan Africa. Despite being a monogenic disease, SCA shows a remarkably high clinical heterogeneity. Several studies have already demonstrated the existence of some polymorphisms that can provide major clinical benefits, producing a mild phenotype. Moreover, the existence of distinct haplotypes can also influence the phenotype patterns of certain populations, leading to different clinical manifestations. Our aim was to assess the association between polymorphisms in genes previously related to SCA disease severity in an Angolan pediatric population. Methods. This study analyzed clinical and biological data collected from 192 Angolan children. Using NGS data, we classified the HBB haplotypes based on four previously described SNPs (rs3834466, rs28440105, rs10128556, and rs968857) and the genotype for the SNPs in HBG2 (rs7482144), BCL11A (rs4671393, rs11886868, rs1427407, rs7557939), HBS1L-MYB (rs66650371) and BGLT3 (rs7924684) genes. Results. The CAR haplotype was undoubtedly the most common HBB haplotype in our population. The HbF values and the ratio of gamma chains were statistically significant for almost all of the variants studied. We reported for the first time an association between rs7924684 in the BGLT3 gene and gamma chains ratio. Conclusions. The current findings emphasize the importance personalized medicine would have if applied to SCA patient care, since some of the variants studied might predict the phenotype and the overall response to treatment.
Comparative Analysis of Lifetime Suicide Attempts among Mexican Adolescents, over the Past 12 Years
Authors: Valdez-Santiago Rosario , Villalobos Aremis , Arenas-Monreal Luz , González-Forteza Catalina , Hermosillo-de-la-Torre Alicia Edith , Benjet Corina , Wagner Fernando A.
Published: May 2021

Objective. To compare the occurrence of suicide attempts across nationally representative samples of the Mexican adolescent population over the past 12 years, and to analyze its association with sociodemographic, lifestyle and mental-health indicators. Methodology. Data were drawn from the 2006, 2012 and 2018 National Health and Nutrition Surveys (n = 25,056; 21,509; and 17,925 adolescents, respectively). Estimates were based on standardized measurements. Results. The estimated lifetime prevalence rates of suicide attempts were 1.1% in 2006, 2.7% in 2012, and 3.9% in 2018, indicating a 3.4-fold increase. Across the three survey periods, women yielded rates nearly three times higher than men. Lifetime prevalence grew the most among adolescents aged 13–15 years. Compared to the other respondents, the odds of lifetime suicide attempts proved seven times as high for those who had been sexually abused during their childhood, five times as high for those who had been diagnosed with a depressive disorder, three times as high for those who had suffered physical aggression and twice as high for those who had smoked 100+ cigarettes in their lifetimes and those who consumed alcohol. Conclusion: The sharp increase in suicide attempts in Mexico calls for an urgent public-health response via universal and targeted interventions supported by national policy and sustained federal funding.
The Effectiveness of Environmental Taxes in Reducing CO2 Emissions in Passenger Vehicles: The Case of Mediterranean Countries
Authors: Meireles Mónica , Robaina Margarita , Magueta Daniel
Published: May 2021

The transport sector is the biggest source of CO2 emissions in Europe. It is responsible for over a quarter of all greenhouse gas emissions. Passenger vehicles, alone, account for nearly 41% of these emissions, resulting in human health impacts. To meet the Paris climate commitments, cars and vans should be decarbonized until 2050. Such a transformation requires general changes, such as how the vehicles are owned, taxed, and driven. The European Federation for Transport and Environment revealed that Mediterranean countries tend to emit less per vehicle compared to the northern and central Europeans. Intriguingly, this does not necessarily correspond to motorization rates. In this article, we assess whether the observed reductions in CO2 emissions in the Mediterranean countries can be attributed to vehicle taxation on CO2 emissions. We apply panel data econometric techniques using data on annual registrations from 2008 to 2018 and model the demand for new-vehicle purchases and their responsiveness to changes in both CO2-based taxation and circulation tax. Our results show the determinants of new-vehicle demand and the change in the emissions rate in each country under the taxation currently adopted. We found that fiscal policies can have an important role in reducing the emission in the Mediterranean countries.
Mapping the Burden of Hypertension in South Africa: A Comparative Analysis of the National 2012 SANHANES and the 2016 Demographic and Health Survey
Authors: Kandala Ngianga-Bakwin , Nnanatu Chibuzor Christopher , Dukhi Natisha , Sewpaul Ronel , Davids Adlai , Reddy Sasiragha Priscilla
Published: May 2021

This study investigates the provincial variation in hypertension prevalence in South Africa in 2012 and 2016, adjusting for individual level demographic, behavioural and socio-economic variables, while allowing for spatial autocorrelation and adjusting simultaneously for the hierarchical data structure and risk factors. Data were analysed from participants aged ≥15 years from the South African National Health and Nutrition Examination Survey (SANHANES) 2012 and the South African Demographic and Health Survey (DHS) 2016. Hypertension was defined as blood pressure ≥ 140/90 mmHg or self-reported health professional diagnosis or on antihypertensive medication. Bayesian geo-additive regression modelling investigated the association of various socio-economic factors on the prevalence of hypertension across South Africa’s nine provinces while controlling for the latent effects of geographical location. Hypertension prevalence was 38.4% in the SANHANES in 2012 and 48.2% in the DHS in 2016. The risk of hypertension was significantly high in KwaZulu-Natal and Mpumalanga in the 2016 DHS, despite being previously nonsignificant in the SANHANES 2012. In both survey years, hypertension was significantly higher among males, the coloured population group, urban participants and those with self-reported high blood cholesterol. The odds of hypertension increased non-linearly with age, body mass index (BMI), waist circumference. The findings can inform decision making regarding the allocation of public resources to the most affected areas of the population.
Hypovitaminosis D in Young Basketball Players: Association with Jumping and Hopping Performance Considering Gender
Authors: Ricart Borja , Monteagudo Pablo , Blasco-Lafarga Cristina
Published: May 2021

This study aimed to verify whether a group of young well-trained basketball players presented deficiencies in vitamin D concentration, and to analyze whether there was an association between vitamin D concentration and jumping and hopping performance. Gender differences were considered. Twenty-seven players from an international high-level basketball club (14 female, 16.00 ± 0.55 years; 13 male, 15.54 ± 0.52 years) participated in this cross-sectional study. Rate of force development was evaluated by means of the Abalakov test (bilateral: AbB; right leg: AbR; left leg: AbL); and the triple hop test (right leg: THR; left leg: THL). Blood samples were collected for the determination of serum 25-hydroxyvitamin D and nutritional status. Vitamin D insufficiency was found in both women (29.14 ± 6.08 ng/mL) and men (28.92 ± 6.40 ng/mL), with no gender differences regarding nutritional scores. Jumping and hopping performance was confirmed to be significantly larger in males (AbL, THR, and THL p < 0.005), whose CV% were always smaller. A positive correlation was found between AbB and vitamin D (r = 0.703) in males, whereas this correlation was negative (−0.611) for females, who also presented a negative correlation (r = −0.666) between THR and vitamin D. A prevalence of hypovitaminosis D was confirmed in young elite athletes training indoors. Nutritional (i.e., calciferol) controls should be conducted throughout the season. Furthermore, whilst performance seems to be affected by low levels of this vitamin in men, these deficiencies appear to have a different association with jumping and hopping in women, pointing to different performance mechanisms. Further studies accounting for differences in training and other factors might delve into these gender differences.
Effect of Psychophysiological Stress and Socio-Emotional Competencies on the Clinical Performance of Nursing Students during a Simulation Practice
Authors: Mauriz Elba , Caloca-Amber Sandra , Córdoba-Murga Lucía , Vázquez-Casares Ana María
Published: May 2021

Psychophysiological stress can affect the cognitive response and effective learning of students during medical simulation practices. This study aimed to explore the effect of psychophysiological stress and socio-emotional competencies on clinical performance during a simulation experience. A pre-test/post-test design was used to assess physiological (blood pressure, heart rate and blood oxygen saturation) and psychological parameters (stress and anxiety) as well as socio-emotional skills (cognitive load, self-efficacy and motivation) in nursing students (n = 40) before and after the simulation of a cardiopulmonary resuscitation practice. Physiological responses showed statistically significant differences between pre-test and post-test conditions for blood pressure and heart rate (p < 0.0001). Moderate and significant correlations were also observed when comparing self-efficacy with stress (r = −0.445, p = 0.004), anxiety (r = −0.467, p = 0.002) and motivation (r = −0.406, p = 0.009) measures. Similarly, cognitive-load dimensions were significantly associated with either physiological (r = −0.335, p = 0.034) or psychological (r = −0.448, p = 0.004) indicators. The analysis of multiple regression models revealed a relationship between the effectiveness of the simulated experience, post-test blood oxygen saturation, heart rate, workload and self-efficacy (R2 = 0.490; F (3, 39) = 8.305; p < 0.0001; d = 1.663). Therefore, the evaluation of psychophysiological parameters and socio-emotional skills seems to provide a promising framework for predicting the quality of simulated clinical practices.
Lifestyle and Sociodemographic Parameters Associated with Mental and Physical Health during COVID-19 Confinement in Three Ibero-American Countries. A Cross-Sectional Pilot Study
Authors: Gutiérrez-Pérez Ilse , Delgado-Floody Pedro , Jerez-Mayorga Daniel , Soto-García Diego , Caamaño-Navarrete Felipe , Parra-Rojas Isela , Molina-Gutiérrez Nacim , Guzmán-Guzmán Iris
Published: May 2021

Background: The aim of the present study was to determine the association between the health-related quality of life (HRQoL) with sociodemographic parameters and lifestyle during COVID-19 confinement in Mexico, Chile, and Spain. Methods: A cross-sectional pilot study, with 742 observations of online surveys in 422, 190, and 130 individuals from Mexico, Chile, and Spain, respectively. Sociodemographic data, presence of comorbidities, food habits, and physical activity (PA) patterns were evaluated. The HRQoL was evaluated according to the SF-36 Health Survey. The multilinear regression analysis was developed to determine the association of variables with HRQoL and its physical and mental health dimensions. Results: The female sex in the three countries reported negative association with HRQoL (Mexico: β −4.45, p = 0.004; Chile: β −8.48, p < 0.001; Spain: β −6.22, p = 0.009). Similarly, bad eating habits were associated negatively with HRQoL (Mexico: β −6.64, p < 0.001; Chile: β −6.66, p = 0.005; Spain: β −5.8, p = 0.032). In Mexico, PA limitations presented a negative association with HRQoL (β −4.71, p = 0.011). In Chile, a sedentary lifestyle (h/day) was linked negatively with HRQoL (β −0.64, p = 0.005). In Spain, the highest associations with HRQoL were the presence of comorbidity (β −11.03, p < 0.001) and smoking (β −6.72, p = 0.02). Moreover, the PA limitation in Mexico (β −5.67, p = 0.023) and Chile (β −9.26, p = 0.035) was linked negatively with mental health. Conclusions: The bad eating habits, PA limitations, female sex, comorbidity presence, and smoking were parameters linked negatively with HRQoL.
Essential Role of CRIM1 on Endometrial Receptivity in Goat
Authors: Yang Diqi , Liu Ai , Zhang Yanyan , Nan Sha , Yin Ruiling , Lei Qianghui , Zhu Hongmei , Chen Jianguo , Han Li , Ding Mingxing , Ding Yi
Published: May 2021

In domestic ruminants, endometrial receptivity is related to successful pregnancy and economic efficiency. Despite several molecules having been reported in the past regarding endometrial receptivity regulation, much regarding the mechanism of endometrial receptivity regulation remains unknown due to the complex nature of the trait. In this work, we demonstrated that the cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1 (CRIM1) served as a novel regulator in the regulation of goat endometrial receptivity in vitro. Our results showed that hormones and IFN-τ increased the expression of CRIM1 in goat endometrial epithelial cells (EECs). Knockdown of CRIM1 via specific shRNA hindered cell proliferation, cell adhesion and prostaglandins (PGs) secretion and thus derailed normal endometrial receptivity. We further confirmed that receptivity defect phenotypes due to CRIM1 interference were restored by ATG7 overexpression in EECs while a loss of ATG7 further impaired receptivity phenotypes. Moreover, our results showed that changing the expression of ATG7 affected the reactive oxygen species (ROS) production. Moreover, mR-143-5p was shown to be a potential upstream factor of CRIM1-regulated endometrial receptivity in EECs. Overall, these results suggest that CRIM1, as the downstream target of miR-143-5p, has effects on ATG7-dependent autophagy, regulating cell proliferation, cell adhesion and PG secretion, and provides a new target for the diagnosis and treatment of early pregnancy failure and for improving the success rates of artificial reproduction.
The Role of ZEB2 in Human CD8 T Lymphocytes: Clinical and Cellular Immune Profiling in Mowat–Wilson Syndrome
Authors: Frith Katie , Munier C. Mee Ling , Hastings Lucy , Mowat David , Wilson Meredith , Seddiki Nabila , Macintosh Rebecca , Kelleher Anthony D. , Gray Paul , Zaunders John James
Published: May 2021

The Zeb2 gene encodes a transcription factor (ZEB2) that acts as an important immune mediator in mice, where it is expressed in early-activated effector CD8 T cells, and limits effector differentiation. Zeb2 homozygous knockout mice have deficits in CD8 T cells and NK cells. Mowat–Wilson syndrome (MWS) is a rare genetic disease resulting from heterozygous mutations in ZEB2 causing disease by haploinsufficiency. Whether ZEB2 exhibits similar expression patterns in human CD8 T cells is unknown, and MWS patients have not been comprehensively studied to identify changes in CD8 lymphocytes and NK cells, or manifestations of immunodeficiency. By using transcriptomic assessment, we demonstrated that ZEB2 is expressed in early-activated effector CD8 T cells of healthy human volunteers following vaccinia inoculation and found evidence of a role for TGFß-1/SMAD signaling in these cells. A broad immunological assessment of six genetically diagnosed MWS patients identified two patients with a history of recurrent sinopulmonary infections, one of whom had recurrent oral candidiasis, one with lymphopenia, two with thrombocytopenia and three with detectable anti-nuclear antibodies. Immunoglobulin levels, including functional antibody responses to protein and polysaccharide vaccination, were normal. The MWS patients had a significantly lower CD8 T cell subset as % of lymphocytes, compared to healthy controls (median 16.4% vs. 25%, p = 0.0048), and resulting increased CD4:CD8 ratio (2.6 vs. 1.8; p = 0.038). CD8 T cells responded normally to mitogen stimulation in vitro and memory CD8 T cells exhibited normal proportions of subsets with important tissue-specific homing markers and cytotoxic effector molecules. There was a trend towards a decrease in the CD8 T effector memory subset (3.3% vs. 5.9%; p = 0.19). NK cell subsets were normal. This is the first evidence that ZEB2 is expressed in early-activated human effector CD8 T cells, and that haploinsufficiency of ZEB2 in MWS patients had a slight effect on immune function, skewing T cells away from CD8 differentiation. To date there is insufficient evidence to support an immunodeficiency occurring in MWS patients.
A Keratin 7 and E-Cadherin Signature Is Highly Predictive of Tubo-Ovarian High-Grade Serous Carcinoma Prognosis
Authors: Communal Laudine , Roy Noemi , Cahuzac Maxime , Rahimi Kurosh , Köbel Martin , Provencher Diane M. , Mes-Masson Anne-Marie
Published: May 2021

During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard epithelial markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, KRT19 were quantified in 18 HGSC cell lines by Western blot and in a Discovery cohort tissue microarray (TMA) (n = 101 patients) using immunofluorescence. E-CADH and KRT7 levels were subsequently analyzed in the TMA of the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n = 1158 patients) and in public datasets. Epithelial marker expression was highly variable in HGSC cell lines and tissues. In the Discovery cohort, high levels of KRT7 and KRT19 were associated with an unfavorable prognosis, whereas high E-CADH expression indicated a better outcome. Expression of KRT7 and E-CADH gave a robust combination to predict overall survival (OS, p = 0.004) and progression free survival (PFS, p = 5.5 × 10−4) by Kaplan–Meier analysis. In the COEUR cohort, the E-CADH-KRT7 signature was a strong independent prognostic biomarker (OS, HR = 1.6, p = 2.9 × 10−4; PFS, HR = 1.3, p = 0.008) and predicted a poor patient response to chemotherapy (p = 1.3 × 10−4). Our results identify a combination of two epithelial markers as highly significant indicators of HGSC patient prognosis and treatment response.
Epigenetic DNA Methylation of EBI3 Modulates Human Interleukin-35 Formation via NFkB Signaling: A Promising Therapeutic Option in Ulcerative Colitis
Authors: Wetzel Alexandra , Scholtka Bettina , Schumacher Fabian , Rawel Harshadrai , Geisendörfer Birte , Kleuser Burkhard
Published: May 2021

Ulcerative colitis (UC), a severe chronic disease with unclear etiology that is associated with increased risk for colorectal cancer, is accompanied by dysregulation of cytokines. Epstein–Barr virus-induced gene 3 (EBI3) encodes a subunit in the unique heterodimeric IL-12 cytokine family of either pro- or anti-inflammatory function. After having recently demonstrated that upregulation of EBI3 by histone acetylation alleviates disease symptoms in a dextran sulfate sodium (DSS)-treated mouse model of chronic colitis, we now aimed to examine a possible further epigenetic regulation of EBI3 by DNA methylation under inflammatory conditions. Treatment with the DNA methyltransferase inhibitor (DNMTi) decitabine (DAC) and TNFα led to synergistic upregulation of EBI3 in human colon epithelial cells (HCEC). Use of different signaling pathway inhibitors indicated NFκB signaling was necessary and proportional to the synergistic EBI3 induction. MALDI-TOF/MS and HPLC-ESI-MS/MS analysis of DAC/TNFα-treated HCEC identified IL-12p35 as the most probable binding partner to form a functional protein. EBI3/IL-12p35 heterodimers (IL-35) induce their own gene upregulation, something that was indeed observed in HCEC cultured with media from previously DAC/TNFα-treated HCEC. These results suggest that under inflammatory and demethylating conditions the upregulation of EBI3 results in the formation of anti-inflammatory IL-35, which might be considered as a therapeutic target in colitis.
Ablation of Selenbp1 Alters Lipid Metabolism via the Pparα Pathway in Mouse Kidney
Authors: Song Yingxia , Kurose Atsushi , Li Renshi , Takeda Tomoki , Onomura Yuko , Koga Takayuki , Mutoh Junpei , Ishida Takumi , Tanaka Yoshitaka , Ishii Yuji
Published: May 2021

Selenium-binding protein 1 (Selenbp1) is a 2,3,7,8-tetrechlorodibenzo-p-dioxin inducible protein whose function is yet to be comprehensively elucidated. As the highly homologous isoform, Selenbp2, is expressed at low levels in the kidney, it is worthwhile comparing wild-type C57BL mice and Selenbp1-deficient mice under dioxin-free conditions. Accordingly, we conducted a mouse metabolomics analysis under non-dioxin-treated conditions. DNA microarray analysis was performed based on observed changes in lipid metabolism-related factors. The results showed fluctuations in the expression of numerous genes. Real-time RT-PCR confirmed the decreased expression levels of the cytochrome P450 4a (Cyp4a) subfamily, known to be involved in fatty acid ω- and ω-1 hydroxylation. Furthermore, peroxisome proliferator-activated receptor-α (Pparα) and retinoid-X-receptor-α (Rxrα), which form a heterodimer with Pparα to promote gene expression, were simultaneously reduced. This indicated that reduced Cyp4a expression was mediated via decreased Pparα and Rxrα. In line with this finding, increased levels of leukotrienes and prostaglandins were detected. Conversely, decreased hydrogen peroxide levels and reduced superoxide dismutase (SOD) activity supported the suppression of the renal expression of Sod1 and Sod2 in Selenbp1-deficient mice. Therefore, we infer that ablation of Selenbp1 elicits oxidative stress caused by increased levels of superoxide anions, which alters lipid metabolism via the Pparα pathway.
Contribution of Syndecans to the Cellular Entry of SARS-CoV-2
Authors: Hudák Anett , Letoha Annamária , Szilák László , Letoha Tamás
Published: May 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel emerging pathogen causing an unprecedented pandemic in 21st century medicine. Due to the significant health and economic burden of the current SARS-CoV-2 outbreak, there is a huge unmet medical need for novel interventions effectively blocking SARS-CoV-2 infection. Unknown details of SARS-CoV-2 cellular biology hamper the development of potent and highly specific SARS-CoV-2 therapeutics. Angiotensin-converting enzyme-2 (ACE2) has been reported to be the primary receptor for SARS-CoV-2 cellular entry. However, emerging scientific evidence suggests the involvement of additional membrane proteins, such as heparan sulfate proteoglycans, in SARS-CoV-2 internalization. Here, we report that syndecans, the evolutionarily conserved family of transmembrane proteoglycans, facilitate the cellular entry of SARS-CoV-2. Among syndecans, the lung abundant syndecan-4 was the most efficient in mediating SARS-CoV-2 uptake. The S1 subunit of the SARS-CoV-2 spike protein plays a dominant role in the virus’s interactions with syndecans. Besides the polyanionic heparan sulfate chains, other parts of the syndecan ectodomain, such as the cell-binding domain, also contribute to the interaction with SARS-CoV-2. During virus internalization, syndecans colocalize with ACE2, suggesting a jointly shared internalization pathway. Both ACE2 and syndecan inhibitors exhibited significant efficacy in reducing the cellular entry of SARS-CoV-2, thus supporting the complex nature of internalization. Data obtained on syndecan specific in vitro assays present syndecans as novel cellular targets of SARS-CoV-2 and offer molecularly precise yet simple strategies to overcome the complex nature of SARS-CoV-2 infection.
Solvent-Induced Formation of Novel Ni(II) Complexes Derived from Bis-Thiosemicarbazone Ligand: An Insight from Experimental and Theoretical Investigations
Authors: Mahmoudi Ghodrat , Babashkina Maria , Maniukiewicz Waldemar , Afkhami Farhad , Nunna Bharath , Zubkov Fedor , Ptaszek Aleksandra , Szczepanik Dariusz , Mitoraj Mariusz , Safin Damir
Published: May 2021

In this work, we report solvent-induced complexation properties of a new N2S2 tetradentate bis-thiosemicarbazone ligand (H2LI), prepared by the condensation of 4-phenylthiosemicarbazide with bis-aldehyde, namely 2,2’-(ethane-1,2-diylbis(oxy)dibenzaldehyde, towards nickel(II). Using ethanol as a reaction medium allowed the isolation of a discrete mononuclear homoleptic complex [NiLI] (1), for which its crystal structure contains three independent molecules, namely 1-I, 1-II, and 1-III, in the asymmetric unit. The doubly deprotonated ligand LI in the structure of 1 is coordinated in a cis-manner through the azomethine nitrogen atoms and the thiocarbonyl sulfur atoms. The coordination geometry around metal centers in all the three crystallographically independent molecules of 1 is best described as the seesaw structure. Interestingly, using methanol as a reaction medium in the same synthesis allowed for the isolation of a discrete mononuclear homoleptic complex [Ni(LII)2] (2), where LII is a monodeprotonated ligand 2-(2-(2-(2-(dimethoxymethyl)phenoxy)ethoxy)benzylidene)-N-phenylhydrazine-1-carbothioamide (HLII). The ligand LII was formed in situ from the reaction of LI with methanol upon coordination to the metal center under synthetic conditions. In the structure of 2, two ligands LII are coordinated in a trans-manner through the azomethine nitrogen atom and the thiocarbonyl sulfur atom, also yielding a seesaw coordination geometry around the metal center. The charge and energy decomposition scheme ETS-NOCV allows for the conclusion that both structures are stabilized by a bunch of London dispersion-driven intermolecular interactions, including predominantly N–H∙∙∙S and N–H∙∙∙O hydrogen bonds in 1 and 2, respectively; they are further augmented by less typical C–H∙∙∙X (where X = S, N, O, π), CH∙∙∙HC, π∙∙∙π stacking and the most striking, attractive long-range intermolecular C–H∙∙∙Ni preagostic interactions. The latter are found to be determined by both stabilizing Coulomb forces and an exchange-correlation contribution as revealed by the IQA energy decomposition scheme. Interestingly, the analogous long-range C–H∙∙∙S interactions are characterized by a repulsive Coulomb contribution and the prevailing attractive exchange-correlation constituent. The electron density of the delocalized bonds (EDDB) method shows that the nickel(II) atom shares only ~0.8|e| due to the σ-conjugation with the adjacent in-plane atoms, demonstrating a very weak σ-metalloaromatic character.
Exposure to RF-EMF Alters Postsynaptic Structure and Hinders Neurite Outgrowth in Developing Hippocampal Neurons of Early Postnatal Mice
Authors: Kim Ju Hwan , Chung Kyung Hwun , Hwang Yeong Ran , Park Hye Ran , Kim Hee Jung , Kim Hyung-Gun , Kim Hak Rim
Published: May 2021

Exposure to radiofrequency electromagnetic fields (RF-EMFs) has increased rapidly in children, but information on the effects of RF-EMF exposure to the central nervous system in children is limited. In this study, pups and dams were exposed to whole-body RF-EMF at 4.0 W/kg specific absorption rate (SAR) for 5 h per day for 4 weeks (from postnatal day (P) 1 to P28). The effects of RF-EMF exposure on neurons were evaluated by using both pups’ hippocampus and primary cultured hippocampal neurons. The total number of dendritic spines showed statistically significant decreases in the dentate gyrus (DG) but was not altered in the cornu ammonis (CA1) in hippocampal neurons. In particular, the number of mushroom-type dendritic spines showed statistically significant decreases in the CA1 and DG. The expression of glutamate receptors was decreased in mushroom-type dendritic spines in the CA1 and DG of hippocampal neurons following RF-EMF exposure. The expression of brain-derived neurotrophic factor (BDNF) in the CA1 and DG was significantly lower statistically in RF-EMF-exposed mice. The number of post-synaptic density protein 95 (PSD95) puncta gradually increased over time but was significantly decreased statistically at days in vitro (DIV) 5, 7, and 9 following RF-EMF exposure. Decreased BDNF expression was restricted to the soma and was not observed in neurites of hippocampal neurons following RF-EMF exposure. The length of neurite outgrowth and number of branches showed statistically significant decreases, but no changes in the soma size of hippocampal neurons were observed. Further, the memory index showed statistically significant decreases in RF-EMF-exposed mice, suggesting that decreased synaptic density following RF-EMF exposure at early developmental stages may affect memory function. Collectively, these data suggest that hindered neuronal outgrowth following RF-EMF exposure may decrease overall synaptic density during early neurite development of hippocampal neurons.
Delivery Systems of Retinoprotective Proteins in the Retina
Authors: Rebustini Ivan T. , Bernardo-Colón Alexandra , Nalvarte Alejandra Isasi , Becerra S. Patricia
Published: May 2021

Retinoprotective proteins play important roles for retinal tissue integrity. They can directly affect the function and the survival of photoreceptors, and/or indirectly target the retinal pigment epithelium (RPE) and endothelial cells that support these tissues. Retinoprotective proteins are used in basic, translational and in clinical studies to prevent and treat human retinal degenerative disorders. In this review, we provide an overview of proteins that protect the retina and focus on pigment epithelium-derived factor (PEDF), and its effects on photoreceptors, RPE cells, and endothelial cells. We also discuss delivery systems such as pharmacologic and genetic administration of proteins to achieve photoreceptor survival and retinal tissue integrity.
Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity
Authors: Chou Ching-Hsuan , Yang Chia-Ron
Published: May 2021

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease, and it manifests as progressive memory loss and cognitive decline. However, there are no effective therapies for AD, which is an urgent problem to solve. Evodiamine, one of the main bioactive ingredients of Evodia rutaecarpa, has been reported to ameliorate blood–brain barrier (BBB) permeability and improve cognitive impairment in ischemia and AD mouse models. However, whether evodiamine alleviates tauopathy remains unclear. This study aimed to examine whether evodiamine ameliorates tau phosphorylation and cognitive deficits in AD models. Methods: A protein phosphatase 2A inhibitor, okadaic acid (OA), was used to induce tau phosphorylation to mimic AD-like models in neuronal cells. Protein expression and cell apoptosis were detected using Western blotting and flow cytometry, respectively. Spatial memory/cognition was assessed using water maze, passive avoidance tests, and magnetic resonance imaging assay in OA-induced mice models, and brain slices were evaluated further by immunohistochemistry. Results: The results showed that evodiamine significantly reduced the expression of phosphor-tau, and further decreased tau aggregation and neuronal cell death in response to OA treatment. This inhibition was found to be via the inhibition of glycogen synthase kinase 3β, cyclin-dependent kinase 5, and mitogen-activated protein kinase pathways. In vivo results indicated that evodiamine treatment ameliorated learning and memory impairments in mice, whereas Western blotting and immunohistochemical analysis of the mouse brain also confirmed the neuroprotective effects of evodiamine. Conclusions: Evodiamine can decrease the neurotoxicity of tau aggregation and exhibit a neuroprotective effect. Our results demonstrate that evodiamine has a therapeutic potential for AD treatment.
Genome-Wide Characterization of WRKY Transcription Factors Revealed Gene Duplication and Diversification in Populations of Wild to Domesticated Barley
Authors: Kan Jinhong , Gao Guangqi , He Qiang , Gao Qian , Jiang Congcong , Ahmar Sunny , Liu Jun , Zhang Jing , Yang Ping
Published: May 2021

The WRKY transcription factors (WRKYs) are known for their crucial roles in biotic and abiotic stress responses, and developmental and physiological processes. In barley, early studies revealed their importance, whereas their diversity at the population scale remains hardly estimated. In this study, 98 HsWRKYs and 103 HvWRKYs have been identified from the reference genome of wild and cultivated barley, respectively. The tandem duplication and segmental duplication events from the cultivated barley were observed. By taking advantage of early released exome-captured sequencing datasets in 90 wild barley accessions and 137 landraces, the diversity analysis uncovered synonymous and non-synonymous variants instead of loss-of-function mutations that had occurred at all WRKYs. For majority of WRKYs, the haplotype and nucleotide diversity both decreased in cultivated barley relative to the wild population. Five WRKYs were detected to have undergone selection, among which haplotypes of WRKY9 were enriched, correlating with the geographic collection sites. Collectively, profiting from the state-of-the-art barley genomic resources, this work represented the characterization and diversity of barley WRKY transcription factors, shedding light on future deciphering of their roles in barley domestication and adaptation.
Suppression of NtZIP4A/B Changes Zn and Cd Root-to-Shoot Translocation in a Zn/Cd Status-Dependent Manner
Authors: Maślińska-Gromadka Karolina , Barabasz Anna , Palusińska Małgorzata , Kozak Katarzyna , Antosiewicz Danuta Maria
Published: May 2021

In tobacco, the efficiency of Zn translocation to shoots depends on Zn/Cd status. Previous studies pointed to the specific contribution of root parts in the regulation of this process, as well as the role of NtZIP4A/B (from the ZIP family; Zrt Irt-like Proteins). Here, to verify this hypothesis, NtZIP4A/B RNAi lines were generated. Then, in plants exposed to combinations of Zn and Cd concentrations in the medium, the consequences of NtZIP4A/B suppression for the translocation of both metals were determined. Furthermore, the apical, middle, and basal root parts were examined for accumulation of both metals, for Zn localization (using Zinpyr-1), and for modifications of the expression pattern of ZIP genes. Our results confirmed the role of NtZIP4A/B in the control of Zn/Cd-status-dependent transfer of both metals to shoots. Furthermore, they indicated that the middle and basal root parts contributed to the regulation of this process by acting as a reservoir for excess Zn and Cd. Expression studies identified several candidate ZIP genes that interact with NtZIP4A/B in the root in regulating Zn and Cd translocation to the shoot, primarily NtZIP1-like in the basal root part and NtZIP2 in the middle one.
The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review
Authors: Reginato Andressa , Veras Alana Carolina Costa , Baqueiro Mayara da Nóbrega , Panzarin Carolina , Siqueira Beatriz Piatezzi , Milanski Marciane , Lisboa Patrícia Cristina , Torsoni Adriana Souza
Published: May 2021

Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition to targets for the development of new drugs that can be used in humans to decrease body weight. Recently, sphingolipids were described as having a lipotoxic effect in peripheral tissues and the central nervous system. Specifically, lipid overload, mainly from long-chain saturated fatty acids, such as palmitate, leads to excessive ceramide levels that can be sensed by the hypothalamus, triggering the dysregulation of energy balance control. However, no systematic review has been undertaken regarding studies of sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), the hypothalamus, and obesity. This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. However, in contrast to ceramide, S1P appears to be a central satiety factor in the hypothalamus. Thus, our work describes current evidence related to sphingolipids and their role in hypothalamic energy balance control. Hypothetically, the manipulation of sphingolipid levels could be useful in enabling clinicians to treat obesity, particularly by decreasing ceramide levels and the inflammation/endoplasmic reticulum stress induced in response to overfeeding with saturated fatty acids.