bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Rolling Abilities in Primary School Children: Physical Education Specialists vs. Generalists
Authors: Invernizzi Pietro Luigi , Signorini Gabriele , Colella Dario , Raiola Gaetano , Bosio Andrea , Scurati Raffaele
Published: November 2020

Teaching physical education requires competencies to conduct the classes and to assess the motor skills of practitioners. Specialists (physical education professionals) and generalists (primary school teachers) differently experienced motor tasks during their academic education. This study aimed to compare the teachers’ ability in assessing the children’s forward and backward rolls from the analysis of the reliability of an evaluation grid of rolling abilities (Information Scale for Agility on the Soil, InfoSAS), which was investigated in a first study with teachers. A second study in young children explored the responsiveness of the InfoSAS to discriminate by skill level or by training effects. When administered by specialists, the InfoSAS resulted in being reliable (forward: p = 0.087 and p = 0.908; backward: p = 0.926 and p = 0.910; intra- and inter-rater reliability, respectively) and responsive in detecting differences due to expertise (gymnasts vs. primary school children; forward: p = 0.003, backward: p = 0.016) or improvements after specific training in rolling (pre- vs. post-children’s training; forward: p = 0.005, backward: p = 0.001). The results support the conclusion that specialists exhibit higher competence than generalists, which allows proper application of the InfoSAS, possibly because of the practice of skills and reflective teaching styles in physical activity they experienced, along with their academic education in sport sciences.
Estimating the Combined Effects of Natural and Built Environmental Exposures on Birthweight among Urban Residents in Massachusetts
Authors: Yitshak-Sade Maayan , Fabian M. Patricia , Lane Kevin J. , Hart Jaime E. , Schwartz Joel D. , Laden Francine , James Peter , Fong Kelvin C. , Kloog Itai , Zanobetti Antonella
Published: November 2020

Intrauterine growth has health implications both in childhood and adulthood. Birthweight is partially determined by prenatal environmental exposures. We aim to identify important predictors of birthweight out of a set of environmental, built environment exposures, and socioeconomic environment variables during pregnancy (i.e., fine particulate matter (PM2.5), temperature, greenness, walkability, noise, and economic indices). We included all singleton live births of mothers who resided in urban census block-groups and delivered in Massachusetts between 2001 and 2011 (n = 640,659). We used an elastic-net model to select important predictors of birthweight and constructed a multivariate model including the selected predictors, with adjustment for confounders. We additionally used a weighted quantile sum regression to assess the contribution of each exposure to differences in birthweight. All exposures were selected as important predictors of birthweight. In the multivariate model, lower birthweight was significantly associated with lower greenness and with higher temperature, walkability, noise, and segregation of the “high income” group. Treating the exposures individually, nighttime noise had the highest weight in its contribution to lower birthweight. In conclusion, after accounting for individual confounders, maternal environmental exposures, built environment exposures, and socioeconomic environment during pregnancy were important predictors of birthweight, emphasizing the role of these exposures in fetal growth and development.
Prevalence of Workplace Sexual Violence against Healthcare Workers Providing Home Care: A Systematic Review and Meta-Analysis
Authors: Clari Marco , Conti Alessio , Scacchi Alessandro , Scattaglia Marco , Dimonte Valerio , Gianino Maria Michela
Published: November 2020

This systematic review and meta-analysis sought to explore the prevalence of sexual violence including both sexual harassment and abuse, perpetrated by clients against home healthcare workers (HCWs), including professional and paraprofessional HCWs. To this end, we systematically searched five relevant databases. Two reviewers extracted data from the included studies independently and performed a quality appraisal. Overall and subgroup random-effects pooled prevalence meta-analyses were performed. Due to high heterogeneity, a more robust model using a quality effect estimator was used. Fourteen studies were included, and the prevalence of sexual violence was 0.06 (95% confidence interval (CI): 0.01–0.13). Paraprofessionals had a higher prevalence of sexual violence (0.07, 95% CI: 0.00–0.18 vs. 0.05, 95% CI: 0.00–0.12), and the prevalence of sexual abuse was lower than that of sexual harassment (0.04, 95% CI: 0.00–0.10 vs. 0.10, 95% CI: 0.03–0.18). This systematic review estimated the prevalence of sexual violence across home HCWs from different high-income countries, highlighting the presence of this phenomenon to a lesser but nevertheless considerable extent compared to other healthcare settings. Health management should consider interventions to prevent and reduce the risk of home HCWs from being subjected to sexual violence, as the home-care sector presents particular risks for HCWs because clients’ homes expose them to a relatively uncontrolled work environment.
Sexuality in Patients with Hidradenitis Suppurativa: Beliefs, Behaviors and Needs
Authors: Cuenca-Barrales Carlos , Molina-Leyva Alejandro
Published: November 2020

Little is known about the impact of hidradenitis suppurativa (HS) on patients’ sexuality. The aim of this research is to investigate the impact of HS on several previously unexplored aspects of sexuality. In March 2018, we conducted a crowd-sourced cross-sectional online survey hosted by the Spanish association of patients with HS (ASENDHI) and available in Spanish. A panel of experts and patients from ASENDHI designed various questions in order to explore the extent to which HS influenced participants’ sex lives. The final sample consisted of 386 participants, 79.27% (306/386) of which were women and 20.73% (80/306) of which were men. Seventy-seven point one percent (236/306) of women and 67.5% (54/80) of men were in stable relationships; the rest of the participants were single. Forty-seven point nine percent (185/386) admitted to feeling fear of rejection. Pain was the symptom that most interfered with sexual relations in women and suppuration in men. Forty-four point three percent (171/386) of the participants considered themselves to be less attractive than average. Considering the participants in a stable relationship, women described receiving more emotional support from their partners, while men received more help with lesion dressing in intimate areas. Seventy-one point four percent (207/290) of participants stated that HS negatively affected their relationship. Among single patients, women experienced greater fear of rejection and were less willing to meet new people because of HS. Ninety-four point three percent (66/70) of women and 80.8% (21/26) of men stated that HS had a negative influence on their chances of having a relationship or sexual relations. In conclusion, HS has a significant, unrecognized and misunderstood impact on sexuality which must be addressed.
In Vitro and In Vivo Effects of Fermented Oyster-Derived Lactate on Exercise Endurance Indicators in Mice
Authors: Reid Storm N. S. , Park Joung-Hyun , Kim Yunsook , Kwak Yi Sub , Jeon Byeong Hwan
Published: November 2020

Exogenous lactate administration has more recently been investigated for its various prophylactic effects. Lactate derived from potential functional foods, such as fermented oyster extract (FO), may emerge as a practical and effective method of consuming exogenous lactate. The current study endeavored to ascertain whether the lactate derived from FO may act on muscle cell biology, and to what extent this may translate into physical fitness improvements. We examined the effects of FO in vitro and in vivo, on mouse C2C12 cells and exercise performance indicators in mice, respectively. In vitro, biochemical analysis was carried out to determine the effects of FO on lactate content and muscle cell energy metabolism, including adenosine triphosphate (ATP) activity. Western blot analysis was also utilized to measure the protein expression of total adenosine monophosphate-activated protein kinase (AMPK), p-AMPK (Thr172), lactate dehydrogenase (LDH), succinate dehydrogenase (SDHA) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in response to FO administration. Three experimental groups were formed: a positive control (PC) treated with 1% horse serum, FO10 treated with 10 μg/mL and FO50 treated with 50 μg/mL. In vivo, the effects of FO supplementation on exercise endurance were measured using the Rota-rod test, and Western blot analysis measured myosin heavy-chain 2 (MYH2) to assess skeletal muscle growth, alongside p-AMPK, total-AMPK, PGC-1α, cytochrome C and UCP3 protein expression. Biochemical analysis was also performed on muscle tissue to measure the changes in concentration of liver lactate, lactate dehydrogenase (LDH), glycogen and citrate. Five groups (n = 10/per group) consisted of a control group (CON), exercise group (Ex), positive control treated with Ex and 500 mg/kg Taurine (Ex-Tau), Ex and 100 mg/kg FO supplementation (Ex-FO100) and Ex and 200 mg/kg FO supplementation (Ex-FO200) orally administered over the 4-week experimental period.FO50 significantly increased PGC-1α expression (p < 0.001), whereas both FO10 and FO50 increased the expression of p-AMPK (p < 0.001), in C2C12 muscle cells, showing increased signaling important for mitochondrial metabolism and biogenesis. Muscle lactate levels were also significantly increased following FO10 (p < 0.05) and FO50 (p < 0.001). In vivo, muscle protein expression of p-AMPK (p < 0.05) and PGC-1α were increased, corroborating our in vitro results. Cytochrome C also significantly increased following FO200 intake. These results suggest that the effects of FO supplementation may manifest in a dose-response manner. FO administration, in vitro, and supplementation, in vivo, both demonstrate a potential for improvements in mitochondrial metabolism and biogenesis, and even for potentiating the adaptive effects of endurance exercise. Mechanistically, lactate may be an important molecule in explaining the aforementioned positive effects of FO.
Coach Burnout in Relation to Perfectionistic Cognitions and Self-Presentation
Authors: Hassmén Peter , Lundkvist Erik , Flett Gordon L. , Hewitt Paul L. , Gustafsson Henrik
Published: November 2020

Coaching athletes is highly rewarding yet stressful, especially at the elite level where media, fans, and sponsors can contribute to an environment that, if not well-managed by the coach, can lead to burnout. Coaches who display perfectionistic tendencies, such as striving for flawlessness, may be particularly vulnerable—even more so if they are overly critical of themselves and have a tendency to ruminate over their performance, or if they are attempting to convey an image of faultlessness, or both. A total of 272 coaches completed a battery of inventories assessing burnout, perfectionistic thoughts, and the tendency for perfectionistic self-presentation. All variables correlated significantly: coaches with higher scores on exhaustion scored higher both on perfectionistic thoughts and self-presentation. However, when three subscales of perfectionistic self-presentation were considered separately, lower and nonsignificant correlations emerged. We believe that this can be explained by the heterogeneous group of coaches participating in this study. Whereas all coaches may at times ruminate privately—self-oriented perfectionism—about their perceived failure to perform to expectations, not all may feel the pressure to present themselves to others as faultless—a more socially prescribed perfectionism. This finding warrants further investigation, preferably comparing coaches at different levels of public scrutiny.
Association of Internet Addiction with Family Functionality, Depression, Self-Efficacy and Self-Esteem among Early Adolescents
Authors: Chen Hsiao-Ching , Wang Jiun-Yi , Lin Ying-Lien , Yang Shang-Yu
Published: November 2020

Early adolescents usually have worse self-control and poor time management abilities. They are a higher-risk group for Internet addiction than older adolescents or adults. This study aims to explore the prevalence of Internet addiction and associated factors in early adolescents. Participants included 451 fifth and sixth-grade students in Central Taiwan. This study adopted a cross-sectional design and a structured questionnaire that consisted of demographics, Young’s Internet Addiction Test, the Centre for Epidemiological Studies-Depression scale, the General Self-Efficacy Scale and the Rosenberg Self-Esteem Scale. The participants were 50.8% male, and the mean age was 11.35, with a range of 10.33–12.92 years. A total of 33.7% of all participants were prone to Internet addiction. The results showed that participants who were male and had high money allowance, poor family atmosphere, parents who did not limit Internet usage time, high depression, low self-efficacy and low self-esteem were more prone to Internet addiction. A multiple logistic regression analysis revealed that being male, having parents who did not limit Internet usage time and higher degrees of depression were the associated factors of Internet addiction in early adolescents. The phenomenon of Internet addiction among early adolescents seems to be increasing. Improving family functionality and individual mental health may be effective ways to reduce Internet addiction.
A Moderated-Mediation Model of the Relationship between Dietary Satisfaction and Fatigue in Older Adults with Diabetes: The Role of Meal Planning and Depressive Symptoms
Authors: Kim Hyerang , Son Heesook
Published: November 2020

Little research has examined the pathways between psychological factors and fatigue in older adults with diabetes. This study explored the pathways between diet-related quality of life and depressive symptoms in predicting fatigue using a moderated-mediation model. A convenience sample of adults ≥65 years (n = 127) with diabetes completed a cross-sectional survey including measures of fatigue severity, diet-related quality of life, and depressive symptoms, and a moderated-mediation analysis assessed the relationships between them. Diet satisfaction was negatively related to fatigue, which was mediated by depressive symptoms. In the moderated-mediation model, diet satisfaction had a conditional effect on fatigue through the mediating effect of depressive symptoms, moderated by meal planning difficulty. At higher levels of perceived meal planning difficulty, lower diet satisfaction was indirectly associated with higher fatigue through depressive symptoms, but this pathway was non-significant at lower levels. Findings suggest that supportive care for diet therapy might improve psychological outcomes in older adults with diabetes, especially for those having difficulties with daily dietary practice. Meal planning difficulties in the dietary management of diabetes accompanied by low diet satisfaction may lead to negative psychological outcomes. Monitoring satisfaction and burdens associated with dietary practices could improve fatigue in this population.
Reliability of Low-Cost Near-Infrared Spectroscopy in the Determination of Muscular Oxygen Saturation and Hemoglobin Concentration during Rest, Isometric and Dynamic Strength Activity
Authors: Miranda-Fuentes Claudia , Guisado-Requena Isabel María , Delgado-Floody Pedro , Arias-Poblete Leonidas , Pérez-Castilla Alejandro , Jerez-Mayorga Daniel , Chirosa-Rios Luis Javier
Published: November 2020

Background: The objective of this study was to establish the reliability of the Humon Hex near-infrared reflectance spectroscopy (NIRS) in determining muscle oxygen saturation (SmO2) and hemoglobin concentration (Hgb) at rest and during isometric and dynamic strength exercises using a functional electromechanical dynamometer (FEMD). Methods: The SmO2 and Hgb values of sixteen healthy adults (mean ± standard deviation (SD): Age = 36.1 ± 6.4 years) were recorded at rest and during isometry (8 s), dynamic strength I (initial load of 40% of the average isometric load, with 2 kg increments until muscle failure) and dynamic strength II (same as I, but with an initial load of 40% of the maximum isometric load) activity. To evaluate the reliability in the determination of SmO2 and Hgb of this device, intraclass correlation coefficient (ICC), standard error of measurement (SEM) and coefficient of variation (CV) were obtained. Results: The main results obtained are SmO2 at rest (CV = 5.76%, SEM = 3.81, ICC = 0.90), isometric strength (CV = 3.03%, SEM = 2.08, ICC = 0.92), dynamic strength I (CV = 10.6, SEM = 7.17, ICC = 0.22) and dynamic strength II (CV = 9.69, SEM = 6.75, ICC = 0.32); Hgb at rest (CV = 1.97%, SEM = 0.24, ICC = 0.65), isometric strength (CV = 0.98%, SEM = 0.12, ICC = 0.96), dynamic strength I (CV = 3.25, SEM = 0.40, ICC = 0.54) and dynamic strength II (CV = 2.74, SEM = 0.34, ICC = 0.65). Conclusions: The study shows that Humon Hex is a reliable device to obtain SmO2 and Hgb data in healthy adult subjects at rest and during isometric strength, providing precision for measurements made with this device.
Research on Spent LiFePO4 Electric Vehicle Battery Disposal and Its Life Cycle Inventory Collection in China
Authors: Zhu Lingyun , Chen Ming
Published: November 2020

The main research direction for the disposal of spent lithium-ion batteries is focused on the recovery of precious metals. However, few studies exist on the recycling of LiFePO4 electric vehicle (EV) batteries because of their low recycling value. In addition, a detailed life cycle inventory (LCI) of waste plays a significant role in its life cycle assessment (LCA) for an environmental perspective. In this study, an end-of-life (EOL) LiFePO4 EV battery is disposed to achieve the LCI result. The approach comprises manual dismantling of the battery pack/module and crushing and pyrolysis of cells. The authors classify the dismantling results and use different disposal methods, such as recycling or incineration. Regarding the environmental emissions during pyrolysis, the authors record and evaluate the results according to the experimental data, the bill of materials (BOM), the mass conservation, and the chemical reaction equations. In addition, the electricity power demand is related to the electricity mix in China, and the waste gases and solid residue are treated by using neutralization and landfill, respectively. Finally, the authors integrate the LCI data with analysis data and a background database (Ecoinvent). After the integration of the total emission and consumption data, the authors obtained the total detailed LCI resulting from the disposal of the LiFePO4 vehicle battery. This LCI mainly includes the consumption of energy and materials, and emissions to air, water, and soil, which can provide the basis for the future LCA of LiFePO4 (LFP) batteries. Furthermore, the potential of industrial scale process research on the disposal of spent LiFePO4 batteries is discussed.
Evaluating Fertilizer Use Efficiency and Spatial Correlation of Its Determinants in China: A Geographically Weighted Regression Approach
Authors: Bai Xiuguang , Zhang Tianwen , Tian Shujuan
Published: November 2020

Improving fertilizer use efficiency (FUE) is an effective means to reduce fertilizer use and environmental contamination. Few studies have considered the spatial effects of FUE and its determinants. This paper calculated the FUE of agricultural production by adopting panel data on 31 provinces in China from 2007 to 2017 using a stochastic frontier method with a heteroscedastic inefficiency term, and discussed the spatial characteristics. Further, the geographical weighted regression model (GWR) was employed to examine the spatial impact of factors on FUE and revealed the spatial dispersion and agglomeration effect. The results show that averaged FUE in China was 0.722, and had a significantly decreasing trend with a significant regional difference and spatial positive correlation in different provinces. The non-agricultural employment ratio was the leading factor for increasing FUE, and its degree of influence showed a decreasing trend from eastern to western China. The different agricultural industry development modes, crop planting patterns adjustment, labor transfer, and policy incentive systems for increasing the non-agricultural employment ratio should be developed for different regions. Farmers’ income had a negative impact on FUE, but the influence degree decreased annually. Education level had a negative impact on FUE and was relatively weak, but the influence degree was increasing. This should strengthen the exploration of a scientific and practical technical training system for farmers on fertilizer use while improving educational levels in different regions on the basis of local characteristics. The impact of disasters on FUE depended on their severity, and a combined weather and disaster forecasting mechanism should be developed.
Assessment of Human Health Risks Posed by Nano-and Microplastics Is Currently Not Feasible
Authors: Brachner Andreas , Fragouli Despina , Duarte Iola F. , Farias Patricia M. A. , Dembski Sofia , Ghosh Manosij , Barisic Ivan , Zdzieblo Daniela , Vanoirbeek Jeroen , Schwabl Philipp , Neuhaus Winfried
Published: November 2020

The exposure of humans to nano-and microplastic particles (NMPs) is an issue recognized as a potential health hazard by scientists, authorities, politics, non-governmental organizations and the general public. The concentration of NMPs in the environment is increasing concomitantly with global plastic production and the usage of plastic materials. NMPs are detectable in numerous aquatic organisms and also in human samples, therefore necessitating a risk assessment of NMPs for human health. So far, a comprehensive risk assessment of NMPs is hampered by limited availability of appropriate reference materials, analytical obstacles and a lack of definitions and standardized study designs. Most studies conducted so far used polystyrene (PS) spheres as a matter of availability, although this polymer type accounts for only about 7% of total plastic production. Differently sized particles, different concentration and incubation times, and various biological models have been used, yielding hardly comparable data sets. Crucial physico-chemical properties of NMPs such as surface (charge, polarity, chemical reactivity), supplemented additives and adsorbed chemicals have been widely excluded from studies, although in particular the surface of NMPs determines the interaction with cellular membranes. In this manuscript we give an overview about the critical parameters which should be considered when performing risk assessments of NMPs, including novel reference materials, taking into account surface modifications (e.g., reflecting weathering processes), and the possible role of NMPs as a substrate and/or carrier for (pathogenic) microbes. Moreover, we make suggestions for biological model systems to evaluate immediate toxicity, long-term effects and the potential of NMPs to cross biological barriers. We are convinced that standardized reference materials and experimental parameters along with technical innovations in (nano)-particle sampling and analytics are a prerequisite for the successful realization of conclusive human health risk assessments of NMPs.
Supporting SDG 15, Life on Land: Identifying the Main Drivers of Land Degradation in Honghe Prefecture, China, between 2005 and 2015
Authors: Wang Tuo , Giuliani Gregory , Lehmann Anthony , Jiang Yangming , Shao Xiaodong , Li Liping , Zhao Huihui
Published: November 2020

The essence of the 2030 Agenda for Sustainable Development adopted by the United Nations is described in 17 Sustainable Development Goals (SDGs). SDG 15 focuses on Life on Land, in other words, terrestrial biodiversity and ecosystems, as well as their services. Land degradation is a severe anthropic and natural phenomenon that is affecting land use/cover globally; therefore, a dedicated target of the SDG 15 (the indicator 15.3.1) was proposed. The identification of the areas where land degradation has occurred and the analysis of its drivers allow for the design of solutions to prevent further degradation in the studied areas. We followed the methodology proposed by the United Nations Convention to Combat Desertification (UNCCD) to study the land degradation in the Honghe Prefecture in southwest China between 2005 and 2015. Through spatial analysis, we found that the degraded areas were consistent with the areas of active human activities (such as urban centers), while the impact of natural factors (such as disasters) on land degradation existed in small areas at high altitudes. Land degradation was affected primarily by the loss of land productivity and secondly by land cover changes caused by the growth of artificial areas. Changes in the soil organic carbon were not significant. We concluded that human activity was the main driver of land degradation in Honghe Prefecture. Decision makers should work to find a balance between economic development and environmental protection to restore degraded land and strive to achieve a land degradation-neutral prefecture to defend all ecosystem services.
Triangular Relationship between p53, Autophagy, and Chemotherapy Resistance
Authors: Xu Jingwen , Patel Nipa H. , Gewirtz David A.
Published: November 2020

Chemotherapy and radiation often induce a number of cellular responses, such as apoptosis, autophagy, and senescence. One of the major regulators of these processes is p53, an essential tumor suppressor that is often mutated or lost in many cancer types and implicated in early tumorigenesis. Gain of function (GOF) p53 mutations have been implicated in increased susceptibility to drug resistance, by compromising wildtype anti-tumor functions of p53 or modulating key p53 processes that confer chemotherapy resistance, such as autophagy. Autophagy, a cellular survival mechanism, is initially induced in response to chemotherapy and radiotherapy, and its cytoprotective nature became the spearhead of a number of clinical trials aimed to sensitize patients to chemotherapy. However, increased pre-clinical studies have exemplified the multifunctional role of autophagy. Additionally, compartmental localization of p53 can modulate induction or inhibition of autophagy and may play a role in autophagic function. The duality in p53 function and its effects on autophagic function are generally not considered in clinical trial design or clinical therapeutics; however, ample pre-clinical studies suggest they play a role in tumor responses to therapy and drug resistance. Further inquiry into the interconnection between autophagy and p53, and its effects on chemotherapeutic responses may provide beneficial insights on multidrug resistance and novel treatment regimens for chemosensitization.
Evolutionary Overview of Molecular Interactions and Enzymatic Activities in the Yeast Cell Walls
Authors: Teparić Renata , Lozančić Mateja , Mrša Vladimir
Published: November 2020

Fungal cell walls are composed of a polysaccharide network that serves as a scaffold in which different glycoproteins are embedded. Investigation of fungal cell walls, besides simple identification and characterization of the main cell wall building blocks, covers the pathways and regulations of synthesis of each individual component of the wall and biochemical reactions by which they are cross-linked and remodeled in response to different growth phase and environmental signals. In this review, a survey of composition and organization of so far identified and characterized cell wall components of different yeast genera including Saccharomyces, Candida, Kluyveromyces, Yarrowia, and Schizosaccharomyces are presented with the focus on their cell wall proteomes.
EGFR Expression in HER2-Driven Breast Cancer Cells
Authors: Weinberg Florian , Peckys Diana B. , de Jonge Niels
Published: November 2020

The epidermal growth factor receptor HER2 is overexpressed in 20% of breast cancer cases. HER2 is an orphan receptor that is activated ligand-independently by homodimerization. In addition, HER2 is able to heterodimerize with EGFR, HER3, and HER4. Heterodimerization has been proposed as a mechanism of resistance to therapy for HER2 overexpressing breast cancer. Here, a method is presented for the simultaneous detection of individual EGFR and HER2 receptors in the plasma membrane of breast cancer cells via specific labeling with quantum dot nanoparticles (QDs). Correlative fluorescence microscopy and liquid phase electron microscopy were used to analyze the plasma membrane expression levels of both receptors in individual intact cells. Fluorescent single-cell analysis of SKBR3 breast cancer cells dual-labeled for EGFR and HER2 revealed a heterogeneous expression for receptors within both the cell population as well as within individual cells. Subsequent electron microscopy of individual cells allowed the determination of individual receptors label distributions. QD-labeled EGFR was observed with a surface density of (0.5–5) × 101 QDs/µm2, whereas labeled HER2 expression was higher ranging from (2–10) × 102 QDs/µm2. Although most SKBR3 cells expressed low levels of EGFR, an enrichment was observed at large plasma membrane protrusions, and amongst a newly discovered cellular subpopulation termed EGFR-enriched cells.
Can Serum Nitrosoproteome Predict Longevity of Aged Women?
Authors: Capitanio Daniele , Barbacini Pietro , Arosio Beatrice , Guerini Franca Rosa , Torretta Enrica , Trecate Fabio , Cesari Matteo , Mari Daniela , Clerici Mario , Gelfi Cecilia
Published: November 2020

Aging is characterized by increase in reactive oxygen (ROS) and nitrogen (RNS) species, key factors of cardiac failure and disuse-induced muscle atrophy. This study focused on serum nitroproteome as a trait of longevity by adopting two complementary gel-based techniques: two-dimensional differential in gel electrophoresis (2-D DIGE) and Nitro-DIGE coupled with mass spectrometry of albumin-depleted serum of aged (A, n = 15) and centenarian (C, n = 15) versus young females (Y, n = 15). Results indicate spots differently expressed in A and C compared to Y and spots changed in A vs. C. Nitro-DIGE revealed nitrosated protein spots in A and C compared to Y and spots changed in A vs. C only (p-value < 0.01). Nitro-proteoforms of alpha-1-antitripsin (SERPINA1), alpha-1-antichimotripsin (SERPINA3), ceruloplasmin (CP), 13 proteoforms of haptoglobin (HP), and inactive glycosyltransferase 25 family member 3 (CERCAM) increased in A vs. Y and C. Conversely, nitrosation levels decreased in C vs. Y and A, for immunoglobulin light chain 1 (IGLC1), serotransferrin (TF), transthyretin (TTR), and vitamin D-binding protein (VDBP). Immunoblottings of alcohol dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR) and thioredoxin reductase 1 (TRXR1) indicated lower levels of ADH5 in A vs. Y and C, whereas TRXR1 decreased in A and C in comparison to Y. In conclusion, the study identified putative markers in C of healthy aging and high levels of ADH5/GSNOR that can sustain the denitrosylase activity, promoting longevity.
Epigenetics and Heart Failure
Authors: Ameer Syeda Shegufta , Hossain Mohammad Bakhtiar , Knöll Ralph
Published: November 2020

Epigenetics refers to changes in phenotypes without changes in genotypes. These changes take place in a number of ways, including via genomic DNA methylation, DNA interacting proteins, and microRNAs. The epigenome is the second dimension of the genome and it contains key information that is specific to every type of cell. Epigenetics is essential for many fundamental processes in biology, but its importance in the development and progression of heart failure, which is one of the major causes of morbidity and mortality worldwide, remains unclear. Our understanding of the underlying molecular mechanisms is incomplete. While epigenetics is one of the most innovative research areas in modern biology and medicine, compounds that directly target the epigenome, such as epidrugs, have not been well translated into therapies. This paper focuses on epigenetics in terms of genomic DNA methylation, such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications. These appear to be more dynamic than previously anticipated and may underlie a wide variety of conditions, including heart failure. We also outline possible new strategies for the development of novel therapies.
The Effect of Virulence and Resistance Mechanisms on the Interactions between Parasitic Plants and Their Hosts
Authors: Hu Luyang , Wang Jiansu , Yang Chong , Islam Faisal , Bouwmeester Harro , Muños Stéphane , Zhou Weijun
Published: November 2020

Parasitic plants have a unique heterotrophic lifestyle based on the extraction of water and nutrients from host plants. Some parasitic plant species, particularly those of the family Orobanchaceae, attack crops and cause substantial yield losses. The breeding of resistant crop varieties is an inexpensive way to control parasitic weeds, but often does not provide a long-lasting solution because the parasites rapidly evolve to overcome resistance. Understanding mechanisms underlying naturally occurring parasitic plant resistance is of great interest and could help to develop methods to control parasitic plants. In this review, we describe the virulence mechanisms of parasitic plants and resistance mechanisms in their hosts, focusing on obligate root parasites of the genera Orobanche and Striga. We noticed that the resistance (R) genes in the host genome often encode proteins with nucleotide-binding and leucine-rich repeat domains (NLR proteins), hence we proposed a mechanism by which host plants use NLR proteins to activate downstream resistance gene expression. We speculated how parasitic plants and their hosts co-evolved and discussed what drives the evolution of virulence effectors in parasitic plants by considering concepts from similar studies of plant–microbe interaction. Most previous studies have focused on the host rather than the parasite, so we also provided an updated summary of genomic resources for parasitic plants and parasitic genes for further research to test our hypotheses. Finally, we discussed new approaches such as CRISPR/Cas9-mediated genome editing and RNAi silencing that can provide deeper insight into the intriguing life cycle of parasitic plants and could potentially contribute to the development of novel strategies for controlling parasitic weeds, thereby enhancing crop productivity and food security globally.
Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells
Authors: Janitschke Daniel , Lauer Anna A. , Bachmann Cornel M. , Seyfried Martin , Grimm Heike S. , Hartmann Tobias , Grimm Marcus O. W.
Published: November 2020

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class.
Mechanisms of Colorectal Cancer Prevention by Aspirin—A Literature Review and Perspective on the Role of COX-Dependent and -Independent Pathways
Authors: Sankaranarayanan Ranjini , Kumar D. Ramesh , Altinoz Meric A. , Bhat G. Jayarama
Published: November 2020

Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin’s chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin’s anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin’s chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC.
Effect of Prostanoids on Human Platelet Function: An Overview
Authors: Braune Steffen , Küpper Jan-Heiner , Jung Friedrich
Published: November 2020

Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D2 (PGD2), prostaglandin-E1, -E2 and E3 (PGE1, PGE2, PGE3), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane-A2 (TXA2) on platelet activation and aggregation via their respective receptors.
Soluble Endoglin as a Potential Biomarker of Nonalcoholic Steatohepatitis (NASH) Development, Participating in Aggravation of NASH-Related Changes in Mouse Liver
Authors: Igreja Sá Ivone Cristina , Tripska Katarina , Hroch Milos , Hyspler Radomir , Ticha Alena , Lastuvkova Hana , Schreiberova Jolana , Dolezelova Eva , Eissazadeh Samira , Vitverova Barbora , Najmanova Iveta , Vasinova Martina , Pericacho Miguel , Micuda Stanislav , Nachtigal Petr
Published: November 2020

Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) expression is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression. Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, Liquid chromatography–mass spectrometry (LC/MS) analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using Real-Time Quantitative Reverse Transcription Polymerase Chain reaction (qRT-PCR) and Western blot. The FFC diet significantly increases mouse sEng levels and increases hepatic expression of Eng. High levels of human sEng results in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirects the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by β-oxidation combined with reduced hepatic efflux. We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.
High-Throughput Flow Cytometry Combined with Genetic Analysis Brings New Insights into the Understanding of Chromatin Regulation of Cellular Quiescence
Authors: Zahedi Yasaman , Durand-Dubief Mickael , Ekwall Karl
Published: November 2020

Cellular quiescence is a reversible differentiation state when cells are changing the gene expression program to reduce metabolic functions and adapt to a new cellular environment. When fission yeast cells are deprived of nitrogen in the absence of any mating partner, cells can reversibly arrest in a differentiated G0-like cellular state, called quiescence. This change is accompanied by a marked alteration of nuclear organization and a global reduction of transcription. Using high-throughput flow cytometry combined with genetic analysis, we describe the results of a comprehensive screen for genes encoding chromatin components and regulators that are required for the entry and the maintenance of cellular quiescence. We show that the histone acetylase and deacetylase complexes, SAGA and Rpd3, have key roles both for G0 entry and survival during quiescence. We reveal a novel function for the Ino80 nucleosome remodeling complex in cellular quiescence. Finally, we demonstrate that components of the MRN complex, Rad3, the nonhomologous end-joining, and nucleotide excision DNA repair pathways are essential for viability in G0.
Efficient Photodynamic Killing of Gram-Positive Bacteria by Synthetic Curcuminoids
Authors: Hung Sung-Jen , Hong Yi-An , Lin Kai-Yu , Hua Yi-Wen , Kuo Chia-Jou , Hu Anren , Shih Tzenge-Lien , Chen Hao-Ping
Published: November 2020

In our previous study, we have demonstrated that curcumin can efficiently kill the anaerobic bacterium Propionibacterium acnes by irradiation with low-dose blue light. The curcuminoids present in natural plant turmeric mainly include curcumin, demethoxycurcumin, and bisdemethoxycurcumin. However, only curcumin is commercially available. Eighteen different curcumin analogs, including demethoxycurcumin and bisdemethoxycurcumin, were synthesized in this study. Their antibacterial activity against Gram-positive aerobic bacteria Staphylococcus aureus and Staphylococcus epidermidis was investigated using the photodynamic inactivation method. Among the three compounds in turmeric, curcumin activity is the weakest, and bisdemethoxycurcumin possesses the strongest activity. However, two synthetic compounds, (1E,6E)-1,7-bis(5-methylthiophen-2-yl)hepta-1,6-diene-3,5-dione and (1E,6E)-1,7-di(thiophen-2-yl)hepta-1,6-diene-3,5-dione, possess the best antibacterial activity among all compounds examined in this study. Their chemical stability is also better than that of bisdemethoxycurcumin, and thus has potential for future clinical applications.
An Automated Functional Annotation Pipeline That Rapidly Prioritizes Clinically Relevant Genes for Autism Spectrum Disorder
Authors: Veatch Olivia J. , Butler Merlin G. , Elsea Sarah H. , Malow Beth A. , Sutcliffe James S. , Moore Jason H.
Published: November 2020

Human genetic studies have implicated more than a hundred genes in Autism Spectrum Disorder (ASD). Understanding how variation in implicated genes influence expression of co-occurring conditions and drug response can inform more effective, personalized approaches for treatment of individuals with ASD. Rapidly translating this information into the clinic requires efficient algorithms to sort through the myriad of genes implicated by rare gene-damaging single nucleotide and copy number variants, and common variation detected in genome-wide association studies (GWAS). To pinpoint genes that are more likely to have clinically relevant variants, we developed a functional annotation pipeline. We defined clinical relevance in this project as any ASD associated gene with evidence indicating a patient may have a complex, co-occurring condition that requires direct intervention (e.g., sleep and gastrointestinal disturbances, attention deficit hyperactivity, anxiety, seizures, depression), or is relevant to drug development and/or approaches to maximizing efficacy and minimizing adverse events (i.e., pharmacogenomics). Starting with a list of all candidate genes implicated in all manifestations of ASD (i.e., idiopathic and syndromic), this pipeline uses databases that represent multiple lines of evidence to identify genes: (1) expressed in the human brain, (2) involved in ASD-relevant biological processes and resulting in analogous phenotypes in mice, (3) whose products are targeted by approved pharmaceutical compounds or possessing pharmacogenetic variation and (4) whose products directly interact with those of genes with variants recommended to be tested for by the American College of Medical Genetics (ACMG). Compared with 1000 gene sets, each with a random selection of human protein coding genes, more genes in the ASD set were annotated for each category evaluated (p ≤ 1.99 × 10−2). Of the 956 ASD-implicated genes in the full set, 18 were flagged based on evidence in all categories. Fewer genes from randomly drawn sets were annotated in all categories (x = 8.02, sd = 2.56, p = 7.75 × 10−4). Notably, none of the prioritized genes are represented among the 59 genes compiled by the ACMG, and 78% had a pathogenic or likely pathogenic variant in ClinVar. Results from this work should rapidly prioritize potentially actionable results from genetic studies and, in turn, inform future work toward clinical decision support for personalized care based on genetic testing.