bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat- and Ultrasound-Assisted Aqueous Extraction of Soluble Carbohydrates and Phenolics from Carob Kibbles of Variable Size and Source Material
Authors: Antoniou Chrystalla , Kyratzis Angelos , Rouphael Youssef , Stylianou Stelios , Kyriacou Marios C.
Published: September 2020

Aqueous extraction of carob kibbles is the fundamental step in the production of carob juice and carob molasses. Improving the theoretical yield in sugars during organic solvent-free aqueous extraction is of prime interest to the food industry. Collateral extraction of phenolics, however, must be monitored as it influences the sensory and functional profile of carob juice. We presently examined the impact of source material, kibble size, temperature, and duration on the efficiency of extracting sugars and phenolics aqueously by conventional heat-assisted (HAE) and ultrasound-assisted (UAE) methods. Source material was the most influential factor determining the concentration of phenolics extracted by either method. Source material also influenced the relative proportions of sucrose, glucose, and fructose, which may impact the perceived sweetness of the juice. Kibble size (medium size M = 9–13 mm; powder size P = 1–4 mm) was more influential with UAE than HAE for both sugars and phenolics but was rendered less influential with prolonged UAE duration. Increasing HAE temperature (from 25 °C to 75 °C) favored the extraction of phenolics over sugars; however, prolonging extraction at 25 °C improved sugar yield without excessive yield in phenolics. Disproportionate extraction of phenolics over sugars limits the use of heat-assisted extraction to improve sugar yield in carob juice production and may shift the product’s sensory profile toward astringency. Prolonged extraction at near ambient temperature can, however, improve sugar yield, keeping collateral extraction of phenolics low. Ultrasound agitation constitutes an effective means of extracting sugars from powder-size kibbles. Industrial application of both methodologies depends on the targeted functional and sensory properties of carob juice.
Variable Magellanic HMXB Sources versus Variable ULX Sources: Nothing to Brag about the ULX Sources
Authors: Christodoulou Dimitris M. , Laycock Silas G. T. , Cappallo Rigel , Roy Ankur , Bhattacharya  Sayantan , Kazanas Demosthenes
Published: September 2020

We carry out a meta-analysis of ultraluminous X-ray (ULX) sources that show large variabilities (by factors of >10) between their highest and lowest emission states in the X-ray energy range of 0.3–10 keV. We are guided by a recent stringent compilation of 25 such X-ray sources by Song et al. We examine the relation of logN versus logSmax, where N is the number of sources radiating above the maximum-flux level Smax. We find a strong deviation from all previously determined slopes in various high-mass X-ray binary (HMXB) samples. In fact, the ULX data clearly show a slope of −0.91. Thus, ULX sources do not appear to be uniform and isotropic in our Universe. We compare the ULX results against the local X-ray luminosity function of HMXBs in the Small Magellanic Cloud (SMC) constructed from our latest library that includes 41 Chandra 0.3–8 keV sources and 56 XMM-Newton 0.2–12 keV sources. The ULX data are not drawn from the same continuous distribution as the SMC data (the ULX data peak at the low tails of the SMC distributions), and none of our data sets is drawn from a normal distribution or from a log-normal distribution (they all show marked excesses at both tails). At a significance level of α=0.05 (2σ), the two-sample p-value of the Kolmogorov–Smirnov (KS) test gives p=4.7×10−3<α for the ULX versus the small Chandra sample and p=1.1×10−5<<α for the ULX versus the larger XMM-Newton sample, respectively. This adds to the evidence that ULX sources are not simply the higher end of the known local Be/X-ray pulsar distribution, but they represent a class of X-ray sources different from the young sources found in the SMC and in individual starburst galaxies. On the other hand, our two main SMC data sets are found to be statistically consistent, as they are drawn from the same continuous parent distribution (null hypothesis H0): at the α=0.05 significance level, the two-sample KS test shows an asymptotic p-value of 0.308>α, which tells us to accept H0.
The Female-Specific W Chromosomes of Birds Have Conserved Gene Contents but Are Not Feminized
Authors: Xu Luohao , Zhou Qi
Published: September 2020

Sex chromosomes are unique genomic regions with sex-specific or sex-biased inherent patterns and are expected to be more frequently subject to sex-specific selection. Substantial knowledge on the evolutionary patterns of sex-linked genes have been gained from the studies on the male heterogametic systems (XY male, XX female), but the understanding of the role of sex-specific selection in the evolution of female-heterogametic sex chromosomes (ZW female, ZZ male) is limited. Here we collect the W-linked genes of 27 birds, covering the three major avian clades: Neoaves (songbirds), Galloanserae (chicken), and Palaeognathae (ratites and tinamous). We find that the avian W chromosomes exhibit very conserved gene content despite their independent evolution of recombination suppression. The retained W-linked genes have higher dosage-sensitive and higher expression level than the lost genes, suggesting the role of purifying selection in their retention. Moreover, they are not enriched in ancestrally female-biased genes, and have not acquired new ovary-biased expression patterns after becoming W-linked. They are broadly expressed across female tissues, and the expression profile of the W-linked genes in females is not deviated from that of the homologous Z-linked genes. Together, our new analyses suggest that female-specific positive selection on the avian W chromosomes is limited, and the gene content of the W chromosomes is mainly shaped by purifying selection.
The Potential Mediation of the Effects of Physical Activity on Cognitive Function by the Gut Microbiome
Authors: Sanborn Victoria , Gunstad John
Published: September 2020

The population of older adults is growing dramatically worldwide. As older adults are at greater risk of developing disorders associated with cognitive dysfunction (i.e., dementia), healthcare costs are expected to double by 2040. Evidence suggests dementia may be slowed or prevented by lifestyle interventions, including physical activity (PA). PA is associated with improved cognitive function and may reduce risk for dementia by mitigating known risk factors (i.e., cardiovascular diseases) and/or by enhancing neurochemical processes. An emerging area of research suggests the gut microbiome may have similar neuroprotective effects. Altering the gut microbiome has been found to target physiological processes associated with dementia risk, and it influences gut-brain-microbiome axis signaling, impacting cognitive functioning. The gut microbiome can be altered by several means (i.e., disease, diet, prebiotics, probiotics), including PA. As PA and the gut microbiome independently influence cognitive function and PA changes the composition of the gut microbiome, cognitive improvement due to PA may be partially mediated by the gut microbiome. The present article provides an overview of the literature regarding the complex associations among PA, cognitive function, and the gut microbiome, as well as their underlying biological mechanisms. A comprehensive, theoretical model integrating evidence for the potential mediation is proposed.
Measurement Development for Japanese Clients’ Experiences during Adult Day Care Service Use (The J-AdaCa Tool)
Authors: Naruse Takashi , Tuckett Anthony G. , Matsumoto Hiroshige , Yamamoto-Mitani Noriko
Published: September 2020

Adult day care (ADC) is among the most common services in the Japanese long-term care context, but information on how such care is offered remains scarce. This study aimed to develop a measurement tool to assess the richness of clients’ experiences regarding their ADC service use. Through a collaboration with ADC administrators and staff, semi-structured interviews were conducted with three ADC clients (in one ADC agency), and a questionnaire survey (17 items about clients’ and their families’ experiences within ADC) was applied to 360 ADC clients (in 11 ADC agencies). Principle component analysis showed four factors regarding experience of ADC use: “Social participation”, “Hygiene and health”, “Exercise and eating habits”, and “Family support”. These positive experiences might be effectively provided if stakeholders refer to clients’ needs during ADC experiences, and their effective provision may relate to better care outcomes.
Does Educational Attainment Affect Residents’ Health?
Authors: Long Cuihong , Liu Pei , Yi Chengzhi
Published: September 2020

Based on the data of the Chinese General Social Survey 2015 (CGSS2015), this article conducts an empirical analysis on the relationship between education and health status of Chinese residents by using the structural equation model (SEM), the propensity score matching (PSM) method, and generalized ordered logit (Gologit) model. Our study found that education promotes both the subjective and objective health of residents, and the finding holds true after considering the selection bias. In addition to having a direct role, education could promote health through improved mental health, economic status, and healthy behaviors. The finding is consistent with the explanations in existing research of “efficiency-improving effect”, “mental health effect”, and “budget relaxation effect”. Further research on the mechanism of education affecting health through structural equation modeling finds that mental health plays a more important role than healthy behaviors and economic status. In terms of the differences of various groups, education has stronger effect on vulnerable groups with fewer social resources, which shows that education helps reduce health inequality. The conclusion has important policy significance.
Influencing Factors of Undermet Care Needs of the Chinese Disabled Oldest Old People When Their Children Are Both Caregivers and Older People: A Cross-Sectional Study
Authors: Zhang Qilin , Wu Yanli , Liu Erpeng
Published: September 2020

We examined the influencing factors of the undermet care needs of the Chinese disabled oldest old people when their children are both caregivers and are themselves older people. Data were obtained from a cross-sectional survey: the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018. The study participants included 1617 disabled oldest old people whose primary caregiver were their children or children-in-law and were aged 60 years and over. The results showed that the prevalence of undermet needs remained high, with 49.6% disabled oldest old people reporting undermet care needs. Binary logistic regression analysis revealed that living in a rural area (OR = 1.309, 95% CI = 1.133–1.513) and a higher frailty index (OR = 1.103, 95% CI = 1.075–1.131) were significantly positively associated with higher odds for undermet care needs, while a higher annual household income (OR = 0.856, 95% CI = 0.795–0.923), more financial support from children (OR = 0.969, 95% CI = 0.941–0.997), higher care expenditures (OR = 1.044, 95% CI = 1.002–1.088), better caregiver’s performance (OR = 0.282, 95% CI = 0.196–0.407) and sufficient income to pay for daily expenses (OR = 0.710, 95% CI = 0.519–0.973) were significantly inversely associated with higher odds for undermet care needs. This evidence suggests the importance of policies to establish a community-based socialized long-term care system and supporting family caregivers of the disabled oldest old people.
Analysis of Altmetrics in Social Recognition of Neurology and Neurological Disorders
Authors: Kim Yerim , Kim Jee-Eun , Lee Sang-Hwa , Yoon Dae Young , Bae Jong Seok
Published: September 2020

This study used Altmetric analysis to rank neurological articles and assessed the implications in relation to the social recognition of neurology and neurological disorders. An Altmetric Explorer search was conducted on 25 May 2018 for articles published in the 91 journals included in the 2015 InCites™ Journal Citation Report®. We identified and analyzed the 100 articles with the highest Altmetric Attention Scores (AASs). A major proportion of the social impact (high AASs) was focused on neurodegenerative disorders such as dementia and neurodegenerative disorders. About half of the high-ranking articles provided academic information such as disease information (29 articles, 29%), new or advanced treatments (17%), and side effects of treatment (8%). The journal with largest number of top 100 articles was the New England Journal of Medicine (29 articles). Some of the data gathered via altmetrics can change a field of study, the public’s health, or a larger society. This is the first report on the impact of academic articles in neurological disorder on the general public living in our altered information society.
Impact of Freeze–Thaw Cycles on Die-Off of E. coli and Intestinal Enterococci in Deer and Dairy Faeces: Implications for Landscape Contamination of Watercourses
Authors: Afolabi Emmanuel O. , Quilliam Richard S. , Oliver David M.
Published: September 2020

Characterising faecal indicator organism (FIO) survival in the environment is important for informing land management and minimising public health risk to downstream water users. However, key gaps in knowledge include understanding how wildlife contribute to catchment-wide FIO sources and how FIO survival is affected by low environmental temperatures. The aim of this study was to quantify E. coli and intestinal enterococci die-off in dairy cow versus red deer faecal sources exposed to repeated freeze–thaw cycles under controlled laboratory conditions. Survival of FIOs in water exposed to freeze–thaw was also investigated to help interpret survival responses. Both E. coli and intestinal enterococci were capable of surviving sub-freezing conditions with the faeces from both animals able to sustain relatively high FIO concentrations, as indicated by modelling, and observations revealing persistence in excess of 11 days and in some cases confirmed beyond 22 days. Die-off responses of deer-derived FIOs in both faeces and water exposed to low temperatures provide much needed information to enable better accounting of the varied catchment sources of faecal pollution and results from this study help constrain the parameterisation of die-off coefficients to better inform more integrated modelling and decision-making for microbial water quality management.
Wage Penalties or Wage Premiums? A Socioeconomic Analysis of Gender Disparity in Obesity in Urban China
Authors: Dou Jiangli , Du Limin , Wang Ken , Sun Hailin , Zhang Chenggang
Published: September 2020

Global obesity as a major public health problem has increased at pandemic rate, with men often outpacing women. Survey data show that the overall prevalence of obesity is higher among women than men, yet in high-income developed countries, the prevalence of overweight is higher among men than women. The differential impact of different economic stages has prompted research in transition economies such as China. Using an instrumental variable approach based on a sample of 13,574 individuals from nine provinces in the Chinese Household Income Project (CHIP), we find a 7% excess-weight premium in wages for overweight men and a 4.6% penalty for overweight women, compared to their healthy-weight peers. We also find an inverse u-shaped association between the body mass index (BMI) and logarithm of monthly income for men, with an implied optimum above the threshold of obesity, while women are better off the slimmer they are. The excess-weight premium in wages for Chinese urban men might be associated with entrenched business practices of excessive dining and drinking associated with senior positions. Policies aimed at reducing obesity in China must be adapted to its unique sociocultural context in order to have gender-differentiated effects.
Cigarette or E-Cigarette Use as Strong Risk Factors for Heated Tobacco Product Use among Korean Adolescents
Authors: Hwang Jun Hyun , Ryu Dong Hee , Park Inho , Park Soon-Woo
Published: September 2020

Heated tobacco products (HTPs) were first introduced in Korea in June 2017. This study examined the prevalence of current HTP use among Korean adolescents and its association with conventional cigarette (CC) or electronic cigarette (EC) use. The study analyzed nationally representative data (the 2019 Korea Youth Risk Behavior Web-based Survey) from a sample of 57,303 Korean students from grades 7–12. Multinomial logistic regression models were designed to evaluate the association between EC or CC use and HTP use. A total of 2.6% of respondents were current HTP users and 95.9% of them were dual or triple users of CC or EC. The likelihood of HTP use was higher among current CC or EC users and highest among dual users. When the association between each tobacco product and current HTP use was analyzed, the dual use tendency of HTPs and other products steadily increased with the increase of CC or EC smoking frequency. Adolescents who use ECs and/or CCs are likely to use HTPs. Thus, HTPs could be a new public health concern for adolescents in terms of dual or triple use patterns of CC or EC.
Children with Developmental Disabilities in Low- and Middle-Income Countries: More Neglected and Physically Punished
Authors: Bizzego Andrea , Lim Mengyu , Schiavon Greta , Esposito Gianluca
Published: September 2020

Little is known about parenting in the context of developmental disabilities in low- and middle-income countries (LMIC), penalized by both lack of data and a research bias toward western societies. In this study, we apply data mining methods on a large (N = 25,048) dataset from UNICEF to highlight patterns of association between developmental disabilities of children and parental involvement. We focus on the co-presence of multiple disabilities and the quality of childcare in three parenting domains: discipline, caregiving, and education. Our results show that, in LMIC, children with more severe developmental conditions are also more likely to receive low-quality parental care. Specific policies of parental training are needed to improve parental practices in LMIC.
Mental Health and the SARS-COV-2 Epidemic—Polish Research Study
Authors: Talarowska Monika , Chodkiewicz Jan , Nawrocka Natalia , Miniszewska Joanna , Biliński Przemysław
Published: September 2020

Background: The aim of this study was to assess the mental state of Poles in the first weeks of the SARS-COV-2 epidemic. Methods: In the study, the General Health Questionnaire-28 (GHQ-18), The Perceived Stress Scale (PSS-10), and Mini-Cope were used. Results: The study was conducted on a group of 443 individuals, including 348 women (78.6%) and 95 men (21.4%). There were more women (χ2 = 6.42, p = 0.02) in the group of people with high results in the GHQ-28 questionnaire and the differentiating factors between those with sten scores above 7 (significantly deteriorated mental health) and those with average or low results (sten score below 7) turned out to be: treatment for mental disorders before the pandemic (χ2 = 19.57, p < 0.001) and the use of psychotherapy during the pandemic (χ2 = 4.21, p = 0.04) and psychiatric pharmacotherapy (χ2 = 8.31, p = 0.01). The presence of suicidal thoughts since the appearance of the pandemic-related restraints and limitations significantly differentiates the compared groups (χ2 = 38.48, p < 0.001). Conclusions: Every fourth person in the examined group (over 26% of the respondents) recorded results that indicate a high probability of mental functioning disorders. Approximately 10% of the respondents signalled the occurrence of suicidal thoughts since the beginning of the pandemic. The respondents complain mainly about problems in everyday life, lack of satisfaction from one’s own activities, tension, trouble sleeping, and feelings of exhaustion. Individuals with significantly reduced mental well-being use non-adaptive coping strategies, such as denying problems, emotional discharge, taking substances, discontinuation of action, and blaming themselves for the situation. The risk factors for the deterioration of the mental state of the respondents during the pandemic include psychiatric treatment before the beginning of the pandemic, the presence of suicidal thoughts during forced isolation, and the use of non-adaptive coping strategies (denial of the existence of problems, emotional discharge, use of psychoactive substances, discontinuation of action, and blaming oneself for the situation).
An Overview of the World Current and Future Assessment of Novel COVID-19 Trajectory, Impact, and Potential Preventive Strategies at Healthcare Settings
Authors: Al-Anzi Bader S. , Alenizi Mohammad , Al Dallal Jehad , Abookleesh Frage Lhadi , Ullah Aman
Published: September 2020

This study is an overview of the current and future trajectory, as well as the impact of the novel Coronavirus (COVID-19) in the world and selected countries including the state of Kuwait. The selected countries were divided into two groups: Group A (China, Switzerland, and Ireland) and Group B (USA, Brazil, and India) based on their outbreak containment of this virus. Then, the actual data for each country were fitted to a regression model utilizing the excel solver software to assess the current and future trajectory of novel COVID-19 and its impact. In addition, the data were fitted using the Susceptible–Infected–Recovered (SIR) Model. The Group A trajectory showed an “S” shape trend that suited a logistic function with r2 > 0.97, which is an indication of the outbreak control. The SIR models for the countries in this group showed that they passed the expected 99% end of pandemic dates. Group B, however, exhibited a continuous increase of the total COVID-19 new cases, that best suited an exponential growth model with r2 > 0.97, which meant that the outbreak is still uncontrolled. The SIR models for the countries in this group showed that they are still relatively far away from reaching the expected 97% end of pandemic dates. The maximum death percentage varied from 3.3% (India) to 7.2% with USA recording the highest death percentage, which is virtually equal to the maximum death percentage of the world (7.3%). The power of the exponential model determines the severity of the country’s trajectory that ranged from 11 to 19 with the USA and Brazil having the highest values. The maximum impact of this COVID-19 pandemic occurred during the uncontrolled stage (2), which mainly depended on the deceptive stage (1). Further, some novel potential containment strategies are discussed. Results from both models showed that the Group A countries contained the outbreak, whereas the Group B countries still have not reached this stage yet. Early measures and containment strategies are imperative in suppressing the spread of COVID-19.
Motivations for the Use of Video Game Streaming Platforms: The Moderating Effect of Sex, Age and Self-Perception of Level as a Player
Authors: Cabeza-Ramírez Luis Javier , Sánchez-Cañizares Sandra M. , Fuentes-García Fernando J.
Published: September 2020

A particularly striking new phenomenon in recent years is the live streaming of video games through popular platforms, such as Twitch. This study focuses on the motivations and types of use underlying viewer participation in live streaming platforms. Based on the uses and gratifications theory, this paper aims to analyse how three basic motivations are related to the use of video game streaming platforms. Furthermore, it examines the moderating effects that significant variables, such as the audience member’s age, sex or self-perception of level as a player may exert on this relationship. The results reveal that the three types of motivations are positively associated with use of the platform, although notable differences appear, with informational motivations outweighing entertainment and social motivations. At the same time, no moderating effects on the results of the proposed model were found for the heterogeneity stemming from sex and age. Conversely, the influence of informational motivations on the use of these platforms is moderated by the self-perception of level as a player.
Social Networking Sites and Perceived Content Influence: An Exploratory Analysis from Focus Groups with French Adolescents
Authors: Chapoton Boris , Régnier Denois Véronique , Nekaa Mabrouk , Chauvin Franck , Flaudias Valentin
Published: September 2020

Social networking sites (SNSs) are invested in heavily by marketers aiming to reach a growing number of consumers. Concerns regarding the influence of posts displayed on SNSs in relation to behaviour were raised, in particular the promotion of ill-health behaviour directed to adolescents who may be at risk from suggestible practices. Although adolescents tend to be critical towards traditional forms of advertising, little is known about their perception of influencing strategies developed online, especially where sponsor- and user-generated content coexist. This exploratory study aims to gather information directly from adolescents about their use of SNSs their awareness of the influence that SNS content may have, particularly when it comes to tobacco and alcohol messages. Ten focus groups were conducted with 39 adolescents (11–16 years old; 56.4% male). Qualitative analysis documents the differences associated with adolescents’ favourite SNSs. The different parameters linked to each SNS and the expectation to find entertaining content and values associated with friendship may decrease adolescents’ perception of potential risk for health associated with SNS use. Authors advocate for the development of educational programs based on eHealth literacy and the use of social marketing techniques to facilitate and motivate adolescents to develop their competences.
The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer
Authors: De Palma Fatima Domenica Elisa , Luglio Gaetano , Tropeano Francesca Paola , Pagano Gianluca , D’Armiento Maria , Kroemer Guido , Maiuri Maria Chiara , De Palma Giovanni Domenico
Published: September 2020

The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.
Genome-Wide Identification of CsATGs in Tea Plant and the Involvement of CsATG8e in Nitrogen Utilization
Authors: Huang Wei , Ma Dan-Ni , Liu Hong-Ling , Luo Jie , Wang Pu , Wang Ming-Le , Guo Fei , Wang Yu , Zhao Hua , Ni De-Jiang
Published: September 2020

Nitrogen (N) is a macroelement with an indispensable role in the growth and development of plants, and tea plant (Camellia sinensis) is an evergreen perennial woody species with young shoots for harvest. During senescence or upon N stress, autophagy has been shown to be induced in leaves, involving a variety of autophagy-related genes (ATGs), which have not been characterized in tea plant yet. In this study, a genome-wide survey in tea plant genome identified a total of 80 Camellia Sinensis autophagy-related genes, CsATGs. The expression of CsATG8s in the tea plant showed an obvious increase from S1 (stage 1) to S4 (stage 4), especially for CsATG8e. The expression levels of AtATGs (Arabidopsis thaliana) and genes involved in N transport and assimilation were greatly improved in CsATG8e-overexpressed Arabidopsis. Compared with wild type, the overexpression plants showed earlier bolting, an increase in amino N content, as well as a decrease in biomass and the levels of N, phosphorus and potassium. However, the N level was found significantly higher in APER (aerial part excluding rosette) in the overexpression plants relative to wild type. All these results demonstrated a convincing function of CsATG8e in N remobilization and plant development, indicating CsATG8e as a potential gene for modifying plant nutrient utilization.
OsExo70B1 Positively Regulates Disease Resistance to Magnaporthe oryzae in Rice
Authors: Hou Hongna , Fang Jianbo , Liang Jiahui , Diao Zhijuan , Wang Wei , Yang Dewei , Li Shengping , Tang Dingzhong
Published: September 2020

The exocyst, an evolutionarily conserved octameric protein complex, mediates tethering of vesicles to the plasma membrane in the early stage of exocytosis. Arabidopsis Exo70, a subunit of the exocyst complex, has been found to be involved in plant immunity. Here, we characterize the function of OsExo70B1 in rice. OsExo70B1 mainly expresses in leaf and shoot and its expression is induced by pathogen-associated molecular patterns (PAMPs) and rice blast fungus Magnaporthe oryzae (M. oryzae). Knocking out OsExo70B1 results in significantly decreased resistance and defense responses to M. oryzae compared to the wild type, including more disease lesions and enhanced fungal growth, downregulated expression of pathogenesis-related (PR) genes, and decreased reactive oxygen species accumulation. In contrast, the exo70B1 mutant does not show any defects in growth and development. Furthermore, OsExo70B1 can interact with the receptor-like kinase OsCERK1, an essential component for chitin reception in rice. Taken together, our data demonstrate that OsExo70B1 functions as an important regulator in rice immunity.
B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role
Authors: Purvis Ian J. , Velpula Kiran K. , Guda Maheedhara R. , Nguyen Daniel , Tsung Andrew J. , Asuthkar Swapna
Published: September 2020

(1) Aim: Medulloblastoma is the most common aggressive pediatric cancer of the central nervous system. Improved therapies are necessary to improve life outcomes for medulloblastoma patients. Exosomes are a subset of extracellular vesicles that are excreted outside of the cell, and can transport nucleic acids and proteins from donor cells to nearby recipient cells of the same or dissimilar tissues. Few publications exist exploring the role that exosomes play in medulloblastoma pathogenesis. In this study, we found B7-H3, an immunosuppressive immune checkpoint, present in D283 cell-derived exosomes. (2) Methods: Utilizing mass spectrometry and immunoblotting, the presence of B7-H3 in D283 control and B7-H3 overexpressing exosomes was confirmed. Exosomes were isolated by Systems Biosciences from cultured cells as well as with an isolation kit that included ultracentrifugation steps. Overlay experiments were performed to determine mechanistic impact of exosomes on recipient cells by incubating isolated exosomes in serum-free media with target cells. Impact of D283 exosome incubation on endothelial and UW228 medulloblastoma cells was assessed by immunoblotting. Immunocytochemistry was employed to visualize exosome fusion with recipient cells. (3) Results: Overexpressing B7-H3 in D283 cells increases exosomal production and size distribution. Mass spectrometry revealed a host of novel, pathogenic molecules associated with B7-H3 in these exosomes including STAT3, CCL5, MMP9, and PI3K pathway molecules. Additionally, endothelial and UW228 cells incubated with D283-derived B7-H3-overexpressing exosomes induced B7-H3 expression while pSTAT1 levels decreased in UW228 cells. (4) Conclusions: In total, our results reveal a novel role in exosome production and packaging for B7-H3 that may contribute to medulloblastoma progression.
Mechanisms of Arrhythmias in the Brugada Syndrome
Authors: Blok Michiel , Boukens Bastiaan J.
Published: September 2020

Arrhythmias in Brugada syndrome patients originate in the right ventricular outflow tract (RVOT). Over the past few decades, the characterization of the unique anatomy and electrophysiology of the RVOT has revealed the arrhythmogenic nature of this region. However, the mechanisms that drive arrhythmias in Brugada syndrome patients remain debated as well as the exact site of their occurrence in the RVOT. Identifying the site of origin and mechanism of Brugada syndrome would greatly benefit the development of mechanism-driven treatment strategies.
In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond
Authors: Wawrzkiewicz-Jałowiecka Agata , Kowalczyk Karolina , Trybek Paulina , Jarosz Tomasz , Radosz Patrycja , Setlak Marcin , Madej Paweł
Published: September 2020

In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17α-hydroxylase), 3β-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.
Exosomes: Insights from Retinoblastoma and Other Eye Cancers
Authors: Lande Kashmiri , Gupta Jitesh , Ranjan Ravi , Kiran Manjari , Torres Solis Luis Fernando , Solís Herrera Arturo , Aliev Gjumrakch , Karnati Roy
Published: September 2020

Exosomes, considered as cell debris or garbage bags, have been later characterized as nanometer-sized extracellular double-membrane lipid bilayer bio-vesicles secreted by the fusion of vesicular bodies with the plasma membrane. The constituents and the rate of exosomes formation differ in different pathophysiological conditions. Exosomes are also observed and studied in different parts of the eye, like the retina, cornea, aqueous, and vitreous humor. Tear fluid consists of exosomes that are shown to regulate various cellular processes. The role of exosomes in eye cancers, especially retinoblastoma (RB), is not well explored, although few studies point towards their presence. Retinoblastoma is an intraocular tumor that constitutes 3% of cases of cancer in children. Diagnosis of RB may require invasive procedures, which might lead to the spread of the disease to other parts. Due to this reason, better ways of diagnosis are being explored. Studies on the exosomes in RB tumors and serum might help designing better diagnostic approaches for RB. In this article, we reviewed studies on exosomes in the eye, with a special emphasis on RB. We also reviewed miRNAs expressed in RB tumor, serum, and cell lines and analyzed the targets of these miRNAs from the proteins identified in the RB tumor exosomes. hsa-miR-494 and hsa-miR-9, upregulated and downregulated, respectively in RB, have the maximum number of targets. Although oppositely regulated, they share the same targets in the proteins identified in RB tumor exosomes. Overall this review provides the up-to-date progress in the area of eye exosome research, with an emphasis on RB.
Multi-Compartment, Early Disruption of cGMP and cAMP Signalling in Cardiac Myocytes from the mdx Model of Duchenne Muscular Dystrophy
Authors: Brescia Marcella , Chao Ying-Chi , Koschinski Andreas , Tomek Jakub , Zaccolo Manuela
Published: September 2020

Duchenne muscular dystrophy (DMD) is the most frequent and severe form of muscular dystrophy. The disease presents with progressive body-wide muscle deterioration and, with recent advances in respiratory care, cardiac involvement is an important cause of morbidity and mortality. DMD is caused by mutations in the dystrophin gene resulting in the absence of dystrophin and, consequently, disturbance of other proteins that form the dystrophin-associated protein complex (DAPC), including neuronal nitric oxide synthase (nNOS). The molecular mechanisms that link the absence of dystrophin with the alteration of cardiac function remain poorly understood but disruption of NO-cGMP signalling, mishandling of calcium and mitochondrial disturbances have been hypothesized to play a role. cGMP and cAMP are second messengers that are key in the regulation of cardiac myocyte function and disruption of cyclic nucleotide signalling leads to cardiomyopathy. cGMP and cAMP signals are compartmentalised and local regulation relies on the activity of phosphodiesterases (PDEs). Here, using genetically encoded FRET reporters targeted to distinct subcellular compartments of neonatal cardiac myocytes from the DMD mouse model mdx, we investigate whether lack of dystrophin disrupts local cyclic nucleotide signalling, thus potentially providing an early trigger for the development of cardiomyopathy. Our data show a significant alteration of both basal and stimulated cyclic nucleotide levels in all compartments investigated, as well as a complex reorganization of local PDE activities.
Cellular Prion Protein (PrPc): Putative Interacting Partners and Consequences of the Interaction
Authors: Miranzadeh Mahabadi Hajar , Taghibiglou Changiz
Published: September 2020

Cellular prion protein (PrPc) is a small glycosylphosphatidylinositol (GPI) anchored protein most abundantly found in the outer leaflet of the plasma membrane (PM) in the central nervous system (CNS). PrPc misfolding causes neurodegenerative prion diseases in the CNS. PrPc interacts with a wide range of protein partners because of the intrinsically disordered nature of the protein’s N-terminus. Numerous studies have attempted to decipher the physiological role of the prion protein by searching for proteins which interact with PrPc. Biochemical characteristics and biological functions both appear to be affected by interacting protein partners. The key challenge in identifying a potential interacting partner is to demonstrate that binding to a specific ligand is necessary for cellular physiological function or malfunction. In this review, we have summarized the intracellular and extracellular interacting partners of PrPc and potential consequences of their binding. We also briefly describe prion disease-related mutations at the end of this review.
STING-Mediated Autophagy Is Protective against H2O2-Induced Cell Death
Authors: Abdullah Amar , Mobilio Frank , Crack Peter J. , Taylor Juliet M.
Published: September 2020

Stimulator of interferon genes (STING)-mediated type-I interferon signaling is a well characterized instigator of the innate immune response following bacterial or viral infections in the periphery. Emerging evidence has recently linked STING to various neuropathological conditions, however, both protective and deleterious effects of the pathway have been reported. Elevated oxidative stress, such as neuroinflammation, is a feature of a number of neuropathologies, therefore, this study investigated the role of the STING pathway in cell death induced by elevated oxidative stress. Here, we report that the H2O2-induced activation of the STING pathway is protective against cell death in wildtype (WT) MEFSV40 cells as compared to STING−/− MEF SV40 cells. This protective effect of STING can be attributed, in part, to an increase in autophagy flux with an increased LC3II/I ratio identified in H2O2-treated WT cells as compared to STING−/− cells. STING−/− cells also exhibited impaired autophagic flux as indicated by p62, LC3-II and LAMP2 accumulation following H2O2 treatment, suggestive of an impairment at the autophagosome-lysosomal fusion step. This indicates a previously unrecognized role for STING in maintaining efficient autophagy flux and protecting against H2O2-induced cell death. This finding supports a multifaceted role for the STING pathway in the underlying cellular mechanisms contributing to the pathogenesis of neurological disorders.
Functional Recovery of a GCDH Variant Associated to Severe Deflavinylation—Molecular Insights into Potential Beneficial Effects of Riboflavin Supplementation in Glutaric Aciduria-Type I Patients
Authors: Ribeiro Joana V. , Gomes Cláudio M. , Henriques Bárbara J.
Published: September 2020

Riboflavin is the biological precursor of two important flavin cofactors—flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)—that are critical prosthetic groups in several redox enzymes. While dietary supplementation with riboflavin is a recognized support therapy in several inborn errors of metabolism, it has yet unproven benefits in several other pathologies affecting flavoproteins. This is the case for glutaric aciduria type I (GA-I), a rare neurometabolic disorder associated with mutations in the GCDH gene, which encodes for glutaryl-coenzyme A (CoA) dehydrogenase (GCDH). Although there are a few reported clinical cases that have responded to riboflavin intake, there is still not enough molecular evidence supporting therapeutic recommendation. Hence, it is necessary to elucidate the molecular basis in favor of riboflavin supplementation in GA-I patients. Here, using a combination of biochemical and biophysical methodologies, we investigate the clinical variant GCDH-p.Val400Met as a model for a phenotype associated with severe deflavinylation. Through a systematic analysis, we establish that recombinant human GCDH-p.Val400Met is expressed in a nonfunctional apo form, which is mainly monomeric rather than tetrameric. However, we show that exogenous FAD is a driver for structural reorganization of the mutant enzyme with concomitant functional recovery, improved thermolability, and resistance to trypsin digestion. Overall, these results establish proof of principle for the beneficial effects of riboflavin supplementation in GA-I patients.
Induced Short-Term Hearing Loss due to Stimulation of Age-Related Factors by Intermittent Hypoxia, High-Fat Diet, and Galactose Injection
Authors: Park Dong Jun , Ha Sunmok , Choi Jin Sil , Lee Su Hoon , Park Jeong-Eun , Seo Young Joon
Published: September 2020

Age-related hearing loss (ARHL) is the most common sensory disorder among the elderly, associated with aging and auditory hair cell death due to oxidative-stress-induced mitochondrial dysfunction. Although transgenic mice and long-term aging induction cultures have been used to study ARHL, there are currently no ARHL animal models that can be stimulated by intermittent environmental changes. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined on the basis of expression of hearing-loss-induced phenotypes and aging-related factors. The incidence of hearing loss was significantly higher in dual- and triple-exposure conditions than in intermittent hypoxic conditions, high-fat diet (HFD), or d-galactose injection alone. Continuous oxidative stress and HFD accelerated cellular aging. An increase in Ucp2, usually expressed during mitochondrial dysfunction, was observed. Expression of Cdh23, Slc26a4, Kcnq4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in the cells of the hearing organ. We found that intermittent hypoxia, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects the effects of intermittent environmental changes, will benefit future research on ARHL.
Differential Production of Cartilage ECM in 3D Agarose Constructs by Equine Articular Cartilage Progenitor Cells and Mesenchymal Stromal Cells
Authors: Schmidt Stefanie , Abinzano Florencia , Mensinga Anneloes , Teßmar Jörg , Groll Jürgen , Malda Jos , Levato Riccardo , Blunk Torsten
Published: September 2020

Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and MSCs when cultured in hydrogels. Therefore, in this study, we compared chondrogenic differentiation of equine ACPCs and MSCs in agarose constructs as monocultures and as zonally layered co-cultures under both normoxic and hypoxic conditions. ACPCs and MSCs exhibited distinctly differential production of the cartilaginous extracellular matrix (ECM). For ACPC constructs, markedly higher glycosaminoglycan (GAG) contents were determined by histological and quantitative biochemical evaluation, both in normoxia and hypoxia. Differential GAG production was also reflected in layered co-culture constructs. For both cell types, similar staining for type II collagen was detected. However, distinctly weaker staining for undesired type I collagen was observed in the ACPC constructs. For ACPCs, only very low alkaline phosphatase (ALP) activity, a marker of terminal differentiation, was determined, in stark contrast to what was found for MSCs. This study underscores the potential of ACPCs as a promising cell source for cartilage engineering.
Influence Factor Analysis of Bicycle Free-Flow Speed for Determining the Design Speeds of Separated Bicycle Lanes
Authors: Yan Xingchen , Chen Jun , Bai Hua , Wang Tao , Yang Zhen
Published: September 2020

To provide a knowledge basis for updating the design speed in bicycle facility codes, this paper examines factors that influence bicycle free-flow speed. We investigated six segments of Nanjing’s separated bicycle lane and established a generalized linear model of the relationship between bicycle free-flow speed and bicyclists’ gender, age, bicycle type, lane width, bicycle lateral position, and travel period. With the model, we determined the statistical significance of each factor and assessed each factor’s impact extent. Through comparing the 85th percentile speeds of different groups, we proposed the recommended values and a method for calculating the design speed of separate bicycle lanes. The following results and conclusions were obtained: (1) The significant influential factors of bicycle free-flow speed were bicyclists’ gender and age, bicycle type, lane width, and bicycles’ lateral position. (2) Bicycle type had the greatest impact on bicycle free-flow speed, following by bicycle lateral position, gender, age, and lane width in sequence. (3) The recommended design speeds for separate lanes of less than 3.5 m and the wider lanes were 25 km/h and 30 km/h, respectively.