bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimated Cardiorespiratory Fitness Attenuates the Impacts of Sarcopenia and Obesity on Non-Alcoholic Fatty Liver in Korean Adults
Authors: Lee Inhwan , Kim Jeonghyeon , Kang Hyunsik
Published: June 2020

This population-based, cross-sectional study examined the preventive role of non-exercise-based estimation of cardiorespiratory fitness (eCRF) against the impacts of sarcopenia and obesity on the non-alcoholic fatty liver (NAFL) in Korean adults. Data were obtained from the 2008–2011 Korea National Health and Nutrition Examination Surveys IV and V (n = 14,015 Koreans aged ≥ 18 years, 64% women). eCRF was calculated with the age- and sex-specific algorithms, and classified as lower (lowest 25%), middle (middle 50%) and upper (highest 25%). Individuals were classified as optimal (i.e., the absence of both sarcopenia and obesity), sarcopenia (i.e., the presence of sarcopenia), obesity (i.e., the presence of obesity) or sarcopenic obesity (i.e., the coexistence of sarcopenia and obesity). Limited to the sarcopenia phenotype, the adjusted odds ratio (OR) of NAFL was 2.2 (95% confidence interval, CI, 1.5–3.1) for the lower eCRF, 1.6 (95% CI, 1.3–2.1) for the middle eCRF and 2.1 (95% CI, 1.4–3.1) for the upper eCRF, compared to the optimal phenotype. Limited to the obesity phenotype, the adjusted OR of NAFL was 2.9 (95% CI, 2.0–4.2) for the lower eCRF, 3.5 (95% CI, 2.7–4.6) for the middle eCRF and 1.8 (95% CI, 1.2–2.8) for the upper eCRF, compared to the optimal phenotype. Limited to the sarcopenic obesity phenotype, the adjusted OR of NAFL was 5.9 (95% CI, 4.3–8.2) for the lower eCRF, 4.2 (95% CI, 3.2–5.5) for the middle eCRF and 2.5 (95% CI, 1.5–4.1) for the upper eCRF, compared to the optimal phenotype. The current findings suggest that high eCRF attenuates the individual and synergistic impacts of sarcopenia and obesity on NAFL in Korean adults.
Spatial Statistics and Influencing Factors of the COVID-19 Epidemic at Both Prefecture and County Levels in Hubei Province, China
Authors: Xiong Yongzhu , Wang Yunpeng , Chen Feng , Zhu Mingyong
Published: June 2020

The coronavirus disease 2019 (COVID-19) epidemic has had a crucial influence on people’s lives and socio-economic development. An understanding of the spatiotemporal patterns and influencing factors of the COVID-19 epidemic on multiple scales could benefit the control of the outbreak. Therefore, we used spatial autocorrelation and Spearman’s rank correlation methods to investigate these two topics, respectively. The COVID-19 epidemic data reported publicly and relevant open data in Hubei province were analyzed. The results showed that (1) at both prefecture and county levels, the global spatial autocorrelation was extremely significant for the cumulative confirmed COVID-19 cases (CCC) in Hubei province from 30 January to 18 February 2020. Further, (2) at both levels, the significant hotspots and cluster/outlier areas were observed solely in Wuhan city and most of its districts/sub-cities from 30 January to 18 February 2020. (3) At the prefecture level in Hubei province, the number of CCC had a positive and extremely significant correlation (p < 0.01) with the registered population (RGP), resident population (RSP), Baidu migration index (BMI), regional gross domestic production (GDP), and total retail sales of consumer goods (TRS), respectively, from 29 January to 18 February 2020 and had a negative and significant correlation (p < 0.05) with minimum elevation (MINE) from 2 February to 18 February 2020, but no association with the land area (LA), population density (PD), maximum elevation (MAXE), mean elevation (MNE), and range of elevation (RAE) from 23 January to 18 February 2020. (4) At the county level, the number of CCC in Hubei province had a positive and extremely significant correlation (p < 0.01) with PD, RGP, RSP, GDP, and TRS, respectively, from 27 January to 18 February 2020, and was negatively associated with MINE, MAXE, MNE, and RAE, respectively, from 26 January to 18 February 2020, and negatively associated with LA from 30 January to 18 February 2020. It suggested that (1) the COVID-19 epidemics at both levels in Hubei province had evident characteristics of significant global spatial autocorrelations and significant centralized high-risk outbreaks. (2) The COVID-19 epidemics were significantly associated with the natural factors, such as LA, MAXE, MNE, and RAE, -only at the county level, not at the prefecture level, from 2 February to 18 February 2020. (3) The COVID-19 epidemics were significantly related to the socioeconomic factors, such as RGP, RSP, TRS, and GDP, at both levels from 26 January to 18 February 2020. It is desired that this study enrich our understanding of the spatiotemporal patterns and influencing factors of the COVID-19 epidemic and benefit classified prevention and control of the COVID-19 epidemic for policymakers.
Teaching-Learning Processes: Application of Educational Psychodrama in the University Setting
Authors: Maya Jesús , Maraver Jesús
Published: June 2020

The use of effective teaching strategies should be developed from teachers’ reflections on educational needs. This study has a twofold objective: to identify needs in teaching-learning processes in the university setting as well as to present and examine the effectiveness of four psychodramatic techniques: psychodramatic images, soliloquy, role-playing and roda viva. A qualitative design using thematic analysis was followed. All 128 teachers participating in the Training in Teaching Skills: Educational Psychodrama (nine courses) were evaluated. Teachers (62.5% women) were from different disciplines. Two semi-structured group interviews were conducted using the focus group procedure. Focus groups were held at the beginning and end of each course (18 in total). The phases of thematic analysis were used as discourse analysis strategies. Teachers reported the need to develop active teaching practices with large groups, strategies to motivate students and skills for conflict resolution with students. Concerning psychodramatic techniques, emphasis was placed on the psychodramatic images to promote active learning and group construction of contents, exploring previous ideas and as an evaluation resource. In addition, the structured use of role-playing was positively assessed. These results identify specific teaching needs and support the use of psychodramatic techniques as a valuable educational resource in higher education.
Injury Profile of Male and Female Senior and Youth Handball Players: A Systematic Review
Authors: Raya-González Javier , Clemente Filipe Manuel , Beato Marco , Castillo Daniel
Published: June 2020

Handball is a team sport in which players are exposed to high physical conditioning requirements and several contacts and collisions, so they must face various musculoskeletal injuries throughout their career. The aim of this study was to summarize the characteristics of handball injuries both in training and in competition contexts, differentiating by gender and age. A systematic review was conducted and a total of 15 studies (33 cohorts) met the inclusion criteria. Higher injury incidence was reported during matches compared to training sessions in all groups (i.e., male and female senior and youth players), with male senior players presenting the greatest values. Lower extremities were more frequently injured, being contusions and sprains the most common type of injuries. Females reported more serious injuries than males, who presented a higher percentage of acute injuries caused by direct contact, while in female players these injuries were not caused by direct contact actions. Wings and backs presented the highest injury incidence; additionally, players registered higher match incidence during international championships compared to national leagues. Due to the differences in the injury profile of handball players, specific preventive strategies should be implemented for each group to optimize the injury prevention process.
Type 2 Diabetes Mellitus in Class II and III Obesity: Prevalence, Associated Factors, and Correlation between Glycemic Parameters and Body Mass Index
Authors: Silveira Erika Aparecida , de Souza Rosa Lorena Pereira , de Carvalho Santos Annelisa Silva e Alves , de Souza Cardoso Camila Kellen , Noll Matias
Published: June 2020

Despite the worldwide growth of class II and III obesity, the factors associated with type 2 diabetes mellitus (T2DM) in these obese individuals are not widely understood. Moreover, no study has investigated these associations in South America. Our study aimed to investigate the prevalence of T2DM and its associated factors, with an emphasis on biochemical parameters and eating habits, in class II and III obese individuals. We also aimed to analyze the correlation between glycemic parameters and body mass index (BMI). Baseline data from a randomized clinical trial (DieTBra Trial) of 150 class II and III obese individuals (BMI > 35 kg/m2) was used. An accelerometer, Food Frequency Questionnaire, and bioimpedance analysis were used to assess physical activity levels, eating habits, and body composition, respectively. Blood was collected after 12 h of fasting. Hierarchical multivariate Poisson regression was performed, and prevalence ratios (PRs) were calculated. Correlations between glycemic parameters (fasting blood glucose, glycosylated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin) and BMI were also analyzed. The prevalence of T2DM was 40.0% (95% CI, 32.1–48.3), high fasting blood glucose level was 19.33% (95% CI, 13.3–26.6), and high glycosylated hemoglobin was 32.67% (95% CI, 25.2–40.8). Age ≥ 50 years (PR = 3.17, 95% CI, 1.26–7.98) was significantly associated with T2DM; there was a positive linear trend between age and T2DM (p = 0.011). Multivariate analysis showed an association with educational level (PR = 1.49, 1.07–2.09, p = 0.018), nonconsumption of whole grains daily (PR = 1.67, 1.00–2.80, p = 0.049), and high HOMA-IR (PR = 1.54, 1.08–2.18, p = 0.016). We found a high prevalence of T2DM and no significant correlations between BMI and glycemic parameters.
A Quantitative Model Supporting Socially Responsible Public Investment Decisions for Sustainable Tourism
Authors: Skrame Aurora , Ciancio Claudio , Corvello Vincenzo , Musmanno Roberto
Published: June 2020

The purpose of this article is to develop a quantitative model that supports policy makers in the tourism sector in making socially responsible investment decisions. In particular, this paper proposes a methodological approach to assess the impact of strategic decisions at the policy level, in the field of tourism, from an economic, environmental and social point of view. The Calabria region, in Italy, has been chosen as a real-world case study. Based on historical data, the study identifies the main levers that influence tourism-related dynamics in Calabria. A quantitative forecasting model to support future investment decisions for sustainable tourism has then been developed. This problem is modeled through a multi-criteria optimization framework. To initialize such a framework, a non-linear autoregressive network with exogenous inputs (NARX) has been used. The proposed model is a flexible instrument to evaluate public investment policies in the field of tourism from the point of view of sustainability and social responsibility.
Investor Sentiment and Herding Behavior in the Korean Stock Market
Authors: Choi Ki-Hong , Yoon Seong-Min
Published: June 2020

This paper investigates herding behavior and the connection between herding behavior and investor sentiment. We apply a Cross-Sectional Absolute Deviation (CSAD) approach and the quantile regression method to capture herding behavior in the KOSPI and KOSDAQ stock markets. The analysis results are outlined as follows. First, we find that herding behavior is exhibited during down-market periods in the KOSPI and KOSDAQ stock markets. However, we show that adverse herding behavior occurs in low-trading volume and low-volatility periods. Second, according to the results of the quantile regression, herding behavior is found in the low and high quantiles of the KOSPI and KOSDAQ stock markets. However, adverse herding behavior is also found, which means that investors herd in extreme market conditions. Third, the relationship between investor sentiment and herding behavior is analyzed through regression and quantile regression, and investor sentiment is confirmed to be one of the important factors that can cause herding behavior in the Korean stock market.
An Illumination Insensitive Descriptor Combining the CSLBP Features for Street View Images in Augmented Reality: Experimental Studies
Authors: Xiang Zejun , Yang Ronghua , Deng Chang , Teng Mingxing , She Mengkun , Teng Degui
Published: June 2020

The common feature matching algorithms for street view images are sensitive to the illumination changes in augmented reality (AR), this may cause low accuracy of matching between street view images. This paper proposes a novel illumination insensitive feature descriptor by integrating the center-symmetric local binary pattern (CS-LBP) into a common feature description framework. This proposed descriptor can be used to improve the performance of eight commonly used feature-matching algorithms, e.g., SIFT, SURF, DAISY, BRISK, ORB, FREAK, KAZE, and AKAZE. We perform the experiments on five street view image sequences with different illumination changes. By comparing with the performance of eight original algorithms, the evaluation results show that our improved algorithms can improve the matching accuracy of street view images with changing illumination. Further, the time consumption only increases a little. Therefore, our combined descriptors are much more robust against light changes to satisfy the high precision requirement of augmented reality (AR) system.
Genome-Wide Characterization of GRAS Family and Their Potential Roles in Cold Tolerance of Cucumber (Cucumis sativus L.)
Authors: Lu Xiaohong , Liu Wenqian , Xiang Chenggang , Li Xiaojun , Wang Qing , Wang Tao , Liu Zixi , Zhang Jiali , Gao Lihong , Zhang Wenna
Published: June 2020

Cucumber (Cucumis sativus L.) is one of the most important cucurbit vegetables but is often subjected to stress during cultivation. GRAS (gibberellic acid insensitive, repressor of GAI, and scarecrow) genes encode a family of transcriptional factors that regulate plant growth and development. In the model plant Arabidopsis thaliana, GRAS family genes function in formation of axillary meristem and root radial structure, phytohormone (gibberellin) signal transduction, light signal transduction and abiotic/biological stress. In this study, a gene family was comprehensively analyzed from the aspects of evolutionary tree, gene structure, chromosome location, evolutionary and expression pattern by means of bioinformatics; 37 GRAS gene family members have been screened from cucumber. We reconstructed an evolutionary tree based on multiple sequence alignment of the typical GRAS domain and conserved motif sequences with those of other species (A. thaliana and Solanum lycopersicum). Cucumber GRAS family was divided into 10 groups according to the classification of Arabidopsis and tomato genes. We conclude that tandem and segmental duplication have played important roles in the expansion and evolution of the cucumber GRAS (CsaGRAS) family. Expression patterns of CsaGRAS genes in different tissues and under cold treatment, combined with gene ontology annotation and interaction network analysis, revealed potentially different functions for CsaGRAS genes in response to cold tolerance, with members of the SHR, SCR and DELLA subfamilies likely playing important roles. In conclusion, this study provides valuable information and candidate genes for improving cucumber tolerance to cold stress.
β-Funaltrexamine Displayed Anti-Inflammatory and Neuroprotective Effects in Cells and Rat Model of Stroke
Authors: Wu Chih-Cheng , Chang Cheng-Yi , Shih Kuei-Chung , Hung Chih-Jen , Wang Ya-Yu , Lin Shih-Yi , Chen Wen-Ying , Kuan Yu-Hsiang , Liao Su-Lan , Wang Wen-Yi , Chen Chun-Jung
Published: June 2020

Chronic treatment involving opioids exacerbates both the risk and severity of ischemic stroke. We have provided experimental evidence showing the anti-inflammatory and neuroprotective effects of the μ opioid receptor antagonist β-funaltrexamine for neurodegenerative diseases in rat neuron/glia cultures and a rat model of cerebral Ischemia/Reperfusion (I/R) injury. Independent of in vitro Lipopolysaccharide (LPS)/interferon (IFN-γ)-stimulated neuron/glia cultures and in vivo cerebral I/R injury in Sprague–Dawley rats, β-funaltrexamine downregulated neuroinflammation and ameliorated neuronal degeneration. Alterations in microglia polarization favoring the classical activation state occurred in LPS/IFN-γ-stimulated neuron/glia cultures and cerebral I/R-injured cortical brains. β-funaltrexamine shifted the polarization of microglia towards the anti-inflammatory phenotype, as evidenced by decreased nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2, along with increased CD163 and arginase 1. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by β-funaltrexamine was accompanied by the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein, along with signal transducers and activators of transcription transcriptional activities and associated upstream activators. The effects of β-funaltrexamine are closely linked with its action on neuroinflammation by switching microglia polarization from pro-inflammatory towards anti-inflammatory phenotypes. These findings provide new insights into the anti-inflammatory and neuroprotective mechanisms of β-funaltrexamine in combating neurodegenerative diseases, such as stroke.
Recovery of BDNF and CB1R in the Prefrontal Cortex Underlying Improvement of Working Memory in Prenatal DEHP-Exposed Male Rats after Aerobic Exercise
Authors: Wang Dean-Chuan , Lin Hwai-Ting , Lee Yi-Ju , Yu Hsien-Fu , Wu Sin-Ru , Qamar Muhammad Usama
Published: June 2020

Early-life exposure to di-(2-ethylhexyl)-phthalate (DEHP) has been suggested to relate to hyperactivity, lack of attention, and working memory deficits in school-age children. Brain-derived neurotrophic factor (BDNF) and endocannabinoids are induced by aerobic exercises to provide beneficial effects on brain functions. This study investigated the mechanisms underlying working memory impairment and the protective role of exercise in prenatal DEHP-exposed male rats. Sprague Dawley dams were fed with vehicle or DEHP during gestation. The male offspring were trained to exercise on a treadmill for 5 weeks, which was followed by an assessment of their working memory with a T-maze delayed non-match-to-sample task. The expressions of BDNF, dopamine D1 receptor (D1R), cannabinoid receptor 1 (CB1R), and fatty acid amide hydrolase (FAAH) in the prefrontal cortex were detected by Western blot. The results showed that DEHP-exposed rats exhibited working memory impairments without significant alterations in locomotor activities. The reduced expressions of prefrontal BDNF and CB1R were obtained in the DEHP-exposed rats, while D1R and FAAH were barely affected. Importantly, aerobic exercise during childhood-adolescence prevented the impairment of working memory in the DEHP-exposed rats by recovering the BDNF and CB1R expressions in the prefrontal cortex. These findings suggest that exercise may provide beneficial effects in ameliorating the impairment of working memory in the prenatal DEHP-exposed male rats at late adolescence.
Emerging Roles of Gemin5: From snRNPs Assembly to Translation Control
Authors: Martinez-Salas Encarnacion , Embarc-Buh Azman , Francisco-Velilla Rosario
Published: June 2020

RNA-binding proteins (RBPs) play a pivotal role in the lifespan of RNAs. The disfunction of RBPs is frequently the cause of cell disorders which are incompatible with life. Furthermore, the ordered assembly of RBPs and RNAs in ribonucleoprotein (RNP) particles determines the function of biological complexes, as illustrated by the survival of the motor neuron (SMN) complex. Defects in the SMN complex assembly causes spinal muscular atrophy (SMA), an infant invalidating disease. This multi-subunit chaperone controls the assembly of small nuclear ribonucleoproteins (snRNPs), which are the critical components of the splicing machinery. However, the functional and structural characterization of individual members of the SMN complex, such as SMN, Gemin3, and Gemin5, have accumulated evidence for the additional roles of these proteins, unveiling their participation in other RNA-mediated events. In particular, Gemin5 is a multidomain protein that comprises tryptophan-aspartic acid (WD) repeat motifs at the N-terminal region, a dimerization domain at the middle region, and a non-canonical RNA-binding domain at the C-terminal end of the protein. Beyond small nuclear RNA (snRNA) recognition, Gemin5 interacts with a selective group of mRNA targets in the cell environment and plays a key role in reprogramming translation depending on the RNA partner and the cellular conditions. Here, we review recent studies on the SMN complex, with emphasis on the individual components regarding their involvement in cellular processes critical for cell survival.
Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension
Authors: Ishigami Tomoaki , Kino Tabito , Minegishi Shintaro , Araki Naomi , Umemura Masanari , Ushio Hisako , Saigoh Sae , Sugiyama Michiko
Published: June 2020

Ubiquitination is a representative, reversible biological process of the post-translational modification of various proteins with multiple catalytic reaction sequences, including ubiquitin itself, in addition to E1 ubiquitin activating enzymes, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligase, deubiquitinating enzymes, and proteasome degradation. The ubiquitin–proteasome system is known to play a pivotal role in various molecular life phenomena, including the cell cycle, protein quality, and cell surface expressions of ion-transporters. As such, the failure of this system can lead to cancer, neurodegenerative diseases, cardiovascular diseases, and hypertension. This review article discusses Nedd4-2/NEDD4L, an E3-ubiquitin ligase involved in salt-sensitive hypertension, drawing from detailed genetic dissection analysis and the development of genetically engineered mice model. Based on our analyses, targeting therapeutic regulations of ubiquitination in the fields of cardio-vascular medicine might be a promising strategy in future. Although the clinical applications of this strategy are limited, compared to those of kinase systems, many compounds with a high pharmacological activity were identified at the basic research level. Therefore, future development could be expected.
The Impact of Single- and Double-Strand DNA Breaks in Human Spermatozoa on Assisted Reproduction
Authors: Agarwal Ashok , Barbăroșie Cătălina , Ambar Rafael , Finelli Renata
Published: June 2020

Several cellular insults can result in sperm DNA fragmentation either on one or both DNA strands. Oxidative damage, premature interruption of the apoptotic process and defects in DNA compaction during spermatogenesis are the main mechanisms that cause DNA breaks in sperm. The two-tailed Comet assay is the only technique that can differentiate single- (SSBs) from double- (DSBs) strand DNA breaks. Increased levels of the phosphorylated isoform of the H2AX histone are directly correlated with DSBs and proposed as a molecular biomarker of DSBs. We have carried out a narrative review on the etiologies associated with SSBs and DSBs in sperm DNA, their association with reproductive outcomes and the mechanisms involved in their repair. Evidence suggests a stronger negative impact of DSBs on reproductive outcomes (fertilization, implantation, miscarriage, pregnancy, and live birth rates) than SSBs, which can be partially overcome by using intracytoplasmic sperm injection (ICSI). In sperm, SSBs are irreversible, whereas DSBs can be repaired by homologous recombination, non-homologous end joining (NHEJ) and alternative NHEJ pathways. Although few studies have been published, further research is warranted to provide a better understanding of the differential effects of sperm SSBs and DSBs on reproductive outcomes as well as the prognostic relevance of DNA breaks discrimination in clinical practice.
Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson’s Models
Authors: Di Rosa Gabriele , Brunetti Giovanni , Scuto Maria , Trovato Salinaro Angela , Calabrese Edward J. , Crea Roberto , Schmitz-Linneweber Christian , Calabrese Vittorio , Saul Nadine
Published: June 2020

Parkinson’s disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years. Thus, in the current study we test the health-promoting effects of two hydroxytyrosol preparations, pure HT and Hidrox® (HD), which is hydroxytyrosol in its “natural” environment, in the established invertebrate model organism Caenorhabditis elegans. HD exposure led to much stronger beneficial locomotion effects in wild type worms compared to HT in the same concentration. Consistent to this finding, in OW13 worms, a PD-model characterized by α-synuclein expression in muscles, HD exhibited a significant higher effect on α-synuclein accumulation and swim performance than HT, an effect partly confirmed also in swim assays with the UA44 strain, which features α-synuclein expression in DA-neurons. Interestingly, beneficial effects of HD and HT treatment with similar strength were detected in the lifespan and autofluorescence of wild-type nematodes, in the neuronal health of UA44 worms as well as in the locomotion of rotenone-induced PD-model. Thus, the hypothesis that HD features higher healthspan-promoting abilities than HT was at least partly confirmed. Our study demonstrates that HD polyphenolic extract treatment has the potential to partly prevent or even treat ageing-related neurodegenerative diseases and ageing itself. Future investigations including mammalian models and human clinical trials are needed to uncover the full potential of these olive compounds.
Correction: Zhang, Z.; et al. Roles of MicroRNAs in Establishing and Modulating Stem Cell Potential. Int. J. Mol. Sci. 2019, 20, 3643
Authors: Zhang Zhenwu , Zhuang Lili , Lin Chao-Po
Published: June 2020

The authors wish to make the following correction to this paper [...]
Interactive Effects of Perinatal BPA or DES and Adult Testosterone and Estradiol Exposure on Adult Urethral Obstruction and Bladder, Kidney, and Prostate Pathology in Male Mice
Authors: Taylor Julia A. , Jones Maren Bell , Besch-Williford Cynthia L. , Berendzen Ashley F. , Ricke William A. , vom Saal Frederick S.
Published: June 2020

Obstructive voiding disorder (OVD) occurs during aging in men and is often, but not always, associated with increased prostate size, due to benign prostatic hyperplasia (BPH), prostatitis, or prostate cancer. Estrogens are known to impact the development of both OVD and prostate diseases, either during early urogenital tract development in fetal–neonatal life or later in adulthood. To examine the potential interaction between developmental and adult estrogen exposure on the adult urogenital tract, male CD-1 mice were perinatally exposed to bisphenol A (BPA), diethylstilbestrol (DES) as a positive control, or vehicle negative control, and in adulthood were treated for 4 months with Silastic capsules containing testosterone and estradiol (T+E2) or empty capsules. Animals exposed to BPA or DES during perinatal development were more likely than negative controls to have urine flow/kidney problems and enlarged bladders, as well as enlarged prostates. OVD in adult T+E2-treated perinatal BPA and DES animals was associated with dorsal prostate hyperplasia and prostatitis. The results demonstrate a relationship between elevated exogenous estrogen levels during urogenital system development and elevated estradiol in adulthood and OVD in male mice. These findings support the two-hit hypothesis for the development of OVD and prostate diseases.
Wound Trauma Exacerbates Acute, but not Delayed, Effects of Radiation in Rats: Mitigation by Lisinopril
Authors: Medhora Meetha , Gasperetti Tracy , Schamerhorn Ashley , Gao Feng , Narayanan Jayashree , Lazarova Zelmira , Jacobs Elizabeth R. , Tarima Sergey , Fish Brian L.
Published: June 2020

The goal of this study is to understand and mitigate the effects of wounds on acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), for preparedness against a radiological attack or accident. Combined injuries from concomitant trauma and radiation are likely in these scenarios. Either exacerbation or mitigation of radiation damage by wound trauma has been previously reported in preclinical studies. Female WAG/RijCmcr rats received 13 Gy X-rays, with partial-body shielding of one leg. Within 2 h, irradiated rats and non-irradiated controls were given full-thickness skin wounds with or without lisinopril, started orally 7 days after irradiation. Morbidity, skin wound area, breathing interval and blood urea nitrogen were measured up to 160 days post-irradiation to independently evaluate wound trauma and DEARE. Wounding exacerbated morbidity in irradiated rats between 5 and 14 days post-irradiation (during the ARS phase), and irradiation delayed wound healing. Wounding did not alter delayed morbidities from radiation pneumonitis or nephropathy after 30 days post-irradiation. Lisinopril did not mitigate wound healing, but markedly decreased morbidity during DEARE from 31 through 160 days. The results derived from this unique model of combined injuries suggest different molecular mechanisms of injury and healing of ARS and DEARE after radiation exposure.
Evaluation of the Effect of Selected Brominated Flame Retardants on Human Serum Albumin and Human Erythrocyte Membrane Proteins
Authors: Jarosiewicz Monika , Miłowska Katarzyna , Krokosz Anita , Bukowska Bożena
Published: June 2020

Brominated flame retardants (BFRs) have been using to reduce the flammability of plastics contained in many products, such as household articles, furniture, mattresses, textiles or insulation. Considering the fact that these compounds may be released into the environment leading to the exposure of living organisms, it is necessary to study their possible effects and mechanisms of action. Proteins play a crucial role in all biological processes. For this reason, a simple model of human serum albumin (HSA) was chosen to study the mechanism of BFRs’ effect on proteins. The study determined interactions between selected BFRs, i.e., tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP), and HSA by measurement of fluorescence of intrinsic tryptophan and absorbance of circular dichroism (CD). In addition, in order to understand the possible effect of these compounds in their native environment, the effect of BFRs on membrane proteins of human erythrocytes (red blood cells, RBCs) was also assessed. Among bromophenols, PBP had the strongest oxidative effect on RBC membrane, and 2,4-DBP demonstrated the weakest fluorescence-quenching effect of both membrane tryptophan and HSA. By contrast to PBP, 2,4-DBP and 2,4,6-TBP caused spatial changes of HSA. We have observed that among all analyzed BFRs, TBBPA caused the strongest oxidation of RBC membrane proteins and the model HSA protein, causing reduction of fluorescence of tryptophan contained in them. TBBPA also changed albumin conformation properties, leading to impairment of the α-helix structure. However, TBBPS had the weakest oxidative effect on proteins among studied BFRs and did not affect the secondary structure of HSA.
Advances in DNA Repair—Emerging Players in the Arena of Eukaryotic DNA Repair
Authors: Kciuk Mateusz , Bukowski Karol , Marciniak Beata , Kontek Renata
Published: June 2020

Genomic DNA is constantly damaged by factors produced during natural metabolic processes as well as agents coming from the external environment. Considering such a wide array of damaging agents, eukaryotic cells have evolved a DNA damage response (DRR) that opposes the influence of deleterious factors. Despite the broad knowledge regarding DNA damage and repair, new areas of research are emerging. New players in the field of DDR are constantly being discovered. The aim of this study is to review current knowledge regarding the roles of sirtuins, heat shock proteins, long-noncoding RNAs and the circadian clock in DDR and distinguish new agents that may have a prominent role in DNA damage response and repair.
The Cell Membrane of Sulfolobus spp.—Homeoviscous Adaption and Biotechnological Applications
Authors: Rastädter Kerstin , Wurm David J. , Spadiut Oliver , Quehenberger Julian
Published: June 2020

The microbial cell membrane is affected by physicochemical parameters, such as temperature and pH, but also by the specific growth rate of the host organism. Homeoviscous adaption describes the process of maintaining membrane fluidity and permeability throughout these environmental changes. Archaea, and thereby, Sulfolobus spp. exhibit a unique lipid composition of ether lipids, which are altered in regard to the ratio of diether to tetraether lipids, number of cyclopentane rings and type of head groups, as a coping mechanism against environmental changes. The main biotechnological application of the membrane lipids of Sulfolobus spp. are so called archaeosomes. Archaeosomes are liposomes which are fully or partly generated from archaeal lipids and harbor the potential to be used as drug delivery systems for vaccines, proteins, peptides and nucleic acids. This review summarizes the influence of environmental parameters on the cell membrane of Sulfolobus spp. and the biotechnological applications of their membrane lipids.
Insight into the Genome of Diverse Penicillium chrysogenum Strains: Specific Genes, Cluster Duplications and DNA Fragment Translocations
Authors: Martín Juan F.
Published: June 2020

Background: There are eighteen species within the Penicillium genus section chrysogena, including the original penicillin producers Penicillium notatum (Fleming strain) and Penicillium chrysogenum NRRL 1951. Other wild type isolates of the Penicillium genus are relevant for the production of useful proteins and primary or secondary metabolites. The aim of this article is to characterize strain specific genes and those genes which are involved in secondary metabolite biosynthesis, particularly the mutations that have been introduced during the β-lactams strain improvement programs. Results: The available genomes of several classical and novel P. chrysogenum strains have been compared. The first genome sequenced was that of the reference strain P. chrysogenum Wis54-1255, which derives from the wild type P. chrysogenum NRRL 1951; its genome size is 32.19 Mb and it encodes 12,943 proteins. Four chromosomes were resolved in P. chrysogenum and P. notatum by pulse field gel electrophoresis. The genomes of three industrial strains have a similar size but contain gene duplications and truncations; the penicillin gene cluster copy number ranges from one in the wild type to twelve in the P. chrysogenum ASP-E1 industrial strain and is organized in head to tail tandem repeats. The genomes of two new strains, P. chrysogenum KF-25, a producer of antifungal proteins isolated from a soil sample, and P. chrysogenum HKF2, a strain with carbohydrate-converting activities isolated from a sludge treatment plant, showed strain specific genes. Conclusions: The overall comparison of all available P. chrysogenum genomes indicates that there are a significant number of strain-specific genes, mutations of structural and regulatory genes, gene cluster duplications and DNA fragment translocations. This information provides important leads to improve the biosynthesis of enzymes, antifungal agents, prebiotics or different types of secondary metabolites.
DFNA5 (GSDME) c.991-15_991-13delTTC: Founder Mutation or Mutational Hotspot?
Authors: Booth Kevin T. , Azaiez Hela , Smith Richard J. H.
Published: June 2020

Deafness due to mutations in the DFNA5 gene is caused by the aberrant splicing of exon 8, which results in a constitutively active truncated protein. In a large family of European descent (MORL-ADF1) segregating autosomal dominant nonsyndromic hearing loss, we used the OtoSCOPE platform to identify the genetic cause of deafness. After variant filtering and prioritization, the only remaining variant that segregated with the hearing loss in the family was the previously described c.991-15_991-13delTTC mutation in DFNA5. This 3-base pair deletion in the polypyrimidine of intron 7 is a founder mutation in the East Asian population. Using ethnicity-informative markers and haplotype reconstruction within the DFNA5 gene, we confirmed family MORL-ADF1 is of European ancestry, and that the c.991-15_991-13delTTC mutation arose on a unique haplotype, as compared to that of East Asian families segregating this mutation. In-depth audiometric analysis showed no statistical difference between the audiometric profile of family MORL-ADF1 and the East Asian families. Our data suggest the polypyrimidine tract in intron 7 may be a hotspot for mutations.
Mapping Quantitative Trait Loci for 1000-Grain Weight in a Double Haploid Population of Common Wheat
Authors: Liu Tao , Wu Lijun , Gan Xiaolong , Chen Wenjie , Liu Baolong , Fedak George , Cao Wenguang , Chi Dawn , Liu Dengcai , Zhang Huaigang , Zhang Bo
Published: June 2020

Thousand-grain weight (TGW) is a very important yield trait of crops. In the present study, we performed quantitative trait locus (QTL) analysis of TGW in a doubled haploid population obtained from a cross between the bread wheat cultivar “Superb” and the breeding line “M321” using the wheat 55-k single-nucleotide polymorphism (SNP) genotyping assay. A genetic map containing 15,001 SNP markers spanning 2209.64 cM was constructed, and 9 QTLs were mapped to chromosomes 1A, 2D, 4B, 4D, 5A, 5D, 6A, and 6D based on analyses conducted in six experimental environments during 2015–2017. The effects of the QTLs qTgw.nwipb-4DS and qTgw.nwipb-6AL were shown to be strong and stable in different environments, explaining 15.31–32.43% and 21.34–29.46% of the observed phenotypic variance, and they were mapped within genetic distances of 2.609 cM and 5.256 cM, respectively. These novel QTLs may be used in marker-assisted selection in wheat high-yield breeding.
Modulation of VEGF Expression and Oxidative Stress Response by Iodine Deficiency in Irradiated Cancerous and Non-Cancerous Breast Cells
Authors: Vanderstraeten Jessica , Baselet Bjorn , Buset Jasmine , Ben Said Naziha , de Ville de Goyet Christine , Many Marie-Christine , Gérard Anne-Catherine , Derradji Hanane
Published: June 2020

Breast cancer remains a major concern and its physiopathology is influenced by iodine deficiency (ID) and radiation exposure. Since radiation and ID can separately induce oxidative stress (OS) and microvascular responses in breast, their combination could additively increase these responses. Therefore, ID was induced in MCF7 and MCF12A breast cell lines by medium change. Cells were then X-irradiated with doses of 0.05, 0.1, or 3 Gy. In MCF12A cells, both ID and radiation (0.1 and 3 Gy) increased OS and vascular endothelial growth factor (VEGF) expression, with an additive effect when the highest dose was combined with ID. However, in MCF7 cells no additive effect was observed. VEGF mRNA up-regulation was reactive oxygen species (ROS)-dependent, involving radiation-induced mitochondrial ROS. Results on total VEGF mRNA hold true for the pro-angiogenic isoform VEGF165 mRNA, but the treatments did not modulate the anti-angiogenic isoform VEGF165b. Radiation-induced antioxidant response was differentially regulated upon ID in both cell lines. Thus, radiation response is modulated according to iodine status and cell type and can lead to additive effects on ROS and VEGF. As these are often involved in cancer initiation and progression, we believe that iodine status should be taken into account in radiation prevention policies.
Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone
Authors: Timoshnikov Viktor A. , Kobzeva Tatyana V. , Polyakov Nikolay E. , Kontoghiorghes George J.
Published: June 2020

Ascorbic acid (AscH2) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in medical practice especially for increasing iron absorption and as an adjuvant therapeutic in iron chelation therapy, but its mode of action and implications in iron metabolism and toxicity are not yet clear. In this study, we used UV–Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe3+ to Fe2+, followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe3+ ↔ Fe2+ in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron–ascorbate complex compared to the FeL13 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL13 chelate complex resulting in the formation of mixed L12AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4–5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid, iron, and L1.
Reduced Fecal Calprotectin and Inflammation in a Murine Model of Atopic Dermatitis Following Probiotic Treatment
Authors: Kim Myoung-Ju , Kim Ji-Young , Kang Minje , Won Moo-Ho , Hong Seok-Ho , Her Young
Published: June 2020

Atopic dermatitis (AD) is one of the most common skin diseases with inflammation, chronic relapses, and intense pruritus. Its pathogenesis includes genetic susceptibility, an abnormal epidermal lipid barrier, and an increased production of IgE due to immune dysregulation. Recently, AD has been reported to be associated with intestinal inflammation and dysbiosis in human and murine models. Various probiotics are being used to control intestinal dysbiosis and inflammatory reactions. However, it is difficult to predict or determine the therapeutic effects of the probiotics, since it is rare for clinicians to use the probiotics alone to treat AD. It is also difficult to check whether the intestinal inflammation in patients with AD has improved since probiotic treatment. The aim of the present study was to determine whether mice with induced atopic dermatitis had any changes in fecal calprotectin, an indicator of intestinal inflammation, after probiotic administration. Our results showed that the fecal calprotectin levels in mice with induced dermatitis decreased significantly after the administration of probiotics. In addition, epidermal skin lesions were attenuated and inflammatory-related cytokines were downregulated after the administration of probiotics in mice with induced dermatitis. These results suggest that changes in fecal calprotectin levels could be used to assess the effectiveness of a probiotic strain as an adjuvant treatment for AD.
S100A6 and Its Brain Ligands in Neurodegenerative Disorders
Authors: Filipek Anna , Leśniak Wiesława
Published: June 2020

The S100A6 protein is present in different mammalian cells and tissues including the brain. It binds Ca2+ and Zn2+ and interacts with many target proteins/ligands. The best characterized ligands of S100A6, expressed at high level in the brain, include CacyBP/SIP and Sgt1. Research concerning the functional role of S100A6 and these two ligands indicates that they are involved in various signaling pathways that regulate cell proliferation, differentiation, cytoskeletal organization, and others. In this review, we focused on the expression/localization of these proteins in the brain and on their possible role in neurodegenerative diseases. Published results demonstrate that S100A6, CacyBP/SIP, and Sgt1 are expressed in various brain structures and in the spinal cord and can be found in different cell types including neurons and astrocytes. When it comes to their possible involvement in nervous system pathology, it is evident that their expression/level and/or subcellular localization is changed when compared to normal conditions. Among diseases in which such changes have been observed are Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), epileptogenesis, Parkinson’s disease (PD), Huntington’s disease (HD), and others.
AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress
Authors: Brun Thierry , Jiménez-Sánchez Cecilia , Madsen Jesper Grud Skat , Hadadi Noushin , Duhamel Dominique , Bartley Clarissa , Oberhauser Lucie , Trajkovski Mirko , Mandrup Susanne , Maechler Pierre
Published: June 2020

Chronic exposure of pancreatic β-cells to elevated nutrient levels impairs their function and potentially induces apoptosis. Like in other cell types, AMPK is activated in β-cells under conditions of nutrient deprivation, while little is known on AMPK responses to metabolic stresses. Here, we first reviewed recent studies on the role of AMPK activation in β-cells. Then, we investigated the expression profile of AMPK pathways in β-cells following metabolic stresses. INS-1E β-cells and human islets were exposed for 3 days to glucose (5.5–25 mM), palmitate or oleate (0.4 mM), and fructose (5.5 mM). Following these treatments, we analyzed transcript levels of INS-1E β-cells by qRT-PCR and of human islets by RNA-Seq; with a special focus on AMPK-associated genes, such as the AMPK catalytic subunits α1 (Prkaa1) and α2 (Prkaa2). AMPKα and pAMPKα were also evaluated at the protein level by immunoblotting. Chronic exposure to the different metabolic stresses, known to alter glucose-stimulated insulin secretion, did not change AMPK expression, either in insulinoma cells or in human islets. Expression profile of the six AMPK subunits was marginally modified by the different diabetogenic conditions. However, the expression of some upstream kinases and downstream AMPK targets, including K-ATP channel subunits, exhibited stress-specific signatures. Interestingly, at the protein level, chronic fructose treatment favored fasting-like phenotype in human islets, as witnessed by AMPK activation. Collectively, previously published and present data indicate that, in the β-cell, AMPK activation might be implicated in the pre-diabetic state, potentially as a protective mechanism.