bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Biomarkers of Panic Disorder: A Systematic Review
Authors: Tretiakov Artemii , Malakhova Alena , Naumova Elena , Rudko Olga , Klimov Eugene
Published: November 2020

(1) Background: Although panic disorder (PD) is one of the most common anxiety disorders severely impacting quality of life, no effective genetic testing exists; known data on possible genetic biomarkers is often scattered and unsystematic which complicates further studies. (2) Methods: We used PathwayStudio 12.3 (Elsevier, The Netherlands) to acquire literature data for further manual review and analysis. 229 articles were extracted, 55 articles reporting associations, and 32 articles reporting no associations were finally selected. (3) Results: We provide exhaustive information on genetic biomarkers associated with PD known in the scientific literature. Data is presented in two tables. Genes COMT and SLC6A4 may be considered the most promising for PD diagnostic to date. (4) Conclusions: This review illustrates current progress in association studies of PD and may indicate possible molecular mechanisms of its pathogenesis. This is a possible basis for data analysis, novel experimental studies, or developing test systems and personalized treatment approaches.
Assessment of Imputation from Low-Pass Sequencing to Predict Merit of Beef Steers
Authors: Snelling Warren M. , Hoff Jesse L. , Li Jeremiah H. , Kuehn Larry A. , Keel Brittney N. , Lindholm-Perry Amanda K. , Pickrell Joseph K.
Published: November 2020

Decreasing costs are making low coverage sequencing with imputation to a comprehensive reference panel an attractive alternative to obtain functional variant genotypes that can increase the accuracy of genomic prediction. To assess the potential of low-pass sequencing, genomic sequence of 77 steers sequenced to >10X coverage was downsampled to 1X and imputed to a reference of 946 cattle representing multiple Bos taurus and Bos indicus-influenced breeds. Genotypes for nearly 60 million variants detected in the reference were imputed from the downsampled sequence. The imputed genotypes strongly agreed with the SNP array genotypes (r¯=0.99) and the genotypes called from the transcript sequence (r¯=0.97). Effects of BovineSNP50 and GGP-F250 variants on birth weight, postweaning gain, and marbling were solved without the steers’ phenotypes and genotypes, then applied to their genotypes, to predict the molecular breeding values (MBV). The steers’ MBV were similar when using imputed and array genotypes. Replacing array variants with functional sequence variants might allow more robust MBV. Imputation from low coverage sequence offers a viable, low-cost approach to obtain functional variant genotypes that could improve genomic prediction.
New Cadanav Methodology for Rock Fall Hazard Zoning Based on 3D Trajectory Modelling
Authors: Abbruzzese Jacopo M. , Labiouse Vincent
Published: November 2020

Most rock fall hazard zoning methodologies are currently based on trajectory modelling, usually performed along 2D slope profiles. For many topographic configurations, this approach cannot provide a realistic description of the way rock fall trajectories and, ultimately, hazard are spatially distributed all over a slope. This paper presents a new methodology for rock fall hazard zoning, directly applicable to 3D topographies, starting from 3D trajectory simulation results. The procedure is an extension of the Cadanav methodology introduced for hazard zoning along 2D slope profiles. As such, it is fully quantitative and attempts at reducing as much as possible uncertainties and subjective elements affecting current methods for rock fall hazard analysis and zoning. It is also among the first to introduce a “fully-coupled” rock fall intensity-frequency approach. Hazard is estimated by means of “hazard curves”, described at each point of the slope by rock fall intensity-return period couples. These curves may be superimposed on any intensity-return period diagram prescribed in national or regional land use planning regulations, in order to determine which hazardous condition prevails at each point of the slope. The application of the new Cadanav methodology is illustrated for both a theoretical case of simple topography underlying a linear cliff and a real configuration involving a complex topography, characterised by strong three-dimensional features affecting the paths of the blocks. For all topographic models, results obtained for several scenarios involving either localised or diffuse source areas proved that the methodology performs extremely well, providing objective and reproducible results based on a rigorous combination of rock fall energy and return period. Additional tests and real case studies are currently under investigation, for strengthening even further the validation of the approach and extend its applicability to even more complex rock fall scenarios.
Psychological Analysis among Goal Orientation, Emotional Intelligence and Academic Burnout in Middle School Students
Authors: Usán Supervía Pablo , Salavera Bordás Carlos , Murillo Lorente Víctor
Published: November 2020

During schooling, students can undergo, for more or less long periods of time, different contextual settings that can negatively affect their personal and academic development, leading them not to meet their academic goals. The main objective of this research responds to examine the relationships between the constructs of goal orientations, emotional intelligence, and burnout in students. Method: This research comprised 2896 students from 15 Spanish high schools with ages between 12 and 18 years distributed across male (N = 1614; 55.73%) and female (N = 1282; 44.26%) genders. The measurements were made through Perception of Success Questionnaire (POSQ), the Trait Meta Mood Scale (TMMS-24) and the Maslach Burnout Inventory Student Survey (MBI-SS). Results: Results showed links between task orientation, high emotional intelligence levels, and adaptive behaviors and between ego orientation, academic burnout and less adaptive behavior. Similarly, it was shown that emotional intelligence can be used to predict goal-oriented behaviors. Conclusion: It is argued that the promotion of task orientation among secondary school students can lead to the adoption of adaptive behaviors and this, in turn, improve the development of students toward academic and personal settings.
Differences in the Estimation of Wildfire-Associated Air Pollution by Satellite Mapping of Smoke Plumes and Ground-Level Monitoring
Authors: Fadadu Raj P. , Balmes John R. , Holm Stephanie M.
Published: November 2020

Wildfires, which are becoming more frequent and intense in many countries, pose serious threats to human health. To determine health impacts and provide public health messaging, satellite-based smoke plume data are sometimes used as a proxy for directly measured particulate matter levels. We collected data on particulate matter <2.5 μm in diameter (PM2.5) concentration from 16 ground-level monitoring stations in the San Francisco Bay Area and smoke plume density from satellite imagery for the 2017–2018 California wildfire seasons. We tested for trends and calculated bootstrapped differences in the median PM2.5 concentrations by plume density category on a 0–3 scale. The median PM2.5 concentrations for categories 0, 1, 2, and 3 were 16, 22, 25, and 63 μg/m3, respectively, and there was much variability in PM2.5 concentrations within each category. A case study of the Camp Fire illustrates that in San Francisco, PM2.5 concentrations reached their maximum many days after the peak for plume density scores. We found that air pollution characterization by satellite imagery did not precisely align with ground-level PM2.5 concentrations. Public health practitioners should recognize the need to combine multiple sources of data regarding smoke patterns when developing public guidance to limit the health effects of wildfire smoke.
Changes in Salivary Levels of Creatine Kinase, Lactate Dehydrogenase, and Aspartate Aminotransferase after Playing Rugby Sevens: The Influence of Gender
Authors: González Fernández Álvaro , de la Rubia Ortí Jose Enrique , Franco-Martinez Lorena , Ceron Jose Joaquín , Mariscal Gonzalo , Barrios Carlos
Published: November 2020

Rugby sevens is characterised by continuous exertion and great physical contact per unit of time, leading to muscle damage. It is important to identify markers that can quantify muscle damage in order to improve recovery strategies. The objective of this study was to evaluate the release dynamics of muscle damage markers creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in saliva samples when playing rugby sevens, analysing the influence of gender, during the rugby sevens university championship of Spain. The total sample included 27 athletes, divided into two teams of 14 men and 13 women between 18 and 31 years of age. CK, LDH, and AST were quantified from salivary samples collected from each athlete before and after three rugby sevens matches. The modified Borg scale of perceived exertion was also used after each match. When the results were analysed globally, there were no differences in CK and LDH before and after any match, but AST did show differences after two days of completing all matches. In terms of gender, the three enzymes showed different responses in men and women. Regarding the Borg scale, there were only significant differences between men and women after completing all mataches, with a greater perceived exertion in women. Based on our results, it can be stated that that serial matches of rugby sevens can cause changes of different magnitude in AST, CK and LDH activities in saliva, with AST showing the most significant variations and these changes are more pronounced in men than in women.
The Moderating Role of Extroversion and Neuroticism in the Relationship between Autonomy at Work, Burnout, and Job Satisfaction
Authors: Farfán Jesús , Peña Marta , Fernández-Salinero Samuel , Topa Gabriela
Published: November 2020

The main aim of this research project was to determine the relationship that exists between autonomy at work and both burnout and job satisfaction, taking into account the moderating effect of the personality factors extroversion and neuroticism. The study was carried out with 971 volunteers (553 women and 418 men) with a mean age of 37.58 years. The majority had either a university degree (485 participants) or higher education qualifications (Spanish baccalaureate) (202 participants). The following instruments were administered: the Maslach Burnout Inventory (MBI), to measure burnout among participants; the Mini International Personality Item Pool Scale (Mini-IPIP) by Donnellan, Oswald, Baird, and Lucas (2006) to measure the personality factors extroversion and neuroticism; the Brief Index of Affective Job Satisfaction (BIAJS) by Thompson and Phua (2012); and the Job Content Questionnaire (JCQ) by Karasek (1985) to measure autonomy at work. The results obtained indicate that those who enjoy greater autonomy at work have lower levels of emotional exhaustion. The stronger the effect is, the higher the score for extroversion. The personality factors studied were not found to have a direct influence on the criterion variables. However, the interaction effects were significant, except in the case of neuroticism. The results indicate that there are no differences between those who score highly for extroversion and neuroticism and the rest of the population in terms of predicting emotional exhaustion or job satisfaction. The present study aims to serve as a guideline for recruitment specialists, business owners, and job designers, encouraging them to take into account all these variables in order to foster the development of healthy and competitive organizations. Environmental moderators that could interfere with the result have not been introduced in this research. It has focused on the study of the personality factors of the workers, considering that the professional functions performed by the workers were similar.
Current Pharmacological Treatment of Type 2 Diabetes Mellitus in Undocumented Migrants: Is It Appropriate for the Phenotype of the Disease?
Authors: Fiorini Gianfrancesco , Cortinovis Ivan , Corrao Giovanni , Franchi Matteo , Pincelli Angela Ida , Perotti Mario , Rigamonti Antonello Emilio , Sartorio Alessandro , Cella Silvano Gabriele
Published: November 2020

Type 2 diabetes is increasingly recognized as a spectrum of metabolic disorders sharing chronic hyperglycaemia. In Europe, the continually growing number of migrants from developing countries could affect diabetes phenotypes. We evaluated a population of 426 Italians and 412 undocumented migrants. Using 17 variables (with the exclusion of ethnic origin) we performed a multiple component analysis to detect potential clusters, independently from ethnicity. We also compared the two groups to evaluate potential ethnicity associated differences. We found five clusters of patients with different disease phenotypes. Comparing Italians with undocumented migrants, we noted that the first had more often cardiovascular risk factors and neurologic involvement, while the latter had a higher frequency of diabetic ulcers and renal involvement. Metformin was used in a comparable percentage of patients in all clusters, but other antidiabetic treatments showed some differences. Italians were more often on insulin, due to a larger use of long acting insulin, and received a larger number of oral antidiabetics in combination. Pharmacological treatment of comorbidities showed some differences too. We suggest that type 2 diabetes should be considered as a spectrum of diseases with different phenotypes also in heterogeneous populations, and that this is not due only to ethnic differences.
Why Do Some Spanish Nursing Students with Menstrual Pain Fail to Consult Healthcare Professionals?
Authors: Ramos-Pichardo Juan Diego , Ortega-Galán Ángela María , Iglesias-López María Teresa , Abreu-Sánchez Ana , Fernández-Martínez Elia
Published: November 2020

Dysmenorrhea is a problem that affects a large percentage of young women worldwide. Alarmingly, the majority of these women choose to self-medicate rather than consult a healthcare professional, despite the risks involved. The present study aimed to explore the reasons why undergraduate nursing students do not consult health care professionals regarding their menstrual pain. A qualitative study was conducted using an open question: “Why didn’t you consult a healthcare professional?” within the context of a research project on primary dysmenorrhea among nursing students at the University of Huelva, Spain. The responses of 202 women were analyzed using content analysis. Three categories were identified: assessment of the pain experienced, expectations, and experiences of professional care and selfcare. We found a striking normalization of the problem; notably, students downplayed the importance of the problem, considering that it was not worth consulting a physician. Furthermore, there was a notable degree of self-medication using non-steroidal anti-inflammatories (NSAIDs). These results may be useful for orienting policies to raise social awareness of this problem and for designing health education strategies aimed at women with primary dysmenorrhea.
Dopamine Receptor D2 Gene (DRD2) Polymorphisms, Job Stress, and Their Interaction on Sleep Dysfunction
Authors: Jiang Yu , Liu Baoying , Wu Chuancheng , Gao Xiaoyan , Lu Yaoqin , Lian Yulong , Liu Jiwen
Published: November 2020

Recent studies have shown that incessant job stress could eventually result in sleep dysfunction (SD), and most importantly, the essential role dopamine receptor D2 (DRD2) gene polymorphisms play in the psychopathological mechanism of SD. The Effort-Reward Imbalance scale and the Pittsburgh Sleep Quality Index were both used to access SD and job stress (JS). A significant negative correlation was observed between the sDA levels and SD subscale scores (sleep efficiency, daytime dysfunction). The findings revealed that high levels of JS were linked to a higher SD score (OR = 2.13, 95% CI: 1.46–3.12). Likewise, the homozygous A1A1 genotype of DRD2 rs1800497 was more likely to be associated with SD (OR = 2.90, 95% CI: 1.75–4.82). Compared to participants with low JS and heterozygous A1A2/A2A2 genotype, those with both high JS and homozygous A1A1 genotype had a higher SD score (OR = 5.40, 95% CI: 2.89–10.11). The A1 allele of the DRD2 rs1800497 polymorphism also enhances the likelihood of SD when undergoing JS. Besides, subjects with low JS and the homozygous A1A1 genotype also showed an increased possibility for sleep dysfunction (OR = 2.05, 95% CI: 1.03–4.11). Our results suggest that the DA system may interrelate with JS to affect sleep.
Associations between Stress and Physical Activity in Korean Adolescents with Atopic Dermatitis Based on the 2018–2019 Korea Youth Risk Behavior Web-Based Survey
Authors: Kong Sunga , Koo Jaisun , Lim Seung Kil
Published: November 2020

This study aimed to confirm the associations between stress and physical activity (PA) in Korean adolescents with atopic dermatitis (AD) based on data from the 2018–2019 Korea Youth Risk Behavior Web-Based Survey. The AD groups were divided into adolescents who were not diagnosed with AD, adolescents who were diagnosed with AD more than one year ago, and adolescents who were diagnosed with AD within one year. We defined the regular PA group and the non-PA group using the American College of Sports Medicine guidelines for children and adolescents: moderate to vigorous PA ≥5 times per week, including vigorous PA ≥3 days per week and muscle strengthening exercises ≥3 times per week. We performed logistic regression analysis to calculate the stress odds ratio (OR) and 95% confidence interval (CI) by group using model 1, adjusted for age, sex, and body mass index, and model 2, additionally adjusted for drinking, smoking, economic statuses, academic achievement, asthma, and rhinitis. In the group diagnosed with AD within one year, stress was 41% and 32% higher according to models 1 (1.41 (1.31–1.52)) and 2 (1.34 (1.20–1.50)), respectively. However, the stress OR was 30% lower in adolescents who completed regular PA than in the non-PA group (model 1: 0.71 (0.58–0.87); model 2: 0.68 (0.57–0.84)), even if diagnosed with AD within one year. In conclusion, the stress of adolescents with AD was significantly higher than that of adolescents without AD. The stress was significantly lower in the group with regular PA, and it was more robust in adolescents diagnosed with AD within one year.
The Influence of Aerobic Fitness on Heart Rate Responses of Custody Assistant Recruits during Circuit Training Sessions
Authors: Moreno Matthew R. , Rodas Karly A. , Bloodgood Ashley M. , Dawes J. Jay , Dulla Joseph M. , Orr Robin M. , Lockie Robert G.
Published: November 2020

This study captured heart rate (HR) responses of custody assistant (CA) recruits undertaking circuit training sessions. Data from 10 male and 12 female CA recruits were analyzed. Based on YMCA step test recovery HR, recruits were divided into higher fitness (HF; top 25%), lower fitness (LF; bottom 25%), and moderate fitness (MF; remaining recruits) groups. HR was measured during two circuit training sessions featuring calisthenics and running. HR zones were defined as: very light (<57% of age-predicted maximum heart-rate [HRmax]); light (57–63% HRmax); moderate (64–76% HRmax); vigorous (77–95% HRmax); and very vigorous (>95% HRmax). A one-way ANOVA, with Bonferroni post hoc, calculated between-group differences in time spent, and percentage of total time, in the HR zones. In session one, the LF group spent less time in the light training zone compared to the MF group, and more time in the very vigorous zone compared to the HF group (p = 0.027–0.047). In session two, the LF group spent more time in the moderate zone compared to both groups, and a greater percentage of time in the very vigorous zone compared to the MF group (p = 0.002–0.004). LF recruits generally worked harder during circuit training than their fitter counterparts, which supported recommendations for ability-based modifications.
Psychotherapy via the Internet: What Programs Do Psychotherapists Use, How Well-Informed Do They Feel, and What Are Their Wishes for Continuous Education?
Authors: Humer Elke , Stippl Peter , Pieh Christoph , Schimböck Wolfgang , Probst Thomas
Published: November 2020

The outbreak of the COVID-19 pandemic has caused changes in the provision of psychotherapy around the world. The common format of delivering in-person psychotherapy is replaced by psychotherapy via the Internet to a great extent. This study examined how well Austrian psychotherapists feel informed about the use of the Internet in psychotherapy, where additional information needs exist, and which software is used. A link to an online survey was sent to all psychotherapists providing a valid email address in the official list of licensed psychotherapists at the start of the COVID-19 lockdown in Austria. A total of 1547 people took part in the survey. The results show that psychotherapy via the Internet was primarily offered via Skype and Zoom during the COVID-19 pandemic and that the majority of the therapists felt well-informed about psychotherapy via the Internet; however, several therapists stated that they wish to have further information on data protection and security. Overall, the study shows that Austrian psychotherapists coped well with the rapid change from the provision of psychotherapy through personal contact to psychotherapy via the Internet. Security and data protection aspects of therapy via the Internet should be addressed in training and further education of psychotherapists. As this study was conducted online, it might have caused some respondent bias towards a higher participation of psychotherapists with higher preference for new technologies.
Strength Training Habits in Amateur Endurance Runners in Spain: Influence of Athletic Level
Authors: García-Pinillos Felipe , Lago-Fuentes Carlos , Jaén-Carrillo Diego , Bujalance-Moreno Pascual , Latorre-Román Pedro Ángel , Roche-Seruendo Luis Enrique , Ramirez-Campillo Rodrigo
Published: November 2020

This study determined the strength training (ST) habits of amateur endurance runners in Spain regarding athletic level. A sixteen-item online questionnaire comprised of (i) demographic information, (ii) performance, and (iii) training contents was completed by 1179 athletes. Five group levels were determined according to the personal best times of the athletes in a 10-km trial (LG1: level group 1, 50–55 min; LG2: level group 2, 45–50 min; LG3: level group 3, 40–45 min; LG4: level group 4, 35–40 min; LG5: level group 5, 30–35 min). Most athletes (n = 735, 62.3%) perceived ST as being a key component in their training program. Resistance training (RT) was reported as a ST type used by 63.4% of the athletes, 66.9% reported using bodyweight exercises, 46.8% reported using plyometric training, 65.6% reported using uphill runs, and 17.8% reported using resisted runs. The prevalence of runners who excluded ST from their training programs decreased as the athletic performance level increased (18.2% in lower-level athletes vs. 3.0% in higher-level), while the inclusion of RT, bodyweight exercises, plyometric training, and uphill and resisted runs was more frequent within higher-level groups. Most athletes included ST using low-to-moderate loads and high a number of repetitions/sets comprised of RT, plyometric training, resisted runs, and core, respiratory, and foot muscles training.
Study of the Motivation of Spanish Amateur Runners Based on Training Patterns and Gender
Authors: Manzano-Sánchez David , Postigo-Pérez Lucas , Gómez-López Manuel , Valero-Valenzuela Alfonso
Published: November 2020

The objectives of the present study are to analyze the different training patterns of the amateur runners, according to their gender, and to find out a correlation between the training pattern and the motivation. The sample was composed of 457 amateur runners. For the collection of data, a two-part questionnaire was used. The first part consisted of questions about sporting and healthy patterns and the second part consisted of the Perception of Success Questionnaire (POSQ), adapted to Spanish. The obtained results indicated that their motives for starting to practice running and to continue their involvement are health and fun. The training pattern is as follows: they practise one to three days per week, running from three to five hours overall plus additional stretching and high intensity training. They participated in less than one running event per month. Most of them did not belong to an athletic club, did not have a coach, were not federated and have more than four years’ experience of running. What concerns the gender differences, the men trained more than the women, and they did it with relatives and friends; women preferred to do it with friends or by themselves with the assistance of a coach. Age and running hours per week were the best variables to predict the task goal orientation, especially for men. For women, training hours per week predicted the goal orientation but to the ego. This finding could be especially helpful for coaches. A high number of training hours for men was linked with a task goal orientation, and on the other hand, for women it meant an ego goal orientation. The consequences of their behaviours were likely to be markedly different.
Depleting RhoA/Stress Fiber-Organized Fibronectin Matrices on Tumor Cells Non-Autonomously Aggravates Fibroblast-Driven Tumor Cell Growth
Authors: Huang Li-Tzu , Tsai Chen-Lung , Huang Shin-Huei , Chang Ming-Min , Chang Wen-Tsan , Cheng Li-Hsin , Cheng Hung-Chi
Published: November 2020

Fibronectin (FN) expressed by tumor cells has been known to be tumor suppressive but the pericellular FN (periFN) assembled on circulating tumor cells appears to evidently promote distant metastasis. Whereas the regulation of periFN assembly in suspended cells has currently been under investigation, how it is regulated in adherent tumor cells and the role of periFN in primary tumor growth remain elusive. Techniques of RNAi, plasmid transfections, immunoblotting, fluorescence/immunohistochemistry staining, cell proliferation assays, and primary tumor growth in C57BL6 mice and Fischer 344 rats were employed in this study. We found that endogenously synthesized FN in adherent tumor cells was required for periFN assembly which was aligned by RhoA-organized actin stress fiber (SF). Depleting periFN on adherent tumor cells congruently promoted in vivo tumor growth but surprisingly did not autonomously impact on in vitro tumor cell proliferation and apoptosis, suggestive of a non-autonomous role of periFN in in vivo tumor growth. We showed that the proliferative ability of shFN-expressing tumor cells was higher than shScramble cells did in the presence of fibroblasts. Altogether, these results suggested that depriving RhoA/SF-regulated periFN matrices non-autonomously promotes fibroblast-mediated tumor cell growth.
Targeting DNA Damage Response in Prostate and Breast Cancer
Authors: Wengner Antje M. , Scholz Arne , Haendler Bernard
Published: November 2020

Steroid hormone signaling induces vast gene expression programs which necessitate the local formation of transcription factories at regulatory regions and large-scale alterations of the genome architecture to allow communication among distantly related cis-acting regions. This involves major stress at the genomic DNA level. Transcriptionally active regions are generally instable and prone to breakage due to the torsional stress and local depletion of nucleosomes that make DNA more accessible to damaging agents. A dedicated DNA damage response (DDR) is therefore essential to maintain genome integrity at these exposed regions. The DDR is a complex network involving DNA damage sensor proteins, such as the poly(ADP-ribose) polymerase 1 (PARP-1), the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the ataxia–telangiectasia-mutated (ATM) kinase and the ATM and Rad3-related (ATR) kinase, as central regulators. The tight interplay between the DDR and steroid hormone receptors has been unraveled recently. Several DNA repair factors interact with the androgen and estrogen receptors and support their transcriptional functions. Conversely, both receptors directly control the expression of agents involved in the DDR. Impaired DDR is also exploited by tumors to acquire advantageous mutations. Cancer cells often harbor germline or somatic alterations in DDR genes, and their association with disease outcome and treatment response led to intensive efforts towards identifying selective inhibitors targeting the major players in this process. The PARP-1 inhibitors are now approved for ovarian, breast, and prostate cancer with specific genomic alterations. Additional DDR-targeting agents are being evaluated in clinical studies either as single agents or in combination with treatments eliciting DNA damage (e.g., radiation therapy, including targeted radiotherapy, and chemotherapy) or addressing targets involved in maintenance of genome integrity. Recent preclinical and clinical findings made in addressing DNA repair dysfunction in hormone-dependent and -independent prostate and breast tumors are presented. Importantly, the combination of anti-hormonal therapy with DDR inhibition or with radiation has the potential to enhance efficacy but still needs further investigation.
Crosstalk between Androgen-ZIP9 Signaling and Notch Pathway in Rodent Sertoli Cells
Authors: Kamińska Alicja , Marek Sylwia , Pardyak Laura , Brzoskwinia Małgorzata , Bilinska Barbara , Hejmej Anna
Published: November 2020

Our recent study demonstrated altered expression of Notch ligands, receptors, and effector genes in testes of pubertal rats following reduced androgen production or signaling. Herein we aimed to explore the role of nuclear androgen receptor (AR) and membrane androgen receptor (Zrt- and Irt-like protein 9; ZIP9) in the regulation of Notch pathway activation in rodent Sertoli cells. Experiments were performed using TM4 and 15P-1 Sertoli cell lines and rat primary Sertoli cells (PSC). We found that testosterone (10−8 M–10−6 M) increased the expression of Notch1 receptor, its active form Notch1 intracellular domain (N1ICD) (p < 0.05, p < 0.01, p < 0.001), and the effector genes Hey1 (p < 0.05, p < 0.01, p < 0.001) and Hes1 (p < 0.05, p < 0.001) in Sertoli cells. Knockdown of AR or ZIP9 as well as antiandrogen exposure experiments revealed that (i) action of androgens via both AR and ZIP9 controls Notch1/N1ICD expression and transcriptional activity of recombination signal binding protein (RBP-J), (ii) AR-dependent signaling regulates Hey1 expression, (iii) ZIP9-dependent pathway regulates Hes1 expression. Our findings indicate a crosstalk between androgen and Notch signaling in Sertoli cells and point to cooperation of classical and non-classical androgen signaling pathways in controlling Sertoli cell function.
Diurnal Changes in Water Soluble Carbohydrate Components in Leaves and Sucrose Associated TaSUT1 Gene Expression during Grain Development in Wheat
Authors: Al-Sheikh Ahmed Sarah , Zhang Jingjuan , Farhan Hussein , Zhang Yingquan , Yu Zitong , Islam Shahidul , Chen Jiansheng , Cricelli Sanda , Foreman Andrew , Ende Wim Van den , Ma Wujun , Dell Bernard
Published: November 2020

In plant tissues, sugar levels are determined by the balance between sugar import, export, and sugar synthesis. So far, water soluble carbohydrate (WSC) dynamics have not been investigated in a diurnal context in wheat stems as compared to the dynamics in flag leaves during the terminal phases of grain filling. Here, we filled this research gap and tested the hypothesis that WSC dynamics interlink with gene expression of TaSUT1. The main stems and flag leaves of two genotypes, Westonia and Kauz, were sampled at four hourly intervals over a 24 h period at six developmental stages from heading to 28 DAA (days after anthesis). The total levels of WSC and WSC components were measured, and TaSUT1 gene expression was quantified at 21 DAA. On average, the total WSC and fructan levels in the stems were double those in the flag leaves. In both cultivars, diurnal patterns in the total WSC and sucrose were detected in leaves across all developmental stages, but not for the fructans 6-kestose and bifurcose. However, in stems, diurnal patterns of the total WSC and fructan were only found at anthesis in Kauz. The different levels of WSC and WSC components between Westonia and Kauz are likely associated with leaf chlorophyll levels and fructan degradation, especially 6-kestose degradation. High correlation between levels of TaSUT1 expression and sucrose in leaves indicated that TaSUT1 expression is likely to be influenced by the level of sucrose in leaves, and the combination of high levels of TaSUT1 expression and sucrose in Kauz may contribute to its high grain yield under well-watered conditions.
Insight into the Interactome of Intramitochondrial PKA Using Biotinylation-Proximity Labeling
Authors: Ould Amer Yasmine , Hebert-Chatelain Etienne
Published: November 2020

Mitochondria are fully integrated in cell signaling. Reversible phosphorylation is involved in adjusting mitochondrial physiology to the cellular needs. Protein kinase A (PKA) phosphorylates several substrates present at the external surface of mitochondria to maintain cellular homeostasis. However, few targets of PKA located inside the organelle are known. The aim of this work was to characterize the impact and the interactome of PKA located inside mitochondria. Our results show that the overexpression of intramitochondrial PKA decreases cellular respiration and increases superoxide levels. Using proximity-dependent biotinylation, followed by LC-MS/MS analysis and in silico phospho-site prediction, we identified 21 mitochondrial proteins potentially targeted by PKA. We confirmed the interaction of PKA with TIM44 using coimmunoprecipitation and observed that TIM44-S80 is a key residue for the interaction between the protein and the kinase. These findings provide insights into the interactome of intramitochondrial PKA and suggest new potential mechanisms in the regulation of mitochondrial functions.
Tandem Electrospray Mass Spectrometry of Cyclic N-Substituted Oligo-β-(1→6)-D-glucosamines
Authors: Chizhov Alexander O. , Gening Marina L. , Tsvetkov Yury E. , Nifantiev Nikolay E.
Published: November 2020

High-resolution electrospray mass spectra (MS and MS/MS CID) of positive ions of a series of protonated, ammoniated, and metallated molecules of cyclic N-substituted oligo-β-(1→6)-D-glucosamines differing in cycle size and N-acyl substituents were registered and interpreted. It was shown that the main type of fragmentation is a cleavage of glycosidic bonds of a cycle, and in some cases fragmentation of amide side chains is possible. If labile fragments in substituents (e.g., carbohydrate chains) are present, a decay of the cycle and an elimination of labile fragments are of comparable possibility. It was found that in some cases rearrangements with loss of an internal carbohydrate residue (IRL), or an internal part of a side chain, are feasible.
L1CAM as an E-selectin Ligand in Colon Cancer
Authors: Deschepper Fanny M. , Zoppi Roberta , Pirro Martina , Hensbergen Paul J. , Dall’Olio Fabio , Kotsias Maximillianos , Gardner Richard A. , Spencer Daniel I.R. , Videira Paula A.
Published: November 2020

Metastasis is the main cause of death among colorectal cancer (CRC) patients. E-selectin and its carbohydrate ligands, including sialyl Lewis X (sLeX) antigen, are key players in the binding of circulating tumor cells to the endothelium, which is one of the major events leading to organ invasion. Nevertheless, the identity of the glycoprotein scaffolds presenting these glycans in CRC remains unclear. In this study, we firstly have characterized the glycoengineered cell line SW620 transfected with the fucosyltransferase 6 (FUT6) coding for the α1,3-fucosyltransferase 6 (FUT6), which is the main enzyme responsible for the synthesis of sLeX in CRC. The SW620FUT6 cell line expressed high levels of sLeX antigen and E-selectin ligands. Moreover, it displayed increased migration ability. E-selectin ligand glycoproteins were isolated from the SW620FUT6 cell line, identified by mass spectrometry, and validated by flow cytometry and Western blot (WB). The most prominent E-selectin ligand we identified was the neural cell adhesion molecule L1 (L1CAM). Previous studies have shown association of L1CAM with metastasis in cancer, thus the novel role as E-selectin counter-receptor contributes to understand the molecular mechanism involving L1CAM in metastasis formation.
Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response
Authors: Kaartinen Mari T. , Arora Mansi , Heinonen Sini , Rissanen Aila , Kaprio Jaakko , Pietiläinen Kirsi H.
Published: November 2020

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.
An Immunological Approach to the Biocompatibility of Mesoporous SiO2-CaO Nanospheres
Authors: Montes-Casado María , Sanvicente Adrian , Casarrubios Laura , Feito María José , Rojo José M. , Vallet-Regí María , Arcos Daniel , Portolés Pilar , Portolés María Teresa
Published: November 2020

Mesoporous bioactive glass nanospheres (NanoMBGs) have high potential for clinical applications. However, the impact of these nanoparticles on the immune system needs to be addressed. In this study, the biocompatibility of SiO2-CaO NanoMBGs was evaluated on different mouse immune cells, including spleen cells subsets, bone marrow-derived dendritic cells (BMDCs), or cell lines like SR.D10 Th2 CD4+ lymphocytes and DC2.4 dendritic cells. Flow cytometry and confocal microscopy show that the nanoparticles were rapidly and efficiently taken up in vitro by T and B lymphocytes or by specialized antigen-presenting cells (APCs) like dendritic cells (DCs). Nanoparticles were not cytotoxic and had no effect on cell viability or proliferation under T-cell (anti-CD3) or B cell (LPS) stimuli. Besides, NanoMBGs did not affect the balance of spleen cell subsets, or the production of intracellular or secreted pro- and anti-inflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-6, IL-10) by activated T, B, and dendritic cells (DC), as determined by flow cytometry and ELISA. T cell activation surface markers (CD25, CD69 and Induced Costimulator, ICOS) were not altered by NanoMBGs. Maturation of BMDCs or DC2.4 cells in vitro was not altered by NanoMBGs, as shown by expression of Major Histocompatibility Complex (MHC) and costimulatory molecules (CD40, CD80, CD86), or IL-6 secretion. The effect of wortmannin and chlorpromazine indicate a role for phosphoinositide 3-kinase (PI3K), actin and clathrin-dependent pathways in NanoMBG internalization. We thus demonstrate that these NanoMBGs are both non-toxic and non-inflammagenic for murine lymphoid cells and myeloid DCs despite their efficient intake by the cells.
Design of Novel 4-Aminobenzofuroxans and Evaluation of Their Antimicrobial and Anticancer Activity
Authors: Chugunova Elena , Gazizov Almir , Sazykina Marina , Akylbekov Nurgali , Gildebrant Anastasiya , Sazykin Ivan , Burilov Alexander , Appazov Nurbol , Karchava Shorena , Klimova Maria , Voloshina Alexandra , Sapunova Anastasia , Gumerova Syumbelya , Khamatgalimov Ayrat , Gerasimova Tatiana , Dobrynin Alexey , Gogoleva Olga , Gorshkov Vladimir
Published: November 2020

A series of novel 4-aminobenzofuroxan derivatives containing aromatic/aliphatic amines fragments was achieved via aromatic nucleophilic substitution reaction of 4,6-dichloro-5-nitrobenzofuroxan. The quantum chemistry calculations were performed to identify the factors affecting the regioselectivity of the reaction. The formation of 4-substituted isomer is favored both by its greater stability and the lower activation barrier. Antimicrobial activity of the obtained compounds has been evaluated and some of them were found to suppress effectively bacterial biofilm growth. Fungistatic activity of 4-aminobenzofuroxans were tested on two genetically distinct isolates of M. nivale. The effect of some benzofuroxan derivatives is likely to be more universal against different varieties of M. nivale compared with benzimidazole and carbendazim. Additionally, their anti-cancer activity in vitro has been tested. 4-aminofuroxans possessing aniline moiety showed a high selectivity towards MCF-7 and M-HeLa tumor cell lines. Moreover, they exhibit a significantly lower toxicity towards normal liver cells compared to Doxorubicin and Tamoxifen. Thus, benzofuroxans containing aromatic amines fragments in their structure are promising candidates for further development both as anti-cancer and anti-microbial agents.
TaDrAp1 and TaDrAp2, Partner Genes of a Transcription Repressor, Coordinate Plant Development and Drought Tolerance in Spelt and Bread Wheat
Authors: Zotova Lyudmila , Shamambaeva Nasgul , Lethola Katso , Alharthi Badr , Vavilova Valeriya , Smolenskaya Svetlana E. , Goncharov Nikolay P. , Kurishbayev Akhylbek , Jatayev Satyvaldy , Gupta Narendra K. , Gupta Sunita , Schramm Carly , Anderson Peter A. , Jenkins Colin L. D. , Soole Kathleen L. , Shavrukov Yuri
Published: November 2020

Down-regulator associated protein, DrAp1, acts as a negative cofactor (NC2α) in a transcription repressor complex together with another subunit, down-regulator Dr1 (NC2β). In binding to promotors and regulating the initiation of transcription of various genes, DrAp1 plays a key role in plant transition to flowering and ultimately in seed production. TaDrAp1 and TaDrAp2 genes were identified, and their expression and genetic polymorphism were studied using bioinformatics, qPCR analyses, a 40K Single nucleotide polymorphism (SNP) microarray, and Amplifluor-like SNP genotyping in cultivars of bread wheat (Triticum aestivum L.) and breeding lines developed from a cross between spelt (T. spelta L.) and bread wheat. TaDrAp1 was highly expressed under non-stressed conditions, and at flowering, TaDrAp1 expression was negatively correlated with yield capacity. TaDrAp2 showed a consistently low level of mRNA production. Drought caused changes in the expression of both TaDrAp1 and TaDrAp2 genes in opposite directions, effectively increasing expression in lower yielding cultivars. The microarray 40K SNP assay and Amplifluor-like SNP marker, revealed clear scores and allele discriminations for TaDrAp1 and TaDrAp2 and TaRht-B1 genes. Alleles of two particular homeologs, TaDrAp1-B4 and TaDrAp2-B1, co-segregated with grain yield in nine selected breeding lines. This indicated an important regulatory role for both TaDrAp1 and TaDrAp2 genes in plant growth, ontogenesis, and drought tolerance in bread and spelt wheat.
Tobacco Hornworm (Manduca sexta) Oral Secretion Elicits Reactive Oxygen Species in Isolated Tomato Protoplasts
Authors: Gandhi Akanksha , Kariyat Rupesh R. , Chappa Cruz , Tayal Mandeep , Sahoo Nirakar
Published: November 2020

Plants are under constant attack by a suite of insect herbivores. Over millions of years of coexistence, plants have evolved the ability to sense insect feeding via herbivore-associated elicitors in oral secretions, which can mobilize defense responses. However, herbivore-associated elicitors and the intrinsic downstream modulator of such interactions remain less understood. In this study, we show that tobacco hornworm caterpillar (Manduca sexta) oral secretion (OS) induces reactive oxygen species (ROS) in tomato (Solanum lycopersicum) protoplasts. By using a dye-based ROS imaging approach, our study shows that application of plant-fed (PF) M. sexta OS generates significantly higher ROS while artificial diet-fed (DF) caterpillar OS failed to induce ROS in isolated tomato protoplasts. Elevation in ROS generation was saturated after ~140 s of PF OS application. ROS production was also suppressed in the presence of an antioxidant NAC (N-acetyl-L-cysteine). Interestingly, PF OS-induced ROS increase was abolished in the presence of a Ca2+ chelator, BAPTA-AM (1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid). These results indicate a potential signaling cascade involving herbivore-associated elicitors, Ca2+, and ROS in plants during insect feeding. In summary, our results demonstrate that plants incorporate a variety of independent signals connected with their herbivores to regulate and mount their defense responses.
The Role of Ionic Liquids in the Pharmaceutical Field: An Overview of Relevant Applications
Authors: Pedro Sónia N. , R. Freire Carmen S. , Silvestre Armando J. D. , Freire Mara G.
Published: November 2020

Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some of these drawbacks, ionic liquids (ILs) have been investigated as solvents, reagents, and anti-solvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs), as solvents, co-solvents and emulsifiers in drug formulations, as pharmaceuticals (API-ILs) aiming liquid therapeutics, and in the development and/or improvement of drug-delivery-based systems. The present review focuses on the use of ILs in the pharmaceutical field, covering their multiple applications from pharmaceutical synthesis to drug delivery. The most relevant research conducted up to date is presented and discussed, together with a critical analysis of the most significant IL-based strategies in order to improve the performance of therapeutics and drug delivery systems.
Effects of Estrogen Receptor and Wnt Signaling Activation on Mechanically Induced Bone Formation in a Mouse Model of Postmenopausal Bone Loss
Authors: Liedert Astrid , Nemitz Claudia , Haffner-Luntzer Melanie , Schick Fabian , Jakob Franz , Ignatius Anita
Published: November 2020

In the adult skeleton, bone remodeling is required to replace damaged bone and functionally adapt bone mass and structure according to the mechanical requirements. It is regulated by multiple endocrine and paracrine factors, including hormones and growth factors, which interact in a coordinated manner. Because the response of bone to mechanical signals is dependent on functional estrogen receptor (ER) and Wnt/β-catenin signaling and is impaired in postmenopausal osteoporosis by estrogen deficiency, it is of paramount importance to elucidate the underlying mechanisms as a basis for the development of new strategies in the treatment of osteoporosis. The present study aimed to investigate the effectiveness of the activation of the ligand-dependent ER and the Wnt/β-catenin signal transduction pathways on mechanically induced bone formation using ovariectomized mice as a model of postmenopausal bone loss. We demonstrated that both pathways interact in the regulation of bone mass adaption in response to mechanical loading and that the activation of Wnt/β-catenin signaling considerably increased mechanically induced bone formation, whereas the effects of estrogen treatment strictly depended on the estrogen status in the mice.