Estradiol-regulated MicroRNAs Control Estradiol Response in Breast Cancer Cells

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). E2-inducible proteins c-Myc and E2Fs are required for optimal ERα activity and secondary estrogen responses, respectively. We show that E2 induces 21 microRNAs and represses seven microRNAs in MCF-7 breast cancer cells; these microRNAs have the potential to control 420 E2-regulated and 757 non-E2-regulated mRNAs at the post-transcriptional level. The serine/threonine kinase, AKT, alters E2-regulated expression of microRNAs. E2 induced the expression of eight Let-7 family members, miR-98 and miR-21 microRNAs; these microRNAs reduced the levels of c-Myc and E2F2 proteins. Dicer, a ribonuclease III enzyme required for microRNA processing, is also an E2-inducible gene. Several E2-regulated microRNA genes are associated with ERα-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ERα-positive breast cancers is dependent on the balance between E2-regulated tumor-suppressor microRNAs and oncogenic microRNAs. Additionally, our studies reveal a negative-regulatory loop controlling E2 response through microRNAs as well as differences in E2-induced transcriptome and proteome

Replacement of Doped Olympic Medalists

A summary of the outcomes of the IOC Re-Testing programme from 2008-2012 to date was recently released (1). Key outcomes include 104 offenses, of which 86 cases were related to the territory of the former Soviet Union. Russia lost 19 medals, Kazakhstan 9, Belarus 6, the Ukraine 5, Armenia and Moldova 2 each, Azerbaijan and Uzbekistan 1 each. China lost 3 medals, Turkey 2, Cuba and Greece 1 medal. 5 athletes tested positive for both the 2008 and 2012 Olympic Games (2). However, it remains to be determined who has received or will receive these medals. This uncertainty is due to the fact that the responsibility for changing the results lies with the respective International Federation (IF) and the responsibility for redistributing the medals lies with the International Olympic Committee (IOC). The most common scenario is that the next-placed athlete is moved up, although this can cause difficulties and there are precedents not to award these medals. In the 94 kg men's weightlifting competition in the 2012 London Olympic Games, the 5th, 8th and 9th ranked athletes, theoretically at least, remain in contention for the medal positions (3). With the present system, it is difficult to determine whether all of these potentially "eligible" athletes have undergone doping-control. The International Weightlifting Federation (IWF) has published on its web site a list of all male and another of all female competitors who underwent doping control in 2012 Olympic Games and this data reveals the originally 9th and now 3rd position athlete was subject to doping control at the 2012 Olympic Games (4). Nevertheless, there is the theoretical possibility that the re-distribution of Olympic medals could lead to non-tested athletes becoming holders of medals

Sport and exercise genomics: the FIMS 2019 consensus statement update

Rapid advances in technologies in the field of genomics such as high throughput DNA sequencing, big data processing by machine learning algorithms and gene-editing techniques are expected to make precision medicine and gene-therapy a greater reality. However, this development will raise many important new issues, including ethical, moral, social and privacy issues. The field of exercise genomics has also advanced by incorporating these innovative technologies. There is therefore an urgent need for guiding references for sport and exercise genomics to allow the necessary advancements in this field of sport and exercise medicine, while protecting athletes from any invasion of privacy and misuse of their genomic information. Here, we update a previous consensus and develop a guiding reference for sport and exercise genomics based on a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis. This SWOT analysis and the developed guiding reference highlight the need for scientists/clinicians to be well-versed in ethics and data protection policy to advance sport and exercise genomics without compromising the privacy of athletes and the efforts of international sports federations. Conducting research based on the present guiding reference will mitigate to a great extent the risks brought about by inappropriate use of genomic information and allow further development of sport and exercise genomics in accordance with best ethical standards and international data protection principles and policies. This guiding reference should regularly be updated on the basis of new information emerging from the area of sport and exercise medicine as well as from the developments and challenges in genomics of health and disease in general in order to best protect the athletes, patients and all other relevant stakeholders

Consensus on Molecular Subtypes of High-grade Serous Ovarian Carcinoma

Purpose: The majority of ovarian carcinomas are of high-grade serous histology, which is associated with poor prognosis. Surgery and chemotherapy are the mainstay of treatment, and molecular characterization is necessary to lead the way to targeted therapeutic options. To this end, various computational methods for gene expression-based subtyping of high-grade serous ovarian carcinoma (HGSOC) have been proposed, but their overlap and robustness remain unknown. Experimental Design: We assess three major subtype classifiers by meta-analysis of publicly available expression data, and assess statistical criteria of subtype robustness and classifier concordance. We develop a consensus classifier that represents the subtype classifications of tumors based on the consensus of multiple methods, and outputs a confidence score. Using our compendium of expression data, we examine the possibility that a subset of tumors are unclassifiable based on currently proposed subtypes. Results: HGSOC subtyping classifiers exhibit moderate pairwise concordance across our data compendium (58.9%-70.9%, p \u3c 10-5) and are associated with overall survival in a metaanalysis across datasets (p \u3c 10-5). Current subtypes do not meet statistical criteria for robustness to re-clustering across multiple datasets (Prediction Strength \u3c 0.6). A new subtype classifier is trained on concordantly classified samples to yield a consensus classification of patient tumors that correlates with patient age, survival, tumor purity, and lymphocyte infiltration. Conclusion: A new consensus ovarian subtype classifier represents the consensus of methods, and demonstrates the importance of classification approaches for cancer that do not require all tumors to be assigned to a distinct subtype

Impact of long-term agricultural management practices on therhizosphere microbiome and plant health

Increasing food and energy demands have resulted in a considerable intensification of farming practices, whichbrought about severe consequences for agricultural soils during last decades. In order to maintain soil quality andhealth for the future, the development of more extensive and sustainable farming strategies is urgently needed.The soil and rhizosphere microbiome play an integral role in virtually all soil processes and are intimately linkedto plant performance. Various studies indicated that agricultural management practices affect soil microbiomes.We therefore hypothesized that this external impact is conveyed by the microbial communities to the currentcrops at the time of their establishment. We used twelve differently managed soils from three long-term fieldtrials established in 1978 (Therwil, Switzerland), 1992 (Bernburg, Germany), and 2006 (Thyrow, Germany) toanalyze the impact of various management strategies (crop rotation, fertilization, tillage) on soil and its associatedrhizosphere microbiomes under consideration of plant productivity, plant health, and the ability of the soils tosuppress soil-borne phytopathogens. The model plant lettuce (Lactuca sativa L.) was cultivated for ten weeks undergrowth-chamber conditions in these soils. High-throughput sequencing of bacterial 16S rRNA genes or fungalITS fragments, respectively, PCR- amplified from total community DNA of rhizosphere and soil samples showedsignificant differences in microbial community compositions between soils that originated from the different fieldsites and long-term farming practices. Moreover, differences depending on long-term agricultural managementin plant productivity and health as measured by RT-qPCR of stress-related plant genes were observed. Localizedanalysis of rhizosphere soil solution was performed using non-invasive sampling techniques with sorption filtersplaced onto the surface of soil-grown roots along the root observation windows with subsequent HPLC-MSprofiling. Amino acids, sugars and antifungal organic acids such as benzoic acid detected in the rhizosphere soilsolutions confirmed variations in concentrations depending on the site and management practice indicating differ-ent stress potentials of farming practices for plants. Agricultural management also affected soil suppressiveness tothe soil-borne model pathogen Rhizoctonia solani.Under controlled growth chamber conditions, we could show the legacy of long-term agricultural managementpractices on the establishment and performance of a subsequent plant generation and its associated rhizospheremicrobiome

Estradiol-regulated microRNAs control estradiol response in breast cancer cells.

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). E2-inducible proteins c-Myc and E2Fs are required for optimal ERalpha activity and secondary estrogen responses, respectively. We show that E2 induces 21 microRNAs and represses seven microRNAs in MCF-7 breast cancer cells; these microRNAs have the potential to control 420 E2-regulated and 757 non-E2-regulated mRNAs at the post-transcriptional level. The serine/threonine kinase, AKT, alters E2-regulated expression of microRNAs. E2 induced the expression of eight Let-7 family members, miR-98 and miR-21 microRNAs; these microRNAs reduced the levels of c-Myc and E2F2 proteins. Dicer, a ribonuclease III enzyme required for microRNA processing, is also an E2-inducible gene. Several E2-regulated microRNA genes are associated with ERalpha-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ERalpha-positive breast cancers is dependent on the balance between E2-regulated tumor-suppressor microRNAs and oncogenic microRNAs. Additionally, our studies reveal a negative-regulatory loop controlling E2 response through microRNAs as well as differences in E2-induced transcriptome and proteome

Infographic. Clinical recommendations for return to play during the COVID-19 pandemic

COVID-19 AND RETURN TO PLAY The world of sport has recently returned to training and competition following suspension due to the COVID-19 pandemic. It is concerning that a number of athletes have tested positive for COVID-19 after returning to competition. 1 Numerous authors have attempted to address return to play given the importance and complexity of the issue, with notable attention on possible cardiac implications.2–6 SCOPE OF THE INFOGRAPHIC The specific recommendations shown in the present infographic (figure 1) have been generated by a panel of international experts and represent a compilation of the numerous approaches used to inform resumption of regular sports during the COVID-19 pandemic. Despite the different regulations around the world and the particular characteristics of each sport, it is essential to provide informative, consistent and specific guidance for safe return to training and competition at this most difficult time. ..

Recommendations for return to sport during the SARS-CoV-2 pandemic

In this viewpoint we make specific recommendations that can assist and make the return to sport/exercise as safe as possible for all those impacted - from the recreational athlete to the elite athlete. We acknowledge that there are varying rules and regulations around the world, not to mention the varying philosophies and numerous schools of thought as it relates to return to sport/exercise and we have been cognisant of this in our recommendations. Despite the varying rules and circumstances around the world, we believe it is essential to provide some helpful and consistent guidance for return to training and sport for sport and exercise physicians around the world at this most difficult time. The present viewpoint provides practical and medical recommendations on the resumption to sport process