The transcriptome of corona radiata cells from individual MII oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

BACKGROUND: Corona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls. METHODS: All patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays. RESULTS: The transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5). CONCLUSION: The overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-014-0110-6) contains supplementary material, which is available to authorized users

Transcriptome profiling of mice testes following low dose irradiation

BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). RESULTS: We identified a subset of transcripts (n = 988) where changes in expression pi can be explained by changes in cellularity. We separated the transcripts into five unique clusters that we associated with spermatogonia, spermatocytes, early spermatids, late spermatids and somatic cells, respectively. Transcripts in the somatic cell cluster showed large changes in expression pi, mainly caused by changes in cellularity. Further investigations revealed that the low dose irradiation seemed to cause Leydig cell hyperplasia, which contributed to the detected expression changes in the somatic cell cluster. CONCLUSIONS: The five clusters represent gene expression in distinct cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production and inadequate inhibin signalling due to missing germ cells

The potential role of Alu Y in the development of resistance to SN38 (Irinotecan) or oxaliplatin in colorectal cancer

BACKGROUND: Irinotecan (SN38) and oxaliplatin are chemotherapeutic agents used in the treatment of colorectal cancer. However, the frequent development of resistance to these drugs represents a considerable challenge in the clinic. Alus as retrotransposons comprise 11% of the human genome. Genomic toxicity induced by carcinogens or drugs can reactivate Alus by altering DNA methylation. Whether or not reactivation of Alus occurs in SN38 and oxaliplatin resistance remains unknown. RESULTS: We applied reduced representation bisulfite sequencing (RRBS) to investigate the DNA methylome in SN38 or oxaliplatin resistant colorectal cancer cell line models. Moreover, we extended the RRBS analysis to tumor tissue from 14 patients with colorectal cancer who either did or did not benefit from capecitabine + oxaliplatin treatment. For the clinical samples, we applied a concept of ‘DNA methylation entropy’ to estimate the diversity of DNA methylation states of the identified resistance phenotype-associated methylation loci observed in the cell line models. We identified different loci being characteristic for the different resistant cell lines. Interestingly, 53% of the identified loci were Alu sequences- especially the Alu Y subfamily. Furthermore, we identified an enrichment of Alu Y sequences that likely results from increased integration of new copies of Alu Y sequence in the drug-resistant cell lines. In the clinical samples, SOX1 and other SOX gene family members were shown to display variable DNA methylation states in their gene regions. The Alu Y sequences showed remarkable variation in DNA methylation states across the clinical samples. CONCLUSION: Our findings imply a crucial role of Alu Y in colorectal cancer drug resistance. Our study underscores the complexity of colorectal cancer aggravated by mobility of Alu elements and stresses the importance of personalized strategies, using a systematic and dynamic view, for effective cancer therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1552-y) contains supplementary material, which is available to authorized users

Local Chatter or International Buzz? Language Differences on Posts about Zika Research on Twitter and Facebook

Background When the Zika virus outbreak became a global health emergency in early 2016, the scientific community responded with an increased output of Zika-related research. This upsurge in research naturally made its way into academic journals along with editorials, news, and reports. However, it is not yet known how or whether these scholarly communications were distributed to the populations most affected by Zika. Methodology/Principal findings To understand how scientific outputs about Zika reached global and local audiences, we collected Tweets and Facebook posts that linked to Zika-related research in the first six months of 2016. Using a language detection algorithm, we found that up to 90% of Twitter and 76% of Facebook posts are in English. However, when none of the authors of the scholarly article are from English-speaking countries, posts on both social media are less likely to be in English. The effect is most pronounced on Facebook, where the likelihood of posting in English is between 11 and 16% lower when none of the authors are from English-speaking countries, as compared to when some or all are. Similarly, posts about papers written with a Brazilian author are 13% more likely to be in Portuguese on Facebook than when made on Twitter. Conclusions/Significance Our main conclusion is that scholarly communication on Twitter and Facebook of Zikarelated research is dominated by English, despite Brazil being the epicenter of the Zika epidemic. This result suggests that scholarly findings about the Zika virus are unlikely to be distributed directly to relevant populations through these popular online mediums. Nevertheless, there are differences between platforms. Compared to Twitter, scholarly communication on Facebook is more likely to be in the language of an author’s country. The Zika outbreak provides a useful case-study for understanding how scientific outputs are communicated to relevant populations. Our results suggest that Facebook is a more effective channel than Twitter, if communication is desired to be in the native language of the affected country. Further research should explore how local media—such as governmental websites, newspapers and magazines, as well as television and radio—disseminate scholarly publication

Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance

Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mechanisms associated with chemoresistance, and departing from three distinct CRC cell models, we generated a panel of human colorectal cancer cell lines with acquired resistance to either oxaliplatin or irinotecan. We characterized the resistant cell line variants with regards to their drug resistance profile and transcriptome, and matched our results with datasets generated from relevant clinical material to derive putative resistance biomarkers. We found that the chemoresistant cell line variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles, with non-reciprocal cross-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance. In addition, and given the potential implications for selection of subsequent treatment, we also performed an exploratory analysis, in relevant patient cohorts, of the predictive value of each of the specific genes identified in our cellular models

The short-term effect of swimming training load on shoulder rotational range of motion, shoulder joint position sense and pectoralis minor length

Background: Shoulder pain or injury is the most common issue facing elite competitive swimmers and the most frequent reason for missed or modified training. Literature suggests that highly repetitive upper limb loading leads to inappropriate adaptations within the shoulder complex. The most likely maladaptations to occur are variations in shoulder rotational range of motion, reduction in joint position sense and shortened pectoralis minor length. This has yet to have been confirmed in experimental studies. The aim of this study was to investigate the short-term effects of swimming training load upon internal and external rotation range of motion, joint position sense and pectoralis minor length. Method: Sixteen elite swimmers training in the British Swimming World Class programme participated. Measures of internal and external range of motion, joint position sense error score and pectoralis minor length were taken before and after a typical 2h swimming session. Results: Following swimming training shoulder external rotation range of motion and pectoralis minor length reduced significantly (-3.4°,p=&lt;0.001 and -0.7cm, p=&lt;0.001, respectively), joint position sense error increased significantly (+2.0° error angle, p=&lt;0.001). Internal rotation range of motion demonstrated no significant change (-0.6, p=0.53). Discussion: This study determined that elite level swimming training results in short-term maladaptive changes in shoulder performance that could potentially predispose them to injury

Post-traumatic glenohumeral cartilage lesions: a systematic review

<p>Abstract</p> <p>Background</p> <p>Any cartilage damage to the glenohumeral joint should be avoided, as these damages may result in osteoarthritis of the shoulder. To understand the pathomechanism leading to shoulder cartilage damage, we conducted a systematic review on the subject of articular cartilage lesions caused by traumas where non impression fracture of the subchondral bone is present.</p> <p>Methods</p> <p>PubMed (MEDLINE), ScienceDirect (EMBASE, BIOBASE, BIOSIS Previews) and the COCHRANE database of systematic reviews were systematically scanned using a defined search strategy to identify relevant articles in this field of research. First selection was done based on abstracts according to specific criteria, where the methodological quality in selected full text articles was assessed by two reviewers. Agreement between raters was investigated using percentage agreement and Cohen's Kappa statistic. The traumatic events were divided into two categories: 1) acute trauma which refers to any single impact situation which directly damages the articular cartilage, and 2) chronic trauma which means cartilage lesions due to overuse or disuse of the shoulder joint.</p> <p>Results</p> <p>The agreement on data quality between the two reviewers was 93% with a Kappa value of 0.79 indicating an agreement considered to be 'substantial'. It was found that acute trauma on the shoulder causes humeral articular cartilage to disrupt from the underlying bone. The pathomechanism is said to be due to compression or shearing, which can be caused by a sudden subluxation or dislocation. However, such impact lesions are rarely reported. In the case of chronic trauma glenohumeral cartilage degeneration is a result of overuse and is associated to other shoulder joint pathologies. In these latter cases it is the rotator cuff which is injured first. This can result in instability and consequent impingement which may progress to glenohumeral cartilage damage.</p> <p>Conclusion</p> <p>The great majority of glenohumeral cartilage lesions without any bony lesions are the results of overuse. Glenohumeral cartilage lesions with an intact subchondral bone and caused by an acute trauma are either rare or overlooked. And at increased risk for such cartilage lesions are active sportsmen with high shoulder demand or athletes prone to shoulder injury.</p

Novel variation and <i>de novo </i>mutation rates in population-wide <i>de novo</i> assembled Danish trios

Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e−8 and 1.5e−9 per nucleotide per generation for SNVs and indels, respectively

Measurement of nat{}^{nat}Pb(νe\nu_e,Xnn) production with a stopped-pion neutrino source

Using neutrinos produced at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory (ORNL), the COHERENT collaboration has studied the Pb($\nu_e$,X$n$) process with a lead neutrino-induced-neutron (NIN) detector. Data from this detector are fit jointly with previously collected COHERENT data on this process. A combined analysis of the two datasets yields a cross section that is $0.29^{+0.17}_{-0.16}$ times that predicted by the MARLEY event generator using experimentally-measured Gamow-Teller strength distributions, consistent with no NIN events at 1.8$\sigma$. This is the first inelastic neutrino-nucleus process COHERENT has studied, among several planned exploiting the high flux of low-energy neutrinos produced at the SNS.Comment: 11 pages, 9 figures, version accepted by Phys. Rev.