Next Generation Sequencing Detects Premeiotic Errors in Human Oocytes

Autosomal aneuploidy is the leading cause of embryonic and foetal death in humans. This arises mainly from errors in meiosis I or II of oogenesis. A largely ignored source of error stems from germinal mosaicism, which leads to premeiotic aneuploidy. Molecular cytogenetic studies employing metaphase fluorescence in situ hybridization and comparative genomic hybridisation suggest that premeiotic aneuploidy may affect 10–20% of oocytes overall. Such studies have been criticised on technical grounds. We report here an independent study carried out on unmanipulated oocytes that have been analysed using next generation sequencing (NGS). This study confirms that the incidence of premeiotic aneuploidy in an unselected series of oocytes exceeds 10%. A total of 140 oocytes donated by 42 women gave conclusive results; of these, 124 (88.5%) were euploid. Sixteen out of 140 (11.4%) provided evidence of premeiotic aneuploidy. Of the 140, 112 oocytes were immature (germinal vesicle or metaphase I), of which 10 were aneuploid (8.93%); the remaining 28 were intact metaphase II-first polar body complexes, and six of these were aneuploid (21.4%). Of the 16 aneuploid cells, half contained simple errors (one or two abnormal chromosomes) and half contained complex errors. We conclude that germinal mosaicism leading to premeiotic aneuploidy is a consistent finding affecting at least 10% of unselected oocytes from women undergoing egg collection for a variety of reasons. The importance of premeiotic aneuploidy lies in the fact that, for individual oocytes, it greatly increases the risk of an aneuploid mature oocyte irrespective of maternal age. As such, this may account for some cases of aneuploid conceptions in very young women

Chronic liver diseases and erectile dysfunction

Chronic liver diseases (CLDs) are characterized by progressive necrosis of hepatocytes, which leads to liver fibrosis and cirrhosis, and ultimately liver dysfunction. The statistics of 2020 shows that the number of patients with CLDs, including chronic hepatitis, fatty liver, and cirrhosis, may exceed 447 million in China. The liver is a crucial organ for the metabolism of various substances, including sex hormones and lipids. CLDs frequently result in abnormalities in the metabolism of sex hormones, glucose, and lipids, as well as mental and psychological illnesses, all of which are significant risk factors for erectile dysfunction (ED). It has been reported that the prevalence of ED in male patients with CLDs ranges from 24.6 to 85.0%. According to a survey of Caucasians, liver transplantation may improve the erectile function of CLDs patients with ED. This finding supports the link between CLDs and ED. In addition, ED is often a precursor to a variety of chronic diseases. Given this correlation and the significant prevalence of CLDs, it is important to evaluate the epidemiology, risk factors, etiology, and treatment outcomes of ED in male patients with CLDs, expecting to attract widespread attention

mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation

This study aimed to explore the efficacy and potential mechanisms of rechallenge therapy with microtubule-targeting agents (MTAs) in patients with HER2-low metastatic breast cancer (MBC). We performed a systematic review to investigate the rechallenge treatment concept in the field of HER2-low MBC treatment and utilized a series of cases identified in the literature to illustrate the concept. Here we reported two clinical cases of HER2-low MBC patients whose disease progressed after prior treatment with MTAs such as docetaxel and vincristine. When rechallenged with disitamab vedotin ((RC48-antibody-drug conjugate (ADC), a monomethyl auristatin (MMAE) MTA)), both patients achieved a partial response and the final progression-free survival (PFS) was 13.5 and 9 months, respectively. Genomic profiling detected a PIK3CA H1047R mutation in the patients. The patients were treated with everolimus before being rechallenged with RC48, which may lead to a better response. This study further summarizes and analyzes the potential mechanism of the PI3K-AKT signaling pathway in MTA resistance and reveals that the PIK3CA H1047R mutation may be a potential molecular marker for the efficacy prediction of mTOR inhibitors, providing new insights and potential therapeutic strategies for the application of MTAs to MBC patients

Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism

Malignant pleural mesothelioma (MPM) is an aggressive human cancer and miRNAs can play a key-role for this disease. In order to broaden the knowledge in this field, the miRNA expression was investigated in a large series of MPM to discover new pathways helpful in diagnosis, prognosis and therapy. We employed nanoString nCounter system for miRNA profiling on 105 MPM samples and 10 healthy pleura. The analysis was followed by the validation of the most significantly deregulated miRNAs by RT-qPCR in an independent sample set. We identified 63 miRNAs deregulated in a statistically significant way. MiR-185, miR-197, and miR-299 were confirmed differentially expressed, after validation study. In addition, the results of the microarray analysis corroborated previous findings concerning miR-15b-5p, miR-126-3p, and miR-145-5p. Kaplan-Meier curves were used to explore the association between miRNA expression and overall survival (OS) and identified a 2-miRNA prognostic signature (Let-7c-5p and miR-151a-5p) related to hypoxia and energy metabolism respectively. In silico analyses with DIANA-microT-CDS highlighted 5 putative targets in common between two miRNAs. With the present work we showed that the pattern of miRNAs expression is highly deregulated in MPM and that a 2-miRNA signature can be a new useful tool for prognosis in MPM

Planck intermediate results. XXIII. Galactic plane emission components derived from Planck with ancillary data

Planck data when combined with ancillary data provide a unique opportunity to separate the diffuse emission components of the inner Galaxy. The purpose of the paper is to elucidate the morphology of the various emission components in the strong star-formation region lying inside the solar radius and to clarify the relationship between the various components. The region of the Galactic plane covered is l = 300\ub0 \u2192 0\ub0 \u2192 60\ub0 wherestar-formation is highest and the emission is strong enough to make meaningful component separation. The latitude widths in this longitude range lie between 1 and 2, which correspond to FWHM z-widths of 100-200 pc at a typical distance of 6 kpc. The four emission components studied here are synchrotron, free-free, anomalous microwave emission (AME), and thermal (vibrational) dust emission. These components are identified by constructing spectral energy distributions (SEDs) at positions along the Galactic plane using the wide frequency coverage of Planck (28.4-857GHz) in combination with low-frequency radio data at 0.408-2.3 GHz plus WMAP data at 23-94 GHz, along with far-infrared (FIR) data from COBE-DIRBE and IRAS. The free-free component is determined from radio recombination line (RRL) data. AME is found to be comparable in brightness to the free-free emission on the Galactic plane in the frequency range 20-40 GHz with a width in latitude similar to that of the thermal dust; it comprises 45 \ub1 1% of the total 28.4 GHz emission in the longitude range l = 300\ub0 \u2192 0\ub0 \u2192 60\ub0. The free-free component is the narrowest, reflecting the fact that it is produced by current star-formation as traced by the narrow distribution of OB stars. It is the dominant emission on the plane between 60 and 100 GHz. RRLs from this ionized gas are used to assess its distance, leading to a free-free z-width of FWHM 48 100 pc. The narrow synchrotron component has a low-frequency brightness spectral index \u3b2synch 48 -2.7 that is similar to the broad synchrotron component indicating that they are both populated by the cosmic ray electrons of the same spectral index. The width of this narrow synchrotron component is significantly larger than that of the other three components, suggesting that it is generated in an assembly of older supernova remnants that have expanded to sizes of order 150 pc in 3 7 105 yr; pulsars of a similar age have a similar spread in latitude. The thermal dust is identified in the SEDs with average parameters of Tdust = 20.4 \ub1 0.4 K, \u3b2FIR = 1.94 \ub1 0.03 (> 353 GHz), and \u3b2mm = 1.67 \ub1 0.02 (< 353 GHz). The latitude distributions of gamma-rays, CO, and the emission in high-frequency Planck bands have similar widths, showing that they are all indicators of the total gaseous matter on the plane in the inner Galaxy. \ua9 ESO, 2015

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

the recognition and enhancement of traffic sign for the computer-generated image

Image recognition in image understanding is very challenge research topic. However, the study of recognition and enhancement of the specific target for the computer generated image is very less. Compared with the natural image, this cause may be the characteristics (simple in overall) and the scene of applications (the 3D roaming, the game and so on) for the computer-generated image. For recognition and enhancement of the specific target (such as traffic sign) in the computer-generated image, the difficulty is how to accurately recognize and enhance the specific target, and maintaining other information of object do not been changed. In this paper, adopting stepwise refinement method attempts to solve the problem. The proposed method is based on three steps including image preprocessing, image recognition and enhancement. The experimental results show the method can be very good to deal with such issues. The research result shows that the image recognition and image enhancement is still not simple process. Therefore, we imagine that image recognition for complex real scene image also isn't simple issues. But the research idea of stepwise refinement which is proposed in the paper provides a methodological reference for complex image recognition. &copy; 2012 IEEE.State Industry Base of Digital Home; Application and Demonstration; Panyu Dist. Serv. Comm. State Ind.; Base Digit. Home Appl. Demonstr.; Research Institute of Sun Yat-sen University in ShenzhenImage recognition in image understanding is very challenge research topic. However, the study of recognition and enhancement of the specific target for the computer generated image is very less. Compared with the natural image, this cause may be the characteristics (simple in overall) and the scene of applications (the 3D roaming, the game and so on) for the computer-generated image. For recognition and enhancement of the specific target (such as traffic sign) in the computer-generated image, the difficulty is how to accurately recognize and enhance the specific target, and maintaining other information of object do not been changed. In this paper, adopting stepwise refinement method attempts to solve the problem. The proposed method is based on three steps including image preprocessing, image recognition and enhancement. The experimental results show the method can be very good to deal with such issues. The research result shows that the image recognition and image enhancement is still not simple process. Therefore, we imagine that image recognition for complex real scene image also isn't simple issues. But the research idea of stepwise refinement which is proposed in the paper provides a methodological reference for complex image recognition. &copy; 2012 IEEE