TEspeX: consensus-specific quantification of transposable element expression preventing biases from exonized fragments

Summary: Transposable elements (TEs) play key roles in crucial biological pathways. Therefore, several tools enabling the quantification of their expression were recently developed. However, many of the existing tools lack the capability to distinguish between the transcription of autonomously expressed TEs and TE fragments embedded in canonical coding/non-coding non-TE transcripts. Consequently, an apparent change in the expression of a given TE may simply reflect the variation in the expression of the transcripts containing TE-derived sequences. To overcome this issue, we have developed TEspeX, a pipeline for the quantification of TE expression at the consensus level. TEspeX uses Illumina RNA-seq short reads to quantify TE expression avoiding counting reads deriving from inactive TE fragments embedded in canonical transcripts. Availability and implementation: The tool is implemented in python3, distributed under the GNU General Public License (GPL) and available on Github at https://github.com/fansalon/TEspeX (Zenodo URL: https://doi.org/10.5281/zenodo.6800331). Supplementary information: Supplementary data are available at Bioinformatics online

Meta-Analysis Suggests That Intron Retention Can Affect Quantification of Transposable Elements from RNA-Seq Data

Simple Summary Transposable elements (TEs) are repetitive sequences comprising more than one third of the human genome with the original ability to change their location within the genome. Owing to their repetitive nature, the quantification of TEs results often challenging. RNA-seq is a useful tool for genome-wide TEs quantification, nevertheless it also presents technical issues, including low reads mappability and erroneous quantification derived from the transcription of TEs fragments embedded in canonical transcripts. Fragments derived from TEs are found within the introns of most genes, which led to the hypothesis that intron retention (IR) can affect the unbiased quantification of TEs expression. Performing meta-analysis of public RNA-seq datasets, here we observe that IR can indeed impact the quantification of TEs by increasing the number of reads mapped on intronic TE copies. Our work highlights a correlation between IR and TEs expression measurement by RNA-seq that should be taken into account to achieve reliable TEs quantification, especially in samples characterized by extensive IR, because differential IR might be confused with differential TEs expression. Transposable elements (TEs), also known as "jumping genes", are repetitive sequences with the capability of changing their location within the genome. They are key players in many different biological processes in health and disease. Therefore, a reliable quantification of their expression as transcriptional units is crucial to distinguish between their independent expression and the transcription of their sequences as part of canonical transcripts. TEs quantification faces difficulties of different types, the most important one being low reads mappability due to their repetitive nature preventing an unambiguous mapping of reads originating from their sequences. A large fraction of TEs fragments localizes within introns, which led to the hypothesis that intron retention (IR) can be an additional source of bias, potentially affecting accurate TEs quantification. IR occurs when introns, normally removed from the mature transcript by the splicing machinery, are maintained in mature transcripts. IR is a widespread mechanism affecting many different genes with cell type-specific patterns. We hypothesized that, in an RNA-seq experiment, reads derived from retained introns can introduce a bias in the detection of overlapping, independent TEs RNA expression. In this study we performed meta-analysis using public RNA-seq data from lymphoblastoid cell lines and show that IR can impact TEs quantification using established tools with default parameters. Reads mapped on intronic TEs were indeed associated to the expression of TEs and influence their correct quantification as independent transcriptional units. We confirmed these results using additional independent datasets, demonstrating that this bias does not appear in samples where IR is not present and that differential TEs expression does not impact on IR quantification. We concluded that IR causes the over-quantification of intronic TEs and differential IR might be confused with differential TEs expression. Our results should be taken into account for a correct quantification of TEs expression from RNA-seq data, especially in samples in which IR is abundant

Transposons Acting as Competitive Endogenous RNAs: In-Silico Evidence from Datasets Characterised by L1 Overexpression

LINE L1 are transposable elements that can replicate within the genome by passing through RNA intermediates. The vast majority of these element copies in the human genome are inactive and just between 100 and 150 copies are still able to mobilize. During evolution, they could have been positively selected for beneficial cellular functions. Nonetheless, L1 deregulation can be detrimental to the cell, causing diseases such as cancer. The activity of miRNAs represents a fundamental mechanism for controlling transcript levels in somatic cells. These are a class of small non-coding RNAs that cause degradation or translational inhibition of their target transcripts. Beyond this, competitive endogenous RNAs (ceRNAs), mostly made by circular and non-coding RNAs, have been seen to compete for the binding of the same set of miRNAs targeting protein coding genes. In this study, we have investigated whether autonomously transcribed L1s may act as ceRNAs by analyzing public dataset in-silico. We observed that genes sharing miRNA target sites with L1 have a tendency to be upregulated when L1 are overexpressed, suggesting the possibility that L1 might act as ceRNAs. This finding will help in the interpretation of transcriptomic responses in contexts characterized by the specific activation of transposons

Stability of Oscillating Gaseous Masses in Massive Brans-Dicke Gravity

This paper explores the instability of gaseous masses for the radial oscillations in post-Newtonian correction of massive Brans-Dicke gravity. For this purpose, we derive linearized perturbed equation of motion through Lagrangian radial perturbation which leads to the condition of marginal stability. We discuss radius of instability of different polytropic structures in terms of the Schwarzschild radius. It is concluded that our results provide a wide range of difference with those in general relativity and Brans-Dicke gravity.Comment: 31 pages, 11 figures, to appear in IJMP

The Operative management in Bariatric Acute abdomen (OBA) Survey: long-term complications of bariatric surgery and the emergency surgeon\u27s point of view.

Background: The number of bariatric procedures is increasing worldwide. No consensus or guidelines about the emergency management of long-term complications following bariatric surgery are currently available. The aim of this study is to investigate by a web survey how an emergency surgeon approaches this unique group of patients in an emergency medical scenario and to report their personal experience. Method: An international web survey was sent to 197 emergency surgeons with the aim to collect data about emergency surgeons\u27 experience in the management of patients admitted in the emergency department for acute abdominal pain after bariatric surgery. The survey was conceived as a questionnaire composed by 26 (multiple choice and open) questions and approved by a steering committee. Results: One hundred seventeen international emergency surgeons decided to join the project and answered to the web survey with a response rate of 59.39%. Conclusions: The aim of this WSES web survey was to highlight the current management of patients previously submitted to bariatric surgical procedures by ES.Emergency surgeons must be mindful of postoperative bariatric surgery complications. CT scan with oral intestinal opacification may be useful in making a diagnosis if carefully interpreted by the radiologist and the surgeon.In case of inconclusive clinical and radiological findings, when symptoms fail to improve, surgical exploration for bariatric patients presenting acute abdominal pain, by laparoscopy if expertise is available, is mandatory in the first 12-24 h, to have good outcomes and decrease morbidity rate

The need for new "patient-related" guidelines for the treatment of acute cholecystitis

Heterogeneity of patients affected by acute cholecystitis, and their co-morbidities make very difficult to standardize the therapy for this very common condition. The staging system suggested in the recent "Tokyo guidelines", did not show a relevant impact on the management of patients and on the outcome of the disease. The relation among local pathological picture, patient clinical status and treatment algorithm, has to be better studied

Small bowel emergency surgery: literature's review

Emergency surgery of the small bowel represents a challenge for the surgeon, in the third millennium as well. There is a wide number of pathologies which involve the small bowel. The present review, by analyzing the recent and past literature, resumes the more commons. The aim of the present review is to provide the main indications to face the principal pathologies an emergency surgeon has to face with during his daily activity

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

Dietary restriction in the form of fasting is a putative key to a healthier and longer life, but these benefits may come at a trade‐off with reproductive fitness and may affect the following generation(s). The potential inter‐ and transgenerational effects of long‐term fasting and starvation are particularly poorly understood in vertebrates when they originate from the paternal line. We utilised the externally fertilising zebrafish amenable to a split‐egg clutch design to explore the male‐specific effects of fasting/starvation on fertility and fitness of offspring independently of maternal contribution. Eighteen days of fasting resulted in reduced fertility in exposed males. While average offspring survival was not affected, we detected increased larval growth rate in F1 offspring from starved males and more malformed embryos at 24 h post‐fertilisation in F2 offspring produced by F1 offspring from starved males. Comparing the transcriptomes of F1 embryos sired by starved and fed fathers revealed robust and reproducible increased expression of muscle composition genes but lower expression of lipid metabolism and lysosome genes in embryos from starved fathers. A large proportion of these genes showed enrichment in the yolk syncytial layer suggesting gene regulatory responses associated with metabolism of nutrients through paternal effects on extra‐embryonic tissues which are loaded with maternal factors. We compared the embryo transcriptomes to published adult transcriptome datasets and found comparable repressive effects of starvation on metabolism‐associated genes. These similarities suggest a physiologically relevant, directed and potentially adaptive response transmitted by the father, independently from the offspring's nutritional state, which was defined by the mother

WSES classification and guidelines for liver trauma

The severity of liver injuries has been universally classified according to the American Association for the Surgery of Trauma (AAST) grading scale. In determining the optimal treatment strategy, however, the haemodynamic status and associated injuries should be considered. Thus the management of liver trauma is ultimately based on the anatomy of the injury and the physiology of the patient. This paper presents the World Society of Emergency Surgery (WSES) classification of liver trauma and the management Guidelines

Timing of Early Cholecystectomy for Acute Calculous Cholecystitis: A Multicentric Prospective Observational Study

The definition of Early Cholecystectomy (EC) is still debatable. This paper aims to find whether the timing of EC affects outcomes. The article reports a multicentric prospective observational study including patients with acute calculous cholecystitis (ACC) who had cholecystectomy within ten days from the onset of symptoms. Kruskall-Wallis test, Fisher’s Exact test, and Spearman rank correlation were used for statistical analysis. The patients were divided into three groups depending on the timing of the operation: 0–3 days, 4–7 days, or 8–10 days from the onset of symptoms. 1117 patients were studied over a year. The time from the onset of symptoms to EC did not affect the post-operative complications and mortality, the conversion, and the reintervention rate. The time represented a significant risk factor for intraoperative complications (0–3 days, 2.8%; 4–7 days, 5.6%; 8–10 days, 7.9%; p = 0.01) and subtotal cholecystectomies (0–3 days, 2.7%; 4–7 days, 5.6%; 8–10 days, 10.9%; p < 0.001). ACC is an evolutive inflammatory process and, as the days go by, the local and systemic inflammation increases, making surgery more complex and difficult with a higher risk of intraoperative complications. We recommend performing EC for ACC as soon as possible, within the first ten days of the onset of symptoms