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Competing endogenous RNA (ceRNA) molecules have emerged as key players in regulating gene expression, increasing the complexity of the range of possible dynamics within a cell. The actions of competing RNA typically are sponging behaviors, in a manner that fine-tunes gene expression, but there are particular network structures that may show destabilization due to ceRNA interactions. In this chapter, we discuss how these interactions can be modeled and probed from a mathematical, first-principles perspective.Transcription termination is a critical stage for the production of legitimate mRNAs, and consequently functional proteins. However, the transcription machinery can ignore the stop signs and continue elongating beyond gene boundaries, invading downstream neighboring genes. Such phenomenon, designated transcription readthrough, can trigger the expression of pseudogenes usually silenced or lacking the proper regulatory signals. Due to the sequence similarity to parental genes, readthrough transcribed pseudogenes can regulate relevant protein-coding genes and impact biological functions. Here, we describe a computational pipeline that employs already existent bioinformatic tools to detect readthrough transcribed pseudogenes from expression profiles. Tanespimycin research buy We also unveil that combining strand-specific transcriptome data and epigenetic profiles can enhance and corroborate the results. By applying such approach to renal cancer biopsies, we show that pseudogenes can be readthrough transcribed as part of unspliced transcripts or processed RNA chimeras. Overall, our pipeline allows us to scrutinize transcriptome profiles to detect a diversity of readthrough events leading to expression of pseudogenes.Pseudogenes have long been considered nonfunctional elements. The influx of large-scale sequencing projects over the last decade have provided rich sources of evidence that pseudogenes can play key evolutionary and regulatory roles, highlighting the need for high quality annotation for both human and key model organisms. To date, GENCODE has completed the manual annotation of pseudogenes in human and has undertaken the task to curate and characterize pseudogenes in the mouse reference genome. Capitalizing on available high-quality annotations as well as on the functional-genomics, evolutionary, and phenotypical data, we were able to create a comprehensive picture of both the human and mouse pseudogene complements' creation, development, and activity. Thus, we found that while human pseudogenes were created through a single burst of retrotransposition events, the active transposable element content in mouse allows for a continuous renewal of the pseudogene pool. Despite their differences, the two organisms share a number of similarities in terms of pseudogene activity, with ~10% of pseudogenes being transcribed. Finally, we highlight a variety of resources developed based on the available GENCODE annotations that help shed light on pseudogene biology.Long intergenic noncoding RNAs (lincRNAs) are known to be tissue specifically expressed and able to regulate functional protein-coding genes some can even act as competing endogenous RNAs (ceRNAs), because microRNAs can bind to them instead of the corresponding mRNA binding sites. Some lincRNAs contain remnants of protein-coding sequences and it has been hypothesized that they might arise after a pseudogenization processes. However, a major limitation in the study of such phenomenon is the lack of proper computational tools designed to align/analyze protein-coding sequences and noncoding sequences. To overcome this limitation, we published a method that finds the remnants of protein-coding sequences within the sequence of lincRNAs, as well as the corresponding sequences in parental proteins. This method, together with the visualization platform for tracing frameshifts and single point mutations within this type of sequences, are described here.The number of complete genome sequences explodes more and more with each passing year. Thus, methods for genome annotation need to be honed constantly to handle the deluge of information. Annotation of pseudogenes (i.e., gene copies that appear not to make a functional protein) in genomes is a persistent problem; here, we overview pseudogene annotation methods that are based on the detection of sequence homology in genomic DNA.The discovery that pseudogenes are involved in important biological processes has excited enthusiasm and increased the research interest on them. An accurate detection and analysis of pseudogenes can be achieved using comparative methods, but only the use of phylogenetic tools can provide accurate information about their birth, their evolution and their death, hence about the impact that they have on genes and genomes. Here, phylogenetic methods that allow for studying pseudogene history are described.A pseudogene is defined as a genomic DNA sequence that looks like a mutated or truncated version of a known functional gene. Nearly four decades since their first discovery it has been estimated that between ~12,000 and ~20,000 pseudogenes exist in the human genome. Early efforts to characterize functions for pseudogenes were unsuccessful, thus they were considered functionless relics of evolutionary selection, junk DNA or genetic fossils. Remarkably, an increasing number of pseudogenes have been reported to be expressed as RNA transcripts above and beyond levels considered accidental or spurious transcription. There is emerging evidence that some expressed pseudogene transcripts have biological functions and should be defined as a subclass of functional long noncoding RNAs (lncRNA). In this introductory chapter, I briefly summarize the history and the current knowledge of pseudogenes, and highlight the emerging functions of some pseudogenes in human biology and disease. This second iteration of Pseudogenes in Methods in Molecular Biology highlights new methodological approaches to investigate this intriguing family of lncRNAs and the extent of their biological function.

Disparities in obesity highlight the need for an examination of determinants that may be uniquely experienced by race and sex. An understudied factor is household composition with the potential for variation in its obesogenic impacts. This study examines the association between household composition and body mass index (BMI) among Black, Hispanic, and White adults and determines whether income moderates these associations.

Using cross-sectional data from the 2011-2018 National Health and Nutrition Examination Survey, the number of children and adults aged ≥ 60 years in the household were reported among non-Hispanic Black and White adults as well as Hispanic adults aged 20-59 years old. Multivariable linear regressions were used to assess the associations between household composition and BMI with income as a potential moderator.

Having multiple school-aged children was associated with higher BMI (β = 1.34, standard error (s.e.) = 0.50) among Hispanic men, while having older adults in the household was associated with lower BMI among Black women (β = - 3.21, s.e. = 1.42). Income moderated the associations between household composition and BMI among Black women and men. There were no associations between household composition and BMI in White women or men.

Future studies should further explicate the mechanisms of household composition that uniquely impact obesity outcomes among Black women and men by income. Efforts to address higher BMI among those with more young children in the household should target Hispanic men.

Future studies should further explicate the mechanisms of household composition that uniquely impact obesity outcomes among Black women and men by income. Efforts to address higher BMI among those with more young children in the household should target Hispanic men.

There are numerous biomarkers which may have potential predictive and prognostic significance in breast cancer. This is extremely important in older adults, who may opt for less aggressive therapy. This work outlines the literature on biological assessment outside of standard biomarkers (defined as ER, PgR, HER2, Ki67) in women ≥ 65years with primary operable invasive breast cancer, to determine which additional biomarkers are relevant to outcome in older women.

Medline and Embase databases were searched. Studies were eligible if included ≥ 50 patients aged ≥ 65years; stratified results by age; measured a biomarker outside of standard assay and reported patient data.

A total of 12 studies were appraised involving 5000 patients, measuring 28 biomarkers. The studies were extremely varied in methodology and outcome but three themes emerged 1. Differences in biomarker expression between younger and older women, indicating that breast cancer in older women is generally less aggressive compared to younger womese biomarkers in larger cohorts and in women undergoing non-operative therapies are required.The liver is a vital organ responsible for various physiological functions, such as metabolism, immune response, digestion, and detoxification. Crosstalk between hepatocytes, hepatic macrophages, and hepatic stellate cells is critical for liver pathology. Exosomes are small extracellular vesicles (50-150 nm) that play an important role in cell-cell or organ-organ communication as they transfer their cargo, such as protein, DNA, and RNA to recipient cells or distant organs. In various liver diseases, the number of liver cell-derived exosomes is increased and the exosomal microRNA (miRNA) profile is altered. Early studies investigated the value of circulating exosomal miRNAs as biomarkers. Several exosomal miRNAs showed excellent diagnostic values, suggesting their potential as diagnostic biomarkers in liver diseases. Exosomal miRNAs have emerged as critical regulators of liver pathology because they control the expression of multiple genes in recipient cells. In this review, we discuss the biology of exosomes and summarize the recent findings of exosome-mediated intercellular and organ-to-organ communication during liver pathology. As there are many review articles dealing with exosomal miRNAs in liver cancer, we focused on non-malignant liver diseases. The therapeutic potential of exosomal miRNAs in liver pathology is also highlighted.

In patients with chronic hypoparathyroidism disordered calcium homeostasis has been associated with risk of cardiovascular diseases, including cardiomyopathy, congestive heart failure, and arrhythmia; however, larger-scale studies are needed to examine these risks. This study evaluated the risk of cardiovascular conditions among patients with chronic hypoparathyroidism.

Adults with and without chronic hypoparathyroidism were selected from a medical insurance claims database in the USA from January 2007 to June 2017, and were followed for up to 5years. Associations between chronic hypoparathyroidism and incident atrial fibrillation (AF), tachyarrhythmia, myocardial infarction (MI), coronary artery disease (CAD), heart failure (HF), stroke, cerebrovascular disease, peripheral vascular disease (PVD), and a combined cardiovascular endpoint of cerebrovascular disease, CAD, HF, and PVD were compared between cohorts using Kaplan-Meier analyses and unadjusted and adjusted Cox proportional hazards models.

In 8097 patients with chronic hypoparathyroidism compared with 40,485 patients without, respectively, mean ± SD ages were 58.