Human Retrotransposon Insertion Polymorphisms Are Associated with Health and Disease via Gene Regulatory Phenotypes

AbstractBiological systems exhibit unique phenotypes as the result of the expression of a genomic program. The regulation of this program is a complex phenomenon, wherein different regulatory mechanisms are involved. The deregulation of this program is at the centre of the emergence of diseases such as breast cancer. In particular, it has been observed that coregulation patterns between physically distant genes are lost in breast cancer.In this work, we present a systematic study of chromosome-wide gene coregulation patterns in breast cancer as inferred by information theoretical measures over large (whole-genome expression in several hundred transcriptomes) experimental data corpora. We analyzed the chromosomal distance decay of correlations and found it to be with fat-tail distribution in breast cancer while being fundamentally constant in nontumour samples.After model discrimination analyses, we concluded that the behaviour of the breast cancer distributions belongs to an intermediate regime between power law and Weibull distributions, with distinctive contributions corresponding to different chromosomes. This behaviour may have biological implications in terms of the organization of the gene regulatory program, and the changes found in this program between health and disease.

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Switching On Static Gene Regulatory Networks to Compute Cellular Decisions

10.1101/2020.05.29.122200 ◽

2020 ◽

Author(s):

Clara E. Pavillet ◽

Dimitrios Voukantsis ◽

Francesca M. Buffa

Keyword(s):

Gene Regulatory Networks ◽

Gene Networks ◽

Gene Network ◽

Regulatory Networks ◽

Computational Models ◽

Cell Behaviour ◽

Cellular Processes ◽

Health And Disease ◽

Gene Regulatory ◽

Cellular Behaviour

AbstractMotivationGene networks are complex sets of regulators and interactions that govern cellular processes. Their perturbations can disrupt regular biological functions, translating into a change in cell behaviour and ability to respond to internal and external cues. Computational models of these networks can boost translation of our scientific knowledge into medical applications by predicting how cells will behave in health and disease, or respond to stimuli such as a drug treatment. The development of such models requires effective ways to read, manipulate and analyse the increasing amount of existing, and newly deposited gene network data.ResultsWe developed BioSWITCH, a command-line program using the BioPAX standardised language to “switch on” static regulatory networks so that they can be executed in GINML to predict cellular behaviour. Using a previously published haematopoiesis gene network, we show that BioSWITCH successfully and faithfully automates the network de-coding and re-coding into an executable logical network. BioSWITCH also supports the integration of a BioPAX model into an existing GINML graph.AvailabilitySource code available at https://github.com/CBigOxf/[email protected]; [email protected]

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

Biochemical Society Transactions ◽

10.1042/bst20190944 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1019-1034 ◽

Cited By ~ 1

Author(s):

Rachel M. Woodhouse ◽

Alyson Ashe

Keyword(s):

Histone Modifications ◽

Molecular Mechanisms ◽

Epigenetic Inheritance ◽

Nematode Caenorhabditis Elegans ◽

Histone Methyltransferases ◽

Transgenerational Epigenetic Inheritance ◽

C Elegans ◽

Recent Developments ◽

Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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The Laryngeal Epithelium in Reflux

Perspectives on Voice and Voice Disorders ◽

10.1044/vvd21.3.112 ◽

2011 ◽

Vol 21 (3) ◽

pp. 112-117 ◽

Cited By ~ 2

Author(s):

Elizabeth Erickson-Levendoski ◽

Mahalakshmi Sivasankar

Keyword(s):

Laryngopharyngeal Reflux ◽

Critical Role ◽

Structure And Function ◽

Laryngeal Disease ◽

Health And Disease ◽

And Function ◽

The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

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