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Yale Journal of Biology and Medicine

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https://www.readbyqxmd.com/read/28018148/epigenetics-and-common-ophthalmic-diseases
#1
REVIEW
Wendy Li, Ji Liu, Jennifer A Galvin
The study of ocular diseases and epigenetic dysregulation is an emerging area of research. The knowledge from the epigenetic mechanisms of DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs regarding the pathogenesis of ocular diseases will be helpful for improved treatment modalities for our patients. In particular, we focus upon the how epigenetic regulatory mechanisms impact five common ocular diseases: age related macular degeneration, age-related cataract, pterygium, retinoblastoma, and uveal melanoma...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018147/receptor-signaling-directs-global-recruitment-of-pre-existing-transcription-factors-to-inducible-elements
#2
REVIEW
Peter N Cockerill
Gene expression programs are largely regulated by the tissue-specific expression of lineage-defining transcription factors or by the inducible expression of transcription factors in response to specific stimuli. Here I will review our own work over the last 20 years to show how specific activation signals also lead to the wide-spread re-distribution of pre-existing constitutive transcription factors to sites undergoing chromatin reorganization. I will summarize studies showing that activation of kinase signaling pathways creates open chromatin regions that recruit pre-existing factors which were previously unable to bind to closed chromatin...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018146/pancreatic-cancer-a-mis-interpreter-of-the-epigenetic-language
#3
REVIEW
Eriko Iguchi, Stephanie L Safgren, David L Marks, Rachel L Olson, Martin E Fernandez-Zapico
Pancreatic cancer is the third leading cause of cancer mortality in the U.S. with close to 40,000 deaths per year. Pancreatic ductal adenocarcinoma (PDAC) represents approximately 90 percent of all pancreatic cancer cases and is the most lethal form of the disease. Current therapies for PDAC are ineffective and most patients cannot be treated by surgical resection. Most research efforts have primarily focused on how genetic alterations cause, alter progression, contribute to diagnosis, and influence PDAC management...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018145/epigenetics-of-renal-development-and-disease
#4
REVIEW
Sylvia A Hilliard, Samir S El-Dahr
An understanding of epigenetics is indispensable to our understanding of gene regulation under normal and pathological states. This knowledge will help with designing better therapeutic approaches in regenerative tissue medicine. Epigenetics allows us to parse out the mechanisms by which transcriptional regulators gain access to specific gene loci thereby imprinting epigenetic information affecting chromatin function. This epigenetic memory forms the basis of cell lineage specification in multicellular organisms...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018144/deciphering-the-epigenetic-code-in-embryonic-and-dental-pulp-stem-cells
#5
REVIEW
Dashzeveg Bayarsaihan
A close cooperation between chromatin states, transcriptional modulation, and epigenetic modifications is required for establishing appropriate regulatory circuits underlying self-renewal and differentiation of adult and embryonic stem cells. A growing body of research has established that the epigenome topology provides a structural framework for engaging genes in the non-random chromosomal interactions to orchestrate complex processes such as cell-matrix interactions, cell adhesion and cell migration during lineage commitment...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018143/emerging-functions-of-circular-rnas
#6
REVIEW
Mariela Cortés-López, Pedro Miura
Many thousands of Circular RNAs (circRNAs) have recently been identified in metazoan genomes by transcriptome-wide sequencing. Most circRNAs are generated by back-splicing events from exons of protein-coding genes. A great deal of progress has recently been made in understanding the genome-wide expression patterns, biogenesis, and regulation of circRNAs. To date, however, few functions of circRNAs have been identified. CircRNAs are preferentially expressed in neural tissues and some are found at synapses, suggesting possible functions in the nervous system...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018142/the-role-of-the-ubiquitously-expressed-transcription-factor-sp1-in-tissue-specific-transcriptional-regulation-and-in-disease
#7
REVIEW
Leigh O'Connor, Jane Gilmour, Constanze Bonifer
Sp1 belongs to the 26 member strong Sp/KLF family of transcription factors. It is a paradigm for a ubiquitously expressed transcription factor and is involved in regulating the expression of genes associated with a wide range of cellular processes in mammalian cells. Sp1 can interact with a range of proteins, including other transcription factors, members of the transcription initiation complex and epigenetic regulators, enabling tight regulation of its target genes. In this review, we discuss the mechanisms involved in Sp1-mediated transcriptional regulation, as well as how a ubiquitous transcription factor can be involved in establishing a tissue-specific pattern of gene expression and mechanisms by which its activity may be regulated...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018141/what-drives-positive-selection-in-the-drosophila-pirna-machinery-the-genomic-autoimmunity-hypothesis
#8
REVIEW
Justin P Blumenstiel, Alexandra A Erwin, Lucas W Hemmer
In animals, PIWI-interacting RNAs (piRNAs) play a crucial role in genome defense. Moreover, because piRNAs can be maternally transmitted, they contribute to the epigenetic profile of inheritance. Multiple studies, especially in Drosophila, have demonstrated that the machinery of piRNA biogenesis is often the target of positive selection. Because transposable elements (TEs) are a form of genetic parasite, positive selection in the piRNA machinery is often explained by analogy to the signatures of positive selection commonly observed in genes that play a role in host-parasite dynamics...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018140/friend-or-foe-epigenetic-regulation-of-retrotransposons-in-mammalian-oogenesis-and-early-development
#9
REVIEW
Alexei V Evsikov, Caralina Marín de Evsikova
Epigenetics is the study of phenotypic variation arising from developmental and environmental factors regulating gene transcription at molecular, cellular, and physiological levels. A naturally occurring biological process driven by epigenetics is the egg-to-embryo developmental transition when two fully differentiated adult cells - egg and sperm - revert to an early stem cell type with totipotency but subsequently differentiates into pluripotent embryonic stem cells that give rise to any cell type. Transposable elements (TEs) are active in mammalian oocytes and early embryos, and this activity, albeit counterintuitive because TEs can lead to genomic instability in somatic cells, correlates to successful development...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018139/crispr-mediated-epigenome-editing
#10
REVIEW
Paul Enríquez
Mounting evidence has called into question our understanding of the role that the central dogma of molecular biology plays in human pathology. The conventional view that elucidating the mechanisms for translating genes into proteins can account for a panoply of diseases has proven incomplete. Landmark studies point to epigenetics as a missing piece of the puzzle. However, technological limitations have hindered the study of specific roles for histone post-translational modifications, DNA modifications, and non-coding RNAs in regulation of the epigenome and chromatin structure...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018138/editing-the-neuronal-genome-a-crispr-view-of-chromatin-regulation-in-neuronal-development-function-and-plasticity
#11
REVIEW
Marty G Yang, Anne E West
The dynamic orchestration of gene expression is crucial for the proper differentiation, function, and adaptation of cells. In the brain, transcriptional regulation underlies the incredible diversity of neuronal cell types and contributes to the ability of neurons to adapt their function to the environment. Recently, novel methods for genome and epigenome editing have begun to revolutionize our understanding of gene regulatory mechanisms. In particular, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has proven to be a particularly accessible and adaptable technique for genome engineering...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018137/dna-hypomethylation-in-intragenic-and-intergenic-enhancer-chromatin-of-muscle-specific-genes-usually-correlates-with-their-expression
#12
Kenneth C Ehrlich, Heather L Paterson, Michelle Lacey, Melanie Ehrlich
Tissue-specific enhancers are critical for gene regulation. In this study, we help elucidate the contribution of muscle-associated differential DNA methylation to the enhancer activity of highly muscle-specific genes. By bioinformatic analysis of 44 muscle-associated genes, we show that preferential gene expression in skeletal muscle (SkM) correlates with SkM-specific intragenic and intergenic enhancer chromatin and overlapping foci of DNA hypomethylation. Some genes, e.g., CASQ1 and FBXO32, displayed broad regions of both SkM- and heart-specific enhancer chromatin but exhibited focal SkM-specific DNA hypomethylation...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28018136/cbx-chromodomain-inhibition-enhances-chemotherapy-response-in-glioblastoma-multiforme
#13
Katelyn E Connelly, Emily C Martin, Emily C Dykhuizen
Glioblastoma multiforme (GBM) lacks effective therapeutic options leaving patients with a survival time of approximately one year. Recently, the alteration of chromatin modulators has been implicated in the pathogenesis and chemoresistance of numerous cancers; in particular, the Polycomb Group Proteins have been shown to play a role in glioblastoma progression and maintenance [1-5]. In this study, we aimed to identify drug combinations that decrease GBM cell viability by combining small molecule inhibitors against the Polycomb family with two standard chemotherapies...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27698624/integrative-therapies-in-anxiety-treatment-with-special-emphasis-on-the-gut-microbiome
#14
Stephanie L Schnorr, Harriet A Bachner
Over the past decade, research has shown that diet and gut health affects symptoms expressed in stress related disorders, depression, and anxiety through changes in the gut microbiota. Psycho-behavioral function and somatic health interaction have often been ignored in health care with resulting deficits in treatment quality and outcomes. While mental health care requires the professional training in counseling, psychotherapy and psychiatry, complimentary therapeutic strategies, such as attention to a nutritional and diverse diet and supplementation of probiotic foods, may be integrated alongside psychotherapy treatment models...
September 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27698623/striking-a-balance-with-help-from-our-little-friends-how-the-gut-microbiota-contributes-to-immune-homeostasis
#15
REVIEW
Kathleen L Arnolds, Catherine A Lozupone
The trillions of microbes that inhabit the human gut (the microbiota) together with the host comprise a complex ecosystem, and like any ecosystem, health relies on stability and balance. Some of the most important members of the human microbiota are those that help maintain this balance via modulation of the host immune system. Gut microbes, through both molecular factors (such as capsular components) and by-products of their metabolism (such as Short Chain Fatty Acids (SCFAs)), can influence both innate and adaptive components of the immune system, in ways that can drive both effector, and regulatory responses...
September 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27698622/treating-obesity-and-metabolic-syndrome-with-fecal-microbiota-transplantation
#16
REVIEW
Clarisse A Marotz, Amir Zarrinpar
The worldwide prevalence of metabolic syndrome, which includes obesity and its associated diseases, is rising rapidly. The human gut microbiome is recognized as an independent environmental modulator of host metabolic health and disease. Research in animal models has demonstrated that the gut microbiome has the functional capacity to induce or relieve metabolic syndrome. One way to modify the human gut microbiome is by transplanting fecal matter, which contains an abundance of live microorganisms, from a healthy individual to a diseased one in the hopes of alleviating illness...
September 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27698621/the-impact-of-the-gut-microbiota-on-drug-metabolism-and-clinical-outcome
#17
Elaine F Enright, Cormac G M Gahan, Susan A Joyce, Brendan T Griffin
The significance of the gut microbiota as a determinant of drug pharmacokinetics and accordingly therapeutic response is of increasing importance with the advent of modern medicines characterised by low solubility and/or permeability, or modified-release. These physicochemical properties and release kinetics prolong drug residence times within the gastrointestinal tract, wherein biotransformation by commensal microbes can occur. As the evidence base in support of this supplementary metabolic "organ" expands, novel opportunities to engineer the microbiota for clinical benefit have emerged...
September 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27698620/the-hoops-hopes-and-hypes-of-human-microbiome-research
#18
REVIEW
Elisabeth M Bik
Recent developments in sequencing methods and bioinformatics analysis tools have greatly enabled the culture-independent analysis of complex microbial communities associated with environmental samples, plants, and animals. This has led to a spectacular increase in the number of studies on both membership and functionalities of these hitherto invisible worlds, in particular those of the human microbiome. The wide variety in available microbiome tools and platforms can be overwhelming, and making sound conclusions from scientific research can be challenging...
September 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27698619/metagenomic-assembly-overview-challenges-and-applications
#19
Jay S Ghurye, Victoria Cepeda-Espinoza, Mihai Pop
Advances in sequencing technologies have led to the increased use of high throughput sequencing in characterizing the microbial communities associated with our bodies and our environment. Critical to the analysis of the resulting data are sequence assembly algorithms able to reconstruct genes and organisms from complex mixtures. Metagenomic assembly involves new computational challenges due to the specific characteristics of the metagenomic data. In this survey, we focus on major algorithmic approaches for genome and metagenome assembly, and discuss the new challenges and opportunities afforded by this new field...
September 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27698618/an-ecological-framework-of-the-human-virome-provides-classification-of-current-knowledge-and-identifies-areas-of-forthcoming-discovery
#20
REVIEW
Michael T Parker
Recent advances in sequencing technologies have opened the door for the classification of the human virome. While taxonomic classification can be applied to the viruses identified in such studies, this gives no information as to the type of interaction the virus has with the host. As follow-up studies are performed to address these questions, the description of these virus-host interactions would be greatly enriched by applying a standard set of definitions that typify them. This paper describes a framework with which all members of the human virome can be classified based on principles of ecology...
September 2016: Yale Journal of Biology and Medicine
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