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Progress in Molecular Biology and Translational Science

David B Teplow
No abstract text is available yet for this article.
2018: Progress in Molecular Biology and Translational Science
Chang Ho Lee, Seung Ryul Han, Seong-Wook Lee
In 1982, the Cech group discovered that an intron structure in an rRNA precursor of Tetrahymena thermophila is sufficient to complete splicing without assistance from proteins. This was the first moment that scientists recognized RNAs can have catalytic activities derived from their own unique three-dimensional structures and thus play more various roles in biological processes than thought before. Several additional catalytic RNAs, called ribozymes, were subsequently identified in nature followed by intense studies to reveal their mechanisms of action and to engineer them for use in fields such as molecular cell biology, therapeutics, imaging, etc...
2018: Progress in Molecular Biology and Translational Science
Kaitlyn R Kelly, Bryan W Brooks
Rapid urbanization represents a global megatrend that is resulting in an increasingly urban water cycle frequently contaminated by human medicines and other chemicals. Concentration of chemical consumption is occurring faster than implementation of environmental health systems and interventions, particularly in megacities of developing countries, while 80% of global sewage production remains untreated. In these urban areas, antibiotics in the environment influence development of antibiotic resistance (ABR) by pathogens...
2018: Progress in Molecular Biology and Translational Science
Anastasios Lymperopoulos
Three major functional roles for the two ubiquitous G protein-coupled receptor (GPCR) adapter proteins, βarrestin1 and -2 (also known as Arrestin2 and -3, respectively), have been described: (a) functional desensitization, i.e., G-protein uncoupling from the receptor, (b) GPCR internalization via clathrin-coated pits, and (c) formation of signalosomes. Either while bound to the GPCR or after dissociating from it, and either while trafficking inside the cell or from the plasma membrane, both βarrestins are known to mediate a large part of the G protein-independent signaling elicited by GPCRs...
2018: Progress in Molecular Biology and Translational Science
Sara M O'Rourke, William G Scott
Natural or full-length hammerhead ribozymes are up to 1000-fold more active than their minimal counterparts that lack a complex tertiary interaction that pre-organizes and stabilizes the ribozyme active site, positioning RNA functional groups to facilitate acid-base catalysis. The recent discovery that a single tertiary contact (an AU Hoogsteen pair) between Stems I and II confers essentially all of the enhanced activity greatly simplifies our understanding of the structural requirements for hammerhead ribozyme activity...
2018: Progress in Molecular Biology and Translational Science
Arun Pandian Chandrasekaran, Minjung Song, Kye-Seong Kim, Suresh Ramakrishna
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) is comprised of repetitive bases followed by short fragments of DNA from a previously invading organism that provide immunity to the most prokaryotic organisms. An RNA-dependent spacer is required for CRISPR/Cas9 to recognize the target DNA. Delivery of the CRISPR/Cas9-guide RNA (gRNA) complex to any cell results in modification of the target sequence. The CRISPR/Cas9-mediated genome editing technique is currently in the spotlight and has several research interests, including molecular medicine and agriculture...
2018: Progress in Molecular Biology and Translational Science
Ricardo F Dos Santos, Ana P Quendera, Sofia Boavida, André F Seixas, Cecília M Arraiano, José M Andrade
3'-5' exoribonucleases are key enzymes in the degradation of superfluous or aberrant RNAs and in the maturation of precursor RNAs into their functional forms. The major bacterial 3'-5' exoribonucleases responsible for both these activities are PNPase, RNase II and RNase R. These enzymes are of ancient nature with widespread distribution. In eukaryotes, PNPase and RNase II/RNase R enzymes can be found in the cytosol and in mitochondria and chloroplasts; RNase II/RNase R-like enzymes are also found in the nucleus...
2018: Progress in Molecular Biology and Translational Science
Lindsay M Lueptow, Lakshmi A Devi, Amanda K Fakira
G-protein coupled receptors (GPCRs) are a superfamily of receptors responsible for initiation of a myriad of intracellular signaling cascades. Currently, GPCRs represent approximately 34% of marketed pharmaceuticals, a large portion of which have no known endogenous ligand. These orphan GPCRs represent a large pool of novel targets for drug development. Very recently, the neuropeptide PEN, derived from the proteolytic processing of the precursor proSAAS, has been identified as a selective, high-affinity endogenous ligand for the orphan receptor, GPR83...
2018: Progress in Molecular Biology and Translational Science
Stephan Claes
Life does not start at birth but at conception. What a person experiences during the first 9 months of life in the intrauterine environment will have lasting effects on health and disease later in life. Psychological stress in pregnant women has a number of potential negative consequences for the physical and psychological function of their children. The mechanisms driving this association are, among others, epigenetic modifications at specific loci in the infant DNA. In the chapter, the relevant animal and human studies underlying these assumptions are reviewed, and it is argued that they are convincingly supported by the evidence...
2018: Progress in Molecular Biology and Translational Science
Roy Lardenoije, Ehsan Pishva, Katie Lunnon, Daniel L van den Hove
Neurodegenerative diseases are complex, progressive disorders and affect millions of people worldwide, contributing significantly to the global burden of disease. In recent years, research has begun to investigate epigenetic mechanisms for a potential role in disease etiology. In this chapter, we describe the current state of play for epigenetic research into neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. We focus on the recent evidence for a potential role of DNA modifications, histone modifications and non-coding RNA in the etiology of these disorders...
2018: Progress in Molecular Biology and Translational Science
Chiara Renzi, Nadine Provencal, Katherine C Bassil, Kathinka Evers, Ulrik Kihlbom, Elizabeth J Radford, Ilona Koupil, Bertram Mueller-Myhsok, Mats G Hansson, Bart P F Rutten
The development of mental disorders constitutes a complex phenomenon driven by unique social, psychological and biological factors such as genetics and epigenetics, throughout an individual's life course. Both environmental and genetic factors have an impact on mental health phenotypes and act simultaneously to induce changes in brain and behavior. Here, we describe and critically evaluate the current literature on gene-environment interactions and epigenetics on mental health by highlighting recent human and animal studies...
2018: Progress in Molecular Biology and Translational Science
Elizabeth J Radford
The astonishing array of cellular phenotypes required to make a complex organism such as a human is generated from an identical genetic sequence in the nucleus of each cell. The central nervous system is a highly ordered, complex system composed of multiple neuronal and glial cell types. Both neurons and glia are derived from neural stem/precursor cells (NPCs) in a temporally and spatially patterned process of cellular division and differentiation, migration, maturation and the establishment of neuronal connectivity...
2018: Progress in Molecular Biology and Translational Science
Ali Jawaid, Martin Roszkowski, Isabelle M Mansuy
Traumatic stress is a type of environmental experience that can modify behavior, cognition and physiological functions such as metabolism, in mammals. Many of the effects of traumatic stress can be transmitted to subsequent generations even when individuals from these generations are not exposed to any traumatic stressor. This book chapter discusses the concept of epigenetic/non-genomic inheritance of such traits involving the germline in mammals. It includes a comprehensive review of animal and human studies on inter- and transgenerational inheritance of the effects of traumatic stress, some of the epigenetic changes in the germline currently known to be associated with traumatic stress, and possible mechanisms for their induction and maintenance during development and adulthood...
2018: Progress in Molecular Biology and Translational Science
Laura M Fiori, Rixing Lin, Chelsey Ju, Raoul Belzeaux, Gustavo Turecki
Major depressive disorder is a chronic and debilitating illness. It is most commonly treated with antidepressant drugs, however, as the majority of patients do not respond on their first trial or following several adequate trials, there is great interest in identifying biological factors that may help select the most appropriate treatment for each patient and in understanding biological processes that mediate treatment response. Epigenetic factors, such as non-coding RNAs (ncRNAs), hold potential as biomarkers of antidepressant response...
2018: Progress in Molecular Biology and Translational Science
Grace S Kim, Alicia K Smith, Caroline M Nievergelt, Monica Uddin
While diagnosis of PTSD is based on behavioral symptom clusters that are most directly associated with brain function, epigenetic studies of PTSD in humans to date have been limited to peripheral tissues. Animal models of PTSD have been key for understanding the epigenetic alterations in the brain most directly relevant to endophenotypes of PTSD, in particular those pertaining to fear memory and stress response. This chapter provides an overview of neuroepigenetic studies based on animal models of PTSD, with an emphasis on the effect of stress on fear memory...
2018: Progress in Molecular Biology and Translational Science
Giovanna Punzi, Rahul Bharadwaj, Gianluca Ursini
Schizophrenia is a complex disorder of the brain, where genetic variants explain only a portion of risk. Neuroepigenetic mechanisms may explain the remaining share of risk, as well as the transition from susceptibility to the actual disease. Here, we discuss the most recent findings in the field of brain epigenetics applied to the study of schizophrenia. Methylome studies have found several candidates exhibiting methylation modifications in association with the disorder, but genes affected do not always overlap...
2018: Progress in Molecular Biology and Translational Science
Mathilde Règue-Guyon, Laurence Lanfumey, Raymond Mongeau
This review examines the epigenetic of neurotrophin signaling in anxiety, affective disorders and related symptoms associated with drug addiction, in particular alcoholism. It is first important to understand the epigenetics of aversion memories, as they are so central to anxiety and affective disorders symptomology. The crucial role of neurotrophins in memory formation, in particular the brain-derived nerve growth factor (BDNF), is explored at the physiological and behavioral levels. Numerous studies describe how various epigenetic phenomena, mainly histone acetylation, histone methylation, DNA methylation, but also other less known epigenetic phenomena such as histone poly[ADP]-ribosylation and 5-HT2C receptor pre-mRNA editing, exert significant regulatory roles in aversion memory and fear extinction memory formation...
2018: Progress in Molecular Biology and Translational Science
Clara Snijders, Katherine C Bassil, Laurence de Nijs
Over the last years, interest in epigenetic mechanisms has strongly increased in the field of neuroscience. Neuroepigenetics has intensely evolved and now refers to the assessment of a variety of epigenetic marks which can be found across several regions of the healthy or diseased brain. These marks include DNA (hydroxy)methylation, a large diversity of post-translational histone modifications and an increasing number of non-coding RNAs. The present chapter aims to concisely summarize the techniques used to study these mechanisms in the brain and provides an overview of their current challenges along with future perspectives that will allow the field to move forward...
2018: Progress in Molecular Biology and Translational Science
Ramona A J Zwamborn, Clara Snijders, Ning An, Alix Thomson, Bart P F Rutten, Laurence de Nijs
The Wnt signaling pathway has been recognized as an important pathway, extending its function throughout the lifespan. Evidence suggests that dysfunctional Wnt signaling in the adult brain leads to aberrant neurogenesis, synaptogenesis, modulation of mature synapses and neurotransmitter release in the hippocampus. Due to the involvement of Wnt proteins in hippocampal functioning, altered Wnt signaling has been suggested to be an important factor in the pathophysiology of mood disorders. Interestingly, the effects of mood-stabilizing drugs are believed to work through interactions with Wnt molecules, and epigenetic mechanisms have been shown to interact with components of the Wnt pathway and impact mechanisms such as synaptic plasticity...
2018: Progress in Molecular Biology and Translational Science
Alec Dick, Nadine Provencal
Dynamic adaptation to stressful life events requires the co-ordinated action of the central stress response, which is mediated by the hypothalamic-pituitary-adrenal (HPA) axis, to restore and maintain homeostasis. Excessive exposure to stress or traumatic life events, such as childhood maltreatment, has been linked to HPA axis dysfunction increasing the risk of developing stress-related psychopathologies such as major depressive disorder and post-traumatic-stress-disorder. Mounting evidence supports the notion that stressors throughout pre- and postnatal development as well as adulthood can induce neuroepigenetic regulation of gene expression within key nodes of the brain, which may in part mediate such HPA axis dysfunction...
2018: Progress in Molecular Biology and Translational Science
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