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Developing Stem Cell-Based Therapies For Neural Repair

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194025 Year: Pages: 114 DOI: 10.3389/978-2-88919-402-5 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Current pharmacotherapies and surgical intervention provide limited benefit in the treatment of neural injuries or halting disease progression and has resulted in significant hope for the successes of stem cell research. The properties of stem cells render them appropriate for cell replacement therapy, endogenous repair, disease modeling as well as high-throughput drug screening and development. Such applications will aide in increasing our knowledge and developing treatments for neurodegenerative disorders such as Parkinson’s disease and Huntington’s diseases as well as neural traumas including ischemic brain damage and traumatic brain injury. This Frontiers Research topic encouraged contributions from the general field of stem cell biology, with a particular emphasis on utilizing these cells to develop new therapies for neural repair. Related articles deal with issues such as: breakthroughs in stem cell proliferation/differentiation methodologies, using pluripotent and neural stem cells for transplantation and endogenous repair, the use of patient derived stem cells for disease modeling, using stem cells for drug discovery as well as the ethical issues related to the use of stem cells.

30 years of the Comet Assay: an overview with some new insights

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196494 Year: Pages: 174 DOI: 10.3389/978-2-88919-649-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2016-08-16 10:34:25
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By means of this ‘Frontiers in Genetics’ research topic, we are celebrating 30 years of the Comet Assay. The first paper on this single-cell gel electrophoresis assay was published in 1984 by O. Ostling and K.J. Johanson (Biochem. Biophys. Res. Commun. Vol.123: 291-298). The comet assay is a versatile and sensitive method for measuring single - and double-strand breaks in DNA. By including lesion-specific enzymes in the assay, its range and sensitivity are greatly increased, but it is important to bear in mind that their specificity is not absolute. The comet assay (with and without inclusion of lesion-specific enzymes) is widely used as a biomarker assay in human population studies - primarily to measure DNA damage, but increasingly also to assess the capacity of cells for DNA repair. Ostling and Johanson (Biochem. Biophys. Res. Commun., 1984) were also the first to report experiments to measure DNA repair, by simply following the decrease of DNA damage over time after challenging cells with ionising radiation. However, this approach is time-consuming and laborious as it requires an extended period of cell culture and is therefore not ideal for biomonitoring studies, which typically require high-throughput processing of many samples. As an alternative approach, the in vitro comet-based repair assay was developed: a cell extract is incubated with a DNA substrate containing specific lesions, and DNA incisions accumulate. The in vitro comet-based repair assay has been modified and improved over the past decade: it was first devised to measure base excision repair of oxidised purines in lymphocytes (Collins et al., Mutagenesis, 2001), but has since been adapted for other lesions and thus other repair pathways, as well as being applied to tissue samples in addition to cell suspensions. Even after 30 years, the comet assay is still in a growth phase, with many new users each year. Many questions are repeatedly raised, which may seem to have self-evident answers, but clearly, it is necessary to reiterate them for the benefit of the new audience, and sometimes being forced to think again about old topics can shed new light. Different applications of the comet assay are discussed in this special issue, including: genotoxicity testing in different organisms, human biomonitoring, DNA repair studies, environmental biomonitoring and clinical studies. Furthermore, we consider and where possible answer questions, including the ones raised by Raymond Tice at the 8th International Comet Assay Workshop in Perugia (Italy 2009): What is the spectrum of DNA damage detected by the various versions of the comet assay?; What are the limitations associated with each application?; What should be done to standardize the assay for biomonitoring studies?; Can the comet assay be used to monitor changes in global methylation status?; What cell types are suitable for detecting genotoxic substances and their effects in vivo and in vitro?; Can the assay be fully automated?; and more. So this ‘Frontiers in Genetics’ research topic is written for the beginner as well as for the experienced users of the comet assay.

DNA Replication Controls

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ISBN: 9783038425724 9783038425731 Year: Volume: 2 Pages: X, 346 DOI: 10.3390/books978-3-03842-573-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-12-27 08:38:10
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The conditions for DNA replication are not ideal, owing to endogenous and exogenous replication stresses that lead to arrest of the replication fork. Arrested forks are among the most serious threats to genomic integrity because they can break or rearrange, leading to genomic instability, which is a hallmark of cancers and aging-related disorders. This title, “DNA Replication Controls”, presents series of new reviews and original research articles, providing a comprehensive guide to theoretical advancements in the field of DNA replication research in both prokaryotic and eukaryotic systems. The topics include DNA polymerases and helicases; replication initiation; replication timing; replication-associated DNA repair; and replication of difficult-to-replicate genomic regions, including telomeres, centromeres and highly-transcribed regions. This title also provides recent advancements in studies of cellular processes that are coordinated with DNA replication and how defects in the DNA replication program result in genetic disorders, including cancer. Written by leading experts in DNA replication regulation, this book will be an important resource for a wide variety of audiences, including junior graduate students and established investigators who have interests in DNA replication and genome maintenance mechanisms.

DNA Replication Controls

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ISBN: 9783038425687 9783038425694 Year: Volume: 1 Pages: X, 304 DOI: 10.3390/books978-3-03842-569-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2018-01-02 15:17:59
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The conditions for DNA replication are not ideal, owing to endogenous and exogenous replication stresses that lead to arrest of the replication fork. Arrested forks are among the most serious threats to genomic integrity because they can break or rearrange, leading to genomic instability, which is a hallmark of cancers and aging-related disorders.

On the Origin and Function of Human NK-like CD8+ T Cells: Charting New Territories

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453962 Year: Pages: 121 DOI: 10.3389/978-2-88945-396-2 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2018-11-16 17:17:57
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Human CD8+ T cells expressing NK receptors and receptors found on innate immune cells, and designated as NK-like or innate CD8+ T cells, have been long considered as terminally differentiated lymphocytes responsible for tissue inflammation and destruction. However, a growing body of knowledge is unveiling that NK-like CD8+ T cells have many, sometimes contrasting, functions. The limited knowledge of the biology of this type of CD8+ T cells and the role they play within peripheral tissues and organs under homeostatic conditions has hampered our understanding of disease and therefore the possible development of disease diagnostic tools and effective immunotherapies. In this Research Topic are presented a variety of topics and views, some of them overlooked for many years, on human NK-like CD8+ T cells, which may open new and novel avenues of research to further our understanding of these polyfunctional T cells.

Mobile Genetic Elements in Cellular Differentiation, Genome Stability, and Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453894 Year: Pages: 123 DOI: 10.3389/978-2-88945-389-4 Language: English
Publisher: Frontiers Media SA
Subject: Biology --- Science (General) --- Chemistry (General)
Added to DOAB on : 2018-11-22 11:50:10
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The human genome, as with the genome of most organisms, is comprised of various types of mobile genetic element derived repeats. Mobile genetic elements that mobilize by an RNA intermediate, include both autonomous and non-autonomous retrotransposons, and mobilize by a “copy and paste” mechanism that relies of the presence of a functional reverse transcriptase activity. The extent to which these different types of elements are actively mobilizing varies among organisms, as revealed with the advent of Next Generation DNA sequencing (NGS).To understand the normal and aberrant mechanisms that impact the mobility of these elements requires a more extensive understanding of how these elements interact with molecular pathways of the cell, including DNA repair, recombination and chromatin. In addition, epigenetic based-mechanisms can also influence the mobility of these elements, likely by transcriptional activation or repression in certain cell types. Studies regarding how mobile genetic elements interface and evolve with these pathways will rely on genomic studies from various model organisms. In addition, the mechanistic details of how these elements are regulated will continue to be elucidated with the use of genetic, biochemical, molecular, cellular, and bioinformatic approaches. Remarkably, the current understanding regarding the biology of these elements in the human genome, suggests these elements may impact developmental biology, including cellular differentiation, neuronal development, and immune function. Thus, aberrant changes in these molecular pathways may also impact disease, including neuronal degeneration, autoimmunity, and cancer.

Soft-Tissue Reconstruction Using Biologic Tissue Matrix: Where Do We Stand?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455034 Year: Pages: 91 DOI: 10.3389/978-2-88945-503-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Surgery
Added to DOAB on : 2019-01-23 14:53:42
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Soft-tissue reconstruction for a variety of surgical conditions, such as abdominal wall hernia, hiatal hernia, stomal hernia, anal fistula and pelvic floor replacement remains a challenge. There is an insufficient level of high-quality evidence in the literature on the value of bioprosthetics for soft-tissue reconstruction. An expanded knowledge about their clinical efficacy is urgently needed.

Adult neurogenesis twenty years later: physiological function versus brain repair

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194940 Year: Pages: 120 DOI: 10.3389/978-2-88919-494-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-16 15:44:59
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The discovery that mammalian brains contain neural stem cells which perform adult neurogenesis - the production and integration of new neurons into mature neural circuits - has provided a fully new vision of neural plasticity. On a theoretical basis, this achievement opened new perspectives for therapeutic approaches in restorative and regenerative neurology. Nevertheless, in spite of striking advancement concerning the molecular and cellular mechanisms which allow and regulate the neurogenic process, its exploitation in mammals for brain repair strategies remains unsolved. In non-mammalian vertebrates, adult neurogenesis also contributes to brain repair/regeneration. In mammals, neural stem cells do respond to pathological conditions in the so called "reactive neurogenesis", yet without substantial regenerative outcome. Why, even in the presence of stem cells in the brain, we lack an effective reparative outcome in terms of regenerative neurology, and which factors hamper the attainment of this goal? Essentially, what remains unanswered is the question whether (and how) physiological functions of adult neurogenesis in mammals can be exploited for brain repair purposes.

Pattern recognition receptors and cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196746 Year: Pages: 201 DOI: 10.3389/978-2-88919-674-6 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-08-16 10:34:25
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The group of pattern recognition receptors (PRRs) includes families of Toll-like receptors (TLRs), NOD-like receptors (NLRs), C-type lectin receptors (CLRs), RIG-I-like receptors (RLRs), and AIM-2-like receptors (ALRs). Conceptually, receptors constituting these families are united by two general features. Firstly, they directly recognize common antigen determinants of virtually all classes of pathogens (so-called pathogen-associated molecular patterns, or simply PAMPs) and initiate immune response against them via specific intracellular signaling pathways. Secondly, they recognize endogenous ligands (since they are usually released during cell stress, they are called damage-associated molecular patterns, DAMPs), and, hence, PRR-mediated immune response can be activated without an influence of infectious agents. So, pattern recognition receptors play the key role performing the innate and adaptive immune response. In addition, many PRRs have a number of other vital functions apart from participation in immune response realization. The fundamental character and diversity of PRR functions have led to amazingly rapid research in this field. Such investigations are very promising for medicine as immune system plays a key role in vast majority if not all human diseases, and the process of discovering the new aspects of the immune system functioning is rapidly ongoing. The role of Toll-like receptors in cancer was analyzed in certain reviews but the data are still scattered. This collection of reviews systematizes the key information in the field.

The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454105 Year: Pages: 174 DOI: 10.3389/978-2-88945-410-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology --- Biology --- Physiology
Added to DOAB on : 2018-11-16 17:17:57
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Tissues and organs have, although sometimes limited, the capacity for endogenous repair, which is aimed to re-establish integrity and homeostasis. Tissue repair involves pro- and anti-inflammatory processes, new tissue formation and remodelling. Depending on the local microenvironment, tissue repair results either in scar tissue formation or in regeneration. The latter aims to recapitulate the original tissue structure and architecture with the proper functionality. Although some organisms (such as planarians) have a high regenerative capacity throughout the body, in humans this property is more restricted to a few organs and tissues. Regeneration in the adult is possible in particular through the existence of tissue-resident pools of stem/progenitor cells. In response to tissue damage, these cells are activated, they proliferate and migrate, and differentiate into mature cells. Angiogenesis and neovascularization play a crucial role in tissue repair. Besides providing with oxygen and nutrients, angiogenesis generates a vascular niche (VN) consisting of different blood-derived elements and endothelial cells surrounded by basement membrane as well as perivascular cells. The newly generated VN communicates with the local stem/progenitor cells and contributes to tissue repair. For example, platelets, macrophages, neutrophils, perivascular cells and other VN components actively participate in the repair of skin, bone, muscle, tendon, brain, spinal cord, etc. Despite these observations, the exact role of the VN in tissue repair and the underlying mechanisms are still unclear and are awaiting further evidence that, indeed, will be required for the development of regenerative therapies for the treatment of traumatic injuries as well as degenerative diseases.

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