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The Origin of the Plasma Cell Heterogeneity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197347 Year: Pages: 80 DOI: 10.3389/978-2-88919-734-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Plasma cells (PCs) are terminally differentiated B-cells producing large amounts of immunoglobulins (Ig). In humans, most of circulating Ig are produced by bone marrow plasma cells. PCs differentiate from activated naïve or memory B-cells usually activated by specific antigens. It is still controversial whether the regulation of PCs numbers and the “active” in vivo Ig diversity depend or not on non-specific reactivation of B-cells during infections. Depending on the stimulus (T-independent/T-dependent antigen, cytokines, partner cells) and B-cell types (naïve or memory, circulating or germinal center, lymph nodes or spleen, B1 or B2...), both the phenotype and isotype of PCs differ suggesting that PC diversity is either linked to B-cell diversity or to the type of stimulus or to both. Knowledge of the mechanisms supporting PC diversity has important consequences for the management of i) plasma cell neoplasia such as Multiple Myeloma and Waldenström's Macroglobulinemia, ii) vaccine protection against pathogens and iii) auto-immune diseases.

Keywords

Plasma cell --- B-cell --- differentiation --- Cell Cycle --- IL21 --- Autophagy --- B1 --- Autoimmunity --- Myeloma

Mitogen Activated Protein Kinases

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453399 Year: Pages: 163 DOI: 10.3389/978-2-88945-339-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2018-02-27 16:16:45
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Mitogen-activated protein kinase (MAPK) pathways are evolutionarily conserved in all eukaryotes and allow cells to respond to changes in the physical and chemical properties of the environment and to produce an appropriate response by altering many cellular functions. MAPKs are among the most intensively studied signal transduction systems. MAPK research is a very dynamic field in which new perspectives are continuously opening to the scientific community. Importantly, many MAPK inhibitors have been developed during the last years and are currently being tested in preclinical and clinical assays for inflammatory diseases and cancer treatment. In this research topic, we have gathered 14 papers covering recent advances in different aspects of the MAPK research area that have provided valuable insight into the spatiotemporal dynamics, the regulation and functions of MAPK pathways, as well as their therapeutic potential. We hope that this Research Topic helps readers to have a better understanding of the progresses that have been made recently in the field of MAPK signalling. A deeper understanding of the these pathways will facilitate the development of innovative therapeutic approaches.

Keywords

MAPK --- p38 --- ERK --- JNK --- MSK --- kinase --- scaffold --- cancer --- inflammation --- cell differentiation

iPS Cells for Modelling and Treatment of Human Diseases

ISBN: 9783038421221 9783038421214 Year: Pages: 422 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2016-05-09 15:30:07
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The field of reprogramming somatic cells into induced pluripotent stem cells (iPSC) has moved very quickly, from bench to bedside in just eight years since its first discovery. The best example of this is the RIKEN clinical trial this year in Japan, which will use iPSC derived retinal pigmented epithelial (RPE) cells to treat macular degeneration (MD). This is the first human disease to be tested for regeneration and repair by iPSC-derived cells and others will follow in the near future. Currently, there is an intense worldwide research effort to bring stem cell technology to the clinic for application to treat human diseases and pathologies. Human tissue diseases (including those of the lung, heart, brain, spinal cord, and muscles) drive organ bioengineering to the forefront of technology concerning cell replacement therapy. Given the critical mass of research and translational work being performed, iPSCs may very well be the cell type of choice for regenerative medicine in the future. Also, basic science questions, such as efficient differentiation protocols to the correct cell type for regenerating human tissues, the immune response of iPSC replacement therapy and genetic stability of iPSC-derived cells, are currently being investigated for future clinical applications.

Assessing Prenatal and Neonatal Gonadal Steroid Exposure for Studies of Human Development: Methodological and Theoretical Challenges

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196074 Year: Pages: 80 DOI: 10.3389/978-2-88919-607-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2016-08-16 10:34:25
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There is extensive evidence from animal models that gonadal steroids, produced in fetal and neonatal life, act on the developing organism to produce sex differences far beyond the reproductive system. That early gonadal steroid exposure also plays an important role in human development is supported by studies of individuals with disorders of sex determination and differentiation. It is much less clear whether normal variation in gonadal steroid exposure predicts sexually dimorphic health outcomes or within-sex variation. This is largely due to challenges related to the assessment of gonadal steroid exposure in the developing fetus and neonate. Regarding the prenatal period, serial measurements of serum hormone levels in the fetus, for use in studies of later development, are not possible for ethical reasons. Researchers have measured hormones in maternal blood, umbilical cord blood, and amniotic fluid; used putative anthropometric indices such as the relative lengths of the 2nd and 4th digits (2D:4D); evaluated common variants in genes related to hormone production, transport, and metabolism; and examined development in opposite sex twins and the offspring of mothers with hyperandrogeny. Each of these approaches has particular strengths and notable weaknesses. Regarding the neonatal period, serial measurements in serum are often impractical for studies of typical development. Salivary hormone assays, frequently used in studies of older children and adults, have not been extensively investigated in neonates. The most appropriate timing for testing is also open to debate. Early work suggested that testosterone levels in males begin to rise after the first postnatal week, peak around the 3rd to 4th months of life, and then drop back to very low levels by 1 year. However a more recent study of 138 infants did not demonstrate this pattern. Testosterone was highest on the day of birth and gradually dropped over the first 6 months. Even less is known about patterns of early estrogen exposure, though highly sensitive bioassays indicated that sex differences are present in early childhood. In addition, the design and interpretation of studies may be impacted by widespread acceptance of conceptual frameworks that are not well-supported empirically. For example, many researchers presume that the free hormone hypothesis, which states that unbound hormone is more readily diffusible into tissues and thus a better measure of actual exposure, is true. However this hypothesis has been challenged on multiple grounds. A second example: it is generally accepted that masculinization of the human brain is primarily mediated by the androgen receptor (in contrast to rodents where the estrogen receptor plays a major role), in part because chromosomal males with complete androgen insensitivity generally espouse a female gender identity. However this is not always the case, and other sexually dimorphic outcomes have not been carefully assessed in CAIS. The aim of this research topic is to gather together experimental and review papers which address the diverse challenges in assessing prenatal and neonatal gonadal steroid exposure for studies of human development with the expectation that this will allow more critical appraisal of existing studies, identify critical research gaps, and improve the design of future studies.

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

Authors: ---
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.

Physiology and Pathophysiology of the Extracellular Calcium-Sensing Receptor

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455126 Year: Pages: 189 DOI: 10.3389/978-2-88945-512-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology
Added to DOAB on : 2019-01-23 14:53:42
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Calcium is vital for human physiology; it mediates multiple signaling cascades, critical for cell survival, differentiation, or death both as first and as second messenger. The role of calcium as first messenger is mediated by the G-protein coupled receptor, the extracellular calcium-sensing receptor (CaSR). The CaSR is a multifaceted molecule that senses changes in the concentration of a wide variety of environmental factors including di- and trivalent cations, amino acids, polyamines, and pH. In calcitropic tissues with obvious roles in calcium homeostasis such as parathyroid, kidney, and bone it regulates circulating calcium concentrations. The germline mutations of the CaSR cause parathyroid disorders demonstrating the importance of the CaSR for the maintenance of serum calcium homeostasis. The CaSR has an important role also in a range of non-calcitropic tissues, such as the intestine, lungs, central and peripheral nervous system, breast, skin and reproductive system, where it regulates molecular and cellular processes such as gene expression, proliferation, differentiation and apoptosis; as well as regulating hormone secretion and lactation.This Research Topic is an overview of the CaSR and its molecular signaling properties together with the various organ systems where it plays an important role. The articles highlight the current knowledge regarding many aspects of the calcitropic and non-calcitropic physiology and pathophysiology of the CaSR.

In Search of In Vivo MSC

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452354 Year: Pages: 102 DOI: 10.3389/978-2-88945-235-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2017-10-13 14:57:01
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The Biology and Treatment of Myeloid Leukaemias

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ISBN: 9783038427957 9783038427964 Year: Pages: VI, 190 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Oncology
Added to DOAB on : 2018-04-17 13:45:41
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There has been an observed decrease in the global mortality from cancer, mostly atributable to improved, particularly early, detection and prevention. For many carcinomas and leukaemias in adults, once the disease has reached a certain stage there are no therapies that are able to erradicate the cancer cells and cure patients. There has been progress in the treatment of acute myeloid leukaemia (AML) and remissions are achievable; however, the presence of chemoresistent blast cells leads to most patients relapsing, and relapse is difficult to treat and thus patients die due to their disease. Targeting these resistent cells and the leukaemia stem cells, which sustain the leukaemia, is crucial for an effective therapy for AML. Moreover, an increasing number of diverse mutations have been described in AML cells that disrupt the ability of these cells to undergo differentiation. The use of pro-differentiating agents to drive the blast cells to mature, and subsequently undergo apoptosis, provides another approach to therapy. Differentiation therapy, using all-trans retinoic acid (ATRA), an inducer of granulocyte differentiation, has been highly successful in the case of acute promyeloicytic leukaemia, a sub-type of AML, turning this disease into a curable malignancy.

Immune System Modeling and Analysis

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195015 Year: Pages: 401 DOI: 10.3389/978-2-88919-501-5 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-12-03 13:02:24
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The rapid development of new methods for immunological data collection - from multicolor flow cytometry, through single-cell imaging, to deep sequencing - presents us now, for the first time, with the ability to analyze and compare large amounts of immunological data in health, aging and disease. The exponential growth of these datasets, however, challenges the theoretical immunology community to develop methods for data organization and analysis. Furthermore, the need to test hypotheses regarding immune function, and generate predictions regarding the outcomes of medical interventions, necessitates the development of mathematical and computational models covering processes on multiple scales, from the genetic and molecular to the cellular and system scales. The last few decades have seen the development of methods for presentation and analysis of clonal repertoires (those of T and B lymphocytes) and phenotypic (surface-marker based) repertoires of all lymphocyte types, and for modeling the intricate network of molecular and cellular interactions within the immune systems. This e-Book, which has first appeared as a ‘Frontiers in Immunology’ research topic, provides a comprehensive, online, open access snapshot of the current state of the art on immune system modeling and analysis.

Dual Specificity Phosphatases: From Molecular Mechanisms to Biological Function

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ISBN: 9783039216888 9783039216895 Year: Pages: 240 DOI: 10.3390/books978-3-03921-689-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:16
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Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of protein tyrosine phosphatases with the ability to dephosphorylate Ser/Thr and Tyr residues from proteins, as well as from other non-proteinaceous substrates including signaling lipids. DUSPs include, among others, MAP kinase (MAPK) phosphatases (MKPs) and small-size atypical DUSPs. MKPs are enzymes specialized in regulating the activity and subcellular location of MAPKs, whereas the function of small-size atypical DUSPs seems to be more diverse. DUSPs have emerged as key players in the regulation of cell growth, differentiation, stress response, and apoptosis. DUSPs regulate essential physiological processes, including immunity, neurobiology and metabolic homeostasis, and have been implicated in tumorigenesis, pathological inflammation and metabolic disorders. Accordingly, alterations in the expression or function of MKPs and small-size atypical DUSPs have consequences essential to human disease, making these enzymes potential biological markers and therapeutic targets. This Special Issue covers recent advances in the molecular mechanisms and biological functions of MKPs and small-size atypical DUSPs, and their relevance in human disease.

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