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Towards a molecular classification of colorectal cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195671 Year: Pages: 62 DOI: 10.3389/978-2-88919-567-1 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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In 2007, Jeremy Jass proposed a molecular classification of colorectal cancer including KRAS, BRAF, Mismatch Repair, CIMP and MGMT Status. Since then, many prognostic and predictive studies have been published on this topic, mainly focusing on one single molecular marker. The aim of the e-book is to summarize the knowledge in 2014 from a multidisciplinary point of view that can potentially be used as a manual by CRC researchers in every field.

Mesothelioma Heterogeneity: Potential Mechanisms

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ISBN: 9783038974734 / 9783038974741 Year: Pages: 204 DOI: 10.3390/books978-3-03897-474-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology --- Oncology
Added to DOAB on : 2019-01-11 11:18:51
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Mesothelioma is a rare aggressive cancer that develops from the mesothelium. Recent molecular analyses have defined four different types of mesothelioma based on gene expression and two major molecularly-defined groups based on prognosis. In this volume, potential mechanisms causing this heterogeneity are explored. The different chapters include heterogeneity learned from experimental animal models in NF2/Hippo pathway signaling, stem cell signaling pathways, the tumor microenvironment, and micro RNA secretome. Novel aspects deserving attention such as the implication of long, non-coding RNA in disease heterogeneity are described. The volume also includes the description of tools useful to address some specific questions such as an assessment of the copy number variations of two tumor suppressors frequently mutated in mesothelioma or an investigation of Macrophage Inhibition Factor signaling in mesothelioma.

Synthetic Biology: Engineering complexity and refactoring cell capabilities

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196852 Year: Pages: 123 DOI: 10.3389/978-2-88919-685-2 Language: English
Publisher: Frontiers Media SA
Subject: Biotechnology --- General and Civil Engineering
Added to DOAB on : 2015-10-30 16:33:44
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One of the key features of biological systems is complexity, where the behavior of high level structures is more than the sum of the direct interactions between single components. Synthetic Biologists aim to use rational design to build new systems that do not already exist in nature and that exhibit useful biological functions with different levels of complexity. One such case is metabolic engineering, where, with the advent of genetic and protein engineering, by supplying cells with chemically synthesized non-natural amino acids and sugars as new building blocks, it is now becoming feasible to introduce novel physical and chemical functions and properties into biological entities. The rules of how complex behaviors arise, however, are not yet well understood. For instance, instead of considering cells as inert chassis in which synthetic devices could be easily operated to impart new functions, the presence of these systems may impact cell physiology with reported effects on transcription, translation, metabolic fitness and optimal resource allocation. The result of these changes in the chassis may be failure of the synthetic device, unexpected or reduced device behavior, or perhaps a more permissive environment in which the synthetic device is allowed to function. While new efforts have already been made to increase standardization and characterization of biological components in order to have well known parts as building blocks for the construction of more complex devices, also new strategies are emerging to better understand the biological dynamics underlying the phenomena we observe. For example, it has been shown that the features of single biological components [i.e. promoter strength, ribosome binding affinity, etc] change depending on the context where the sequences are allocated. Thus, new technical approaches have been adopted to preserve single components activity, as genomic insulation or the utilization of prediction algorithms able to take biological context into account. There have been noteworthy advances for synthetic biology in clinical technologies, biofuel production, and pharmaceuticals production; also, metabolic engineering combined with microbial selection/adaptation and fermentation processes allowed to make remarkable progress towards bio-products formation such as bioethanol, succinate, malate and, more interestingly, heterologous products or even non-natural metabolites. However, despite the many progresses, it is still clear that ad hoc trial and error predominates over purely bottom-up, rational design approaches in the synthetic biology community. In this scenario, modelling approaches are often used as a descriptive tool rather than for the prediction of complex behaviors. The initial confidence on a pure reductionist approach to the biological world has left space to a new and deeper investigation of the complexity of biological processes to gain new insights and broaden the categories of synthetic biology. In this Research Topic we host contributions that explore and address two areas of Synthetic Biology at the intersection between rational design and natural complexity: (1) the impact of synthetic devices on the host cell, or "chassis" and (2) the impact of context on the synthetic devices. Particular attention will be given to the application of these principles to the rewiring of cell metabolism in a bottom-up fashion to produce non-natural metabolites or chemicals that should eventually serve as a substitute for petrol-derived chemicals, and, on a long-term view, to provide economical, ecological and ethical solutions to today’s energetic and societal challenges.

PI3K signalling

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194193 Year: Pages: 139 DOI: 10.3389/978-2-88919-419-3 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-12-10 11:59:06
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The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.

30 years old: O-GlcNAc Reaches Age of Reason - Regulation of Cell Signaling and Metabolism by O-GlcNAcylation

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195916 Year: Pages: 113 DOI: 10.3389/978-2-88919-591-6 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2016-03-10 08:14:32
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Hundreds post-translational modifications (PTM) were characterized among which a large variety of glycosylations including O-GlcNAcylation. Since its discovery, O-GlcNAcylation has emerged as an unavoidable PTM widespread in the living beings including animal and plant cells, protists, bacteria and viruses. In opposition to N- and O-glycosylations, O-GlcNAcylation only consists in the transfer of a single N-acetylglucosamine moiety through a beta-linkage onto serine and threonine residues of proteins confined within the cytosol, the nucleus and the mitochondria. The O-GlcNAc group is provided by UDP-GlcNAc, the end-product of the hexosamine biosynthetic pathway located at the crossroad of cell metabolisms making O-GlcNAcylation a PTM which level tightly reflects nutritional status; therefore regulation of cell homeostasis should be intimately correlated to lifestyle and environment. Like phosphorylation, with which it can compete, O-GlcNAcylation is reversible. This versatility is managed by OGT (O-GlcNAc transferase) that transfers the GlcNAc group and OGA (O-GlcNAcase) that removes it. Also, like its unsweetened counterpart, O-GlcNAcylation controls fundamental processes, e.g. protein fate, chromatin topology, DNA demethylation and, as recently revealed, circadian clock. Deregulation of O-GlcNAc dynamism may be involved in the emergence of cancers, neuronal and metabolic disorders such as Alzheimer's or diabetes respectively. This Research Topic in Frontiers in Endocrinology is the opportunity to celebrate the thirtieth anniversary of the discovery of "O-GlcNAc" by Gerald W. Hart.

The metabolic challenges of immune cells in health and disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196227 Year: Pages: 80 DOI: 10.3389/978-2-88919-622-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-08-16 10:34:25
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Obesity and its co-morbidities, including atherosclerosis, insulin resistance and diabetes, are a world-wide epidemic. Inflammatory immune responses in metabolic tissues have emerged as a universal feature of these metabolic disorders. While initial work highlighted the contribution of macrophages to tissue inflammation and insulin resistance, recent studies demonstrate that cells of the adaptive immune compartment, including T and B lymphocytes and dendritic cells also participate in obesity-induced pathogenesis of these conditions. However, the molecular and cellular pathways by which the innate and adaptive branches of immunity control tissue and systemic metabolism remain poorly understood. To engage in growth and activation, cells need to increase their biomass and replicate their genome. This process presents a substantial bioenergetic challenge: growing and activated cells must increase ATP production and acquire or synthesize raw materials, including lipids, proteins and nucleic acids. To do so, they actively reprogram their intracellular metabolism from catabolic mitochondrial oxidative phosphorylation to glycolysis and other anabolic pathways. This metabolic reprogramming is under the control of specific signal transduction pathways whose underlying molecular mechanisms and relevance to physiology and disease are subject of considerable current interest and under intense study. Recent reports have elucidated the physiological role of metabolic reprogramming in macrophage and T cell activation and differentiation, B- and dendritic cell biology, as well as in the crosstalk of immune cells with endothelial and stem cells. It is also becoming increasingly evident that alterations of metabolic pathways play a major role in the pathogenesis of chronic inflammatory disorders. Due to the scientific distance between immunologists and experts in metabolism (e.g., clinicians and biochemists), however, there has been limited cross-talk between these communities. This collection of articles aims at promoting such cross-talk and accelerating discoveries in the emerging field of immunometabolism.

State-of-the-Art Research on C1q and the Classical Complement Pathway

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450589 Year: Pages: 100 DOI: 10.3389/978-2-88945-058-9 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-02-27 16:16:44
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C1q is the target recognition protein of the classical complement pathway and a major connecting link between innate and acquired immunity. As a charge pattern recognition molecule of innate immunity, C1q can engage a broad range of ligands derived from self, non-self and altered self via its heterotrimeric globular (gC1q) domain and thus trigger the classical complement pathway. The trimeric gC1q signature domain has been identified in a variety of non-complement proteins that can be grouped together as a C1q family. C1q circulates in serum as part of the C1 complex, in association with a catalytic tetrameric assembly of two homologous yet distinct serine proteases, C1r and C1s. Binding of C1q to appropriate targets leads to sequential activation of C1r and C1s, the latter being able to cleave complement components C4 and C2 thereby triggering the complement cascade. Activation of the classical pathway plays an important role in innate immune protection against pathogens and damaged elements from self. However, its involvement has been shown in various pathologies including ischemia-reperfusion injury and hereditary angioedema. Unexpected roles for the classical pathway have also been discovered recently, linked to both physiological and pathological aspects of development, including brain and cancer cells. These new perspectives should arouse renewed interest in a search for specific inhibitors of the classical pathway. In addition, C1q has recently been shown to have a number of functions that are independent of the activation of the classical pathway. This research topic is aimed at providing a state-of-the-art overview of the classical pathway, including, but not restricted to emerging functions of C1q and of the C1 complex, as well as pathological consequences of C1 activation or of the presence of anti-C1q autoantibodies . Contributions are included in the areas such as structural basis of C1q ligand recognition, C1q family proteins, inhibitors of the classical pathway identified in pathogens and improved derived inhibitors, structural determinants of the substrate specificities of C1r and C1s, elucidation of the architecture of C1, structural and functional homology of C1 with the initiating complexes of the lectin complement pathway, and novel involvement of C1q in processes such as ageing, cancer, synaptic pruning, and pregnancy.

Limbic-Brainstem Roles in Perception, Cognition, Emotion and Behavior

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455409 Year: Pages: 221 DOI: 10.3389/978-2-88945-540-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology --- Medicine (General) --- Psychiatry --- Psychology
Added to DOAB on : 2019-01-23 14:53:42
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The brainstem-limbic regions, including the superior colliculus, pulvinar and amygdala, receive direct perceptual information as a rapid, coarse, subcortical sensory system bypassing early sensory cortical systems, and play a central role in innate behaviors, including motivated and avoidance behaviors. Recent human neuropsychological studies including those on cortical blindness suggest that these subcortical sensory pathways are functional in the intact human brain and interact with more evolutionary recent cortical systems. This eBook presents up-to-date advancements in this area and to highlight the functions of the brainstem-limbic regions in a variety of perceptual, cognitive, affective and behavioral domains. We hope that this current Research Topic provides a comprehensive review to understand roles of the subcortical brainstem-limbic regions in some forms of sensory-motor coupling, cognitive and affective functions.

Biogenesis of the oxidative phosphorylation machinery in plants. From gene expression to complex assembly

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192786 Year: Pages: 98 DOI: 10.3389/978-2-88919-278-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology --- Botany
Added to DOAB on : 2015-12-03 13:02:24
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Mitochondrial biogenesis is an extremely complex process. A hint of this complexity is clearly indicated by the many steps and factors required to assemble the respiratory complexes involved in oxidative phosphorylation. These steps include the expression of genes present in both the nucleus and the organelle, intricate post-transcriptional RNA processing events, the coordinated synthesis, transport and assembly of the different subunits, the synthesis and assembly of co-factors and, finally, the formation of supercomplexes or respirasomes. It can be envisaged, and current knowledge supports this view, that plants have evolved specific mechanisms for the biogenesis of respiratory complexes. For example, expression of the mitochondrial genome in plants has special features, not present in other groups of eukaryotes. Moreover, plant mitochondrial biogenesis and function should be considered in the context of the presence of the chloroplast, a second organelle involved in energetic and redox metabolism. It implies the necessity to discriminate between proteins destined for each organelle and requires the establishment of functional interconnections between photosynthesis and respiration. In recent years, our knowledge of the mechanisms involved in these different processes in plants has considerably increased. As a result, the many events and factors necessary for the correct expression of proteins encoded in the mitochondrial genome, the cis acting elements and factors responsible for the expression of nuclear genes encoding respiratory chain components, the signals and mechanisms involved in the import of proteins synthesized in the cytosol and the many factors required for the synthesis and assembly of the different redox co-factors (heme groups, iron-sulfur clusters, copper centers) are beginning to be recognized at the molecular level. However, detailed knowledge of these processes is still not complete and, especially, little is known about how these processes are interconnected. Questions such as how the proteins, once synthesized in the mitochondrial matrix, are inserted into the membrane and assembled with other components, including those imported from the cytosol, how the expression of both genomes is coordinated and responds to changes in mitochondrial function, cellular requirements or environmental cues, or which factors and conditions influence the assembly of complexes and supercomplexes are still open and will receive much attention in the near future. This Research Topic is aimed at establishing a collection of articles that focus on the different processes involved in the biogenesis of respiratory complexes in plants as a means to highlight recent advances. In this way, it intends to help to construct a picture of the whole process and, not less important, to expose the existing gaps that need to be addressed to fully understand how plant cells build and modulate the complex structures involved in respiration.

Integrating Computational and Neural Findings in Visual Object Perception

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198733 Year: Pages: 137 DOI: 10.3389/978-2-88919-873-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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The articles in this Research Topic provide a state-of-the-art overview of the current progress in integrating computational and empirical research on visual object recognition. Developments in this exciting multidisciplinary field have recently gained momentum: High performance computing enabled breakthroughs in computer vision and computational neuroscience. In parallel, innovative machine learning applications have recently become available for datamining the large-scale, high resolution brain data acquired with (ultra-high field) fMRI and dense multi-unit recordings. Finally, new techniques to integrate such rich simulated and empirical datasets for direct model testing could aid the development of a comprehensive brain model. We hope that this Research Topic contributes to these encouraging advances and inspires future research avenues in computational and empirical neuroscience.

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