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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.

The truth in complexes: why unraveling ion channel multi-protein signaling nexuses is critical for understanding the function of the nervous system

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194452 Year: Pages: 160 DOI: 10.3389/978-2-88919-445-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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In the search for simple explanations of the natural world, its complicated textures are often filed down to a smoothened surface of our liking. The impetus for this Research Topic was borne out of a need to re-ignite interest in the complex – in this case in the context of ion channels in the nervous system. Ion channels are the large proteins that form regulated pores in the membranes of cells and, in the brain, are essential for the transfer, processing and storage of information. These pores full of twists and turns themselves are not just barren bridges into cells. More and more we are beginning to understand that ion channels are like bustling medieval bridges (packed with apartments and shops) rather than the more sleek modern variety – they are dynamic hubs connected with many structures facilitating associated activities. Our understanding of these networks continues to expand as our investigative tools advance. Together these articles highlight how the complexity of ion channel signaling nexuses is critical to the proper functioning of the nervous system.

Structural and computational glycobiology: immunity and infection

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196388 Year: Pages: 102 DOI: 10.3389/978-2-88919-638-8 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-10-30 16:33:44
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Interest in understanding the biological role of carbohydrates has increased significantly over the last 20 years. The use of structural techniques to understand carbohydrate-protein recognition is still a relatively young area, but one that is of emerging importance. The high flexibility of carbohydrates significantly complicates the determination of high quality structures of their complexes with proteins. Specialized techniques are often required to understand the complexity of carbohydrate recognition by proteins. In this Research Topic, we will focus on structural and computational approaches to understanding carbohydrate recognition by proteins involved in immunity and infection. Particular areas of focus include cancer immunotherapeutics, carbohydrate-lectin interactions, glycosylation and glycosyltransferases.

The Coming of Age of Insulin-Signalling in Insects

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193141 Year: Pages: 138 DOI: 10.3389/978-2-88919-314-1 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
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The new millennium has seen a major paradigm shift in insect endocrinology. Great advancements are being made which establish that nutrition and growth play a central role in diverse cellular and physiological phenomena during insect development and reproduction. Nutrition affects rates of growth and is mainly regulated by the function of the pathway of insulin/insulin-like growth factor signalling. This pathway is highly conserved across species and ultimately regulates rates of cell growth and proliferation in growing organs. Insulin and insulin-like peptides (ILPs) are some of the best studied hormones in the animal kingdom and all share a common structural motif and initiate a wide range of closely similar physiological processes in higher organisms. In insects, nutrition, via circulating sugar, promotes release of ILPs from brain neurosecretory cells into the haemolymph, which act on peripheral tissues and stimulate protein synthesis and cell growth. Therefore, insect ILPs are common mediators between nutrition and growth in insects and are functionally analogous to mammalian insulin. The 1980s and 1990s witnessed great progress in elucidation of the physiological and molecular mechanism of action of numerous insect hormones involved in regulation of growth, development, reproduction and metabolism. But the signals for the initiation or termination of controlled events remained largely unknown. ILPs were first identified from the silkmoth Bombyx mori and were named bombyxins, but related peptides were soon found in numerous species and their functions elucidated. The insulin signalling pathway is now recognized as a central factor in the timing of cell proliferation, growth, longevity, reproduction, and reproductive diapause, as well as social behaviour. Recent work has revealed that the insulin signalling pathway is closely integrated with that of various other hormones, including ecdysteroids, the juvenile hormones and neuropeptide(s) such a prothoracicotropic hormone. In addition, the pathway is also linked with both circadian (daily) and photoperiodic (seasonal) clocks potentially providing a basis for its timing function. This Research Topic aims to provide the only current collection of recent advances on insect ILPs. We encouraged submissions on all areas related to identification, characterization, regulation and physiological functions of insect ILPs. We welcomed both full and short reviews and original research articles.

Glycolysis at 75: Is it time to tweak the first elucidated metabolic pathway in history?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195862 Year: Pages: 126 DOI: 10.3389/978-2-88919-586-2 Language: English
Publisher: Frontiers Media SA
Subject: Nutrition and Food Sciences --- Medicine (General) --- Neurology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Glycolysis, the pathway of enzymatic reactions responsible for the breakdown of glucose into two trioses and further into pyruvate or lactate, was elucidated in 1940. For more than seven decades, it has been taught precisely the way its sequence was proposed by Embden, Meyerhof and Parnas. Accordingly, two outcomes of this pathway were proposed, an aerobic glycolysis, with pyruvate as its final product, and an anaerobic glycolysis, identical to the aerobic one, except for an additional reaction, where pyruvate is reduced to lactate. Several studies in the 1980s have shown that both muscle and brain tissues can oxidize and utilize lactate as an energy substrate, challenging this monocarboxylate’s reputation as a useless end-product of anaerobic glycolysis. These findings were met with great skepticism about the idea that lactate could be playing a role in bioenergetics. In the past quarter of a century monocarboxylate transporters (MCTs) were identified and localized in both cellular and mitochondrial membranes. A lactate receptor has been identified. Direct and indirect evidence now indicate that the enzyme lactate dehydrogenase (LDH) resides not only in the cytosol, as part of the glycolytic pathway machinery, but also in the mitochondrial outer membrane. The mitochondrial form of the enzyme oxidizes lactate to pyruvate and concomitantly produces the reducing agent NADH. These findings have shed light on a major drawback of the originally proposed aerobic version of the glycolytic pathway i.e., its inability to regenerate NAD+, as opposed to anaerobic glycolysis that features the cyclical ability of regenerating NAD+ upon pyruvate reduction to lactate by the cytosolic form of LDH. The malate-aspartate shuttle (MAS), a major redox shuttle in the brain, was proposed as an alternative pathway for NAD+ generation for aerobic glycolysis. Nonetheless, would MAS really be necessary for that function if glycolysis always proceeds to the end-products, lactate and NAD+? An additional dilemma the originally proposed aerobic glycolysis presents has to do with the glycolytic pathway of erythrocytes, which despite its highly aerobic environment, always produces lactate as its end-product. It is time to reexamine the original, dogmatic separation of glycolysis into two distinct pathways and put to test the hypothesis of a unified, singular pathway, the end-product of which is lactate, the real substrate of the mitochondrial TCA cycle.

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.

Promiscuous functions of the prion protein gene family

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196050 Year: Pages: 113 DOI: 10.3389/978-2-88919-605-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2016-08-16 10:34:25
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The cellular prion protein PrPC is a ubiquitous GPI-anchored protein. While PrPC has been the focus of intense research for its involvement in a group of neurodegenerative disorders known as transmissible spongiform encephalopathies (TSE), much less attention has been devoted to its physiological function. This notably relates to the lack of obvious abnormalities of mice, goat or cattle lacking PrPC. This apparently normal phenotype in these PrPC-deficient animals however contrasts with the very high degree of conservation of the prion protein gene (Prnp) in mammalian species (over 80%), and the presence of genes with similarities to Prnp in birds, reptiles, amphibians and fish. This high conservation together with its ubiquitous expression, - albeit at highest levels in the brain-, suggest that PrPC has major physiological functions. Dissecting PrPC function is further complicated by the occurrence, in mammals, of two potentially partially redundant homologues, Doppel, and Shadoo. The biological overlaps between members of the prion protein family are still under investigation and much debated. Similarly, although in vitro analyses have suggested various functions for PrPC, notably in cell death and survival processes, some have yielded conflicting results and/or discrepancies with in vivo studies. This Research Topic brings together the accumulated knowledge regarding the biological roles of the prion protein family, from the animal to the molecular scale.

Second hand smoke and COPD: lessons from animal studies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193165 Year: Pages: 91 DOI: 10.3389/978-2-88919-316-5 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Cigarette smoke exposure is the key initiator of chronic inflammation, alveolar destruction, and the loss of alveolar blood vessels that lead to the development of chronic obstructive pulmonary disease (COPD) which is comprised of emphysema and chronic bronchitis. Exposure to secondhand smoke (SHS) is the major risk factor for non-smokers to develop emphysema. While the first-hand smoke is directly inhaled by smokers, passive smoking occurs when non-smokers are involuntary exposed to environmental tobacco smoke also known as second hand smoke (SHS). SHS is a mixture of 2 forms of smoke that come from burning tobacco: side stream smoke (smoke that comes from the end of a lit cigarette, pipe, or cigar) and mainstream smoke (smoke that is exhaled by a smoker). These two types of smoke have basically the same composition, however in SHS many toxic components are more concentrated than in first-hand smoke, therefore more hazardous for people’s health. Several pathological events have been implicated in the development of SHS-induced COPD, but many aspects of this pathology remain poorly understood halting the development of new advanced treatments for this detrimental disease. In this respect we have welcomed leading investigators in the field to share their research findings and provide their thoughts regarding the mechanisms of the SHS exposure-induced immune responses and inflammatory mechanisms of lung destruction in SHS-induced COPD and related comorbidities.

Monitoring endogenous GPCRs: lessons for drug design

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196517 Year: Pages: 134 DOI: 10.3389/978-2-88919-651-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2016-08-16 10:34:25
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G protein-coupled receptors (GPCRs) are integral membrane proteins forming the fourth largest superfamily in the human genome. Many of these receptors play key physiological roles and several pathologies have been associated with receptor functional abnormalities. GPCRs therefore represent important goals for drug design in pharmaceutical companies since they constitute the target of about one third of the drugs currently on the market. However, endogenous GPCRs are most often difficult to study because of a lack of tools to target them specifically and single out their response to physiological or drug-elicited stimulations. Hence, studies mostly focused on recombinant receptors expressed in a variety of cellular models that do not always closely reflect the receptor natural environment and often deal with levels of expression exceeding by far physiological ranges. Recent technological developments combining for example genetically modified animals and advanced imaging approaches have improved our ability to visualize endogenous GPCRs. To date, trailing receptor activation, subsequent intracellular redistribution, changes in signaling cascade up to integrated response to a drug-elicited stimulation is at hand though the impact of a physiological challenge on receptor dynamics remains a major issue. Data however suggest that the receptor may embrace a different fate depending on the type of stimulation in particular if sustained or repeated. This suggests that current drugs may only partially mimic the genuine response of the receptor and may explain, at least in part, their secondary effects. Commonalities and specificities between physiological and drug-induced activation can thus represent valuable guidelines for the design of future drugs.

Immune System Modeling and Analysis

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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.

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