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Schizophrenia: A Consequence of Gene-Environment Interactions?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195312 Year: Pages: 126 DOI: 10.3389/978-2-88919-531-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors (e.g. stress and cannabis use). In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. Eventually, it might help advance studies of the molecular pathways involved in this mental disorder and propose more specific molecular medicine. However, the complexity of this multi-factorial line of research has also caused difficulties in data interpretation and comparison. Our research topic is intended to cover past and current directions in research dedicated to the understanding and measurement of gene-environment interactions (GxE) in schizophrenia, the neurobiological and behavioural consequences of such interactions as well as the challenges and limitations one encounters when working on complex aetiological systems.

Antimicrobial Peptides

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ISBN: 9783038420729 9783038420736 Year: Pages: 336 DOI: 10.3390/books978-3-03842-073-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-10-22 10:29:38
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Antimicrobial peptides (AMPs) are gene-encoded, ancient (and important) mediators of innate host defense that exert direct or indirect antimicrobial action as well as possessing other important biologic activities (e.g., neutralization of endotoxin and anti-biofilm action) that help to protect vertebrates, invertebrates and plants from invading pathogens. While the emergence of multi-antibiotic resistant pathogens (and the desperate need to develop new anti-infectives) has been a recent force driving the field, interest in AMPs has an earlier origin in studies of how phagocytes kill bacteria by oxygen-independent processes. AMPs responsible for such killing of microbes by rabbit and human neutrophils were later purified by Ganz, Selsted and Lehrer, which they termed defensins; at the time of this writing, literally thousands of defensin-based publications can be found in the scientific literature! The initial reports on defensins and the earlier report by Boman’s group on the purification and action of an insect AMP represented a historical and defining point for the AMP field as they, in hindsight, demanded the recognition of AMP research as a unique discipline that has important linkages to other important fields of medicine, especially those of microbiology, infectious diseases and immunology. On a personal note, I remember conferences on phagocytes and host defense in the early 1980s where the topic of AMPs was relegated to one short session in a five day period! Now, we have hundreds of international “AMPologists” with expertise in chemistry, biochemistry, molecular and structural biology, cell biology, microbiology, pharmacology, or medicine who have built their research careers around AMPs and can now attend international conferences dedicated to advances in AMP research.

Thinking Beyond Sectors for Sustainable Development

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ISBN: 9781909188426 9781909188433 9781909188440 9781909188457 Year: Pages: 110 DOI: 10.5334/bao Language: English
Publisher: Ubiquity Press Grant: University College London
Subject: Environmental Sciences --- Economics --- Political Science
Added to DOAB on : 2015-07-05 11:01:17
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"This book brings together a series of working papers, produced by interdisciplinary groups of academics within the project, on progress made under the Millennium Development Goals and introduces current debates surrounding the Sustainable Development Goals and the post-2015 agenda. Originating from an interdisciplinary, multi-institution research collaboration, Thinking Beyond Sectors for Sustainable Development, funded by UCL Grand Challenges. The project brought together over thirty academics from UCL, SOAS, London School of Hygiene and Tropical Medicine, Birkbeck, Institute of Education, and the Royal Veterinary College, and was coordinated by the London International Development Centre (LIDC). The book explores potential interactions between sustainable development goals in the post-2015 development agenda.&#xD;Introduced and edited by Prof Jeff Waage (LIDC) and Christopher Yap (LIDC), chapters are dedicated to the topics of Biodiversity and Ecosystems, Human Health, Urban Poverty, Climate and Climate Change, Population Growth, Food and Agriculture, Information, Education and Knowledge, and Governance. Each chapter reflects on the three principle questions of 1) What is the historical process by which goal setting in this sector has developed?, 2) What progress has been achieved with this sector through MDGs and other processes? and 3) What is the current debate about future goal setting?"

Mechanisms of antibiotic resistance

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195268 Year: Pages: 224 DOI: 10.3389/978-2-88919-526-8 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Antibiotics represent one of the most successful forms of therapy in medicine. But the efficiency of antibiotics is compromised by the growing number of antibiotic-resistant pathogens. Antibiotic resistance, which is implicated in elevated morbidity and mortality rates as well as in the increased treatment costs, is considered to be one of the major global public health threats (www.who.int/drugresistance/en/) and the magnitude of the problem recently prompted a number of international and national bodies to take actions to protect the public (http://ec.europa.eu/dgs/health_consumer/docs/road-map-amr_en.pdf: http://www.who.int/drugresistance/amr_global_action_plan/en/; http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf). Understanding the mechanisms by which bacteria successfully defend themselves against the antibiotic assault represent the main theme of this eBook published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy. The articles in the eBook update the reader on various aspects and mechanisms of antibiotic resistance. A better understanding of these mechanisms should facilitate the development of means to potentiate the efficacy and increase the lifespan of antibiotics while minimizing the emergence of antibiotic resistance among pathogens.

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.

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.

Towards translating research to clinical practice: Novel Strategies for Discovery and Validation of Biomarkers for Brain Injury

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193912 Year: Pages: 178 DOI: 10.3389/978-2-88919-391-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2015-12-03 13:02:24
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Traumatic brain injury (TBI) is a major cause of death and disability and one of the greatest unmet needs in medicine and public health. TBI not only has devastating effects on patients and their relatives but results in huge direct and indirect costs to society. Although guidelines for the management of patients have been developed and more than 200 clinical trials have been conducted, they have resulted in few improvements in clinical outcomes and no effective therapies approved for TBI. It is now apparent that the heterogeneity of clinical TBI is underlain by molecular phenotypes more complex and interactive than initially conceived and current approaches to the characterization, management and outcome prediction of TBI are antiquated, unidimensional and inadequate to capture the interindividual pathophysiological heterogeneity. Recent advances in proteomics and biomarker development provide unparalleled opportunities for unraveling substantial injury-specific and patient-specific variability and refining disease characterization. The identification of novel, sensitive, objective tools, referred to as biomarkers, can revolutionize pathophysiological insights, enable targeted therapies and personalized approaches to clinical management. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. Finally, suggestions are provided for the way forward, with an emphasis on need for a multidimensional approach that integrate a panel of pathobiologically diverse biomarkers with clinical variables and imaging-based assessments to improve diagnosis and classification of TBI and to develop best clinical practice guidelines.

Multi-omic Data Integration

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196487 Year: Pages: 135 DOI: 10.3389/978-2-88919-648-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology --- Genetics
Added to DOAB on : 2016-08-16 10:34:25
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Stable, predictive biomarkers and interpretable disease signatures are seen as a significant step towards personalized medicine. In this perspective, integration of multi-omic data coming from genomics, transcriptomics, glycomics, proteomics, metabolomics is a powerful strategy to reconstruct and analyse complex multi-dimensional interactions, enabling deeper mechanistic and medical insight. At the same time, there is a rising concern that much of such different omic data –although often publicly and freely available- lie in databases and repositories underutilised or not used at all. Issues coming from lack of standardisation and shared biological identities are also well-known. From these considerations, a novel, pressing request arises from the life sciences to design methodologies and approaches that allow for these data to be interpreted as a whole, i.e. as intertwined molecular signatures containing genes, proteins, mRNAs and miRNAs, able to capture inter-layers connections and complexity. Papers discuss data integration approaches and methods of several types and extents, their application in understanding the pathogenesis of specific diseases or in identifying candidate biomarkers to exploit the full benefit of multi-omic datasets and their intrinsic information content. Topics of interest include, but are not limited to: • Methods for the integration of layered data, including, but not limited to, genomics, transcriptomics, glycomics, proteomics, metabolomics;• Application of multi-omic data integration approaches for diagnostic biomarker discovery in any field of the life sciences;• Innovative approaches for the analysis and the visualization of multi-omic datasets;• Methods and applications for systematic measurements from single/undivided samples (comprising genomic, transcriptomic, proteomic, metabolomic measurements, among others);• Multi-scale approaches for integrated dynamic modelling and simulation;• Implementation of applications, computational resources and repositories devoted to data integration including, but not limited to, data warehousing, database federation, semantic integration, service-oriented and/or wiki integration;• Issues related to the definition and implementation of standards, shared identities and semantics, with particular focus on the integration problem. Research papers, reviews and short communications on all topics related to the above issues were welcomed.

Phenotypic screening in the 21st century

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194698 Year: Pages: 67 DOI: 10.3389/978-2-88919-469-8 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs that arose from genomics failed, questioning the validity of the targets and the suitability of target-based drug discovery as an optimal strategy for all disease states. For monogenic diseases, target-based approaches may be well-suited to the identification of novel therapies. Most diseases, however, are caused by a combination of several genetic and environmental factors and are likely to require simultaneous modulation of multiple molecular targets/pathways for successful treatment. For such diseases, reductionist approaches focusing on individual targets rather than biological networks are unlikely to succeed and new drug development strategies are required. In search of more successful approaches, the pharmaceutical industry is moving towards phenotypic screening beyond individual genes/targets. However, this requires rethinking of diseases and drug discovery approaches from a network and systems biology perspective. Since returning to the pre-genomics era of screening drug candidates in laborious animal models is not a feasible solution, the industry needs to evolve a new paradigm of phenotypic drug discovery within the context of systems biology. Such a paradigm must combine physiologically and disease relevant biological substrates with sufficient throughput, operational simplicity and statistical vigour. Biomarker strategies for translational medicine, as well as preclinical safety and selectivity assessments, would also need to be revised to adapt to the target agnostic style. This focused issue aims to discuss strategies, key concepts and technologies related to systems-based approaches in drug development. Design and implementation of innovative biological assays, featuring multiple target strategies, and rational drug design in the absence of target knowledge during the early drug discovery are illustrated with examples. Specific topics include: • The need for systems-based approaches in drug development • Phenotypic screening strategies • Compound libraries (natural product inspired compound collections) • Target deconvolution and identification • Target agnostic lead discovery and optimization • Multi-target approaches and decoding the phenotype (understanding biological interactions and multiscale systems modelling) • Translational aspects • Early evaluation of selectivity and safety in a target agnostic manner

Developments in Bovine Immunology - An Integrated View

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196326 Year: Pages: 112 DOI: 10.3389/978-2-88919-632-6 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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The world’s population is predicted to hit 9 Billion by 2050, and with it food demand is predicted to increase substantially. The World Bank estimates that cereal and meat production needs to increase by 50% and 85% respectively between 2000 and 2030 to meet demand, putting serious pressure on the global agricultural industry. Critical to meeting this demand for food are mechanisms to reduce the incidence of animal disease. With in excess of 1.3 billion cattle globally, the total cost of infectious diseases is difficult to estimate. However in North America alone, the cost is predicted to be $18 billion annually. Non-infectious diseases also account for another major impediment to the production capacity and welfare of animals as well as the economic sustainability of farming. However animal diseases have implications that spread far beyond the farm gate. Infectious agents can also contaminate the food chain, and potentially affect human health. Controlling diseases, through better preventative and treatment methods requires a detailed understanding of the immune response in livestock species. Multiple studies have identified associations between variation in immune genes and disease susceptibility, which potentially opens up new avenues to select animals with superior disease resistance. Detailed understanding of immunity in cattle is leading to the design of more effective vaccines. Furthermore, appreciation of the significant differences between rodent and human immune responses has also led to bovine models being developed for some human diseases. The publication of the bovine genome and the advent of next-generation sequencing technologies have facilitated a massive expansion in our knowledge of the immune response in cattle. As a result there has been an explosion of exciting research findings including in metagenomics and epigenetics. Recently, there has been a welcome move to integrate our emerging understanding of the immune response with detailed studies of other important physiological processes including nutrition and reproduction. The interactions between the reproductive system, nutrition and the immune system are of particular interest, since each places significant demands on the animal at various stages through the production cycle. The interplay between these morphologically diffuse systems involves widely distributed chemical signals in response to environmental input, and each system must interact for the normal functioning of the other. A comprehensive “systems” approach is improving our understanding of normal physiological interactions between these systems and furthermore, how dysregulation can lead to disease. The successful translation of bovine immunological research into improved treatments for animal disease requires tight interaction between diverse scientific and clinical disciplines including immunology, microbiology, endocrinology, physiology, nutrition, reproduction and clinical veterinary medicine. With so much recent progress in the field, we believe that it is valuable and well-timed to review the broad variety of the relevant studies that attempt to increase our understanding through comprehensive collaboration between these disciplines. We are looking forward to a wide and vivid discussion of developments in bovine immunology and related issues, and we expect that our readers profoundly benefit from new exciting insights and fruitful collaborations.

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