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The role of viable but non-infectious developmental forms in chlamydial biology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193219 Year: Pages: 119 DOI: 10.3389/978-2-88919-321-9 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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The chlamydiae are Gram-negative, obligate intracellular bacteria with a complex developmental cycle comprising a metabolically less-active, infectious stage, the elementary body (EB), and a metabolically more active stage, the reticulate body (RB). They are responsible for many acute and chronic diseases in humans and animals. In order to play a causative role in chronic diseases, chlamydiae would need to persist and to re-activate within infected cells/tissues for extended periods of time. Persistence in vitro is defined as viable but non-cultivable chlamydiae involving morphologically enlarged, aberrant, and nondividing RBs, termed aberrant bodies (AB). In vitro, alterations of the normal developmental cycle of chlamydiae can be induced by the addition of Interferon-? (IFN-?), tumor necrosis factor-a (TNF-a) and penicillin G exposure as well as amino acid or iron deprivation, monocyte infection and co-infection with viruses. In vivo, key questions include whether or not ABs occur in infected patients and animals and whether such ABs can contribute to prolonged, chronic inflammation, fibrosis, and scarring through continuing stimulation of the host immune system known from diseases such as trachoma, pelvic inflammatory disease, reactive arthritis and atherosclerosis. To date, the direct causal role in the pathogenesis of chlamydial infection and persistence in vivo has been questioned since there was no tractable animal model of chlamydial persistence so far. A very recent study was able to establish an experimental animal model of in vivo persistence, when C. muridarum vaginally-infected mice were gavaged with amoxicillin. Amoxicillin treatment induced C. muridarum to enter the persistent state in vivo. Recent in vivo data from patients indicate that viable but non-infectious developmental stages are present in the genital tract of chronically-infected women and that the gastrointestinal tract might be a reservoir for persistent chlamydial infections at other sites.

Industrial and Host Associated Stress Responses in Food Microbes. Implications for Food Technology and Food Safety

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452934 Year: Pages: 295 DOI: 10.3389/978-2-88945-293-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2018-02-27 16:16:44
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Throughout the food processing chain and after ingestion by the host, food associated bacteria have to cope with a range of stress factors such as thermal and/or non-thermal inactivation treatments, refrigeration temperatures, freeze-drying, high osmolarity, acid pH in the stomach or presence of bile salts in the intestine, that threaten bacterial survival. The accompanying plethora of microbial response and adaptation phenomena elicited by these stresses has important implications for food technology and safety. Indeed, while resistance development of pathogenic and spoilage microorganisms may impose health risks for the consumer and impart great economic losses to food industries, reduced survival of probiotic bacteria may strongly compromise their claimed health benefit attributes. As a result, substantial research efforts have been devoted in the last decades to unravel the mechanisms underlying stress response and resistance development in food associated microorganisms in order to better predict and improve (i) the inactivation of foodborne pathogens and spoilage microorganisms on the one hand and (ii) the robustness and performance of beneficial microorganisms on the other. Moreover, the recent implementation of system-wide omics and (single-)cell biology approaches is greatly boosting our insights into the modes of action underlying microbial inactivation and survival. This Research Topic aims to provide an avenue for dissemination of recent advances within the field of microbial stress response and adaptation, with a particular focus not only on food spoilage and pathogenic microorganisms but also on beneficial microbes in foods.

Neuronal Self-Defense: Compensatory Mechanisms in Neurodegenerative Disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197590 Year: Pages: 190 DOI: 10.3389/978-2-88919-759-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Neurodegenerative disorders are characterized by the progressive loss of specific populations of neurons with consequent deterioration of brain's function and dramatic impact on human behavior. At present, there are no effective cures for neurodegenerative diseases. Because unambiguous diagnosis is possible only after manifestation of symptoms, when a large proportion of neurons has been already lost, therapies are necessarily confined to alleviation of symptoms. Development of cures halting the disease course is hampered by our rudimentary understanding of the etiopathology. Most neurodegenerative disorders are sporadic and age-related and - even for those of known genetic origin - the mechanisms influencing disease onset and progression have not been fully characterized. The different diseases, however, share important similarities in the mechanisms responsible for neuronal loss, which is caused by a combination of endogenous and exogenous challenges. Trophic deprivation, oxidative stress, accumulation of abnormal protein aggregates, and bioenergetics defects have been described in most, if not all, neurodegenerative disease. To counterbalance these noxious stimuli cells deploy, at least during the initial pathogenic states, intrinsic neuroprotective responses. These are general compensatory mechanisms, common to several neurodegenerative conditions, which reprogram cellular physiology to overcome stress. Adaptation includes strategies to optimize energetic resources, for instance reduction of rRNA synthesis to repress translation, suppression of transcription, and bioenergetics and metabolic redesign. Additional mechanisms include potentiation of antioxidant capacity, induction of endoplasmic reticulum (ER) stress, and activation of protein quality control systems and autophagy. Ineffective execution of these compensatory strategies severely threatens cellular homeostasis and favors onset of pathology. Therefore, a better understanding of these "buffering" mechanisms and of their interconnections may help to devise more effective therapeutic tools to prolong neuronal survival and activity, independently of the original genetic mutations and stress insults. This Research Topic focuses on the initial compensatory responses protecting against failure of those mechanisms that sustain neuronal survival and activity. The collection intends to summarize the state-of-the-art in this field and to propose novel research contributes, with the ultimate goal of inspiring innovative studies aimed to contrast progression of neurodegenerative diseases.

Tox21 Challenge to Build Predictive Models of Nuclear Receptor and Stress Response Pathways as Mediated by Exposure to Environmental Toxicants and Drugs

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451975 Year: Pages: 102 DOI: 10.3389/978-2-88945-197-5 Language: English
Publisher: Frontiers Media SA
Subject: Environmental Sciences --- Science (General)
Added to DOAB on : 2017-10-13 14:57:01
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Tens of thousands of chemicals are released into the environment every day. High-throughput screening (HTS) has offered a more efficient and cost-effective alternative to traditional toxicity tests that can profile these chemicals for potential adverse effects with the aim to prioritize a manageable number for more in depth testing and to provide clues to mechanism of toxicity. The Tox21 program, a collaboration between the National Institute of Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP), the U.S. Environmental Protection Agency’s (EPA) National Center for Computational Toxicology (NCCT), the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS), and the U.S. Food and Drug Administration (FDA), has generated quantitative high-throughput screening (qHTS) data on a library of 10K compounds, including environmental chemicals and drugs, against a panel of nuclear receptor and stress response pathway assays during its production phase (phase II). The Tox21 Challenge, a worldwide modeling competition, was launched that asks a “crowd” of researchers to use these data to elucidate the extent to which the interference of biochemical and cellular pathways by compounds can be inferred from chemical structure data. In the Challenge participants were asked to model twelve assays related to nuclear receptor and stress response pathways using the data generated against the Tox21 10K compound library as the training set. The computational models built within this Challenge are expected to improve the community’s ability to prioritize novel chemicals with respect to potential concern to human health. This research topic presents the resulting computational models with good predictive performance from this Challenge.

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