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Diacylglycerol Kinase Signalling

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453351 Year: Pages: 96 DOI: 10.3389/978-2-88945-335-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2018-02-27 16:16:45
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Abstract

Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DG), catalyzing its conversion into phosphatidic acid (PA). This reaction attenuates membrane DG levels, limiting the localization/activation of signaling proteins that bind this lipid. Initially recognized as modulators of classical and novel PKC family members, the function of the DGK has further expanded with the identification of novel DG effectors including Ras Guanyl nucleotide-releasing proteins (RasGRP) and chimaerin Rac GTPases. The product of the DGK reaction, PA, is also a signaling lipid that mediates activation of multiple proteins including the mammalian target of rapamycin (mTOR). The DGK pathway thus modulates two lipids with important signaling properties that are also key intermediates in lipid metabolism and membrane trafficking. The DGK family in eukaryotes comprises 10 different members grouped into five different subfamilies characterized by the presence of particular regulatory motifs. These regions allow the different DGK isoforms to establish specific complexes and/or to be recruited to specific subcellular compartments. The subtle regulation of DG and PA catalyzed byspecific DGKs is sensed by a restricted set of molecules, providing the means for spatio-temporal regulation of signals in highly specialized cell systems.In the recent years, multiple studies have unveiled the functions of specific isoforms, their mechanisms of regulation and their participation in different pathways leading to and from DG and PA. Animal models have greatly helped to understand the specialized contribution of DGK mediated signals, particularly in the immune and central nervous systems. Mice deficient for individual DGK isoforms show defects in T and B cell functions, dendritic spine maintenance, osteoclast and mechanical-induced skeletal muscle formation. Studies in flies and worms link DGK mediated DAG metabolism with mTOR- mediated regulation of lifespan and stress responses. In plants DGK mediated PA formation contributes to plant responses to environmental signals.Aberrant DGK function has been recently associated with pathological states, an expected consequence of the essential role of these enzymes in the regulation of multiple tissue and systemic functions. DGK mutations/deletions have been related to human diseases including diabetes, atypical hemolytic-uremic syndrome, Parkinson disease and bipolar disorders. On the contrary DGK upregulation emerges as a non-oncogenic addition of certain tumors and represents one of the main mechanism by which cancer evades the immune attack. As a result, the DGK field emerges an exciting new area of research with important therapeutic potential.

Drinking Water Quality and Human Health

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ISBN: 9783038977261 Year: Pages: 374 DOI: 10.3390/books978-3-03897-727-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Sociology --- Social Sciences
Added to DOAB on : 2019-04-05 10:34:31
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Abstract

The quality of drinking water is paramount for public health. Despite important improvements in the last decades, access to safe drinking water is not universal. The World Health Organization estimates that almost 10% of the population in the world do not have access to improved drinking water sources. Among other diseases, waterborne infections cause diarrhea, which kills nearly one million people every year, mostly children under 5 years of age. On the other hand, chemical pollution is a concern in high-income countries and an increasing problem in low- and middle-income countries. Exposure to chemicals in drinking water may lead to a range of chronic non-communicable diseases (e.g., cancer, cardiovascular disease), adverse reproductive outcomes, and effects on children’s health (e.g., neurodevelopment), among other health effects. Although drinking water quality is regulated and monitored in many countries, increasing knowledge leads to the need for reviewing standards and guidelines on a nearly permanent basis, both for regulated and newly identified contaminants. Drinking water standards are mostly based on animal toxicity data, and more robust epidemiologic studies with accurate exposure assessment are needed. The current risk assessment paradigm dealing mostly with one-by-one chemicals dismisses the potential synergisms or interactions from exposures to mixtures of contaminants, particularly at the low-exposure range. Thus, evidence is needed on exposure and health effects of mixtures of contaminants in drinking water. Finally, water stress and water quality problems are expected to increase in the coming years due to climate change and increasing water demand by population growth, and new evidence is needed to design appropriate adaptation policies.This Special Issue of International Journal of Environmental Research and Public Health (IJERPH) focuses on the current state of knowledge on the links between drinking water quality and human health.

Keywords

Vibrio pathogens --- rural water resources --- public health --- sub-Saharan Africa --- diarrhoeal disease --- HWTS implementation --- water and sanitation --- drinking water guidance --- infant exposure --- chemical risk assessment --- duration extrapolation --- acute gastroenteritis --- risk --- tap water --- time series study --- turbidity --- urban area --- water operation data --- THMs --- cancer --- effect measure modification --- drinking water --- drinking water --- exposure assessment --- sodium --- potassium --- magnesium --- calcium --- spatial variations --- Denmark --- water safety plans --- drinking water quality --- risk management --- impact assessment --- Asia-Pacific region --- diarrhea --- fever --- cough --- Nigeria --- infant health --- drinking water --- inorganic manganese --- health-based guideline --- infants --- pharmaceuticals --- human health --- environment --- drug labels --- screening method --- LTD --- uncertainty factors --- risk assessment --- risk context --- biomonitoring --- dental health --- drinking water --- fluoride --- pharmacokinetic modeling --- waterborne disease outbreak --- simulation study --- health insurance data --- space–time detection --- drinking water --- nitrate --- cancer --- adverse reproductive outcomes --- methemoglobinemia --- thyroid disease --- endogenous nitrosation --- N-nitroso compounds --- E. coli --- monitoring --- drinking water --- water safety plan --- sanitary inspection --- gravity-fed piped water scheme --- risk management --- chlorination by-product --- France --- environmental exposure --- organic matter --- tap water --- trihalomethanes --- private wells --- groundwater --- drinking water --- animal feeding operation --- fecal coliforms --- enterococci --- E. coli --- Maryland --- nitrite --- disinfection by-product --- drinking water distribution systems --- seasonality --- atrazine --- community water system --- low birth weight --- preterm birth --- small for gestational age --- water contamination --- endocrine disruptor --- drinking water --- radioactivity --- annual effective dose --- carcinogenic --- chronic kidney disease --- end-stage renal disease --- water contaminants --- zinc --- ammonia --- chemical oxygen demand --- dissolved oxygen --- arsenic

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