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      Nicotinamide and Demographic and Disease transitions: Moderation is Best

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          Abstract

          Good health and rapid progress depend on an optimal dose of nicotinamide. Too little meat triggers the neurodegenerative condition pellagra and tolerance of symbionts such as tuberculosis (TB), risking dysbioses and impaired resistance to acute infections. Nicotinamide deficiency is an overlooked diagnosis in poor cereal-dependant economies masquerading as ‘environmental enteropathy’ or physical and cognitive stunting. Too much meat (and supplements) may precipitate immune intolerance and autoimmune and allergic disease, with relative infertility and longevity, via the tryptophan-nicotinamide pathway. This switch favours a dearth of regulatory T (Treg) and an excess of T helper cells. High nicotinamide intake is implicated in cancer and Parkinson’s disease. Pro-fertility genes, evolved to counteract high-nicotinamide-induced infertility, may now be risk factors for degenerative disease. Moderation of the dose of nicotinamide could prevent some common diseases and personalised doses at times of stress or, depending on genetic background or age, may treat some other conditions.

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          Early development and fitness in birds and mammals.

          Conditions experienced during early development affect survival and reproductive performance in many bird and mammal species. Factors affecting early development can therefore have an important influence both on the optimization of life histories and on population dynamics. The understanding of these evolutionary and dynamic consequences is just starting to emerge.
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            IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance.

            Indoleamine 2,3-dioxygenase (IDO) has immunoregulatory roles associated with tryptophan metabolism. These include counter-regulation (controlling inflammation) and acquired tolerance in T cells. Recent findings reveal that IDO can be triggered by innate responses during tumorigenesis, and also by attempted T cell activation, either spontaneous or due to immunotherapy. Here we review the current understanding of mechanisms by which IDO participates in the control of inflammation and in peripheral tolerance. Focusing on the tumor microenvironment, we examine the role of IDO in response to apoptotic cells and the impact of IDO on Treg cell function. We discuss how the counter-regulatory and tolerogenic functions of IDO can be targeted for cancer immunotherapy and present an overview of the current clinical progress in this area.
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              Why do we age?

              The evolutionary theory of ageing explains why ageing occurs, giving valuable insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence. Such understanding also helps to clarify how the genome shapes the ageing process, thereby aiding the study of the genetic factors that influence longevity and age-associated diseases.
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                Author and article information

                Journal
                Int J Tryptophan Res
                Int J Tryptophan Res
                TRY
                sptry
                International Journal of Tryptophan Research : IJTR
                SAGE Publications (Sage UK: London, England )
                1178-6469
                03 July 2019
                2019
                : 12
                : 1178646919855940
                Affiliations
                [1 ]Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
                [2 ]School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, Birmingham, UK
                Author notes
                [*]Adrian C Williams, Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2WB, UK. Email: Adrian.Williams@ 123456uhb.nhs.uk
                Author information
                https://orcid.org/0000-0001-8431-7029
                Article
                10.1177_1178646919855940
                10.1177/1178646919855940
                6610439
                31320805
                307dc708-52fa-41bb-a076-cc2691bd7209
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 25 April 2019
                : 3 May 2019
                Categories
                TRY-12 Tryptophan supplements: History, Potential Advantages and Toxicity
                Review
                Custom metadata
                January-December 2019

                Biochemistry
                tregs,pellagra,environmental enteropathy,tb,hypervitaminosis b3,immune intolerance,antagonistic pleiotropy,thrifty phenotype,disposable soma,cancer,parkinson’s disease,flynn effect,iq,dementia

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