Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Dec 2015
Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses.
In vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and preimplantation genetic screening (PGS) help patients to select embryos free of monogenic diseases and aneuploidy (chromosome abnormality). Next-generation sequencing (NGS) methods, while experiencing a rapid cost reduction, have improved the precision of PGD/PGS. However, the precision of PGD has been limited by the false-positive and false-negative single-nucleotide variations (SNVs), which are not acceptable in IVF and can be circumvented by linkage analyses, such as short tandem repeats or karyomapping. ⋯ The false-positive and -negative SNVs are avoided by an NGS-based linkage analysis. Two healthy babies, free of the monogenic diseases of their parents, were born after such embryo selection. The monogenic diseases originated from a single base mutation on the autosome and the X-chromosome of the disease-carrying father and mother, respectively.
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Deficiency in essential omega-3 polyunsaturated fatty acids (PUFAs), particularly the long-chain form of docosahexaenoic acid (DHA), has been linked to health problems in mammals, including many mental disorders and reduced cognitive performance. Insects have very low long-chain PUFA concentrations, and the effect of omega-3 deficiency on cognition in insects has not been studied. We show a low omega-6:3 ratio of pollen collected by honey bee colonies in heterogenous landscapes and in many hand-collected pollens that we analyzed. ⋯ The shift from a low to high omega-6:3 ratio in the Western human diet is deemed a primary cause of many diseases and reduced mental health. A similar shift seems to be occurring in bee forage, possibly an important factor in colony declines. Our study shows the detrimental effect on cognitive performance of omega-3 deficiency in a nonmammal.
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Proc. Natl. Acad. Sci. U.S.A. · Dec 2015
CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity.
Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund's adjuvant (CFA) as a model of adjuvant- and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. ⋯ By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G(+)CD11b(+) neutrophils and T-cell receptor (TCR) β(+) T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b(+)Ly6G(-) myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2(+)Ly6C(hi)) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b(+)Ly6G(-) myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation.
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Proc. Natl. Acad. Sci. U.S.A. · Nov 2015
Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution.
The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. ⋯ DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.