Biology subjects

David, E.

Publications and source records attributed to David, E..

21 records · Page 2Linked to original sources

bioRxiv2019

Background radiation impacts human longevity and cancer mortality: Reconsidering the linear no-threshold paradigm

BACKGROUNDThe current linear-no-threshold paradigm assumes that any exposure to ionizing radiation carries some risk, thus every effort should be made to maintain the exposures as low as possible. Here, we examined whether background radiation impacts human longevity and cancer mortality.\n\nMETHODSOur data covered the entire US population of the 3139 US counties, encompassing over 320 million people. The data on background radiation levels, the average of 5-year age-adjusted cancer mortality rates, and life expectancy for both males and females in each county, was extracted using publicly available tools from official sources, and analyzed with JMP(R) software.\n\nRESULTSWe found for the first time that life expectancy, the most integrative index of population health, was approximately 2.5 years longer in people living in areas with a relatively high vs. low background radiation ([≥] 180 mrem/year and [≤] 100 mrem/year, respectively; p < 0.005; 95% confidence interval [CI]). This radiation-induced lifespan extension could to a great extent be associated with the decrease in cancer mortality rate observed for several common cancers (lung, pancreas and colon cancers for both genders, and brain and bladder cancers for males only; p < 0.05; 95% CI).\n\nCONCLUSIONSExposure to a high background radiation displays clear beneficial health effects in humans. These hormetic effects provide strong evidence for re-considering the linear no-threshold paradigm, at least within the natural range of low-dose radiation.

cancer biology↗

bioRxiv2019

Defining Monocyte Differentiation into Colonic and Ileal Macrophages

Monocytes are circulating short-lived macrophage precursors that are recruited on demand from the blood to sites of inflammation and challenge. In steady state, classical monocytes give rise to vasculature-resident cells that patrol the luminal side of the endothelium. In addition, classical monocytes feed macrophage compartments of selected organs, including barrier tissues, such as the skin and intestine, as well as the heart. Monocyte differentiation under conditions of inflammation has been studied in considerable detail. In contrast, monocyte differentiation under non-inflammatory conditions remains less well understood. Here we took advantage of a combination of cell ablation and precursor engraftment to investigate the generation of gut macrophages from monocytes. Collectively, we identify factors associated with the gradual adaptation of monocytes to tissue residency. Moreover, comparison of monocyte differentiation into the colon and ileum-resident macrophages revealed the graduated acquisition of gut segment-specific gene expression signatures.

immunology↗

bioRxiv2018

Engrafted parenchymal brain macrophages differ from host microglia in transcriptome, epigenome and responsiveness to challenge

Microglia are yolk sac-derived macrophages residing in the parenchyma of brain and spinal cord, where they interact with neurons and other glial cells by constantly probing their surroundings with dynamic extensions. Following different conditioning paradigms and bone marrow (BM) / hematopoietic stem cell (HSC) transplantation, graft-derived cells seed the brain and persistently contribute to the parenchymal brain macrophage compartment. Here we establish that these cells acquire over time microglia characteristics, including ramified morphology, longevity, radio-resistance and clonal expansion. However, even following prolonged CNS residence, transcriptomes and epigenomes of engrafted HSC-derived macrophages remain distinct from yolk sac-derived host microglia. Furthermore, BM graft-derived cells display discrete responses to peripheral endotoxin challenge, as compared to host microglia. Also in human HSC transplant recipients, engrafted cells remain distinct from host microglia, extending our finding to clinical settings. Collectively, our data emphasize the molecular and functional heterogeneity of parenchymal brain macrophages and highlight potential clinical implications for patients treated by HSC gene therapy.

immunology↗