Pan-European atmospheric lead pollution, enhanced blood lead levels, and cognitive decline from Roman-era mining and smelting

Ancient texts and archaeological evidence indicate substantial lead exposure during antiquity that potentially impacted human health. Although lead exposure routes were many and included use of glazed tablewares, paints, cosmetics, and even intentional ingestion, the most significant for the nonelite, rural majority of the population may have been through background air pollution from mining and smelting of silver and lead ores that underpinned the Roman economy. Here we determined potential health effects of this air pollution using Arctic ice core measurements of Roman-era lead pollution, atmospheric modeling, and modern epidemiology-based relationships between air concentrations, blood lead levels, and cognitive decline. Findings suggest air lead concentrations exceeded 150 ng/m3 near metallurgical emission sources, with average enhancements of >1.0 ng/m3 over Europe during the Pax Romana apogee of the Roman Empire. The result was blood lead enhancements in young children of about 2.4 µg/dl above an estimated Neolithic background of 1.0 µg/dl, leading to widespread cognitive decline including a 2.5-to-3 point reduction in intelligence quotient throughout the Roman Empire. Significance: The detrimental effects of modern lead exposure on human health are widely recognized. Evidence from the Roman era indicates substantial lead exposure that potentially impacted human health more than 2,000 y ago. The most significant exposure for the rural, nonelite population may have been to background air pollution from silver mining and smelting that underpinned the Roman economy. Using detailed records of Roman-era lead pollution measured in Arctic ice cores and atmospheric modeling, we show that lead emissions from these activities elevated air concentrations throughout Europe. Based on modern epidemiological studies, this air pollution enhanced childhood blood lead levels (BLLs) by about 2.4 µg/dl leading to widespread cognitive decline including an estimated 2.5-to-3 point reduction in intelligence quotient

HIV Replication Enhances Production of Free Fatty Acids, Low Density Lipoproteins and Many Key Proteins Involved in Lipid Metabolism: A Proteomics Study

BACKGROUND: HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. RESULTS: Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. CONCLUSIONS: We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid-related disorders. The target proteins could then be used for future studies in the development of inhibitors for preventing lipid-metabolic anomalies. This is the first direct evidence that HIV-modulates production of proteins that are significantly involved in disrupting the normal lipid-metabolic pathways

The mycotoxin alternariol induces DNA damage and modify macrophage phenotype and inflammatory responses

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