In only months-to-years a primary cancer can progress to an advanced phenotype that is metastatic and resistant to clinical treatments. As early as the 1900s, it was discovered that the progression ...of a cancer to the advanced phenotype is often associated with a shift in the metabolic profile of the disease from a state of respiration to anaerobic fermentation — a phenomenon denoted as the Warburg Effect.
Reports in the literature strongly suggest that the Warburg Effect is generated as a response to a loss in the integrity of the sequence and/or copy number of the mitochondrial genome content within a cancer.
Multiple studies regarding the progression of cancer indicate that mutation, and/or, a flux in the copy number, of the mitochondrial genome content can support the early development of a cancer, until; the mutational load and/or the reduction-to-depletion of the copy number of the mitochondrial genome content induces the progression of the disease to an advanced phenotype.
Collectively, evidence has revealed that the human cell has incorporated the mitochondrial genome content into a cellular mechanism that, when pathologically actuated, can de(un)differentiate a cancer from the parental tissue of origin into an autonomous disease that disrupts the hierarchical structure-and-function of the human body. This article is part of a Special Issue entitled: Biochemistry of Mitochondria.
►This review describes change in mitochondrial genome in cancer. ►Evidence shows that mitochondrial genome is predisposed to mutation in carcinogenesis. ►Then a burst of mutations occurred associated with advanced malignant phenotype.
The growth of LNCaP, a human prostate adenocarcinoma cell line, and MCF‐7, a human breast adenocarcinoma cell line, is initially hormone dependent. We previously demonstrated that LNρ0‐8 and MCFρ0, ...derived from LNCaP and MCF‐7 by depleting mitochondrial DNA (mtDNA), exhibited hormone‐independent growth that led to progressed phenotypes. Here, we demonstrate that LNρ0‐8 and MCFρ0 have invasive characters as evaluated by the ability of invasion through the extracellular matrix (ECM) in vitro. In addition, the induction of vimentin and the repression of E‐cadherin expression in ρ0 cells indicate that they are mesenchymal cells. Since LNρ0‐8 and MCFρ0 were derived from epithelial cancer cell lines, LNCaP and MCF‐7 must have lost epithelial features and gained the mesenchymal phenotype by epithelial‐mesenchymal transition (EMT) during the mtDNA depletion. In the ρ0 cell lines, the Raf/MAPK signaling cascade was highly activated together with the expressions of transforming growth factor‐beta (TGF‐β) and type I TGF‐β receptor (TGF‐βRI). EMT requires cooperation of TGF‐β signaling with activation of the Raf/MAPK cascade, suggesting that EMT was induced in mtDNA depleted cells resulting in the acquisition of progressive tumor features, such as higher invasiveness and loss of hormone dependent growth. Our results indicate that decreasing mtDNA content induces EMT, enabling the progressive phenotypes observed in cancer. (Cancer Sci 2008; 99: 1584–1588)
Abstract
The growth of the “gig” economy generates worker flexibility that, some have speculated, will favour women. We explore this by examining labour supply choices and earnings among more than a ...million rideshare drivers on Uber in the U.S. We document a roughly 7% gender earnings gap amongst drivers. We show that this gap can be entirely attributed to three factors: experience on the platform (learning-by-doing), preferences and constraints over where to work (driven largely by where drivers live and, to a lesser extent, safety), and preferences for driving speed. We do not find that men and women are differentially affected by a taste for specific hours, a return to within-week work intensity, or customer discrimination. Our results suggest that, in a “gig” economy setting with no gender discrimination and highly flexible labour markets, women’s relatively high opportunity cost of non-paid-work time and gender-based differences in preferences and constraints can sustain a gender pay gap.
Rat cerebellar Purkinje neurons are vulnerable to ethanol exposure during the brain growth spurt, especially during early postnatal exposure. A prominent hypothesis is that ethanol induces oxidative ...types of alterations that result in the neurodegeneration. The purpose of this study was to test this hypothesis in two ways. One was to determine if the reactive oxidative species, nitrotyrosine (NT), was produced in the cerebellum following ethanol exposure. Second, was to determine if co-administration of the clinically useful antioxidant
N-acetylcysteine (NAC) afforded any protection from Purkinje neuron loss. Rat pups were treated on postnatal day 4 with a single ethanol (6.0
g/kg) or isocaloric intragastric intubation. The cerebelli were analyzed for NT with ELISA assays at 2, 4, 6, or 8
h following the single exposure. No evidence of NT was found at any of these time points. Another group of animals received ethanol exposure on PN4, or ethanol exposure plus NAC. Control groups included isocaloric intubated controls (IC), IC plus NAC, and mother reared controls. Twenty-four hours following the exposures, the pups were perfused and the cerebellum processed for cell counting. Ethanol exposure reduced the number of Purkinje neurons in the cerebellum. Concurrent treatment with antioxidant did not protect the Purkinje neurons from ethanol-related cell loss. These in vivo analyses do not support a robust oxidative mechanism involving the production of reactive nitrogen species as a significant means of Purkinje cell neurodegeneration.
A survey of agricultural chemicals in Wisconsin groundwater was conducted between October 2000 and April 2001 to obtain a current picture of agricultural chemicals in groundwater used for private ...drinking water. A stratified, random sampling procedure was used to select 336 sampling locations. Water from private drinking water wells randomly selected from within the 336 sampling locations was analyzed for 18 compounds including herbicides, herbicide metabolites, and nitrate. This report focuses on the frequency and concentration of chloroacetanilide herbicides and their metabolites. Analysis of data resulted in an estimated proportion of 38 ± 5.0% of wells that contained detectable levels of a herbicide or herbicide metabolite. The most commonly detected compound was alachlor ESA with a proportion estimate of 28 ± 4.6%. Other detected compounds in order of prevalence were metolachlor ESA, metolachlor OA, alachlor OA, acetochlor ESA, and parent alachlor. Estimates of the mean concentration for the detects ranged from 0.15 ± 0.082 μg/L for acetochlor ESA to 1.8 ± 0.60 μg/L for alachlor OA. Water quality standards have not been developed for these chloroacetanilide herbicide metabolites. The results of this survey emphasize the need for toxicological assessments of herbicide metabolite compounds and establishment of water quality standards at the state and federal levels.
Older Workers and the Gig Economy Cook, Cody; Diamond, Rebecca; Oyer, Paul
AEA papers and proceedings,
05/2019, Letnik:
109
Journal Article
Recenzirano
As the workforce ages, how will the work lives of older people evolve? One way to ease into retirement is to move to the gig economy where workers choose hours and intensity of work that fit their ...needs and capabilities. However, older workers are often reaping the benefits of the latter end of an implicit contract while gig economy workers are paid their marginal product. We show that age/earnings profiles in the traditional labor market are different than for Uber drivers. While the move to the gig economy generates flexibility, older workers are paid less than their younger coworkers.
Wildfire is an important ecological process which exerts direct and indirect costs on both natural and human systems. The social-ecological fire landscape is a complex interaction between rapid ...increases in the number of people living in flammable landscapes, a hotter and drier climate, and accumulation of fuels in some areas related to years of fire suppression. Coinciding with rapid growth of human settlements in flammable landscapes and changes in fire activity, communities in the western United States are being exposed to more catastrophic wildfire events. In this study, we leverage novel data sources to explore the landscape (weather, fuels, and topography), human settlement, and fire growth patters as drivers of two outcomes: the magnitude (total count) and proportion (ratio between destroyed and exposed) of home loss within historic wildfire perimeters. We harmonize multiple data sources across 694 wildfire events, representing 369,617 estimated directly exposed properties and 38,846 destroyed residential structures (78.8% of total losses) from 2001-2018 in the western United States. We then apply a flexible modeling approach to explore the effects of various drivers on wildfire-related home losses. We found that single-day maximum fire growth predicts higher magnitude and proportion of residential structure loss during historic wildfires. Fast-growing wildfires are creating dangerous situations for rural communities, particularly if that growth occurs within the first 20 days of the wildfire. Moreover, human settlement patterns, such as median property density within fire perimeters, effects the proportion of destroyed homes where areas of more dispersed wildland development typically have a higher proportion of residential structure loss. Furthermore, remote sensing-derived metrics of fuel characteristics effect the proportion of destroyed residential structures, particularly during extreme fire weather events. Extreme fire weather also effects the magnitude and proportion of home loss during the critical time when human settlements are exposed to wildfire. These results suggest that targeted fuels management projects (e.g., defensible space and fuel breaks near communities), early fire detection systems, and land use planning can mitigate risk to homes and firefighter safety and effectiveness. This research leverages novel datasets to explore the drivers of wildfire-related home loss in the western United States.
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