Mice deficient in CuZn superoxide dismutase (CuZnSOD) showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in ...the liver. Greater than 70% of Sod1-/- mice developed liver nodules that were either nodular hyperplasia or hepatocellular carcinoma (HCC). Cross-sectional studies with livers collected from Sod1-/- and age-matched +/+ controls revealed extensive oxidative damage in the cytoplasm and, to a lesser extent, in the nucleus and mitochondria from as early as 3 months of age. A marked reduction in cytosolic aconitase, increased levels of 8-oxo dG and F2-isoprostanes, and a moderate reduction in glutathione peroxidase activities and porin levels were observed in all age groups of Sod1-/- mice examined. There were also age-related reductions in Mn superoxide dismutase activities and carbonic anhydrase III. Parallel to the biochemical changes, there were progressive increases in the DNA repair enzyme APEX1, the cell cycle control proteins cyclin D1 and D3, and the hepatocyte growth factor receptor Met. Increased cell proliferation in the presence of persistent oxidative damage to macromolecules likely contributes to hepatocarcinogenesis later in life.
The art of imparting information onto a light wave by optical signal modulation is fundamental to all forms of optical communication. Among many schemes, direct modulation of laser diodes stands out ...as a simple, robust, and cost-effective method. However, the simultaneous changes in intensity, frequency, and phase have prevented its application in the field of secure quantum communication. Here, we propose and experimentally demonstrate a directly phase-modulated light source which overcomes the main disadvantages associated with direct modulation and is suitable for diverse applications such as coherent communications and quantum cryptography. The source separates the tasks of phase preparation and pulse generation between a pair of semiconductor lasers leading to very pure phase states. Moreover, the cavity-enhanced electro-optic effect enables the first example of subvolt half-wave phase modulation at high signal rates. The source is compact, stable, and versatile, and we show its potential to become the standard transmitter for future quantum communication networks based on attenuated laser pulses.
Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Recent studies have reported associations between perinatal exposure to air ...pollutants and autism spectrum disorder (ASD) in children. We tested the hypothesis that perinatal exposure to air pollutants is associated with ASD, focusing on pollutants associated with ASD in prior studies.
We estimated associations between U.S. Environmental Protection Agency-modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in the Nurses' Health Study II (325 cases, 22,101 controls). Our analyses focused on pollutants associated with ASD in prior research. We accounted for possible confounding and ascertainment bias by adjusting for family-level socioeconomic status (maternal grandparents' education) and census tract-level socioeconomic measures (e.g., tract median income and percent college educated), as well as maternal age at birth and year of birth. We also examined possible differences in the relationship between ASD and pollutant exposures by child's sex.
Perinatal exposures to the highest versus lowest quintile of diesel, lead, manganese, mercury, methylene chloride, and an overall measure of metals were significantly associated with ASD, with odds ratios ranging from 1.5 (for overall metals measure) to 2.0 (for diesel and mercury). In addition, linear trends were positive and statistically significant for these exposures (p < .05 for each). For most pollutants, associations were stronger for boys (279 cases) than for girls (46 cases) and significantly different according to sex.
Perinatal exposure to air pollutants may increase risk for ASD. Additionally, future studies should consider sex-specific biological pathways connecting perinatal exposure to pollutants with ASD.
Please cite this paper as: Lee Y, Roberts C, Dobbins T, Stavrou E, Black K, Morris J, Young J. Incidence and outcomes of pregnancy‐associated cancer in Australia, 1994–2008: a population‐based ...linkage study. BJOG 2012;119:1572–1582.
Objective To determine trends in pregnancy‐associated cancer and associations between maternal cancer and pregnancy outcomes.
Design Population‐based cohort study.
Setting New South Wales, Australia, 1994–2008.
Population A total of 781 907 women and their 1 309 501 maternities.
Methods Cancer and maternal information were obtained from linked cancer registry, birth and hospital records for the entire population. Generalised estimating equations with a logit link were used to examine associations between cancer risk factors and pregnancy outcomes.
Main outcome measures Incidence of pregnancy‐associated cancer (diagnosis during pregnancy or within 12 months of delivery), maternal morbidities, preterm birth, and small‐ and large‐for‐gestational‐age (LGA).
Results A total of 1798 new cancer diagnoses were identified, including 499 during pregnancy and 1299 postpartum. From 1994 to 2007, the crude incidence rate of pregnancy‐associated cancer increased from 112.3 to 191.5 per 100 000 maternities (P < 0.001), and only 14% of the increase was explained by increasing maternal age. Cancer diagnosis was more common than expected in women aged 15–44 years (observed‐to‐expected ratio 1.49; 95% CI 1.42–1.56). Cancers were predominantly melanoma (33.3%) and breast cancer (21.0%). Women with cancer diagnosed during pregnancy had high rates of labour induction (28.5%), caesarean section (40.0%) and planned preterm birth (19.7%). Novel findings included a cancer association with multiple pregnancies (adjusted odds ratio 1.52, 95% CI 1.13–2.05) and LGA (aOR 1.47, 95% CI 1.14–1.89).
Conclusions Pregnancy‐associated cancers have increased, and this increase is only partially explained by increasing maternal age. Pregnancy increases women’s interaction with health services and the possibility for diagnosis, but may also influence tumour growth.
α-Synuclein misfolding and aggregation is often accompanied by β-amyloid deposition in some neurodegenerative diseases. We hypothesised that α-synuclein promotes β-amyloid production from APP. ...β-Amyloid levels and APP amyloidogenic processing were investigated in neuronal cell lines stably overexpressing wildtype and mutant α-synuclein. γ-Secretase activity and β-secretase expression were also measured. We show that α-synuclein expression induces β-amyloid secretion and amyloidogenic processing of APP in neuronal cell lines. Certain mutations of α-synuclein potentiate APP amyloidogenic processing. γ-Secretase activity was not enhanced by wildtype α-synuclein expression, however β-secretase protein levels were induced. Furthermore, a correlation between α-synuclein and β-secretase protein was seen in rat brain striata. Iron chelation abolishes the effect of α-synuclein on neuronal cell β-amyloid secretion, whereas overexpression of the ferrireductase enzyme Steap3 is robustly pro-amyloidogenic. We propose that α-synuclein promotes β-amyloid formation by modulating β-cleavage of APP, and that this is potentially mediated by the levels of reduced iron and oxidative stress.
Isoprostanes Roberts, L. Jackson; Milne, Ginger L.
Journal of lipid research,
04/2009, Letnik:
50, Številka:
Suppl
Journal Article
Recenzirano
Odprti dostop
The isoprostanes (IsoPs) are a unique series of prostaglandin-like compounds formed in vivo via a nonenzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid. This ...article summarizes our current knowledge of these compounds. Herein, a historical account of their discovery and the mechanism of their formation are described. A specific class of IsoPs, the F2-IsoPs, are stable, robust molecules that can be measured as indices of endogenous oxidant stress. The utility of these molecules as biomarkers and methods by which these compounds can be quantified are discussed. In addition to the F2-IsoPs, isoprostanes with other prostane ring structures as well as oxidation products with furan and dioxolane rings can be generated from arachidonic acid. And, in more recent years, isoprostane-like compounds have been shown to be formed from polyunsaturated fatty acids including eicosapentaenoic acid C20:5, ω-3, docosahexaenoic acid C22:6, ω-3, and adrenic acid C22:4, ω-6. These findings will be summarized as well.
For most organisms, the number of described species considerably underestimates how many exist. This is itself a problem and causes secondary complications given present high rates of species ...extinction. Known numbers of flowering plants form the basis of biodiversity "hotspots"--places where high levels of endemism and habitat loss coincide to produce high extinction rates. How different would conservation priorities be if the catalog were complete? Approximately 15% more species of flowering plant are likely still undiscovered. They are almost certainly rare, and depending on where they live, suffer high risks of extinction from habitat loss and global climate disruption. By using a model that incorporates taxonomic effort over time, regions predicted to contain large numbers of undiscovered species are already conservation priorities. Our results leave global conservation priorities more or less intact, but suggest considerably higher levels of species imperilment than previously acknowledged.
infects every niche of the human host. In response to microbial infection, vertebrates have an arsenal of antimicrobial compounds that inhibit bacterial growth or kill bacterial cells. One class of ...antimicrobial compounds consists of polyunsaturated fatty acids, which are highly abundant in eukaryotes and encountered by
at the host-pathogen interface. Arachidonic acid (AA) is one of the most abundant polyunsaturated fatty acids in vertebrates and is released in large amounts during the oxidative burst. Most of the released AA is converted to bioactive signaling molecules, but, independently of its role in inflammatory signaling, AA is toxic to
Here, we report that AA kills
through a lipid peroxidation mechanism whereby AA is oxidized to reactive electrophiles that modify
macromolecules, eliciting toxicity. This process is rescued by cotreatment with antioxidants as well as in a
strain genetically inactivated for
(USA300
mutant) that produces lower levels of reactive oxygen species. However, resistance to AA stress in the USA300
mutant comes at a cost, making the mutant more susceptible to β-lactam antibiotics and attenuated for pathogenesis in a murine infection model compared to the parental methicillin-resistant
(MRSA) strain, indicating that resistance to AA toxicity increases susceptibility to other stressors encountered during infection. This report defines the mechanism by which AA is toxic to
and identifies lipid peroxidation as a pathway that can be modulated for the development of future therapeutics to treat
infections.
Despite the ability of the human immune system to generate a plethora of molecules to control
infections,
is among the pathogens with the greatest impact on human health. One class of host molecules toxic to
consists of polyunsaturated fatty acids. Here, we investigated the antibacterial properties of arachidonic acid, one of the most abundant polyunsaturated fatty acids in humans, and discovered that the mechanism of toxicity against
proceeds through lipid peroxidation. A better understanding of the molecular mechanisms by which the immune system kills
, and by which
avoids host killing, will enable the optimal design of therapeutics that complement the ability of the vertebrate immune response to eliminate
infections.
Post-traumatic stress disorder (PTSD) has been linked to hypertension, but most research on PTSD and hypertension is cross-sectional, and potential mediators have not been clearly identified. ...Moreover, PTSD is twice as common in women as in men, but understanding of the PTSD-hypertension relationship in women is limited. We examined trauma exposure and PTSD symptoms in relation to incident hypertension over 22 years in 47 514 civilian women in the Nurses' Health Study II.
We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset hypertension (N = 15 837).
PTSD symptoms assessed with a screen were modestly associated with incident hypertension in a dose-response fashion after adjusting for potential confounders. Compared to women with no trauma exposure, women with 6-7 PTSD symptoms had the highest risk of developing hypertension (HR 1.20, 95% CI 1.12-1.30), followed by women with 4-5 symptoms (HR 1.17, 95% CI 1.10-1.25), women with 1-3 symptoms (HR 1.12, 95% CI 1.06-1.18), and trauma-exposed women with no symptoms (HR 1.04, 95% CI 1.00-1.09). Findings were maintained, although attenuated, adjusting for hypertension-relevant medications, medical risk factors, and health behaviors. Higher body mass index and antidepressant use accounted for 30% and 21% of the PTSD symptom-hypertension association, respectively.
Screening for hypertension and reducing unhealthy lifestyle factors, particularly obesity, in women with PTSD may hold promise for offsetting cardiovascular risk.
Fly-ash particles formed during industrial fossil-fuel combustion show a globally observed rapid increase in concentration within natural archives post-1950 and have been proposed as a marker for the ...Anthropocene Epoch. Here, we present the first record of fly-ash particles incorporated into coral skeletons. Particles are present in Mediterranean corals between CE 1957 and 1992 at concentrations of 8–30 g−1 coral, mirroring the period of increased industrial activity in the area, and corroborating with spheroidal carbonaceous particle (SCP) records globally. The findings have important implications for the use of SCPs as markers in natural archives. With the exception of microplastics, this is the first evidence of particulate contamination in corals collected from natural environments. Further research is needed to understand incorporation pathways into coral skeletons, any subsequent ecotoxicological impact of contaminants, and the influence on overall coral health globally.
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•The first record of fly-ash particles incorporated into coral skeletons.•Particles are present in Mediterranean corals between CE 1957 and 1992.•Presence corroborates with peak SCP concentrations in records globally.
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