Tracing Dacian gold in Roman aurei

Here the LA-ICP-MS results from 66 Roman gold coins (aurei) issued between AD 101 and AD 196 are presented. Aurei issued between AD 129 and AD 165 seemed to have been made from an antimony- and tellurium-rich gold. The Roman gold mines at Roșia Montană in Dacia, modern day Romania, produce antimony- and tellurium-rich gold, and we have precisely dated documentary evidence that suggests intensive mining activity occurred here from at least AD 131 until AD 167. The intensity of the proposed antimony- and tellurium-rich Roșia Montană ‘fingerprint’ in Roman gold coinage almost perfectly matches the chronological window of intensive exploitation of the Roșia Montană gold source. As such, gold from Dacia appears to have been one of the most dominant sources for the Roman supply network in the mid-second century, and the strategic importance of the province at this time should not be underestimated

Fate of Steroid Estrogens in Australian Inland and Coastal Wastewater Treatment Plants

A comparison of estrone (E1), 17b-estradiol (E2) and 17a-ethinylestradiol (EE2) removal at a coastal enhanced primary and inland advanced sewage treatment plant (STP) is reported. The average concentration of estrogens in the raw sewage is similar to reports in other studies. The sequential batch reactor at the advanced STP removed on average 85% of the incoming E1 and 96% of the E2. Further removal was observed during later microfiltration with the estrogen concentration below detection (<0.1 ng.L-1) after reverse osmosis. Some 6% of the influent E1+E2 was removed in the waste activated sludge. The detection of EE2 in the waste activated sludge (0.42 ng.g-1 solids dry weight), undetectable in the raw sewage, suggests that EE2 is resistant to biological treatment in the sequential batch reactor and is primarily removed due to sorption. Little estrogen removal was observed at the enhanced primary with only 7% of E1 and 0% of E2 removed. Low removal is expected based on the degree of estrogens partitioning in the organic fraction given the relatively low solids concentration, but surprisingly, some 43% of E2, 24% of E1 and 100% of EE2 remains associated with the solids fraction in the treated effluent. Further research is necessary to determine whether the low level of estrogen removal for the coastal treatment plant will adversely affect the receiving marine environment

Steroid estrogens in primary and tertiary wastewater treatment plants

The concentrations of two natural estrogens (Estrone (E1) and Estradiol (E2)) and one synthetic progestin (Ethinylestradiol (EE2)) were measured for different unit operations in an advanced sewage treatment plant and in a large coastal enhanced primary sewage treatment plant. The average influent concentration to both plants was similar – 55 and 53 ng/L for E1 and 22 and 12 ng/L for E2 for the advanced and enhanced primary STPs, respectively. The activated sludge process at the advanced STP removed up to 85% and 96% of E1 and E2, respectively. The enhanced primary sewage treatment plant was mostly ineffective at removing the steroids with only 14% of E1 and 5% of E2 being removed during the treatment process. EE2 was not been detected during the study period in the influent or effluent of either STP. The difference in the observed removal between the two plants is primarily linked to plant performance but the extent to which removal of steroid estrogens is due to bacterial metabolism (i.e. the advanced STP) rather than adsorption to the bacterial biomass remains unclear. The poor removal observed for the coastal enhanced primary STP may have implications for the receiving environment in terms of a greater potential for abnormal reproductive systems in marine animals, particularly if discharges are into large bays or harbours where flushing is limited

Differential expression of sirtuins in the aging rat brain

Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of "physiologically" aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging.16 page(s

Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies

Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice.

Published versio

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

<div><h3>Objectives</h3><p>Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort.</p> <h3>Methods</h3><p>664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique.</p> <h3>Results</h3><p>At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years.</p> <h3>Conclusions</h3><p>Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.</p> </div

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity