Genomic instability and aging-like phenotype in the absence of mammalian SIRT6

The Sir2 histone deacetylase functions as a chromatin silencer to regulate recombination, genomic stability, and aging in budding yeast. Seven mammalian Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER). SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks. We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes.     

Corrosion of aluminum alloy 2024 by microorganisms isolated from aircraft fuel tanks

Microorganisms frequently contaminate jet fuel and cause corrosion of fuel tank metals. In the past, jet fuel contaminants included a diverse group of bacteria and fungi. The most common contaminant was the fungus Hormoconis resinae. However, the jet fuel community has been altered by changes in the composition of the fuel and is now dominated by bacterial contaminants. The purpose of this research was to determine the composition of the microbial community found in fuel tanks containing jet propellant-8 (JP-8) and to determine the potential of this community to cause corrosion of aluminum alloy 2024 (AA2024). Isolates cultured from fuel tanks containing JP-8 were closely related to the genus Bacillus and the fungi Aureobasidium and Penicillium. Biocidal activity of the fuel system icing inhibitor diethylene glycol monomethyl ether is the most likely cause of the prevalence of endospore forming bacteria. Electrochemical impedance spectroscopy and metallographic analysis of AA2024 exposed to the fuel tank environment indicated that the isolates caused corrosion of AA2024. Despite the limited taxonomic diversity of microorganisms recovered from jet fuel, the community has the potential to corrode fuel tanks.     

Augmentation of inorganic pyrophosphate elaboration in cartilage by serum factors

The disordered production of inorganic pyrophosphate (PPi) by articular cartilage is thought to have an important role in the pathogenesis of calcium pyrophosphate dihydrate deposition disease and perhaps osteoarthritis. We have previously shown that fetal calf serum added to the culture media of porcine articular cartilage explants increases the elaboration of PPi into the ambient media. We have examined this PPi stimulatory activity by studying the effects of adult human serum (HS), serum derived from adult human plasma (HP), and an acid-alcohol extract of human platelets (PE) on PPi production in cartilage organ culture. Ten percent HS produces a 1.4-fold increase in PPi production after 48 h of culture, while cartilage incubated in media containing 10% HP produces no more PPi than that incubated in media alone. PE stimulates a mean 2-fold increase in PPi production at 48 h in the presence of low concentrations of HP, and has no effect alone. It does not appear to up-regulate the activity of the ectoenzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH), nor does it promote the release of enzyme substrate into the extracellular space. Cartilage exposed to 0.5% HP and PE has 1.51 +/- 0.36 units of NTPPPH activity whereas cartilage exposed to 0.5% HP alone has 1.52 +/- 0.41 units of enzyme activity. PE does not increase the release of [14C]adenine-labeled compounds into the media. Approximately 13% of soluble 14C counts was found in the media of chondrocytes treated with PE while 18% of counts was released in the presence of HP alone. We have demonstrated a factor or factors present in FCS, HS, and an acid-ethanol extract of human platelets which represent(s) the first known physiologic modulators of PPi production in articular cartilage and may increase PPi production without affecting NTPPPH activity.     

Charcoal production in the Mopane woodlands of Mozambique: what are the trade-offs with other ecosystem services?

African woodlands form a major part of the tropical grassy biome and support the livelihoods of millions of rural and urban people. Charcoal production in particular is a major economic activity, but its impact on other ecosystem services is little studied. To address this, our study collected biophysical and social datasets, which were combined in ecological production functions, to assess ecosystem service provision and its change under different charcoal production scenarios in Gaza Province, southern Mozambique. We found that villages with longer histories of charcoal production had experienced declines in wood suitable for charcoal, firewood and construction, and tended to have lower perceived availabilities of these services. Scenarios of future charcoal impacts indicated that firewood and woody construction services were likely to trade-off with charcoal production. However, even under the most extreme charcoal scenario, these services were not completely lost. Other provisioning services, such as wild food, medicinal plants and grass, were largely unaffected by charcoal production. To reduce the future impacts of charcoal production, producers must avoid increased intensification of charcoal extraction by avoiding the expansion of species and sizes of trees used for charcoal production. This is a major challenge to land managers and policymakers in the area.This article is part of the themed issue ‘Tropical grassy biomes: linking ecology, human use and conservation’.     

Regulation of cytosolic phospholipase A2 in rat endometrial stromal cells: the role of epidermal growth factor

The effect of epidermal growth factor on the levels of cytosolic phospholipase A2 mRNA and protein in cultured rat endometrial stromal cells isolated from uteri sensitized for the decidual cell reaction was examined. Treatment with epidermal growth factor increased the steady-state cytosolic phospholipase A2 mRNA and protein levels as demonstrated by Northern and Western blot analyses, respectively. Immunocytochemical analysis demonstrated an increase of cytosolic phospholipase A2 protein in most cells, as opposed to a small subpopulation of cells in culture. These results show that epidermal growth factor causes an increase in steady-state cytosolic phospholipase A2 mRNA and protein levels in rat endometrial stromal cells from uteri sensitized for the decidual cell reaction. Epidermal growth factor receptor ligands may regulate cytosolic phospholipase A2 and thus prostaglandin production in the endometrial stromal cells during implantation.     

Seasonal patterns in soil surface CO<Subscript>2</Subscript> flux under snow cover in 50 and 300 year old subalpine forests

Soil CO₂ flux can contribute as much as 60–80% of total ecosystem respiration in forests. Although considerable research has focused on quantifying this flux during the growing season, comparatively little effort has focused on non-growing season fluxes. We measured soil CO₂ efflux through snow in 50 and ~300 year old subalpine forest stands near Fraser CO. Our objectives were to quantify seasonal patterns in wintertime soil CO₂ flux; determine if differences in soil CO₂ flux between the two forest ages during the growing season persist during winter; and to quantify the sample size necessary to discern treatment differences. Soil CO₂ flux during the 2002–2003 and 2003–2004 snow season averaged 0.31 and 0.35 μmols m⁻² s⁻¹ for the young and old forests respectively; similar to the relative difference observed during summer. There was a significant seasonal pattern of soil CO₂ flux during the winter with fluxes averaging 0.22 μmols m⁻² s⁻¹ in December and January and increasing to an average of 0.61 μmols m⁻² s⁻¹ in May. Within-plot variability for measurements used in calculating flux was low. The coefficients of variation (CV) for CO₂ concentration, snowpack density, and snow depth were 17, 8 and 14%, respectively, yielding a CV for flux measurements within-plot of 29%. A within plot CV of 29% requires 8 sub-samples per plot to estimate the mean flux with a standard error of ±10% of the mean. Variability in CO₂ flux estimates among plots (size = 400 m²) was similar to that within plot and was also low (CV = ~28%). With a CV of 28% among plots, ten plots per treatment would have a 50% probability of detecting a 25% difference in treatment means for α = 0.05.     

Inhibition of NF-κB and DNA double-strand break repair by DMAPT sensitizes non-small-cell lung cancers to X-rays

We investigated the efficacy and mechanism of dimethylaminoparthenolide (DMAPT), an NF-κB inhibitor, to sensitize human lung cancer cells to X-ray killing in vitro and in vivo. We tested whether DMAPT increased the effectiveness of single and fractionated X-ray treatment through inhibition of NF-κB and/or DNA double-strand break (DSB) repair. Treatment with DMAPT decreased plating efficiency, inhibited constitutive and radiation-induced NF-κB binding activity, and enhanced radiation-induced cell killing by dose modification factors of 1.8 and 1.4 in vitro. X-ray fractionation demonstrated that DMAPT inhibited split-dose recovery/repair, and neutral DNA comet assays confirmed that DMAPT altered the fast and slow components of X-ray-induced DNA DSB repair. Knockdown of the NF-κB family member p65 by siRNA increased radiation sensitivity and completely inhibited split-dose recovery in a manner very similar to DMAPT treatment. The data suggest a link between inhibition of NF-κB and inhibition of DSB repair by DMAPT that leads to enhancement of X-ray-induced cell killing in vitro in non-small-cell lung cancer cells. Studies of A549 tumor xenografts in nude mice demonstrated that DMAPT enhanced X-ray-induced tumor growth delay in vivo.