Anti‐proliferative activity of bovine blood hydrolysates towards cancer cells in culture

Four proteins, α/β globulin, serum albumin, γ‐globulin and fibrinogen, were isolated from bovine blood and hydrolysed using papain. Hydrolysates were assessed for non‐cellular and cellular antioxidant activity. The anti‐proliferative activity of hydrolysed fractions was assessed in a number of cancer cell lines including U937 lymphoma cells, MCF‐7 breast cancer cells, HepG2 hepatocytes and Caco‐2 epithelial colorectal adenocarcinoma cells. Anti‐inflammatory activity of the hydrolysates was also assessed. Hydrolysates generated from γ‐globulin or fibrinogen had significant antioxidant activity in non‐cellular assays. Hydrolysates were also found to be highly toxic to different cancer cell lines, in particular U937 lymphoma cells when assessed using the MTT assay. The fibrinogen hydrolysate was the most toxic sample and toxicity appeared to correlate with its non‐cellular antioxidant activity. None of the hydrolysates had significant anti‐inflammatory activity. The high cytotoxicity of the γ‐globulin and the fibrinogen hydrolysates towards cancer cells may indicate a potential use as anti‐proliferative agents.     

Housing Equity Withdrawal in Australia: Prevalence,Patterns and Motivations in Mid-to-late Life

In an era of population ageing, the primary home is increasingly viewed as a personal resource that can perform a pension role in retirement. This article assesses the extent to which Australians aged 45 years and over withdraw housing equity through in situ mortgage equity withdrawal (MEW), downsizing and selling up. We find that the incidence of housing equity withdrawal has increased over the last decade despite a global financial crisis. MEW is the dominant form of equity release among those under pension age, while downsizing or selling up is more frequent among those above pension age. Downsizing and selling up are more likely to be prompted by adverse life events than MEW. Selling up is typically an option of last resort. Our findings offer insights into important debates around homeownership societies and the welfare role performed by owner-occupied housing in mid-to-late life.     

Local dopamine production in the dorsal striatum restores goal-directed behavior in dopamine-deficient mice.

To determine whether dopamine signaling in the dorsal striatum is sufficient for performance of goal-directed behaviors, local dopamine production was restored in the dorsal striatum of dopamine-deficient (DD) mice through viral-mediated gene therapy. Virally rescued DD (vrDD) mice were tested for learning of an appetitive T-maze task designed to measure goal-directed behavior. The results indicate that in contrast with the performance of DD mice that have dysregulated dopamine signaling, vrDD mice were able to perform the T-maze task and reverse their behavior as well as sham-operated control mice. The authors conclude that finely tuned dopaminergic signaling within the dorsal striatum is sufficient for performance of goal-directed behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microbially mediated mineral carbonation: roles of phototrophy and heterotrophy

Ultramafic mine tailings from the Diavik Diamond Mine, Canada and the Mount Keith Nickel Mine, Western Australia are valuable feedstocks for sequestering CO? via mineral carbonation. In microcosm experiments, tailings were leached using various dilute acids to produce subsaline solutions at circumneutral pH that were inoculated with a phototrophic consortium that is able to induce carbonate precipitation. Geochemical modeling of the experimental solutions indicates that up to 2.5% and 16.7% of the annual emissions for Diavik and Mount Keith mines, respectively, could be sequestered as carbonate minerals and phototrophic biomass. CO? sequestration rates are mainly limited by cation availability and the uptake of CO?. Abundant carbonate mineral precipitation occurred when heterotrophic oxidation of acetate acted as an alternative pathway for CO? delivery. These experiments highlight the importance of heterotrophy in producing sufficient DIC concentrations while phototrophy causes alkalinization of waters and produces biomass (fatty acids = 7.6 wt.%), a potential feedstock for biofuel production. Tailings storage facilities could be redesigned to promote CO? sequestration by directing leachate waters from tailings piles into specially designed ponds where carbonate precipitation would be mediated by both chemical and biological processes, thereby storing carbon in stable carbonate minerals and potentially valuable biomass.     

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain–gut interactions, but their role in microbiota–neuro–immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut–neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.     

Nonfunctionalized nanocrystals can exploit a cell's active transport machinery delivering them to specific nuclear and cytoplasmic compartments

We use high content cell analysis, live cell fluorescent imaging, and transmission electron microscopy approaches combined with inhibitors of cellular transport and nuclear import to conduct a systematic study of the mechanism of interaction of nonfunctionalized quantum dots (QDs) with live human blood monocyte-derived primary macrophages and cell lines of phagocytic, epithelial, and endothelial nature. Live human macrophages are shown to be able to rapidly uptake and accumulate QDs in distinct cellular compartment specifically to QDs size and charge. We show that the smallest QDs specifically target histones in cell nuclei and nucleoli by a multistep process involving endocytosis, active cytoplasmic transport, and entering the nucleus via nuclear pore complexes. Treatment of the cells with an anti-microtubule agent nocodazole precludes QDs cytoplasmic transport whereas a nuclear import inhibitor thapsigargin blocks QD import into the nucleus. These results demonstrate that the nonfunctionalized QDs exploit the cell's active transport machineries for delivery to specific intranuclear destinations.     

Probing Cell‐Type‐Specific Intracellular Nanoscale Barriers Using Size‐Tuned Quantum Dots

The compartmentalization of size‐tuned luminescent semiconductor nanocrystal quantum dots (QDs) in four distinctive cell lines, which would be representative of the most likely environmental exposure routes to nanoparticles in humans, is studied. The cells are fixed and permeabilized prior to the addition of the QDs, thus eliminating any cell‐membrane‐associated effects due to active QD uptake mechanisms or to specificity of signaling routes in different cell types, but leaving intact the putative physical subcellular barriers. All quantitative assays are performed using a high content analysis (HCA) platform, thereby obtaining robust data on large cell populations. While smaller QDs 2.1 nm in diameter enter the nuclei and localize to the nucleoli in all cell types, the rate and dynamics of their passage vary depending on the cell origin. As the QD size is increased to 4.4 nm, penetration into the cell is reduced but each cell line displays its own cutoff size thresholds reflecting cell‐type‐determined cytoplasmic and nuclear pore penetration specificity. These results give rise to important considerations regarding the differential compartmentalization and susceptibility of organs, tissues, and cells to nanoparticles, and may be of prime importance for biomedical imaging and drug‐delivery research employing nanoparticle‐based probes and systems.     

Lipidomic Analyses of Female Mice Lacking Hepatic Lipase and Endothelial Lipase Indicate Selective Modulation of Plasma Lipid Species

Hepatic lipase (HL) and endothelial lipase (EL) share overlapping and complementary roles in lipoprotein metabolism. The deletion of HL and EL alleles in mice raises plasma total cholesterol and phospholipid concentrations. However, the influence of HL and EL in vivo on individual molecular species from each class of lipid is not known. We hypothesized that the loss of HL, EL, or both in vivo may affect select molecular species from each class of lipids. To test this hypothesis, we performed lipidomic analyses on plasma and livers from fasted female wild-type, HL-knockout, EL-knockout, and HL/EL-double knockout mice. Overall, the loss of HL, EL, or both resulted in minimal changes to hepatic lipids; however, select species of CE were surprisingly reduced in the livers of mice only lacking EL. The loss of HL, EL, or both reduced the plasma concentrations for select molecular species of triacylglycerol, diacylglycerol, and free fatty acid. On the other hand, the loss of HL, EL, or both raised the plasma concentrations for select molecular species of phosphatidylcholine, cholesteryl ester, diacylglycerol, sphingomyelin, ceramide, plasmanylcholine, and plasmenylcholine. The increased plasma concentration of select ether phospholipids was evident in the absence of EL, thus suggesting that EL might exhibit a phospholipase A₂ activity. Using recombinant EL, we showed that it could hydrolyse the artificial phospholipase A₂ substrate 4-nitro-3-(octanoyloxy)benzoic acid. In summary, our study shows for the first time the influence of HL and EL on individual molecular species of several classes of lipids in vivo using lipidomic methods.     

Extreme breeding: Leveraging genomics for crop improvement

The genomic revolution has led to dramatic increases in our understanding of plant biology in the past 10 years, especially in model plant species such as Arabidopsis. The technologies associated with this revolution, such as tilling, array mapping, and association mapping, will see widespread application to crop improvement in the near future. The genes for desirable traits identified through such efforts may be introgressed at an accelerated rate into elite germplasm by marker‐assisted breeding. Copyright © 2007 Society of Chemical Industry