ACTIVE SUPPRESSION AS A POSSIBLE MECHANISM OF TOLERANCE IN TETRAPARENTAL MICE

Previous work has indicated that tetraparental mice, chimeric since the eight-cell stage because of embryo fusion using histoincompatible strain combinations, possess autospecific immune cells and blocking antibodies. Although this phenomenon has been demonstrated in vitro, it may have relevance to the self-tolerance shown by these mice in vivo. The experiments described here indicate that spleen cells from tetraparental mice can block mixed lymphocyte reactions between the two parental cell types, but not between unrelated strains. Furthermore, this suppressive ability is not affected by an otherwise effective treatment of the tetraparental spleen cells with anti-θ antibody and complement. The in vitro experimental system elaborated here should help to characterize the cell type responsible for the suppression

Biomolecular condensation of the microtubule-associated protein tau.

Cells contain multiple compartments dedicated to the regulation and control of biochemical reactions. Cellular compartments that are not surrounded by membranes can rapidly form and dissolve in response to changes in the cellular environment. The physicochemical processes that underlie the formation of non-membrane-bound compartments in vivo are connected to liquid-liquid phase separation of proteins and nucleic acids in vitro. Recent evidence suggests that the protein tau, which plays an important role in Alzheimer's disease and other neurodegenerative disorders, phase separates in solution, forms tau phases with microtubules, and associates with phase-separated RNA-binding protein granules in cells. Here we review the experimental evidence that supports the ability of tau to phase separate in solution and form biomolecular condensates in cells. As for other disease-relevant proteins, the physiological and pathological functions of tau are tightly connected - through loss of normal function or gain of toxic function - and we therefore discuss how tau phase separation plays a role for both, and with respect to different cellular functions of tau

Normalisation against circadian and age-related disturbances enables robust detection of gene expression changes in liver of aged mice

The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature. A subset of genes was selected based on rigorous statistical assessment of their variability using both RNA-sequencing and Nanostring hybridization experiments. The robustness of these marker genes was then verified by the analysis of 130 publicly available data sets using the mouse liver transcriptome. Altogether, a set of three genes, Atp5h, Gsk3β, and Sirt2 fulfilled our strict selection criteria in all assessments, while four more genes, Nono, Tprkb, Tspo, and Ttr passed all but one assessment and were included into the final set of marker genes to enhance robustness of normalisation against outliers. Using the geometric mean of expression of the genes to normalise Nanostring hybridization experiments we reliably identified age-related increases in the expression of Casein kinase 1δ and 1ϵ, and Sfpq, while the expression of the glucose transporter Glut2 decreased. The age- related changes were verified by real-time PCR and Western blot analysis. As conclusion, proper normalisation enhances the robustness of quantitative methods addressing age-related changes of a transcriptome

Rationale for a Stronger Disposition of Chardonnay Wines for Stuck and Sluggish Fermentation

The aim of this study was to identify and evaluate factors that contribute to fermentation problems inChardonnay, since this variety is reported to have frequent problems. Analytical methods included gaschromatography mass spectrometry, as well as atomic absorption spectroscopy and FT-MIR spectroscopy.Chardonnay, Pinot blanc, Pinot noir and Pinot noir précoce were screened to relate observations to specificvarietal properties. The results show a significant distinction in the amino acid profile of Chardonnay,which can be correlated with sluggish fermentation. A comparison between the fatty acid profile ofChardonnay and Pinot blanc reveals that Chardonnay contains more toxic compounds, which inhibityeast metabolism. Mineral supply and potential metal toxicity were also analysed. The concentrationsof iron, copper, magnesium, zinc and manganese show significant variations among the grape varieties.In conclusion, the possible causes for stuck fermentation in Chardonnay could be more related more tovariety than to oenological decisions

No detection of brodifacoum residues in the marine and terrestrial food web three years after rat eradication at Palmyra Atoll, Central Pacific

Invasive alien species represent one of the greatest threats to native plants and animals on islands. Rats (Rattus spp.) have invaded most of the world’s oceanic islands, causing lasting or irreversible damage to ecosystems and biodiversity. To counter this threat, techniques to eradicate invasive rats from islands have been developed and applied across the globe. Eradication of alien rats from large or complex island ecosystems has only been successful with the use of bait containing a rodenticide. While effective at eradicating rats from islands, rodenticide can persist in the ecosystem longer than the time required to eradicate the target rat population and can potentially harm non-target species. However, the persistence of rodenticides in ecosystems following rat eradication campaigns is poorly understood, though predictions can be made based on the chemical properties of the rodenticide and the environment it is applied in. Brodifacoum, a relatively persistent second-generation anticoagulant, was used to successfully eradicate rats from Palmyra Atoll. With this study, we evaluated the persistence of brodifacoum residues in terrestrial and marine species at Palmyra Atoll (Northern Line Islands) three years after rat eradication. We collected 44 pooled samples containing 121 individuals of the following: mullet (Moolgarda engeli), cockroaches (Periplaneta sp.), geckos (Lepidodactylus lugubris), hermit crabs (Coenobita perlatus), and fiddler crabs (Uca tetragonon). Despite detection of brodifacoum residue in all five of the species sampled in this study 60 days after the application of bait to Palmyra Atoll in 2011, brodifacoum residue was not found in any of the pooled samples collected three years after bait application. Our study demonstrates how brodifacoum residues are unlikely to persist in the marine and terrestrial food web, in a wet tropical environment, three years after rat eradication

Nuclear Shape Fluctuations in Fermi-Liquid Drop Model

Within the nuclear Fermi-liquid drop model, quantum and thermal fluctuations are considered by use of the Landau-Vlasov-Langevin equation. The spectral correlation function of the nuclear surface fluctuations is evaluated in a simple model of an incompressible and irrotational Fermi liquid. The dependence of the spectral correlation function on the dynamical Fermi-surface distortion is established. The temperature at which the eigenvibrations become overdamped is calculated. It is shown that, for realistic values of the relaxation time parameter and in the high temperature regime, there is a particular eigenmode of the Fermi liquid drop where the restoring force is exclusively due to the dynamical Fermi-surface distortion.Comment: 23 pages, revtex, file and 3 figures, accepted for publication in Nuclear Physics

β-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of C. eutactus-related strains harboured two GH9-encoding and four GH5-encoding genes, but the strains did not appear to degrade cellulose. Instead, they grew well on β-glucans and one of the strains also grew on galactomannan, galactan, glucomannan and starch. Coprococcus comes and Coprococcus catus strains did not harbour GH9 genes and were not able to grow on β-glucans. Gene expression and proteomic analysis of C. eutactus ART55/1 grown on cellobiose, β-glucan and lichenan revealed similar changes in expression in comparison to glucose. On β-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan led to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, β-glucans are a major growth substrate for species related to C. eutactus, with glucomannan and galactans alternative substrates for some strains

Simultaneous Swift X-ray and UV views of comet C/2007 N3 (Lulin)

We present an analysis of simultaneous X-Ray and UV observations ofcomet C/2007 N3 (Lulin) taken on three days between January 2009 and March 2009 using the Swift observatory. For our X-ray observations, we used basic transforms to account for the movement of the comet to allow the combination of all available data to produce an exposure-corrected image. We fit a simple model to the extracted spectrum and measured an X-ray flux of 4.3+/-1.3 * 10^-13 ergs cm-2 s-1 in the 0.3 to 1.0 keV band. In the UV, we acquired large-aperture photometry and used a coma model to derive water production rates given assumptions regarding the distribution of water and its dissociation into OH molecules about the comet's nucleus. We compare and discuss the X-ray and UV morphology of the comet. We show that the peak of the cometary X-ray emission is offset sunward of the UV peak emission, assumed to be the nucleus, by approximately 35,000 km. The offset observed, the shape of X-ray emission and the decrease of the X-ray emission comet-side of the peak, suggested that the comet was indeed collisionally thick to charge exchange, as expected from our measurements of the comet's water production rate (6--8 10^28 mol. s-1). The X-ray spectrum is consistent with solar wind charge exchange emission, and the comet most likely interacted with a solar wind depleted of very highly ionised oxygen. We show that the measured X-ray lightcurve can be very well explained by variations in the comet's gas production rates, the observing geometry and variations in the solar wind flux.Comment: Paper accepted for publication in Astronomy and Astrophysics, 6 March 2012, 12 pages, 8 colour figures, one tabl

Spectral Analysis of the Chandra Comet Survey

We present results of the analysis of cometary X-ray spectra with an extended version of our charge exchange emission model (Bodewits et al. 2006). We have applied this model to the sample of 8 comets thus far observed with the Chandra X-ray observatory and ACIS spectrometer in the 300-1000 eV range. The surveyed comets are C/1999 S4 (LINEAR), C/1999 T1 (McNaught-Hartley), C/2000 WM1 (LINEAR), 153P/2002 (Ikeya-Zhang), 2P/2003 (Encke), C/2001 Q4 (NEAT), 9P/2005 (Tempel 1) and 73P/2006-B (Schwassmann-Wachmann 3) and the observations include a broad variety of comets, solar wind environments and observational conditions. The interaction model is based on state selective, velocity dependent charge exchange cross sections and is used to explore how cometary X-ray emission depend on cometary, observational and solar wind characteristics. It is further demonstrated that cometary X-ray spectra mainly reflect the state of the local solar wind. The current sample of Chandra observations was fit using the constrains of the charge exchange model, and relative solar wind abundances were derived from the X-ray spectra. Our analysis showed that spectral differences can be ascribed to different solar wind states, as such identifying comets interacting with (I) fast, cold wind, (II), slow, warm wind and (III) disturbed, fast, hot winds associated with interplanetary coronal mass ejections. We furthermore predict the existence of a fourth spectral class, associated with the cool, fast high latitude wind.Comment: 16 pages, 16 figures, and 7 Tables; accepted A&A (Due to space limits, this version has lower resolution jpeg images.