The Amborella genome: an evolutionary reference for plant biology

The nuclear genome sequence of Amborella trichopoda, the sister species to all other extant angiosperms, will be an exceptional resource for plant genomics

Alcohol dehydrogenase 1B (ADH1B) genotype, alcohol consumption and breast cancer risk by age 50 years in a German case–control study

In a population-based study of 613 cases and 1082 controls, alcohol dehydrogenase 1B (ADH1B) genotype was not an independent risk factor for breast cancer, athough the possibility was raised that it modifies risk associated with high levels of alcohol consumption (OR 1.1, 95% confidence interval (CI) 0.8–1.6 for ADH1B*1/*1 genotype vs 0.2, 95% CI 0.1–1.0 for ADH1B*2 carriers)

Genetic and Microbial Associations to Plasma and Fecal Bile Acids in Obesity Relate to Plasma Lipids and Liver Fat Content

Bile acids (BAs) have been implicated in obesity-related conditions such as NAFLD and hyperlipidemia. Different human BAs exert variable biological activities. Chen et al. define genetic and microbial associations to plasma and fecal BA concentrations and composition in persons with obesity and establish their relationships with liver fat and lipid phenotypes

Role of aldosterone on lung structural remodelling and right ventricular function in congestive heart failure

<p>Abstract</p> <p>Background</p> <p>The mechanisms of benefit of mineralocorticoid receptors antagonists in congestive heart failure (CHF) are still debated. We hypothesized that aldosterone contributes to pulmonary remodelling and right ventricular (RV) dysfunction associated with CHF by stimulation of lung myofibroblasts (MYFs) proliferation.</p> <p>Methods</p> <p>Rats with moderate to large myocardial infarcts (MI) and CHF were studied. Two weeks after MI, spironolactone 100 mg/kg/day (n = 21) or no treatment (n = 24) were given for 3 weeks and compared to sham (n = 8).</p> <p>Results</p> <p>Infarct size was similar by ultrasound and pathologic measures in both MI groups.</p> <p>The MI-untreated group developed important lung remodelling with nearly doubling of dry lung weight (p < 0.01), reduced left ventricular (LV) fractional shortening (16 ± 2% vs. 53 ± 1%; mean ± SEM, p < 0.0001), pulmonary hypertension (RV systolic pressure: 40 ± 3 mmHg vs. 27 ± 1 mmHg, p < 0.01) and RV hypertrophy (RV/(LV + septum): 38 ± 3% vs. 24 ± 1%, p < 0.05). Spironolactone had no effect on these parameters and did not improve LV or RV performance (tricuspid annular plane systolic excursion and RV myocardial performance index) measured by echocardiography. CHF induced a restrictive respiratory syndrome with histological lung fibrosis: this was also unaffected by spironolactone. Finally, isolated lung MYFs did not proliferate after exposure to aldosterone.</p> <p>Conclusion</p> <p>Aldosterone does not significantly contribute to pulmonary remodelling and RV dysfunction associated with CHF. Other mechanisms are responsible for the beneficial effects of spironolactone in CHF.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Floral gene resources from basal angiosperms for comparative genomics research

BACKGROUND: The Floral Genome Project was initiated to bridge the genomic gap between the most broadly studied plant model systems. Arabidopsis and rice, although now completely sequenced and under intensive comparative genomic investigation, are separated by at least 125 million years of evolutionary time, and cannot in isolation provide a comprehensive perspective on structural and functional aspects of flowering plant genome dynamics. Here we discuss new genomic resources available to the scientific community, comprising cDNA libraries and Expressed Sequence Tag (EST) sequences for a suite of phylogenetically basal angiosperms specifically selected to bridge the evolutionary gaps between model plants and provide insights into gene content and genome structure in the earliest flowering plants. RESULTS: Random sequencing of cDNAs from representatives of phylogenetically important eudicot, non-grass monocot, and gymnosperm lineages has so far (as of 12/1/04) generated 70,514 ESTs and 48,170 assembled unigenes. Efficient sorting of EST sequences into putative gene families based on whole Arabidopsis/rice proteome comparison has permitted ready identification of cDNA clones for finished sequencing. Preliminarily, (i) proportions of functional categories among sequenced floral genes seem representative of the entire Arabidopsis transcriptome, (ii) many known floral gene homologues have been captured, and (iii) phylogenetic analyses of ESTs are providing new insights into the process of gene family evolution in relation to the origin and diversification of the angiosperms. CONCLUSION: Initial comparisons illustrate the utility of the EST data sets toward discovery of the basic floral transcriptome. These first findings also afford the opportunity to address a number of conspicuous evolutionary genomic questions, including reproductive organ transcriptome overlap between angiosperms and gymnosperms, genome-wide duplication history, lineage-specific gene duplication and functional divergence, and analyses of adaptive molecular evolution. Since not all genes in the floral transcriptome will be associated with flowering, these EST resources will also be of interest to plant scientists working on other functions, such as photosynthesis, signal transduction, and metabolic pathways

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

The effect of blue light exposure in an ocular melanoma animal model

<p>Abstract</p> <p>Background</p> <p>Uveal melanoma (UM) cell lines, when exposed to blue light in vitro, show a significant increase in proliferation. In order to determine if similar effects could be seen in vivo, we investigated the effect of blue light exposure in a xenograft animal model of UM.</p> <p>Methods</p> <p>Twenty New Zealand albino rabbits were injected with 1.0 × 10⁶human UM cells (92.1) in the suprachoroidal space of the right eye. Animals were equally divided into two groups; the experimental group was exposed to blue light, while the control group was protected from blue light exposure. The eyes were enucleated after sacrifice and the proliferation rates of the re-cultured tumor cells were assessed using a Sulforhodamine-B assay. Cells were re-cultured for 1 passage only in order to maintain any in vivo cellular changes. Furthermore, Proliferating Cell Nuclear Antigen (PCNA) protein expression was used to ascertain differences in cellular proliferation between both groups in formalin-fixed, paraffin-embedded eyes (FFPE).</p> <p>Results</p> <p>Blue light exposure led to a statistically significant increase in proliferation for cell lines derived from intraocular tumors (p < 0.01). PCNA expression was significantly higher in the FFPE blue light treated group when compared to controls (p = 0.0096).</p> <p>Conclusion</p> <p>There is an increasing amount of data suggesting that blue light exposure may influence the progression of UM. Our results support this notion and warrant further studies to evaluate the ability of blue light filtering lenses to slow disease progression in UM patients.</p

Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms

The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values

Patterns of transmitted HIV drug resistance in Europe vary by risk group

Background: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. Methods: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. Results: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). Conclusions: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs