From molecular noise to behavioural variability in a single bacterium

The chemotaxis network that governs the motion of Escherichia coli has long been studied to gain a general understanding of signal transduction. Although this pathway is composed of just a few components, it exhibits some essential characteristics of biological complexity, such as adaptation and response to environmental signals. In studying intracellular networks, most experiments and mathematical models have assumed that network properties can be inferred from population measurements. However, this approach masks underlying temporal fluctuations of intracellular signalling events. We have inferred fundamental properties of the chemotaxis network from a noise analysis of behavioural variations in individual bacteria. Here we show that certain properties established by population measurements, such as adapted states, are not conserved at the single-cell level: for timescales ranging from seconds to several minutes, the behaviour of non-stimulated cells exhibit temporal variations much larger than the expected statistical fluctuations. We find that the signalling network itself causes this noise and identify the molecular events that produce it. Small changes in the concentration of one key network component suppress temporal behavioural variability, suggesting that such variability is a selected property of this adaptive system.     

Palaeogeography: Devonian tetrapod from western Europe

Several discoveries of Late Devonian tetrapods (limbed vertebrates) have been made during the past two decades, but each has been confined to one locality. Here we describe a tetrapod jaw of about 365 million years (Myr) old from the Famennian of Belgium, which is the first from western continental Europe. The jaw closely resembles that of Ichthyostega, a Famennian tetrapod hitherto known only from Greenland. The environment of this fossil provides information about the conditions that prevailed just before the virtual disappearance of tetrapods from the fossil record for 20 Myr.     

The origin of red algae and the evolution of chloroplasts

Chloroplast structure and genome analyses support the hypothesis that three groups of organisms originated from the primary photosynthetic endosymbiosis between a cyanobacterium and a eukaryotic host: green plants (green algae + land plants), red algae and glaucophytes (for example, Cyanophora). Although phylogenies based on several mitochondrial genes support a specific green plants/red algae relationship, the phylogenetic analysis of nucleus-encoded genes yields inconclusive, sometimes contradictory results. To address this problem, we have analysed an alternative nuclear marker, elongation factor 2, and included new red algae and protist sequences. Here we provide significant support for a sisterhood of green plants and red algae. This sisterhood is also significantly supported by a multi-gene analysis of a fusion of 13 nuclear markers (5,171 amino acids). In addition, the analysis of an alternative fusion of 6 nuclear markers (1,938 amino acids) indicates that glaucophytes may be the closest relatives to the green plants/red algae group. Thus, our study provides evidence from nuclear markers for a single primary endosymbiosis at the origin of these groups, and supports a kingdom Plantae comprising green plants, red algae and glaucophytes.     

Modulation of Saturn's radio clock by solar wind speed

The internal rotation rates of the giant planets can be estimated by cloud motions, but such an approach is not very precise because absolute wind speeds are not known a priori and depend on latitude: periodicities in the radio emissions, thought to be tied to the internal planetary magnetic field, are used instead. Saturn, despite an apparently axisymmetric magnetic field, emits kilometre-wavelength (radio) photons from auroral sources. This emission is modulated at a period initially identified as 10 h 39 min 24 +/- 7 s, and this has been adopted as Saturn's rotation period. Subsequent observations, however, revealed that this period varies by +/-6 min on a timescale of several months to years. Here we report that the kilometric radiation period varies systematically by +/-1% with a characteristic timescale of 20-30 days. Here we show that these fluctuations are correlated with solar wind speed at Saturn, meaning that Saturn's radio clock is controlled, at least in part, by conditions external to the planet's magnetosphere. No correlation is found with the solar wind density, dynamic pressure or magnetic field; the solar wind speed therefore has a special function. We also show that the long-term fluctuations are simply an average of the short-term ones, and therefore the long-term variations are probably also driven by changes in the solar wind.     

新物相Eu2P2Se6的合成与表征

用高温固相反应合成新物相Ｅｕ２Ｐ２Ｓｅ６．Ｅｕ２Ｐ２Ｓｅ６的晶体结构由ＸＲＤ经Ｒｉｅｔｖｅｌｄ方法修正得到,其空间群为Ｐ２１／ｎ,晶胞参数：ａ＝０．９７９０（１７）ｎｍ,ｂ＝０．７７７５（４）ｎｍ,ｃ＝０．６９２７（１２）ｎｍ,β＝９１．４５（３）°,Ｚ＝２．阴离子基团Ｐ２Ｓｅ６４－由Ｒａｍａｎ光谱确证;磁性研究结果表明标题化合物的顺磁离子为Ｅｕ２＋．     

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.     

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.     

Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat metabolism

The LIM domain only 4 (LMO4) protein is expressed in the hypothalamus, but its function there is not known. Using mice with LMO4 ablated in postnatal glutamatergic neurons, including most neurons of the paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei where LMO4 is expressed, we asked whether LMO4 is required for metabolic homeostasis. LMO4 mutant mice exhibited early onset adiposity. These mice had reduced energy expenditure and impaired thermogenesis together with reduced sympathetic outflow to adipose tissues. The peptide hormone leptin, produced from adipocytes, activates Jak/Stat3 signaling at the hypothalamus to control food intake, energy expenditure, and fat metabolism. Intracerebroventricular infusion of leptin suppressed feeding similarly in LMO4 mutant and control mice. However, leptin-induced fat loss was impaired and activation of Stat3 in the VMH was blunted in these mice. Thus, our study identifies LMO4 as a novel modulator of leptin function in selective hypothalamic nuclei to regulate fat metabolism.     

The intestinal epithelium tuft cells: specification and function

The intestinal epithelium, composed of at least seven differentiated cell types, represents an extraordinary model to understand the details of multi-lineage differentiation, a question that is highly relevant in developmental biology as well as for clinical applications. This review focuses on intestinal epithelial tuft cells that have been acknowledged as a separate entity for more than 60?years but whose function remains a mystery. We discuss what is currently known about the molecular basis of tuft cell fate and differentiation and why elucidating tuft cell function has been so difficult. Finally, we summarize the current hypotheses on their potential involvement in diseases of the gastro-intestinal tract.