Binding of 11-cis retinaldehyde to the partially purified cellular retinaldehyde binding protein from bovine retinal pigment epithelium

Summary 11-cis retinaldehyde binding analysis was performed on a bovine retinal pigment epithelium preparation of cellular retinaldehyde binding protein (CRALBP), whose purity degree was estimated as 75%. Equilibrium binding studies were carried out measuring the replacement of tritium-labeled with unlabeled 11-cis retinaldehyde at 25°C. Analysis of the experimental data both by a direct curve-fitting procedure utilizing a non linear least square regression analysis and by a conventional Scatchard plot revealed a single non-interacting binding site with an apparent equilibrium constant of 0.9×10^–7 M.A binding stoichiometry of approximately 1 mol of 11-cis retinaldehyde/mol of binding protein can be calculated from the experimental data. Competition studies carried out in the presence of unlabeled trans and cis isomers of Vitamin A derivatives confirm the high degree of specificity of the 11-cis retinaldehyde binding.     

Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans

Wild isolates of Caenorhabditis elegans can feed either alone or in groups. This natural variation in behaviour is associated with a single residue difference in NPR-1, a predicted G-protein-coupled neuropeptide receptor related to Neuropeptide Y receptors. Here we show that the NPR-1 isoform associated with solitary feeding acts in neurons exposed to the body fluid to inhibit social feeding. Furthermore, suppressing the activity of these neurons, called AQR, PQR and URX, using an activated K(+) channel, inhibits social feeding. NPR-1 activity in AQR, PQR and URX neurons seems to suppress social feeding by antagonizing signalling through a cyclic GMP-gated ion channel encoded by tax-2 and tax-4. We show that mutations in tax-2 or tax-4 disrupt social feeding, and that tax-4 is required in several neurons for social feeding, including one or more of AQR, PQR and URX. The AQR, PQR and URX neurons are unusual in C. elegans because they are directly exposed to the pseudocoelomic body fluid. Our data suggest a model in which these neurons integrate antagonistic signals to control the choice between social and solitary feeding behaviour.     

Functional annotation of a full-length mouse cDNA collection

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.     

Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells

Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.     

Binding of 11-cis retinaldehyde to the partially purified cellular retinaldehyde binding protein from bovine retinal pigment epithelium

11-cis retinaldehyde binding analysis was performed on a bovine retinal pigment epithelium preparation of cellular retinaldehyde binding protein (CRALBP), whose purity degree was estimated as 75%. Equilibrium binding studies were carried out measuring the replacement of tritium-labeled with unlabeled 11-cis retinaldehyde at 25 degrees C. Analysis of the experimental data both by a direct curve-fitting procedure utilizing a non linear least square regression analysis and by a conventional Scatchard plot revealed a single non-interacting binding site with an apparent equilibrium constant of 0.9 X 10(-7) M. A binding stoichiometry of approximately 1 mol of 11-cis retinaldehyde/mol of binding protein can be calculated from the experimental data. Competition studies carried out in the presence of unlabeled 'trans' and 'cis' isomers of vitamin A derivatives confirm the high degree of specificity of the 11-cis retinaldehyde binding.     

The dynamical mass of a classical Cepheid variable star in an eclipsing binary system

Stellar pulsation theory provides a means of determining the masses of pulsating classical Cepheid supergiants-it is the pulsation that causes their luminosity to vary. Such pulsational masses are found to be smaller than the masses derived from stellar evolution theory: this is the Cepheid mass discrepancy problem, for which a solution is missing. An independent, accurate dynamical mass determination for a classical Cepheid variable star (as opposed to type-II Cepheids, low-mass stars with a very different evolutionary history) in a binary system is needed in order to determine which is correct. The accuracy of previous efforts to establish a dynamical Cepheid mass from Galactic single-lined non-eclipsing binaries was typically about 15-30% (refs 6, 7), which is not good enough to resolve the mass discrepancy problem. In spite of many observational efforts, no firm detection of a classical Cepheid in an eclipsing double-lined binary has hitherto been reported. Here we report the discovery of a classical Cepheid in a well detached, double-lined eclipsing binary in the Large Magellanic Cloud. We determine the mass to a precision of 1% and show that it agrees with its pulsation mass, providing strong evidence that pulsation theory correctly and precisely predicts the masses of classical Cepheids.     

低碳锰钢中周期性带状组织

用扫描电镜和电子探针研究了低碳锰钢中的周期性带状组织，结果表明，在全部研究用钢中，钢锭经热轧后均出现这种组织，其严重程度随钢的成分而异，并随坯带加工顺序而增加，带状组织与锰的显微偏析等因素有关，适当的调整碳锰以及形成模跨铁素体带的转变产物可降低带状组织的严重程度。     

Translating cancer research into targeted therapeutics

The emphasis in cancer drug development has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted, rationally designed drugs promising greater efficacy and less side effects. Nevertheless, despite some successes drug development remains painfully slow. Here, we highlight the issues involved and suggest ways in which this process can be improved and expedited. We envision an increasing shift to integrated cancer research and biomarker-driven adaptive and hypothesis testing clinical trials. The goal is the development of specific cancer medicines to treat the individual patient, with treatment selection being driven by a detailed understanding of the genetics and biology of the patient and their cancer.