Clustering environment of BL Lac object RGB 1745+398

The BL Lac object RGB 1745+398 lies in an environment that makes it possible to study the cluster around it more deeply than the environments of other BL Lac objects. The cluster centered on the BL Lac works as a strong gravitational lens, forming a large arc around itself. The aim of this paper is to study the environment and characteristics of this object more accurately than the environments of other BL Lac objects have been before.We measured the redshifts of galaxies in the cluster from the absorption lines in their spectra. The velocity dispersion was then obtained from the redshifts. The gravitational lensing was used for measuring the mass at the center of the cluster. The mass of the whole cluster could then be estimated using the softened isothermal sphere mass distribution. Finally, the richness of the cluster was determined by counting the number of galaxies near the BL Lac object and obtaining the galaxy-BL Lac spatial covariance function, $B_{gb}$. The redshifts of nine galaxies in the field were measured to be near the redshift of the BL Lac object, confirming the presence of a cluster. The average redshift of the cluster is 0.268, and the velocity dispersion $(470^{+190}_{-110})$ km s$^{-1}$. The mass of the cluster is M_{500}=(4^{+3}_{-2})\times10^{14} M_{\sun} which implies a rather massive cluster. The richness measurement also suggests that this is a rich cluster: the result for covariance function is $B_{gb}=(600\pm200)$ Mpc$^{1.77}$, which corresponds to Abell richness class 1 and which is consistent with the mass and velocity dispersion of the cluster.Comment: 5 pages, accepted to A&

Synthesis, in vitro and in vivo evaluation of 1,3,5-triazines as cannabinoid CB2 receptor agonists

The cannabinoid receptors type 2 (CBR2) are attractive therapeutic targets of the endocannabinoid signaling system (ECS) as they are not displaying the undesired psychotropic and cardiovascular side-effects seen with cannabinoid receptor type 1 (CB1R) agonists. In continuation of our previous work on 2,4,6-trisubstituted 1,3,5-triazines as potent CB2 agonists, we synthesized an additional series of more polar analogues (1-10), which were found to possess high CB2R agonist activity with enhanced water solubility. The most potent compound in the series was N-(adamantan-1-yl)-4-ethoxy-6-(4-(2-fluoroethyl)piperazin-1-yl)-1,3,5-triazin-2-amine (9) with EC50 value of 0.60nM. To further evaluate the biological effects of the compounds, the selected compounds were tested in vitro against four different cell lines. A human retinal pigment epithelial cell line (ARPE-19) was used to evaluate the cytotoxicity of the compounds whereas an androgen-sensitive human prostate adenocarcinoma cell line (LNCaP), a Jurkat leukemia cell line and a C8161 melanoma cell line were used to assess the antiproliferative activity of the compounds. The most interesting results were obtained for N-(adamantan-1-yl)-4-ethoxy-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (6), which induced cell viability decrease in prostate and leukemia cell lines, and diminished proliferation of C8161 melanoma cells. The results could be reversed in leukemia cells with the selective CB2R antagonist AM630, whereas in prostate cells the AM630 induced a significant cell viability decrease with a mechanism probably unlinked to CB2 cannabinoid receptor. The antiproliferative effect of 6 on the melanoma cells seemed not to be mediated via the CB1R or CB2R. No cytotoxicity was detected against ARPE-19 cell line at concentrations of 1 and 10μM for compound 6. However, at 30μM concentration the compound 6 decreased the cell viability. Finally, in order to estimate in vivo behavior of these compounds, (18)F labeled PET ligand, N-cyclopentyl-4-ethoxy-6-(4-(2-fluoro-18-ethyl)piperazin-1-yl)-1,3,5-triazin-2-amine ([(18)F]5), was synthesized and its biodistribution was determined in healthy male Sprague-Dawley rats. As a result, the tracer showed a rapid (<15min) elimination in urine accompanied by a slower excretion via the hepatobiliary route. In conclusion, we further demonstrated that 1,3,5-triazine scaffold serves as a suitable template for the design of highly potent CB2R agonists with reasonable water solubility properties. The compounds may be useful when studying the role of the endocannabinoid system in different diseases. The triazine scaffold is also a promising candidate for the development of new CB2R PET ligands

Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis

BACKGROUND: Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. METHODS: Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). RESULTS: There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. CONCLUSIONS: Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention

Chicken genome analysis reveals novel genes encoding biotin-binding proteins related to avidin family

BACKGROUND: A chicken egg contains several biotin-binding proteins (BBPs), whose complete DNA and amino acid sequences are not known. In order to identify and characterise these genes and proteins we studied chicken cDNAs and genes available in the NCBI database and chicken genome database using the reported N-terminal amino acid sequences of chicken egg-yolk BBPs as search strings. RESULTS: Two separate hits showing significant homology for these N-terminal sequences were discovered. For one of these hits, the chromosomal location in the immediate proximity of the avidin gene family was found. Both of these hits encode proteins having high sequence similarity with avidin suggesting that chicken BBPs are paralogous to avidin family. In particular, almost all residues corresponding to biotin binding in avidin are conserved in these putative BBP proteins. One of the found DNA sequences, however, seems to encode a carboxy-terminal extension not present in avidin. CONCLUSION: We describe here the predicted properties of the putative BBP genes and proteins. Our present observations link BBP genes together with avidin gene family and shed more light on the genetic arrangement and variability of this family. In addition, comparative modelling revealed the potential structural elements important for the functional and structural properties of the putative BBP proteins

Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns

Background: Inflammatory processes contribute to the pathophysiology of multiple chronic conditions. Genetic factors play a crucial role in modulating the inflammatory load, but the exact mechanisms are incompletely understood.Objective: To assess genetic determinants of 16 circulating cytokines and cell adhesion molecules (inflammatory phenotypes) in Finns.Methods: Genome-wide associations of the inflammatory phenotypes were studied in Northern Finland Birth Cohort 1966 (N=5284). A subsequent meta-analysis was completed for 10 phenotypes available in a previous genome-wide association study, adding up to 13 577 individuals in the study. Complementary association tests were performed to study the effect of the ABO blood types on soluble adhesion molecule levels.Results: We identified seven novel and six previously reported genetic associations (pConclusion: The present results extend the knowledge about genetic factors contributing to the inflammatory load. Our findings suggest that two distinct mechanisms contribute to the soluble adhesion molecule levels in the ABO locus and that elevated soluble adhesion molecule levels per se may not increase risk for cardiovascular disease.</p

The WEBT BL Lac Campaign 2000

We present UBVRI light curves of BL Lacertae from May 2000 to January 2001, obtained by 24 telescopes in 11 countries. More than 15000 observations were performed in that period, which was the extension of the Whole Earth Blazar Telescope (WEBT) campaign originally planned for July-August 2000. Rapid flux oscillations are present all the time, involving variations up to a few tenths of mag on hour time scales, and witnessing an intense intraday activity of this source. Colour indexes have been derived by coupling the highest precision B and R data taken by the same instrument within 20 min and after subtracting the host galaxy contribution from the fluxes. The 620 indexes obtained show that the optical spectrum is weakly sensitive to the long-term trend, while it strictly follows the short-term flux behaviour, becoming bluer when the brightness increases. Thus, spectral changes are not related to the host galaxy contribution, but they are an intrinsic feature of fast flares. We suggest that the achromatic mechanism causing the long-term flux base-level modulation can be envisaged in a variation of the relativistic Doppler beaming factor, and that this variation is likely due to a change of the viewing angle. Discrete correlation function (DCF) analysis reveals the existence of a characteristic time scale of variability of about 7 h in the light curve of the core WEBT campaign, while no measurable time delay between variations in the B and R bands is found.Comment: 14 pages, 8 PostScript figures, 5 JPEG figures, in press for A&

Terveydenhuollon kansalliset laaturekisteripilotit loppusuoralla

Pilottiprojektin tulokset laaturekisterien toiminnan organisoimisesta kannustavat ­jatkamaan työtä moniammatillisesti ja pitkäjänteisesti. Kansallinen koordinaatio on välttämätöntä laatu- ja vaikuttavuustiedon vertailukelpoisuuden ja hyödyntämisen varmistamiseksi