Relationship Information (relationship + information)

Distribution by Scientific Domains


Selected Abstracts


The use of marker-based relationship information to estimate the heritability of body weight in a natural population: a cautionary tale

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2002
S. C. Thomas
A number of procedures have been developed that allow the genetic parameters of natural populations to be estimated using relationship information inferred from marker data rather than known pedigrees. Three published approaches are available; the regression, pair-wise likelihood and Markov Chain Monte Carlo (MCMC) sib-ship reconstruction methods. These were applied to body weight and molecular data collected from the Soay sheep population of St. Kilda, which has a previously determined pedigree. The regression and pair-wise likelihood approaches do not specify an exact pedigree and yielded unreliable heritability estimates, that were sensitive to alteration of the fixed effects. The MCMC method, which specifies a pedigree prior to heritability estimation, yielded results closer to those determined using the known pedigree. In populations of low average relationship, such as the Soay sheep population, determination of a reliable pedigree is more useful than indirect approaches that do not specify a pedigree. [source]


Synthesis, in-vitro Cytotoxicity, and a Preliminary Structure-Activity Relationship Investigation of Pyrimido[4,5- c]quinolin-1(2H)-ones

ARCHIV DER PHARMAZIE, Issue 8 2010
Kamel Metwally
Abstract As part of our ongoing research effort to develop new antimitotic agents based on the recently reported pyrimido[4,5- c]quinoline-1(2H)-one ring skeleton, we were interested in identifying structural elements that contribute to the cytotoxicity of this class of compounds. The effect of several quinoline-ring substituents was examined and the new compounds were evaluated in vitro for cytotoxicity against three human cancer cell lines namely, lung fibrosarcoma HT-1080, colon adenocarcinoma HT-29, and breast carcinoma MDA-MB-231. Most of the compounds showed cytotoxic activity in the low micromolar and sub-micromolar range. Structure-activity relationship information revealed that a combination of electronic and steric factors may be involved. Flow cytometric cell cycle analysis performed on HT-1080 cells revealed that the most cytotoxic compounds 48, 50, 54, 59, and 63 inhibit the S-phase and arrest the cells in the G2/M phase of the cell cycle suggesting an antimitotic action of these compounds. [source]


Research Article: Effective and Specific Inhibition of the CD40,CD154 Costimulatory Interaction by a Naphthalenesulphonic Acid Derivative

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2010
Emilio Margolles-Clark
Costimulatory interactions are important regulators of T-cell activation and, hence, promising therapeutic targets in autoimmune diseases as well as in transplant recipients. Following our recent identification of the first small-molecule inhibitors of the CD40,CD154 costimulatory protein,protein interaction (J Mol Med 87, 2009, 1133), we continued our search within the chemical space of organic dyes, and we now report the identification of the naphthalenesulphonic acid derivative mordant brown 1 as a more active, more effective, and more specific inhibitor. Flow cytometry experiments confirmed its ability to concentration-dependently inhibit the CD154(CD40L)-induced cellular responses in human THP-1 cells at concentrations well below cytotoxic levels. Binding experiments showed that it not only inhibits the CD40,CD154 interaction with sub-micromolar activity, but it also has considerably more than 100-fold selectivity toward this interaction even when compared to other members of the tumor necrosis factor superfamily pairs such as TNF-R1,TNF-,, BAFF-R(CD268),BAFF(CD257/BLys), OX40(CD134),OX40L(CD252), RANK(CD265),RANKL(CD254/TRANCE), or 4-1BB(CD137),4-1BBL. There is now sufficient structure-activity relationship information to serve as the basis of a drug discovery initiative targeting this important costimulatory interaction. [source]