Validation of models for analysis of ranks in horse breeding evaluation

Background

Ranks have been used as phenotypes in the genetic evaluation of horses for a long time through the use of earnings, normal score or raw ranks. A model, ("underlying model" of an unobservable underlying variable responsible for ranks) exists. Recently, a full Bayesian analysis using this model was developed. In addition, in reality, competitions are structured into categories according to the technical level of difficulty linked to the technical ability of horses (horses considered to be the "best" meet their peers). The aim of this article was to validate the underlying model through simulations and to propose a more appropriate model with a mixture distribution of horses in the case of a structured competition. The simulations involved 1000 horses with 10 to 50 performances per horse and 4 to 20 horses per event with unstructured and structured competitions.

Results

The underlying model responsible for ranks performed well with unstructured competitions by drawing liabilities in the Gibbs sampler according to the following rule: the liability of each horse must be drawn in the interval formed by the liabilities of horses ranked before and after the particular horse. The estimated repeatability was the simulated one (0.25) and regression between estimated competing ability of horses and true ability was close to 1. Underestimations of repeatability (0.07 to 0.22) were obtained with other traditional criteria (normal score or raw ranks), but in the case of a structured competition, repeatability was underestimated (0.18 to 0.22). Our results show that the effect of an event, or category of event, is irrelevant in such a situation because ranks are independent of such an effect. The proposed mixture model pools horses according to their participation in different categories of competition during the period observed. This last model gave better results (repeatability 0.25), in particular, it provided an improved estimation of average values of competing ability of the horses in the different categories of events.

Conclusions

The underlying model was validated. A correct drawing of liabilities for the Gibbs sampler was provided. For a structured competition, the mixture model with a group effect assigned to horses gave the best results.     

FCP: functional coverage of the proteome by structures

MOTIVATION: Tools and resources for translating the remarkable growth witnessed in recent years in the number of protein structures determined experimentally into actual gain in the functional coverage of the proteome are becoming increasingly necessary. We introduce FCP, a publicly accessible web tool dedicated to analyzing the current state and trends of the population of structures within protein families. FCP offers both graphical and quantitative data on the degree of functional coverage of enzymes and nuclear receptors by existing structures, as well as on the bias observed in the distribution of structures along their respective functional classification schemes. AVAILABILITY: http://cgl.imim.es/fcp CONTACT: jmestres@imim.es.     

Research involving prisoners: consensus and controversies in international and European regulations

This article examines international and European regulations on research involving prisoners for consensus, differences, and their consequences, and offers a critical evaluation of the various approaches. Agreement exists that prisoners are at risk of coercion, which might interfere with their ability to provide voluntary informed consent to research. Controversy exists about the magnitude of this risk and the consequences that should follow from this risk. Two strategies are proposed for a method of protecting prisoners that does not lead to discrimination: first, more caution to assure non-coerced consent and second, restrictions on the type of research. Most regulations stress the importance of the principle of equivalence of healthcare in places of detention as part of an efficient protection against research risks and discrimination.
All the presented approaches have shortcomings. While 'over-use' of prisoners for research as compared to the general population is ethically unjustified, not granting prisoners access to studies beneficial to their own health because of over-strict regulations is equally unjustified. A middle solution should be preferred, one that grants a minimum of protection together with the lowest possible barriers. Research that does not entail a direct benefit for the individual detainee should be restricted to types of research that have a benefit for detainees as a group and that are of low risk. What will ultimately protect prisoners best, while producing the greatest benefit for them, is access to the same healthcare available to members of the community including research as a true option.     

Functional clustering of mutations in the dimer interface of the nucleotide binding folds of the sulfonylurea receptor

ATP-sensitive K(+) (K(ATP)) channels modulate their activity as a function of inhibitory ATP and stimulatory Mg-nucleotides. They are constituted by two proteins: a pore-forming K(+) channel subunit (Kir6.1, Kir6.2) and a regulatory sulfonylurea receptor (SUR) subunit, an ATP-binding cassette (ABC) transporter that confers MgADP stimulation to the channel. Channel regulation by MgADP is dependent on nucleotide interaction with the cytoplasmic nucleotide binding folds (NBF1 and NBF2) of the SUR subunit. Crystal structures of bacterial ABC proteins indicate that NBFs form as dimers, suggesting that NBF1-NBF2 heterodimers may form in SUR and other eukaryotic ABC proteins. We have modeled SUR1 NBF1 and NBF2 as a heterodimer, and tested the validity of the predicted dimer interface by systematic mutagenesis. Engineered cysteine mutations in this region have significant effects, both positive and negative, on MgADP stimulation of K(ATP) channels in excised patches and on macroscopic channel activity in intact cells. Additionally, the mutations cluster in the model structure according to their functional effect, such that patterns of alteration emerge. Of note, three gain-of-function mutations, leading to MgADP hyperstimulation of the channel, are located in the D-loop region at the center of the predicted dimer interface. Overall, the data support the idea that SUR1 NBFs assemble as heterodimers and that this interaction is functionally critical.     

First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum

Background

Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP.

Results

WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector.

Conclusions

The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1.     

七种糕点对赤拟谷盗(鞘翅目：拟步甲科)感染的抗性（英文）

Biscuits are flour-based products,which areconsumed by majority of people,both old and young,throughout the world and most especially by children,teenagers and mid-adults(Majumder,1970).It can beserved as a desert or snacks and as a breakfast foodwhentaken with beverages.Its ready-to-serve state andlong shelf life contribute to its acceptability by themasses.Wheat as humanfoodis used principallyintheformof flour for baked products such as bread,bis-cuits,pastries and crackers(Kent,1983).In th…     

La diatomée Chaetoceros simplex calcitrans Paulsen et son environnement. II. Effets de la lumière et des irradiations ultra-violettes sur la production primaire et la biosynthèse des stérols

12-day cultures of the diatom Chaetoceros simplex calcitrans Paulsen in sea water have been analysed under different conditions of light. With a $\text{12 h}\text{24 h}$ photophase the primary production is 106 % higher than under continuous light but the unsaponifiable fraction is lower (?42 %) and the sterols increase by 100 %. When ultra-violet irradiation is added to the $\text{12 h}\text{24 h}$ photophase the primary production is lowered (?56 %) but the unsaponifiable fraction increases by 191 %, and the sterols by 110 %. When ultra-violet irradiation is added to the continuous light there is an increase in primary production (+30 %) and a decrease in the unsaponifiable fraction (?16%).Modifications of the sterol composition are reported. C₂₆ sterols have never been detected in these experiments.     

The succinic dehydrogenase activity of eptocephalus dichotomus Baird

Summary The succinic dehydrogenase activity in Streptocephalus dichotomus in the entire animals as well as in the different regions of the body, increased with increase in temperature up to 30°C and at 33°C it decreased.In both males and females there exists a linear relationship between body weight and enzyme activity.Analyses of covariance revealed that the F ratios are not significant in the case of rate of succinic dehydrogenase activity between the two sexes or when the comparison is made within the sexes at the different temperatures.The succinic dehydrogenase activity in the thoracic region is higher than in the head and abdominal regions.This work formed a part of a thesis submitted for the Degree of Doctor of Phylosophy to the University of Madras in 1970.