Selecting high-dimensional mixed graphical models using minimal AIC or BIC forests

Background  

Chow and Liu showed that the maximum likelihood tree for multivariate discrete distributions may be found using a maximum weight spanning tree algorithm, for example Kruskal's algorithm. The efficiency of the algorithm makes it tractable for high-dimensional problems.     

Deletion analysis of the essentiality of penicillin-binding proteins 1A, 2B and 2X of Streptococcus pneumoniae

Abstract An internal fragment from each of the penicillinebinding protein (PBP) 1A, 2B and 2X genes of Streptococcus pneumoniae , which included the region encoding the active-site serine residue, was replaced by a fragment encoding spectinomycin resistance. The resulting constructs were tested for their ability to transform S. pneumoniae strain R6 to spectinomycin resistance. Spectinomycin-resistant transformants could not be obtained using either the inactivated PBP 2X or 2B genes, suggesting that deletion of either of these genes was a lethal event, but they were readily obtained using the inactivated PBP 1A gene. Analysis using the polymerase chain reaction confirmed that the latter transformants had replaced their chromosomal copy of the PBP 1A gene with the inactivated copy of the gene. Deletion of the PBP 1A gene was therefore tolerated under laboratory conditions and appeared to have little effect on growth or susceptibility to benzylpenicillin.     

Genetics of high level penicillin resistance in clinical isolates of Streptococcus pneumoniae

Abstract Mosaic penicillin-binding proteins (PBP) 1A, 2X and 2B genes were cloned from four clinical isolates of Streptococcus pneumoniae with levels of susceptibility to penicillin ranging from 1.5 to 16 μg benzylpenicillin ml⁻¹. In each instance it was possible to transform either the penicillin-sensitive laboratory strain R6 or a sensitive clinical isolate 110K/70 to the full level of penicillin resistance with these three penicillin-binding proteins alone. Until now it has not been possible to clearly determine whether alterations to PBP1A, 2X and 2B alone were sufficient to attain high level penicillin resistance.     

Enlarging a training set for genomic selection by imputation of un-genotyped animals in populations of varying genetic architecture

Background

The most common application of imputation is to infer genotypes of a high-density panel of markers on animals that are genotyped for a low-density panel. However, the increase in accuracy of genomic predictions resulting from an increase in the number of markers tends to reach a plateau beyond a certain density. Another application of imputation is to increase the size of the training set with un-genotyped animals. This strategy can be particularly successful when a set of closely related individuals are genotyped.

Methods

Imputation on completely un-genotyped dams was performed using known genotypes from the sire of each dam, one offspring and the offspring’s sire. Two methods were applied based on either allele or haplotype frequencies to infer genotypes at ambiguous loci. Results of these methods and of two available software packages were compared. Quality of imputation under different population structures was assessed. The impact of using imputed dams to enlarge training sets on the accuracy of genomic predictions was evaluated for different populations, heritabilities and sizes of training sets.

Results

Imputation accuracy ranged from 0.52 to 0.93 depending on the population structure and the method used. The method that used allele frequencies performed better than the method based on haplotype frequencies. Accuracy of imputation was higher for populations with higher levels of linkage disequilibrium and with larger proportions of markers with more extreme allele frequencies. Inclusion of imputed dams in the training set increased the accuracy of genomic predictions. Gains in accuracy ranged from close to zero to 37.14%, depending on the simulated scenario. Generally, the larger the accuracy already obtained with the genotyped training set, the lower the increase in accuracy achieved by adding imputed dams.

Conclusions

Whenever a reference population resembling the family configuration considered here is available, imputation can be used to achieve an extra increase in accuracy of genomic predictions by enlarging the training set with completely un-genotyped dams. This strategy was shown to be particularly useful for populations with lower levels of linkage disequilibrium, for genomic selection on traits with low heritability, and for species or breeds for which the size of the reference population is limited.     

Bacterial colonization of Hydra hatchlings follows a robust temporal pattern

Animals are colonized by complex bacterial communities. The processes controlling community membership and influencing the establishment of the microbial ecosystem during development are poorly understood. Here we aimed to explore the assembly of bacterial communities in Hydra with the broader goal of elucidating the general rules that determine the temporal progression of bacterial colonization of animal epithelia. We profiled the microbial communities in polyps at various time points after hatching in four replicates. The composition and temporal patterns of the bacterial communities were strikingly similar in all replicates. Distinct features included high diversity of community profiles in the first week, a remarkable but transient adult-like profile 2 weeks after hatching, followed by progressive emergence of a stable adult-like pattern characterized by low species diversity and the preponderance of the Betaproteobacterium Curvibacter. Intriguingly, this process displayed important parallels to the assembly of human fecal communities after birth. In addition, a mathematical modeling approach was used to uncover the organizational principles of this colonization process, suggesting that both, local environmental or host-derived factor(s) modulating the colonization rate, as well as frequency-dependent interactions of individual bacterial community members are important aspects in the emergence of a stable bacterial community at the end of development.     

Does small-sided-games’ court area influence metabolic,perceptual, and physical performance parameters of young elite basketball players?

The purpose of this study was to investigate the effect of court size on physiological responses and physical performance of young elite basketball players. Twelve male basketball players (18.6 ± 0.5 years; 88.8 ± 14.5 kg; 192.6 ± 6.5 cm) from an under-19 team performed two small-sided games (matches) with different court areas (28x15 m and 28x9 m; 28x15 and 28x9 protocols). The number of players (3x3) was kept the same in each protocol. The players performed a repeated-sprint ability (RSA) test before and after each match. Blood lactate concentration was collected before (pre) and after (post) the matches, and the session rating of perceived exertion (session-RPE) was determined 30 minutes after the match. Best and mean time in the RSA test were not different between the 28x15 and the 28x9 match protocols (p > 0.05). A significant difference was observed for lactate concentration from pre- to post-match (p < 0.05) in both protocols (28x15 and 28x9); however, there was no significant interaction between protocols. A similar session-RPE mean score (28x15: 7.2 ± 1.4 and 28x9: 6.6 ± 1.4) was detected for both protocols (p > 0.05, ES=0.41). In summary, the results of the current study suggest that the different court areas induced similar responses. Although there was no significant difference in effort perception, players tended to perceive a greater effort in the larger court size.     

Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors

Ligase MurM catalyses the addition of Ala from alanyl-tRNA^Ala, or Ser from seryl-tRNA^Ser, to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNA^Ala showed no inhibition of MurM, but adenosine 3′-phosphonate analogues showed inhibition of MurM, the most active being a 2′-deoxyadenosine analogue (IC₅₀ 100 μM). Structure/function studies upon this analogue established that modification of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modification of the adenosine 5′-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria.