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.     

Industrial Pentachlorophenol Poisoning in Winnipeg

Enquiry into the occupational history of a patient presenting with stupor, hyperpyrexia and profuse sweating, and dying at a Winnipeg hospital a few hours later in coma, finally led to the identification of pentachlorophenol-a substance widely used as a wood preservative-as the cause of death of this worker and the cause of non-fatal intoxication in four other workers engaged by wood-processing plants. In these latter four cases the prominent clinical symptoms were sweating, weight loss and gastrointestinal complaints. A review of the literature revealed that pentachlorophenol exerts its toxicity following cutaneous absorption or inhalation by interference with oxidative phosphorylation, resulting in excessive release of heat. This substance has been the cause of several deaths in other countries. Observance of simple precautionary measures that ensure adequate ventilation and skin protection should suffice in making this industrially useful product safe.     

Airway contractility and smooth muscle Ca(2+) signaling in lung slices from different mouse strains.

To investigate the hypothesis that altered Ca2+ signaling in airway smooth muscle cells (SMCs) is responsible for airway hyperreactivity, we compared, with the use of confocal and phase-contrast microscopy, the airway contractility and Ca2+ changes in SMCs induced by acetylcholine (ACh) in lung slices from different mouse strains (A/J, Balb/C, and C3H/ HeJ). The airways from each mouse strain displayed a concentration-dependent contraction to ACh. The contractile response of the airways of the C3H/HeJ mice was found, in contrast to earlier studies, to be much greater and faster than that of A/J and Balb/C mice. This difference in airway reactivity can be, in part, attributable to halothane, a volatile anesthetic that was previously used during in vivo measurements of airway reactivity but found here to significantly alter the ACh contractile response of airways in lung slices. The ACh-induced Ca2+ response of the airway SMCs in all of the various mouse strains was also concentration dependent. The magnitude of the initial Ca2+ increase and the frequency of the subsequent Ca2+ oscillations induced by ACh increased with ACh concentration. However, no differences in the Ca2+ responses to ACh could be distinguished between the mouse strains. These results suggest that the mechanism responsible for airway hyperreactivity in different mouse strains resides with the Ca2+ sensitivity of the contractile apparatus of the SMCs rather than with the Ca2+ signaling itself.     

Biological activity of gibberellin analogues

In order to determine the significance of the C-6 carboxyl group for the biological activity gibberellin A₃, 6-epigibberellin A₃, 7-norgibberellin A₃, 6-methyl-7-norgibberellin A₃, and 7-homogibberellin A₃ were studied using dwarf pea, dwarf maize, dwarf rice, dwarf barley and -amylase bioassays. All gibberellin A₃(GA₃)derivatives tested were considerably less active than GA₃. In all biossays, 6-epi-GA₃ showed a low activity of the same order, whereas 6-methyl-7-nor-GA₃ was inactive. Surprisingly, 7-nor-GA₃ had some activity in the dwarf rice (root application), dwarf barley, and -amylase bioassay, in contrary to its low potency in the dwarf pea, dwarf maize, and dwarf rice (micro drop) bioassay. 7-Homo-GA₃ was primarily active in the dwarf maize, dwarf barley and dwarf rice bioassay. It also caused antigibberellin effects in dwarf rice. The results demonstrate that the C-6 carboxyl group is not absolutely essential for biological activity of gibberellins. The different activities of 7-nor-GA₃ observed in the various test systems may indicate that the C-6 carboxyl group is a structural requirement more for uptake and/or transport processes than for receptor affinity.Abbreviation GA₃ gibberellic acid     

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.     

The human mast cell tryptase tetramer: a fascinating riddle solved by structure

Tryptases, the predominant proteins of human mast cells, have been implicated as pathogenetic mediators of allergic and inflammatory conditions, most notably asthma. Until recently, the fascinating properties that distinguish tryptases among the serine proteinases, particularly their activity as a heparin-stabilized tetramer, resistance to most proteinaceous inhibitors, and preference for peptidergic over macromolecular substrates presented a riddle. This review solves this riddle with the help of the crystal structure of the human beta(2)-tryptase tetramer, but also indicates controversies between the unique quaternary architecture and some experimental data.     

Fatty Acid Transport and Utilization for the Developing Brain

Abstract: To determine the transport and utilization of dietary saturated, monounsaturated, and n-6 and n-3 polyunsaturated fatty acids for the developing brain and other organs, artificially reared rat pups were fed a rat milk substitute containing the perdeuterated (each 97 atom% deuterium) fatty acids, i.e., palmitic, stearic, oleic, linoleic, and linolenic, from day 7 after birth to day 14 as previously described. Fatty acids in lipid extracts of the liver, lung, kidney, and brain were analyzed by gas chromatography-mass spectrometry to determine their content of each of the deuterated fatty acids. The uptake and metabolism of perdeuterated fatty acid lead to the appearance of three distinct groups of isotopomers: the intact perdeuterated, the newly synthesized (with recycled deuterium), and the natural unlabeled fatty acid. The quantification of these isotopomers permits the estimation of uptake and de novo synthesis of these fatty acids. Intact perdeuterated palmitic, stearic, and oleic acids from the diet were found in liver, lung, and kidney, but not in brain. By contrast, perdeuterated linoleic acid was found in all these organs. Isotopomers of fatty acid from de novo synthesis were observed in palmitic, oleic, and stearic acids in all tissues. The highest enrichment of isotopomers with recycled deuterium was found in the brain. The data indicate that, during the brain growth spurt and the prelude to myelination, the major saturated and monounsaturated fatty acids in brain lipids are exclusively produced locally by de novo biosynthesis. Consequently, the n-6 and n-3 polyunsaturated fatty acids must be transported and delivered to the brain by highly specific mechanisms.     

The head-fixed behaving rat--procedures and pitfalls

This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models--the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging.