Functional linear models for region-based association analysis

Regional association analysis is one of the most powerful tools for gene mapping because instead analysis of individual variants it simultaneously considers all variants in the region. Recent development of the models for regional association analysis involves functional data analysis approach. In the framework of this approach, genotypes of variants within region as well as their effects are described by continuous functions. Such approach allows us to use information about both linkage and linkage disequilibrium and reduce the influence of noise and/or observation errors. Here we define a functional linear mixed model to test association on independent and structured samples. We demonstrate how to test fixed and random effects of a set of genetic variants in the region on quantitative trait. Estimation of statistical properties of new methods shows that type I errors are in accordance with declared values and power is high especially for models with fixed effects of genotypes. We suppose that new functional regression linear models facilitate identification of rare genetic variants controlling complex human and animal traits. New methods are implemented in computer software FREGAT which is available for free download at http://mga.bionet.nsc.ru/soft/FREGAT/.     

Honeybee Colony Vibrational Measurements to Highlight the Brood Cycle

Insect pollination is of great importance to crop production worldwide and honey bees are amongst its chief facilitators. Because of the decline of managed colonies, the use of sensor technology is growing in popularity and it is of interest to develop new methods which can more accurately and less invasively assess honey bee colony status. Our approach is to use accelerometers to measure vibrations in order to provide information on colony activity and development. The accelerometers provide amplitude and frequency information which is recorded every three minutes and analysed for night time only. Vibrational data were validated by comparison to visual inspection data, particularly the brood development. We show a strong correlation between vibrational amplitude data and the brood cycle in the vicinity of the sensor. We have further explored the minimum data that is required, when frequency information is also included, to accurately predict the current point in the brood cycle. Such a technique should enable beekeepers to reduce the frequency with which visual inspections are required, reducing the stress this places on the colony and saving the beekeeper time.     

Direct and Conceptual Replications of Burgmer & Englich (2012): Power May Have Little to No Effect on Motor Performance

Burgmer and Englich (2012) have reported that manipulating feelings of power can substantially improve performance on two motor tasks: golf and darts. We conducted two high-powered direct replications of the effects of power on golf, two online conceptual replications using mirror-tracing as a performance measure, and an additional conceptual replication using a cognitive performance measure (word-search). Overall, we found little to no effect of power on motor skill (d = 0.09, 95% CI[-0.07, 0.22], n = 603). We varied task difficulty, re-analyzed data without participants showing weak responses on manipulation checks, and tried adjusting performance scores for age, gender, and initial task skill. None of these secondary analyses revealed a strong effect of power on performance. A meta-analysis integrating our data with Burgmer & Englich leaves open the possibility that manipulating power could provide a modest boost in motor skill (d = 0.19, 95% CI [0.001, 0.38], n = 685). Unfortunately, the pattern of performance changes we observed was unrelated to group differences in perceived and rated power, suggesting that what motor effects do occur with this protocol may not be directly related to the construct of power. [Burgmer, P., &Englich, B. (2012). Bullseye!: How Power Improves Motor Performance. Social Psychological and Personality Science, 4(2), 224–232.]     

Probing alamethicin channels with water-soluble polymers. Effect on conductance of channel states.

Channel access resistance has been measured to estimate the characteristic size of a single ion channel. We compare channel conductance in the presence of nonpenetrating water-soluble polymers with that obtained for polymer-free electrolyte solution. The contribution of the access resistance to the total alamethicin channel resistance is approximately 10% for first three open channel levels. The open alamethicin channel radii inferred for these first three levels from the access resistance are 6.3, 10.3, and 11.4 A. The dependence of channel conductance on polymer molecular weight also allows evaluation of the channel dimensions from polymer exclusion. Despite varying conductance, it was shown that steric radii of the alamethicin channel at different conductance levels remain approximately unchanged. These results support a model of the alamethicin channel as an array of closely packed parallel pores of nearly uniform diameter.     

Suppression of dexamethasone-stimulated DNA synthesis in an oncogene construct containing rat cell line by a DNA site-oriented ligand of poly-ADP-ribose polymerase: 6-amino-1,2-benzopyrone

The cellular inhibitory effects of 6-amino-1,2-benzopyrone (6-ABP), a DNA site-specific ligand of adenosine diphosphoribosyl transferase (ADPRT), were determined in a dexamethasone-sensitive EJ-ras gene construct containing cell line (14C cells). Dexamethasone in vitro transforms these cells to a tumorigenic phenotype and also stimulates cell replication. At a non-toxic concentrations (0.2 mM) 6-ABP treatment of intact cells for 4 days inhibits the dexamethasone-stimulated increment of cellular DNA content, depresses replicative DNA synthesis as assayed by thymidine incorporation to the level of cells that were not exposed to dexamethasone, and in permeabilized cells reduces the dexamethasone-stimulated increase of deoxyribonucleotide incorporation into DNA to the level of untreated cells. In situ pulse labeling of cells pretreated with 6-ABP indicated an inhibition of DNA synthesis at a stage prior to the formation of the 10-kb intermediate species. The drug had no direct effect on cellular DNA polymerases as tested in vitro, and the inhibition of DNA synthesis in permeabilized cells following drug treatment for 4 days was abolished by externally added DNA templates. Neither dexamethasone nor the drug influenced the cellular quantity of ADPRT molecules, tested immunochemically.     

Chemical and microbiological solubilization of silicates

The solubilization of silicates was investigated using kaolin and quartz sand as model substances. The mineral solubilization was studied in the concentration of solubilized Si and Al. The chemical leaching of the silicates was carried out using inorganic and organic acids as well as sodium hydroxide. The process was more effective in the alkine than in the acid pH range. In the acid medium, oxalic acid showed maximum acidity and a tendency to form complex structures, especially with aluminium, and was most effective in leaching. The microbiological influence on solubilization reactions was tested using a number of microorganisms among them acid, alkali and slime-forming species. The highest leaching activity was observed in the case of Thiobacillus thiooxidans, whereas the heterotrophic microorganisms (among them Bacillus mucilaginosus) did not exercise a sollubilizing effect on the silicates. X-ray phase analysis of leached kaolin samples did not show any differences from the non-leached mineral.     

Rapid activation of astrocyte-specific expression of GFAP-lacZ transgene by focal injury

Astrocytes form a key cellular component of the central nervous system. They respond vigorously to diverse neurologic insults by undergoing hypertrophy and increasing expression of the glial fibrillary acidic protein (GFAP) gene, but their functions are largely unknown. To analyze astrocytes in vivo we constructed a transgenic vector from GFAP gene sequences and monitored its efficiency by fusing it to lacZ. Injection of the GFAP-lacZ hybrid gene into the germline of mice yielded six different lines of transgenic mice. In all lines the expression of lacZ was astrocyte-specific. In unmanipulated transgenic animals beta-galactosidase activity was much more prominent in astrocytes of the hippocampal formation, selected white matter tracts, and glial limitans than in astrocytes of other areas. This pattern of expression illustrates the physiologic heterogeneity of astrocytes and probably reflects differences in functional demands placed on these cells in different brain regions. Upmodulation of transgene expression was used to determine the time frame within which astroglial activation and increased GFAP gene expression occur following a neurologic insult. Induction of GFAP-lacZ expression was detectable within 1 hour after focal mechanical trauma. This demonstrates that the response of astrocytes to neurologic injury is very rapid and implies that these cells could fulfill important early functions in wound healing within the central nervous system.     

Improvement of a Vero cell assay to determine diphtheria antitoxin content in sera

Diphtheria antitoxin content in sera were determined automatically in Vero cell assay by spectrophotometric determination of the equivalence point between toxin and antitoxin followed by computer analysis of absorption values. The method was more accurate than visual reading and made handling of many samples easy.