Use of Wishart Prior and Simple Extensions for Sparse Precision Matrix Estimation

A conjugate Wishart prior is used to present a simple and rapid procedure for computing the analytic posterior (mode and uncertainty) of the precision matrix elements of a Gaussian distribution. An interpretation of covariance estimates in terms of eigenvalues is presented, along with a simple decision-rule step to improve the performance of the estimation of sparse precision matrices and associated graphs. In this, elements of the estimated precision matrix that are zero or near zero can be detected and shrunk to zero. Simulated data sets are used to compare posterior estimation with decision-rule with two other Wishart-based approaches and with graphical lasso. Furthermore, an empirical Bayes procedure is used to select prior hyperparameters in high dimensional cases with extension to sparsity.     

Non-Selective Calcium Channel Blocker Bepridil Decreases Secondary Pathology in Mice after Photothrombotic Cortical Lesion

Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPP_SL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPP_SL (n = 33) and non-transgenic (n = 30) male mice (4–5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent Aβ accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPP_SL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia.     

Stable-light producingEscherichia coli

Summary Stable light production inEscherichia coli is achieved by cloning the genes encoding bacterial luciferase fromVibrio harveyi. To gain advantage of sensitive detection of light we transferred the genes under the control of a regulatable promoter system and searched for growth and buffer conditions where bacteria emitted stable light. Based on our findings an automated biosensor system can be developed to monitor the effects of biologically active compounds against stable-light producing bacteria.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

Comparison of diagnostic methods for detection of low infestation levels ofVarroa jacobsoni in honey-bee (Apis mellifera) colonies

Thirty-five honey-bee colonies, originally free fromVarroa jacobsoni (Oudemans) were monitored approximately every third week for the presence of the mite during 16 months following an initial introduction of five to eight adultVarroa females in early July. Investigations of hive debris detected the presence ofV. jacobsoni in 22 colonies (63%) within three months of the mite introduction. During the first winter period (October–April), mites were found in the hive debris of 13 colonies (37%). In terms of detectingVarroa during the summer in colonies with sealed brood, investigations of hive debris were more effective than sampling of brood. Brood sampling was more effective than sampling of live bees. In colonies without sealed brood, investigations of hive debris or of live bee samples seemed approximately equally efficient. The highest correlation between sampling methods was found between daily mite downfall and mites per live bee (r=0.81) in colonies with sealed brood. During the winter, investigations of dead bees and hive debris were approximately equally efficient in detectingVarroa.     

Fidelity of DNA synthesis by the Thermococcus litoralis DNA polymerase--an extremely heat stable enzyme with proofreading activity

We demonstrate that the DNA polymerase isolated from Thermococcus litoralis (VentTM DNA polymerase) is the first thermostable DNA polymerase reported having a 3'----5' proofreading exonuclease activity. This facilitates a highly accurate DNA synthesis in vitro by the polymerase. Mutational frequencies observed in the base substitution fidelity assays were in the range of 30 x 10(-6). These values were 5-10 times lower compared to other thermostable DNA polymerases lacking the proofreading activity. All classes of DNA polymerase errors (transitions, transversions, frameshift mutations) were assayed using the forward mutational assay (1). The mutation frequencies of Thermococcus litoralis DNA polymerase varied between 15-35 x 10(-4) being 2-4 times lower than the respective values obtained using enzymes without proofreading activity. We also noticed that the fidelity of the DNA polymerase from Thermococcus litoralis responds to changes in dNTP concentration, units of enzyme used per one reaction and the concentration of MgSO4 relative to the total concentration of dNTPs present in the reaction. The high fidelity DNA synthesis in vitro by Thermococcus litoralis DNA polymerase provides good possibilities for maintaining the genetic information of original target DNA sequences intact in the DNA amplification applications.     

Serum selenium,glutathione peroxidase,lipids, and human liver microsomal enzyme activity

This study evaluated selenium status in relation to lipid peroxidation, liver microsomal function, and serum lipids in humans. Serum selenium concentration, glutathione peroxidase (GSH-Px) activity, liver microsomal enzyme activity, assessed by plasma antipyrine clearance (AP-CL) rate, and serum lipids were determined in 23 healthy subjects in a double-blind placebo-controlled trial of selenium supplementation. The low selenium concentration (74.0±14.2 μg/L, mean±SD) is attributable to the low selenium content of the diet. Subjects with the lowest selenium levels (n=11) had reduced serum GSH-Px activity, AP-CL rate, high-density lipoprotein cholesterol (HDL-C), and total cholesterol (T-C) as compared with subjects with higher selenium concentrations (n=12). Low AP-CL rates were associated with low HDL-C: T-C ratios. Selenium supplementation, 96 μg/d for 2 wk, increased serum selenium, GSH-Px activity, and the HDL-C: T-C ratio. The results suggest that a low serum selenium level is associated with a decrease in liver microsomal enzyme activity and serum HDL-C and T-C concentrations. Selenium supplementation in subjects with low serum selenium may favorably influence relations between serum lipoproteins connected with the development of atherosclerotic vascular disease.     

Chemical modification of cyclomaltodextrin glucanotransferase from Bacillus circulans var. alkalophilus.

Counting of integral numbers of cysteine residues of the reduced and denaturated form of cyclomaltodextrin glucanotransferase (CGTase) from Bacillus circulans var. alkalophilus (ATCC 21783) showed two cysteine residues per enzyme molecule. Titrations of the enzyme with 5,5'-dithiobis-(2-nitrobenzoic acid) led to the same result. No free SH-group was detected in denatured form of CGTase, indicating that the two cysteine residues are linked by one disulfide bridge. Cyclizing activity of the GdmCl-denaturated and reduced enzyme was 13% of that of the native one. Incubation of CGTase with diethylpyrocarbonate (DEP) showed a pseudo-first-order inhibition with second-order rate constant of 3.2 M-1 s-1. Reaction with hydroxylamine and spectroscopic studies implied that inactivation of CGTase by DEP is due to modification of one histidine residue concomitantly with a 50% decrease in the cyclizing activity (t1/2 = 10.8 min). The inhibition was partially reversible. CGTase was protected against inactivation by alpha- and beta-cyclodextrins suggesting that the modified histidine residue is at or near the active site. Conversion of starch with DEP-modified enzyme resulted in a decreased formation of cyclodextrins while the relative amount of reducing sugars increased. Preliminary results on modification of CGTase with other reagents, e.g., Woodward's reagent K, 2,3-butanedione and carbodiimide are included.