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.     

Membrane-associated interleukin 1 is required for the activation of T cells in the anti-CD3 antibody-induced T cell response

To establish the role of the membrane-associated form of IL 1 in T cell activation, we tested the accessory function of monocytes (Mo) that were unable to secrete or release soluble IL 1. The data obtained show that strictly purified resting T cells start to proliferate in response to anti-CD3 antibody (OKT3) stimulation in the presence of paraformaldehyde (PFA)-fixed Mo or 3-day cultured Mo (macrophages). The findings that i) PFA-fixed Mo did not produce or release IL 1, ii) the accessory function of PFA-fixed Mo could be inhibited with pretreatment with anti-IL 1 antibody, iii) PFA-fixed Mo had a comitogenic effect in the murine thymocyte assay, and iv) there was a temporal difference between the capacities to function in the comitogenic assay and to produce soluble IL 1, suggest that human Mo can express membrane-associated IL 1 and that it is functionally relevant.     

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.     

Characterization of natural killer cells and their precursors in the murine bone marrow

We have fractionated murine bone marrow cells according to their density on bovine serum albumin (BSA) gradient and studied (a) the NK activity against YAC-1 targets, (b) the proportion of asialo GM1+ lymphocytes, (c) and the presence of large granular lymphocytes (LGL) in the different fractions (A, B, C, D). The NK activity was found mainly in the C fraction, but the proportion of asialo GM1+ cells was the same in every fraction. No LGLs were found in the bone marrow. Cells from the various fractions were also transplanted into irradiated recipients. Seven days later the highest NK activity was found in the spleens of mice injected with cells from the A + B fractions indicating that the immediate precursors for NK cells reside in the low density fractions of the BSA gradient. Mice transplanted with C or D fractions needed longer time to develop normal NK levels. The treatment of bone marrow cells before transplantation with anti-asialo GM1+ complement did not inhibit the development of NK activity, so it can be concluded that the precursor for NK is asialo GM1-.     

Uukuniemi virus maturation: immunofluorescence microscopy with monoclonal glycoprotein-specific antibodies.

Monoclonal antibodies directed against Uukuniemi virus glycoproteins G1 and G2 in combination with polyclonal antibodies against the nucleoprotein (N) were used to study the maturation of the virus in Golgi complexes of infected chicken embryo fibroblasts and BHK cells. Of 25 monoclonal antibodies obtained, 10 were shown to be G1 specific and 15 were shown to be G2 specific by immunoblotting and immunoprecipitation. In double-staining experiments, some of the monoclonal antibodies gave similar distributions of fluorescence as compared with the staining obtained from polyclonal rabbit anti-G1-G2 antibodies. Others, however, preferentially stained either the glycoproteins in the Golgi complex or those at the cell surface. This may indicate that the glycoproteins underwent conformational changes during their transport. Uukuniemi virus infection resulted in the vacuolization of the membranes of Golgi complexes where the maturation of the virus was taking place. Double-staining experiments with monoclonal antibodies which preferentially stained the Golgi-associated viral glycoproteins and with anti-N polyclonal rabbit antiserum showed a correlation between the progressive vacuolization of the Golgi complex and the accumulation of viral nucleoprotein in the Golgi region, suggesting that a morphological alteration of the Golgi complex may be a prerequisite for intracellular maturation of the virus. Treatment of Uukuniemi virus-infected cells with tunicamycin, a drug which inhibits N-linked glycosylation, resulted in the accumulation of both glycoproteins at an intracellular location, apparently representing the endoplasmic reticulum. Double-staining experiments showed a parallel accumulation of nucleoprotein at these sites, indicating that local accumulation of glycoproteins is required for nucleoprotein binding to intracellular membranes.     

Transforming growth factor-beta does not alter interleukin-1 expression in cultured human macrophages

Transforming growth factor-beta (TGF beta) is a growth modulator that stimulates the growth of fibroblastic cells but inhibits the growth of cells of epithelial origin. TGF beta also influences the production of extracellular matrix proteins, and of proteases and the type 1 plasminogen activator inhibitor (PAI-1) by cultured cells. TGF beta appears also to have various immunoregulatory effects, suppressing both T- and B-cell activities. It has been proposed that it might increase the expression of interleukin-1 (IL-1) mRNA in cultured human monocytes, thus potentiating immune functions. To analyze the role of TGF beta in IL-1 production we have now quantitated the effect of this factor on the production of biologically active IL-1 as well as IL-1 beta mRNA expression. The effect of TGF beta on IL-1 production optimally activated with bacterial lipopolysaccharide (LPS) was also studied. It was found that IL-1 activity and mRNA levels were rapidly elevated by LPS but not by TGF beta. Culture fluids from monocytes treated with TGF beta alone or with TGF beta plus LPS inhibited the proliferation of the test thymocytes. After gel filtration, the media from TGF beta-treated cultures showed no activity in the molecular weight area of IL-1 (approx. 15 kD), while the supernatants from TGF beta plus LPS-induced cells contained IL-1 activity in these fractions, the magnitude of which was, however, at the same level as in the culture fluids derived from cells stimulated with LPS alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Valve movement of the freshwater mussel Anodonta anatina: a reciprocal transplant experiment between lake and river

The effects of source and caging on the valve movements of the freshwater unionid mussel (Anodonta anatina) were studied in a reciprocal transplant experiment between a lake and its outflow. Caged mussels were moved and compared with those remaining in their natural environment on the lake or river bottom. At both sites, the mussels from the study site and the transplanted mussels from the opposite site were monitored simultaneously. In river the averaged weighted valve openness was higher and the number of valve movements was lower than in the lake. The mussels monitored in the lake exhibited a diurnal rhythm of valve movements which differed between the lake-bottom and the caged animals. Caging was found to increase valve openness. On the other hand, little variation appeared in valve openness between caged and bottom animals in the river, where diurnal rhythms were almost nonexistent. In the river the valve movements were more variable in respect to time than in the lake.     

Eutrophication and recovery of Lake Vesijärvi (south Finland): Diatom frustules in varved sediments over a 30-year period

Lake Vesijärvi was loaded by sewage from the City of Lahti for 60 years until 1976 when the discharge was diverted. Paleolimnological analyses of the varved bottom sediment indicate that the sedimentation rate within the Enonselka basin, the most eutrophic part of the lake, has been as high as 2 cm yr^–1, and total phosphorus accumulation was 20–40 g P m^–2 yr^–1, during the last 20 years. Within the less eutrophic Laitialanselkä basin, the sedimentation rate did not exceed 1 cm yr^–1, and the formation of varved sediment only began at the end of the 1960's, i.e. about 10 years later than in Enonselkä.Planktonic diatom production was highest in the Enonselka basin. The most abundant diatoms in the sediment between 1970–1985 were Asterionella formosa, Aulacoseira islandica and Stephanodiscus spp. Fragilaria crotonensis and Tabellaria fenestrata had low abundances in the middle of the 1970's but increased again at the end of the 1970's. Asterionella formosa and Diatoma elongatum reached their maxima between 1979–1984 when the hypolimnion of the Enonselk/:a basin was aerated artificially. In the Laitialanselkä basin, the production of planktonic diatoms has been lower and the species composition of the diatom community differed from that in Enonselkä. However, at the end of 1980's the total accumulation of diatoms in Laitialanselkä approached levels which were observed at the end of 1950's in Enonselkä, prior to the rapid eutrophication period.The production and thereby the sedimentation of diatoms has decreased towards the end of the 1980's in Enonselkä, indicating reduced nutrient availability in the lake water. This reduction was due to the decreased external loading of phosphorus as well as to the decreased release of phosphorus from the sediment as a result of improved oxygen balance in the hypolimnion.