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.     

Infantile neuronal ceroid-lipofuscinosis is not an allelic form of Batten disease: exclusion of chromosome 16 region with linkage analyses

Infantile neuronal ceroid-lipofuscinosis (CLN1) is the form of neuronal ceroid-lipofuscinoses (NCL) with the earliest onset of symptoms. The locus of the most common form of these disorders, juvenile NCL (CLN3), has been mapped to chromosome 16. We report here linkage data of the same region in Finnish CLN1 families. Our results indicate that CLN1 is not allelic with CLN3 but represents a different locus, which is not located within about 70 cM in chromosome 16.     

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.     

Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease

Summary Salla disease is an inherited lysosomal storage disorder caused by accumulation of free sialic acid in the lysosomes. Lamp genes, lamp A and lamp B (lysosome associated membrane proteins), are the first known genes encoding for human lysosomal membrane proteins. Absence of linkage in a large group of families shows that lamp genes are not involved in Salla disease. The lamp genes were localized, using Southern hybridization in hamster — human hybrid cell panels, to chromosomes 13 (lamp A) and X (lamp B).     

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.     

A Novel Mutation of the Fibrillin Gene Causing Ectopia Lentis

Ectopia lentis (EL), a dominantly inherited connective tissue disorder, has been genetically linked to the fibrillin gene on chromosome 15 (FBN1) in earlier studies. Here, we report the first EL mutation in the FBN1 gene confirming that EL is caused by mutations of this gene. So far, several mutations in the FBN1 gene have been reported in patients with Marfan syndrome (MFS). EL and MFS are clinically related but distinct conditions with typical manifestations in the ocular and skeletal systems, the fundamental difference between them being the absence of cardiovascular involvement in EL. We report a point mutation, cosegregating with the disease in the described family, that displays EL over four generations. The mutation changes a conserved glutamic acid residue in an EGF-like motif, which is the major structural component of the fibrillin and is repeated throughout the polypeptide. In vitro mutagenetic studies have demonstrated the necessity of an analogous glutamic acid residue for calcium binding in an EGF-like repeat of human factor IX. This provides a possible explanation for the role of this mutation in the disease pathogenesis.     

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.     

Extensive MHC class II DRB3 diversity in African and European cattle

Genetic deversity at the highly polymorphic BoLA-DRB3 locus was investigated by DNA sequence analyses of 18 African cattle from two breeds representing the two subspecies of cattle, Bos primigenius indicus and Bos primigenius taurus. Yhe polymorphism was compared with that found in a sample ofd 32 European cattle from four breeds, all classified as B. p. taurus. Particularly extensive genetic diversity was found among African cattle, in which as many as 18 alleles were recognized in this small random sample of animals from two breeds. The observed similarity in allele frequency distribution between the two African populations, N'Dama and Zebu cattle, is consistent with the recent recognition of gene flow between B. p. indicus and B. P taurus cattle in Africa. A total of 30 DRB3 alleles were documented and as many as 26 of these were classified as major allelic types showing at least five amino acid substitutions compared with other major types. The observation of extensive genetic diversity at MHC loci in cattle, as well as in other farm animals, provides a compelling argument against matin-type preferences as a primary cause in maintaining major histocompatibility complex diversity, since the reproduction of these animals has been controlled by humans for many generations.The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been given the accession numbers X87641-X87670