Correlated pedigree and molecular estimates of inbreeding and their ability to detect inbreeding depression in the Icelandic sheepdog, a recently bottlenecked population of domestic dogs

We examine the relationship of the inbreeding coefficient (f) and molecular estimates of inbreeding (IR, sMLH) in the Icelandic sheepdog. The breed experienced a severe genetic bottleneck and near extinction in the last century. Molecular estimates and the inbreeding coefficient are significantly correlated despite the moderate number of markers and individuals used in this study. This is most likely an effect of the extreme relatedness and relatively high variance in individual inbreeding coefficients in the population. There is a significant relationship between inbreeding (f) and the occurrence of hip dysplasia. However, the molecular measures did not detect hip dysplasia as an inbreeding effect.     

Chromatin organization in relation to the nuclear periphery

In the limited space of the nucleus, chromatin is organized in a dynamic and non-random manner. Three ways of chromatin organization are compaction, formation of loops and localization within the nucleus. To study chromatin localization it is most convenient to use the nuclear envelope as a fixed viewpoint. Peripheral chromatin has both been described as silent chromatin, interacting with the nuclear lamina, and active chromatin, interacting with nuclear pore proteins. Current data indicate that the nuclear envelope is a reader as well as a writer of chromatin state, and that its influence is not limited to the nuclear periphery.     

Benzimidazole- and benzoxazole-based inhibitors of Rho kinase

Inhibitors of Rho kinase have been developed based on two distinct scaffolds, benzimidazoles, and benzoxazoles. SAR studies and efforts to optimize the initial lead compounds are described. Novel selective inhibitors of ROCK-II with excellent potency in both enzyme and cell-based assays were obtained. These inhibitors possess good microsomal stability, low cytochrome P-450 inhibitions and good oral bioavailability.     

Growth on nitrate and occurrence of nitrate reductase-encoding genes in a phylogenetically diverse range of ectomycorrhizal fungi

Ectomycorrhizal (ECM) fungi are often considered to be most prevalent under conditions where organic sources of N predominate. However, ECM fungi are increasingly exposed to nitrate from anthropogenic sources. Currently, the ability of ECM fungi to metabolize this nitrate is poorly understood. Here, growth was examined among 106 isolates, representing 68 species, of ECM fungi on nitrate as the sole N source. In addition, the occurrence of genes coding for the nitrate reductase enzyme (nar gene) in a broad range of ectomycorrhizal fungi was investigated. All isolates grew on nitrate, but there was a strong taxonomic signature in the biomass production, with the Russulaceae and Amanita showing the lowest growth. Thirty-five partial nar sequences were obtained from 43 tested strains comprising 31 species and 10 genera. These taxa represent three out of the four clades of the Agaricales within which ECM fungi occur. No nar sequences were recovered from the Russulaceae and Amanita, but Southern hybridization showed that the genes were present. The results demonstrate that the ability to utilize nitrate as an N source is widespread in ECM fungi, even in those fungi from boreal forests where the supply of nitrate may be very low.     

Modeling of nitrogen transformations and translocations

Different submodels within complex model packages on N regimes-for plant N-uptake, net N-mineralization, nitrate leaching and microbial N immobilization-are critically reviewed mainly with regard to their prediction ability on the basis of three comparative papers. Only for some of the processes adequate statistical evaluation of the models was possible. Compared to the other statistically evaluable process, nitrate leaching, modeling of plant N-uptake yields the better results. Most models for mineralization use arbitrary approaches rather than empirical ones. Although only approximate estimates of N mineralisation were at hand, the models generally behave expectedly poor. Only one model-DAISY-out of 16 involved in the comparison uses an explicit microbial biomass sub-model including microbial growth, decline and maintenance terms. So DAISY is the only model coupling C and N cycles. But what is true for an individual model describing the C and N transformation of a lab incubation experiment seems to be valid for most of the complex simulation work on the C and N regimes: this model was said to be overparameterized with respect to the available data.     

Cleavage of the Phosphodiester Bond of Uridylyl-(3′,5′)-8-Carboxymethylaminoadenosine by Hydronium,Hydroxide and Zinc(Ii) Ions: A Model Study Aimed at Elucidating the Potential of a Carboxylate Function as an Intramolecular Catalyst

Abstract

Uridylyl-(3′,5′)-8-carboxymethylaminoadenosine has been synthesised, and its transesterification to uridine 2′,3′-cyclic phosphate in the presence and absence of Zn²⁺ ion has been studied. The results show that a carboxylate function in the vicinity of the phosphodiester bond accelerates the metal ion promoted cleavage but not the metal ion independent reaction. Under acidic conditions, the predominant reaction is the cleavage of the side chain, giving the 8-amino derivative.     

Synthesis of Analogues of 3′-Deoxypsicothymidine

Abstract

Preparation of 3′-deoxypsicothymidines bearing a tether group at O1′ is described. Selective protection of the primary hydroxy functions of the starting nucleoside is briefly discussed.     

Recovery after Shift Work: Relation to Coronary Risk Factors in Women

Shift work increases the risk for developing cardiovascular disease. There is, however, little knowledge of what aspects of shift scheduling that are detrimental and what characteristics promote good health. The aim of the present study was to evaluate whether coronary risk factors deteriorate after a hard work period and whether recovery, in the form of a week off, was sufficient to improve them. A total of 19 women worked an extremely rapidly rotating and clockwise shift schedule at a paper and pulp factory. They underwent two health examinations, one at the end of the work period and one after the week off. In addition, the women were divided into a tolerant and a vulnerable group, depending on their satisfaction with their work hours. Most risk factors did not change, but total cholesterol and low‐density lipoprotein (LDL)‐cholesterol were lower after the working period than after the week‐off. In addition, vulnerable women had higher levels of total cholesterol and a higher ratio of total cholesterol/high‐density lipoprotein (HDL) than tolerant ones. In conclusion, the finding that a week‐off worsens cholesterol levels was against our hypothesis and suggests further studies on how activities/responsibilities outside the workplace affect shift‐working women. It was also shown that susceptible shift workers had worse lipid profiles.     

Predictors of post-stroke body temperature elevation

Background

Growing evidence indicates that elevated body temperature after stroke is associated with unfavorable outcome. The aim of the current study was to investigate which factors predict temperature elevation within 48 h of stroke onset. Specifically, we hypothesized that temperature elevation would be associated with stroke symptom severity and that hemorrhagic stroke would cause a more pronounced temperature increase compared to ischemic stroke.

Methods

The medical records of 400 stroke patients were retrospectively reviewed. Multiple linear regression analysis was used to determine which factors were associated with elevated body temperature.

Results

Several factors were significantly associated with peak body temperature (the highest recorded body temperature) within 48 h of stroke onset: stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) (regression coefficient; (RC) 0.022), female gender (RC 0.157), tympanic/non-rectal temperature reading (RC ?0.265), swallowing difficulties (RC 0.335), intubation (RC 0.470), antipyretic treatment (RC 0.563), and C-reactive protein?>?50 or signs of infection at admission (RC 0.298). Contrary to our expectations, patients with intracerebral hemorrhage did not have higher peak body temperatures than patients with ischemic stroke.

Conclusions

In conclusion, temperature elevation within the first 48 h of stroke onset is common, can be partially predicted using information at admission and is strongly associated with stroke severity. The strong association with stroke severity may, at least partly, explain the previously described association between post-stroke temperature elevation and unfavorable outcome.

     

Analysis of Clostridium botulinum serotype E strains by using multilocus sequence typing, amplified fragment length polymorphism, variable-number tandem-repeat analysis, and botulinum neurotoxin gene sequencing

A total of 41 Clostridium botulinum serotype E strains from different geographic regions, including Canada, Denmark, Finland, France, Greenland, Japan, and the United States, were compared by multilocus sequence typing (MLST), amplified fragment length polymorphism (AFLP) analysis, variable-number tandem-repeat (VNTR) analysis, and botulinum neurotoxin (bont) E gene sequencing. The strains, representing environmental, food-borne, and infant botulism samples collected from 1932 to 2007, were analyzed to compare serotype E strains from different geographic regions and types of botulism and to determine whether each of the strains contained the transposon-associated recombinase rarA, involved with bont/E insertion. MLST examination using 15 genes clustered the strains into several clades, with most members within a cluster sharing the same BoNT/E subtype (BoNT/E1, E2, E3, or E6). Sequencing of the bont/E gene identified two new variants (E7, E8) that showed regions of recombination with other E subtypes. The AFLP dendrogram clustered the 41 strains similarly to the MLST dendrogram. Strains that could not be differentiated by AFLP, MLST, or bont gene sequencing were further examined using three VNTR regions. Both intact and split rarA genes were amplified by PCR in each of the strains, and their identities were confirmed in 11 strains by amplicon sequencing. The findings suggest that (i) the C. botulinum serotype E strains result from the targeted insertion of the bont/E gene into genetically conserved bacteria and (ii) recombination events (not random mutations) within bont/E result in toxin variants or subtypes within strains.