A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci

Crohn''s disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10⁻⁶). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10⁻⁸; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10⁻⁹; OR = 1.16), 8q21.11 (rs12677663, p = 2×10⁻⁸; OR = 1.15), 10q26.3 (rs10734105, p = 3×10⁻⁸; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10⁻⁹; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.     

Production of cyclomaltodextrin glucanotransferase of Bacillus circulans var. alkalophilus ATCC21783 in B. subtilis

Summary The cyclomaltodextrin glucanotransferase (CGTase, E.C. 2.4.1.19) gene from an alkalophilic Bacillus circulans var. alkalophilus ATCC21783 was cloned into Escherichia coli and B. subtilis. When cloned from E. coli to B. subtilis, the entire insert containing the CGTase gene was, depending on the plasmid construction, either unstable or the recombinant B. subtilis did not secrete the enzyme in significant amounts. To achieve efficient enzyme production in B. subtilis, the gene was placed under the control of the B. amyloliquefaciens -amylase promoter. In one of the constructions, both the promoter and the signal sequence of the gene were replaced with those of B. amyloliquefaciens, whereas in another construction only the promoter area was exchanged. The recombinant B. subtilis clones transformed with these plasmid constructions secreted CGTase into the culture medium 14 times as much as did the parental strain in shake flask cultures. In fermentor cultures in an industrially feasible medium the enzyme production was substantially higher, yielding 1.2 g/l of CGTase, which is about 33 times the amount of the enzyme produced by the parental strain in corresponding fermentations. Both of the plasmid constructions were stable when grown over 50 generations without antibiotic selection.     

A new approach for studying correlations between the chemical structure and the rheological properties in carboxymethyl cellulose

Two model sodium carboxymethyl celluloses (CMC) with similar monomer composition but with significant differences in the viscoelastic properties, that could not be assigned to variations in the average molar mass or molar mass distribution, were investigated with respect to the fraction of nonsubstituted cellulose segments in the polymers. The CMCs were hydrolyzed by a purified highly selective endoglucanase. The average molar mass and molar mass distribution of the enzyme products, as measured by size-exclusion chromatography with online multi-angle light scattering and refractive index detection (SEC/MALS/RI), revealed that the enzyme-catalyzed hydrolysis was more effective on one of the CMCs. To investigate whether this was due to a higher fraction of nonsubstituted cellulose segments in the polymer, the concentrations of nonsubstituted enzyme products, e.g., cellotetraose and cellopentaose, were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). It was concluded that the two CMCs displayed significant differences in the fraction of nonsubstituted cellulose segments. Furthermore, the CMC with the strongest attractive intermolecular interactions, according to rheometry, also contained the highest fraction of nonsubstituted cellulose segments.     

Ribosomal RNA genes in Scots pine (Pinus sylvestris L.): Chromosomal organization and structure

The nuclear 18S, 5.8S and 25S rRNA genes exist as thousands of rDNA repeats in the Scots pine genome. The number and location of rDNA loci (nucleolus organizers, NORs) were studied by cytological methods, and a restriction map from the coding region of the Scots pine rDNA repeat was constructed using digoxigenin-labeled flax rDNA as a probe. Based on the maximum number of nucleoli and chromosomal secondary constrictions, Scots pine has at least eight NORs in its haploid genome. The size of the Scots pine rDNA repeat unit is approximately 27 kb, two- or threefold larger than the typical angiosperm rDNA unit, but similar in size to other characterized conifer rDNA repeats. The intergenic spacer region (IGS) of the rDNA repeat unit in Scots pine is longer than 20 kb, and the transcribed spacer regions surrounding the 5.8S gene (ITS1 and ITS2) span a region of 2.9 kb. Restriction analysis revealed that although the coding regions of rDNA repeats are homogeneous, heterogeneity exists in the intergenic spacer region between individuals, as well as among the rDNA repeats within individuals.     

Modelling crop growth and biomass partitioning to shoots and roots in relation to nitrogen and water availability,using a maximization principle

Many crop models relate the allocation of dry matter between shoots and roots exclusively to the crop development stage. Such models may not take into account the effects of changes in environment on allocation, unless the allocation parameters are altered. In this paper a crop model with a dynamic allocation parameter for dry matter between shoots and roots is described. The basis of the model is that a plant allocates dry matter such that its growth is maximized. Consequently, the demand and supply of carbon, nitrogen, and water is maintained in balance. This model supports the hypothesis that a functional equilibrium exists between shoots and roots.This paper explains the mathematical computation procedure of the crop model. Moreover, an analysis was made of the ability of a crop model to simulate plant dry matter production and allocation of dry matter between plant organs. The model was tested using data from a greenhouse experiment in which spring wheat (Triticum aestivum L.) was grown under different soil moisture and nitrogen (N) levels.Generally, the model simulations agreed well with data recorded for total plant dry matter. For validation data the coefficient of determination (r²) between simulated and measured shoot dry weight was 0.96. For the validation treatments r² was slightly lower, 0.94. In addition to dry matter production the model succeeded satisfactorily in simulating the dry weight of different plant organs. The response of simulated root to shoot ratio to the level of soil moisture was mainly in accordance with the measured data. In contrast, the simulated ratio seemed to be insensitive to the changes in the levels soil N concentration used in the experiment.The data used in the present study were not extensive, and more data are needed to validate the model. However, the results showed that the model responses to the changes in soil N and water level were realistic and mostly agreed with the data. Thus, we suggest that the model and the method employed to allocate dry matter between roots and shoots are useful when modelling the growth of crops under N and water limited conditions.     

Histochemistry and ultrastructure of adrenergic and acetylcholinesterase-containing nerves supplying follicles and endocrine cells in the guinea-pig ovary

Summary With the use of an anti-human S-100 protein antibody, it was possible to reveal a characteristic cell type in the anterior lobe of the normal human pituitary. These cells, so-called folliculo-stellate cells, were present in all pituitaries studied but their number varied from one gland to another. Immunoreactive cells, isolated or grouped, were arranged close to various secretory granulated cells. Especially by use of double immunoenzymatic labeling, it was evident that these cells are spatially related either to somatotropes, prolactin cells and corticotropes, or to glycoprotein-containing cells. Such immunoreactive cells were rare or absent in pseudo-follicular arrangements of secretory granulated cells. Since it is now possible to identify this cell type by light microscopy and since no reliable functional significance is known, it seems more advisable to term this cell type stellate cell instead of folliculostellate cell.