Estimating effects of global warming from past range changes for cold demanding refugial taxa: A case study on South-west Anatolian species Poecilimon birandi

Although changes in biodiversity and in ecosystems are surely caused by a range of interacting drivers, such as natural or human-induced factors, one of the important drivers having major impacts on climate and biodiversity and leading to range changes and fragmentation is global warming. Defining past range changes/fragmentations during interglacial periods may provide tools to understand possible impacts of global warming on present biodiversity. To test this assumption we studied a marker gene in the bush-cricket Poecilimon birandi, a species confined to South-west Anatolia that demands a cold climate. Haplotypes of P. birandi constituted three main phylogroups,West, East and Demre. All haplotypes are unique to the respective phylogroup. An AMOVA suggested considerable divergence at all hierarchical levels. Though there is a strong isolation between phylogroups, the East and West groups harbour considerable haplotype diversity. Most of the demographic analyses suggest stable historical populations for the West and East phylogroups, but a coalescent-based demographic analysis indicates a bottleneck for the West phylogroup. The main conclusions are; (i) P. birandi contains considerable phylogenetic signal in 16S rDNA, (ii) there were at least three contemporaneous radiations, which might have originated from isolated refugial populations during Pleistocene, (iii) within a refugium, range changes induced by climatic shifts may be only vertical through an altitudinal gradient, (iv) significant genetic structure can arise in a small heterogeneous area, if the species requires particular habitats and has weak dispersal ability, (v) climatic shifts may cause fragmentation or extinction of populations, but can also lead to divergence of populations suffering from fragmentation, and (vi) altitudinal heterogeneity plays a buffering role, allowing for survival of the refugial biodiversity.     

The evolution of meningococcal infection in Mongolia]

On the basis of the generalization and analysis of the results of bacteriological and immunological investigations the epidemic process of meningococcal infection (MI) in Mongolia was found to undergo definite changes during the last 20 years. Group A meningococci prevailing in the etiology of MI were replaced by strains belonging to group B affecting mainly young children (aged up to 3 years). MI morbidity rate caused by group B meningococci was found to be higher in Mongolia than in other countries of the world. These data substantiate the necessity of using more effective remedies for the control of this infection and, in particular, specific immunization with vaccines against group B meningococci; profound study of the properties of the circulating meningococcal strains is to be carried out.     

Double promoter expression systems for recombinant protein production by industrial microorganisms

Applied Microbiology and Biotechnology - Using double promoter expression systems is a promising approach to increase heterologous protein production. In this review, current double promoter...     

Single-channel studies on linear gramicidins with altered amino acid side chains. Effects of altering the polarity of the side chain at position 1 in gramicidin A.

The modulation of gramicidin A single-channel characteristics by the amino acid side chains was investigated using gramicidin A analogues in which the NH2 terminal valine was chemically replaced by other amino acids. The replacements were chosen such that pairs of analogues would have essentially isosteric side chains of different polarities at position 1 (valine vs. trifluorovaline or hexafluorovaline; norvaline vs. S-methyl-cysteine; and norleucine vs. methionine). Even though the side chains are not in direct contact with the permeating ions, the single-channel conductances for Na+ and Cs+ are markedly affected by the changes in the physico-chemical characteristics of the side chains. The maximum single-channel conductance for Na+ is decreased by as much as 10-fold in channels formed by analogues with polar side chains at position 1 compared with their counterparts with nonpolar side chains, while the Na+ affinity is fairly insensitive to these changes. The relative conductance changes seen with Cs+ were less than those seen with Na+; the ion selectivity of the channels with polar side chains at position 1 was increased. Hybrid channels could form between compounds with a polar side chain at position 1 and either valine gramicidin A or their counterparts with a nonpolar side chain at position 1. The structure of channels formed by the modified gramicidins is thus essentially identical to the structure of channels formed by valine gramicidin A. The polarity of the side chain at position 1 is an important determinant of the permeability characteristics of the gramicidin A channel. We discuss the importance of having structural information when interpreting the functional consequences of site-directed amino acid modifications.     

An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region

The Kcnq1 imprinting control region (ICR) located in intron 10 of the Kcnq1 gene is unmethylated on the paternal chromosome and methylated on the maternal chromosome and has been implicated in the manifestation of parent-of-origin-specific expression of six neighboring genes. The unmethylated Kcnq1 ICR harbors bidirectional silencer activity and drives expression of an antisense RNA, Kcnq1ot1, which overlaps the Kcnq1 coding region. To elucidate whether the Kcnq1ot1 RNA plays a role in the bidirectional silencing activity of the Kcnq1 ICR, we have characterized factor binding sites by genomic footprinting and tested the functional consequence of various deletions of these binding sites in an episome-based system. Deletion of the elements necessary for Kcnq1ot1 promoter function resulted in the loss of silencing activity. Furthermore, interruption of Kcnq1ot1 RNA production by the insertion of a polyadenylation sequence downstream of the promoter also caused a loss of both silencing activity and methylation spreading. Thus, the antisense RNA plays a key role in the silencing function of the ICR. Double-stranded RNA (dsRNA)-mediated RNA interference is unlikely to be involved, as the ICR is active irrespective of the simultaneous production of dsRNA from the genes it silences.     

Aldosterone suppresses expression of an avian colonic sodium-glucose cotransporter

Transport in the colon of the domestic fowl switches from sodium-linked hexose and amino acid cotransport on high-salt intake to amiloride-sensitive sodium channel expression on low-salt (LS) diets. The present experiments were designed to investigate the role of aldosterone in suppression of the colonic sodium-glucose luminal cotransporter (SGLT). LS-adapted hens were resalinated with or without simultaneous aldosterone treatment. Changes in the electrophysiological responses and SGLT protein expression levels were examined at 1, 3, and 7 days of treatment. Serum aldosterone levels fell from approximately 400 pmol/l in LS-adapted hens to values below the detection limit (<44 pmol/l) after 1 day of resalination. At the same time, glucose-stimulated short circuit current (I(SC)) increased from 20.9 +/- 8.7 to 56.3 +/- 15.5 microA/cm(2), whereas amiloride-sensitive I(SC) decreased from -68.9 +/- 12.7 microA/cm(2) on LS to +0.6 +/- 12.0 microA/cm(2). Glucose-stimulated I(SC) increased further at 3 and 7 days of resalination, whereas amiloride-sensitive I(SC) remained suppressed. When resalinated birds were simultaneously treated with aldosterone, the LS pattern of high amiloride-sensitive I(SC) and low glucose-stimulated I(SC) was maintained. Immunoblotting results from the same tissues demonstrated that SGLT-like protein expression increased following resalination. Aldosterone treatment completely blocked this effect. These results demonstrate that aldosterone suppresses both activity and protein expression of hen colonic SGLT. Resalination either through decreased aldosterone or other factors may be able to activate SGLT activity independently of increases in protein expression.     

Determination of the basicity of Mannich ketones by capillary electrophoresis

Capillary electrophoretic (CE) method to characterise Mannich ketones (MKs) containing morpholine moiety was developed. Basicity (pKa,exp) of the MKs was characterised by measured data derived from the electrophoretic mobility values obtained in the CE separation. The MKs were found to be weaker bases than the parent morpholine molecule itself and the experimentally determined basicity values proved to be dependent on the chemical structure of the MKs. Since the basicity of the MKs has an influence on their reactivity and biological activity it seems to be useful to determine experimentally the pKa,exp values of the newly synthesised compounds to support rational drug design or screening of the molecule libraries.     

Mixture models with multiple levels, with application to the analysis of multifactor gene expression data

Model-based clustering is a popular tool for summarizing high-dimensional data. With the number of high-throughput large-scale gene expression studies still on the rise, the need for effective data- summarizing tools has never been greater. By grouping genes according to a common experimental expression profile, we may gain new insight into the biological pathways that steer biological processes of interest. Clustering of gene profiles can also assist in assigning functions to genes that have not yet been functionally annotated. In this paper, we propose 2 model selection procedures for model-based clustering. Model selection in model-based clustering has to date focused on the identification of data dimensions that are relevant for clustering. However, in more complex data structures, with multiple experimental factors, such an approach does not provide easily interpreted clustering outcomes. We propose a mixture model with multiple levels, , that provides sparse representations both "within" and "between" cluster profiles. We explore various flexible "within-cluster" parameterizations and discuss how efficient parameterizations can greatly enhance the objective interpretability of the generated clusters. Moreover, we allow for a sparse "between-cluster" representation with a different number of clusters at different levels of an experimental factor of interest. This enhances interpretability of clusters generated in multiple-factor contexts. Interpretable cluster profiles can assist in detecting biologically relevant groups of genes that may be missed with less efficient parameterizations. We use our multilevel mixture model to mine a proliferating cell line expression data set for annotational context and regulatory motifs. We also investigate the performance of the multilevel clustering approach on several simulated data sets.     

Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes.

With the rationale that the neuropathological similarities between scrapie and Alzheimer's disease reflect convergent pathological mechanisms involving altered gene expression, we set out to identify molecular events involved in both processes, using scrapie as a model to study the time course of these changes. We differentially screened a cDNA library constructed from scrapie-infected mice to identify mRNAs that increase or decrease during disease and discovered in this way two mRNAs that are increased in scrapie and Alzheimer's disease. These mRNAs were subsequently shown by sequence analysis to encode apolipoprotein E and cathepsin D (EC 3.4.23.5). Using in situ hybridization and immunocytochemistry to define the cellular and anatomic pathology of altered gene expression, we found that in both diseases the increase in apolipoprotein E and cathepsin D mRNAs and proteins occurred in activated astrocytes. In scrapie, the increase in gene expression occurred soon after the amyloid-forming abnormal isoform of the prion protein has been shown to accumulate in astrocytes. In Alzheimer's disease, the increased expression of cathepsin D also occurred in association with beta-amyloid. These studies reveal some of the molecular antecedents of neuropathological changes in scrapie and Alzheimer's disease and accord new prominence to the role of astrocytes in neurodegenerative conditions.