What can we learn from noncoding regions of similarity between genomes?

Background  

In addition to known protein-coding genes, large amounts of apparently non-coding sequence are conserved between the human and mouse genomes. It seems reasonable to assume that these conserved regions are more likely to contain functional elements than less-conserved portions of the genome.     

Management of threatened insect species in Australia, with particular reference to butterflies

Abstract   Advances in determination of conservation status of insects through evaluation of threats (rather than simple 'rarity' alone) help to set priorities for allocation of conservation resources, and formulate effective legislative treatment and field management for the most needy species. Summaries of several recent conservation studies on butterflies exemplify the variety of practical needs, amongst which habitat protection and enhancement is paramount. However, the paucity of biological and distributional information on most Australian insects necessitates considerable flexibility in approach, so that perceptions of conservation need may be highly subjective. Listing species for protection and conservation priority must be viewed as a dynamic process, with opportunity for rapid action, either to list or de-list taxa as research and recovery actions lead to change in perceived or real status and conservation need.     

SynTReN: a generator of synthetic gene expression data for design and analysis of structure learning algorithms

Background  

The development of algorithms to infer the structure of gene regulatory networks based on expression data is an important subject in bioinformatics research. Validation of these algorithms requires benchmark data sets for which the underlying network is known. Since experimental data sets of the appropriate size and design are usually not available, there is a clear need to generate well-characterized synthetic data sets that allow thorough testing of learning algorithms in a fast and reproducible manner.     

Structure of antimicrobial peptides and lipid membranes probed by interface-sensitive X-ray scattering

The conformation and correlations of amphiphilic and antimicrobial peptides and the associated changes of lipid bilayers can be studied in oriented lipid membranes deposited on solid substrates. Here we review recent work on these systems, as studied by modern interface-sensitive X-ray and neutron scattering methods. Density profile, short range order of acyl chains and molecular conformations of peptides and lipids are probed in the fluid state of the bilayer. With an emphasis on technical aspects, we review recent work illustrating the potential of the methods and discuss its potential in the field.     

Evidence for histone eviction in trans upon induction of the yeast PHO5 promoter

The yeast PHO5 promoter is a model system for the role of chromatin in eukaryotic gene regulation. Four positioned nucleosomes in the repressed state give way to an extended DNase I hypersensitive site upon induction. Recently this hypersensitive site was shown to be devoid of histone DNA contacts. This raises the mechanistic question of how histones are removed from the promoter. A displacement in trans or movement in cis, the latter according to the well established nucleosome sliding mechanism, are the major alternatives. In this study, we embedded the PHO5 promoter into the context of a small plasmid which severely restricts the space for nucleosome sliding along the DNA in cis. Such a construct would either preclude the chromatin transition upon induction altogether, were it to occur in cis, or gross changes in chromatin around the plasmid would be the consequence. We observed neither. Instead, promoter opening on the plasmid was indistinguishable from opening at the native chromosomal locus. This makes a sliding mechanism for the chromatin transition at the PHO5 promoter highly unlikely and points to histone eviction in trans.     

Identification of clinically relevant protein targets in prostate cancer with 2D-DIGE coupled mass spectrometry and systems biology network platform

Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.     

Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E‐cadherin to disrupt intercellular adhesion

Mammalian and prokaryotic high‐temperature requirement A (HtrA) proteins are chaperones and serine proteases with important roles in protein quality control. Here, we describe an entirely new function of HtrA and identify it as a new secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain of the cell‐adhesion protein E‐cadherin. E‐cadherin shedding disrupts epithelial barrier functions allowing H. pylori designed to access the intercellular space. We then designed a small‐molecule inhibitor that efficiently blocks HtrA activity, E‐cadherin cleavage and intercellular entry of H. pylori.     

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

Histone deacetylases (HDACs) regulate the acetylation of histones in the control of gene expression. Many non-histone proteins are also targeted for acetylation, including TGF-β signalling pathway components such as Smad2, Smad3 and Smad7. Our studies in mouse C3H10T1/2 fibroblasts suggested that a number of TGF-β-induced genes that regulate matrix turnover are selectively regulated by HDACs. Blockade of HDAC activity with trichostatin A (TSA) abrogated the induction of a disintegrin and metalloproteinase 12 (Adam12) and tissue inhibitor of metalloproteinases-1 (Timp-1) genes by TGF-β, whereas plasminogen activator inhibitor-1 (Pai-1) expression was unaffected. Analysis of the activation of cell signalling pathways demonstrated that TGF-β induced robust ERK and PI3K activation with delayed kinetics compared to the phosphorylation of Smads. The TGF-β induction of Adam12 and Timp-1 was dependent on such non-Smad signalling pathways and, importantly, HDAC inhibitors completely blocked their activation without affecting Smad signalling. Analysis of TGF-β-induced Adam12 and Timp-1 expression and ERK/PI3K signalling in the presence of semi-selective HDAC inhibitors valproic acid, MS-275 and apicidin implicated a role for class I HDACs. Furthermore, depletion of HDAC3 by RNA interference significantly down-regulated TGF-β-induced Adam12 and Timp-1 expression without modulating Pai-1 expression. Correlating with the effect of HDAC inhibitors, depletion of HDAC3 also blocked the activation of ERK and PI3K by TGF-β. Collectively, these data confirm that HDACs, and in particular HDAC3, are required for activation of the ERK and PI3K signalling pathways by TGF-β and for the subsequent gene induction dependent on these signalling pathways.     

Ecohydrology of a seasonal wetland in the Rift Valley: ecological characterization of Lake Solai

The following research describes through an ecohydrological approach, the first assessment of the ecology of Lake Solai, with a particular emphasis on the vegetation. Lake Solai is located 50 km north of Nakuru in the Rift Valley in Kenya at E36°80'–36°84' to N00°05'–00°08'. It is a shallow lake that follows a very peculiar seasonal water regime, and that faces conflicts between agriculture and conservation water users. In the upper catchment, an overview of the agricultural practices was implemented and river water uses were identified to assess river flows. Crops/grassland and woodland/shrubland were the major land uses, covering c. 65% of the catchment. Closer to the lake, vegetation samples were collected around the lake together with samples of environmental factors such as soil and water quality. Thirteen vegetation communities were identified within four main zonations: forest, grassland, river inlet and rocky outcrop. These communities showed abundance, distribution and diversity determined mostly by the human pressures, the flooding periods and the salinity. Cynodon , Cyperus and Sporobolus genera were the most abundant.