Replacement of the arginine biosynthesis operon in Xanthomonadales by ateral gene transfer

The role of lateral gene transfer (LGT) in prokaryotes has been shown to rapidly change the genome content, providing new gene tools for environmental adaptation. Features related to pathogenesis and resistance to strong selective conditions have been widely shown to be products of gene transfer between bacteria. The genomes of the gamma-proteobacteria from the genus Xanthomonas, composed mainly of phytopathogens, have potential genomic islands that may represent imprints of such evolutionary processes. In this work, the evolution of genes involved in the pathway responsible for arginine biosynthesis in Xanthomonadales was investigated, and several lines of evidence point to the foreign origin of the arg genes clustered within a potential operon. Their presence inside a potential genomic island, bordered by a tRNA gene, the unusual ranking of sequence similarity, and the atypical phylogenies indicate that the metabolic pathway for arginine biosynthesis was acquired through LGT in the Xanthomonadales group. Moreover, although homologues were also found in Bacteroidetes (Flavobacteria group), for many of the genes analyzed close homologues are detected in different life domains (Eukarya and Archaea), indicating that the source of these arg genes may have been outside the Bacteria clade. The possibility of replacement of a complete primary metabolic pathway by LGT events supports the selfish operon hypothesis and may occur only under very special environmental conditions. Such rare events reveal part of the history of these interesting mosaic Xanthomonadales genomes, disclosing the importance of gene transfer modifying primary metabolism pathways and extending the scenario for bacterial genome evolution.

Cathepsin L-like genes of Trypanosoma vivax from Africa and South America - characterization, relationships and diagnostic implications

We characterized sequences from genes encoding cathepsin L-like (CatL-like) cysteine proteases from African and South American isolates of Trypanosoma vivax and T. vivax-like organisms, and evaluated their suitability as genetic markers for population structure analysis and diagnosis. Phylogenetic analysis of sequences corresponding to CatL-like catalytic domains revealed substantial polymorphism, and clades of sequences (TviCatL1-9) were separated by large genetic distances. TviCatL1-4 sequences were from cattle isolates from West Africa (Nigeria and Burkina Faso) and South America (Brazil and Venezuela), which belonged to the same T. vivax genotype. T. vivax-like genotypes from East Africa showed divergent sequences, including TviCatL5-7 for isolates from Mozambique and TviCatL8-9 for an isolate from Kenya. Phylogenetic analysis of CatL-like gene data supported the relationships among trypanosome species reflected in the phylogenies based on the analysis of small subunit (SSU) of ribosomal RNA gene sequence data. The discovery of different CatL-like sequences for each genotype, defined previously by ribosomal DNA data, indicate that these sequences provide useful targets for epidemiological and population genetic studies. Regions in CatL-like sequences shared by all T. vivax genotypes but not by other trypanosomes allowed the establishment of a specific and sensitive diagnostic PCR for epidemiological studies in South America and Africa. (C) 2008 Elsevier Ltd. All rights reserved.

Characterization of the SOS regulon of Caulobacter crescentus

The SOS regulon is a paradigm of bacterial responses to DNA damage. A wide variety of bacterial species possess homologs of lex,4 and recA, the central players in the regulation of the SOS circuit. Nevertheless, the genes actually regulated by the SOS have been determined only experimentally in a few bacterial species. In this work, we describe 37 genes regulated in a LexA-dependent manner in the alphaproteobacterium Caulobacter crescentus. In agreement with previous results, we have found that the direct repeat GTTCN(7)GTTC is the SOS operator of C. crescentus, which was confirmed by site-directed mutagenesis studies of the imuA promoter. Several potential promoter regions containing the SOS operator were identified in the genome, and the expression of the corresponding genes was analyzed for both the wild type and the lex,4 strain, demonstrating that the vast majority of these genes are indeed SOS regulated. Interestingly, many of these genes encode proteins with unknown functions, revealing the potential of this approach for the discovery of novel genes involved in cellular responses to DNA damage in prokaryotes, and illustrating the diversity of SOS-regulated genes among different bacterial species.

Seamlessly integrating similarity queries in SQL

Modern database applications are increasingly employing database management systems (DBMS) to store multimedia and other complex data. To adequately support the queries required to retrieve these kinds of data, the DBMS need to answer similarity queries. However, the standard structured query language (SQL) does not provide effective support for such queries. This paper proposes an extension to SQL that seamlessly integrates syntactical constructions to express similarity predicates to the existing SQL syntax and describes the implementation of a similarity retrieval engine that allows posing similarity queries using the language extension in a relational DBM. The engine allows the evaluation of every aspect of the proposed extension, including the data definition language and data manipulation language statements, and employs metric access methods to accelerate the queries. Copyright (c) 2008 John Wiley & Sons, Ltd.

Border trees of complex networks

The comprehensive characterization of the structure of complex networks is essential to understand the dynamical processes which guide their evolution. The discovery of the scale-free distribution and the small-world properties of real networks were fundamental to stimulate more realistic models and to understand important dynamical processes related to network growth. However, the properties of the network borders (nodes with degree equal to 1), one of its most fragile parts, remained little investigated and understood. The border nodes may be involved in the evolution of structures such as geographical networks. Here we analyze the border trees of complex networks, which are defined as the subgraphs without cycles connected to the remainder of the network (containing cycles) and terminating into border nodes. In addition to describing an algorithm for identification of such tree subgraphs, we also consider how their topological properties can be quantified in terms of their depth and number of leaves. We investigate the properties of border trees for several theoretical models as well as real-world networks. Among the obtained results, we found that more than half of the nodes of some real-world networks belong to the border trees. A power-law with cut-off was observed for the distribution of the depth and number of leaves of the border trees. An analysis of the local role of the nodes in the border trees was also performed.

Influence from the sulfonate group (RSO(3)(-)) on the conversion process and emission efficiency of poly(p-phenylene vinylene)

The discovery of an alternative route to convert poly(xylyliden tetrahydrothiophenium chloride) (PTHT) into poly(p-phenylene vinylene) (PPV) using dodecylbenzenesulfonate (DBS) has allowed the formation of ultrathin films with unprecedented control of architecture and emission properties. In this work, we show that this route may be performed with several sufonated compounds where RSO(3)(-) replaces the counter-ion (Cl(-)) of PTHT, some of which are even more efficient than DBS. Spin-coating films were produced from PTHT and azo-dye molecules, an azo-polymer and organic salts as counter-ions of PTHT. The effects of the thermal annealing step of PTHT/RSO(3)(-) films at 110 and 230 degrees C were monitored by measuring the absorption and emission spectra. The results indicate that the exchange of the counterion Cl(-) of PTHT by a linear long chain with RSO(3)(-) group is a general procedure to obtain PPV polymer at lower conversion temperature (ca. 110 degrees C) with significant increase in the emission efficiency, regardless of the chemical position and the number of sulfonate groups. With the enhanced emission caused by Congo Red and Tinopal as counter-ions, it is demonstrated that the new synthetic route is entirely generic, which may allow accurate control of conversion and emission properties. (C) 2010 Elsevier B.V. All rights reserved.

In silico screening of HIV-1 non-nucleoside reverse transcriptase and protease inhibitors

Two targets, reverse transcriptase (RT) and protease from HIV-1, were used during the past two decades to the discovery of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) that belong to the arsenal of the antiretroviral therapy. Herein these enzymes were chosen as templates for conducting a computer-aided ligand design. Ligand and structure-based drug designs were the starting points to select compounds from a database bearing more than five million compounds by means of cheminformatic tools. New promising lead structures are retrieved from the database, which are open to acquisition and test. Classes of molecules already described as NNRTI or PI in the literature also came out and were useful to prove the reliability of the workflow, and thus validating the work carried out so far. (c) 2007 Elsevier Masson SAS. All rights reserved.

Acridone alkaloids as potent inhibitors of cathepsin V

Cathepsin V is a lysosomal cysteine peptidase highly expressed in thymus, testis and corneal epithelium. Eleven acridone alkaloids were isolated from Swinglea glutinosa (Bl.) Merr. (Rutaceae), with eight of them being identified as potent and reversible inhibitors of cathepsin V (IC(50) values ranging from 1.2 to 3.9 mu M). Detailed mechanistic characterization of the effects of these compounds on the cathepsin V-catalyzed reaction showed clear competitive inhibition with respect to substrate, with dissociation constants (K(i)) in the low micromolar range (2, K(i) = 1.2 mu M; 6, K(i) = 1.0 mu M; 7, K(i) = 0.2 mu M; and 11, K(i) = 1.7 mu M). Molecular modeling studies provided important insight into the structural basis for binding affinity and enzyme inhibition. Experimental and computational approaches, including biological evaluation, mode of action assessment and modeling studies were successfully employed in the discovery of a small series of acridone alkaloid derivatives as competitive inhibitors of catV. The most potent inhibitor (7) has a K(i) value of 200 nM. (C) 2011 Elsevier Ltd. All rights reserved.

Structural basis for selective inhibition of purine nucleoside phosphorylase from Schistosoma mansoni: Kinetic and structural studies

Selectivity plays a crucial role in the design of enzyme inhibitors as novel antiparasitic agents, particularly in cases where the target enzyme is also present in the human host. Purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive target for the discovery of potential antischistosomal agents. In the present work, kinetic studies were carried out in order to determine the inhibitory potency, mode of action and enzyme selectivity of a series of inhibitors of SmPNP. In addition, crystallographic studies provided important structural insights for rational inhibitor design, revealing consistent structural differences in the binding mode of the inhibitors in the active sites of the SmPNP and human PNP (HsPNP) structures. The molecular information gathered in this work should be useful for future medicinal chemistry efforts in the design of new inhibitors of SmPNP having increased affinity and selectivity. (C) 2010 Elsevier Ltd. All rights reserved.

One, two or no record of late neoproterozoic glaciation in South-East Cameroon?

Severe climate changes culminating in at least three major glacial events have been recognized in the Neoproterozoic sedimentary record from many parts of the world Supportive to the global nature of these climatic shifts a considerable amount of data have been acquired from deposits exposed in Pan-African orogenic belts in southwestern and western Africa By comparison published data from the Pan-African belts in Central Africa are scarce We report here evidence of possibly two glacial events recorded in the Mintom Formation that is located on the margin of the Pan-African orogenic Yaounde belt in South-East Cameroon In the absence of reliable radiometric data only maximum and minimum age limits of 640 and 580 Ma respectively can at present be applied to the Mintom Formation The formation consists of two lithostratigraphic ensembles each subdivided in two members (i e in ascending stratigraphic order the Kol Metou Momibole and Atog Adjap Members) The basal ensemble exhibits a typical glacial to post-glacial succession It includes diamictites comprising cobbles and boulders in a massive argillaceous siltstone matrix and laminated siltstones followed by in sharp contact a 2 m-thick massive dolostone that yielded negative delta(13)C values (<-3 parts per thousand. V-PDB) similar to those reported for Marinoan cap carbonates elsewhere However uncertainty remains regarding the glacial influence on the siliciclastic facies because the diamictite is better explained as a mass-flow deposit and diagnostic features such as dropstones have not been seen in the overlying siltstones The Mintom Formation may thus provide an example of an unusual succession of non-glacial diamictite overlain by a truly glacial melt-related cap-carbonate We also report the recent discovery of ice-striated pavements on the structural surface cut in the Mintom Formation suggesting that glaciers developed after the latter had been deposited and deformed during the Pan-African orogeny Striations which consistently exhibit two principal orientations (N60 and N110) were identified in two different localities in the west of the study area on siltstones of the Kol Member and in the east on limestones of the Atog Adjap Member respectively N60-oriented striae indicate ice flow towards the WSW Assigning an age to these features remains problematical because they were not found associated with glaciogenic deposits Two hypotheses can equally be envisaged e either the striated surfaces are correlated (1) to the Gaskiers (or Neoproterozoic post-Gaskiers) glaciation and represent the youngest Ediacaran glacial event documented in the southern Yaounde belt or (2) to the Late Ordovician Hirnantian (Saharan) glaciation thereby providing new data about Hirnantian ice flows in Central Africa (C) 2010 Elsevier Ltd All rights reserved

Microbial diversity associated with algae, ascidians and sponges from the north coast of Sao Paulo state, Brazil

Little is known about the microbial diversity associated with marine macroorganisms, despite the vital role microorganisms may play in marine ecosystems. The aim of the present study was to investigate the diversity of bacteria and fungi isolated from eight marine invertebrate and one algae samples. Data derived from ARDRA and sequencing analyses allowed the identification of marine-derived microorganisms isolated from those samples. Microbial strains identified up to the genus level revealed 144 distinct ribotypes out of 256 fungal strains and 158 distinct ribotypes out of 181 bacterial strains. Filamentous fungi were distributed among 24 different genera belonging to Ascomycota, Zygomycota and Basidiomycota, some of which had never been reported in the literature as marine invertebrate-inhabiting fungi (Pestalotiopsis, Xylaria, Botrysphaeria and Cunnninghamella). Bacterial isolates were affiliated to 41 different genera, being Bacillus, Ruegeria, Micrococcus, Pseudovibrio and Staphylococcus the most abundant ones. Results revealed an unexpected high microbial diversity associated to the macroorganisms which have been collected and suggested the selection of certain microbial taxonomic groups according to the host. The combined data gathered from this investigation contribute to broaden the knowledge of microbial diversity associated to marine macroorganisms, including as a promising source for the discovery of new natural products. (C) 2009 Elsevier GmbH. All rights reserved.

Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery

The enzyme dihydroorotate dehydrogenase (DHODH) has been suggested as a promising target for the design of trypanocidal agents. We report here the discovery of novel inhibitors of Trypanosoma cruzi DHODH identified by a combination of virtual screening and ITC methods. Monitoring of the enzymatic reaction in the presence of selected ligands together with structural information obtained from X-ray crystallography analysis have allowed the identification and validation of a novel site of interaction (S2 site). This has provided important structural insights for the rational design of T cruzi and Leishmania major DHODH inhibitors. The most potent compound (1) in the investigated series inhibits TcDHODH enzyme with K(i)(app) value of 19.28 mu M and possesses a ligand efficiency of 0.54 kcal mol(-1) per non-H atom. The compounds described in this work are promising hits for further development. (C) 2010 Elsevier Masson SAS. All rights reserved.

Rhynchopora and blasispirifer (brachiopoda) from the middle permian of the Hida Gaien belt, Central Japan, and their paleobiogeographical significance

Two Permian brachiopod genera, Rhynchopora King and Blasispirifer Kulikov, are reported for the first time from the Middle Permian, lower part of the Moribu Formation in the Hida Gaien Belt, central Japan. The Moribu species are closely compared with similar forms from the Middle Permian Barabash Formation (lower Chandalaz Series) in the Barabash area of South Primorye, Russian Far East. The discovery of these two genera, which exhibit close relationships with Middle Permian brachiopod faunas of South Primorye and the broad Boreal Realm, implies that tha Hida Gaien Belt was paleobiogeographically and paleogeographically close to the western part (Voznesenka Belt) of South Primorye, both situated in a middle latitudinal setting in the Northern Hemisphere on the southeastern side of the Bureya Block and lay proximal to and slightly northeast of the Sino-Korea Block during the Permian.

A preliminary study of 16S rRNA sequence variation in Australia Macrobrachium shrimps (Palaemonidae: Decapoda) reveals inconsistencies in their current classification

The systematic relationships among Australian palaemonid shrimps have been the subject of speculation for some time. A preliminary phylogenetic study was undertaken to clarify the relationships of five species, Macrobrachium intermedium (Stimpson), M. australiense (Holthuis), M. atactum (Riek), M. rosenbergii (de Man) and Palaemon serenus (Heller), using 16S rRNA mitochondrial gene sequences. Phylogenetic analyses indicated inconsistencies with the current classification in two respects. First, M. intermedium formed a very well-supported clade with P. serenus distinct from M. australiense, M. atactum and M. rosenbergii. Second, the two species from inland Australia, M. australiense and M. atactum, showed a high level of genetic similarity over a substantial geographic range, suggesting that they may represent conspecific populations. The taxonomic and biogeographic implications of these findings for Macrobrachium in Australia are discussed.

Obesity and diabetes gene discovery approaches

New treatments are currently required for the common metabolic diseases obesity and type 2 diabetes. The identification of physiological and  biochemical factors that underlie the metabolic disturbances observed in obesity and type 2 diabetes is a key step in developing better therapeutic outcomes. The discovery of new genes and pathways involved in the  pathogenesis of these diseases is critical to this process, however  identification of genes that contribute to the risk of developing these diseases represents a significant challenge as obesity and type 2 diabetes are complex diseases with many genetic and environmental causes. A number of diverse approaches have been used to discover and validate potential new targets for obesity and diabetes. To date, DNA-based approaches using candidate gene and genome-wide linkage analysis have had limited success in identifying genomic regions or genes involved in the development of these diseases. Recent advances in the ability to evaluate linkage analysis data from large family pedigrees using variance components based linkage analysis show great promise in robustly identifying genomic regions associated with the development of obesity and diabetes. RNA-based technologies such as cDNA microarrays have identified many genes differentially expressed in tissues of healthy and diseased subjects. Using a combined approach, we are endeavouring to focus attention on differentially expressed genes located in chromosomal regions previously linked with obesity and / or diabetes. Using this strategy, we have identified Beacon as a potential new target for obesity and diabetes.