Genome-wide survey and phylogeny of S-Ribosylhomocysteinase (LuxS) enzyme in bacterial genomes

Background: The study of survival and communication of pathogenic bacteria is important to combat diseases caused by such micro-organisms. Bacterial cells communicate with each other using a density-dependent cell-cell communication process called Quorum Sensing (QS). LuxS protein is an important member of interspecies quorumsensing system, involved in the biosynthesis of Autoinducer-2 (AI-2), and has been identified as a drug target. Despite the above mentioned significance, their evolution has not been fully studied, particularly from a structural perspective. Results: Search for LuxS in the non-redundant database of protein sequences yielded 3106 sequences. Phylogenetic analysis of these sequences revealed grouping of sequences into five distinct clusters belonging to different phyla and according to their habitat. A majority of the neighbouring genes of LuxS have been found to be hypothetical proteins. However, gene synteny analyses in different bacterial genomes reveal the presence of few interesting gene neighbours. Moreover, LuxS gene was found to be a component of an operon in only six out of 36 genomes. Analysis of conserved motifs in representative LuxS sequences of different clusters revealed the presence of conserved motifs common to sequences of all the clusters as well as motifs unique to each cluster. Homology modelling of LuxS protein sequences of each cluster revealed few structural features unique to protein of each cluster. Analyses of surface electrostatic potentials of the homology models of each cluster showed the interactions that are common to all the clusters, as well as cluster-specific potentials and therefore interacting partners, which may be unique to each cluster. Conclusions: LuxS protein evolved early during the course of bacterial evolution, but has diverged into five subtypes. Analysis of sequence motifs and homology models of representative members reveal cluster-specific structural properties of LuxS. Further, it is also shown that LuxS protein may be involved in various protein-protein or proteinRNA interactions, which may regulate the activity of LuxS proteins in bacteria

Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma : a preclinical F98 glioblastoma rat model study

Purpose Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma. Cx43-mediated gap junctional communication has been observed between tumor cells, between astrocytes and between tumor cells and astrocytes. Therefore, gap junction directed therapy using a pharmacological suppressor or modulator, such as tonabersat, could be a promising target in the treatment of GB. In this preclinical study, we evaluated the possible therapeutic potential of tonabersat in the F98 model. Procedures Female Fischer rats were inoculated with +/- 25.000 F98 tumor cells in the right frontal lobe. Eight days post-inoculation contrast-enhanced T1-weighted (CE-T1w) magnetic resonance (MR) images were acquired to confirm tumor growth in the brain. After tumor confirmation, rats were randomized into a Control Group, a Connexin Modulation Group (CM), a Standard Medical Treatment Group (ST), and a Standard Medical Treatment with adjuvant Connexin Modulation Group (STCM). To evaluate therapy response, T2-weighted (T2w) and CE-T1w sequences were acquired at several time points. Tumor volume analysis was performed on CE-T1w images and statistical analysis was performed using a linear mixed model. Results Significant differences in estimated geometric mean tumor volumes were found between the ST Group and the Control Group and also between the STCM Group and the Control Group. In addition, significant differences in estimated geometric mean tumor volumes between the ST Group and the STCM Group were demonstrated. No significant differences in estimated geometric mean tumor volumes were found between the Control Group and the CM Group. Conclusion Our results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy

The Janthinobacterium sp. HH01 genome encodes a homologue of the V. cholerae CqsA and L. pneumophila LqsA autoinducer synthases

Janthinobacteria commonly form biofilms on eukaryotic hosts and are known to synthesize antibacterial and antifungal compounds. Janthinobacterium sp. HH01 was recently isolated from an aquatic environment and its genome sequence was established. The genome consists of a single chromosome and reveals a size of 7.10 Mb, being the largest janthinobacterial genome so far known. Approximately 80% of the 5,980 coding sequences (CDSs) present in the HH01 genome could be assigned putative functions. The genome encodes a wealth of secretory functions and several large clusters for polyketide biosynthesis. HH01 also encodes a remarkable number of proteins involved in resistance to drugs or heavy metals. Interestingly, the genome of HH01 apparently lacks the N-acylhomoserine lactone (AHL)-dependent signaling system and the AI-2-dependent quorum sensing regulatory circuit. Instead it encodes a homologue of the Legionella- and Vibrio-like autoinducer (lqsA/cqsA) synthase gene which we designated jqsA. The jqsA gene is linked to a cognate sensor kinase (jqsS) which is flanked by the response regulator jqsR. Here we show that a jqsA deletion has strong impact on the violacein biosynthesis in Janthinobacterium sp. HH01 and that a jqsA deletion mutant can be functionally complemented with the V. cholerae cqsA and the L. pneumophila lqsA genes

Small RNAs and extracellular vesicles in filarial nematodes: from nematode development to diagnostics

Parasitic nematodes have evolved sophisticated mechanisms to communicate with their hosts in order to survive and successfully establish an infection. The transfer of RNA within extracellular vesicles (EVs) has recently been described as a mechanism that could contribute to this communication in filarial nematodes. It has been shown that these EVs are loaded with several types of RNAs, including microRNAs, leading to the hypothesis that parasites could actively use these molecules to manipulate host gene expression and to the exciting prospect that these pathways could result in new diagnostic and therapeutic strategies. Here we review the literature on the diverse RNAi pathways that operate in nematodes and more specifically our current knowledge of extracellular RNA (exRNA) and EVs derived from filarial nematodes in vitro and within their hosts. We further detail some of the issues and questions related to the capacity of RNA-mediated communication to function in parasite-host interactions and the ability of exRNA to enable us to distinguish and detect different nematode parasites in their hosts

Hierarchical Models for Relational Event Sequences

Interaction within small groups can often be represented as a sequence of events, where each event involves a sender and a recipient. Recent methods for modeling network data in continuous time model the rate at which individuals interact conditioned on the previous history of events as well as actor covariates. We present a hierarchical extension for modeling multiple such sequences, facilitating inferences about event-level dynamics and their variation across sequences. The hierarchical approach allows one to share information across sequences in a principled manner---we illustrate the efficacy of such sharing through a set of prediction experiments. After discussing methods for adequacy checking and model selection for this class of models, the method is illustrated with an analysis of high school classroom dynamics

Effects of Anticipation in Individually Motivated Behaviour on Control and Survival in a Multi-Agent Scenario with Resource Constraints

This is an open access article distributed under the Creative Commons Attribution License CC BY 3.0 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Self-organization and survival are inextricably bound to an agent’s ability to control and anticipate its environment. Here we assess both skills when multiple agents compete for a scarce resource. Drawing on insights from psychology, microsociology and control theory, we examine how different assumptions about the behaviour of an agent’s peers in the anticipation process affect subjective control and survival strategies. To quantify control and drive behaviour, we use the recently developed information-theoretic quantity of empowerment with the principle of empowerment maximization. In two experiments involving extensive simulations, we show that agents develop risk-seeking, risk-averse and mixed strategies, which correspond to greedy, parsimonious and mixed behaviour. Although the principle of empowerment maximization is highly generic, the emerging strategies are consistent with what one would expect from rational individuals with dedicated utility models. Our results support empowerment maximization as a universal drive for guided self-organization in collective agent systemsPeer reviewedFinal Published versio

The placement of the head that maximizes predictability. An information theoretic approach

The minimization of the length of syntactic dependencies is a well-established principle of word order and the basis of a mathematical theory of word order. Here we complete that theory from the perspective of information theory, adding a competing word order principle: the maximization of predictability of a target element. These two principles are in conflict: to maximize the predictability of the head, the head should appear last, which maximizes the costs with respect to dependency length minimization. The implications of such a broad theoretical framework to understand the optimality, diversity and evolution of the six possible orderings of subject, object and verb are reviewed.Comment: in press in Glottometric

Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon

Current models of the virus-like agents of scrapie and bovine spongiform encephalopathy (BSE) have to take into account that structural changes in a host-encoded protein (PrP protein) exhibit an effect on the time course of these diseases and the survival time of any man or animal exposed to these pathogens. We report here the sequence of different forms of the bovine PrP gene which contain either five or six copies of a short, G-C-rich element which encodes the octapeptide Pro-His-Gly-Gly-Gly-Trp-Gly-Gln or its longer variants Pro-Gln/His-Gly-Gly-Gly-Gly-Trp-Gly-Gln. Out of 12 cattle, we found eight animals homozygous for genes with six copies of the Gly-rich peptide (6:6), while four were heterozygous (6:5). Two confirmed cases of BSE occurred in (6: 6) homozygous animals. Bovine spongiform encephalopathy (BSE) is a transmissible disease (Fraser et al., 1988; Dawson et al., 1990; Barlow & Middleton, 1990) which produces neuropathological lesions in cattle similar to those seen in ovine scrapie (Wells et al., 1987) and the rare human dementias Creutzfeldt-Jakob disease (CJD) and Gerstmann-Str/iussler syndrome (GSS) (Beck & Daniel, 1987). A cellular membrane protein (PrP) has a key role in the transmission and development of these diseases. This protein accumulates in the brain and other tissues during the protracted time course of these diseases and, in a disease-specific, protease-resistant isoform (SAF-PrP), has been purified by subcellular fractionation of scrapie