Analysis of the unexplored features of rrs (16S rDNA) of the Genus Clostridium

<p>Abstract</p> <p>Background</p> <p>Bacterial taxonomy and phylogeny based on <it>rrs </it>(16S rDNA) sequencing is being vigorously pursued. In fact, it has been stated that novel biological findings are driven by comparison and integration of massive data sets. In spite of a large reservoir of <it>rrs </it>sequencing data of 1,237,963 entries, this analysis invariably needs supplementation with other genes. The need is to divide the genetic variability within a taxa or genus at their <it>rrs </it>phylogenetic boundaries and to discover those fundamental features, which will enable the bacteria to naturally fall within them. Within the large bacterial community, <it>Clostridium </it>represents a large genus of around 110 species of significant biotechnological and medical importance. Certain <it>Clostridium </it>strains produce some of the deadliest toxins, which cause heavy economic losses. We have targeted this genus because of its high genetic diversity, which does not allow accurate typing with the available molecular methods.</p> <p>Results</p> <p>Seven hundred sixty five <it>rrs </it>sequences (> 1200 nucleotides, nts) belonging to 110 <it>Clostridium </it>species were analyzed. On the basis of 404 <it>rrs </it>sequences belonging to 15 <it>Clostridium </it>species, we have developed species specific: (i) phylogenetic framework, (ii) signatures (30 nts) and (iii) <it>in silico </it>restriction enzyme (14 Type II REs) digestion patterns. These tools allowed: (i) species level identification of 95 <it>Clostridium </it>sp. which are presently classified up to genus level, (ii) identification of 84 novel <it>Clostridium </it>spp. and (iii) potential reduction in the number of <it>Clostridium </it>species represented by small populations.</p> <p>Conclusions</p> <p>This integrated approach is quite sensitive and can be easily extended as a molecular tool for diagnostic and taxonomic identification of any microbe of importance to food industries and health services. Since rapid and correct identification allows quicker diagnosis and consequently treatment as well, it is likely to lead to reduction in economic losses and mortality rates.</p

A logic for concurrent programming

Typically, program design involves constructing a program P that implements a given specification S; that is, the set P of executions of P is a subset of the set S of executions satisfying S. In many cases, we seek a program P that not only implements S, but for which P = S. Then, every execution satisfying the specification is a possible execution of the program; we then call P maximal for the specification S. We argue that maximality is an important criterion in the context of designing concurrent programs because it disallows implementations that do not exhibit enough concurrency. In addition, a maximal solution can serve as a basis for deriving a variety of implementations, each appropriate for execution on a specific computing platform. This paper also describes a method for proving the maximality of a program with respect to a given specification. Even though we prove facts about possible executions of programs, there is no need to appeal to branching time logics; we employ a fragment of linear temporal logic for our proofs. The method results in concise proofs of maximality for several non-trivial examples. The method may also serve as a guide in constructing maximal programs.

Cyclooxygenase-2 identified as a potential target for novel radiomodulator scopolamine methyl bromide: An in silico study

Background: The lack of a safe and effective drug against radiation injury is a major hurdle in management of these diseases. Owing to unprecedented radionuclear threats and accidents that may occur, screening of Johns Hopkins Clinical Compound Library (JHCCL) was carried out in zebrafish embryos for identifying novel radio modulators against lethal radiation injury and death. This repositioning strategy with the Food and Drug Administration (FDA) approved small molecules identified scopolamine methyl bromide (SMB) as a novel radioprotective and mitigative agent against 20 Gy gamma irradiation dose. The present study is an attempt to identify the potential target of SMB, which may also prove beneficial as a therapeutic target for other SMB like molecules in ameliorating radiation induced injury and death. Method: We have performed in silico studies with structural similarity search tool, using Tanimoto coefficient (Tc) index for identification of a molecule amongst known radioprotectors that acts as the lead reference compound and helps predict SMB activity. A similar analysis with JHCCL was done to predict and identify more SMB like molecules that may contribute to radiomodulation in a similar manner. Further, molecular docking was performed on computational AutoDock Vina platform to predict the novel target for SMB, with identified lead from the known radiomodulators (RM) as the reference compound. DUD-E decoys were used as benchmark for validating our virtual studies. Results: A structural analysis of SMB with JHCCL and collection of known radioprotectors has revealed its close resemblance to atropine, a known radioprotector. It exhibited Tc index of 0.66. Four more structural entities were found from JHCCL bearing close structural resemblance to SMB and atropine. Molecular docking studies performed with muscarinic receptor M2 (reported target of atropine) exhibited similar binding energies (BEs) for atropine and SMB (−9.4 and −9.7 kcal/mol respectively), and a three-dimensional superimposed binding conformation of SMB and atropine. Due to known activity of atropine as an anti-inflammatory agent and as Cyclooxygenase-2 (Cox-2) antagonist, SMB when evaluated for antagonism against Cox-2 receptor exhibited novel inhibitory action. SMB exhibited BE similar to indomethacin (chosen as the reference lead), an established radioprotector due to its potent Cox-2 inhibitory activity. Molecular docking studies revealed similar binding conformation of SMB and indomethacin with BE of −8.0 and −8.2 kcal/mol respectively. DUD-E study further validated SMB to behave as an active ligand for antagonizing Cox-2 in comparison to the decoys. Conclusion: These results emphasised that SMB could be a potent non-steroidal anti-inflammatory agent contributing towards radioprotection/mitigation by inhibiting Cox-2

Seuss: What the Doctor Ordered

Reconciling the conflicting goals of simplicity and efficiency has traditionally been a major challenge in the development of concurrent programs. Seuss [16] is a methodology for concurrent programming that attempts to achieve the right balance between these competing concerns. The goal of Seuss is to permit a disentanglement of the issues of correctness and efficiency. On the one hand, programmers can reason about Seuss programs by assuming a single thread of control; on the other hand, implementation designers can exploit design knowledge in achieving better performance. This paper provides a short overview of the Seuss programming model and describes the main challenges in designing an efficient implementation of Seuss and in applying Seuss to large applications. 1. Introduction Distributed programming has long been recognized as being far more difficult than sequential programming. The myriad of interactions that may occur in a distributed system introduces a complexity that is f..

Choline chloride attenuates the allergic airway disease by inhibiting the lysophosphatidylcholine induced response in mouse model

Aims: Allergic airway disease manifestation is induced by lysophosphatidylcholine (LPC) through CD1d-restricted Natural killer T (NKT) cells. Choline chloride (ChCl) and LPC both have the “choline” moiety in their structure and this may interplay the effect in allergic airway disease pathway. Main methods: To test the hypothesis, mice were sensitized with cockroach extract (CE); challenged with CE or exposed to LPC and were given ChCl 1hr later. Key findings: A significant increase in Airway hyperresponsiveness (AHR), total and differential cell count, Th2 cytokines, 8-isoprostanes level in bronchoalveolar lavage fluid (BALF) and inflammation score based on lung histology were observed on challenge with CE or exposure to LPC (p ​< ​0.05) indicating LPC induced airway disease manifestation in mice. These parameters were reduced significantly after administering mice with ChCl (p ​< ​0.05). The inflammatory parameters were significantly increased in LPC exposed mice, not sensitized with CE, which were significantly decreased when mice were administered with ChCl demonstrating its role in the inhibition of LPC induced allergic airway disease manifestation. Docking of CD1d with LPC and ChCl indicated the competitive inhibition of LPC induced effect by ChCl. This was validated in vivo in the form of decreased CD1d-restricted NKT cells in BALF and lung of the immunized mice on ChCl administration. There was no effect of ChCl administration on CD1d expression in BALF and lung cells. Significance: This study shows that ChCl attenuates the allergic response by inhibiting the LPC induced- NKT cell mediated AHR, inflammation and oxidative stress by competitive inhibition to LPC in binding to CD1d