In silico Study of Bacillus brevis Xylanase - Structure Prediction and Comparative Analysis with Other Bacterial and Fungal Xylanase

The most important building block of hemicelluloses is xylan. It is broken down into xylose oligomer residues by Xylanase - an enzyme, produced by most organisms, to utilize xylose as primary source of carbon. The Xylanase produced are classified into families, viz 5, 8, 10, 11 and 43 - of Glycoside Hydrolases (GH).

Xylanase from family GH 11 are monospecific, they consist solely of Xylanase activity, exclusively active on D-xylose containing substrates.They are inactive on aryl cellobiosidase. The fungal Xylanase are produced in higher concentrations, as compared to bacterial Xylanase, but have limited use in pulp bleaching, as they affect the viscosity and strength of the product. In the present study, we have worked upon the Xylanase of Bacillus brevis, which is fulfilling all the required quality needed to be a commercial Xylanase, and thus is used by many industries. The enzyme, when studied after modelling, provided similar structural configuration with high stability. When compared with other bacterial and fungal Xylanase structures, it provided better potential to ‘activity enhancement’ and ‘in silico handling’.

Human-Organoid Models: Accomplishments to Salvage Test-Animals

Late stage attritions in drug discovery are costly and consuming. Improbable response of test molecules acquired in non-human systems is attributed to be the major cause of clinical failures. While conventional in vitro methods of drug discovery do not truly represent the human system, the animal models used for in vivo validation are also genetically and phenotypically distant from humans. 

However, recent developments in organoid culture are motivating and elevate hopes for replacing test animals with artificial human tissue models. Possibility of creating functional tissue ex vivo has a potential to revolutionize the way human therapeutics is perceived. Not only will it bridge the gap between drug development and its clinical efficacy but also help strategizing regenerative medicine. Successful human-tissue surrogates would liberate test animals or at least minimize their use for research purposes. Potential drug candidates tested on human-tissue equivalents are expected to generate clinically much more relevant data. Here we deliberate upon the options and possibilities of accomplishing human organoid models for in vitro testing and their significance in therapeutics.

Bio-Analytical Method Development and Validation for Estimation of Lume fantrine in Human Plasma by Using Lc-Ms/Ms

Lumefantrine and Glimepiride (IS) were extracted from human plasma by Precipitation followed by Solid phase extraction using Orochem (30 mg/1 CC) solid phase extraction cartridge. The chromatographic separation was performed on Hypurity C18 (50 cm×4.6 mm), 5 μ column. The mobile phase consisted of Acetonitrile: 2 mM Ammonium Acetate (pH: 3.5) (90:10, % v/v) was delivered at rate of 0.600 mL/min with Splitter. Detection and quantitation were performed by a triple quadrupole equipped with electro spray ionization and multiple reaction monitoring inpositive ionization mode (API 3000). The most intense [M-H]- transition for Lume fantrine at m/z 528.0→510.0 and for IS at m/z 491.2→352.0 were used for quantification. 

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Cardiopulmonary Resuscitation as a Graduation Requirement for Biomedical Engineering Students

At the end of a mountain road in Austria during the summer of 2003, I waited for a boat with my family on a dock at a large lake. Suddenly I saw a man fall to the side walk. His skin had turned that ashen blue color, and it was clear to me that he was in cardiac arrest. There was a crowd of more than 75 persons just standing and looking at him. 

I knew what to do when there was no detectable pulse or breathing. Cardio-Pulmonary Resuscitation (CPR) chest compressions were started immediately. His skin color returned to nearly normal. After a few minutes, a single bystander came up and said they knew how to do breaths. At that time, recommendations were for intermittent breathing as well as chest compressions. The stricken person made it alive to the EMS vehicle that took nearly 30 minutes to arrive. While I do not know the eventual outcome, I do know he was successfully resuscitated using an Automated External Defibrillator (AED). Furthermore with the quick application of CPR, he likely had a full recovery. Unfortunately, from the crowd response at that time, there were not enough people trained to act in this emergency situation where seconds really count.

Horizontal Saccadic Eye Movements to Visual and Auditory-Visual Double-Step Stimuli: Saccade Characteristics and Neural Input Estimations

Goal-oriented human saccades were recorded under double-step paradigm. The stimuli consisted of either visual or auditory-visual bi-sensory targets. Eye movement data were analyzed based on a 3rd-order linear horizontal saccadic eye movement model,where the inputs to the muscle were agonist and antagonist active-state tensions that were described by pulse-slide-step wave forms with a post inhibitory rebound burst (PIRB) based on a time optimal controller. Parameter estimations were calculated using the system identification technique for saccade parameters and neural inputs. Saccade amplitude transition function (ATF) and response latency indicated the saccade programming mechanism. The responses were affected by when the second peripheral target was presented. 

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Role of In-silico methods in the identification of Novel Drugs

Drug designing and the molecular dynamic studies are lengthy, intensified and inter-disciplinary activity. Approaches like computational chemistry and molecular modeling are widely applied in the development of in-silico drug design because it is cost effective.  Currently, a vast number of software is used in drug design. Using in-silico drug designing techniques it is possible to produce active lead molecule right from the preclinical discovery stage to late stage clinical development. The lead molecules will be helpful in the selection of potent leads to cure particular diseases. In-silico methods thus are important in target identification and prediction of novel drugs.

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Sequence Features and Subset Selection Technique for the Prediction of Protein Trafficking Phenomenon in Eukaryotic Non Membrane Proteins

Protein trafficking or protein sorting is the mechanism by which a cell transports proteins to the appropriate position in the cell or outside of it. This targeting is based on the information contained in the protein. Many methods predict the sub cellular location of proteins in eukaryotes from the sequence information. However, most of these methods use a flat structure to perform prediction. In this work, we introduce ensemble methods to predict locations in the eukaryotic protein-sorting non membrane pathway hierarchically.

We used features that were extracted exclusively from full length protein sequences with feature subset selection for classification. Sequence driven features, sequence mapped features and sequence auto correlation features were tested with ensemble learners and classifier performances were compared with and without feature subset selection technique. This study shows the new features extracted from full length eukaryotic protein sequences are effective at capturing biological features among compartments in eukaryotic non membrane pathways at two levels. Feature subset selection techniques helped to reduce the time taken for building the classification model.