Microbial Sociality in Biofilms

Biofilms are communities of microorganisms attached to surfaces through various self-secreted matrix materials. Biofilms are dynamic communities with extensive interactions between their residents. Microorganisms compete, cooperate, and communicate with each other in biofilms. These ecological interactions determine the emergence or loss of strains/species and are critical in the formation and proliferation of biofilms. Furthermore, most natural biofilms are formed by multiple microbial species and strains and these interactions within the biofilm dramatically influence community composition and structure over time. Microbial interactions also influence clinically relevant outcomes such as antibiotic resistance and host virulence. In this thesis we explore the potential interactions of microbial populations with their environment, different strains and species using a combination of molecular techniques, microfluidics, and confocal microscopy. In the first study we explored surface competition and biofilm invasion strategies of two strains of Pseudomonas aeruginosa. We found that different extracellular matrix composition and biofilm production strategies effect their direct competition. One strain was able to outcompete the later during early colonization and growth. In contrast the later strain was able to better invade existing biofilms and more inclined to stay during starvation conditions. This sheds light on the advantages of different colonization strategies and their advantages in diverse environmental settings. In the second project, we explored the effect of nutrition on Candida albicans biofilms by growing them in different media. We studied C. albicans biofilm characteristics in three distinct nutritional niches and found that biofilm architecture and properties were distinct in each nutritional niche. This study highlights the importance of nutrient media, and the effects metabolism has on biofilm formation. Finally, in the last project we studied the interaction of Pseudomonas aeruginosa and Candida albicans in a Cystic Fibrosis (CF) lung environment. We found an increase in biovolume for both species and this result was specific to the biofilm environment. Although we could not identify the mechanism of action, we saw this robust result of increase of biovolume in dual species biofilms across multiple mutants and CF isolates. These studies showcase the importance of microbial ecology in understanding biofilm properties and characteristics

Aseptic Orbital Cellulitis as a Complication of Suprachoroidal Hemorrhage

Suprachoroidal hemorrhage is a rare and potentially devastating clinical entity seen in individuals on anticoagulation presenting with severe unilateral eye pain, sudden vision loss, and elevated intraocular pressures. Herein, we report the first case of aseptic orbital cellulitis caused by recurrent spontaneous suprachoroidal hemorrhage. This case highlights an example of non-infectious orbital cellulitis arising from choroidal pathology in the setting of uncontrolled intraocular pressures and recurrent intraocular bleeding. Surgical intervention with blood drainage should be considered to prevent complications and preserve the globe

Unveiling the role of Dps in the organization of mycobacterial nucleoid

In order to preserve genetic information in stress conditions, bacterial DNA is organized into higher order nucleoid structure. In this paper, with the help of Atomic Force Microscopy, we show the different structural changes in mycobacterial nucleoid at different points of growth in the presence of different concentrations of glucose in the medium. We also observe that in Mycobacterium smegmatis, two different Dps proteins (Dps1 and Dps2) promote two types of nucleoid organizations. At the late stationary phase, under low glucose availability, Dps1 binds to DNA to form a very stable toroid structure. On the other hand, under the same condition, Dps2-DNA complex forms an incompletely condensed toroid and finally forms a further stable coral reef structure in the presence of RNA. This coral reef structure is stable in high concentration of bivalent ion like Mg2+

The Impact of Mergers and Acquisitions on Firm Performance: Evidence from the Pharmaceutical Industry

The recent past has witnessed a significant increase in mergers and acquisition activity. Firms mainly engage in mergers to achieve corporate growth and realise their business strategy. Mergers and Acquisitions has been a popular strategy among companies, but however they may not always improve firm performance. Various theoretical and empirical studies have been conducted to measure the impact of mergers and acquisitions. Theoretically mergers and acquisitions have shown to improve company performance due to diversification, synergy gains, economies of scale and various other factors. Empirically accounting based studies and stock market event based studies have all reached varied conclusions showing positive to negative to no impact on company performance. In light of the above, the main aim of this dissertation is to analyze the impact of mergers and acquisitions on the operating performance of firms in the US pharmaceutical industry during the period 2004-2008. The pharmaceutical industry has been undergoing significant transformation since the 1990’s, and companies in the industry widely engage in mergers and acquisitions to achieve synergies and overcome competitive pressures. This research tries to highlight the rationale behind the mergers and acquisitions in the pharmaceutical industry as well as tests the effects of these mergers on firm performance. The study mainly employs the accounting based method to evaluate the returns from M&A. Operating performance is assessed in terms of profitability which is measured using key financial ratios. The first study compares pre and post merger performance using a simple paired sample ‘t’ test, while the second study compares merged and non merged firms using a more advanced multivariate regression analysis. The results of both the studies suggest that in the US pharmaceutical industry, mergers and acquisitions have a negative effect on the wealth creation for shareholders of the firm

Vertebrate TFPI-2 C-terminal peptides exert therapeutic applications against Gram-negative infections

Background: Tissue factor pathway inhibitor-2 (TFPI-2) is a serine protease inhibitor that exerts multiple physiological and patho-physiological activities involving the modulation of coagulation, angiogenesis, tumor invasion, and apoptosis. In previous studies we reported a novel role of human TFPI-2 in innate immunity by serving as a precursor for host defense peptides. Here we employed a number of TFPI-2 derived peptides from different vertebrate species and found that their antibacterial activity is evolutionary conserved although the amino acid sequence is not well conserved. We further studied the theraputic potential of one selected TFPI-2 derived peptide (mouse) in a murine sepsis model. Results: Hydrophobicity and net charge of many peptides play a important role in their host defence to invading bacterial pathogens. In vertebrates, the C-terminal portion of TFPI-2 consists of a highly conserved cluster of positively charged amino acids which may point to an antimicrobial activity. Thus a number of selected C-terminal TFPI-2 derived peptides from different species were synthesized and it was found that all of them exert antimicrobial activity against E. coli and P. aeruginosa. The peptide-mediated killing of E. coli was enhanced in human plasma, suggesting an involvement of the classical pathway of the complement. Under in vitro conditions the peptides displayed anti-coagulant activity by modulating the intrinsic pathway of coagulation and in vivo treatment with the mouse derived VKG24 peptide protects mice from an otherwise lethal LPS shock model. Conclusions: Our results suggest that the evolutionary conserved C-terminal part of TFPI-2 is an interesting agent for the development of novel antimicrobial therapies

A Novel Approach and Implementation Concept For A Nanosatellite Backup on-Board Computer

STUDSAT-2 (STUDENT SATellite-2) is a one-of-a-kind satellite technology project undertaken by Indian undergraduate students. The aim of this project is to demonstrate the On-Board Computer's redundancy (OBC). The OBC subsystem is one of the many subsystems that make up the STUDSAT-2 satellite system. It is critical to the satellite's operation. Even a minor malfunction in this system could lead to the mission's complete failure. As a result, OBC redundancy management is required to overcome this. As a result, the proposed model of Backup On-Board Computer for STUDSAT-2 was planned and built by incorporating redundancy in both software and hardware, thus increasing the OBC's reliability

Tissue eosinophilia in head and neck squamous neoplasia: an update

Eosinophils are multifunctional granulocytes that play an imperative role in health and disease. They have also been found to be a crucial component of peri- and intratumoral inflammatory infiltrate. Tumor-associated tissue eosinophilia (TATE) has been observed and described in many tumors, including head and neck neoplasia. The process of eosinophil recruitment and its function in tumors has not been exactly defined yet. Correlation of tissue eosinophilia with prognosis has shown variable results ranging from favourable to unfavourable prognosis or even having no influence on patients outcome. Eosinophils are hypothesized to have tumor defensive as well as tumor promotive function. This dichotomous role of tissue eosinophilia with regard to prognosis has also been noted in head and neck neoplasia and premalignancies. So, the present review attempts to discuss TATE and its possible pros and cons in head and neck neoplasia. Key Words: eosinophils, tumor-associated tissue eosinophilia, head and neck squamous neoplasia, special stains

Effect of Conventional and Microwave Tissue Processing Technique on DNA Integrity: A Comparative Molecular Analysis

BACKGROUND: Methods of diagnostic molecular biology are routinely applied on formalin-fixed, paraffin-embedded tissues processed via conventional method. Recently, there has been a growing interest to use microwave technology in histopathology laboratories to overcome the deficiencies of the conventional processing method. Thefore, this study was aimed to compare and analyze the quality and quantity of DNA obtained from tissues processed by conventional and microwave tissue processing techniques and to further ascertain the applicability of the latter for PCR (polymerase chain reaction based research).METHODS: Thirty fresh tissues of oral squamous cell carcinoma (OSCC) were included, and each sample was cut into two equivalent halves. One tissue half was processed by conventional manual method whereas the other half was processed using a domestic microwave oven. DNA was obtained from all the tissues which were then subjected to Polymerase chain reaction (PCR) to evaluate GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) gene expression.RESULTS: The results revealed better DNA yield from microwave processed tissue while the quality of the DNA was alike from both the techniques.CONCLUSION: On the basis of the results obtained, it can be concluded that DNA produced by microwave processed tissues was similar to that obtained by conventional processing technique in terms of quantity and quality. Thus, microwave processed tissue samples can be successfully used for further molecular studies and researches

Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin

Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length-and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (> 12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest