Studies of effector functions in mycobacterium tuberculosis-infected macrophages with implications for host-directed therapies

Tuberculosis infection remains a global health problem and the emergence of multidrugresistant TB (MDR-TB) adds further challenges in the battle to stop the spread of infection. Macrophages are the primary host cells to be infected with Mycobacterium tuberculosis (Mtb), and are therefore key cells in the initial control of TB infection. However, to survive and persist in activated macrophages, Mtb has developed strategies to counteract antimicrobial immunity. This thesis work aimed to explore macrophage responses in Mtbinfected cells, the nature of innate effector mechanisms and how these can be enhanced. For this purpose, we used an in vitro macrophage infection model as well as an organotypic lung tissue model system. The thesis work is based on four papers, Study I and III, involved studies on the effects of the immunomodulatory compounds, vitamin D3 (VitD3) and phenylbutyrate (PBA), on the induction of antimicrobial peptides, primarily human cathelicidin LL-37, and the ability to kill intracellular Mtb. In Study I, we observed that Mtb can down-regulate the expression of LL-37 in infected macrophages, but this effect was effectively counteracted by treatment with VitD3 and/or PBA. PBA and/or VitD3 prevented intracellular Mtb growth via induction of LL-37 as well as activation of autophagy in Mtb-infected macrophages. In Study III, we further demonstrated that PBA+VitD3 enhanced intracellular Mtb killing of both MDR-TB and drug-susceptible strains and this effect was dependent on LL-37. In Study IV, we explored the role of VitD3 in polarization of macrophages in comparison to activation with conventional stimuli such as GM-CSF (polarization of inflammatory M1 macrophages) or MCSF (polarization of anti-inflammatory M2 macrophages). The findings from Study IV, suggested that polarization with VitD3 enhanced the ability of Mtb-infected macrophages to control intracellular Mtb growth in comparison to M1 and M2 subsets. Enhanced Mtb growth control was associated with elevated levels of pro-inflammatory cytokines and LL-37, but reduced Mtb-induced expression of the immunosuppressive enzyme IDO (indoleamine 2,3-dioxygenase). Study II, aimed to investigate the expression and function of matrix metalloproteinases (MMPs) in early TB granuloma formation using the organotypic lung tissue model that enabled studies on macrophage-Mtb interactions in a more physiological environment in tissue. In this study, we found that pre-treatment of macrophages with the global MMP inhibitor, marimastat, resulted in effective inhibition of TB granuloma formation, which was associated with reduced Mtb growth detected in the lung tissue model. Thus, reduced degradation of extracellular matrix proteins, could prevent Mtb multiplication and spread of the infection. The main conclusion from this thesis work is that immunomodulatory compounds with the ability to boost or block innate effector mechanisms in Mtb-infected macrophages may be used as adjunct host-directed therapies that could support standard anti-TB drugs to enhance clinical recovery from TB

A Study on Relationship between Body Condition Score (BCS) and Milk Yield, Fat and Solids-Not-Fat Percent in Murrah Graded Buffaloes under Field Conditions

The present experiment was a study on the relationship of Body Condition Score with milk yield, fat and solids-not-fat percent in murrah graded buffaloes under field conditions. In this murrah graded buffaloes from different commercial farms of Guntur and Krishna districts were selected. Total of 150 murrah graded buffaloes of different parities (1st to 6th parities) were selected. Various parameters like BCS, related to average milk yield, fat per cent, SNF per cent was taken into consideration for the present study and a correlated study of BCS and the milk yield was studied. The selected animals were divided into four groups based on BCS as 2.5-2.99, 3.0-3.49, 3.5-3.99, 4.0-4.49. The mean BCS values of 2.5-2.99, 3.0-3.49, 3.5-3.99, 4.0-4.49 were 2.62, 3.25, 3.56 and 4.25 respectively. Highest milk yield was recorded in second month of lactation and lowest in first month of lactation with 9.445±0.15 and 6.18±0.08 kg per day, respectively. The buffaloes with BCS 4.0-4.49 yielded higher milk yield when compared to other groups. Highest fat and SNF percent was observed in the animals with BCS 4.0-4.49 when compared with others. The BCS had showed high positive correlation with SNF (0.44) and milk yield (0.41). View Article DOI: 10.47856/ijaast.2021.v08i8.00

Crowd sourced modeling approach of human behavior modeling

Generating models from large data setsand determining which subsets of data to mine is becoming increasingly automated. However choosing what data to collect in the first place requires human intuition or experience, usually supplied by a domain expert. This paper describes a new approach to machine science which demonstrates for the first time that non-domain experts can collectively formulate features, and provide values for those features such that they are predictive of some behavioral outcome of interest. This was accomplished by building a web platform in which human groups interact to both respond to questions likely to help predict a behavioral outcome and pose new questions to their peers. This results in a dynamically-growing online survey, but the result of this cooperative behavior also leads to models that can predict user’s outcomes based on their responses to the user-generated survey questions

Structural Effects of Various Commonly used Disinfectant Solutions on Gutta-Percha: An Atomic Force Microscopic Study

Introduction: Gutta-percha cones can be contaminated by various ways. Literature revealed several methods for rapid decontamination of gutta-percha cones in dentistry. Atomic force microscope (AFM) is a well-established methodology for structural characterization of materials. Aim: The purpose of the study is to evaluate the effects of 5% sodium hypochlorite 2% chlorhexidine, 2.2% glutaraldehyde, 6% hydrogen peroxide on the surface structure of standardizedgutta-percha cones in their respective cold sterilization times 1, 10, 15, 10 minutes respectively as found in many studies. Materials and methods: Forty standardized gutta-percha cones (ISO standardized size 60) were cut 3 mm from the tip, attached to a glass base and immersed in 5% sodium hypochlorite, 2% chlorhexidine, 2.2% glutaraldehyde, 6% hydrogen peroxide for 1, 10, 15, 10 minutes. After this, the samples were positioned in the atomic force microscope. Theanalyses were performed between 1 and 2 mm from the tip after each period of immersion in NaOCl. Gutta-percha cone without any NaOCl treatment were used as control. Root mean square (RMS) parameters for contact mode imaging variations were measured. Results: The differences between RMS values were testedby ANOVA with Fisher’s protected LSD test for multiple comparisons (p < 0.05). Aggressive deteriorative effects on gutta-percha cone elasticity were observed for 5.25% NaOCl at 1 minute when compared to the control (p < 0.05). In addition, 2% chlorhexidine has caused topographic changes after 15 minutes when compared to the control (p < 0.05). Conversely, 2.2% glutaraldehyde, 6% hydrogen peroxide solution did cause minimal alteration on topography or elasticity of gutta-percha cone structure when compared to the control (p > 0.05). Conclusion: Six percent hydrogen peroxide and 2.2% glutaraldehyde are safe alternative for chair side decontamination of gutta-percha cones when compared to 5.25% NaOCl and 2% chlorhexidine.&nbsp

Guidelines for Inputting Data of CSTR and its Database

A collection of Scientific and Technical Reports (CSTR)13; list is a bibliography of new reports. It is an announcement to be made by an Information Centre or Library as and when new reports are received and acquired by it. Information Centre for Aeronautics (ICA) at National Aeronautical Laboratory, Bangalore produces such a CSTR on monthly basis, announcing thereby its new acquisition of reports. This CSTR list is widely circulated to the users of NAL Library. After generating the above list, the same data is deposited and stored permanently in a report database for the purpose of information retrieval.13; 13; In this document, the input formats, standardisation of input of data, rules and guidelines pertaining to inputting of data of reports are discussed in detail. For inputting of data, UDS 2000 Off-line key to floppy Data entry system has been used. The database of reports is stored and maintained on Sperry Univac 1171/H1 Computer System at the Computer Centre, NAL, Bangalore. This document serves as a manual for inputting data of reports.13; 13

Introduction to EDP systems and their life cycles

This paper contains a reference work for the management, technical and administrative problems that arise in a data processing project.The author has developed many EDP systems for National Aeronautical Laboratory, Bangalore and these programming systems had a big migration path of several computer systems like ICL-1004 data processor, TDC-316, ICL-1901A, DEC-1090 and Sperry Univac 1100. The system life cycle standards were followed in migrating from one computer to the other. 13; The various stages of the SLC are described and these are then carefully broken down into activities and sub-activities. The System Life Cycle sets forth a logical order for the events that take place in the development of an application system . It outlines procedures which if followed, will eliminate the problems that would otherwise occu

Clinical data acquisition standards harmonization importance and benefits in clinical data management

In the clinical trial process, precise and concise data collection at the source is imperative and requires statistical analysis to be performed to derive the primary and secondary endpoints. The quality of raw data collection has a direct impact on the statistical outputs generated as per the statistical analysis plan. Hence, the data collection tools used for data transcription must be clear, understandable, and precise, which helps the investigator to provide the accurate subject data. Clinical Data Acquisition Standards Harmonization (CDASH) provides guidance to develop the case report form (CRF) for domains that are commonly used for the majority of the clinical trials across the therapeutic areas. This white paper describes the importance of CDASH standards, its advantages and its impact on the efforts and the cost in designing the CRF

Adaptive control of flocking behavior of robotic vehicles to self align into a triangular formation

Multi robot system is gaining more attention in research. Achieving coordination among the group of mobile robots leads to a complex task. When it comes to cost estimation and simplicity for certain real-time applications like search and rescue in disasters (such as earthquakes), security purposes, defense etc... A group of robots working in formation can have advantages such as ability to cover a search area. This research is inspired from the flocking behavior of birds; the research mainly focuses on distributed control of three robots moving together in a triangular format. Among the three robots there is a lead robot which follows a defined path and the remaining robots follow the lead robot. The algorithm proposed here is simulated for mobile wheeled robots along with the collision avoidance. The model of the robot utilized is the bicycle model. The proposed robots flocking behavior and formation are implemented and simulated using MATLAB software

Guidelines for Inputting Data of RBA and its Database

A Recent Book Addition (RBA) list is a bibliography13; of new books. It is a prompt announcement to be made by13; a library as and when new books are received and acquired13; by it. Information Centre for Aeronautics (ICA) at National13; Aeronautical Laboratory, Bangalore produces such an RBA on monthly basis, announcing thereby its new acquisition of books. This RBA list is widely circulated to the users of NAL library. After generating the above list, the same13; data is deposited and stored permanently in a book database13; for the purpose of information retrieval.13; 13; In this document, the input formats and, standardisation of input of data, rules and guidelines pertaining to inputting of data of recent book additions are discussed in detail. For inputting of data, UDS 2000 Data entry system (key to floppy systern) has been used. The database of books is stored and maintained on Sperry Univac 1100/71 Computer System at the Computer Centre, NAL, Bangalore. This document serves as a manual for inputting data of books