40 research outputs found

    THE ROLE OF PHASE VARIABLE TYPE III RESTRICTION-MODIFICATION SYSTEMS IN GENE REGULATION

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    Phase variation, the high frequency reversible switching of gene expression, is a common feature of host-adapted bacterial pathogens and is generally associated with genes encoding surface factors. Phase variation results in genetically and phenotypically diverse populations, providing a strategy for rapid adaptation to changes within the host environment and evading immune responses. However, in a growing number of host-adapted pathogens, phase variation has been found to occur in genes encoding methyltransferases (mod genes) associated with type III restrictionmodification (R-M) systems. R-M systems traditionally confer protection against foreign DNA, and several roles have been proposed for phase variable R-M systems based on DNA restriction function. The existence of phase variable methyltransferases raises the possibility of further functions for R-M systems such as gene regulation. In this thesis the role of a phase variable methyltransferase (mod) associated with a type III R-M system of Haemophilus influenzae strain Rd was investigated. Microarray expression analysis comparing a wild-type strain expressing mod to a mod knockout mutant strain, revealed altered expression of 15 genes under Mod control, some of which were virulence associated. This key finding confirmed that this phase variable methyltransferase coordinates the random switching of expression of multiple genes. Phylogenetic studies were used to analyse phase variable mod genes associated with type III R-M systems in the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae revealing that these organisms have two distinct mod genes - modA and modB. There are also distinct alleles of modA and modB that differ only in their DNA recognition domain. Phylogenetic analysis was also used to create an up-to-date list of potentially phase variable type III R-M systems present within other host-adapted organisms. To confirm whether phase variable methyltransferases controlled gene expression in other pathogens, the phase variable modA genes of Neisseria were studied. Mutant strains lacking the modA11, modA12 or modA13 genes were made and their phenotype analysed. Microarray analysis revealed that in all three modA alleles multiple genes were either up- or down-regulated, some of which were virulence associated. For example, in N. meningitidis (modA11), 80 genes were differentially expressed including the vaccine antigen candidates lactoferrin binding proteins A and B. Functional studies in N. gonorrhoeae confirmed that wild-type FA1090 modA13 ON and FA1090modA13::kan mutant strains have distinct phenotypes in antimicrobial resistance, a primary human cervical epithelial cell model of infection and biofilm formation. In summary, this thesis provides experimental confirmation that in three important human pathogens, H. influenzae, N. meningitidis and N. gonorrhoeae, alteration of expression of a type III DNA-methyltransferase causes switching of multiple genes. This novel genetic system has been termed the phasevarion (phase variable regulon). The wide distribution of phase variable mod genes indicates that this may be a common strategy used by host-adapted bacterial pathogens to randomly switch between distinct differentiated cell types

    Phase variable type III restriction-modification systems of host-adapted bacterial pathogens

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    Phase variation, the high-frequency on/off switching of gene expression, is a common feature of host-adapted bacterial pathogens. Restriction-modification (R-M) systems, which are ubiquitous among bacteria, are classically assigned the role of cellular defence against invasion of foreign DNA. These enzymes are not obvious candidates for phase variable expression, a characteristic usually associated with surface-expressed molecules subject to host immune selection. Despite this, numerous type III R-M systems in bacterial pathogens contain repetitive DNA motifs that suggest the potential for phase variation. Several roles have been proposed for phase variable R-M systems based on DNA restriction function. However, there is now evidence in several important human pathogens, including Haemophilus influenzae, Neisseria meningitidis and Neisseria gonorrhoeae, that these systems are 'phasevarions' (phasevariable regulons) controlling expression of multiple genes via a novel epigenetic mechanism.No Full Tex

    Performance Analysis on Deep Learning State of Art Algorithms for Object Recognition

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    The goal of computer vision, a subfield of computer science, is to replicate some of the intricacies of the human visual system so that machines can recognize and interpret images and videos in the same manner that humans do. Until recently, computer vision was only used in a restricted capacity. In the past few years, artificial intelligence has advanced significantly, outperforming humans in a number of tasks involving object detection, recognition, and classification. This has allowed computer vision to grow exponentially in terms of increasing the precision with which machines can recognize the objects in and around the surrounding environment. A computer vision technology called object recognition helps find and identify objects in a series of images and videos. Despite the fact that the image of the things varies in different viewpoints, different sizes and scales, or when they are translated or rotated, humans can recognise a large number of objects in images with minimal effort. Even when partially obscured from view, human vision system has the greatest capability to identify the objects. Whereas, for computer vision systems, this task is still a difficulty. Over the years, several different approaches and innovations in the algorithm have been tried to impose the human’s capability into a computer’s vision system. This paper provides a thorough investigation on the evolution of Object Recognition algorithms, datasets used and its performance metrics in a precise manner which will guide the future researchers a direction to proceed their research in innovating algorithms with better accuracy

    Deployment of Medibot in Medical Field

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    During this pandemic situation, most of people's health care is in the need of medicine and doctors' suggestions to improve and protect their health. Also, have seen many such cases where many people have been infected by COVID. To reduce physical contact and help the people from the spread of diseases the proposed methodology is to implement the medibot in hospitals. A medical bot is a Chatbot that uses NLP (Natural Language Processing) by text format. The medibot is supported by AI and Deep Learning for Medical Diagnostics. The goal of the project is to create a medibot that overcomes the proposed methodology. Many people could not meet the doctors for simple problems such as cold and fever. To reduce these cases will implement the medibot. This medibot can communicate with the patients and understand the symptoms, it will also give them medicines

    A PILOT STUDY OF PIPPALYADI TAILA YONIPICHU IN THE MANAGEMENT OF KAPHAJA YONIYVAPAD (NON-SPECIFIC VAGINITIS)

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    Background: Vaginitis is an inflammatory process involving the vagina, expanding often to the contiguous anatomical structures (cervix and vulva). Non-specific vaginitis is usually caused by an alteration (disruption) of the normal vaginal microflora, usually represented by the presence of Lactobacilli. Nonspecific vaginitis can be correlated to Kaphaja Yonivyapad based on its Lakshanas. Objectives: To evaluate the efficacy of Pippalyadi taila yoni Pichu in management of Kaphaja yoni vyapad. Design: This was a pilot study that included twenty female patients of Kaphaja yonivyapad (non specific vaginitis) from the Dept. of Prasooti tantra and Stree roga OPD of Rajiv Gandhi educational society’s Ayurvedic Medical College, Ron. Patients were administered Pippalyadi taila yonipichu for 7 days and were assessed before and after the treatment and followed up on the 14th day. Results: This pilot study showed statistically significant changes in reduction of Katishoola (p<0.001), Kandu (p<0.001), consistency of the srava (p<0.001) and Srava pramana (quantity of the discharge) (p<0.001) showing the effectiveness of Pippalyadi taila yoni Pichu in the management of Kaphaja yonivyapad. Conclusions: Pippalyadi taila yonipichu showed significant changes in the management of Kaphaja yoni Vyapad with the reduction of Katishoola, Kandu, consistency of the Srava and Srava pramana after the treatment

    The Gut-Brain Axis in Multiple Sclerosis: A Systematic Review of Microbiome Modulation and Neurological Outcomes

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    Background: The disease multiple sclerosis (MS) is an autoimmune chronic disorder that afflicts the central nervous system with demyelination and is associated with a variety of neurological symptoms. Increasing research interest is focused on the gut-brain axis, which constitutes a communication network between the gastrointestinal tract and the central nervous system, especially regarding the modulation of immune responses and the influence on neurological health.Objective: The current systematic review looks to establish whether alterations in the human microbiome due to dietary change, probiotics, and prebiotics relate to neurological effects in patients with multiple sclerosis via the gut-brain axis.Methods: The inclusion criteria will be original research articles that include randomized controlled trials, cohort studies, case-control studies, and observational studies on human subjects with all types of MS. The studies should report neurological outcomes such as symptoms, disease progression, and biomarkers of neuroinflammation. Articles published within the last ten years will be included, while animal studies, non-pertinent neurological disorders, and those lacking relevant methodologies will be excluded.Results: The review synthesized the effects of microbiome modulation on immune responses, focusing on cytokine production and inflammatory cell activation. Preliminary findings suggest that dysbiosis exacerbates neuroinflammation and contributes to disease progression. Therapies targeting the gut microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, show potential for improving clinical outcomes, although results remain variable. The variability of individual microbiota, lack of robust clinical trials specifically for MS, and concerns regarding safety and efficacy of these interventions present significant challenges. Membrane technology enhances the study of the gut-brain axis in multiple sclerosis (MS) by enabling the isolation of gut-derived biomolecules, which influence immune responses and neuroinflammation. This integration offers insights into microbial signatures and potential therapeutic interventions, paving the way for innovative treatments targeting gut health to improve MS outcomes. Understanding the interplay between gut microbiota and MS is essential for developing innovative therapeutic strategies. This review aims to provide insights into the GBA\u27s role in MS, paving the way for future research and clinical applications
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