Biology subjects

Bhatia, M.

Publications and source records attributed to Bhatia, M..

3 recordsLinked to original sources

bioRxiv2022

Loss of FOXP3 function causes expansion of two pools of autoreactive T cells in patients with IPEX syndrome.

The monogenic autoimmune disease Immunedysregulation polyendocrynopathy entheropathy X-linked syndrome (IPEX) has elucidated the essential function of the transcription factor FOXP3 and of thymic-derived regulatory T (Treg) cells in controlling autoimmunity. However, the presence of autoreactive T cells in IPEX remains undetermined, thus representing a crucial gap in understanding the origin of autoimmunity in a FOXP3 deficient immune system. Combining epigenetic analysis as a lineage marker of Treg identity and TCR sequencing to assess the self-reactive clones, we showed that IPEX patients have two pools of expanded autoreactive T cells. The first originates from the expansion of autoreactive effector T cells (Teff), likely due to loss of Treg suppressive function since it is absent in carrier mothers, in whom Treg cells are functional. The second pool originates, unexpectedly, from Treg cells which lose their phenotypic markers, including CD25 and FOXP3. We call these loss of identity Treg cells and show that they are i) suppressed by healthy donor Treg in a patient post hematopoietic transplantation despite low donor chimerism, and ii) not detectable in patients with Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED), a monogenic autoimmune disease of thymic origin. Moreover, we demonstrate that FOXP3 knock-out in Treg cells leads to increased Treg expansion and production of Th17 and Th2 cytokines, known to be increased in IPEX patients. These results suggest that the loss of identity Treg cells could directly contribute to immune dysregulation in IPEX. Collectively, we provide a better understanding of autoimmunity and novel ways to monitor the effects of Treg cell therapies in IPEX disease or other autoimmune diseases. One Sentence SummaryMutations of FOXP3 gene in humans cause expansion of autoreactive T cells originating from both effector T cells and regulatory T cells which gain effector function.

immunology↗

bioRxiv2022

Electroencephalographic dynamics of rhythmicbreath-based meditation

Meditation has been practised for millennia but the neuroscientific understanding of the dynamics is still lacking. Sudarshan Kriya Yoga (SKY) is an evidence based breathing based meditation technique that utilizes rhythmic breathing to induce a deep state of relaxation and calm. Multiple studies have found benefits of the SKY technique from genetic, physiological, psychological to behaviour levels. We collected Electroencephalographic (EEG) data in 43 subjects who underwent the SKY technique and analysed the brain rhythms at different stages of the technique namely preparatory breathing (Pranayama), rhythmic breathing (Kriya) and meditation (Yoga Nidra) using newly developed methods to analyse periodic and aperiodic components. Alpha waves amplitude in the parieto-occipital region decreased as the rhythmic breathing progressed and dropped sharply during the meditation period. Theta amplitudes and peak frequency increased in the centro-frontal region during the rhythmic breathing period but were marked by sustained low theta waves during the meditation period. The delta wave amplitude was not affected by breathing but both delta band power and peak frequency increased during the meditation period in the centro-frontal region. We also saw a decrease in the 1/f aperiodic signal across the brain during the meditation period suggesting a modification of excitation-inhibition balance. We see an overall slowing down of brain oscillations from alpha to theta to delta as the meditation progressed. The paper studies in depth the transitional dynamics of the SKY technique analysing the alpha, theta, delta waves and aperiodic signals and demonstrates that each phase in a breathing based meditation has a unique electrophysiological signature.

neuroscience↗

bioRxiv2021

Molecular characterization of carbapenem resistant Klebsiella pneumoniae clinical isolates: Preliminary experience from a tertiary care teaching hospital in the Himalayas

IntroductionKlebsiella pneumoniae is recognized as an urgent threat to human health because of the emergence of multidrug-resistant (MDR) and hypervirulent strains. Development of novel highly effective and safe treatment options is the need of the hour. One of the ways of achieving this goal is by conducting molecular characterization studies of antibiotic resistant bacteria. Hypothesis/Gap StatementThe government of India is committed to generate validated AMR data from different parts of the country. Efforts are being made to perform molecular characterization of MDR and potentially virulent bacteria by whole-genome sequencing (WGS). However, the data that we have at present is skewed as many parts of the country remain underrepresented. Uttarakhand is one such state located in the Himalay an belt of India, with relatively poor access to healthcare and a paucity of research. AimThis study was performed to generate WGS based preliminary data about the population structure, multi-locus sequence types (MLST), and virulence factors of CRKp isolates recovered from patients in a tertiary care teaching hospital and institute of national importance, located in Rishikesh, Uttarakhand, India. MethodologyA cross-sectional study was conducted at a tertiary care teaching hospital. It included twenty-nine randomly selected and archived carbapenem resistant Klebsiella pneumoniae (CR-Kp) isolates obtained from various clinical samples submitted in the Bacteriology laboratory for culture and sensitivity testing, from July 2018 to August 2019. After preliminary identification (ID) and antibiotic susceptibility testing (AST), as per standard guidelines, these isolates were sent to Central Research Laboratory (CRL), Bengaluru, India, for further characterization & WGS. ResultsTwenty-seven out of twenty-nine test isolates were CRKp. Among the 27 CRKp isolates, ST14 was the most common sequence type (8, 29.6%), followed by ST231 (5, 18.5%) and ST147(3, 11.1%) respectively. KL2 (9/27, 33.3%) and KL51 (8/27, 29.6%) were dominant K loci types in this study. Out of 5 O antigens identified, O1 and O2 together accounted for 88.9% (n=27) CRKp isolates. Yersiniabactin and Aerobactin were identified in 88.9% (24/27) & 29.6% (8/27) of the CRKp isolates of the isolate. Regulatory genes rmpA2 and rmpADC were found in 14.8% (4/27) and 3.7% (1/27) isolates respectively. The predominant plasmid replicons present were ColKP3 (55.5%), IncFII(K) (51.8%), IncFIB(pQil) (44.4%), IncFIB(K) (37%), IncR (33.3%) and Col44 0I (18.5%) respectively. A perfect agreement (100%) was observed between phenotypic and genotypic resistance profiles in the case of fluoroquinolones, penicillins, Beta Lactam/Beta Lactam Inhibitor combinations (BL/BLI), and cephalosporins respectively. As compared to phenotypic resistance, higher genotypic resistance for aminoglycosides (96.3%) and folate pathway inhibitors (92.6%) respectively, was observed. ConclusionThis study emphasizes the need for continued genomic surveillance of emerging CRKp and other MDR bacteria in Uttarakhand and neighbouring states of India. This in turn would help in generating critical information that can be used to assess the emergence, dissemination, and potential impact of important variants.

microbiology↗