A5090121966- Anesthesia and Pain Management
- Pregnancy-related medical research
- Anesthesia and Sedative Agents
- Virology and Viral Diseases
- Rabies epidemiology and control
- Nausea and vomiting management
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Estrogen and related hormone effects
- RNA Research and Splicing
- Cell death mechanisms and regulation
- Viral gastroenteritis research and epidemiology
- Genetic Neurodegenerative Diseases
- Peptidase Inhibition and Analysis
- PARP inhibition in cancer therapy
- interferon and immune responses
- Mitochondrial Function and Pathology
- Cancer Immunotherapy and Biomarkers
- Advanced NMR Techniques and Applications
- Animal Disease Management and Epidemiology
- Enzyme Structure and Function
- Anesthesia and Neurotoxicity Research
- Spine and Intervertebral Disc Pathology
- Occupational Health and Performance
- Colorectal Cancer Treatments and Studies
Netaji Subhash Chandra Bose Medical College
2010-2025
The University of Melbourne
2015-2024
Australian Synchrotron
2023-2024
Australian Nuclear Science and Technology Organisation
2024
Allegheny Health Network
2021
VA Butler Healthcare
2021
University of Iowa Hospitals and Clinics
2021
All India Institute of Medical Sciences Bhubaneswar
2019
Creative Commons
2016
Sir Ganga Ram Hospital
2016
Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington's disease. To uncover the physical basis of this toxicity, we performed structural studies soluble Httex1 for wild-type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence conformational rigidity across region. In contrast, hydrogen-deuterium exchange shows absence backbone amide protection, suggesting negligible persistence hydrogen bonds. The seemingly...
Necroptosis is a lytic programmed cell death pathway with origins in innate immunity that frequently dysregulated inflammatory diseases. The terminal effector of the pathway, MLKL, licensed to kill following phosphorylation its pseudokinase domain by upstream regulator, RIPK3 kinase. Phosphorylation provokes unleashing MLKL's N-terminal four-helix bundle (4HB or HeLo) domain, which binds and permeabilizes plasma membrane cause death. precise mechanism 4HB membranes, how differs between...
Abstract H2 relaxin activates the family peptide receptor-1 (RXFP1), a class A G-protein coupled receptor, by poorly understood mechanism. The ectodomain of RXFP1 comprises an N-terminal LDLa module, essential for activation, tethered to leucine-rich repeat (LRR) domain 32-residue linker. is hypothesized bind with high affinity LRR enabling module and activate transmembrane RXFP1. Here we define relaxin-binding site on LDLa-LRR linker, RXFP1, show that residues within linker are critical...
Abstract Transcription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 factors are phosphorylated by mitogen-activated kinases (MAPK) in their transactivation domains (TAD) so-called phosphoswitches, which a hallmark response to growth factors, cytokines or stress. We show that the ATF2 TAD controlled functionally distinct signaling pathways (JNK and p38)...
Ozone therapy, utilizing medical ozone, has gained attention for its therapeutic potential in conditions characterized by chronic hypoxia, inflammation, and redox imbalance. Initially discovered 1839, ozone offers various applications due to properties as a potent oxidizing molecule. Despite instability, been utilized practice over century, demonstrating bactericidal, anti-inflammatory, circulatory stimulating properties. Injected rapidly reacts with water fatty acids human fluids tissues,...
Steep learning curve is found initially in pure endoscopic procedures. Video telescopic operating monitor (VITOM) an advance rigid-lens telescope systems provides alternative method for basics of neuroendoscopy with the help familiar principle microneurosurgery.
To evade immunity, many viruses express interferon antagonists that target STAT transcription factors as a major component of pathogenesis. Because lack direct structural data, these interfaces are poorly understood. We report the analysis full-length STAT1 binding to an antagonist human pathogenic virus. The interface revealed by transferred cross-saturation NMR is complex, involving multiple regions in both viral and cellular proteins. Molecular mapping analysis, combined with biophysical...
The peptide hormone H2 relaxin has demonstrated promise as a therapeutic, but mimetic development been hindered by the poorly understood receptor RXFP1 activation mechanism. is hypothesized to bind two distinct ECD sites, which reorientates N-terminal LDLa module activate transmembrane domain. Here we provide evidence for this model in live cells measuring bioluminescence resonance energy transfer (BRET) between nanoluciferase-tagged constructs and fluorescently labeled (NanoBRET)....
Viruses form extensive interfaces with host proteins to modulate the biology of infected cell, frequently via multifunctional viral proteins. These are conventionally considered as assemblies independent functional modules, where presence or absence modules determines overall composite phenotype. However, this model cannot account for functions observed in specific For example, rabies virus (RABV) P3 protein is a truncated pathogenicity factor P protein, but displays unique phenotype not...
Human immunodeficiency virus type 1 (HIV-1) vaccination of cows has elicited broadly neutralizing antibodies (bNAbs). In this study, monoclonal (mAbs) are isolated from a clade A (KNH1144 and BG505) vaccinated cow using heterologous B antigen (AD8). CD4 binding site (CD4bs) bNAb (MEL-1872) is more potent than majority CD4bs bNAbs so far. MEL-1872 mAb with CDRH3 57 amino acids shows potency (geometric mean half-maximal inhibitory concentration [IC50]: 0.009 μg/mL; breadth: 66%) VRC01 against...
Rabies virus phosphoprotein (P protein) is a multifunctional protein that plays key roles in replication as the polymerase cofactor binds to complex of viral genomic RNA and nucleoprotein (N protein), evading innate immune response by binding STAT transcription factors. These interactions are mediated C-terminal domain P CTD ). The colocation these sites small globular raises question how underlying evasion, central infection, coordinated and, potentially, coregulated. While direct data on...
Abstract Relaxin family peptide receptor 2 (RXFP2) is a GPCR known for its role in reproductive function. It structurally related to the human relaxin RXFP1 and can be activated by gene-2 (H2) as well cognate ligand insulin-like 3 (INSL3). Both receptors possess an N-terminal low-density lipoprotein type (LDLa) module that necessary activation joined leucine-rich repeat domain linker. This linker has been shown important H2 binding of herein we investigate equivalent region RXFP2. We...
Background and Introduction: Spinal block, a known technique to obtain anaesthesia for infraumblical surgeries. Now physician have advantage of using adjuvant prolong the effect intrathecal which can be given either intravenously or intrathecally, dexmedetomidine is one them. We studied intravenous prolongation duration block 0.5% bupivacaine block. Objective: To evaluate on sensory regression, hemodynamic profile, level sedation postoperative analgesia. Methodology: 60 patients ASA grade I...
Peptides and peptidomimetics are attractive drug candidates because of their high target specificity low-toxicity profiles. Developing using hydrocarbon (HC)-stapling or other stapling strategies has gained momentum stability resistance to proteases; however, they have limitations. Here, we take advantage the α-methyl group an aromatic phenyl ring in a unique unnatural amino acid, α-methyl-l-phenylalanine (αF), propose novel, noncovalent strategy stabilize peptides. We utilized this create...
Perforation peritonitis continues to be one of the most common surgical emergencies that need a intervention times. Anesthesiologists are invariably involved in managing such cases efficiently perioperative period.The assessment and evaluation Acute Physiology Chronic Health Evaluation II (APACHE II) score at presentation 24 h after goal-directed optimization, administration empirical broad-spectrum antibiotics, definitive source control postoperatively. Outcome terms duration hospital stay...
The rabies virus (RABV) phosphoprotein (P protein) is expressed as several isoforms, which differ in nucleocytoplasmic localization and microtubule (MT) association, mediated by sequences, including nuclear (NLS) export (NES) sequences. This appears to underpin a functional diversity enabling multiple functions viral replication modulation of host biology. Mechanisms regulating trafficking are poorly defined, but phosphorylation protein kinase C (PKC) the P C-terminal domain (PCTD) regulates...
Abstract Multifunctionality of viral genes is critical for processes in replication and modulation infected cells. P gene rabies virus generates the full-length protein, P1, truncated isoform, P3, which gains unique phenotypes lacking including interactions with multiple cellular membrane-less organelles (MLOs, liquid-liquid phase-separated (LLPS) structures), important to immune evasion. The gain-of-function by P3 proposes that multifunctionality isoforms not merely due their complement...
Abstract The inhibition of the G protein‐coupled receptor, relaxin family peptide receptor 1 (RXFP1), by a small LDLa protein may be potential approach for prostate cancer treatment. However, it is significant challenge to chemically produce 41‐residue and three‐disulfide cross‐bridged module which highly prone aspartimide formation due presence several aspartic acid residues. Known palliative measures, including addition HOBt piperidine N α ‐deprotection, failed completely overcome this...
Immune checkpoint inhibitors (ICIs) in the recent times have transformed landscape of management many solid tumors. Unfortunately, immune-related adverse effects are associated with ICIs, which lead to a negative outcome cancer treatment. We present case 63-year-old female metastatic adenocarcinoma unknown origin, who developed celiac disease during course treatment pembrolizumab. Association this form immunotherapy has never been documented before.