Antimicrobial resistance landscape in a metropolitan city context using open drain wastewater-based metagenomic analysis.

One Health concept recognizes the inextricable interactions of diverse ecosystems and their subsequent effect on human, animal and plant health. Antimicrobial resistance (AMR) is a major One Health concern and is predicted to cause catastrophes if appropriate measures are not implemented. To understand the AMR landscape in a south Indian metropolitan city, metagenomic analysis of open drains was performed.

Spinal muscular atrophy: Molecular mechanism of pathogenesis, diagnosis, therapeutics, and clinical trials in the Indian context.

Spinal muscular atrophy (SMA) is a neuromuscular, rare genetic disorder caused due to loss-of-function mutations in the survival motor neuron-1 () gene, leading to deficiency of the SMN protein. The severity of the disease phenotype is inversely proportional to the copy number of another gene, , that differs from by a few nucleotides. The current diagnostic methods for SMA include symptom-based diagnosis, biochemical methods like detection of serum creatine kinase, and molecular detection of disease-causing mutations using polymerase chain reaction (PCR), multiplex ligation-dependent probe amplification (MLPA), and exome or next-generation sequencing (NGS).

mRNA biotherapeutics landscape for rare genetic disorders.

The medical emergency of COVID-19 brought to the forefront mRNA vaccine technology where the mRNA vaccine candidates mRNA-1273 and BNT162b2 displayed superlative and more than 90% efficacy in protecting against SARS-CoV2 infections. Rare genetic disorders are rare individually, but collectively they are common and represent a medical emergency. In mRNA biotherapeutic technology, administration of a therapeutic protein-encoding mRNA-nanoparticle formulation allows for production of therapeutic proteins to functionally complement the protein functions lacking in rare disease patients.

Regulation of transferrin receptor trafficking by optineurin and its disease-associated mutants.

Transferrin receptor (TFRC) is a transmembrane protein that plays a crucial role in mediating homeostasis of iron in the cell. The binding of transferrin (that is bound to iron) to TFRC at the cell membrane generally starts endocytosis of TFRC-transferrin complex, which leads to formation of vesicles that are positive for TFRC. These vesicles travel to the early endosomes and later to the endocytic recycling compartment.

Detection of SARS-CoV-2 in the air in Indian hospitals and houses of COVID-19 patients.

To understand the transmission characteristics of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) through air, samples from different locations occupied by coronavirus disease (COVID-19) patients were analyzed. Three sampling strategies were used to understand the presence of virus in the air in different environmental conditions. In the first strategy, which involved hospital settings, air samples were collected from several areas of hospitals like COVID-intensive-care units (ICUs), nurse-stations, COVID-wards, corridors, non-COVID-wards, personal protective equipment (PPE) doffing areas, COVID rooms, out-patient (OP) corridors, mortuary, COVID casualty areas, non-COVID ICUs and doctors' rooms.

Autophagy-independent cytoprotection by optineurin from toxicity of aggregates formed by mutant huntingtin and mutant ataxin-3.

An important feature of several neurodegenerative diseases is the formation of pathological structures containing aggregated proteins. The autophagy receptor optineurin/OPTN is frequently observed in these structures. The role played by optineurin in these aggregates is not clear.

Optineurin modulates ER stress-induced signaling pathways and cell death.

We have investigated the physiological role of the autophagy receptor Optineurin/Optn in endoplasmic reticulum (ER) stress response using cellular and animal models. In comparison to their normal counterparts, Optn-deficient mouse embryonic fibroblasts showed significantly higher cell death and caspase-3 activation upon treatment with tunicamycin and thapsigargin, inducers of ER stress. The transcript levels of some of the genes regulated by the IRE1-XBP1 and PERK-ATF4 pathways were upregulated in Optn-deficient cells, in comparison with normal cells, upon treatment with tunicamycin, and also in the brain cortex and liver of tunicamycin treated Optn-deficient mice.

Identification of a splice variant of optineurin which is defective in autophagy and phosphorylation.

Optineurin (Optn) is an autophagy receptor that performs various functions in cargo-selective and non-selective autophagy. Here, we have identified and characterized a splice variant of mouse optineurin mRNA, which produces a truncated protein lacking N-terminal 157 amino acids (d157mOptn). This mRNA and protein are expressed in several tissues and cells.

Autophagy receptor optineurin promotes autophagosome formation by potentiating LC3-II production and phagophore maturation.

Autophagy is an essential physiological process that maintains cellular homeostasis by eliminating harmful protein aggregates, damaged organelles and certain pathogens through lysosomal degradation. During autophagy specialized structures, known as autophagosomes are formed that recruit the cargo through autophagy receptors, and deliver it to lysosomes. Optineurin (Optn) is an autophagy receptor that mediates cargo selective autophagy.

Optineurin promotes autophagosome formation by recruiting the autophagy-related Atg12-5-16L1 complex to phagophores containing the Wipi2 protein.

Autophagy is a quality-control mechanism that helps to maintain cellular homeostasis by removing damaged proteins and organelles through lysosomal degradation. During autophagy, signaling events lead to the formation of a cup-shaped structure called the phagophore that matures into the autophagosome. Recruitment of the autophagy-associated Atg12-5-16L1 complex to Wipi2-positive phagophores is crucial for producing microtubule-associated protein 1 light chain 3-II (LC3-II), which is required for autophagosome formation.