Mutational and evolutionary dynamics of non-structural and spike proteins from variants of concern (VOC) of SARS-CoV-2 in India.

Monitoring the genetic diversity and emerging mutations in SARS-CoV-2 remains crucial for understanding its evolution, given the virus's persistence in India. This study analyzes lineage dynamics, mutation screening, structural analysis, and phylodynamics of SARS-CoV-2 variants of concern (VOC) in India from October 2020 to September 2023. The predominant variants identified were alpha, beta, delta, and omicron, with delta and omicron making up 76.

CCADD: An online webserver for Alzheimer's disease detection from brain MRI.

Alzheimer's disease (AD) imposes a growing burden on public health due to its impact on memory, cognition, behavior, and social skills. Early detection using non-invasive brain magnetic resonance images (MRI) is vital for disease management. We introduce CCADD (Corpus Callosum-based Alzheimer's Disease Detection), a user-friendly webserver that automatically identifies and segments the corpus callosum (CC) region from brain MRI slices.

CMT2A-linked mitochondrial hyperfusion-driving mutant MFN2 perturbs ER-mitochondrial associations and Ca homeostasis.

Background Information: Mitofusin2 (MFN2), an important molecular player that regulates mitochondrial fusion, also helps maintain the inter-organellar contact sites, referred as mitochondria associated membranes (MAMs) that exist between the ER and mitochondria. The study deals with a mutant of MFN2, R364W-MFN2, linked with the neuropathy, Charcot Marie Tooth (CMT) disease. Previous studies show that this mutant promotes mitochondrial hyperfusion.

MITOL-mediated DRP1 ubiquitylation and degradation promotes mitochondrial hyperfusion in a CMT2A-linked MFN2 mutant.

Mutations in mitofusin 2 (MFN2) that are associated with the pathology of the debilitating neuropathy Charcot-Marie-Tooth type 2A (CMT2A) are known to alter mitochondrial morphology. One such abundant MFN2 mutation, R364W, results in the generation of elongated, interconnected mitochondria. However, the mechanism leading to this mitochondrial aberration remains poorly understood.

Corpus Callosum Atrophy in Detection of Mild and Moderate Alzheimer's Disease Using Brain Magnetic Resonance Image Processing and Machine Learning Techniques.

Background: The total number of people with dementia is projected to reach 82 million in 2030 and 152 in 2050. Early and accurate identification of the underlying causes of dementia, such as Alzheimer's disease (AD) is of utmost importance. A large body of research has shown that imaging techniques are most promising technologies to improve subclinical and early diagnosis of dementia.

Structural and Drug Screening Analysis of the Non-structural Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 Virus Extracted From Indian Coronavirus Disease 2019 Patients.

The novel coronavirus 2 (nCoV2) outbreaks took place in December 2019 in Wuhan City, Hubei Province, China. It continued to spread worldwide in an unprecedented manner, bringing the whole world to a lockdown and causing severe loss of life and economic stability. The coronavirus disease 2019 (COVID-19) pandemic has also affected India, infecting more than 10 million till 31st December 2020 and resulting in more than a hundred thousand deaths.

Classification and prediction of protein-protein interaction interface using machine learning algorithm.

Structural insight of the protein-protein interaction (PPI) interface can provide knowledge about the kinetics, thermodynamics and molecular functions of the complex while elucidating its role in diseases and further enabling it as a potential therapeutic target. However, owing to experimental lag in solving protein-protein complex structures, three-dimensional (3D) knowledge of the PPI interfaces can be gained via computational approaches like molecular docking and post-docking analyses. Despite development of numerous docking tools and techniques, success in identification of native like interfaces based on docking score functions is limited.

RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1 -a dual organellar turnover mechanism.

Turnover of cellular organelles, including endoplasmic reticulum (ER) and mitochondria, is orchestrated by an efficient cellular surveillance system. We have identified a mechanism for dual regulation of ER and mitochondria under stress. It is known that AMFR, an ER E3 ligase and ER-ssociated egradation (ERAD) regulator, degrades outer mitochondrial membrane (OMM) proteins, MFNs (mitofusins), via the proteasome and triggers mitophagy.

Loss of tumor susceptibility gene 101 (TSG101) perturbs endoplasmic reticulum structure and function.

Tumor susceptibility gene 101 (TSG101), an ESCRT-I protein, is implicated in multiple cellular processes and its functional depletion can lead to blocked lysosomal degradation, cell cycle arrest, demyelination and neurodegeneration. Here, we show that loss of TSG101 results in endoplasmic reticulum (ER) stress and this causes ER membrane remodelling (EMR). This correlates with an expansion of ER, increased vacuolation, altered relative distribution of the rough and smooth ER and disruption of three-way junctions.

Cytosolic aggregates in presence of non-translocated proteins perturb endoplasmic reticulum structure and dynamics.

Presence of cytosolic protein aggregates and membrane damage are two common attributes of neurodegenerative diseases. These aggregates delay degradation of non-translocated protein precursors leading to their persistence and accumulation in the cytosol. Here, we find that cells with intracellular protein aggregates (of cytosolic prion protein or huntingtin) destabilize the endoplasmic reticulum (ER) morphology and dynamics when non-translocated protein load is high.