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Biology subjects

Bharati, P.

Publications and source records attributed to Bharati, P..

2 recordsLinked to original sources

IIHP: Intelligent Incident Hypertension Prediction in Obstructive Sleep Apnea

The Obstructive sleep apnea (OSA) increases the risk of hypertension, mainly attributed to intermittent hypoxia and sleep fragmentation. Given the multifaceted pathogenesis of hypertension, accurately predicting incident hypertension in individuals with OSA has posed a considerable challenge. In this study, we leveraged Machine Learning (ML) techniques to develop a predictive model for incident hypertension up to five years after OSA diagnosis by polysomnography. We used data from the Sleep Heart Health Study (SHHS), which included 4,797 participants diagnosed with OSA. After excluding those with pre-existing hypertension and Apnea Hypopnea Index (AHI) values below 21 per hour, we had 671 participants with five-year follow-up data. We adopted two distinct methodologies. We first implemented adaptive convolution layers to extract features from the signals and combined them into a 2D array. The 2D array was further processed by a 2D pre-trained neural network to take advantage of transfer learning. Subsequently, we delved into feature extraction from full-length signals across various temporal frames, resulting in a 2D feature array. We studied the use of various 2D networks such as MobileNet, EfficientNet, and a family of RESNETs. The best algorithm achieved an average area under the curve of 72%. These results suggest a promising approach for predicting the risk of incident hypertension in individuals with OSA, providing tools for practice and public health initiatives.

bioengineering↗

Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA

Regulation of RNA stability and translation by RNA-binding proteins (RBPs) is a crucial process altering gene expression. Musashi family of RBPs comprising Msi1 and Msi2 are known to control RNA stability and translation. However, despite the presence of MSI2 in the heart, its function remains entirely unknown. Here, we aim to explore the cardiac functions of MSI2. We confirmed the presence of MSI2 in the adult mouse, rat heart, and neonatal rat cardiomyocytes. Furthermore, Msi2 was significantly enriched in the hearts cardiomyocyte fraction. Next, using RNA-seq data and isoform-specific PCR primers, we identified, Msi2 isoforms 1, 4, and 5 and two novel putative isoforms labeled as Msi2 isoforms 6 and 7 to be expressed in the heart. Overexpression of Msi2 isoforms led to cardiac hypertrophy in cultured cardiomyocytes. Additionally, Msi2 was also found to be significantly increased in a pressure-overload model of cardiac hypertrophy. To validate the hypertrophic effects, we selected isoforms 4 and 7 due to their unique alternative splicing patterns. AAV9-mediated overexpression of Msi2 isoforms 4 and 7 in murine hearts led to cardiac hypertrophy, dilation, heart failure, and eventually early death, confirming a pathological function for Msi2. Using global proteomics, gene ontology, transmission electron microscopy, and transmembrane potential measurement assays increased MSI2 was found to cause mitochondrial dysfunction in the heart. Mechanistically, we identified Cluh and Smyd1 as direct downstream targets of Msi2. Overexpression of Cluh or Smyd1 inhibited Msi2-induced hypertrophy and mitochondrial dysfunction in cardiomyocytes. Collectively, we show that Msi2 induces hypertrophy, mitochondrial dysfunction, and heart failure.

cell biology↗