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Tripathy, K.

Publications and source records attributed to Tripathy, K..

4 recordsLinked to original sources

The RNA m6A reader YTHDF2 depletion phenocopies high glucose induced-cellular stress response in diabetic kidney disease

RNA modification, especially the m6A RNA methylation, has been increasingly associated with several physiological and pathophysiological processes. The proteins that help in establishment of the modification and its removal along with the reader proteins that facilitate the functional outcome, together play an important regulatory role in disease manifestation. Diabetic kidney disease (DKD) is one such example, which is categorized as a multifactorial disorder that involves complex metabolic, oxidative, inflammatory, and fibrotic alterations, mediated through genetic, epigenetic and signalling cascades. However, the contribution of m6A-associated RNA regulators in DKD manifestation is relatively less explored. In this study, using HFD+STZ-induced diabetic mice and high glucose-treated renal cell models, we identified the m6A reader protein, Ythdf2 as a consistently downregulated candidate. YTHDF2 depletion in the renal cell line altered cellular viability, proliferation and increased oxidative stress under high-glucose conditions. Click-IT EU labeling further revealed altered RNA processing effects following YTHDF2 depletion and glucose stress. In corroboration with the above observations in animal and cell line models, independent human DKD transcriptomic datasets demonstrated conserved inflammatory and fibrotic signatures as well as reduced YTHDF2 expression in DKD glomeruli. The YTHDF2 downregulation was found to be inversely correlated with several disease-associated inflammatory and fibrotic genes. Together, these findings identify YTHDF2 dysregulation as a potential post-transcriptional mechanism associated with cellular stress and disease-associated molecular programs in DKD.

physiology↗

Basal Ganglia Dopamine Availability and Immune Activation Interact and Relate to Anhedonia Severity among Youth with Depression

Anhedonia emerges in adolescence, has putative substrates in neural reward and dopamine systems, and is a hallmark of poor course in depression. Psychoneuroimmunology models suggest altered immune and reward systems may jointly underlie its development. When dopamine availability (rather than function) is considered, immune activation may be understood as a moderator amplifying how lower dopamine levels translate into motivational deficits. This cross-sectional study analyzed data from 55 youth with current depression (Mage=21.4 years; Female=75%). Plasma was assayed for relative quantification of 92 immune proteins, followed by dimensionality reduction via principal component (PC) analysis, forming five PC scores. Dopamine availability was indexed by basal ganglia tissue iron, quantified by MRI R2, a measure detectable in youth. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS), thought to capture overall anhedonia, and Positive Valence Systems Scale (PVSS), which provides overall, anticipatory, and consummatory anhedonia scores. PC1 scores--whose loadings indicated broadly distributed immune protein elevations consistent with general immune activation--moderated the relationship between basal ganglia dopamine availability and anhedonia: At higher PC1 levels, lower dopamine availability was linked to greater overall anhedonia (as measured by SHAPS) and anticipatory anhedonia, but not to consummatory anhedonia. Lower PC2 scores were associated with greater PVSS overall and consummatory anhedonia. Analyses examining individual basal ganglia regions suggest potential differences in dopaminergic-immune interactions across these regions, with effects most consistently observed in the putamen. Findings highlight nuanced neuroimmune pathways underlying anhedonia components in youth and support inflammation-based models of depression emphasizing dopaminergic-immune interplay.

neuroscience↗

Identifying Naturalistic Movies from Human Brain Activity with High-Density Diffuse Optical Tomography

Modern neuroimaging modalities, particularly functional MRI (fMRI), can decode detailed human experiences. Thousands of viewed images can be identified or classified, and sentences can be reconstructed. Decoding paradigms often leverage encoding models that reduce the stimulus space into a smaller yet generalizable feature set. However, the neuroimaging devices used for detailed decoding are non-portable, like fMRI, or invasive, like electrocorticography, excluding application in naturalistic use. Wearable, non-invasive, but lower-resolution devices such as electroencephalography and functional near-infrared spectroscopy (fNIRS) have been limited to decoding between stimuli used during training. Herein we develop and evaluate model-based decoding with high-density diffuse optical tomography (HD-DOT), a higher-resolution expansion of fNIRS with demonstrated promise as a surrogate for fMRI. Using a motion energy model of visual content, we decoded the identities of novel movie clips outside the training set with accuracy far above chance for single-trial decoding. Decoding was robust to modulations of testing time window, different training and test imaging sessions, hemodynamic contrast, and optode array density. Our results suggest that HD-DOT can translate detailed decoding into naturalistic use.

bioengineering↗

Ultra-high density imaging arrays for diffuse optical tomography of human brain improve resolution, signal-to-noise, and information decoding

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing ([~]13 mm) than sparse fNIRS ([~]30 mm) and therefore provide higher image quality, with spatial resolution [~]1/2 that of fMRI. Herein, simulations indicated reducing inter-optode spacing to 6.5 mm would further improve image quality and noise-resolution tradeoff, with diminishing returns below 6.5 mm. We then constructed an ultra-high-density DOT system (6.5-mm spacing) with 140 dB dynamic range that imaged stimulus-evoked activations with 30-50% higher spatial resolution and repeatable multi-focal activity with excellent agreement with participant-matched fMRI. Further, this system decoded visual stimulus position with 19-35% lower error than previous HD-DOT, throughout occipital cortex.

bioengineering↗