Biology subjects

Parikh, N.

Publications and source records attributed to Parikh, N..

5 recordsLinked to original sources

bioRxiv2026

Organization of core mitochondrial replication components into multiphasic condensates

Genomes are organized across several hierarchical levels. Intracellular phase transitions compartmentalize many genomic processes, including transcription and DNA repair. However, little is known regarding how phase transitions contribute to replication, in which long strands of double- and single-stranded DNA need to be coordinated. Here, we investigated the molecular interactions driving the condensation of core mitochondrial replication components into mt-nucleoids. Complex phase behavior emerged among purified mt-replication components: each nucleic acid colocalized with its cognate architectural protein within multiphasic condensates. Using single-molecule experiments, we found that formation of ssDNA increased the partitioning of its cognate protein mtSSB within the condensate, consistent with the preferential localization of mtSSB to replicating mt-nucleoids. To develop mechanistic insights, we built a minimalistic coarse-grained model of mt-replication components that showed how interactions between binary pairs dictate their assembly within condensates. The multiphasic organization of mt-nucleoids has implications for how replication can be spontaneously organized in cells. HighlightsO_LIComplex co-phase behavior of TFAM-mtDNA depends on their affinity and DNA length C_LIO_LIMt-replication architectural proteins segregate ssDNA and dsDNA within condensates C_LIO_LImtSSB selectively partitions into actively replicating nucleoids in vivo C_LIO_LIExposure of ssDNA promotes mtSSB partitioning into TFAM-mtDNA condensates C_LI

biophysics↗

bioRxiv2025

Transcription-dependent phase coexistence of mitochondrial nucleoids and RNA granules

The spatiotemporal organization of multiple components within biomolecular condensates helps coordinate gene expression. Mitochondria separate transcription and RNA processing into two distinct condensates: mt-nucleoids and mtRNA granules (MRGs), respectively. However, how mtRNA transcripts are transferred from mt-nucleoids to distant MRGs was unclear. With high-resolution imaging, we examined the steady-state organization of mt-condensates in human cells. We identified a wide distribution of distances between centroids of mt-condensates, from roughly a micron apart to within 100 nm of each other. Live imaging revealed that such organization was dynamic: mt-condensates frequently underwent cycles of mixing and demixing. Indeed, mtRNA transcripts and the mtRNA polymerase co-localized within mixed mt-condensates, while transcription inhibition led to complete dissolution of MRGs, supporting that nascently transcribed mtRNA is a key driver of mt-condensate organization. Together, our results show that active transcription sustains the phase coexistence between mt-nucleoids and MRGs, with implications for transcriptional condensates more broadly.

cell biology↗

bioRxiv2025

Functional connectivity patterns as an early indicator of later very early preterm outcomes

Abnormal functional brain development associated with preterm birth has been widely reported; however, the functional brain architectures of later neurodevelopmental difficulties are not yet fully understood. Here, we applied connectome-based predictive modeling approaches to identify the brain networks associated with later neurocognitive scores at 2-3 years of age in very preterm infants ([≤]31 weeks gestation, N=79) using resting-state functional magnetic resonance imaging (rs-fMRI). The whole-brain functional connectome soon after birth successfully predicted verbal ability at 3 years of corrected age (r=0.53, = 4.0410!") and motor ability at age 2 (r=0.39, = 0.0004) in very preterm infants. In particular, we found that functional edges between the frontoparietal network and limbic, motor, and medial frontal networks at birth contributed significantly to the prediction of future verbal language ability, while the edges connecting the medial frontal network and motor and basal ganglia networks contributed the most to the prediction of future motor ability. In a separate validation analysis, we demonstrated that the mean connectivity strength among these top brain networks significantly differentiated (average accuracy 76%, p<0.001) poor from normal performers at 2 and 3 years of ages. These findings highlight regional functional connectivity soon after birth as a promising biomarker for identifying risks for later brain disorders, which could inform the targeted development of effective early treatments and interventions.

neuroscience↗

bioRxiv2020

Standardization and Harmonization of Distributed Multi-National Proteotype Analysis supporting Precision Medicine Studies

Cancer has no borders: Generation and analysis of molecular data across multiple centers worldwide is necessary to gain statistically significant clinical insights for the benefit of patients. Here we conceived and standardized a proteotype data generation and analysis workflow enabling distributed data generation and evaluated the quantitative data generated across laboratories of the international Cancer Moonshot consortium. Using harmonized mass spectrometry (MS) instrument platforms and standardized data acquisition procedures, we demonstrated robust, sensitive, and reproducible data generation across eleven sites in nine countries on seven consecutive days in a 24/7 operation mode. The data presented from the high-resolution MS1-based quantitative data-independent acquisition (HRMS1-DIA) workflow shows that coordinated proteotype data acquisition is feasible from clinical specimens using such standardized strategies. This work paves the way for the distributed multi-omic digitization of large clinical specimen cohorts across multiple sites as a prerequisite for turning molecular precision medicine into reality.

molecular biology↗

bioRxiv2019

Automated data extraction from historical city directories the rise and fall of mid-century gas stations in Providence, RI

The location of defunct environmentally hazardous businesses like gas stations has many implications for modern American cities. To track down these locations, we present the directoreadr code (github.com/brown-ccv/directoreadr). Using scans of Polk city directories from Providence, RI, directoreadr extracts and parses business location data with a high degree of accuracy. The image processing pipeline ran without any human input for 94.4% of the pages we examined. For the remaining 5.6%, we processed them with some human input. Through hand-checking a sample of three years, we estimate that ~94.6% of historical gas stations are correctly identified and located, with historical street changes and non-standard address formats being the main drivers of errors. As an example use, we look at gas stations, finding that gas stations were most common early in the study period in 1936, beginning a sharp and steady decline around 1950. We are making the dataset produced by directoreadr publicly available. We hope it will be used to explore a range of important questions about socioeconomic patterns in Providence and cities like it during the transformations of the mid-1900s.

ecology↗