Biology subjects

Basu, I.

Publications and source records attributed to Basu, I..

6 recordsLinked to original sources

bioRxiv2026

Odad1 is Required for Deployment of Axonemal Outer Arm Dyneins and Embryonic Left-Right Patterning

Motile cilia generate fluid flow required for development and tissue homeostasis. Defects in ciliary motility cause Primary Ciliary Dyskinesia (PCD), presenting with situs inversus, infertility, chronic respiratory disease, and hydrocephalus. Ciliary beating requires outer dynein arms (ODAs), anchored to microtubules by the ODA docking complex (ODA-DC). ODAD1 is an ODA-DC component and a known PCD protein. ODAD1 alleles are often associated with human laterality defects, however Odad1 has not been reported to localize to 9+0 axonemes. Here, we show that GFP-Odad1 localizes to nodal cilia (9+0) in the gastrocoel roof plate (GRP), the frog's equivalent to the mammalian node where left-right asymmetry is first established. We found that Odad1 knockdown (KD) disrupts left-right patterning in Xenopus, with loss of pitx2 expression and abnormal gut looping reflecting defective 9+0 nodal cilia at the GRP. In 9+2 multiciliated cells (MCC) axonemes, Odad1 loss impaired deployment of ODA motors and ODA-DC subunits, disrupting ciliary motility. Two patient-derived truncating ODAD1 alleles were similarly unstable, failing to rescue ODA docking in MCCs or left-right patterning at the GRP. Together, these results show ODAD1 is required for ODA-DC assembly in both 9+0 and 9+2 cilia, linking its loss to ciliary motility and left-right patterning defects in ODAD1-associated ciliopathy.

developmental biology↗

bioRxiv2024

Anxious/depressed individuals exhibit disrupted frontotemporal synchrony during cognitive conflict encoding

BackgroundDepressive disorders are associated with impaired cognitive control, yet the neural mechanisms underlying these deficits remain poorly understood. We used stereotactic EEG (sEEG) in individuals with medically refractory epilepsy to determine whether a history of comorbid depressive symptoms was associated with altered behavioral and neural responses encoding cognitive conflict. MethodssEEGs were recorded from fronto-temporo-limbic regions in 28 participants (age: 35.4{+/-}8.9, female: 15/28) performing a Multi-Source Interference Task (MSIT). Psychiatric histories, neurobehavioral interviews, and symptom ratings were used to categorize participants with a history of depressive symptoms (EDS, n=13), or as epilepsy controls without depression history (n=15). Behavioral, spectral power, and coherence responses to conflict were determined by generalized linear mixed-effects models. Dynamic Causal Modeling (DCM) estimated theta-alpha (4-15Hz) effective connectivity between dorsolateral prefrontal cortex (dlPFC), dorsal anterior cingulate cortex (dACC), and lateral temporal lobe (LTL) during conflict. ResultsEDS participants demonstrated greater conflict-related slowing without difference in accuracy from controls. Conflict elicited distributed fronto-temporo-limbic oscillations in both groups. EDS participants showed greater conflict-related theta/alpha increases in PFC, LTL, and amygdala, and broadband increases in LTL power, and reduced left dlPFC-LTL theta/alpha coherence compared to controls. DCM model estimated effective connectivity from left dlPFCright LTL and left dACCleft LTL was reduced in EDS. ConclusionIncreased oscillatory responses in EDS may reflect a need for greater cognitive resources due to disrupted communication in fronto-temporo-limbic circuits encoding conflict. Our results highlight a role of these circuits in conflict encoding and can inform interventions for improving cognitive control in these populations.

neuroscience↗

bioRxiv2021

Adipose deficiency and aberrant autophagy in a Drosophila model of MPS VII is corrected by pharmacological stimulators of mTOR

Mucopolysaccharidosis type VII (MPS VII) is a recessively inherited lysosomal storage disorder caused due to {beta}-glucuronidase ({beta}-GUS) enzyme deficiency. Prominent clinical symptoms include hydrops fetalis, musculoskeletal deformities, neurodegeneration and hepatosplenomegaly leading to premature death in most cases. Apart from these, MPS VII is also characterized as adipose storage deficiency disorder although the underlying mechanism of this lean phenotype in the patients or {beta}-GUS-deficient mice still remains a mystery. We addressed this issue using our recently developed Drosophila model of MPS VII (the CG2135-/- fly), which also exhibited a significant loss of adiposity. We report here that the lean phenotype of the CG2135-/- fly is due to fewer number of adipocytes, smaller lipid droplets and reduced adipogenesis. Our data further revealed that there is an abnormal accumulation of autophagosomes in the CG2135-/- larvae due to autophagosome-lysosome fusion defect. Decreased lysosome-mediated turnover also led to attenuated mTOR activity in the CG2135-/- flies. Interestingly, treatment of the CG2135-/- larvae with mTOR stimulators, 3BDO or glucose, led to the restoration of mTOR activity with simultaneous correction of the autophagy defect and adipose storage deficiency. Our finding thus established a hitherto unknown mechanistic link between autophagy dysfunction, mTOR downregulation and reduced adiposity in MPS VII.

cell biology↗

bioRxiv2020

Selection of start codon during mRNA scanning in eukaryotic translation initiation

During translational initiation in eukaryotes, the small ribosomal subunit forms a 48S preinitiation complex (PIC) with initiation factors. The 48S PIC binds to the 5 end of mRNA and inspects long untranslated region (UTR) for the presence of the start codon (AUG). Accurate and high speed of scanning 5 UTR and subsequent selection of the correct start codon are crucial for protein synthesis. However, the conformational state of 48S PIC required for inspecting every codon is not clearly understood. Whether the scanning or open conformation of 48S PIC can accurately select the cognate start codon over near/non-cognate codons, or this discrimination is carried out only in the scanning-arrested or closed conformation of 48S PIC. Here, using atomistic molecular dynamics (MD) simulations and free energy calculations, we show that the scanning conformation of 48S PIC can reject all but 4 of the 63 non-AUG codons. Among nine near-cognate codons with a single mismatch, only codons with a first position mismatch (GUG, CUG and UUG) or a pyrimidine mismatch at the second position (ACG) are not discriminated by scanning state of 48S PIC. In contrast, any mismatch in the third position is rejected. Simulations runs in absence of one or more eukaryotic initiation factors (eIF1, eIF1+eIF1A, eIF2[a] or eIF2{beta}) from the system show critical role of eIF1 and eIF2[a] in start codon selection. The structural analysis indicates that tRNAi dynamics at the widened P site of 48S open state drives codon selection. Further, a stable codon: anticodon interaction prepares the PIC to transit to the closed state. Overall, we provide insights into the selection of start codon during scanning and how the open conformation of 48S PIC can scan long 5 UTRs with accuracy and high speed without the requirement of sampling the closed state for every codon.

biophysics↗

bioRxiv2019

Bidirectional modulation of human emotional conflict resolution using intracranial stimulation

The ability to regulate emotions in the service of meeting ongoing goals and task demands is a key aspect of adaptive human behavior in our volatile social world. Consequently, difficulties in processing and responding to emotional stimuli underlie many psychiatric diseases ranging from depression to anxiety, the common thread being effects on behavior. Behavior, which is made up of shifting, difficult to measure hidden states such as attention and emotion reactivity, is a product of integrating external input and latent mental processes. Directly measuring, and differentiating, separable hidden cognitive, emotional, and attentional states contributing to emotion conflict resolution, however, is challenging, particularly when only using task-relevant behavioral measures such as reaction time. State-space representations are a powerful method for investigating hidden states underlying complex systems. Using state-space modeling of behavior, we identified relevant hidden cognitive states and predicted behavior in a standardized emotion regulation task. After identifying and validating models which best fit the behavior and narrowing our focus to one model, we used targeted intracranial stimulation of the emotion regulation-relevant neurocircuitry, including prefrontal structures and the amygdala, to causally modulate separable states. Finally, we focused on this one validated state-space model to perform real-time, bidirectional closed-loop adaptive stimulation in a subset of participants. These approaches enable an improved understanding of how to sample and understand emotional processing in a way which could be leveraged in neuromodulatory therapy for disorders of emotional regulation.

neuroscience↗

bioRxiv2018

COMPASS: An Open-Source, General-Purpose Software Toolkit for Computational Psychiatry

Mathematical modeling of behavior during psychophysical tasks, referred to as \"computational psychiatry\", could greatly improve our understanding of mental disorders. One barrier to broader adoption of computational methods is that they often require advanced programming skills. We developed the Computational Psychiatry Adaptive State-Space (COMPASS) toolbox, an open-source MATLAB-based software package. After specifying a few parameters in a small set of user-friendly functions, COMPASS allows the user to efficiently fit of a wide range of computational behavioral models. The model output can be analyzed as an experimental outcome or used as a regressor for neural data, and can be tested using goodness-of-fit methods. Here, we demonstrate that COMPASS can replicate two computational behavior analyses from different groups. COMPASS replicates and, in one case, slightly improves on the original modeling results. This flexible, general-purpose toolkit should accelerate the use of computational modeling in psychiatric neuroscience.

bioengineering↗