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Biology subjects

Ghavami, M.

Publications and source records attributed to Ghavami, M..

2 recordsLinked to original sources

Brain states recur across diverse narrative contexts during longitudinal viewing

What does the brain do during the continuous, varied experience of watching a story unfold? One account holds that the brain traverses a finite repertoire of recurring states, but whether that repertoire is a stable property of the individual or is reshaped by each new experience has not been tested across diverse naturalistic content within the same person. We characterized the dynamic brain-state repertoire in six individuals who watched the television series Friends across its six seasons during fMRI (up to [~]146 episodes, [~]54 hours per person). For each individual we fit a sticky hierarchical Dirichlet process hidden Markov model across all episodes, discovering brain states (recurring whole-brain activity patterns with characteristic coupling) without pre-specifying their number. Each individuals brain visited roughly forty-five states arrayed along a continuous recurrence gradient, from states active in nearly every episode to episode-specific ones, with no sharp division between them. The repertoire was heterogeneous in why its states recurred: a minority locked to scan-run structure, the majority remaining eligible for content. Transitions were organized by the functional-connectivity similarity between states (per-individual Spearman {rho} = 0.33-0.55) and, in most individuals, respected resting-state network boundaries. Episode content was associated with which states the brain occupied moment to moment. The recurrence ordering discovered in Friends transferred to state occupancy during other social-narrative films (five of six individuals) and attenuated as stimuli departed from that class, weakening for visual-only reading and audio-only listening. Across diverse narrative experience, the dynamic repertoire is a property of the individual: content varies which states are visited and when, not which states exist.

neuroscience↗

Membrane contact site resident PTP1B limits superoxide production by suppressing a Syk-Shc1-Phagocyte Oxidase relay.

Phagocytosis is a specialized endocytic process used by macrophages and dendritic cells to engulf particles, which requires coordinated signaling cascades, cytoskeletal remodeling, and assembly of antimicrobial machinery to eliminate pathogens. During Fc {gamma} receptor (Fc{gamma}R)-mediated phagocytosis, dynamic actin depolymerization at the base of the phagocytic cup creates permissive conditions for endoplasmic reticulum-plasma membrane (ER-PM) membrane contact sites (MCS) to form. We demonstrate that the ER-resident protein tyrosine phosphatase PTP1B localizes to newly formed or expanded ER-PM MCS during phagocytosis and dephosphorylates Syk. Using TIRF microscopy with MCS residents, including MAPPER, STIM1, and E-Syts, we show that actin clearance allows ER proteins to approach the plasma membrane. PTP1B colocalizes with Fc{gamma}Rs in actin-cleared zones and physically interacts with Syk, a critical mediator of phagocytic signaling. Loss of PTP1B led to sustained Syk hyperphosphorylation without affecting phagocytosis. However, the PTP1B-deficient cells showed a {asymp}3-fold increase in NADPH oxidase 2 (NOX2)-mediated superoxide production. Using unbiased proteomics, we identified the adapter protein Shc1 as a critical intermediate linking Syk phosphorylation to NOX2 activation. Shc1 phosphorylation during phagocytosis is dependent on Src family kinases and Syk, while genetic ablation of SHC1 reduced superoxide production by {asymp}40%. Proximity ligation assays reveal enhanced Shc1-p47phox interactions in PTP1B-deficient cells during phagocytosis. These findings establish an SFK-Syk-Shc1-NOX2 signaling axis that PTP1B negatively regulates at MCS between the ER and the forming phagosome, providing new mechanistic insights into antimicrobial responses during phagocytosis.

cell biology↗