Biology subjects

Bozic, M.

Publications and source records attributed to Bozic, M..

6 recordsLinked to original sources

bioRxiv2026

β-Adrenergic inhibition of exocytotic surface deposition of MHCII molecules in reactive astrocytes is mediated by amisyn

Degeneration of the locus coeruleus, a noradrenergic nucleus, reduces noradrenaline bioavailability in the central nervous system and promotes neuroinflammation via reactive astrocytes, although the underlying mechanisms remain unclear. We investigated whether interferon-{gamma}-induced expression of major histocompatibility complex class II (MHCII), a marker of pro-inflammatory reactive astrocytes, is regulated by adrenergic receptors and amisyn. {beta}-Adrenergic, but not -adrenergic, stimulation increased cyclic adenosine monophosphate (cAMP) and reduced MHCII expression, as detected immunocytochemically, in human and rat astrocytes. {beta}-Adrenergic treatment altered transient exocytosis of lysosome-like vesicles, increasing event frequency and reducing fusion-pore conductance and dwell time, thereby limiting MHCII surface expression. Overexpression of wild-type amisyn inhibited surface expression of MHCII and the lysosomal marker CD63 and reduced fusion-pore conductance and dwell time. Conversely, amisyn knockdown enhanced full fusion exocytosis of larger vesicles and abolished {beta}-adrenergic effects, indicating that amisyn mediates {beta}-adrenergic inhibition of exocytosis and MHCII surface deposition.

neuroscience↗

bioRxiv2026

Language Immersion Enhances Attentional Speech Processing via Low-Frequency Neural Tracking

Language experience is a powerful driver of neurocognitive plasticity, shown to modulate attentional and executive processing in speakers of multiple languages. This paper investigated how immersion in a second-language environment shapes attentional processing of speech. Fifty-eight bilingual Chinese-English speakers matched on their English language proficiency listened to competing continuous speech streams in a naturalistic listening task. They were immersed either in their native language environment (Beijing, China), or in the second language environment (Cambridge, UK). In an identical EEG experiment across the two immersion contexts, we assessed the listeners cortical tracking of attended and unattended speech and task-related attentional allocation using Temporal Response Function (mTRF) and Power Spectral Density (PSD) analyses. Behavioral comprehension of the attended narratives was uniformly high. PSD analyses showed no group difference in task-related attentional allocation, but mTRF results revealed robust differences in cortical tracking, with increased tracking of attended - but not unattended - streams in the immersed group, driven by the delta band (1-4 Hz). This boost in tracking of the attended signal declined with prolonged immersion, indicative of changes to attentional speech processing as the language environment stabilizes and consistent with the expansion-renormalization framework of neurocognitive adaptation. Jointly, these data imply that immersion in second-language environments shapes the way listeners encode speech, sharpening the brains ability to extract target auditory information from background noise. They furthermore suggest that, rather than being static or monotonous, this modulation reflects a flexible and dynamic process that is continuously shaped by changes in environmental demands and their duration. Key pointsO_LISecond language immersion boosts cortical tracking of attended speech, driven by the delta band (1-4 Hz). C_LIO_LIThis boost decreases with prolonged immersion, reflecting the dynamic, expansion-renormalization adaptation trajectory. C_LIO_LIImmersion does not influence task-related attentional allocation. C_LI

neuroscience↗

bioRxiv2025

Language usage modulates the neural mechanisms ofselective attention in bilinguals

The use of multiple languages modulates the neural mechanisms of selective attention, but it is unclear whether these adaptations require continuous engagement and active second language usage. Here we examined whether language usage shapes selective attention in bilingualism, and what neural processes might this engage. 48 highly proficient English-French bilinguals listened to naturalistic speech streams in their first or second language, paired with either linguistic and non-linguistic interference. Participants were matched on their L2 proficiency, but were either Active, Moderate, or Inactive users of their second language. The results revealed usage-related modulation of oscillatory activity in the alpha band, with more efficient inhibitory control in Active and Moderate users leading to behavioural resilience to interference. In contrast, usage did not affect lower-level perceptual tracking of speech, as captured by mTRF decoding of speech envelopes across frequency bands. Taken together, our findings show that resilience to interference during language processing is not dependent on the perceptual speech tracking, but rather on the capacity to recruit higher-level attentional control mechanisms, a process that is dynamically shaped by bilinguals L2 usage.

neuroscience↗

bioRxiv2025

Chronic lysosome damage boosts interferon responses to Palbociclib through a mitochondrial signalling axis

Acute lysosome damage triggers the endolysosome damage response (ELDR) in order to co-ordinate vesicle repair or removal by autophagy (lysophagy). However, it is unclear whether persistent damage, as occurs after chronic challenge to lysosome integrity, triggers wider cellular responses. Here, we show that longitudinal treatment with a lysosomotropic cancer therapeutic, the CDK4/6 inhibitor Palbociclib, invokes chronic lysosome damage in breast and lung cancer cells. Autophagy ameliorates but does not avert this phenotype, which persists over days. Damaged lysosomes form contacts with mitochondria, which correlates with mitochondrial stress and cytosolic efflux of immunostimulatory mitochondrial nucleic acids. Importantly, mitochondrial nucleic acid release is necessary for the anti-cancer interferon response to Palbociclib. In conclusion, chronic lysosome damage rewires cellular signalling responses in a mitochondrion-dependent manner and this effect should be considered when assessing the cellular actions of cancer therapeutics. Summary statementBozic et al suggest that lysosome damage can trigger interferon responses dependent upon mitochondrial release of immunogenic nucleic acid. This is associated with damaged lysosome-mitochondrion contacts and is prevented by autophagy.

cell biology↗

bioRxiv2020

Redistribution of cholesterol from vesicle to plasmalemma controls fusion pore geometry

Eukaryotic vesicles fuse with the plasmalemma to form the fusion pore, previously considered to be unstable with widening of the pore diameter. Recent studies established that the pore diameter is stable, reflecting balanced forces of widening and closure. Proteins are considered key regulators of the fusion pore, whereas the role of membrane lipids remains unclear. Super-resolution microscopy revealed that lactotroph secretory vesicles discharge cholesterol after stimulation of exocytosis; subsequently, vesicle cholesterol redistributes to the outer leaflet of the plasmalemma. Cholesterol depletion in lactotrophs and astrocytes evokes release of vesicle hormone, indicating that cholesterol constricts the fusion pore. A new model of cholesterol-dependent fusion pore diameter regulation is proposed. High-resolution measurements of fusion pore conductance confirmed that the fusion pore widens with cholesterol depletion and constricts with cholesterol enrichment. In fibroblasts lacking the Npc1 protein, in which cholesterol accumulates in vesicles, the fusion pore is narrower than in controls, showing that cholesterol regulates fusion pore geometry. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/027169v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@73168borg.highwire.dtl.DTLVardef@1cd2afdorg.highwire.dtl.DTLVardef@c170f9org.highwire.dtl.DTLVardef@1dfff4f_HPS_FORMAT_FIGEXP M_FIG C_FIG Top: stages through which a vesicle interacts with the plasmalemma. Stage A denotes hemifusion, which proceeds to stage B, with a narrow fusion pore, which can then reversibly open (stage C), before widening fully (stage D). Bottom: redistribution of cholesterol from the vesicle to the outer leaflet of the plasmalemma controls fusion pore constriction. In BriefA membrane pore is formed when the vesicle membrane fuses with the plasmalemma. Proteins were considered key regulators of the opening and closing of this fusion pore. Here, evidence is provided to show that cholesterol, a membrane constituent, determines a radial force constricting the fusion pore, revealing that the fusion pore functions as a proteolipidic structure. HighlightsO_LIIntravesicular cholesterol redistributes to the outer leaflet of the plasmalemma. C_LIO_LICholesterol depletion widens the fusion pore, whereas cholesterol enrichment constricts the fusion pore. C_LIO_LIA model of cholesterol-dependent force preventing fusion pore widening is developed. C_LIO_LIDisease-related increase in vesicle cholesterol constricts the fusion pore. C_LI

cell biology↗

bioRxiv2019

A conserved ATG2-GABARAP interaction is critical for phagophore closure

The intracellular trafficking pathway, macroautophagy, acts as a recycling and disposal service that can be upregulated during periods of stress, to maintain cellular homeostasis. An essential transition point in the pathway is the sealing of the immature phagophore to form an autophagosome, isolating unwanted cargo prior to lysosomal degradation. However, little mechanistic detail is known about phagophore closure. Human ATG2A and ATG2B proteins, through their interaction with WIPI proteins, are thought to be key players during phagophore closure. We have identified a highly-conserved motif driving the interaction between human ATG2 and GABARAP proteins that is in close proximity to the ATG2-WIPI4 interaction site. We show that the ATG2-GABARAP interaction mutants are unable to close phagophores resulting in blocked autophagy, similar to ATG2A/ATG2B double knock-out cells. In contrast, the ATG2-WIPI4 interaction mutant fully restored phagophore closure and autophagy flux, similar to wild type ATG2. Taken together, we provide new mechanistic insights to the requirements for ATG2 function at the phagophore and suggest that an ATG2-GABARAP interaction is essential for phagophore closure, whereas ATG2-WIPI4 interaction is dispensable.

cell biology↗