Search bioRxiv⌕ Search

Biology subjects

De Luca, M.

Publications and source records attributed to De Luca, M..

6 recordsLinked to original sources

Why they move: breeding-site availability drives partial migration in a large terrestrial reptile

1. Migration is a widespread phenomenon across taxa, yet the ecological mechanisms underlying its evolution and maintenance, particularly whether migratory behaviors are primarily driven by access to spatially restricted breeding sites or by seasonal tracking of trophic resources, remain poorly documented outside birds and large mammals. Despite increasing evidence that reptiles perform seasonal migrations, the ecological mechanisms underlying these movements have rarely been formally tested. 2. The critically endangered Galapagos pink land iguana (Conolophus marthae), endemic to Wolf Volcano, Isabela Island, exhibits partial migration along a steep altitudinal gradient, providing an opportunity to disentangle the relative roles of breeding-site availability, trophic resource dynamics, and thermoregulatory conditions as drivers of migration. 3. We used GPS tracking data from 22 individuals (7 males, 15 females) monitored between 2019 and 2023, combined with high-resolution spatio-temporal models of vegetation productivity and air temperature across the species' altitudinal range, to characterize population-level movement patterns and evaluate competing hypotheses explaining the evolution of this migratory behavior. 4. Movement models revealed a clear pattern of partial migration: 16 out of 22 tracked individuals performed seasonal altitudinal movements between a restricted high-elevation mating area and a larger dispersal area at lower elevation, with males reaching the mating area approximately 48 days earlier than females. The dispersal area remained consistently more productive than the mating area throughout the year, rejecting the prediction that individuals should track the shifting trophic resource peaks. Instead, the mating season coincided with the local productivity peak within the mating area, whereas temperature differences between areas were small (ca. 2{degrees}C) and did not explain migration timing. 5. These results support a site-dependent hypothesis of partial migration over a resource-tracking hypothesis, indicating that access to spatially restricted breeding sites is the primary driver of migration in this species, with local trophic resource dynamics fine-tuning reproductive timing. Providing empirical evidence for the ecological mechanisms underlying migration in a large terrestrial reptile, our results extend site-dependent theories of migration beyond birds and mammals and identify breeding-site availability as a key ecological driver of migratory behaviors across taxa.

ecology↗

Departure from OFF-State Microstate Dynamics Tracks Levodopa Response in Parkinson's Disease

Although dopaminergic therapies in Parkinsons disease primarily restore dopamine within nigrostriatal circuits, symptoms are better indexed by whole-brain dynamics than by local activity. In this manuscript, we hypothesize that L-Dopa therapy affects whole-brain dynamics alike, which in turn relate to clinical improvement. To test this hypothesis, we conducted a repeated-measures, source-reconstructed MEG study in 13 bradykinetic-dominant PD patients, recording resting-state cortical activity OFF medication and [~]1 hour after levodopa administration (ON). We characterize brain dynamics using a microstate framework, in which transition probabilities between microstates are used to contrast pathological OFF-state dynamics with those in the ON-state. Microstate dynamics were stable within medication states but reconfigured by L-Dopa, with greater departures from the OFF-state pattern associated, at the individual level, with larger clinical improvements. Our results suggest that individualized changes in microstate dynamics may serve as a neurophysiological marker of dopaminergic responsiveness.

neuroscience↗

Hormone-Dependent Microstates and the Reconfiguration of Resting-State Dynamics across the Menstrual Cycle

While behavioral fluctuations across the menstrual cycle (MC) are well-documented, the neural underpinnings of these changes remain elusive. This study investigated the hypothesis that cyclic variations in sex hormones modulate large-scale brain activation patterns. To test this, longitudinal magnetoencephalographic (MEG) recordings were acquired and source reconstructed from 24 naturally cycling women across three distinct MC phases: early follicular, peri-ovulatory, and mid-luteal. Microstate analysis was employed to characterize large-scale cortical dynamics as "visits" to specific global configurations (i.e., maps) of brain activity. Our results revealed significant variations in the occurrence of specific microstate maps, particularly between the early follicular and mid-luteal phases. Furthermore, the occurrence of these specific configurations was significantly associated with fluctuations in hormone levels. Critically, both the hormonal levels and microstate dynamics were predictive of individual longitudinal changes in psychological well-being. These findings propose a neurophysiological substrate for the behavioral effects of hormonal cycling, identifying specific topographic maps whose dynamics are sensitive to the hormonal profile and carry predictive power for psychological health. Collectively, these results underscore the necessity of accounting for the MC in neuroimaging research and introduce a novel framework for defining microstates (Hormone-Dependent Microstates - HDMs) with respect to slowly changing dynamical properties across a month-long timescale.

neuroscience↗

The role of structural heterogeneity in shaping whole-brain dynamics across scales

The brain must rapidly and dynamically recruit the appropriate brain regions to respond to environmental changes and sustain flexible cognition. An extensive body of literature views the ability to spontaneously explore a rich repertoire of activity patterns, even during rest, as a correlate of the capacity to respond rapidly to internal fluctuations and external stimuli. Moreover, brain flexibility at rest successfully indexes pathological conditions such as Parkinsons disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, previous work provides no information about the contribution of each region to the flexibility of brain dynamics. Given the functional and structural heterogeneity of brain regions, we hypothesized their roles in sustaining flexibility to be heterogeneous and related to regional structural properties. To systematically investigate these hypotheses, we define the flexibility gradient (FG), a new measure, which quantifies regional contributions to flexibility. We employed three datasets spanning different recording techniques and a range of spatial and temporal scales: 47 MEG recordings, 11 EEG recordings, and 77 fMRI recordings along with the corresponding tractographies. We found that FG is not homogeneously distributed, with associative and occipital regions contributing the most. This gradient is symmetric across left and right hemispheres, and the structural properties of brain regions correlate with their contribution to flexibility. Our findings are stable across modalities and temporal scales, highlighting that brain flexibility is not only a global dynamical property but also a spatially structured feature shaped by the anatomical organization of the brain.

neuroscience↗

Revisiting degron motifs in human AURKA required for its targeting by APC/C-FZR1

Mitotic kinase Aurora A (AURKA) diverges from other kinases in its multiple active conformations that may explain its interphase roles and association with cancer, and the limited efficacy of drugs targeting the kinase pocket. Regulation of AURKA activity by the cell is critically dependent on destruction mediated by the Anaphase-Promoting Complex (APC/CFZR1) during mitotic exit and G1 phase and requires an atypical N-terminal degron in AURKA called the A-box in addition to a reported canonical D-box degron in the C-terminus. Here we find that the proposed C-terminal D-box of AURKA does not act as a degron and instead mediates essential structural features of the protein. In living cells, as previously reported in vitro, the N-terminal intrinsically disordered region (IDR) of AURKA containing the A-box is sufficient to confer FZR1-dependent mitotic degradation. Both in silico and in cellulo assays predict the QRVL Short Linear Interacting Motif (SLiM) of the A-box to be a phospho-regulated D-box. We propose that degradation of full-length AURKA additionally depends on an intact C-terminal domain because of critical conformational parameters permissive for both activity and mitotic degradation of AURKA. Summary blurbAURKA degron motifs are redefined to show that the so-called N-terminal A-box is in fact a D-box, and the so-called D-box in the C-terminus is not a degron but a motif critical for the active, degradable conformation of AURKA

cell biology↗

Transient upregulation of translational efficiency in prodromal Tg2576 mice precipitates AD symptoms

Tg2576 mice overexpressing APPK670/671L exhibit elevated hAPP levels from birth but remain at a prodromal stage until 3 months of age. Whether variations in hAPP mRNA specific and overall translation occur during development and precipitates the transition from an asymptomatic to a symptomatic stage is unknown. By performing polysome profiling and distribution of hAPP, and measuring the levels of eukaryotic initial translation factors in hippocampal extracts from pre- and early symptomatic Tg2576 mice, we found that the presence of mRNA and protein polysomal signals was associated with decreased levels of the phosphorylated form of the initial translation factor eIF2 (p-eIF2), revealing a transient upregulation of overall translation. Differently, the reduction of hAPP mRNA polysomal signals was associated with increased p-eIF2 levels - repressing translation-when mice were symptomatic, suggesting a compensatory mechanism aimed at downregulating hAPP mRNA. Confirming that prodromal upregulation of translational efficiency contributes to AD pathogenesis, pharmacological restoration of proper translational control in early symptomatic mice blocked the manifestation of neural and cognitive AD-like alterations.

neuroscience↗