Dynamic Reorganization Research Articles

Study of dynamic brain function in irritable bowel syndrome via Hidden Markov Modeling

Background and purposeIrritable bowel syndrome (IBS) is a common bowel-brain interaction disorder whose pathogenesis is unclear. Many studies have investigated abnormal changes in brain function in IBS patients. In this study, we analyzed the dynamic changes in brain function in IBS patients using a Hidden Markov Model (HMM).MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data and the clinical characteristics of 35 patients with IBS and 31 healthy controls (HCs) were collected. The rs-fMRI data of all participants were analyzed using HMM to identify recurrent brain activity states that evolve over time during the resting state. Additionally, the temporal properties of these HMM states and their correlations with clinical scale scores were examined.ResultThis study utilized the Hidden Markov Model (HMM) method to identify six distinct HMM states. Significant differences in fractional occupancy (FO) and lifetime (LT) were observed in states 5 and 6 between the IBS and HCs. The state transition probabilities differed between IBS and HCs, with an increased probability of transitioning from state 2 to state 6 in IBS patients. The reconfiguration of HMM states over time scales in IBS patients was associated with abnormal activity in the default mode network (DMN), sensorimotor network (SMN), and cingulo-opercular network (CON).ConclusionThis study offers novel insights into the dynamic reorganization of brain activity patterns in IBS and elucidates potential links between these patterns and IBS-related emotional regulation and symptom experience, thereby contributing to a deeper understanding of the neural mechanisms underlying IBS.

LDB1 establishes multi-enhancer networks to regulate gene expression.

How specific enhancer-promoter pairing is established remains mostly unclear. Besides the CTCF/cohesin machinery, few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Using a murine erythroid cell model, we show via acute degradation experiments that LDB1 directly and broadly promotes connectivity among regulatory elements. Most LDB1-mediated contacts, even those spanning hundreds of kb, can form in the absence of CTCF, cohesin, or YY1 as determined using multiple degron systems. Moreover, an engineered LDB1-driven chromatin loop is cohesin independent. Cohesin-driven loop extrusion does not stall at LDB1-occupied sites but aids the formation of a subset of LDB1-anchored loops. Leveraging the dynamic reorganization of nuclear architecture during the transition from mitosis to G1 phase, we observe that loop formation and de novo LDB1 occupancy correlate and can occur independently of structural loops. Tri-C and Region Capture Micro-C reveal that LDB1 organizes multi-enhancer networks to activate transcription. These findings establish LDB1 as a driver of spatial connectivity.

An Immune-Independent Mode of Action of Tacrolimus in Promoting Human Extravillous Trophoblast Migration Involves Intracellular Calcium Release and F-Actin Cytoskeletal Reorganization.

We have previously reported that the calcineurin inhibitor macrolide immunosuppressant Tacrolimus (TAC, FK506) can promote the migration and invasion of the human-derived extravillous trophoblast cells conducive to preventing implantation failure in immune-complicated gestations manifesting recurrent implantation failure. Although the exact mode of action of TAC in promoting implantation has yet to be elucidated, the integral association of its binding protein FKBP12 with the inositol triphosphate receptor (IP3R) regulated intracellular calcium [Ca2+]i channels in the endoplasmic reticulum (ER), suggesting that TAC can mediate its action through ER release of [Ca2+]i. Using the immortalized human-derived first-trimester extravillous trophoblast cells HTR8/SVneo, our data indicated that TAC can increase [Ca2+]I, as measured by fluorescent live-cell imaging using Fluo-4. Concomitantly, the treatment of HTR8/SVneo with TAC resulted in a major dynamic reorganization in the actin cytoskeleton, favoring a predominant distribution of cortical F-actin networks in these trophoblasts. Notably, the findings that TAC was unable to recover [Ca2+]i in the presence of the IP3R inhibitor 2-APB indicate that this receptor may play a crucial role in the mechanism of action of TAC. Taken together, our results suggest that TAC has the potential to influence trophoblast migration through downstream [Ca2+]i-mediated intracellular events and mechanisms involved in trophoblast migration, such as F-actin redistribution. Further research into the mono-therapeutic use of TAC in promoting trophoblast growth and differentiation in clinical settings of assisted reproduction is warranted.

Dynamic reorganization of multivesicular bodies and exosome production impacted by sonoporation

Naturally occurring cell-derived extracellular vesicles (EVs) have emerged as attractive nanocarriers for drug delivery. However, production of large quantities of EVs for clinical applications in a scalable manner remains a significant challenge. This study investigated at the single cell level how sonoporation, or membrane poration produced by ultrasound-induced microbubble cavitation, impacts EV production using mouse macrophage RAW 264.7 cells stably expressing CD63-GFP as a model system. Real-time fluorescence videomicroscopy detected rapid changes in CD63-GFP, a tetraspanin family member highly enriched in intraluminal vesicles tagged with GFP, to track changes in multivesicular bodies (MVBs), which are the cellular compartments where exosomes originate within the cells. Our results revealed distinct dynamic changes in CD63-GFP intensity and distribution in RAW 264.7 cells in terms of response time and duration depending on whether the cells were directly or indirectly impacted by sonoporation, suggesting reorganization of MVBs in response to direct and indirect mechanisms resulted from the mechanical impact of ultrasound pulse on the cells. Analysis of the supernatant from sonoporation-treated RAW 264.7 cells expressing CD63-GFP demonstrated a delayed and sustained increase in the production of CD63-GFP-positive EVs. These results show the robust and detailed effect of sonoporation and reveal insights into sonoporation-induced EV release useful for guiding the application of sonoporation to enhance large-scale EV production.

Touch to text: Spatiotemporal evolution of braille letter representations in blind readers.

Visual deprivation does not silence the visual cortex, which is responsive to auditory, tactile, and other nonvisual tasks in blind persons. However, the underlying functional dynamics of the neural networks mediating such crossmodal responses remain unclear. Here, using braille reading as a model framework to investigate these networks, we presented sighted (N=13) and blind (N=12) readers with individual visual print and tactile braille alphabetic letters, respectively, during MEG recording. Using time-resolved multivariate pattern analysis and representational similarity analysis, we traced the alphabetic letter processing cascade in both groups of participants. We found that letter representations unfolded more slowly in blind than in sighted brains, with decoding peak latencies ~200 ms later in braille readers. Focusing on the blind group, we found that the format of neural letter representations transformed within the first 500 ms after stimulus onset from a low-level structure consistent with peripheral nerve afferent coding to high-level format reflecting pairwise letter embeddings in a text corpus. The spatiotemporal dynamics of the transformation suggest that the processing cascade proceeds from a starting point in somatosensory cortex to early visual cortex and then to inferotemporal cortex. Together our results give insight into the neural mechanisms underlying braille reading in blind persons and the dynamics of functional reorganization in sensory deprivation.

Adaptive rewiring: a general principle for neural network development.

The nervous system, especially the human brain, is characterized by its highly complex network topology. The neurodevelopment of some of its features has been described in terms of dynamic optimization rules. We discuss the principle of adaptive rewiring, i.e., the dynamic reorganization of a network according to the intensity of internal signal communication as measured by synchronization or diffusion, and its recent generalization for applications in directed networks. These have extended the principle of adaptive rewiring from highly oversimplified networks to more neurally plausible ones. Adaptive rewiring captures all the key features of the complex brain topology: it transforms initially random or regular networks into networks with a modular small-world structure and a rich-club core. This effect is specific in the sense that it can be tailored to computational needs, robust in the sense that it does not depend on a critical regime, and flexible in the sense that parametric variation generates a range of variant network configurations. Extreme variant networks can be associated at macroscopic level with disorders such as schizophrenia, autism, and dyslexia, and suggest a relationship between dyslexia and creativity. Adaptive rewiring cooperates with network growth and interacts constructively with spatial organization principles in the formation of topographically distinct modules and structures such as ganglia and chains. At the mesoscopic level, adaptive rewiring enables the development of functional architectures, such as convergent-divergent units, and sheds light on the early development of divergence and convergence in, for example, the visual system. Finally, we discuss future prospects for the principle of adaptive rewiring.

Functional connectivity across the lifespan: a cross-sectional analysis of changes.

In the era of functional brain networks, our understanding of how they evolve across life in a healthy population remains limited. Here, we investigate functional connectivity across the human lifespan using magnetoencephalography in a cohort of 792 healthy individuals, categorized into young (13 to 30 yr), middle (31 to 54 yr), and late adulthood (55 to 80 yr). Employing corrected imaginary phase-locking value, we map the evolving landscapes of connectivity within delta, theta, alpha, beta, and gamma classical frequency bands among brain areas. Our findings reveal significant shifts in functional connectivity patterns across all frequency bands, with certain networks exhibiting increased connectivity and others decreased, dependent on the frequency band and specific age groups, showcasing the dynamic reorganization of neural networks as age increases. This detailed exploration provides, to our knowledge, the first all-encompassing view of how electrophysiological functional connectivity evolves at different life stages, offering new insights into the brain's adaptability and the intricate interplay of cognitive aging and network connectivity. This work not only contributes to the body of knowledge on cognitive aging and neurological health but also emphasizes the need for further research to develop targeted interventions for maintaining cognitive function in the aging population.

Dynamic Reorganization Patterns of Brain Modules after Stroke Reflecting Motor Function.

Advancements in neuroimaging technologies have significantly deepened our understanding of the neural physiopathology associated with stroke. Nevertheless, the majority of studies ignored the characteristics of dynamic changes in brain networks. The relationship between dynamic changes in brain networks and the severity of motor dysfunction after stroke needs further investigation. From the perspective of multilayer network module reconstruction, we aimed to explore the dynamic reorganization of the brain and its relationship with motor function in subcortical stroke patients. We recruited 35 healthy individuals and 50 stroke patients with unilateral limb motor dysfunction (further divided into mild-moderate group and severe group). Using dynamic multilayer network modularity analysis, we investigated changes in the dynamic modular reconfiguration of brain networks. Additionally, we assessed longitudinal clinical scale changes in stroke patients. Correlation and regression analyses were employed to explore the relationship between characteristic dynamic indicators and impairment and recovery of motor function, respectively. We observed increased temporal flexibility in the Default Mode Network (DMN) and decreased recruitment of module reconfiguration in the Attention Network (AN), Sensorimotor Network (SMN), and DMN after stroke. We also observed reduced module loyalty following stroke. Additionally, correlation analysis showed that hyper-flexibility of the DMN was associated with better lower limb motor function performance in stroke patients with mild-to-moderate impairment. Regression analysis indicated that increased flexibility within the DMN and decreased recruitment coefficient within the AN may predict good lower limb function prognosis in patients with mild to moderate motor impairment. Our study revealed more frequent modular reconfiguration and hyperactive interaction of brain networks after stroke. Notably, dynamic modular remodeling was closely related to the impairment and recovery of motor function. Understanding the temporal module reconfiguration patterns in multilayer networks after stroke can provide valuable information for more targeted treatments.

Dynamic functional network connectivity and its association with lipid metabolism in Alzheimer's disease.

The study aims to examine the changing trajectory characteristics of dynamic functional network connectivity (dFNC) and its correlation with lipid metabolism-related factors across the Alzheimer's disease (AD) spectrum populations. Data from 242 AD spectrum subjects, including biological, neuroimaging, and general cognition, were obtained from the Alzheimer's Disease Neuroimaging Initiative for this cross-sectional study. The study utilized a sliding-window approach to assess whole-brain dFNC, investigating group differences and associations with biological and cognitive factors. Abnormal dFNC was used in the classification of AD spectrum populations by support vector machine. Mediation analysis was performed to explore the relationships between lipid-related indicators, dFNC, cerebrospinal fluid (CSF) biomarkers, and cognitive performance. Significant group difference concerning were observed in relation to APOE-ε4 status, CSF biomarkers, and cognitive scores. Two reoccurring connectivity states were identified: state-1 characterized by frequent but weak connections, and state-II characterized by less frequent but strong connections. Pre-AD subjects exhibited a preference for spending more time in state-I, whereas AD patients tended remain in state-II for longer periods. Group difference in dFNC was primarily found between AD and non-AD participants within each state. The dFNC of state-I yielded strong power to distinguish AD from other groups compared with state-II. APOE-ε4+, high polygenic score, and high serum lipid group were strongly associated with network disruption between association cortex system and sensory cortex system that characterized elevation of cognitive function, which may suggest a compensatory mechanism of dFNC in state-I, whereas differential connections of state-II mediated the relationships between APOE-ε4 genotype and CSF biomarkers, and cognitive indicators. The dysfunction of dFNC temporal-spatial patterns and increased cognition in individuals with APOE-ε4, high polygenic score, and higher serum lipid levels shed light on the lipid-related mechanisms of dynamic network reorganization in AD.

LDB1 establishes multi-enhancer networks to regulate gene expression.

How specific enhancer-promoter pairing is established is still mostly unclear. Besides the CTCF/cohesin machinery, only a few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Here, we show via acute degradation experiments that LDB1 directly and broadly promotes enhancer-promoter loops. Most LDB1-mediated contacts, even those spanning hundreds of kb, can form in the absence of CTCF, cohesin, or YY1 as determined via the use of multiple degron systems. Moreover, an engineered LDB1-driven chromatin loop is cohesin independent. Cohesin-driven loop extrusion does not stall at LDB1 occupied sites but may aid the formation of a subset of LDB1 anchored loops. Leveraging the dynamic reorganization of nuclear architecture during the transition from mitosis to G1-phase, we establish a relationship between LDB1-dependent interactions in the context of TAD organization and gene activation. Lastly, Tri-C and Region Capture Micro-C reveal that LDB1 organizes multi-enhancer networks to activate transcription. This establishes LDB1 as a direct driver of regulatory network inter-connectivity.

Magnetic Field Driven Dynamic Reorganization of Electrocatalytic Interface for Sustainable Enhancement in Oxygen Evolution

Hydrogen with high calorific content (150 MJ/kg) and environment-friendly combustion product (H2O) becomes the alternative fossil fuel. Catalytic electrolysis of water is one of the attractive routes for generating H2. Energy-efficient and cost-effective electrolytic production of H2 has predominantly focused on lowering the overpotential for water splitting process by developing newer non-Pt group-based catalysts.This work demonstrates a new direction towards sustainable oxygen evolution reaction (OER) by exploiting the fundamental interplay of electromagnetic forces. Introducing an external magnetic field (Hext = 100 mT) perpendicular to the heterogeneous electrocatalytic interface produces an unprecedented increase in rate of electrocatalytic OER in phosphate buffer with pH=7. Such electromagnetic catalysis is achieved with metal phosphides (NiCoP and NiCoFeP) with different morphology, leading 2.5 fold increase in the OER current density and concomitant lowering of overpotential by 10% (Hext = 100 mT). Thereby, 50% lowering of charge transfer resistance (Rct) is achieved. This is substantiated by the lowering of the Tafel slope (by 5%) in the presence of Hext. Thus, we report two important observations influenced by the magnetic field: (a) direct effect of magnetic field on the catalyst surface to reduce the charge-transfer resistance, (b) spin-dependant OER process to get influenced under magnetic field and (c) indirect effect of magnetic field to sustain the magneto-electrocatalytic enhancement even after removing the magnetic field. The time-scale of magnetic relaxation is million times higher than conventional spin-lattice relaxation events in para/ferromagnetic systems. Such long-term stability of magnetized states is predominantly proposed to be originating from the NiCoP and NiCoFeP interface. So, we attribute the long-lived states to be additionally contributed from the volumetric expansion and active site expansion of the catalyst upon magnetization. Catalyst interface is arising due to the dendritic structure of catalyst. Such synergism of magnetization, is expected to increase the applicability of magneto-electrocatalysis as a more sustainable electrocatalytic approach towards a hydrogen-driven economy. Figure 1

Cytosolic protein translation regulates cell asymmetry and function in early TCR activation of human CD8+ T lymphocytes.

CD8+ cytotoxic T lymphocytes (CTLs) are highly effective in defending against viral infections and tumours. They are activated through the recognition of peptide-MHC-I complex by the T-cell receptor (TCR) and co-stimulation. This cognate interaction promotes the organisation of intimate cell-cell connections that involve cytoskeleton rearrangement to enable effector function and clearance of the target cell. This is key for the asymmetric transport and mobilisation of lytic granules to the cell-cell contact, promoting directed secretion of lytic mediators such as granzymes and perforin. Mitochondria play a role in regulating CTL function by controlling processes such as calcium flux, providing the necessary energy through oxidative phosphorylation, and its own protein translation on 70S ribosomes. However, the effect of acute inhibition of cytosolic translation in the rapid response after TCR has not been studied in mature CTLs. Here, we investigated the importance of cytosolic protein synthesis in human CTLs after early TCR activation and CD28 co-stimulation for the dynamic reorganisation of the cytoskeleton, mitochondria, and lytic granules through short-term chemical inhibition of 80S ribosomes by cycloheximide and 80S and 70S by puromycin. We observed that eukaryotic ribosome function is required to allow proper asymmetric reorganisation of the tubulin cytoskeleton and mitochondria and mTOR pathway activation early upon TCR activation in human primary CTLs. Cytosolic protein translation is required to increase glucose metabolism and degranulation capacity upon TCR activation and thus to regulate the full effector function of human CTLs.

Dynamics of the Boundary Layer in Pulsed CO2 Electrolysis.

Electrochemical reduction of CO2 poses a vast potential to contribute to a defossilized industry. Despite tremendous developments within the field, mass transport limitations, carbonate salt formation, and electrode degradation mechanisms still hamper the process performance. One promising approach to tweak CO2 electrolysis beyond today's limitations is pulsed electrolysis with potential cycling between an operating and a regeneration mode. Here, we rigorously model the boundary layer at a silver electrode in pulsed operation to get profound insights into the dynamic reorganization of the electrode microenvironment. In our simulation, pulsed electrolysis leads to a significant improvement of up to six times higher CO current density and 20 times higher cathodic energy efficiency when pulsing between -1.85 and -1.05 V vs SHE compared to constant potential operation. We found that elevated reactant availability in pulsed electrolysis originates from alternating replenishment of CO2 by diffusion and not from pH-induced carbonate and bicarbonate conversion. Moreover, pulsed electrolysis substantially promotes carbonate removal from the electrode by up to 83 % compared to constant potential operation, thus reducing the risk of salt formation. Therefore, this model lays the groundwork for an accurate simulation of the dynamic boundary layer modulation, which can provide insights into manifold electrochemical conversions.

Dynamics of the Boundary Layer in Pulsed CO2 Electrolysis

AbstractElectrochemical reduction of CO2 poses a vast potential to contribute to a defossilized industry. Despite tremendous developments within the field, mass transport limitations, carbonate salt formation, and electrode degradation mechanisms still hamper the process performance. One promising approach to tweak CO2 electrolysis beyond today's limitations is pulsed electrolysis with potential cycling between an operating and a regeneration mode. Here, we rigorously model the boundary layer at a silver electrode in pulsed operation to get profound insights into the dynamic reorganization of the electrode microenvironment. In our simulation, pulsed electrolysis leads to a significant improvement of up to six times higher CO current density and 20 times higher cathodic energy efficiency when pulsing between −1.85 and −1.05 V vs SHE compared to constant potential operation. We found that elevated reactant availability in pulsed electrolysis originates from alternating replenishment of CO2 by diffusion and not from pH‐induced carbonate and bicarbonate conversion. Moreover, pulsed electrolysis substantially promotes carbonate removal from the electrode by up to 83 % compared to constant potential operation, thus reducing the risk of salt formation. Therefore, this model lays the groundwork for an accurate simulation of the dynamic boundary layer modulation, which can provide insights into manifold electrochemical conversions.

RhoGDI1 regulates cell-cell junctions in polarized epithelial cells.

Cell-cell contact formation of polarized epithelial cells is a multi-step process that involves the co-ordinated activities of Rho family small GTPases. Consistent with the central role of Rho GTPases, a number of Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) have been identified at cell-cell junctions at various stages of junction maturation. As opposed to RhoGEFs and RhoGAPs, the role of Rho GDP dissociation inhibitors (GDIs) during cell-cell contact formation is poorly understood. Here, we have analyzed the role of RhoGDI1/ARHGDIA, a member of the RhoGDI family, during cell-cell contact formation of polarized epithelial cells. Depletion of RhoGDI1 delays the development of linear cell-cell junctions and the formation of barrier-forming tight junctions. In addition, RhoGDI1 depletion impairs the ability of cells to stop migration in response to cell collision and increases the migration velocity of collectively migrating cells. We also find that the cell adhesion receptor JAM-A promotes the recruitment of RhoGDI1 to cell-cell contacts. Our findings implicate RhoGDI1 in various processes involving the dynamic reorganization of cell-cell junctions.

Activity-Dependent Remodeling of Corticostriatal Axonal Boutons During Motor Learning.

Motor skill learning induces long-lasting synaptic plasticity at not only the inputs, such as dendritic spines1-4, but also at the outputs to the striatum of motor cortical neurons5,6. However, very little is known about the activity and structural plasticity of corticostriatal axons during learning in the adult brain. Here, we used longitudinal in vivo two-photon imaging to monitor the activity and structure of thousands of corticostriatal axonal boutons in the dorsolateral striatum in awake mice. We found that learning a new motor skill induces dynamic regulation of axonal boutons. The activities of motor corticostriatal axonal boutons exhibited selectivity for rewarded movements (RM) and un-rewarded movements (UM). Strikingly, boutons on the same axonal branches showed diverse responses during behavior. Motor learning significantly increased the fraction of RM boutons and reduced the heterogeneity of bouton activities. Moreover, motor learning-induced profound structural dynamism in boutons. By combining structural and functional imaging, we identified that newly formed axonal boutons are more likely to exhibit selectivity for RM and are stabilized during motor learning, while UM boutons are selectively eliminated. Our results highlight a novel form of plasticity at corticostriatal axons induced by motor learning, indicating that motor corticostriatal axonal boutons undergo dynamic reorganization that facilitates the acquisition and execution of motor skills.

Tracking glass beads: communities and exchange relationships across the Atlantic in the seventeenth century

Minimally invasive compositional analyses of glass trade beads have revolutionised the study of these highly portable and socially significant items. Here, the authors interrogate new and legacy compositional data to investigate how Indigenous communities in eastern North America, particularly Wendat confederacy members, obtained beads from European traders and connected to broader interregional exchange systems c. AD 1600–1670. Diagnostic chemical elements in glass compositions reveal down-the-line exchange and population movement into the Western Great Lakes region prior to the arrival of European settlers, which highlights active Indigenous participation in transatlantic economic networks during a historical period of dynamic reorganisation and interaction.

Contributions of dysfunctional plasticity mechanisms to the development of atypical perceptual processing.

Experimental studies of sensory plasticity during development in birds and mammals have highlighted the importance of sensory experiences for the construction and refinement of functional neural circuits. We discuss how dysregulation of experience-dependent brain plasticity can lead to abnormal perceptual representations that may contribute to heterogeneous deficits symptomatic of several neurodevelopmental disorders. We focus on alterations of somatosensory processing and the dynamic reorganization of cortical synaptic networks that occurs during early perceptual development. We also discuss the idea that the heterogeneity of strengths and weaknesses observed in children with neurodevelopmental disorders may be a direct consequence of altered plasticity mechanisms during early development. Treating the heterogeneity of perceptual developmental trajectories as a phenomenon worthy of study rather than as an experimental confound that should be overcome may be key to developing interventions that better account for the complex developmental trajectories experienced by modern humans.

Withdrawn: The altered dynamic community structure for adaptive adjustment in stroke patients with multidomain cognitive impairments: A multilayer network analysis

BackgroundInternal capsule strokes can lead to multidomain cognitive impairments, and while the brain showcases adaptability post-stroke, the interplay between this adaptability and multidomain cognitive function remains elusive. In addition, although most studies indicate that adaptive changes after stroke manifest as brain functional network abnormalities, the changes in dynamic topological features, especially dynamic community structure, required for adaptive adjustment in stroke patients are not yet clear. MethodsResting-state fMRI data were acquired from patients with infarct in left-sided (n = 46, CI_L) and right-sided (n = 45, CI_R) internal capsule and 81 healthy controls (HC). Dynamic network matrices were generated using a sliding-window approach. These matrices were partitioned into communities utilizing a multilayer community detection algorithm. The network switching rate were employed as a key metric to characterize the differences of dynamic community structure between stroke and HC groups, and the correlations between these significant intergroup differences and cognitive performance scores was calculated. ResultsCompared to HC, CI_L patients exhibited an increase in network switching rates across all networks in the whole brain. However, these increases were largely unbeneficial for cognitive recovery; CI_R group show a more limited range of increased network switching rates and a more limited negative correlations with cognitive performance. ConclusionsThis study elucidates that following a stroke, the brain continuously adapts its dynamic community structure in an effort to address multidomain cognitive impairments, but this adaptation is often ineffective, unorganized, and disordered. Moreover, these findings elucidate the lateralized effects of stroke lesions on dynamic reorganization.

A circle of life: platelet and megakaryocyte cytoskeleton dynamics in health and disease.

Platelets are blood cells derived from megakaryocytes that play a central role in regulating haemostasis and vascular integrity. The microtubule cytoskeleton of megakaryocytes undergoes a critical dynamic reorganization during cycles of endomitosis and platelet biogenesis. Quiescent platelets have a discoid shape maintained by a marginal band composed of microtubule bundles, which undergoes remarkable remodelling during platelet activation, driving shape change and platelet function. Disrupting or enhancing this process can cause platelet dysfunction such as bleeding disorders or thrombosis. However, little is known about the molecular mechanisms underlying the reorganization of the cytoskeleton in the platelet lineage. Recent studies indicate that the emergence of a unique platelet tubulin code and specific pathogenic tubulin mutations cause platelet defects and bleeding disorders. Frequently, these mutations exhibit dominant negative effects, offering valuable insights into both platelet disease mechanisms and the functioning of tubulins. This review will highlight our current understanding of the role of the microtubule cytoskeleton in the life and death of platelets, along with its relevance to platelet disorders.