Time-dependent Reorganization Research Articles

Dynamic surfactants drive anisotropic colloidal assembly.

Colloidal building blocks with re-configurable shapes and dynamic interactions can exhibit unusual self-assembly behaviors and pathways. In this work, we consider the phase behavior of colloids coated with surface-mobile polymer brushes that behave as "dynamic surfactants." Unlike traditional polymer-grafted colloids, we show that colloids coated with dynamic surfactants can acquire anisotropic macroscopic assemblies, even for spherical colloids with isotropic attractive interactions. We use Brownian Dynamics simulations and dynamic density functional theory to demonstrate that time-dependent reorganization of the dynamic surfactants leads to phase diagrams with anisotropic assemblies. We observed that the microscopic polymer distributions impose unique geometric constraints between colloids that control their packing into lamellar, string, and vesicle phases. Our work may help discover versatile building blocks and provide extensive design freedom for assembly out of thermodynamic equilibrium.

Interfacial Engineering of Fluorescent Carbon Dots with Metal Oxides for Real-Time Visualization of Oxygen Vacancy Dynamics.

Oxygen vacancy (Vo), as one of the most common surface defects, significantly influence the physiochemical properties of metal oxides. However, it remains a challenge for existing techniques to visualize the evolution of Vo during redox process due to its heterogeneous distribution, small size, and dynamic nature. Herein, the real-time monitoring of such microscopic interfacial events is reported by advantage of the high-contrast fluorescence response of carbon dots (H-CDs) to Vo. The green emissive H-CDs possess a unique disc-shaped structure and exceptional hydrophilicity, allowing their tight adhesion to the surfaces of Vo-rich MgO by simple mixing. Subsequently, a water involved interfacial reaction occurred between H-CDs and Vo, resulting in gradual quenching of the original green emission and simultaneously emergence of bright red fluorescence. Moreover, the spatiotemporal diffusion dynamics and reaction kinetics are investigated by confocal laser scanning microscopy, revealing the time-dependent reorganization and structural heterogeneity at the interface. The finding provides a new toolbox for in situ imaging of Vo-triggered phenomena at a microscopic level, which will be helpful in promoting the rational design of oxide materials.

Tensile energy dissipation and mechanical properties of the knee meniscus: relationship with fiber orientation, tissue layer, and water content.

Introduction: The knee meniscus distributes and dampens mechanical loads. It is composed of water (∼70%) and a porous fibrous matrix (∼30%) with a central core that is reinforced by circumferential collagen fibers enclosed by mesh-like superficial tibial and femoral layers. Daily loading activities produce mechanical tensile loads which are transferred through and dissipated by the meniscus. Therefore, the objective of this study was to measure how tensile mechanical properties and extent of energy dissipation vary by tension direction, meniscal layer, and water content. Methods: The central regions of porcine meniscal pairs (n = 8) were cut into tensile samples (4.7mm length, 2.1mm width, and 0.356mm thickness) from core, femoral and tibial components. Core samples were prepared parallel (circumferential) and perpendicular (radial) to the fibers. Tensile testing consisted of frequency sweeps (0.01-1Hz) followed by quasi-static loading to failure. Dynamic testing yielded energy dissipation (ED), complex modulus (E*), and phase shift (δ) while quasi-static tests yielded Young's Modulus (E), ultimate tensile strength (UTS), and strain at UTS (εUTS). To investigate how ED is influenced by the specific mechanical parameters, linear regressions were performed. Correlations between sample water content (φw) and mechanical properties were investigated. A total of 64 samples were evaluated. Results: Dynamic tests showed that increasing loading frequency significantly reduced ED (p < 0.05). Circumferential samples had higher ED, E*, E, and UTS than radial ones (p < 0.001). Stiffness was highly correlated with ED (R2 > 0.75, p < 0.01). No differences were found between superficial and circumferential core layers. ED, E*, E, and UTS trended negatively with φw (p < 0.05). Discussion: Energy dissipation, stiffness, and strength are highly dependent on loading direction. A significant amount of energy dissipation may be associated with time-dependent reorganization of matrix fibers. This is the first study to analyze the tensile dynamic properties and energy dissipation of the meniscus surface layers. Results provide new insights on the mechanics and function of meniscal tissue.

Coordinated hippocampal-thalamic-cortical communication crucial for engram dynamics underneath systems consolidation

Systems consolidation refers to the time-dependent reorganization of memory representations or engrams across brain regions. Despite recent advancements in unravelling this process, the exact mechanisms behind engram dynamics and the role of associated pathways remain largely unknown. Here we propose a biologically-plausible computational model to address this knowledge gap. By coordinating synaptic plasticity timescales and incorporating a hippocampus-thalamus-cortex circuit, our model is able to couple engram reactivations across these regions and thereby reproduce key dynamics of cortical and hippocampal engram cells along with their interdependencies. Decoupling hippocampal-thalamic-cortical activity disrupts systems consolidation. Critically, our model yields testable predictions regarding hippocampal and thalamic engram cells, inhibitory engrams, thalamic inhibitory input, and the effect of thalamocortical synaptic coupling on retrograde amnesia induced by hippocampal lesions. Overall, our results suggest that systems consolidation emerges from coupled reactivations of engram cells in distributed brain regions enabled by coordinated synaptic plasticity timescales in multisynaptic subcortical-cortical circuits.

PET Metabolic Imaging of Time-Dependent Reorganization of Olfactory Cued Fear Memory Networks in Rats.

Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. In contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent versus remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extents of the two networks. Indeed, although the recall of a recent odor fear memory activates a large network of structures spanning from the prefrontal cortex to the cerebellum, significant activations during remote memory retrieval are limited to the piriform cortex. These results strongly support the view that amygdala-dependent memories also undergo system-level reorganization, and that sensory cortical areas might participate in the long-term storage of emotional memories.

Time-dependent re-organization of biological processes by the analysis of the dynamic transcriptional response of yeast cells to doxorubicin.

Doxorubicin is an efficient chemotherapeutic reagent in the treatment of a variety of cancers. However, its underlying molecular mechanism is not fully understood and several severe side effects limit its application. In this study, the dynamic transcriptomic response of Saccharomyces cerevisiae cells to a doxorubicin pulse in a chemostat system was investigated to reveal the underlying molecular mechanism of this drug. The clustering of differentially and significantly expressed genes (DEGs) indicated that the response of yeast cells to doxorubicin is time dependent and may be classified as short-term, mid-term and long-term responses. The cells have started to reorganize their response after the first minute following the injection of the pulse. A modified version of Weighted Gene Co-expression Network Analysis (WGCNA) was used to cluster the positively correlated co-expression profiles, and functional enrichment analysis of these clusters was carried out. DNA replication and DNA repair processes were significantly affected and induced 60 minutes after exposure to doxorubicin. The response to oxidative stress was not identified as a significant term. A transcriptional re-organization of the metabolic pathways seems to be an early event and persists afterwards. The present study reveals for the first time that the RNA surveillance pathway, which is a post-transcriptional regulatory pathway, may be implicated in the short-term reaction of yeast cells to doxorubicin. Integration with regulome revealed the dynamic re-organization of the transcriptomic landscape. Fhl1p, Mbp1p, and Mcm1p were identified as primary regulatory factors responsible for tuning the differentially expressed genes.

Photoinduced Charge Transfer Dynamics in the Carotenoid-Porphyrin-C60 Triad via the Linearized Semiclassical Nonequilibrium Fermi's Golden Rule.

The nonequilibrium Fermi's golden rule (NE-FGR) describes the time-dependent rate coefficient for electronic transitions when the nuclear degrees of freedom start out in a nonequilibrium state. In this paper, the linearized semiclassical (LSC) approximation of the NE-FGR is used to calculate the photoinduced charge transfer (CT) rates in the carotenoid-porphyrin-C60 molecular triad dissolved in explicit tetrahydrofuran. The initial nonequilibrium state corresponds to impulsive photoexcitation from the equilibrated ground state to the ππ* state, and the porphyrin-to-C60 and carotenoid-to-C60 CT rates are calculated. Our results show that accounting for the nonequilibrium nature of the initial state significantly enhances the transition rate of the porphyrin-to-C60 CT process. We also derive the instantaneous Marcus theory (IMT) from LSC NE-FGR, which casts the CT rate coefficients in terms of a Marcus-like expression, with explicitly time-dependent reorganization energy and reaction free energy. IMT is found to reproduce the CT rates in the system under consideration remarkably well.

Motor learning induces time-dependent plasticity that is observable at the spinal cord level.

The spinal cord is an important contributor to motor learning It remains unclear whether short-term spinal cord adaptations are general or task-specific Immediately after task acquisition, neural adaptations were not specific to the trained task (i.e. were general) Twenty-four hours after acquisition, neural adaptations appeared to be task-specific The neural reorganization and generalization of spinal adaptations appears to be time-dependent. Spinal cord plasticity is an important contributor of motor learning in humans, although its mechanisms are still poorly documented. In particular, it remains unclear whether short-term spinal adaptations are general or task-specific. As a marker of neural changes that are observable at spinal level, we measured the Hoffmann reflex (H-reflex) amplitude in the soleus muscle of 18 young healthy human adults before, immediately after (acquisition), and 24 h after (retention) the learning of a skilled task (i.e. one-legged stance on a tilt board). H-reflexes were elicited 46±30ms before touching the tilt board. Additionally, and at the same time points, we measured the H-reflex with the subject sitting at rest and when performing an unskilled and untrained task (i.e. one-legged stance on the floor). After task acquisition, there was a decrease of the H-reflex amplitude measured at rest but not during the skilled or the unskilled task. At retention, there was a decrease of the H-reflex when measured during the skilled task but not during the unskilled task or at rest. Performance increase was not associated with changes in the H-reflex amplitude. After the acquisition of a new skilled task, spinal changes appeared to be general (i.e. observable at rest). However, 24 h after, these changes were task-specific (i.e. observable only during performance of the trained task). These results imply that skill training induces a time-dependent reorganization of the modulation of spinal networks, which possibly reflects a time-dependent optimization of the feedforward motor command.

Recalling old memories.

The neural ensembles within the prelimbic cortex representing remote (long-term) memories undergo time-dependent reorganization.

The organization of leukotriene biosynthesis on the nuclear envelope revealed by single molecule localization microscopy and computational analyses.

The initial steps in the synthesis of leukotrienes are the translocation of 5-lipoxygenase (5-LO) to the nuclear envelope and its subsequent association with its scaffold protein 5-lipoxygenase-activating protein (FLAP). A major gap in our understanding of this process is the knowledge of how the organization of 5-LO and FLAP on the nuclear envelope regulates leukotriene synthesis. We combined single molecule localization microscopy with Clus-DoC cluster analysis, and also a novel unbiased cluster analysis to analyze changes in the relationships between 5-LO and FLAP in response to activation of RBL-2H3 cells to generate leukotriene C4. We identified the time-dependent reorganization of both 5-LO and FLAP into higher-order assemblies or clusters in response to cell activation via the IgE receptor. Clus-DoC analysis identified a subset of these clusters with a high degree of interaction between 5-LO and FLAP that specifically correlates with the time course of LTC4 synthesis, strongly suggesting their role in the initiation of leukotriene biosynthesis.

Temporal evolution of cortical ensembles promoting remote memory retrieval.

Memories of fearful events can last a lifetime. The prelimbic (PL) subregion of prefrontal cortex plays a critical role in fear memory retrieval over time. Most studies have focused on acquisition, consolidation, and retrieval of recent memories, but much less is known about the neural mechanisms of remote memory. Using a new knock-in mouse for activity-dependent genetic labeling (TRAP2), we demonstrate that neuronal ensembles in PL are dynamic. PL neurons TRAPed during later memory retrievals are more likely to be reactivated and make larger behavioral contributions to remote memory retrieval compared to those TRAPed during learning or early memory retrieval. PL activity during learning is required to initiate this time-dependent reorganization in PL ensembles underlying memory retrieval. Finally, while neurons TRAPed during earlier and later retrievals have similar broad projections throughout the brain, PL neurons TRAPed later have a stronger functional recruitment of cortical targets.

Changes in patterns of neural activity underlie a time-dependent transformation of memory in rats and humans.

The dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time-dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context-specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal-frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually-detailed as well as less precise, schematic memories. These findings provide cross-species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation.

Time-dependent memory transformation along the hippocampal anterior\u2013posterior axis

With time, memories undergo a neural reorganization that is linked to a transformation of detailed, episodic into more semantic, gist-like memory. Traditionally, this reorganization is thought to involve a redistribution of memory from the hippocampus to neocortical areas. Here we report a time-dependent reorganization within the hippocampus, along its anterior–posterior axis, that is related to the transformation of detailed memories into gist-like representations. We show that mnemonic representations in the anterior hippocampus are highly distinct and that anterior hippocampal activity is associated with detailed memory but decreases over time. Posterior hippocampal representations, however, are more gist-like at a later retention interval, and do not decline over time. These findings indicate that, in addition to the well-known systems consolidation from hippocampus to neocortex, there are changes within the hippocampus that are crucial for the temporal dynamics of memory.

Reconsolidation-induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens.

Systems consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reconsolidation, that restored the normal course of systems consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying systems consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reconsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of systems consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.

Sequential learning during contextual fear conditioning guides the rate of systems consolidation: Implications for consolidation of multiple memory traces.

Systems consolidation has been described as a time-dependent reorganization process involving the neocortical and hippocampal networks underlying memory storage and retrieval. Previous studies of our lab were able to demonstrate that systems consolidation is a dynamic process, rather than a merely passive, time-dependent phenomenon. Here, we studied the influence of sequential learning in contextual fear conditioning (CFC) with different training intensities in the time-course of hippocampal dependency and contextual specificity. We found that sequential learning with high-intensity shocks during CFC induces generalization of the first learning (context A) and maintains contextual specificity of the second learning (context B) 15 days after acquisition. Moreover, subsequent experiences reorganize brain structures involved in retrieval, accelerating the involvement of cortical structures and diminishing the hippocampal participation. Exposure to original context before novelty seems to only induce context specificity in hippocampal-dependent memories. We propose that systems consolidation could be considered a potential biological mechanism for reducing possible interferences between similar memory traces. © 2017 Wiley Periodicals, Inc.

Programming temporal shapeshifting.

Shapeshifting enables a wide range of engineering and biomedical applications, but until now transformations have required external triggers. This prerequisite limits viability in closed or inert systems and puts forward the challenge of developing materials with intrinsically encoded shape evolution. Herein we demonstrate programmable shape-memory materials that perform a sequence of encoded actuations under constant environment conditions without using an external trigger. We employ dual network hydrogels: in the first network, covalent crosslinks are introduced for elastic energy storage, and in the second one, temporary hydrogen-bonds regulate the energy release rate. Through strain-induced and time-dependent reorganization of the reversible hydrogen-bonds, this dual network allows for encoding both the rate and pathway of shape transformations on timescales from seconds to hours. This generic mechanism for programming trigger-free shapeshifting opens new ways to design autonomous actuators, drug-release systems and active implants.

Novel learning accelerates systems consolidation of a contextual fear memory

After initial encoding memories may undergo a time-dependent reorganization, becoming progressively independent from the hippocampus (HPC) and dependent on cortical regions such as the anterior cingulate cortex (ACC). Although the mechanisms underlying systems consolidation are somewhat known, the factors determining its temporal dynamics are still poorly understood. Here, we studied the influence of novel learning occurring between training and test sessions on the time-course of HPC- and ACC-dependency of contextual fear conditioning (CFC) memory expression. We found that muscimol was disruptive when infused into the HPC up to 35 days after training, while the ACC is vulnerable only after 45 days. However, when animals were subjected to a series of additional, distinct tasks to be learned within the first 3 weeks, muscimol became effective sooner. Muscimol had no effect in the HPC at 20 days after training, exactly when the ACC becomes responsive to this treatment. Thus, our data indicates that the encoding of new information generates a tight interplay between distinct memories, accelerating the reorganization of previously stored long term memories between the hippocampal and cortical areas. © 2016 Wiley Periodicals, Inc.

Self-assembly and sequence length dependence on nanofibrils of polyglutamine peptides

Huntington's disease (HD) is recognized as a currently incurable, inherited neurodegenerative disorder caused by the accumulation of misfolded polyglutamine (polyQ) peptide aggregates in neuronal cells. Yet, the mechanism by which newly formed polyQ chains interact and assemble into toxic oligomeric structures remains a critical, unresolved issue. In order to shed further light on the matter, our group elected to investigate the folding of polyQ peptides – examining glutamine repeat lengths ranging from 3 to 44 residues. To characterize these aggregates we employed a diverse array of technologies, including: nuclear magnetic resonance; circular dichroism; Fourier transform infrared spectroscopy; fluorescence resonance energy transfer (FRET), and atomic force microscopy. The data we obtained suggest that an increase in the number of glutamine repeats above 14 residues results in disordered loop structures, with different repeat lengths demonstrating unique folding characteristics. This differential folding manifests in the formation of distinct nano-sized fibrils, and on this basis, we postulate the idea of 14 polyQ repeats representing a critical loop length for neurotoxicity – a property that we hope may prove amenable to future therapeutic intervention. Furthermore, FRET measurements on aged assemblages indicate an increase in the end-to-end distance of the peptide with time, most probably due to the intermixing of individual peptide strands within the nanofibril. Further insight into this apparent time-dependent reorganization of aggregated polyQ peptides may influence future disease modeling of polyQ-related proteinopathies, in addition to directing novel clinical innovations.

Remodeling of the neuronal circuits underlying opiate-withdrawal memories following remote retrieval

Several types of memory display time-dependent reorganization of their underlying neural substrates, but it remains unclear whether affective memories associated with drug effects also follow similar reorganization. Here, we analyzed the neural circuits reactivated by the re-exposure of former dependent rats to the withdrawal-paired environment 1month after conditioning (remote memory) as compared with recent memory (Frenois, F., Stinus, L., Di Blasi, F., Cador, M., & Le Moine, C. (2005) A specific limbic circuit underlies opiate withdrawal memories The Journal of Neuroscience, 25, 1366–1374). C-fos expression showed that the circuits involved in the retrieval of withdrawal memories are partly different when comparing recent and remote reactivation, showing that, like other type of memories, affective memories linked to opiate withdrawal undergo anatomical reorganization, with a shift from extended amygdala regions toward cortical areas.

Reorganization in motor cortex after brachial plexus avulsion injury and repair with the contralateral C7 root transfer in rats

The purpose of our study was to establish the profile of cortical reorganization in whole BPAI on rats and evaluate changes of cortical reorganization after repair of the median nerve with the contralateral C7 root transfer. Forty adult SD rats underwent whole roots avulsion of left brachial plexus, among them 20 received contralateral C7 root transfer to the injured median nerve. Intracortical microstimulation was performed in primary motor cortex (M1) at intervals of 3, 5, 7, and 10 months, postoperatively. The maps of motor cortical responses were constructed. Five normal rats were used as the control. Results showed that stimulating right M1 elicited motion of left vibrissae, submaxilla, neck, back, and left hindlimb after left BPAI, among them neck representation area replaced the forelimb area throughout the reorganization process. The left forelimb representation area was found in the left motor cortex 5 months after the contralateral C7 root transfer and existed in both motor cortexes at 7th postoperative month. The left forelimb representation area was detected only in right motor cortex at 10th month, postoperatively. In conclusions, after the contralateral C7 root transfer for repair of the median nerve in BPAI, the cortical reorganization occurred in a time-dependent reorganization. The findings from this study demonstrate that brain involves in the functional recovery after BPAI and repair with nerve transfer and suggest that efforts to improve the results from nerve repair should address the peripheral nerve as well as the brain.