Molecular Memory Research Articles

Spatiotemporal fluctuation induces Turing pattern formation in the chemical Brusselator

Chemical reactions are embedded in spatiotemporal fluctuations instead of a constant environment. Here, we aimed to assess reaction–diffusion (RD) with dichotomous noise‐controlling system parameters in the Brusselator and examine the effect of these fluctuations on the dynamic behavior of chemical reactions. By performing a multiscale perturbation analysis, we demonstrated that the correlated noise can broaden the Turing region even if molecular memory (autocorrelation time) exists. However, for small noise, short‐term memory promotes Turing instability. The instability of the Brusselator is determined by the noise strength, which belongs to the optimal region if the diffusion coefficient is fixed. Turing pattern selection and stability are also governed by the dynamic character of the amplitude equation, and the entire Turing instability region shifts to the right in the phase space with noise perturbation. Finally, numerical simulations validate the theoretical derivation that correlated noise can amplify Turing pattern formation to maintain distinct patterns.

Mix and Match Tuning of the Conformational and Multistate Redox Switching Properties of an Overcrowded Alkene.

Overcrowded alkenes have received considerable attention as versatile structural motifs in a range of optical switches and light-driven unidirectional motors. In contrast, their actuation by electrochemical stimuli remains underexplored, even though this alternative energy input may be preferred in various applications and enables additional control over molecular switching states and properties. While symmetric bistricyclic overcrowded enes (BAEs) containing two identical halves based on either thioxanthene (TX) or acridine (Acr) motifs are known to be reversible conformational redox switches, their redox potentials are generally too high or low, respectively, thereby preventing wider applications. Herein, we demonstrate that the "mixed" TX-Acr switch possesses redox properties that lie between those of its parent symmetric analogs, enabling interconversion between three stable redox and conformational states at mild potentials. This includes the neutral anti-folded, the dicationic orthogonal, and a unique twisted monoradical cation state, the latter of which is only accessible in the case of the mixed TX-Acr switch and in a pathway-dependent manner. Consequently, with this multistate redox switch, a myriad of molecular properties, including geometry, polarity, absorbance, and fluorescence, can be modulated with high fidelity and reversibility between three distinct stable states. More generally, this study highlights the versatility of the "mix and match" approach in rationally designing redox switches with specific (redox) properties, which in turn is expected to enable a myriad of applications ranging from molecular logic and memory to actuators and energy storage systems.

The Initiator Caspase Dronc Drives Compensatory Proliferation of Apoptosis-Resistant Cells During Epithelial Tissue Regeneration After Ionizing Radiation.

Caspases, well-known for their role in executing apoptosis, also participate in various non-apoptotic processes. Despite this, their involvement in promoting compensatory proliferation - a key aspect of tissue regeneration following extensive cell death - has been a subject of ongoing ambiguity. In our study, we investigate compensatory proliferation in the Drosophila wing imaginal disc following ionizing radiation, a model epithelial tissue that has been a pioneering system for studying this regenerative response. Using a delayed genetic reporter to monitor the activity of the initiator caspase-2/9 ortholog, Dronc, we identified two populations of apoptosis-resistant epithelial cells involved in compensatory proliferation: those that activate Dronc (termed DARE cells) and those that do not (NARE cells). We show that DARE cells pass their apoptosis-resistance trait to their daughter cells, suggesting a molecular memory. We demonstrate that Dronc in DARE cells, but not the apoptosome adapter Dark and the effector caspases, promotes compensatory proliferation both within these cells and in NARE cells through a non-cell-autonomous mechanism. We found that Myo1D, an unconventional myosin interacting with Dronc, is essential for the survival of DARE cells by preventing the lethal activation of effector caspases and subsequent apoptosis. In contrast, Myo7A/Crinkled, another unconventional myosin that interacts with Dronc, promotes effector caspase activation in DARE cells. We demonstrate that the TNFR>JNK signaling pathway in DARE cells directly regulates their proliferation, which in turn influences NARE cell proliferation. Consequently, we show that maintaining proliferative homeostasis between DARE and NARE cells is vital for balanced tissue regeneration. Given the widespread use of ionizing irradiation in cancer treatment and prevention, our findings have potential implications for understanding treatment-resistant cells and cancer recurrence.

Nascent RNA kinetics with complex promoter architecture: Analytic results and parameter inference.

Transcription is a stochastic process that involves several downstream operations which make it difficult to model and infer transcription kinetics from mature RNA numbers in individual cell. However, recent advances in single-cell technologies have enabled a more precise measurement of the fluctuations of nascent RNA that closely reflect transcription kinetics. In this paper we introduce a general stochastic model to mimic nascent RNA kinetics with complex promoter architecture. We derive the exact distribution and moments of nascent RNA using queuing theory techniques, which provide valuable insights into the effect of the molecular memory created by the multistep activation and deactivation on the stochastic kinetics of nascent RNA. Moreover, based on the analytical results, we develop a statistical method to infer the promoter memory from stationary nascent RNA distributions. Data analysis of synthetic data and a realistic example, the HIV-1 gene, verifies the validity of this inference method.

Multidimensional Dynamic Control of Supramolecular Phthalocyanine Gear: A Self-Assembly System Responding to Solvent, Temperature, and Hydrostatic Pressure.

Smart supramolecular materials that respond toward various external stimuli hold great promise for various applications in molecular memories, logic gates, and drug delivery systems. In this study, the active control over the self-assembly of phathalocyanine gear was achieved by combining temperature and hydrostatic pressure stimuli with a dynamic solvent. Eventually, we found that the supramolecular gear can behave as a logic gate; "engaged" (+1) or "not" (0) state is switchable by solvent, temperature, and hydrostatic pressure. This paper describes not only new aspects for the rational design of smart stimuli-responsive supramolecular materials but also the significance of multidimensional dynamic control.

Epigenomic and transcriptomic persistence of heat stress memory in strawberry (Fragaria vesca)

BackgroundIn plants, epigenetic stress memory has so far been found to be largely transient. Here, we wanted to assess the heritability of heat stress-induced epigenetic and transcriptomic changes following woodland strawberry (Fragaria vesca) reproduction. Strawberry is an ideal model to study epigenetic inheritance because it presents two modes of reproduction: sexual (self-pollinated plants) and asexual (clonally propagated plants named daughter plants). Taking advantage of this model, we investigated whether heat stress-induced DNA methylation changes can be transmitted via asexual reproduction.ResultsOur genome-wide study provides evidence for stress memory acquisition and maintenance in F. vesca. We found that specific DNA methylation marks or epimutations are stably transmitted over at least three asexual generations. Some of the epimutations were associated with transcriptional changes after heat stress.ConclusionOur findings show that the strawberry methylome and transcriptome respond with a high level of flexibility to heat stress. Notably, independent plants acquired the same epimutations and those were inherited by their asexual progenies. Overall, the asexual progenies can retain some information in the genome of past stresses encountered by their progenitors. This molecular memory, also documented at the transcriptional level, might be involved in functional plasticity and stress adaptation. Finally, these findings may contribute to novel breeding approaches for climate-ready plants.

Specific exercise patterns generate an epigenetic molecular memory window that drives long-term memory formation and identifies ACVR1C as a bidirectional regulator of memory in mice

Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.

Analysis of a detailed multi-stage model of stochastic gene expression using queueing theory and model reduction

We introduce a biologically detailed, stochastic model of gene expression describing the multiple rate-limiting steps of transcription, nuclear pre-mRNA processing, nuclear mRNA export, cytoplasmic mRNA degradation and translation of mRNA into protein. The processes in sub-cellular compartments are described by an arbitrary number of processing stages, thus accounting for a significantly finer molecular description of gene expression than conventional models such as the telegraph, two-stage and three-stage models of gene expression. We use two distinct tools, queueing theory and model reduction using the slow-scale linear-noise approximation, to derive exact or approximate analytic expressions for the moments or distributions of nuclear mRNA, cytoplasmic mRNA and protein fluctuations, as well as lower bounds for their Fano factors in steady-state conditions. We use these to study the phase diagram of the stochastic model; in particular we derive parametric conditions determining three types of transitions in the properties of mRNA fluctuations: from sub-Poissonian to super-Poissonian noise, from high noise in the nucleus to high noise in the cytoplasm, and from a monotonic increase to a monotonic decrease of the Fano factor with the number of processing stages. In contrast, protein fluctuations are always super-Poissonian and show weak dependence on the number of mRNA processing stages. Our results delineate the region of parameter space where conventional models give qualitatively incorrect results and provide insight into how the number of processing stages, e.g. the number of rate-limiting steps in initiation, splicing and mRNA degradation, shape stochastic gene expression by modulation of molecular memory.

Transcriptomic profiling of Rana [Lithobates] catesbeiana back skin during natural and thyroid hormone-induced metamorphosis under different temperature regimes with particular emphasis on innate immune system components

As amphibians undergo thyroid hormone (TH)-dependent metamorphosis from an aquatic tadpole to the terrestrial frog, their innate immune system must adapt to the new environment. Skin is a primary line of defense, yet this organ undergoes extensive remodelling during metamorphosis and how it responds to TH is poorly understood. Temperature modulation, which regulates metamorphic timing, is a unique way to uncover early TH-induced transcriptomic events. Metamorphosis of premetamorphic tadpoles is induced by exogenous TH administration at 24 °C but is paused at 5 °C. However, at 5 °C a “molecular memory” of TH exposure is retained that results in an accelerated metamorphosis upon shifting to 24 °C. We used RNA-sequencing to identify changes in Rana (Lithobates) catesbeiana back skin gene expression during natural and TH-induced metamorphosis. During natural metamorphosis, significant differential expression (DE) was observed in >6500 transcripts including classic TH-responsive transcripts (thrb and thibz), heat shock proteins, and innate immune system components: keratins, mucins, and antimicrobial peptides (AMPs). Premetamorphic tadpoles maintained at 5 °C showed 83 DE transcripts within 48 h after TH administration, including thibz which has previously been identified as a molecular memory component in other tissues. Over 3600 DE transcripts were detected in TH-treated tadpoles at 24 °C or when tadpoles held at 5 °C were shifted to 24 °C. Gene ontology (GO) terms related to transcription, RNA metabolic processes, and translation were enriched in both datasets and immune related GO terms were observed in the temperature-modulated experiment. Our findings have implications on survival as climate change affects amphibia worldwide.

Environmental signals driving liquid-liquid phase separation - a molecular memory in plants?

Environmental signals driving liquid-liquid phase separation - a molecular memory in plants?

Computational Design of Photosensitive Polymer Templates To Drive Molecular Nanofabrication.

Molecular electronics promises the ultimate level of miniaturization of computers and other machines as organic molecules are the smallest known physical objects with nontrivial structure and function. But despite the plethora of molecular switches, memories, and motors developed during the almost 50-years long history of molecular electronics, mass production of molecular computers is still an elusive goal. This is mostly due to the lack of scalable nanofabrication methods capable of rapidly producing complex structures (similar to silicon chips or living cells) with atomic precision and a small number of defects. Living nature solves this problem by using linear polymer templates encoding large volumes of structural information into sequence of hydrogen bonded end groups which can be efficiently replicated and which can drive assembly of other molecular components into complex supramolecular structures. In this paper, we propose a nanofabrication method based on a class of photosensitive polymers inspired by these natural principles, which can operate in concert with UV photolithography used for fabrication of current microelectronic processors. We believe that such a method will enable a smooth transition from silicon toward molecular nanoelectronics and photonics. To demonstrate its feasibility, we performed a computational screening of candidate molecules that can selectively bind and therefore allow the deterministic assembly of molecular components. In the process, we unearthed trends and design principles applicable beyond the immediate scope of our proposed nanofabrication method, e.g., to biologically relevant DNA analogues and molecular recognition within hydrogen-bonded systems.

Stacked structure dependence on resistive switching characteristics in sumanene molecular memory

Nonvolatile memories using molecule (molecule memories) are attracting attention. This is because these materials are suitable for miniaturization and higher capacity of memories in terms of their properties and dimensions. We have already demonstrated that the metal–insulator–metal (MIM) devices with sumanene-inserted bilayer graphene show huge resistive switching characteristics. However, the reason why resistive switching occurs in the graphene/sumanene/graphene structure has yet to be clarified. In this work, to investigate the mechanisms of the resistive switching phenomenon in sumanene-inserted bilayer graphene, plural kinds of stacked MIM structures are fabricated and evaluated. As a result, the measurement results clearly show that the graphene/sumanene/graphene structure is indispensable in the resistive switching phenomenon. Furthermore, based on the temperature dependence of the resistive switching, it is confirmed that a significant I ON/I OFF ratio can be obtained at higher operation temperatures.

Molecular-Memory-Induced Counter-Intuitive Noise Attenuator in Protein Polymerization

Gene expression comprises many asymmetric and complex processes. Transcriptional details revealed by the whole genome indicate that genes resort to transcriptional bursting and accumulate molecular memory. However, it is still unclear how the interplay of transcriptional bursting and memory regulates robustness and expression noise. Here, we consider a model of multiple coupled processes of protein polymerization to focus on decoding the effect of molecular memory. Using non-Markovian transformation technology, we first define the memory index to measure the correlation window of expression to decipher the mechanism of regulation. The results indicate that memory from synthesis can amplify expression noise, while memory originating from polymerization can reduce the lower bound of the noise of gene products; that is, the memory from different sources plays distinct regulatory roles to induce non-symmetry. Moreover, it is counterintuitive that the dual regulation from memory and bursting expression can directly suppress system noise, violating the principle that transcriptional bursting enhances noise. Our results not only provide a theoretical framework for investigating the function of memory but also imply that expression noise is not part of a half-power relationship with, nor mediated by, memory.

Retention of the RNA ends provides the molecular memory for maintaining the activation of the Csm complex.

The type III CRISPR-Cas effector complex Csm functions as a molecular Swiss army knife that provides multilevel defense against foreign nucleic acids. The coordinated action of three catalytic activities of the Csm complex enables simultaneous degradation of the invader's RNA transcripts, destruction of the template DNA and synthesis of signaling molecules (cyclic oligoadenylates cAn) that activate auxiliary proteins to reinforce CRISPR-Cas defense. Here, we employed single-molecule techniques to connect the kinetics of RNA binding, dissociation, and DNA hydrolysis by the Csm complex from Streptococcus thermophilus. Although single-stranded RNA is cleaved rapidly (within seconds), dual-color FCS experiments and single-molecule TIRF microscopy revealed that Csm remains bound to terminal RNA cleavage products with a half-life of over 1 hour while releasing the internal RNA fragments quickly. Using a continuous fluorescent DNA degradation assay, we observed that RNA-regulated single-stranded DNase activity decreases on a similar timescale. These findings suggest that after fast target RNA cleavage the terminal RNA cleavage products stay bound within the Csm complex, keeping the Cas10 subunit activated for DNA destruction. Additionally, we demonstrate that during Cas10 activation, the complex remains capable of RNA turnover, i.e. of ongoing degradation of target RNA.

Reactive Astrocytes and Emerging Roles in Central Nervous System (CNS) Disorders.

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond to CNS damage and disease through a process called "reactivity." Recent evidence reveals that astrocyte reactivity is a heterogeneous spectrum of potential changes that occur in a context-specific manner. These changes are determined by diverse signaling events and vary not only with the nature and severity of different CNS insults but also with location in the CNS, genetic predispositions, age, and potentially also with "molecular memory" of previous reactivity events. Astrocyte reactivity can be associated with both essential beneficial functions as well as with harmful effects. The available information is rapidly expanding and much has been learned about molecular diversity of astrocyte reactivity. Emerging functional associations point toward central roles for astrocyte reactivity in determining the outcome in CNS disorders.

Review of: "According to Nano molecular memory, there is a high potential for activity in this field"

Review of: "According to Nano molecular memory, there is a high potential for activity in this field"

Utilization of temperature-mediated activation of thyroid hormone-induced molecular memory to evaluate early signaling events in the olfactory epithelium of Rana [Lithobates] catesbeiana tadpoles

The amphibian olfactory system is highly distinct between aquatic tadpole and terrestrial frog life stages and therefore must remodel extensively during thyroid hormone (TH)-dependent metamorphosis. Developmentally appropriate functioning of the olfactory epithelium is critical for survival. Previous studies in other Rana [Lithobates] catesbeiana premetamorphic tadpole tissues showed that initiation of TH-induced metamorphosis can be uncoupled from execution of TH-dependent programs by holding tadpoles in the cold rather than at warmer permissive temperatures. TH-exposed tadpoles at the nonpermissive (5 °C) temperature do not undergo metamorphosis but retain a “molecular memory” of TH exposure that is activated upon shift to a permissive warm temperature. Herein, premetamorphic tadpoles were held at permissive (24 °C) or nonpermissive (5 °C) temperatures and injected with 10 pmoles/g body weight 3,5,3′-triiodothyronine (T3) or solvent control. Olfactory epithelium was collected at 48 h post-injection. RNA-sequencing (RNA-Seq) and reverse transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) analyses generated differentially expressed transcript profiles of 4328 and 54 contigs for permissive and nonpermissive temperatures, respectively. Translation, rRNA, spliceosome, and proteolytic processes gene ontologies were enriched by T3 treatment at 24 °C while negative regulation of cell proliferation was enriched by T3 at 5 °C. Of note, as found in other tissues, TH-induced basic leucine zipper-containing protein-encoding transcript, thibz, was significantly induced by T3 at both temperatures, suggesting a role in the establishment of molecular memory in the olfactory epithelium. The current study provides critical insights by deconstructing early TH-induced induction of postembryonic processes that may be targets for disruption by environmental contaminants.

Review of: "According to Nano molecular memory, there is a high potential for activity in this field"

Review of: "According to Nano molecular memory, there is a high potential for activity in this field"

MOF-enabled high-density 2D molecular crystal optoelectronic memory transistor with floating gate architecture

A novel MOF floating-gate optical memory transistor was engineered using 2D molecular crystals as the active layer, and it exhibited an excellent electron capture ability, good current retention characteristics, and multi-level memory functionalities.

The molecular memory switch: PKMζ and its role in maintaining old memories

The molecular memory switch: PKMζ and its role in maintaining old memories