The YTHDF proteins display distinct cellular functions on m6A-modified RNA.

YTHDF proteins are main cytoplasmic 'reader' proteins of RNA N6-methyladenosine (m6A) methylation in mammals. They are largely responsible for m6A-mediated regulation in the cell cytosol by controlling both mRNA translation and degradation. Recent functional and mechanistic investigations of the YTHDF proteins revealed that these proteins have different functions to enable versatile regulation of the epitranscriptome. Their divergent functions largely originate from their different amino acid sequences in the low-complexity N termini. Consequently, they have different phase separation propensities and possess distinct post-translational modifications (PTMs). Different PTMs, subcellular localizations, and competition among partner proteins have emerged as three major mechanisms that control the functions of these YTHDF proteins. We also summarize recent progress on critical roles of these YTHDF proteins in anticancer immunity and the potential for targeting these proteins for developing new anticancer therapies.

Gate-tunable subband degeneracy in semiconductor nanowires.

Degeneracy and symmetry have a profound relation in quantum systems. Here, we report gate-tunable subband degeneracy in PbTe nanowires with a nearly symmetric cross-sectional shape. The degeneracy is revealed in electron transport by the absence of a quantized plateau. Utilizing a dual gate design, we can apply an electric field to lift the degeneracy, reflected as emergence of the plateau. This degeneracy and its tunable lifting were challenging to observe in previous nanowire experiments, possibly due to disorder. Numerical simulations can qualitatively capture our observation, shedding light on device parameters for future applications.

The Brain's Best Kept Secret Is Its Degenerate Structure.

Degeneracy is defined as multiple sets of solutions that can produce very similar system performance. Degeneracy is seen across phylogenetic scales, in all kinds of organisms. In neuroscience, degeneracy can be seen in the constellation of biophysical properties that produce a neuron's characteristic intrinsic properties and/or the constellation of mechanisms that determine circuit outputs or behavior. Here, we present examples of degeneracy at multiple levels of organization, from single-cell behavior, small circuits, large circuits, and, in cognition, drawing conclusions from work ranging from bacteria to human cognition. Degeneracy allows the individual-to-individual variability within a population that creates potential for evolution.

Utilizing codon degeneracy in the design of donor DNA for CRISPR/Cas9-mediated gene editing to streamline the screening process for single amino acid mutations.

Chlamydomonas reinhardtii, a unicellular green alga, has been widely used as a model organism for studies of algal, plant and ciliary biology. The generation of targeted amino acid mutations is often necessary, and this can be achieved using CRISPR/Cas9 induced homology-directed repair to install genomic modifications from exogenous donor DNA. Due to the low gene editing efficiency, the technical challenge lies in identifying the mutant cells. Direct sequencing is not practical, and pre-screening is required. Here, we report a strategy for generating and screening for amino acid point mutations using the CRISPR/Cas9 gene editing system. The strategy is based on designing donor DNA using codon degeneracy, which enables the design of specific primers to facilitate mutant screening by PCR. An in vitro assembled RNP complex, along with a dsDNA donor and an antibiotic resistance marker, was electroporated into wild-type cells, followed by PCR screening. To demonstrate this principle, we have generated the E102K mutation in centrin and the K40R mutation in α-tubulin. The editing efficiencies at the target sites for Centrin, TUA1, TUA2 were 4, 24 and 8% respectively, based on PCR screening. More than 80% of the mutants with the expected size of PCR products were precisely edited, as revealed by DNA sequencing. Subsequently, the precision-edited mutants were biochemically verified. The introduction of codon degeneracy did not affect the gene expression of centrin and α-tubulins. Thus, this approach can be used to facilitate the identification of point mutations, especially in genes with low editing rates.

fastDFE: Fast and Flexible Inference of the Distribution of Fitness Effects.

Estimating the distribution of fitness effects (DFE) of new mutations is of fundamental importance in evolutionary biology, ecology, and conservation. However, existing methods for DFE estimation suffer from limitations, such as slow computation speed and limited scalability. To address these issues, we introduce fastDFE, a Python-based software package, offering fast, and flexible DFE inference from site-frequency spectrum (SFS) data. Apart from providing efficient joint inference of multiple DFEs that share parameters, it offers the feature of introducing genomic covariates that influence the DFEs and testing their significance. To further simplify usage, fastDFE is equipped with comprehensive VCF-to-SFS parsing utilities. These include options for site filtering and stratification, as well as site-degeneracy annotation and probabilistic ancestral-allele inference. fastDFE thereby covers the entire workflow of DFE inference from the moment of acquiring a raw VCF file. Despite its Python foundation, fastDFE incorporates a full R interface, including native R visualization capabilities. The package is comprehensively tested and documented at fastdfe.readthedocs.io.

Beyond Spin Models in Orbitally Degenerate Open-Shell Nanographenes.

The study of open-shell nanographenes has relied on a paradigm where spins are the only low-energy degrees of freedom. Here we show that some nanographenes can host low-energy excitations that include strongly coupled spin and orbital degrees of freedom. The key ingredient is the existence of orbital degeneracy, as a consequence of leaving the benzenoid/half-filling scenario. We analyze the case of nitrogen-doped triangulenes, using both density-functional theory and Hubbard model multiconfigurational and random-phase approximation calculations. We find a rich interplay between orbital and spin degrees of freedom that confirms the need to go beyond the spin-only paradigm, opening a new avenue in this field of research.

Ion-channel degeneracy and heterogeneities in the emergence of signature physiological characteristics of dentate gyrus granule cells.

Complex systems are neither fully determined nor completely random. Biological complex systems, including single neurons, manifest intermediate regimes of randomness that recruit integration of specific combinations of functionally specialized subsystems. Such emergence of biological function provides the substrate for the expression of degeneracy, the ability of disparate combinations of subsystems to yield similar function. Here, we present evidence for the expression of degeneracy in morphologically realistic models of dentate gyrus granule cells (GCs) through functional integration of disparate ion-channel combinations. We performed a 45-parameter randomized search spanning 16 active and passive ion channels, each biophysically constrained by their gating kinetics and localization profiles, to search for valid GC models. Valid models were those that satisfied 17 sub- and suprathreshold cellular-scale electrophysiological measurements from rat GCs. A vast majority (>99%) of the 15,000 random models were not electrophysiologically valid, demonstrating that arbitrarily random ion-channel combinations would not yield GC functions. The 141 valid models (0.94% of 15,000) manifested heterogeneities in and cross-dependencies across local and propagating electrophysiological measurements, which matched with their respective biological counterparts. Importantly, these valid models were widespread throughout the parametric space and manifested weak cross-dependencies across different parameters. These observations together showed that GC physiology could neither be obtained by entirely random ion-channel combinations nor is there an entirely determined single parametric combination that satisfied all constraints. The complexity, the heterogeneities in measurement and parametric spaces, and degeneracy associated with GC physiology should be rigorously accounted for while assessing GCs and their robustness under physiological and pathological conditions.NEW & NOTEWORTHY A recent study from our laboratory had demonstrated pronounced heterogeneities in a set of 17 electrophysiological measurements obtained from a large population of rat hippocampal granule cells. Here, we demonstrate the manifestation of ion-channel degeneracy in a heterogeneous population of morphologically realistic conductance-based granule cell models that were validated against these measurements and their cross-dependencies. Our analyses show that single neurons are complex entities whose functions emerge through intricate interactions among several functionally specialized subsystems.

Bipedalism or bipedalisms: The os coxae of StW 573.

There has been a long debate about the possibility of multiple contemporaneous species of Australopithecus in both eastern and southern Africa, potentially exhibiting different forms of bipedal locomotion. Here, we describe the previously unreported morphology of the os coxae in the 3.67 Ma Australopithecus prometheus StW 573 from Sterkfontein Member 2, comparing it with variation in ossa coxae in living humans and apes as well as other Plio-Pleistocene hominins. Statistical comparisons indicate that StW 573 and 431 resemble humans in their anteroposteriorly great iliac crest breadth compared with many other early australopiths, whereas Homo ergaster KNM WT 15000 surprisingly also has a relatively anterioposteriorly short iliac crest. StW 573 and StW 431 appear to resemble humans in having a long ischium compared with Sts 14 and KNM WT 15000. A Quadratic Discriminant Function Analysis of morphology compared with other Plio-Pleistocene hominins and a dataset of modern humans and hominoids shows that, while Lovejoy's heuristic model of the Ardipithecus ramidus os coxae falls with Pongo or in an indeterminate group, StW 573 and StW 431 from Sterkfontein Member 4 are consistently classified together with modern humans. Although clearly exhibiting the classic "basin shaped" bipedal pelvis, Sts 14 (also from Sterkfontein), AL 288-1 Australopithecus afarensis, MH2 Australopithecus sediba and KNM-WT 15000 occupy a position more peripheral to modern humans, and in some analyses are assigned to an indeterminate outlying group. Our findings strongly support the existence of two species of Australopithecus at Sterkfontein and the variation we observe in os coxae morphology in early hominins is also likely to reflect multiple forms of bipedality.

Slow Auger Recombination in Ag2Se Colloidal Quantum Dots.

Efficient Auger recombination (AR) presents a significant challenge for the advancement of colloidal quantum dot (QD)-based devices involving multiexcitons. Here, the AR dynamics of near-infrared Ag2Se QDs were studied through transient absorption experiments. As the QD radius increases from 0.9 to 2.5 nm, the biexciton lifetime (τ2) of Ag2Se QDs increases from 35 to 736 ps, which is approximately 10 times longer than that of comparable-sized CdSe and PbSe QDs. A qualitative analysis based on observables indicates that the slow Auger rate is primarily attributed to the low density of the final states. The biexciton lifetime and triexciton lifetime (τ3) of Ag2Se QDs follow R3 and R2.6 dependence, respectively. Moreover, the ratio of τ2/τ3 is ∼2.3-3.2, which is markedly lower than the value expected from statistical scaling (4.5). These findings suggest that environmentally friendly Ag2Se QDs can serve as excellent candidates for low-threshold lasers and third-generation photovoltaics utilizing carrier multiplication.

DNA Methylation of the Autonomous Pathway Is Associated with Flowering Time Variations in Arabidopsis thaliana.

Plant flowering time is affected by endogenous and exogenous factors, but its variation patterns among different populations of a species has not been fully established. In this study, 27 Arabidopsis thaliana accessions were used to investigate the relationship between autonomous pathway gene methylation, gene expression and flowering time variation. DNA methylation analysis, RT-qPCR and transgenic verification showed that variation in the flowering time among the Arabidopsis populations ranged from 19 to 55 days and was significantly correlated with methylation of the coding regions of six upstream genes in the autonomous pathway, FLOWERING LOCUS VE (FVE), FLOWERING LOCUS Y (FY), FLOWERING LOCUS D (FLD), PEPPER (PEP), HISTONE DEACETYLASE 5 (HAD5) and Pre-mRNA Processing Protein 39-1 (PRP39-1), as well as their relative expression levels. The expression of FVE and FVE(CS) was modified separately through degenerate codon substitution of cytosine and led to earlier flowering of transgenic plants by 8 days and 25 days, respectively. An accurate determination of methylated sites in FVE and FVE(CS) among those transgenic plants and the recipient Col-0 verified the close relationship between the number of methylation sites, expression and flowering time. Our findings suggest that the methylation variation of these six key upstream transcription factors was associated with the gene expression level of the autonomous pathway and flowering time in Arabidopsis. The FVE(CS) and FVE genes in transgenic plants tended to be hypermethylated, which could be a protective mechanism for plants. However, modification of gene sequences through degenerate codon substitution to reduce cytosine can avoid hypermethylated transferred genes in transgenic plants. It may be possible to partially regulate the flowering of plants by modified trans-epigenetic technology.

Derivation of Bose's Entropy Spectral Density from the Multiplicity of Energy Eigenvalues.

The modern textbook analysis of the thermal state of photons inside a three-dimensional reflective cavity is based on the three quantum numbers that characterize photon's energy eigenvalues coming out when the boundary conditions are imposed. The crucial passage from the quantum numbers to the continuous frequency is operated by introducing a three-dimensional continuous version of the three discrete quantum numbers, which leads to the energy spectral density and to the entropy spectral density. This standard analysis obscures the role of the multiplicity of energy eigenvalues associated to the same eigenfrequency. In this paper we review the past derivations of Bose's entropy spectral density and present a new analysis of energy spectral density and entropy spectral density based on the multiplicity of energy eigenvalues. Our analysis explicitly defines the eigenfrequency distribution of energy and entropy and uses it as a starting point for the passage from the discrete eigenfrequencies to the continuous frequency.

Multiscale Computer Model of the Spinal Dorsal Horn Reveals Changes in Network Processing Associated with Chronic Pain.

Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to the brain. That processing profoundly influences whether stimuli are correctly or incorrectly perceived as painful. Significant advances have been made in identifying the types of excitatory and inhibitory neurons that comprise the SDH, and there is some information about how neuron types are connected, but it remains unclear how the overall circuit processes sensory input or how that processing is disrupted under chronic pain conditions. To explore SDH function, we developed a computational model of the circuit that is tightly constrained by experimental data. Our model comprises conductance-based neuron models that reproduce the characteristic firing patterns of spinal neurons. Excitatory and inhibitory neuron populations, defined by their expression of genetic markers, spiking pattern, or morphology, were synaptically connected according to available qualitative data. Using a genetic algorithm, synaptic weights were tuned to reproduce projection neuron firing rates (model output) based on primary afferent firing rates (model input) across a range of mechanical stimulus intensities. Disparate synaptic weight combinations could produce equivalent circuit function, revealing degeneracy that may underlie heterogeneous responses of different circuits to perturbations or pathologic insults. To validate our model, we verified that it responded to the reduction of inhibition (i.e., disinhibition) and ablation of specific neuron types in a manner consistent with experiments. Thus validated, our model offers a valuable resource for interpreting experimental results and testing hypotheses in silico to plan experiments for examining normal and pathologic SDH circuit function.SIGNIFICANCE STATEMENT We developed a multiscale computer model of the posterior part of spinal cord gray matter (spinal dorsal horn), which is involved in perceiving touch and pain. The model reproduces several experimental observations and makes predictions about how specific types of spinal neurons and synapses influence projection neurons that send information to the brain. Misfiring of these projection neurons can produce anomalous sensations associated with chronic pain. Our computer model will not only assist in planning future experiments, but will also be useful for developing new pharmacotherapy for chronic pain disorders, connecting the effect of drugs acting at the molecular scale with emergent properties of neurons and circuits that shape the pain experience.

Ion-channel degeneracy and heterogeneities in the emergence of complex spike bursts in CA3 pyramidal neurons.

Complex spike bursting (CSB) is a characteristic electrophysiological signature exhibited by several neuronal subtypes and has been implicated in neural plasticity, learning, perception, anaesthesia and active sensing. Here, we address how pronounced intrinsic and synaptic heterogeneities affect CSB, with hippocampal CA3 pyramidal neurons (CA3PNs), where CSB emergence and heterogeneities are well characterized, as a substrate. We randomly generated 12,000 unique models and found 236 valid models that satisfied 11 characteristic CA3PN measurements. These morphologically and biophysically realistic valid models accounted for gating kinetics and somatodendritic expression profiles of 10 active ion channels. This heterogeneous population of valid models was endowed with broad distributions of underlying parameters showing weak pairwise correlations. We found two functional subclasses of valid models, intrinsically bursting and regular spiking, with significant differences in the expression of calcium and calcium-activated potassium conductances. We triggered CSB in all 236 models through different intrinsic or synaptic protocols and observed considerable heterogeneity in CSB propensity and properties spanning models and protocols. Finally, we used virtual knockout analyses and showed that synergistic interactions between intrinsic and synaptic mechanisms regulated CSB emergence and dynamics. Specifically, although there was a dominance of calcium and calcium-activated potassium channels in the emergence of CSB, individual deletion of none of the several ion channels or N-methyl-d-aspartate receptors resulted in the complete elimination of CSB across all models. Together, our analyses critically implicate ion-channel degeneracy in the robust emergence of CSB and other characteristic signatures of CA3PNs, despite pronounced heterogeneities in underlying intrinsic and synaptic properties. KEY POINTS: An unbiased stochastic search algorithm yielded a heterogeneous population of morphologically and biophysically realistic CA3 pyramidal neuronal models matching several signature electrophysiological characteristics. Two functional subclasses of valid models were identified with intrinsically bursting (IB) and regular spiking (RS) characteristics, which exhibited differential localization within the parametric space with linear and non-linear dimension reduction analyses. Calcium and calcium-activated potassium channels distinguished IB from RS models, apart from playing dominant roles in the emergence of complex spike bursting (CSB). The impact of deleting individual ion channels or N-methyl-d-aspartate receptors was variable across different models and differential for each channel/receptor, pointing to ion-channel degeneracy in the emergence of CSB. Biological heterogeneities across different neurons of the same subtype, ion-channel degeneracy and state-dependent changes (involving activity-dependent plasticity, pathology, and neuromodulation of intrinsic and synaptic properties) need to be considered carefully in assessing the propensity and dynamics of CSB in different neuronal subtypes.

Modelling the contributions to hyperexcitability in a mouse model of Alzheimer's disease.

Neuronal hyperexcitability is a pathological characteristic of Alzheimer's disease (AD). Three main mechanisms have been proposed to explain it: (i) dendritic degeneration leading to increased input resistance, (ii) ion channel changes leading to enhanced intrinsic excitability, and (iii) synaptic changes leading to excitation-inhibition (E/I) imbalance. However, the relative contribution of these mechanisms is not fully understood. Therefore, we performed biophysically realistic multi-compartmental modelling of neuronal excitability in reconstructed CA1 pyramidal neurons from wild-type and APP/PS1 mice, a well-established animal model of AD. We show that, for synaptic activation, the excitability-promoting effects of dendritic degeneration are cancelled out by decreased excitation due to synaptic loss. We find an interesting balance between excitability regulation and an enhanced degeneration in the basal dendrites of APP/PS1 cells, potentially leading to increased excitation by the apical but decreased excitation by the basal Schaffer collateral pathway. Furthermore, our simulations reveal three pathomechanistic scenarios that can account for the experimentally observed increase in firing and bursting of CA1 pyramidal neurons in APP/PS1 mice: scenario 1: enhanced E/I ratio; scenario 2: alteration of intrinsic ion channels (IAHP down-regulated; INap , INa and ICaT up-regulated) in addition to enhanced E/I ratio; and scenario 3: increased excitatory burst input. Our work supports the hypothesis that pathological network and ion channel changes are major contributors to neuronal hyperexcitability in AD. Overall, our results are in line with the concept of multi-causality according to which multiple different disruptions are separately sufficient but no single particular disruption is necessary for neuronal hyperexcitability. KEY POINTS: This work presents simulations of synaptically driven responses in pyramidal cells (PCs) with Alzheimer's disease (AD)-related dendritic degeneration. Dendritic degeneration alone alters PC responses to layer-specific input but additional pathomechanistic scenarios are required to explain neuronal hyperexcitability in AD as follows. Possible scenario 1: AD-related increased excitatory input together with decreased inhibitory input (E/I imbalance) can lead to hyperexcitability in PCs. Possible scenario 2: changes in E/I balance combined with altered ion channel properties can account for hyperexcitability in AD. Possible scenario 3: burst hyperactivity of the surrounding network can explain hyperexcitability of PCs during AD.

Machine learning approach identifies prominent codons from different degenerate groups influencing gene expression in bacteria.

Unequal usage of synonymous codons is known as codon usage bias (CUB), which is generally different between the high-expression genes (HEG) and low-expression genes (LEG) in organisms is not yet adequately reported across different bacteria. In this study, a machine learning-based approach was implemented initially to find out codons that are significantly different between the HEG and LEG in Escherichia coli. It identified Cys codons such as UGU and UGC, Lys codons such as AAA and AAG that were least influenced by gene expression. Codons such as UCU (Ser), CUG (Leu), GGG (Gly), CGG (Arg) etc. were identified to be influenced maximum by the gene expression. The study was extended to analyze codon usage in 683 other bacterial species. Cys (UGU/UGC) and Ser (AGU/AGC) codons were identified being the least different between the two groups of genes across these bacterial species. Codons such as CGA, CUG, GGG, GCC, ACC, AUA, and AUC were identified to be influenced by the gene expression across majority of these species. This study supports the role of CUB on gene expression across bacteria and demonstrates a commonality among bacteria regarding behavior of certain codons with regard to gene expression.

A Tale of Enduring Myths: Buffon's Theory of Animal Degeneration and the Regeneration of Domesticated Animals in Mid-19th Century Brazil.

The long 19th century was a period of many developments and technical innovations in agriculture and animal biology, during which actors sought to incorporate new practices in light of new information. By the middle of the century, however, while heredity steadily became the dominant concept in animal husbandry, some policies related to livestock improvement in Brazil seemed to have been tailored following a climate-deterministic concept established in the mid-18th century by the French naturalist Georges-Louis Leclerc, the Comte de Buffon. His theory of animal degeneration posited, among other things, the necessity of recurrent crossbreeding to preserve animal species living in nonnative environments from climate-induced degeneration. Although largely discredited by the early 19th century, the teachings of the French naturalist seem to have found supporters in a Brazilian program to modernize national agriculture through the application of the natural sciences. Herein I examine the revival of Buffon's theories in that government-sponsored program to improve animal husbandry and breeding techniques, including actual applications of this theory in the real world. Ultimately, I argue that Buffon's theory of degeneration was used to tailor public policies and funding for the improvement of domesticated animals in Brazil between 1856 and 1860.

Covariant Lyapunov Vectors and Finite-Time Normal Modes for Geophysical Fluid Dynamical Systems.

Dynamical vectors characterizing instability and applicable as ensemble perturbations for prediction with geophysical fluid dynamical models are analysed. The relationships between covariant Lyapunov vectors (CLVs), orthonormal Lyapunov vectors (OLVs), singular vectors (SVs), Floquet vectors and finite-time normal modes (FTNMs) are examined for periodic and aperiodic systems. In the phase-space of FTNM coefficients, SVs are shown to equate with unit norm FTNMs at critical times. In the long-time limit, when SVs approach OLVs, the Oseledec theorem and the relationships between OLVs and CLVs are used to connect CLVs to FTNMs in this phase-space. The covariant properties of both the CLVs, and the FTNMs, together with their phase-space independence, and the norm independence of global Lyapunov exponents and FTNM growth rates, are used to establish their asymptotic convergence. Conditions on the dynamical systems for the validity of these results, particularly ergodicity, boundedness and non-singular FTNM characteristic matrix and propagator, are documented. The findings are deduced for systems with nondegenerate OLVs, and, as well, with degenerate Lyapunov spectrum as is the rule in the presence of waves such as Rossby waves. Efficient numerical methods for the calculation of leading CLVs are proposed. Norm independent finite-time versions of the Kolmogorov-Sinai entropy production and Kaplan-Yorke dimension are presented.

Classic Text No. 134: 'A case of Wernicke-Bostroem's expansive autopsychosis', by Ib Ostenfeld (1944).

Expansive autopsychosis, grouped with cycloid psychoses - an illness entity of double origin: (1) Morel's notion degeneracy, reformulated by Magnan and Legrain (reflected in Wimmer's concept: psychogenic psychosis); (2) Wernicke's, Kleist's, Bostroem's (and later Leonhard's) notion of these purportedly independent conditions. Locked in the Danish language, Strömgren and Ostenfeld provided important contributions to this field, exemplified by Ostenfeld's casuistry, translated in this Classic Text.

Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells.

Neurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, which have been implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic physiologically constrained parametric search to identify the cellular mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We used heterogeneous model populations to ensure that our conclusions were not biased by parametric choices in a single hand-tuned model. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneities in synaptic plasticity profiles obtained with two different induction protocols. However, among the disparate forms of neural-circuit heterogeneities, our analyses demonstrated the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. We found that strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult neurogenesis-induced heterogeneities in neural structure were accounted for. Importantly, our analyses showed that it was not imperative that the manifestation of neural-circuit heterogeneities must translate to heterogeneities in plasticity profiles. Specifically, despite the expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable across all models through synergistic interactions among these heterogeneities. We assessed the parametric combinations required for the manifestation of such degeneracy in the expression of plasticity profiles. We found that immature cells showed physiological plasticity profiles despite receiving afferent inputs with weak synaptic strengths. Thus, the high intrinsic excitability of immature granule cells was sufficient to counterbalance their low excitatory drive in the expression of plasticity profile degeneracy. Together, our analyses demonstrate that disparate forms of neural-circuit heterogeneities could mechanistically drive plasticity heterogeneity, but also caution against treating neural-circuit heterogeneities as proxies for plasticity heterogeneity. Our study emphasizes the need for quantitatively characterizing the relationship between neural-circuit and plasticity heterogeneities across brain regions.

Multifold Integration of Printed and Holographic Meta-Image Displays Enabled by Dual-Degeneracy.

By virtue of the unprecedented ability of manipulating the optical parameters, metasurfaces open up a new avenue for realizing ultra-compact image displays, e.g., nanoprinting on the surface and holographic displaying in the far-field. The multifold integration of these two functions into a single metasurface can undoubtedly expand the functionality and increase the information capacity. In this study, a minimalist tri-channel metasurface is proposed and experimentally demonstrated with multifold integration of printed and holographic displaying, which can generate two N-bit grayscale images and a four-step holographic image simultaneously. Benefiting from exploiting the degeneracy of energy allocation and the degeneracy of nanostructure orientations, the functionalities of nanoprinting and holography are combined without the need of a large amount of nanostructures with varied dimensions, which would facilitate both the metasurface design and fabrication. The proposed scheme provides a new idea in enhancing the functionality and capacity of metasurfaces without complicating their design, which has promising prospects for applications in ultra-compact image displays, high-density optical storage, optical anti-counterfeiting and many other related fields.