Biology subjects

Nakamura, M.

Publications and source records attributed to Nakamura, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Electrical Surface Polarization as a Functionalization Strategy to Improve Bone Regeneration of Apatite-Based Graft Materials

Apatite-based bone graft materials are widely used for bone regeneration; however, their limited bioactivity and slow remodeling often hinder complete replacement by newly formed bone. Electrical surface polarization has emerged as a promising non-chemical strategy to modify biomaterial surface properties without altering bulk characteristics. In this study, we investigated the effects of electrical surface polarization on apatite-based biomaterials using synthesized carbonate apatite (CA) for mechanistic in vitro evaluation and a clinically relevant xenograft material for in vivo validation. Material characterization confirmed the formation of B-type carbonate apatite with bone-like mineral composition. Thermally stimulated depolarization current measurements verified successful induction of surface charges, with polarization intensity dependent on treatment conditions. In vitro studies using human peripheral blood-derived osteoclast precursors demonstrated that electrically polarized CA surfaces significantly enhanced osteoclast differentiation and resorptive activity compared to non-polarized controls, with the strongest effects observed on positively polarized surfaces. Three-dimensional analysis revealed increased resorption pit depth and volume, indicating enhanced osteoclast functionality. In vivo implantation of polarized xenograft materials into rat femoral defects resulted in significantly increased new bone formation and improved implant-bone integration compared to non-polarized materials. Higher polarization conditions promoted more mature bone tissue formation and greater bone-material affinity. These results demonstrate that electrical surface polarization effectively modulates osteoclast-material interactions and enhances bone regeneration, highlighting its potential as a simple and translatable functionalization strategy for apatite-based bone graft materials.

bioengineering↗

bioRxiv2026

Lhcf9 is a novel negative regulator of non-photochemical quenching in the diatom Chaetoceros gracilis

Photosynthetic organisms in aquatic environments experience rapid fluctuations in light intensity, light quality, and carbon availability, requiring tight regulation of photosynthetic energy conversion. In marine diatoms, non-photochemical quenching (NPQ), particularly energy-dependent quenching (qE), plays a central role in dissipating excess excitation energy as heat. However, excessive NPQ can reduce photosynthetic efficiency under light-limiting or carbon-rich conditions, and how this trade-off is regulated remains poorly understood. Here, we identify CgLhcf9, a previously uncharacterized light-harvesting complex (LHC) protein, as a negative regulator of qE-type NPQ in the centric diatom Chaetoceros gracilis. Expression of CgLhcf9 is induced under low red-light and high CO2 conditions and strongly suppressed by blue light, indicating regulation by both light quality and carbon availability. Functional analyses using CgLhcf9 knockout and overexpression lines reveal that CgLhcf9 suppresses qE: NPQ induction is enhanced in the absence of CgLhcf9, whereas its accumulation downregulates NPQ without affecting other established qE effectors, including Lhcx1 or xanthophyll cycle pigments. Notably, CgLhcf9 accumulation improves cellular growth under light-limiting conditions. These results identify CgLhcf9 as a novel LHC-type regulator that fine-tunes photosynthetic energy dissipation in response to environmental signals. Our findings establish a regulatory mechanism that balances photoprotection, electron transport, and carbon fixation, advancing our understanding of how marine diatoms optimize photosynthesis under fluctuating light and CO2 conditions. Significance statementPhotosynthetic microalgae must balance light-driven electron transport with carbon fixation to maximize growth under fluctuating light and CO2 conditions. While non-photochemical quenching (NPQ) protects photosystems from excess light, excessive NPQ can limit photosynthetic efficiency when light or carbon is limiting. Here, we identify the antenna protein CgLhcf9 as a negative regulator of energy-dependent NPQ in the marine diatom Chaetoceros gracilis. CgLhcf9 integrates light-quality and CO2 signals to suppress NPQ without altering canonical quenching effectors, thereby improving growth under light-limiting conditions. This study reveals a regulatory role for a light-harvesting complex protein in tuning the balance between photoprotection and photosynthetic efficiency, providing insight into how marine diatoms coordinate electron transport and carbon fixation in dynamic environments.

plant biology↗

bioRxiv2026

An Alternative DNA Endonuclease Activity is Associated with the LINE-1 ORF2-encoded Protein

Long INterspersed Element-1 (L1) retrotransposons use activities contained within the L1 open reading frame 2-encoded protein (ORF2p) to mobilize throughout the genome via target-site primed reverse transcription (TPRT). The ORF2p endonuclease domain (EN) cleaves genomic DNA to liberate a 3-hydroxyl (3-OH) group that is used by the ORF2p reverse transcriptase domain (RT) to synthesize a cDNA copy of its bound L1 RNA template. L1 also can move by EN-independent retrotransposition (ENi), where a 3-OH group at genomic DNA lesions, dysfunctional telomeres, or stalled replication forks is proposed to prime L1 reverse transcription in the absence of L1 EN cleavage. We previously reported that ribonucleoprotein (RNP) preparations from cells transfected with a human wild-type (WT) L1 or L1 EN-mutant, but not an L1 RT-mutant, can initiate reverse transcription from a DNA oligonucleotide primer/L1 RNA template complex. The WT and EN-deficient L1 RNP preparations also are associated with a nuclease activity that can process a 3 end modification that precludes DNA synthesis from an oligonucleotide prior to priming the L1 RT reaction. Here, we purified recombinant full-length WT, L1 EN-, and L1 RT-mutant human L1 ORF2p from insect cells. We report that the WT and L1 EN-mutant, but not the L1 RT-mutant, contain an alternative endonuclease activity (alt-EN). Alt-EN activity also is detected in a bacterially expressed L1 ORF2p protein that lacks the L1 EN and ORF2p cysteine-rich domains and a thermostable group II intron-encoded protein. Processing of diverse modified primers demonstrates endonucleolytic cleavage that is eliminated by mutations in the RT active site. We propose that alt-EN is an evolutionarily conserved activity within the RT fold that promoted ENi retrotransposition of primordial retrotransposons prior to the acquisition of an EN domain.

molecular biology↗

bioRxiv2026

Neonatal social communication and single genes predict the variability of post-pubertal social behavior in a mouse model of paternal 15q11-13 duplication

Mental illnesses associated with high-risk copy number variations (CNVs) are characterized by incomplete penetrance and variable severity, with their underlying mechanisms remaining inadequately understood. We hypothesized that such phenotypic variability is evident from the neonatal stage and is, at least in part, attributable to individual differences in the expression levels of CNV-encoded genes in the brain. We conducted an analysis of the quantitative and functional structure of neonatal social communication, assessed post-pubertal social interaction, and evaluated the brain expression levels of genes within the same cohort of a mouse model of paternal human 15q11-13 duplication, a high-risk factor variably associated with neurodevelopmental disorders. Subsequently, computational methods were utilized to identify predictive variables for the variability of post-pubertal social interaction. Mice harboring the 15q11-13 duplication exhibited distinctive call sequences characterized by diverse connections, which lacked the incentive value necessary for effective social communication with mother mice. The neonatal call sequences and the expression levels of Magel2, along with, to a lesser extent, Herc2 and Ndn, in the prefrontal cortex of the 15q11-13 duplication model were predictive of post-pubertal social interaction. Our findings demonstrate that variability in post-pubertal social interaction--a dimensional characteristic of neurodevelopmental disorders--can be predicted by the variability of neonatal social communication and is influenced by the expression levels of specific CNV-encoded genes in the prefrontal cortex. This computational approach has the potential to predict the developmental trajectories of various dimensions of mental illness among CNV carriers in humans and to identify CNV-encoded driver genes in preclinical models, thereby providing potential mechanistic bases for the development of gene-based therapeutic strategies.

neuroscience↗

bioRxiv2025

Prenatal valproic acid-exposed autism marmosets increase mutual gaze and reduce inter-individual distance during dyadic social interactions

Autism spectrum disorder (ASD) is associated with differences in social interaction, including alterations in gaze behavior and interpersonal distance. Although most assessments of ASD remain individual-centric, emerging human studies indicate that social difficulties may arise from atypical dyadic coordination rather than from reduced social interest alone. We examined dyadic coordination in a non-human primate model of ASD, focusing on gaze and inter-individual distance during minimally constrained first encounters between prenatal valproic acid-exposed marmosets (VPA) and unexposed conspecifics (UE). Markerless pose estimation quantified frame-by-frame gaze direction and spacing, comparing VPA-UE with UE-UE dyads. VPA-UE pairs exhibited a higher proportion of mutual-gaze events than UE-UE pairs. VPA individuals showed more rapid looks in response to the partners gaze, yet spent less time looking at the partner when unobserved. VPA-UE dyads maintained shorter inter-individual distances than UE-UE dyads, and closer spacing was associated with decreased stability of mutual gaze. These findings reveal a dyadic coordination pattern in VPA-UE pairs, with rapid responsiveness coupled with distance-dependent fragility, paralleling features reported in human ASD. Our dyad-centric, markerless framework yields ecologically grounded readouts and potential intervention targets that leverage intact social responsiveness while accommodating altered spatial coordination.

neuroscience↗

bioRxiv2025

Novel therapy for gastric cancer peritoneal dissemination using genetically modified dental pulp cells and astatine-211

Peritoneal dissemination of gastric cancer is a terminal stage with limited treatment options and a five-year survival rate below 10%. To develop a more effective treatment, we created a new approach that uses genetically engineered human dental pulp cells (DPCs) that express the sodium/iodide symporter (NIS). These cells (NIS-DPCs) deliver astatine-211 (At-211) directly to tumor sites. When injected intraperitoneally into a mouse model of gastric cancer dissemination, DPCs, which were isolated and expanded, showed strong tumor-homing ability. Chemotaxis mediated by the CXCR4/SDF-1 axis has been reported to play a role in this accumulation. In addition to histological analysis, fluorescent imaging confirmed the selective accumulation of NIS-DPCs within tumor lesions. Introducing the NIS gene markedly increased SLC5A5 expression, enabling efficient At-211 uptake. To avoid nonspecific binding, sodium At-211 was utilized. High-resolution alpha-particle imaging visualized alpha-ray emission specifically from NIS-DPCs, confirming the radionuclides intracellular retention. In vivo, the sequential administration of NIS-DPCs, followed by Na[At-211], resulted in the pronounced regression of peritoneal tumors and a significant extension of survival compared to controls. The therapeutic mechanism involves three coordinated steps: tumor-directed migration of NIS-DPCs, At-211 uptake via NIS transporters, and localized alpha-particle-mediated cytotoxicity. This study introduces the novel concept of cell-based alpha-radiotherapy, which integrates regenerative and nuclear medicine. Due to the well-documented safety profile of DPCs in human clinical trials (J-REPAIR, jRCT1080224505), the NIS-DPC platform emerges as a promising approach for the precise, localized irradiation of disseminated gastric cancer and other challenging malignancies.

cancer biology↗

bioRxiv2025

Hyperactivity is linked to elevated cortisol levels: comprehensive behavioral analysis in the prenatal valproic acid-induced marmoset model of autism

Hyperactivity is frequently observed in individuals with autism spectrum disorder (ASD) and significantly affects various aspects of life. This underscores the critical need for effective intervention methods tailored to the needs of individuals with ASD. Non-human primate models offer a promising avenue for elucidating the intricate interplay between ASD characteristics and developing individualized therapeutic strategies. This study examined the activity levels and behavioral dynamics in a prenatal valproic acid-induced (VPA) common marmoset model of ASD using ultraminiature data loggers, employing a more detailed approach to behavioral pattern analysis than is traditionally utilized. Although the overall activity levels showed no significant differences, the VPA group exhibited increased activity during specific hours, which is consistent with human ASD studies. Sample Entropy, a statistical measure used to quantify the regularity and unpredictability of time-series data, was higher during daytime in the VPA group, indicating reduced regularity in activity patterns akin to impulsive behavior in ASD. Subtle patterns that were not discernible through simple group comparisons were identified, highlighting the potential of this method as a valuable tool for the behavioral analysis of human ASD. Associations between erratic activity patterns, brief resting intervals, and elevated cortisol levels were observed, all of which correspond to stress phenotypes in individuals with ASD. The findings revealed variations in activity among the adult VPA groups, potentially linked to stress responses. Additionally, VPA juvenile marmosets showed increased locomotor activity in the social interaction test, complementing the adult behavioral findings and suggesting age-dependent manifestations of hyperactivity in this model. This non-human primate model effectively replicates real-world scenarios encountered by individuals with ASD exhibiting hyperactivity, thus holding significant implications for the advancement of personalized therapeutic strategies.

neuroscience↗

bioRxiv2025

Nitrogen acquisition and selective bacterial attraction through fungal hyphae promote plant growth and health under nitrogen limitation

Plants alleviate nitrogen (N) deficiency through interactions with beneficial microbes, yet mechanisms underlying plant-fungus-bacterium mediated plant growth promotion (PGP) remain poorly understood. Here, we show that the root endophytic fungus Colletotrichum tofieldiae (Ct) enhances the growth of diverse plant species beyond the Brassicaceae under N deficient field and lab conditions. Optimal Ct-mediated PGP requires Arabidopsis thaliana nitrate transporters (AtNRT2.1/2.2/2.4/2.5), as well as the fungal N utilization regulator CtAREA. Isotopic tracing with 15NO3- reveals that Ct transfers N to hosts via CtAREA-dependent yet AtNRT2s-independent route, implicating distinct, parallel pathways in PGP. Moreover, Ct attracts the beneficial bacterium Paraburkholderia monticola through its hyphae, which metabolizes organic N sources and additively enhances plant growth with Ct. Notably, P. monticola suppressed the pathogenic transition of Ct in plant mutants defective in Brassicaceae-specific tryptophan-derived metabolism, potentially accounting for Cts broad beneficial activities. This plant-fungus-bacteria interaction may secure consistent PGP across varied agricultural settings.

plant biology↗

bioRxiv2025

Cross-disease comparison of dermatomyositis and lupus skin identifies inflammatory monocytes and JAK-1 signaling as drivers of vasculopathy in dermatomyositis

Dermatomyositis (DM) is a rare yet devastating autoimmune disease characterized by inflammatory and vasculopathic changes in skin and muscle. DM and systemic lupus erythematosus (lupus) skin lesions have overlapping clinical and histopathological features, yet disparate responses to available therapeutics. DM skin disease is often relapsing and recalcitrant. To investigate DM immunopathogenesis, non-lesional skin, lesional skin, and circulating immune cells from DM patients were analyzed using single-cell RNA-sequencing. Samples were analyzed in parallel with lesional and non-lesional lupus skin, healthy control skin, and peripheral blood. We demonstrate a pervasive type I interferon (IFN) signature in DM stroma that persists in culture and is distinguished from lupus by upregulation of VEGF and IL-18 signaling in DM keratinocytes. Furthermore, endothelial cells (ECs) in lesional DM exhibit decreased proliferation that was not observed in lupus. Using cell communication networks, we identified a population of DM-specific monocytes interacting with non-proliferating DM ECs. Co-culture of monocytes from DM patients with ECs resulted in increased EC apoptosis inhibited by JAK1 blockade. JAK1 inhibition also resulted in reversal of DM-stromal and inflammatory signatures. Together, our data provide a comprehensive cross-disease characterization of lesional and non-lesional skin of DM compared to lupus and implicate monocyte-mediated EC dysfunction in DM vasculopathy and support JAK inhibition for refractory skin disease.

immunology↗

bioRxiv2025

Plastic-Degrading Clusters of Orthologous Groups in Prokaryotes

Micro- and nanoplastic pollution (MNPP) is an increasing environmental threat due to the persistence, dispersal, and potential toxicity of plastic particles. Although microbial biodegradation offers a sustainable mitigation strategy, a comprehensive understanding of plastic-degrading proteins across microbial taxa is lacking. Here, we present the Plastic-Degrading Clusters of Orthologous Groups (PDCOGs) database (https://phylobone.com/microworld/PDCOG), comprising 625,616 potential plastic-degrading proteins (PPDPs) from free-living prokaryotes organized into 51 orthologous groups. The database/PDCOGs enable systematic analysis of microbial plastic-degrading capacity across ecosystems and phylogenetic lineages. Notably, PPDPs constitute [~]3.5% of all prokaryotic proteins, with over 95% of the species having the potential to biodegrade at least one plastic polymer type. This resource provides a genomic tool/framework for exploring the ecological and evolutionary importance of plastic biodegradation and supports future efforts to mitigate the global MNPP crisis.

microbiology↗

bioRxiv2025

A Transcriptomic Atlas of Healthy Human Skin Links Regional Identity to Inflammatory Disease.

Human skin is not a uniform organ but a mosaic of anatomically distinct niches, with each site finely tuned to unique environmental demands and immune pressures. Yet, the molecular determinants that define these regional identities and their relationship to site-specific vulnerability to inflammatory disease remain poorly understood. Here, we generate a high-resolution single-cell atlas of human skin, profiling 274,834 cells from 96 healthy samples across 7 anatomically distinct sites (acral, arm, axilla, back, face, leg and scalp). Our analysis reveals striking region-specific transcriptional and cellular networks, uncovering how local immune-stromal crosstalk governs tissue homeostasis and underpins anatomical susceptibility to distinct inflammatory diseases such as such as systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis. These findings illuminate the tissue-intrinsic foundations of regional immune identity and provide a blueprint/resource for the development of precision therapies tailored to the distinct immunological microenvironments of specific anatomical skin sites.

systems biology↗

bioRxiv2025

Iron deposition and functional connectivity alterations in the right substantia nigra of adult males with autism

The substantia nigra (SN) is a midbrain nucleus implicated not only in motor control and reward processing but also in higher-order cognitive functions. Iron homeostasis in this region is essential for neurotransmitter synthesis, especially for dopamine, and thus, iron dysregulation may contribute to the symptomatology of autism spectrum disorder (ASD). However, iron deposition and functional circuits of the SN in the autistic brain remain underexplored. This study investigated iron deposition and functional connectivity (FC) of the SN in 53 adult males with ASD and 99 typically developing controls using quantitative susceptibility mapping and resting-state fMRI. Compared to controls, the ASD group exhibited higher magnetic susceptibility in the right SN, suggesting elevated iron deposition. Within the ASD group, higher iron deposition was associated with more severe socio-communicative deficits and reduced sensory-seeking behavior. Seed-based FC analyses further revealed that the ASD group exhibited stronger FC between the right SN and bilateral visual cortices and reduced FC with the right superior frontal gyrus. These results highlight the critical role of SN in the autistic brain and indicate that altered iron homeostasis in the SN may contribute to disruptions in the dopaminergic system that underlie the core symptoms of ASD.

neuroscience↗

bioRxiv2025

Ketone Catabolism is Essential for Maintaining Normal Heart Function During Aging

The heart utilizes various nutrient sources for energy production, primarily favoring fatty acid oxidation. While ketones can be fuel substrates, ketolysis has been shown to be dispensable for heart development and function in mice. However, the long-term consequences of ketolysis downregulation in the heart remain unknown. Here we demonstrate that ketone catabolism is essential for preserving cardiac function during aging. The cardiac expression of succinyl-CoA:3-ketoacid CoA transferase (SCOT), a rate-limiting enzyme in ketolysis, decreases with aging in female mice. SCOT cardiomyocyte-specific knockout (cKO) mice exhibit normal heart function at 10 weeks of age but progressively develop cardiac dysfunction and remodeling as they age, without overt hypertrophy in both sexes. Notably, ketone supplementation via a ketogenic diet partially rescues contractile dysfunction in SCOT cKO mice, suggesting ketone oxidation-independent mechanisms contribute to the development of cardiomyopathy caused by SCOT downregulation. These findings indicate that ketone catabolism is crucial for maintaining heart function during aging, and that ketones confer cardioprotection independently of ketone oxidation.

cell biology↗

bioRxiv2025

Sharks and rays have the oldest vertebrate sex chromosome with unique sex determination mechanisms

Sex determination has been investigated across vertebrate lineages to reveal stepwise evolution of sex chromosomes and diversity of responsible molecular mechanisms. However, these studies hardly encompass cartilaginous fishes deeply isolated from the rest of vertebrates, which hinders the comprehensive view of vertebrate sex determination. Here, we produced chromosome-scale genome assemblies of egg-laying shark species and comparatively investigated genome sequences and transcriptome profiles across diverse cartilaginous fishes. Sex chromosome identification, supported by cytogenetic experiments, elucidated the homology of X chromosomes between sharks and rays as well as an extensively degenerating Y chromosome harboring no male-specific genes. These sex chromosomes scarcely included orthologs of previously documented sex determining genes. Transcriptomic analyses combined with histology of embryonic gonads revealed female-biased expressions of X-linked genes including those implicated in TGF-{beta} and IGF signaling pathways, which are attributed to their incomplete dosage compensation. Our findings indicate that sharks and rays share the oldest vertebrate sex chromosomes that originated around 300 million years ago and the dosage-dependent sex determination mechanism comprised of distinct molecules from other vertebrates. This study highlights the antiquity of sex chromosomes and uniqueness of sex determination mechanisms in sharks and rays, which advance our understanding on evolutionary plasticity of vertebrate sex determination.

evolutionary biology↗

bioRxiv2025

KAT6A acetylation drives metabolic adaptation to mediate cellular growth and mitochondrial metabolism through AMPK interaction

Diets influence metabolism and disease susceptibility, with lysine acetyltransferases (KATs) serving as key regulators through acetyl-CoA. We have previously demonstrated that a ketogenic diet alleviates cardiac pathology, though the underlying mechanisms remain largely unknown. Here we show that KAT6A acetylation is crucial for mitochondrial function and cell growth. Proteomic analysis revealed that KAT6A is acetylated at lysine (K)816 in the hearts of mice fed a ketogenic diet under hypertension, which enhances its interaction with AMPK regulatory subunits. RNA-sequencing analysis demonstrated that the KAT6A acetylation-mimetic mutant stimulates AMPK signaling in cardiomyocytes. Moreover, the acetylation-mimetic mutant mitigated phenylephrine-induced mitochondrial dysfunction and cardiomyocyte hypertrophy via AMPK activation. However, KAT6A-K816R acetylation-resistant knock-in mice unexpectedly exhibited smaller hearts with enhanced AMPK activity, conferring protection against neurohumoral stress-induced cardiac hypertrophy and remodeling. These findings indicate that KAT6A regulates metabolism and cellular growth by interacting with and modulating AMPK activity through K816-acetylation in a cell type-specific manner.

cell biology↗

bioRxiv2024

CAMDA 2023: finding patterns in urban microbiomes

The Critical Assessment of Massive Data Analysis (CAMDA) addresses the challenge of effectively utilizing Big Data in life science. Serving as both a conference and a catalyst for research groups, CAMDA annually presents challenges that foster innovative solutions. For the Forensics CAMDA 2023 challenge, we analyzed 365 metagenomic samples from 16 cities worldwide to characterize their origin. The forensic challenge was addressed from two perspectives: using the reduced abundance OTU tables and employing functional annotations. To identify the most informative Operational Taxonomic Units, we fit negative binomial models ultimately reducing variables to 294. After OTU selection, we implemented supervised models and conducted 5-fold cross-validation (CV) with a 4:1 training-to-validation ratio in each scenario. Support vector classification (SVC) achieved the highest F1 score (0.96) for the abundance tables, accurately classifying most cities, although New York City (NYC) posed a challenge. Via functional profiles with Mifaser at level 4, we achieved the best functional classification using the Neural Network (NN) model. Additionally, to gain insight into further associations between bacterial distribution with other covariates, we applied Dirichlet regression over Escherichia, Enterobacter, and Klebsiella bacteria abundances. We considered climatic and demographic variables of the cities, observing that population increase is indeed associated with a rise in the mean of Escherichia while decreasing temperature is linked to higher proportions of Klebsiella. For replicability of the scripts, a Docker container and a Conda environment are available at the repository: GitHub:github.com/ccm-bioinfo/cambda2023.

bioinformatics↗

bioRxiv2024

Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4x10-9 per nt, we report that sun exposure creates pervasive mutations at sites with [~]100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3x10-5 per nt. Clonal expansion by neutral drift or passenger formation was nil. Tumor suppressor gene hotspots reached variant allele frequency 0.1-10% via 30-3,000 fold clonal expansion, in occasional biopsies. CPD hyperhotspots reached those frequencies in every biopsy, with modest clonal expansion. In vitro, tumor hotspot mutations arose occasionally over weeks of chronic low-dose exposure, whereas CPD hyperhotspot mutations arose in days at 1000-fold higher frequencies, growing exponentially. UV targeted mini-drivers in every skin cell.

genomics↗

bioRxiv2024

Curriculum Learning: sequential acquisition of task complexity enhances neuronal discriminability

Curriculum Learning (CL) is a strategy where concepts with increasing complexity are acquired sequentially. Despite its widespread application, its putative neural mechanisms are poorly understood. In this study, using a multi-staged Go/No-Go auditory discrimination paradigm for mice, we show that CL improves and accelerates learning in a unidirectional way. By combining behavioral data with in vivo electrophysiological recordings of the auditory cortex, we demonstrate that neuronal discriminability is enhanced with sequential training. This improvement suggests that CL involves a convergence of common discriminable features in the auditory stimuli shared across tasks of different complexity. Our findings uncover specific properties of CL at the level of neuronal discriminability, distinguishing it from other forms of learning strategies.

neuroscience↗