Biology subjects

Ma, F.

Publications and source records attributed to Ma, F..

At least 19 recordsLinked to original sources

bioRxiv2026

An RGS5-positive fibroblast to WNT-like epithelial TGFB axis in colorectal liver metastasis, replicated in an independent paired cohort

Background: Colorectal cancer liver metastasis is accompanied by coordinated stromal remodelling, but which fibroblast and malignant epithelial states are coupled, and whether any such coupling holds outside the dataset it was found in, is rarely tested. Methods: Paired primary tumours and liver metastases from six patients were analysed by single-cell RNA sequencing with copy-number-based identification of malignant cells, trajectory inference, cell-cell communication and ligand-target modelling, and spatial transcriptomics of three metastatic sections. Protein staining was taken from an independent tissue resource. Every step was then repeated in a second, independent paired cohort of five patients and two further metastatic sections, with cell identities fixed by transfer from the discovery data rather than refitted. Results: An RGS5-positive fibroblast/pericyte-like state (F2) and a WNT-like malignant epithelial state (C2) were both enriched in metastases and occupied late trajectory positions. Communication analysis nominated a directional F2-to-C2 programme with transforming growth factor beta as the highest-ranked pathway and its receptor TGFBR2 enriched in C2. Spatial data placed the two states in the same neighbourhoods. Hub genes of the programme were TPT1, SLC1A5, SOX4 and TSC22D1, and protein staining was higher in tumour than normal colon for the three with available data. In the independent cohort the same states reappeared: F2 was enriched in metastases (Ro/E 1.22 versus 0.52; 32% versus 14% of fibroblasts), C2-like cells were the most metastasis-enriched epithelial state (1.10 versus 0.86), 92% of the cells that cohort's own authors called MCAM-positive fibroblasts mapped to F2, and F2 was again the strongest TGFB sender to C2-like epithelium at both sites. Conclusions: A directional TGFB axis from an RGS5-positive fibroblast state to a WNT-like epithelial state is a reproducible feature of colorectal liver metastasis rather than a property of one dataset. Its spatial expression varies between sections, which constrains how tightly the two states can be said to be co-localised.

cancer biology↗

bioRxiv2026

Developmental enrichment enhances a topographically structured proprioceptive cortical code

The organization of proprioceptive cortex emerges from experience-dependent patterns of limb use during development, rather than merely reflecting peripheral innervation. However, the degree and specifics of these developmental changes remain poorly understood. To address this question, we investigated how early environmental enrichment (EE) reshapes the topography and functional properties of the mouse forelimb proprioceptive cortex. Using wide-field calcium imaging, we found that EE did not induce major reorganization of the mesoscale activation map. To resolve cellular level topology, we developed a large-field fluorescence macroscope enabling unbiased single neuron imaging across the entire activation area. We identified a topographically organized preference in directional tuning in which somatosensory and motor regions of the map encode distinct movement axes within the peripersonal space. Developmental enrichment reshaped this anisotropic representation at the cellular level. Rather than reducing the directional bias by homogenizing tuning across movement directions, EE strengthened the anisotropy by sharpening its topographic segregation and concentrating neuronal tuning around a common peripersonal axis. Our findings therefore reveal that enriched limb use and sensorimotor exploration reinforce an ecologically relevant specialization of the mouse proprioceptive cortex for movements directed toward the body.

neuroscience↗

bioRxiv2026

Scalable platform for cellular and biochemical screening of combinatorial small-molecule libraries in droplets

A new pattern of hit discovery is emerging with the rise of chemocentric modalities, such as chemical induced proximity (CIP). Synthesis and functional screening of dynamic, purpose-built libraries, such as E3 ligase biased libraries for targeted protein degradation (TPD), is redefining the druggable landscape. However, this new paradigm arguably lies beyond the remit of conventional screening methods which have been optimized for static, diversity-oriented libraries. To address this gap, we developed microfluidic compound screening in droplets (MicDrop), a scalable platform where purpose-built DNA-encoded one-bead one-compound library members are individually tested at high concentrations in pico-liter sized droplets for either biochemical or cellular function. A proof-of-concept CRBN library demonstrated the robustness of the workflow through an IKZF3 degradation screen which discovered an unexpected succinimide-based IKZF3 degrader, while reproducing the relative potency ranking of reference compounds. Screening of a prospective VHL library for CDO1 recruitment and degradation demonstrated that orthogonal assays gave an informative consensus hit list and an actionable machine-learning (ML) recruitment model. These findings establish a blueprint for intentional discovery of chemical inducers of proximity, while producing reliable data to accelerate ML-based design-make-test-analyze (DMTA) cycles in pursuit of new therapeutics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/730915v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@12de3cborg.highwire.dtl.DTLVardef@1c6618dorg.highwire.dtl.DTLVardef@12ea42eorg.highwire.dtl.DTLVardef@11cea77_HPS_FORMAT_FIGEXP M_FIG C_FIG

Cell Biology↗

bioRxiv2026

TMEM106B C-terminal fragments drive nucleocytoplasmic transport failure and TDP-43 mislocalization in the aging human brain

TMEM106B is a lysosomal membrane protein and major genetic modifier of multiple neurodegenerative diseases, including frontotemporal lobar degeneration, Alzheimers disease, and amyotrophic lateral sclerosis. Proteolytically generated C-terminal fragments of TMEM106B assemble into amyloid fibrils that accumulate in the brains of individuals with neurodegenerative disease and in cognitively normal aged adults, yet how these fibrils produce neuronal dysfunction has remained unclear. Here, we show that cytosolic and lysosome-directed TMEM106B C-terminal fragments (CTF and gCTF) form detergent-insoluble amyloid aggregates, drive redistribution of endogenous TDP-43 from the nucleus to the cytoplasm, and accelerate neuronal death. Unbiased proximity proteomics identified the inner nuclear membrane LAP1-TorsinA axis as a fragment-specific interactome, and co-immunoprecipitation confirmed a direct physical interaction between gCTF and LAP1 that was not observed with full-length TMEM106B. Fragment expression disrupted Lamin B1 organization, mislocalized the nuclear import machinery KPNB1 and RanGAP1, and impaired importin-dependent nuclear transport in primary cortical neurons. Critically, neurons harboring endogenous TMEM106B fibrillar pathology in aged human frontal cortex exhibited the same phenotypes, namely disrupted Lamin B1 and LAP1 localization and cytoplasmic redistribution of TDP-43, whereas fibril-negative neurons from the same cases and younger control tissue retained intact nuclear envelope organization. These findings define TMEM106B proteinopathy as an upstream driver of nuclear envelope disruption and nucleocytoplasmic transport failure, linking a widespread feature of brain aging to a central mechanism of neurodegeneration.

neuroscience↗

bioRxiv2026

Aberrant oxidative metabolism selects for TET2-deficient hematopoietic stem and progenitor cells

The mechanism(s) driving selective expansion of mutant hematopoietic stem and progenitor cells (HSPC) in clonal hematopoiesis (CH) are incompletely understood. Here, we address the role of metabolism in selection for HSPC with loss of function mutations in TET2. Loss of Tet2 in murine HSPC triggers overexpression of glycolysis and oxidative phosphorylation genes and increased oxidative metabolism via an enlarged mitochondrial network. However, Tet2-deficient HSPC maintain a normal redox state. Strikingly, compound loss of the rate-limiting pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) triggers increased reactive oxygen species and impairs the fitness of Tet2-deficient HSPC. We find that aberrant oxidative metabolism is also a feature of HSPC in human CH and clonal cytopenia of unknown significance (CCUS). Overall, our data point to aberrant metabolism as a critical and conserved driver of selection in TET2-deficient CH and identify the PPP as a crucial compensatory pathway needed to maintain their selective advantage. Statement of SignificanceThis study identifies oxidative metabolism as a critical driver of selection for TET2-deficient HSPC in clonal hematopoiesis (CH). It also demonstrates that cellular redox state is a vulnerability that impairs their fitness. These insights establish targetable metabolic pathway(s) that could be exploited in the setting of TET2 mutant CH.

cancer biology↗

bioRxiv2025

Macrophage EHD1 promotes inflammation and stabilizes sortilin to accelerate atherosclerosis

BackgroundMacrophages are key players in the pathogenesis of atherosclerosis. They trigger immune responses through their cell-surface receptors. However, how macrophages regulate those receptors in response to pro-inflammatory stimuli is not completely understood. Endocytic membrane trafficking involving receptor internalization, followed by endosomal transport and recycling of the internalized receptors, plays essential roles in balancing cell-surface receptors to meet cellular needs. Here, we explored the role of the endocytic regulator EHD1 in immune responses in macrophages and determined its contribution to atherosclerosis progression. MethodsEHD1 expression profiles in mouse and human plaques were determined by single-cell RNA sequencing (scRNA-seq) and immunofluorescence staining. Bone marrow transplantation (BMT) by transplanting bone marrow cells from Ehd1-/- or littermate wild-type mice to irradiated Ldlr-/- mice was performed to determine the effect of EHD1 deletion on atherosclerosis progression. In vitro mechanistic studies including inflammation signaling and endocytosis assays were performed in bone marrow-derived macrophages. ResultsEHD1 expression in macrophages is enhanced as atherosclerosis progresses in both mice and humans. Histological analysis of aortic root sections from BMT mice showed that EHD1 deletion reduces lesion size. ScRNA-seq of aortic CD45+ cells demonstrated that EHD1 deletion attenuates pro-inflammatory responses and cell-cell interactions. Mechanistic studies revealed that EHD1 accelerates the endocytic recycling of TNFR2 and activates NF-kB, leading to increased expression of inflammatory cytokines. Moreover, EHD1 interacts with retromer and stabilizes sortilin, a retrograde cargo of retromer and a risk factor for atherosclerosis. ConclusionsEHD1 promotes inflammation by enhancing TNFR2-NF-kB signaling and stabilizing sortilin, leading to accelerated atherosclerosis. Our study reveals novel roles for EHD1-mediated membrane trafficking in macrophage function and paves the way to innovative therapeutic strategies that aim to address dysregulated membrane trafficking in atherosclerosis.

cell biology↗

bioRxiv2025

CSF1R+ macrophage and osteoclast depletion impairs neural crest proliferation and craniofacial morphogenesis

Despite a wealth of knowledge on the mechanisms underlying craniofacial morphogenesis during gestation, the roles of fetal macrophages and osteoclasts during this process remain less well characterized. Here, we used the pharmacological inhibitor PLX5622 to disrupt colony stimulating factor-1 receptor (CSF1R) signaling, which is essential for macrophage and osteoclast proliferation, differentiation, and survival. Prenatal PLX5622 exposure resulted in [~]50% depletion of CSF1R+ macrophages, with complete loss of osteoclasts. While there were no notable changes in craniofacial nerve or muscle development, prenatal exposure to PLX5622 resulted in skull doming and cranial suture impairments, in addition to disruptions to development of the premaxilla, mandible, ear ossicles, palate, and cranial base. In response to PLX5622 exposure, cytokine and chemokine signaling was altered and neural crest proliferation was impaired. Our data also highlight sex- and strain-specific differences in PLX5622 phenotypes and together demonstrate that CSF1R+ macrophages and osteoclasts are essential for craniofacial morphogenesis.

developmental biology↗

bioRxiv2025

The interaction between aging and DNA damage influences the accumulation of APP in Alzheimer's disease

DNA damage is a major driver of the aging process, and the progression of Alzheimers disease (AD) worsens the situation. Neurons of the AD brain show significantly elevated levels of DNA damage compared to controls. AD is also associated with altered processing of the amyloid precursor protein (APP), best known for its A{beta} proteolytic peptide fragment. In the current work we find that these three elements - age, DNA damage, and APP - are associated with each other. We present evidence from the mouse brain supporting the hypothesis that DNA damage drives increased levels of APP. Using the TUNEL reaction to track DNA damage, we show that TUNEL staining increases significantly with age (6 months to 24 months, 8 females and 14 males total in this study), in lockstep with intracellular APP. To separate correlation from causality we analyzed tissue from mice genetically deficient in ATM (ataxia-telangiectasia mutated), a protein kinase that promotes DNA damage repair. Compared to 6-month wild type mice, the increased TUNEL signal in neurons of 6-month Atm-/- animals was equivalent to that seen in 24-month wild type. Significantly, the APP signal in the Atm-/- cells was also increased, and this correlation was found in both neuronal and non-neuronal cells. These results suggest that the loss of genomic integrity associated with aging is a cellular stressor that increases the levels of APP and thus increases vulnerability to the pathogenesis of AD. SIGNIFICANCE STATEMENTOur work links the genetics of Alzheimers disease (dominant disease-causing mutations in the APP gene) with DNA damage and aging - two factors known as risk factors in AD. The evidence suggests that the enhanced DNA damage associated with the normal aging process, increases the levels of APP thus potentially contributing to A{beta} production and plaque formation.

neuroscience↗

bioRxiv2025

Optimized Quantitative Susceptibility Mapping at 7T MRI for Assessing Iron Deposition in Alzheimers Disease

INTRODUCTIONElevated brain iron levels are common in Alzheimers disease (AD). Quantitative Susceptibility Mapping (QSM) is an advanced MRI technique for assessing iron accumulation. The optimized QSM at 7 Tesla (7T) MRI may further improve the sensitivity to detect subtle susceptibility changes in AD. METHODSWe optimized a QSM processing pipeline for 7T MRI by systematically comparing multiple reconstruction algorithms. Evaluation criteria included image quality, artifact suppression, and anatomical clarity. The finalized pipeline was applied to individuals with AD and healthy controls (HCs). RESULTSThe results revealed significantly elevated magnetic susceptibility values in the globus pallidus and dentate nucleus of the AD group compared to HCs. These findings were confirmed through both visual inspection and quantitative analysis of high-resolution QSM maps. DISCUSSIONOur results highlight the importance of optimizing QSM pipelines at 7T for accurate susceptibility quantification. We identified an optimal pipeline suitable for future applications in patients with AD and other neurological conditions.

neuroscience↗

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

Spatial profiling reveals TREM2+ macrophages as central to Mycobacterium tuberculosis pathogenesis in human pulmonary tuberculosis

Pulmonary tuberculosis (TB) exhibits marked spatial heterogeneity, with alveolar pneumonia and organized granulomas frequently coexisting within the same lung. While granulomas have long dominated conceptual models of TB pathogenesis, the immune programs operating within alveolar TB pneumonia in humans remain incompletely defined. Here, we integrate spatial transcriptomics, single-cell RNA sequencing, high-resolution imaging, and functional assays of human lung biopsies to directly compare alveolar pneumonia with adjacent granulomas from the same individuals. We demonstrate that alveolar TB pneumonia is enriched for TREM2 lipid-laden macrophages characterized by lipid metabolic reprogramming, sparse T-cell infiltration, attenuated antimicrobial gene expression, and abundant Mycobacterium tuberculosis (Mtb) transcripts and antigens. In contrast, neighboring granulomas exhibit organized lymphoid architecture and robust antimicrobial programs. Mechanistically, the mycobacterial virulence lipid phthiocerol dimycocerosate (PDIM) and free mycolic acids induce TREM2 expression and activate TREM2-DAP12 signaling, promoting lipid droplet accumulation, suppressing autophagy, and enhancing intracellular Mtb survival in human macrophages. This immunometabolic state is pharmacologically reversible: 1,25-dihydroxyvitamin D downregulates TREM2, restores autophagy, reduces lipid droplets, and limits bacterial viability. Together, these findings define a spatially localized TREM2 foamy macrophage program within alveolar pneumonia that contrasts sharply with adjacent granulomatous immunity, establishing an niche permissive for bacillary persistence and potentially transmission, as well as identifying a tractable host pathway in human TB pathogenesis.

immunology↗

bioRxiv2025

Targeting ZNRF3 and RNF43 to Restore Regeneration and Reverse Metabolic Dysfunction-Associated Steatotic Liver Disease

Liver regeneration and hepatocyte metabolic identity are disrupted in metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), yet the mechanisms of restore liver regeneration and reprogram metabolism for disease reversal remains poorly understood. Here, we show that {beta}-Catenin activity progressively declines in hepatocytes during MASH in both humans and mice, coinciding with impaired regeneration and defective lipid clearance. Targeted deletion of the endogenous WNT pathway inhibitors ZNRF3 and RNF43 in hepatocytes after MASH onset reactivates {beta}-Catenin signaling, leading to robust regression of steatosis, inflammation, and fibrosis, and restoring regenerative capacity across multiple fatty liver disease models. Mechanistically, this therapeutic effect is driven by {beta}-Catenin-dependent induction of the alternative bile acid synthesis pathway without disrupting systemic lipid homeostasis. Importantly, both short-and long-term deletion of ZNRF3/RNF43 restores liver function without triggering tumorigenesis or hepatotoxicity, indicating a safe therapeutic window. These findings reveal that physiological activation of WNT/{beta}-catenin signaling via ZNRF3 and RNF43 offers a viable regenerative and metabolic strategy for reversing fatty liver disease.

cell biology↗

bioRxiv2025

Locus-specific Convergent Evolution and Interchromosomal Rearrangements Contribute Type I Interferon Diversification in Amniotes

Type I interferons (IFN-Is) play essential roles in antiviral immune responses. The extensive diversification of IFN-Is into multiple subtypes and redundant gene copies has posed significant challenges for evolutionary reconstruction. To address this, we developed an integrated analytical pipeline combining the IFN-SCOPE classification model and GENE-GRADE algorithm. Through comprehensive synteny-guided phylogenetic analysis, we identified three evolutionarily conserved IFN-I loci (HACD4, MOB3B, and UBAP2) that maintain chromosomal colocalization across all major amniote lineages - mammals, squamates, and Archelosauria (turtles, crocodilians, and birds). While MOB3B-locus maintains a single IFN-{kappa} ortholog, the HACD4 (IFN-H) and UBAP2 (IFN-U) loci show lineage-specific expansion patterns: IFN-H proliferated in mammals/reptiles but remained single-copy in birds, whereas IFN-U expanded in birds but not in other lineages. Phylogenetic analysis reveals these independently evolved multicopy genes nevertheless cluster into two conserved subgroups (IFN-H2/H1 and IFN-U2/U1), suggesting convergent functional specialization. Within IFN-H and IFN-U clusters, the single-copy IFN-H2 and IFN-U2 genes - positioned at the ancestral ends of their respective genomic arrays - likely represent the progenitor sequences of each locus. Notably, among mammalian IFN-H2 genes, we identified the poorly characterized IFN-{upsilon} (rather than IFN-{beta}) as the ancestral form of mammalian IFN-H subtypes. Furthermore, we identified IFN-I genes at non-canonical loci resulting from interchromosomal duplication events in tortoises and diving ducks and provide clear evidence that interchromosomal duplications contributed to IFN-I gene diversity. These discoveries advance our understanding of the evolutionary mechanisms shaping intronless IFN-I genes in amniotes, and potentially beneficial for developing novel IFN-I based antiviral treatments through comparative immunological approaches.

bioinformatics↗

bioRxiv2025

APP overexpression delays synaptic development and alters neuronal network properties

The amyloid precursor protein (APP) regulates neuronal excitability by altering the structure of the axon initial segment. Using high density multielectrode arrays we compared the electrophysiological consequences of APP overexpression with exposure to {beta}-amyloid (A{beta}) and found that the two manipulations affected neural activity in largely non-overlapping ways. In mature cultures (>18 days in vitro, DIV18), APP reduced the firing probability of individual neurons, while {beta}-amyloid stripped synapses impacting whole-network connectivity. In immature cultures (DIV10), increasing APP - either acutely with lentiviral vectors or genetically by culturing APP transgenic neurons - revealed a separate developmental function. Synaptogenesis and axonal branch formation were blocked. A{beta}, by contrast, interfered primarily with network behavior. Our findings suggest that Alzheimers disease is likely an amalgamation of APP mis-regulation plus the effects of A{beta} accumulation. They also urge consideration of the idea that familial and sporadic forms of Alzheimers may represent distinct disease processes.

neuroscience↗

bioRxiv2025

Phase separation drives SNARE complexes formation

BackgroundNeuronal exocytosis is mainly driven by the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes. However, little is known about the organization principle of the SNARE complex. MethodsProtein condensates formed by SNARE complex were imaged by confocal microscope. Fluorescence recovery after photobleaching (FRAP) assay together with fusion and division assays at the cellular level and in vitro studies with purified proteins were performed to characterize the dynamic properties of protein condensates. The effect of SNARE complex phase separation on the recruitment of synaptic vesicles was detected by immunofluorescence. ResultsWe discover that phase separation drives SNARE complex formation and aggregation; in addition, nonintrinsically disordered regions (non-IDRs) of the syntaxin1 protein is necessary for the formation of these biological condensates. Functionally, phase separation of the SNARE complex can be regulated by the major cofactors of the fusion machinery and has the ability to recruit synaptic vesicles in neurons. ConclusionsOur study here establishes that phase separation is a promising way to mediate the formation and aggregation of the SNARE complex, and further identified that the non-IDRs of syntaxin1 is necessary for the phase separation of the SNARE complex. Our work answers an vital scientific question: does the SNARE complex function as multiple copies that are dispersed or clustered together to ensure sustained neurotransmitter release. In sum, phase separation provides an ideal working model for SNARE complex-mediated membrane fusion and neurotransmitter release.

neuroscience↗

bioRxiv2025

Lack of motor defects and ALS-like neuropathology in heterozygous Sptlc1 Exon 2 deletion mice

Mutations in the human SPTLC1 gene have recently been linked to early onset amyotrophic lateral sclerosis (ALS), characterized by global atrophy, motor impairments, and symptoms such as tongue fasciculations. All known ALS-linked SPTLC1 mutations cluster within exon 2 and a specific variant, c.58G>T, results in exon 2 skipping. However, it is unclear how the exon 2 deletion affects SPTLC1 function in vivo and contributes to ALS pathogenesis. Leveraging the high genomic sequence similarity between mouse and human SPTLC1, we created a novel mouse model with a CRISPR/Cas9-mediated deletion of exon 2 in the endogenous murine Sptlc1 locus. While heterozygous mice did not develop motor defects or ALS-like neuropathology, homozygous mutants died prematurely. These findings indicate that Sptlc1 {Delta}Exon2 heterozygous mice do not replicate the disease phenotype but provide valuable insights into SPTLC1 biology and serve as a useful resource for future mechanistic studies.

neuroscience↗

bioRxiv2025

Action features dominate cortical representation during natural vision

Cortical resources are allocated into systems specialized for processing ecologically relevant features of the world. These features are typically studied in isolation using controlled experimental stimuli, making it difficult to assess the relative importance of different kinds of features that tend to overlap during natural vision. In the current study, we evaluated the relative contributions of action, agent, and scene features in predicting cortical activity while participants viewed a 1-hour nature documentary. We tested four sets of model features: semantic vectors capturing the observed action, agent, and scene features derived from an annotation of the stimulus, as well as low-level visual motion-energy features. We used banded ridge regression to fit vertex-wise encoding models from the combination of all four sets of features. While each set of features predicted neural activity in the expected areas, the action features predicted more widespread activity. A variance partitioning analysis revealed that the action features captured the most unique variance in neural activity across ten times as many cortical vertices as the agent or scene features. Our findings suggest that cortical activity during dynamic, natural vision is dominated by features for understanding the actions of others.

neuroscience↗

bioRxiv2024

Resolving the design principles that control postnatal vascular growth and scaling

After birth, tissues grow continuously until reaching adult size, with each organ exhibiting unique cellular dynamics, growth patterns, and (stem or non-stem) cell sources. Using a suite of experimental and computational multiscale approaches, we found that aortic expansion is guided by specific biological principles and scales with the vertebral column rather than animal body weight. Expansion proceeds via two distinct waves of arterial cell proliferation along blood flow that are spatially stochastic, yet temporally coordinated. Each wave exhibits unique cell cycle kinetics and properties, with the first wave exhibiting cell cycle durations as fast as 6 hours. Single-cell RNA sequencing showed changes in fatty acid metabolism concomitant with an increase in cell size. Mathematical modeling and experiments indicated endothelial cell extrusion is essential for homeostatic aortic growth and balancing excess proliferation. In a genetic model of achondroplasia, the aorta achieves proper scaling through enhanced cell extrusion while maintaining normal proliferation dynamics. Collectively, these results provide a blueprint of the principles that orchestrate aortic growth which depends entirely on differentiated cell proliferation rather than resident stem cells.

developmental biology↗