Search bioRxiv⌕ Search

Biology subjects

Youngblood, M.

Publications and source records attributed to Youngblood, M..

5 recordsLinked to original sources

Multicellular Spatial Programs Define the Histopathological Architecture of Meningioma

Tumors are often described by cell types or gradients, but the organizing units of tumor tissue remain unclear. Using meningiomas, which show marked morphologic diversity despite constrained and recurrent genetics, we identify reproducible multicellular spatial molecular programs (SMPs) characterized by recurring cell-type mixtures that combine in different proportions across tumors. We built a multi-omic atlas of 147 human meningiomas (1.6 million cells/spots), integrating scRNA-seq, Visium, CosMx-RNA, and CosMx-Protein. Across platforms, SMPs mapped onto canonical whorl-lobule architecture and defined a structured ecological landscape linking hypoxic, immune-evasive states to vascularized, matrix-remodeling, and mineralization-rich states. For translation, we developed MeningNet, a hybrid ConvNeXt-Vision Transformer that infers SMPs directly from hematoxylin-and-eosin sections. MeningNet generalized across an internal replication cohort and 465 external whole-slide images, recovering cross-platform inference and showing significant association with CNS-WHO grade. These findings establish meningioma architecture as a reproducible histopathological framework for inferring spatial molecular state from routine pathology.

Cancer Biology↗

Vocal efficiency in crows

Many communicative systems have been selected for efficiency, shaped by the trade-off between information transmission and energetic or temporal constraints. Linguistic laws such as Menzeraths law--predicting shorter elements in longer sequences--have emerged as widespread principles across vocal communication in many species. While these laws have been predominantly studied at the species level, the influence of individual and social factors remain underexplored. In this study, we investigated adherence to Menzeraths law in the vocal communication of carrion crows, Corvus corone corone, hooded crows, Corvus corone cornix and hybrids. Our findings show that crow call sequences adhere to Menzeraths law, with shorter calls occurring in longer sequences, demonstrating structural efficiency in vocal communication. In carrion crows specifically, we analysed call sequences in relation to individual characteristics (sex, age) and social variables (group size, dominance status, strength of affiliative relationships). Interestingly, adherence to Menzeraths law was stronger in males and younger individuals, while no effects were found for group size, dominance, or affiliative relationships. This study provides the first evidence of Menzeraths law in corvid vocal communication and suggests that individual-level traits, rather than broader social dynamics, may shape vocal efficiency. These findings broaden our understanding of widespread principles in animal communication and raise new questions about the ontogeny and flexibility of vocal efficiency in complex social species.

animal behavior and cognition↗

Content bias in the cultural evolution of house finch song

In this study, we used a longitudinal dataset of house finch (Haemorhous mexicanus) song recordings spanning four decades in the introduced eastern range to assess how individual-level cultural transmission mechanisms drive population-level changes in birdsong. First, we developed an agent-based model (available as a new R package called TransmissionBias) that simulates the cultural transmission of house finch song given different parameters related to transmission biases, or biases in social learning that modify the probability of adoption of particular cultural variants. Next, we used approximate Bayesian computation and machine learning to estimate what parameter values likely generated the temporal changes in diversity in our observed data. We found evidence that strong content bias, likely targeted towards syllable complexity, plays a central role in the cultural evolution of house finch song in western Long Island. Frequency and demonstrator biases appear to be neutral or absent. Additionally, we estimated that house finch song is transmitted with extremely high fidelity. Future studies should use our simulation framework to better understand how cultural transmission and population declines influence song diversity in wild populations.

animal behavior and cognition↗

Relationship between personality and cognitive traits in domestic rabbits (Oryctolagus cuniculus)

Domestication is the process by which species adapt to, and are artificially selected for, human-made environments. Few studies have explored how the process of domestication has affected the connection between behavioral traits and cognitive abilities in animals. This study investigated the relationship between personality and cognitive traits in domestic rabbits (Oryctolagus cuniculus). Fifteen individuals kept in a rabbit rescue facility were tested over a period of two months. We measured the linkage between behavioral traits (response to a novel object and exploration time) and cognitive performance. Our results suggest that there is no relationship between personality traits and problem solving abilities in domestic rabbits. In addition, our results suggest that exploration time is significantly repeatable at the individual level while latency to approach a novel object is not. Thus further research is needed to explore the relationship between cognitive and personality traits in domestic rabbits.

animal behavior and cognition↗

Direct in vivo mapping of functional suppressors in glioblastoma genome

Glioblastoma (GBM) is one of the deadliest cancers, with limited effective treatments and single-digit five-year survival 1-7. A causative understanding of genetic factors that regulate GBM formation is of central importance 8-19. However, a global, quantitative and functional understanding of gliomagenesis in the native brain environment has been lacking due to multiple challenges. Here, we developed an adeno-associated virus (AAV) mediated autochthonous CRISPR screen and directly mapped functional suppressors in the GBM genome. Stereotaxic delivery of an AAV library targeting significantly mutated genes into fully immunocompetent conditional Cas9 mice robustly led to gliomagenesis, resulting in tumors that recapitulate features of human GBM. Targeted capture sequencing revealed deep mutational profiles with diverse patterns across mice, uncovering in vivo roles of previously uncharacterized factors in GBM such as immune regulator B2m, zinc finger protein Zc3h13, transcription repressor Cic, epigenetic regulators Mll2/3 and Arid1b, alongside canonical tumor suppressors Nf1 and Pten. Comparative cancer genomics showed that the mutation frequencies across all genes tested in mice significantly correlate with those in human from two independent patient cohorts. Co-mutation analysis identified frequently co-occurring driver combinations, which were validated using AAV minipools, such as Mll2, B2m-Nf1, Mll3-Nf1 and Zc3h13-Rb1. Distinct from Nf1-oncotype tumors, Rb1-oncotype tumors exhibit undifferentiated histopathology phenotype and aberrant activation of developmental reprogramming signatures such as Homeobox gene clusters. The secondary addition of Zc3h13 or Pten mutations drastically altered the gene expression profiles of Rb1 mutants and rendered them more resistant to the GBM chemotherapeutic temozolomide. Our study provides a systematic functional landscape of GBM suppressors directly in vivo, opening new paths for high-throughput molecular mapping and cancer phenotyping.

systems biology↗