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December 10, 2023


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Age-dependent Powassan Virus Lethality is Directed by Glial Cell Activation and Divergent Neuroinflammatory Cytokine Responses in a Murine Model

Powassan virus (POWV) is an emergent tick-borne flavivirus that causes fatal encephalitis in the elderly and long-term neurologic sequelae in survivors. How age contributes to severe POWV encephalitis remains an enigma and there are currently no animal models that reflect age-dependent POWV neuropathology. Inoculating C57BL/6 mice with a POWV strain (LI9) currently circulating in Ixodes ticks, resulted in age-dependent POWV lethality with overt spongiform brain damage 10-15 dpi. Infection of 50 week old mice resulted in 82% lethality 10-15 dpi that was sequentially reduced by age to 7.1% in 10 week old mice. LI9 encephalitis resulted in early neuronal depletion, with severe CNS damage, persistent inflammatory gliosis and long-term spongiform pathology in survivors (30 dpi).

biorxiv.org     Dec 19, 2023


Persistence of the primary somatosensory system in zebrafish

The somatosensory system detects peripheral stimuli that are translated into behaviors necessary for survival. Fishes and amphibians possess two somatosensory systems in the trunk: the primary somatosensory system, formed by the Rohon-Beard neurons, and the secondary somatosensory system, formed by the neural crest cell-derived neurons of the Dorsal Root Ganglia. Rohon-Beard neurons have been characterized as a transient population that mostly disappears during the first days of life and is functionally replaced by the Dorsal Root Ganglia. Here, I follow Rohon-Beard neurons in vivo and show that the entire repertoire remains present in zebrafish from 1-day post-fertilization until the juvenile stage, 15-days post-fertilization.

biorxiv.org     Dec 19, 2023


Arctos: Community-driven innovations for managing biodiversity and cultural collections

Museum collections house millions of objects and associated data records that document biological and cultural diversity. In recent decades, digitization efforts have greatly increased accessibility to these data, thereby revolutionizing interdisciplinary studies in evolutionary biology, biogeography, epidemiology, cultural change, and human-mediated environmental impacts. Curators and collection managers can make museum data as accessible as possible to scientists and learners by using a collection management system. However, selecting a system can be a challenging task. Here, we describe Arctos, a community solution for managing and accessing collections data for research and education. Specific goals are to: (1) Describe the core elements of Arctos for a broad audience with respect to the biodiversity informatics principles that enable high quality ...

biorxiv.org     Dec 19, 2023


Whole-brain modular dynamics at rest predict sensorimotor learning performance

Predictive biomarkers of cognitive performance are informative about the neural mechanisms underlying cognitive phenomena, and have tremendous potential for the diagnosis and treatment of neuropathologies with cognitive symptoms. Among such biomarkers, the modularity (subnetwork composition) of whole-brain functional networks is especially promising, due to its longstanding theoretical foundations and recent success in predicting clinical outcomes. We used functional magnetic resonance imaging to identify whole-brain modules at rest, calculating metrics of their spatio-temporal dynamics before and after a sensorimotor learning task on which fast learning is widely believed to be supported by a cognitive strategy. We found that participants' learning performance was predicted by the strength of dynamic modularity scores (clarity of subnetwork composition), the degree of coordination ...

biorxiv.org     Dec 19, 2023


Understanding Genome Structure Facilitates the Use of Wild Lentil Germplasm for Breeding: A Case Study with Shattering Loci

Plant breeders are generally reluctant to cross elite crop cultivars with their wild relatives to introgress novel desirable traits due to associated negative traits such as pod shattering. This results in a genetic bottleneck that could be reduced through better understanding of the genomic locations of the gene(s) controlling this trait. We integrated information on parental genomes, pod shattering data from multiple environments, and high-density genetic linkage maps to identify pod shattering QTLs in three lentil (Lens culinaris) interspecific recombinant inbred line (RIL) populations. The broad-sense heritability on a multi-environment basis varied from 0.46 (in LR-70, L. culinaris x L. odemensis) to 0.77 (in LR-68, L. orientalis x L. culinaris).

biorxiv.org     Dec 19, 2023


Within-subject changes in DNA-methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome.

Background: Adverse early-life experiences (ELA), including poverty, trauma and neglect, affect a majority of world children. Whereas the impact of ELA on cognitive and emotional health throughout the lifespan is well-established, it is not clear how distinct types of ELA influence child development, and there are no tools to predict for an individual child their vulnerability or resilience to the consequences of ELAs. Epigenetic markers including DNA-methylation profiles of peripheral cells may encode ELA and provide a predictive outcome marker. However, the rapid dynamic changes in DNA methylation in childhood and the inter-individual variance of the human genome pose barriers to identifying profiles predicting outcomes of ELA exposure.

biorxiv.org     Dec 19, 2023


UVAE: Integration of Heterogeneous Unpaired Data with Imbalanced Classes

We introduce the Unbiasing Variational Autoencoder (UVAE), a novel computational framework developed for the integration of unpaired biomedical data streams, with a particular focus on clinical flow cytometry. UVAE effectively addresses the challenges of batch effect correction and data alignment by training a semi-supervised model on partially labeled datasets. This approach enables the simultaneous normalisation and integration of diverse data within a shared latent space. The framework is implemented in Python with a descriptive interface for the specification and incorporation of multiple, partially overlapping data series. UVAE employs a probabilistic model for batch effect normalisation, with a generative capacity for unbiased data reconstruction and inference from heterogeneous samples.

biorxiv.org     Dec 19, 2023


RSPO/LGR signaling mediates astrocyte-induced proliferation of adult hippocampal neural stem cells

In the dentate gyrus of the adult hippocampus, neurogenesis from neural stem cells (NSCs) is regulated by Wnt signals from the local microenvironment. The Wnt/

biorxiv.org     Dec 19, 2023


Agonism between family groups of cooperative breeding smooth-coated otters (Lutrogale perspicillata)

Intraspecific agonistic interactions are common in the animal kingdom and have significant consequences for animals. With a growing population and limited resources, these interactions have been observed more frequently among smooth-coated otters in Singapore. However, little is known about the behavioral patterns of these interactions and the factors that may affect their outcomes. To address this, we analyzed intraspecific agonistic interactions through publicly available videos from citizen scientists. Our analysis revealed different behavioral patterns and typical behaviors between winning and losing family groups in different environments. We also found suggestive evidence that larger family groups with more individuals than opponents have an advantage in these interactions.

biorxiv.org     Dec 19, 2023


Conformational sampling and interpolation using language-based protein folding neural networks

Protein language models (PLMs), such ESM2, learn a rich semantic grammar of the protein sequence space. When coupled to protein folding neural networks (e.g., ESMFold), they can facilitate the prediction of tertiary and quaternary protein structures at high accuracy. However, they are limited to modeling protein structures in single states. This manuscript demonstrates that ESMFold can predict alternate conformations of some proteins, including de novo designed proteins. Randomly masking the sequence prior to PLM input returned alternate embeddings that ESMFold sometimes mapped to distinct physiologically relevant conformations. From there, inversion of the ESMFold trunk facilitated the generation of high- confidence interconversion paths between the two states.

biorxiv.org     Dec 19, 2023


How to predict binding specificity and ligands for new MHC-II alleles with MixMHC2pred

MHC-II molecules are key mediators of antigen presentation in vertebrate species and bind to their ligands with high specificity. The very high polymorphism of MHC-II genes within species and the fast-evolving nature of these genes across species has resulted in tens of thousands of different alleles, with hundreds of new alleles being discovered yearly through large sequencing projects in different species. Here we describe how to use MixMHC2pred to predict the binding specificity of any MHC-II allele directly from its amino acid sequence. We then show how both MHC-II ligands and CD4+ T-cell epitopes can be predicted in different species with our approach.

biorxiv.org     Dec 19, 2023


😊 A compendium of Amplification-Related Gain Of Sensitivity (ARGOS) genes in human cancer

Chromosomal gains are among the most frequent somatic genetic alterations occurring in cancer. While the effect of sustained oncogene expression has been characterized, the impact of copy-number gains affecting collaterally-amplified "bystander" genes on cellular fitness remains less understood. To investigate this, we built a comprehensive map of dosage compensation across human cancers by integrating expression and copy number profiles from over 8,000 TCGA tumors and CCLE cell lines. Further, we analyzed the effect of gene overexpression across 17 human cancer ORF screens to provide an overview of genes that prove toxic to cancer cells when overexpressed. Combining these two independent approaches we propose a class of 'Amplification-Related Gain Of Sensitivity' (ARGOS) genes.

biorxiv.org     Dec 19, 2023


Development of a sensor for disulfide bond formation in diverse bacteria

In bacteria, disulfide bonds contribute to the folding and stability of proteins important for processes in the cellular envelope. In E. coli, disulfide bond formation is catalyzed by DsbA and DsbB enzymes. DsbA is a periplasmic protein that catalyzes disulfide bond formation in substrate proteins while DsbB is an inner membrane protein that transfers electrons from DsbA to quinones, thereby regenerating the DsbA active state. Actinobacteria including mycobacteria use an alternative enzyme named VKOR which performs the same function as DsbB. Disulfide bond formation enzymes, DsbA and DsbB/ VKOR represent novel drug targets because their inhibition could simultaneously affect the folding of several cell envelope proteins including virulence factors, proteins involved in outer membrane biogenesis, cell division, ...

biorxiv.org     Dec 19, 2023


Fertilisation of agricultural soils with municipal biosolids: Part 1- Glyphosate and aminomethylphosphonic acid inputs to Quebec field crop soils

Municipal biosolids (MBS) are suggested to be abundant, sustainable, inexpensive fertilisers, rich in phosphorus and nitrogen. However, MBS can also contain glyphosate and phosphonates that can degrade to AMPA. Glyphosate-based herbicides (HBG) are used in field crops all over the world. Most glyphosate generally degrades within a few weeks, mainly as aminomethylphosphonic acid (AMPA). AMPA is more persistent than glyphosate, and can accumulate from one crop year to the next. AMPA is phytotoxic even to glyphosate-resistant crops. The aims of this study were to assess whether applications of MBS significantly contribute to: 1) glyphosate and AMPA contents of agricultural soils, 2) trace metal elements contents, and 3) partial replacement of mineral fertilisation while maintaining similar yields.

biorxiv.org     Dec 19, 2023


😊 How Clustering Promotes Biodiversity: A Solution to the Plankton Paradox

It is known that a species-saturated ecological community driven by competitive Lotka-Volterra equations, following a path of competitive exclusion, lingers in a long-term state with species congregated in niche space into well-separated clusters. Characterizing the topology of the niche structure of this state as a hierarchical one, we put forward a generalization of the Lotka-Volterra multi-resource competition model, which recognizes this topology at the basis of its own network structure of interrelated differential equations. This kind of generalization substantially reduces the competitive constraints on species coexistence, offering promising potential for a conceptual resolution of the plankton paradox.

biorxiv.org     Dec 19, 2023


Interpretable deep learning framework towards understanding molecular changes in human brains with Alzheimer's disease: implication for microglia activation and sex differences in AD

INTRODUCTION: The objective of this study is to characterize the molecular changes associated with AD from gene expression data of brain tissues taking an interpretable deep learning approach which has not been fully exploited. METHODS: We trained multi-layer perceptron (MLP) models for the classification of neuropathologically confirmed AD vs. controls using the transcriptomic data of three brain regions from the ROSMAP study. The whole disease spectrum was then modeled as a progressive trajectory. SHAP (SHapley Additive exPlanations) value was derived to explain model predictions and identify significant implicated genes for subsequent network analysis of key gene modules underlying AD progression. The framework was validated using two external datasets: the Mayo RNA-seq study cohort and the Mount Sinai ...

biorxiv.org     Dec 19, 2023







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