Neuropsychological evidence of multi-domain network hubs in the human thalamus.
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ABSTRACT:
SUBMITTER: Hwang K
PROVIDER: S-EPMC8526062 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The thalamus is critical for the brain's integrative hub functions; however, the localization and characterization of the different thalamic hubs remain unclear. Using a voxel-level network measure called functional connectivity overlap ratio (FCOR), we examined the thalamus' association with large-scale resting-state networks (RSNs) to elucidate its connector hub roles. Connections to the core-neurocognitive networks were localized in the anterior and medial parts, such as the anteroventral and mediodorsal nuclei areas. Regions functionally connected to the sensorimotor network were distinctively located around the lateral pulvinar nucleus but to a limited extent. Prominent connector hubs include the anteroventral, ventral lateral, and mediodorsal nuclei with functional connections to multiple RSNs. These findings suggest that the thalamus, with extensive connections to most of the RSNs, is well placed as a critical integrative functional hub and could play an important role for functional integration facilitating brain functions associated with primary processing and higher cognition.
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Project description:We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and that active svb enhancers on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis that these multi-enhancer 'hubs' improve phenotypic resilience to stress by buffering against decreases in transcription factor concentrations and transcriptional output. Deleting a redundant enhancer from the svb locus led to reduced trichome numbers in embryos raised at elevated temperatures. Using high-resolution fluorescence microscopy, we observed lower Ubx concentration and transcriptional output in this deletion allele. Transcription sites of the full svb cis-regulatory region inserted into a different chromosome colocalized with the svb locus, increasing Ubx concentration, the transcriptional output of svb, and partially rescuing the phenotype. Thus, multiple enhancers could reinforce a local transcriptional hub to buffer against environmental stresses and genetic perturbations, providing a mechanism for phenotypical robustness.
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Project description:BACKGROUND: Nutritional systems biology offers the potential for comprehensive predictions that account for all metabolic changes with the intricate biological organization and the multitudinous interactions between the cellular proteins. Protein-protein interaction (PPI) networks can be used for an integrative description of molecular processes. Although widely adopted in nutritional systems biology, these networks typically encompass a single category of functional interaction (i.e., metabolic, regulatory or signaling) or nutrient. Incorporating multiple nutrients and functional interaction categories under an integrated framework represents an informative approach for gaining system level insight on nutrient metabolism. RESULTS: We constructed a multi-level PPI network starting from the interactions of 200 vitamin-related proteins. Its final size was 1,657 proteins, with 2,700 interactions. To characterize the role of the proteins we computed 6 centrality indices and applied model-based clustering. We detected a subgroup of 22 proteins that were highly central and significantly related to vitamin D. Immune system and cancer-related processes were strongly represented among these proteins. Clustering of the centralities revealed a degree of redundancy among the indices; a repeated analysis using subsets of the centralities performed well in identifying the original set of 22 most central proteins. CONCLUSIONS: Hierarchical and model-based clustering revealed multi-centrality hubs in a vitamin PPI network and redundancies among the centrality indices. Vitamin D-related proteins were strongly represented among network hubs, highlighting the pervasive effects of this nutrient. Our integrated approach to network construction identified promiscuous transcription factors, cytokines and enzymes - primarily related to immune system and cancer processes - representing potential gatekeepers linking vitamin intake to disease.
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Project description:BACKGROUND:Although a number of recent studies have uncovered remarkable diversity of microbes associated with plants, understanding and managing dynamics of plant microbiomes remain major scientific challenges. In this respect, network analytical methods have provided a basis for exploring "hub" microbial species, which potentially organize community-scale processes of plant-microbe interactions. METHODS:By compiling Illumina sequencing data of root-associated fungi in eight forest ecosystems across the Japanese Archipelago, we explored hubs within "metacommunity-scale" networks of plant-fungus associations. In total, the metadata included 8080 fungal operational taxonomic units (OTUs) detected from 227 local populations of 150 plant species/taxa. RESULTS:Few fungal OTUs were common across all the eight forests. However, in each of the metacommunity-scale networks representing northern four localities or southern four localities, diverse mycorrhizal, endophytic, and pathogenic fungi were classified as "metacommunity hubs," which were detected from diverse host plant taxa throughout a climatic region. Specifically, Mortierella (Mortierellales), Cladophialophora (Chaetothyriales), Ilyonectria (Hypocreales), Pezicula (Helotiales), and Cadophora (incertae sedis) had broad geographic and host ranges across the northern (cool-temperate) region, while Saitozyma/Cryptococcus (Tremellales/Trichosporonales) and Mortierella as well as some arbuscular mycorrhizal fungi were placed at the central positions of the metacommunity-scale network representing warm-temperate and subtropical forests in southern Japan. CONCLUSIONS:The network theoretical framework presented in this study will help us explore prospective fungi and bacteria, which have high potentials for agricultural application to diverse plant species within each climatic region. As some of those fungal taxa with broad geographic and host ranges have been known to promote the survival and growth of host plants, further studies elucidating their functional roles are awaited.
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