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Biology subjects

Hai, S.

Publications and source records attributed to Hai, S..

2 recordsLinked to original sources

Emergent topological structure in spontaneous brain-organoid activity

Neural activity is widely held to organize on low-dimensional structure embedded in a high-dimensional state space. Persistent homology reads such structure directly from the pattern of pairwise correlations, without assuming in advance which variables are relevant. We apply persistent homology to microelectrode-array (MEA) recordings of spontaneous activity from human (Lancaster) and mouse (Pasca) cortical organoids, spanning 26-234 simultaneously sorted units, and ask whether topological data analysis resolves structure at the node counts that neural recordings actually deliver. Building weighted networks in correlation space and characterizing them by Vietoris-Rips filtration, we find that the first homology (H1, loops) rises significantly above a rate- and population-preserving null in 14 of 18 datasets. This loop structure occupies a non-redundant core: it is robust to random removal of units yet disrupted by targeted removal of the units that carry it. Topological richness grows with network size, and second homology (H2) emerges significantly above the null only in the larger networks. These results show that persistent homology resolves structured topology in neural recordings at the scale experiments actually deliver.

neuroscience↗

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

Magnesium (Mg) deficiency is associated with increased risk and malignancy of colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomics and phosphoproteomics indicated that low tumorous Mg content may activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p upregulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1-ACTN4 interaction by decreasing DBN1S142p, which, in turn, enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may offer a promising preventive and therapeutic strategy for CRC.

cancer biology↗