Zeitschrift Fur Kristallographie-Crystalline Materials最新文献

The brain is closely attuned to visceral signals from the body's internal environment, as evidenced by the numerous associations between neural, hemodynamic, and peripheral physiological signals. We show that these brain-body co-fluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo fMRI data acquisition sequences, we identify widespread co-fluctuations in the low-frequency range (0.01 - 0.1 Hz) between resting-state global fMRI signals, neural activity, and a host of autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain-body co-fluctuations observed at rest are elicited by arousal induced by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Further, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide (PETCO2) variations, suggesting that respiratory-driven fluctuations in arterial CO2 accompanying arousal cannot explain the origin of these signals in the brain. These findings establish the global fMRI signal as a significant component of the arousal response governed by the autonomic nervous system.

Neurodegenerative diseases such as Alzheimer's disease (AD) exhibit pathological changes in the brain that proceed in a stereotyped and regionally specific fashion, but the cellular and molecular underpinnings of regional vulnerability are currently poorly understood. Recent work has identified certain subpopulations of neurons in a few focal regions of interest, such as the entorhinal cortex, that are selectively vulnerable to tau pathology in AD. However, the cellular underpinnings of regional susceptibility to tau pathology are currently unknown, primarily because whole-brain maps of a comprehensive collection of cell types have been inaccessible. Here, we deployed a recent cell-type mapping pipeline, Matrix Inversion and Subset Selection (MISS), to determine the brain-wide distributions of pan-hippocampal and neocortical neuronal and non-neuronal cells in the mouse using recently available single-cell RNA sequencing (scRNAseq) data. We then performed a robust set of analyses to identify general principles of cell-type-based selective vulnerability using these cell-type distributions, utilizing 5 transgenic mouse studies that quantified regional tau in 12 distinct PS19 mouse models. Using our approach, which constitutes the broadest exploration of whole-brain selective vulnerability to date, we were able to discover cell types and cell-type classes that conferred vulnerability and resilience to tau pathology. Hippocampal glutamatergic neurons as a whole were strongly positively associated with regional tau deposition, suggesting vulnerability, while cortical glutamatergic and GABAergic neurons were negatively associated. Among glia, we identified oligodendrocytes as the single-most strongly negatively associated cell type, whereas microglia were consistently positively correlated. Strikingly, we found that there was no association between the gene expression relationships between cell types and their vulnerability or resilience to tau pathology. When we looked at the explanatory power of cell types versus GWAS-identified AD risk genes, cell type distributions were consistently more predictive of end-timepoint tau pathology than regional gene expression. To understand the functional enrichment patterns of the genes that were markers of the identified vulnerable or resilient cell types, we performed gene ontology analysis. We found that the genes that are directly correlated to tau pathology are functionally distinct from those that constitutively embody the vulnerable cells. In short, we have demonstrated that regional cell-type composition is a compelling explanation for the selective vulnerability observed in tauopathic diseases at a whole-brain level and is distinct from that conferred by risk genes. These findings may have implications in identifying cell-type-based therapeutic targets.

The objective of this study was to investigate the protective effects of functional nutrients including various functional amino acids, vitamins, and minerals on chicken intestinal epithelial cells (cIECs) treated with oxidative stress. The cIECs were isolated from specific pathogen free eggs. Cells were exposed to 0 mM supplement (control), 20 mM threonine (Thr), 0.4 mM tryptophan (Trp), 1 mM glycine (Gly), 10 μM vitamin C (VC), 40 μM vitamin E (VE), 5 μM vitamin A (VA), 34 μM chromium (Cr), 0.42 μM selenium (Se), and 50 μM zinc (Zn) for 24 h with 6 replicates for each treatment. After 24 h, cells were further incubated with fresh culture medium (positive control, PC) or 1 mM H₂O₂ with different supplements (negative control, NC and each treatment). Oxidative stress was measured by cell proliferation, whereas tight junction barrier function was analyzed by fluorescein isothiocyanate (FITC)-dextran permeability and transepithelial electrical resistance (TEER). Results indicated that cell viability and TEER values were less (p < 0.05) in NC treatments with oxidative stress than in PC treatments. In addition, FITC-dextran values were greater (p < 0.05) in NC treatments with oxidative stress than in PC treatments. The supplementations of Thr, Trp, Gly, VC, and VE in cells treated with H₂O₂ showed greater (p < 0.05) cell viability than the supplementation of VA, Cr, Se, and Zn. The supplementations of Trp, Gly, VC, and Se in cells treated with H₂O₂ showed the least (p < 0.05) cellular permeability. In addition, the supplementation of Thr, VE, VA, Cr, and Zn in cells treated with H₂O₂ decreased (p < 0.05) cellular permeability. At 48 h, the supplementations of Thr, Trp, and Gly in cells treated with H₂O₂ showed the greatest (p < 0.05) TEER values among all treatments, and the supplementations of VC and VE in cells treated with H₂O₂ showed greater (p < 0.05) TEER values than the supplementations of VA, Cr, Se, and Zn in cells treated with H₂O₂. In conclusion, Thr, Trp, Gly, and VC supplements were effective in improving cell viability and intestinal barrier function of cIECs exposed to oxidative stress.