25 research outputs found
Ba2AlSi5N9
Ba2AlSi5N9 was synthesized starting from Si3N4, AlN, and Ba in a radio-frequency furnace at temperatures of about 1725°C. The new nitridoalumosilicate crystallizes in the triclinic space group P1 (no. 1), a=9.860(1) Å, b=10.320(1) Å, c=10.346(1) Å, α=90.37(2)°, β=118.43(2)°; γ=103.69(2)°, Z=4, R1=0.0314. All synthesized crystals were characteristically twinned by reticular pseudomerohedry with twin law (1 0 0, −0.5 −1 0, −1 0 −1). The crystal structure of Ba2AlSi5N9 was determined from single-crystal X-ray diffraction data of a twinned crystal and confirmed by Rietveld refinement both on X-ray and on neutron powder diffraction data. Statistical distribution Si/Al is corroborated by lattice energy calculations (MAPLE). 29Si and 27Al solid-state NMR are in accordance with the crystallographic results. Ba2AlSi5N9 represents a new type of network structure made up of TN4 tetrahedra (T = Si, Al). Highly condensed layers of dreier rings with nitrogen connecting three neighboring tetrahedral centers occur which are further crosslinked by dreier rings and vierer rings. The dreier rings consist of corner-sharing tetrahedra, whereas some of the vierer rings exhibit two pairs of edge-sharing tetrahedra. In the resulting voids of the network there are eight different Ba2+ sites with coordination numbers between 6 and 10. Thermogravimetric investigations confirmed a thermal stability of Ba2AlSi5N9 up to about 1515°C (He atmosphere). Luminescence measurements on Ba2AlSi5N9:Eu2+ (2 mol % Eu2+) with an excitation wavelength of 450 nm revealed a broadband emission peaking at 584 nm (FWHM=100 nm) originating from dipole-allowed 4f6(7F)5d1 → 4f7(8S7/2) transitions
Ba3Ga3N5 - A Novel Host Lattice for Eu2+ - Doped Luminescent Materials with Unexpected Nitridogallate Substructure
The alkaline earth nitridogallate Ba3Ga3N5 was synthesized from the elements in a sodium flux at 760°C utilizing weld shut tantalum ampules. The crystal structure was solved and refined on the basis of single-crystal X-ray diffraction data. Ba3Ga3N5 (space group C2/c (No. 15), a = 16.801(3), b = 8.3301(2), c = 11.623(2) Å, β = 109.92 (3)°, Z = 8) contains a hitherto unknown structural motif in nitridogallates, namely, infinite strands made up of GaN4 tetrahedra, each sharing two edges and at least one corner with neighboring GaN4 units. There are three Ba2+ sites with coordination numbers six or eight, respectively, and one Ba2+ position exhibiting a low coordination number 4 corresponding to a distorted tetrahedron. Eu2+ - doped samples show red luminescence when excited by UV irradiation at room temperature. Luminescence investigations revealed a maximum emission intensity at 638 nm (FWHM =2123 cm−1). Ba3Ga3N5 is the first nitridogallate for which parity allowed broadband emission due to Eu2+ - doping has been found. The electronic structure of both Ba3Ga3N5 as well as isoelectronic but not isostructural Sr3Ga3N5 was investigated by DFT methods. The calculations revealed a band gap of 1.53 eV for Sr3Ga3N5 and 1.46 eV for Ba3Ga3N5
Enteroendocrine Cells Protect the Stem Cell Niche by Regulating Crypt Metabolism in Response to NutrientsSummary
Background & Aims: The intestinal stem cell niche is exquisitely sensitive to changes in diet, with high-fat diet, caloric restriction, and fasting resulting in altered crypt metabolism and intestinal stem cell function. Unlike cells on the villus, cells in the crypt are not immediately exposed to the dynamically changing contents of the lumen. We hypothesized that enteroendocrine cells (EECs), which sense environmental cues and in response release hormones and metabolites, are essential for relaying the luminal and nutritional status of the animal to cells deep in the crypt. Methods: We used the tamoxifen-inducible VillinCreERT2 mouse model to deplete EECs (Neurog3fl/fl) from adult intestinal epithelium and we generated human intestinal organoids from wild-type and NEUROGENIN 3 (NEUROG3)-null human pluripotent stem cells. We used indirect calorimetry, 1H-Nuclear Magnetic Resonance (NMR) metabolomics, mitochondrial live imaging, and the Seahorse bioanalyzer (Agilent Technologies) to assess metabolism. Intestinal stem cell activity was measured by proliferation and enteroid-forming capacity. Transcriptional changes were assessed using 10x Genomics single-cell sequencing. Results: Loss of EECs resulted in increased energy expenditure in mice, an abundance of active mitochondria, and a shift of crypt metabolism to fatty acid oxidation. Crypts from mouse and human intestinal organoids lacking EECs displayed increased intestinal stem cell activity and failed to activate phosphorylation of downstream target S6 kinase ribosomal protein, a marker for activity of the master metabolic regulator mammalian target of rapamycin (mTOR). These phenotypes were similar to those observed when control mice were deprived of nutrients. Conclusions: EECs are essential regulators of crypt metabolism. Depletion of EECs recapitulated a fasting metabolic phenotype despite normal levels of ingested nutrients. These data suggest that EECs are required to relay nutritional information to the stem cell niche and are essential regulators of intestinal metabolism
Using Human Induced Pluripotent Stem Cell Derived Organoids to Identify New Pathologies in Patients with PDX1 Mutations
BACKGROUND AIMS: Two patients with homozygous mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea and poor weight gain, the causes of which were not identified through routine clinical testing. We aim to perform a deep analysis of the stomach and intestine using organoids derived from induced pluripotent stem cells from PDX1 patients. METHODS: Gastric fundic, antral and duodenal organoids were generated using iPSC lines from a PDX1 patient and an isogenic iPSC line where the PDX1 point mutation was corrected. RESULTS: Patient-derived PDX1 antral organoids exhibited an intestinal phenotype, while intestinal organoids underwent gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsies from both PDX1 patients, which recapitulated the organoid phenotypes. Moreover, antral biopsies also demonstrated increased parietal cells and lacked G-cells suggesting loss of antral identity. All organoid pathologies were reversed upon CRISPR-mediated correction of the mutation. CONCLUSION: These patients will now be monitored for the progression of metaplasia and gastrointestinal complications that might be related to the reduced gastric and intestinal endocrine cells. This study demonstrates the utility of organoids in diagnosing uncovered pathologies
Deciphering Endothelial and Mesenchymal Organ Specification in Vascularized Lung and Intestinal Organoids
To investigate the co-development of vasculature, mesenchyme, and epithelium crucial for organogenesis and the acquisition of organ-specific characteristics, we constructed a human pluripotent stem cell-derived organoid system comprising lung or intestinal epithelium surrounded by organotypic mesenchyme and vasculature. We demonstrated the pivotal role of co-differentiating mesoderm and endoderm via precise BMP regulation in generating multilineage organoids and gut tube patterning. Single-cell RNA-seq analysis revealed organ specificity in endothelium and mesenchyme, and uncovered key ligands driving endothelial specification in the lung (e.g., WNT2B and Semaphorins) or intestine (e.g., GDF15). Upon transplantation under the kidney capsule in mice, these organoids further matured and developed perfusable human-specific sub-epithelial capillaries. Additionally, our model recapitulated the abnormal endothelial-epithelial crosstalk in patients with FOXF1 deletion or mutations. Multilineage organoids provide a unique platform to study developmental cues guiding endothelial and mesenchymal cell fate determination, and investigate intricate cell-cell communications in human organogenesis and disease.HIGHLIGHTS: BMP signaling fine-tunes the co-differentiation of mesoderm and endoderm.The cellular composition in multilineage organoids resembles that of human fetal organs.Mesenchyme and endothelium co-developed within the organoids adopt organ-specific characteristics.Multilineage organoids recapitulate abnormal endothelial-epithelial crosstalk in FOXF1-associated disorders.</p
Deciphering Endothelial and Mesenchymal Organ Specification in Vascularized Lung and Intestinal Organoids
To investigate the co-development of vasculature, mesenchyme, and epithelium crucial for organogenesis and the acquisition of organ-specific characteristics, we constructed a human pluripotent stem cell-derived organoid system comprising lung or intestinal epithelium surrounded by organotypic mesenchyme and vasculature. We demonstrated the pivotal role of co-differentiating mesoderm and endoderm via precise BMP regulation in generating multilineage organoids and gut tube patterning. Single-cell RNA-seq analysis revealed organ specificity in endothelium and mesenchyme, and uncovered key ligands driving endothelial specification in the lung (e.g., WNT2B and Semaphorins) or intestine (e.g., GDF15). Upon transplantation under the kidney capsule in mice, these organoids further matured and developed perfusable human-specific sub-epithelial capillaries. Additionally, our model recapitulated the abnormal endothelial-epithelial crosstalk in patients with FOXF1 deletion or mutations. Multilineage organoids provide a unique platform to study developmental cues guiding endothelial and mesenchymal cell fate determination, and investigate intricate cell-cell communications in human organogenesis and disease.HIGHLIGHTS: BMP signaling fine-tunes the co-differentiation of mesoderm and endoderm.The cellular composition in multilineage organoids resembles that of human fetal organs.Mesenchyme and endothelium co-developed within the organoids adopt organ-specific characteristics.Multilineage organoids recapitulate abnormal endothelial-epithelial crosstalk in FOXF1-associated disorders.</p