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At least 37 records · Page 2

Exotic fluoride molecules in IRC +10216: Confirmation of AlF and searches for MgF and CaF

Three new rotational transitions of aluminum fluoride (AlF) at 0.8 and 1.2 mm have been observed. The J = 10-9, J = 8-7, and J = 7-6 lines of AlF at 230, 263, and 329 GHz, respectively, were seen toward IRC +10216 using the Caltech Submillimter Observatory (CSO). Combined with the earlier data obtained for this species at IRAM at 2 and 3 mm, these measurements confirm the presence of the metal halide in this carbon-rich circumstellar shell. Analysis of the CSO and IRAM data suggests that AlF arises from a source with a diameter of theta(sub s) approximately = 5-10 sec and hence is present chiefly in the inner envelope of IRC +10216. In this region, the molecule has a column density of (0.3-1.1) x 10(exp 15)/sq cm, which indicates a fractional abundance of at least approximately 10(exp -9), relative to H2. Searches for the metal fluoride species CaF and MgF have also been conducted toward IRC +10216, but with negative results. The column density upper limits for MgF and CaF are N(sub tot) less than (1-4) x 10(exp 14)/sq cm. Relative abundances of these metal fluoride molecules can be understood in terms of chemical thermodynamic equilibrium. The presence of AlF in IRC +10216 also indicates that large quantities of fluorine must be present in the inner stellar envelope, suggesting that this element may be produced not primarily in explosive nucleosynthesis but rather in helium shell flashes, as indicated also by HF spectroscopy of red giant stars.

Ziurys, L. M.↗

Materials Data on CaF by Materials Project

CaF is Wurtzite structured and crystallizes in the hexagonal P6_3mc space group. The structure is three-dimensional. Ca is bonded to four equivalent F atoms to form corner-sharing CaF4 tetrahedra. All Ca–F bond lengths are 2.42 Å. F is bonded to four equivalent Ca atoms to form corner-sharing FCa4 tetrahedra.

36 MATERIALS SCIENCE↗

Single-Cell Transcriptomic Analysis of Tumor-Derived Fibroblasts and Normal Tissue-Resident Fibroblasts Reveals Fibroblast Heterogeneity in Breast Cancer

Cancer-associated fibroblasts (CAFs) are a prominent stromal cell type in solid tumors and molecules secreted by CAFs play an important role in tumor progression and metastasis. CAFs coexist as heterogeneous populations with potentially different biological functions. Although CAFs are a major component of the breast cancer stroma, molecular and phenotypic heterogeneity of CAFs in breast cancer is poorly understood. In this study, we investigated CAF heterogeneity in triple-negative breast cancer (TNBC) using a syngeneic mouse model, BALB/c-derived 4T1 mammary tumors. Using single-cell RNA sequencing (scRNA-seq), we identified six CAF subpopulations in 4T1 tumors including: 1) myofibroblastic CAFs, enriched for α-smooth muscle actin and several other contractile proteins; 2) ‘inflammatory’ CAFs with elevated expression of inflammatory cytokines; and 3) a CAF subpopulation expressing major histocompatibility complex (MHC) class II proteins that are generally expressed in antigen-presenting cells. Comparison of 4T1-derived CAFs to CAFs from pancreatic cancer revealed that these three CAF subpopulations exist in both tumor types. Interestingly, cells with inflammatory and MHC class II-expressing CAF profiles were also detected in normal breast/pancreas tissue, suggesting that these phenotypes are not tumor microenvironment-induced. This work enhances our understanding of CAF heterogeneity, and specifically targeting these CAF subpopulations could be an effective therapeutic approach for treating highly aggressive TNBCs.

60 APPLIED LIFE SCIENCES↗

Heterogeneous response of cancer-associated fibroblasts to the glucose deprivation through mitochondrial calcium uniporter

Highlights: • CAFs from a tumor mass are heterogeneous under the glucose deficient condition. • CAFs survive under glucose deficient condition by activation of TGF-β and calcium. • Calcium influx to mitochondria is critical for survival of glucose-deficient CAFs. • MCU in CAFs could be a feasible target for the development of anticancer drugs. Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have distinct features from normal fibroblasts (NFs). However, the discriminative nature of heterogeneous CAFs under glucose starvation remains unknown. In this study, we investigated the changes in the mitochondrial calcium concentration and relevant intracellular machinery in CAFs under glucose-deficient conditions. Xenografted tumor masses were dissected into multiple pieces and subjected to the CAF isolation using magnetically activated cell sorting (MACS). NFs were separated from the normal lung and skin. Under glucose starvation, CAFs from the tumor mass exhibited heterogeneity in cell proliferation, ATP production and calcium concentration. Compared to NFs, mitochondrial calcium concentration was significantly higher in glucose-starved CAFs with upregulation of mitochondrial calcium uniporter (MCU) that led to enhancement of ATP production and cell growth. Intriguingly, treatment of glucose-starved CAFs with oligomycin increased apoptosis by disrupted calcium homeostasis following overactivation of the mPTP. Moreover, oligomycin-induced apoptosis was mitigated by calcium chelation. This study demonstrated that the discriminative calcium influx to mitochondria through MCU coordinated cell growth and apoptosis in glucose-starved CAFs but not in NFs.

60 APPLIED LIFE SCIENCES↗