237 research outputs found
Infantile Hemangiomas: A Disease Model in the Study of Vascular Development, Aberrant Vasculogenesis and Angiogenesis
Structural origin of the anomalous temperature dependence of the local magnetic moments in the CaFeAs family of materials
We report a combination of Fe K x-ray emission spectroscopy and
-intio calculations to investigate the correlation between structural and
magnetic degrees of freedom in CaFe(AsP). The
puzzling temperature behavior of the local moment found in rare earth-doped
CaFeAs [\textit{H. Gretarsson, et al., Phys. Rev. Lett. {\bf 110},
047003 (2013)}] is also observed in CaFe(AsP). We
explain this phenomenon based on first-principles calculations with scaled
magnetic interaction. One scaling parameter is sufficient to describe
quantitatively the magnetic moments in both CaFe(AsP) () and CaLaFeAs at all
temperatures. The anomalous growth of the local moments with increasing
temperature can be understood from the observed large thermal expansion of the
-axis lattice parameter combined with strong magnetoelastic coupling. These
effects originate from the strong tendency to form As-As dimers across the Ca
layer in the CaFeAs family of materials. Our results emphasize the
dual local-itinerant character of magnetism in Fe pnictides
Expression of HES and HEY genes in infantile hemangiomas
Background: Infantile hemangiomas (IHs) are the most common benign tumor of infancy, yet their pathogenesis is poorly understood. IHs are believed to originate from a progenitor cell, the hemangioma stem cell (HemSC). Recent studies by our group showed that NOTCH proteins and NOTCH ligands are expressed in hemangiomas, indicating Notch signaling may be active in IHs. We sought to investigate downstream activation of Notch signaling in hemangioma cells by evaluating the expression of the basic HLH family proteins, HES/HEY, in IHs. Materials and Methods: HemSCs and hemangioma endothelial cells (HemECs) are isolated from freshly resected hemangioma specimens. Quantitative RT-PCR was performed to probe for relative gene transcript levels (normalized to beta-actin). Immunofluorescence was performed to evaluate protein expression. Co-localization studies were performed with CD31 (endothelial cells) and NOTCH3 (peri-vascular, non-endothelial cells). HemSCs were treated with the gamma secretase inhibitor (GSI) Compound E, and gene transcript levels were quantified with real-time PCR. Results: HEY1, HEYL, and HES1 are highly expressed in HemSCs, while HEY2 is highly expressed in HemECs. Protein expression evaluation by immunofluorescence confirms that HEY2 is expressed by HemECs (CD31+ cells), while HEY1, HEYL, and HES1 are more widely expressed and mostly expressed by perivascular cells of hemangiomas. Inhibition of Notch signaling by addition of GSI resulted in down-regulation of HES/HEY genes. Conclusions: HES/HEY genes are expressed in IHs in cell type specific patterns; HEY2 is expressed in HemECs and HEY1, HEYL, HES1 are expressed in HemSCs. This pattern suggests that HEY/HES genes act downstream of Notch receptors that function in distinct cell types of IHs. HES/HEY gene transcripts are decreased with the addition of a gamma-secretase inhibitor, Compound E, demonstrating that Notch signaling is active in infantile hemangioma cells
Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development
Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs
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Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development
Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.</p
A structural study of hcp and liquid iron under shock compression up to 275 GPa
We combine nanosecond laser shock compression with \emph{in-situ} picosecond
X-ray diffraction to provide structural data on iron up to 275 GPa. We
constrain the extent of hcp-liquid coexistence, the onset of total melt, and
the structure within the liquid phase. Our results indicate that iron, under
shock compression, melts completely by 258(8) GPa. A coordination number
analysis indicates that iron is a simple liquid at these pressure-temperature
conditions. We also perform texture analysis between the ambient
body-centered-cubic (bcc) , and the hexagonal-closed-packed (hcp)
high-pressure phase. We rule out the Rong-Dunlop orientation
relationship (OR) between the and phases. However, we
cannot distinguish between three other closely related ORs: Burger's,
Mao-Bassett-Takahashi, and Potter's OR. The solid-liquid coexistence region is
constrained from a melt onset pressure of 225(3) GPa from previously published
sound speed measurements and full melt (246.5(1.8)-258(8) GPa) from X-ray
diffraction measurements, with an associated maximum latent heat of melting of
623 J/g. This value is lower than recently reported theoretical estimates and
suggests that the contribution to the earth's geodynamo energy budget from heat
release due to freezing of the inner core is smaller than previously thought.
Melt pressures for these nanosecond shock experiments are consistent with gas
gun shock experiments that last for microseconds, indicating that the melt
transition occurs rapidly
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