Quantitative order-parameter measurement in lattice-mismatched AlInP using precession electron diffraction.

Precession electron diffraction (PED) was used to measure the long-range order parameter in lattice-mismatched AlInP epitaxial films under investigation for solid-state-lighting applications. Both double- and single-variant films grown at 620, 650 and 680 °C were analysed in TEM cross-section. PED patterns were acquired in selected-area-diffraction mode through external microscope control using serial acquisition, which allows inline image processing. The integrated peak intensities from experimental patterns were fit using dynamical simulations of diffraction from the ordered domain structures. Included in the structure-factor calculations were mean atomic displacements of the anions (P) due to ordering, which were found by valence-force-field calculations to have a nearly linear dependence on order parameter. A maximum order parameter of S = 0.36 was measured for a double-variant specimen grown at 650 °C.

Compound semiconductors play a central role in current light-emitting diodes (LED) technology, but improvements in the red- and amber-emitting components are needed. The semiconductor alloy AlInP offers advantages over incumbent materials by making use of an arrangement in the crystal structure, called 'atomic ordering', that occurs spontaneously under certain deposition conditions. Quantitative measurement of the extent to which the ordering phenomenon occurs is needed to fully exploit the properties of the ordered material. Transmission electron diffraction offers a means to directly probe the ordered structures, but the quantification of electron-diffraction data has been a long-standing challenge, due to multiple scattering processes, referred to as 'dynamical' diffraction. The method of precession electron diffraction (PED) addresses this problem and has found numerous applications in crystallography. We have applied PED to ordered AlInP films, using computer-controlled acquisition to perform alignments and construct data sets during collection. A model of the microscopic, ordered domain structure was developed to compare the diffraction data to simulations. Samples grown at different temperatures, and ordered along either one or two directions, were evaluated. The strongest ordering was observed in a sample grown at 650 °C with ordering along two directions.

Targeting cancer cell adhesion molecule, CD146, with low-dose gold nanorods and mild hyperthermia disrupts actin cytoskeleton and cancer cell migration.

Cluster of differentiation 146 (CD146), a cancer cell adhesion molecule, is over-expressed on the surfaces of melanoma, breast, ovarian, and prostate cancer cells, and its high expression indicates the migration tendency of these cancer cells and poor patient prognosis. Here, we hypothesize that targeting the CD146 with low-dose gold nanorods combined with mild hyperthermia can stop the migration of these cancer cells. Two metastatic cancer cells including a melanoma and a breast cancer cell line are selected as the model systems. Cell migration assays show that the migration of both cell lines can be completely stopped by the treatment. Atomic force microscopy and super resolution fluorescence microscopy reveal the alterations of actin cytoskeleton and cell morphology correspond to the inhibited cell migration. Further mechanistic analysis indicates the treatment disrupts the actin cytoskeleton by a synergistic mechanism including depleting membrane CD146 and interfering ezrin-radixin-moesin phosphorylation. As a result, we believe targeting CD146 with low-dose gold nanorods and mild hyperthermia could be a versatile, effective, and safe approach for stopping cancer metastasis. More broadly, the concept of targeting cancer cell surface markers that connect the underlying actin cytoskeleton, offers enormous potential in treating cancer metastasis, which accounts for more than 90% of cancer-associated mortality.

Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease.

Actin-associated nonmuscle myosin II (NM2) motor proteins play critical roles in a myriad of cellular functions, including endocytosis and organelle transport pathways. Cell type-specific expression and unique subcellular localization of the NM2 proteins, encoded by the Myh9 and Myh10 genes, in the mouse kidney tubules led us to hypothesize that these proteins have specialized functional roles within the renal epithelium. Inducible conditional knockout (cKO) of Myh9 and Myh10 in the renal tubules of adult mice resulted in progressive kidney disease. Prior to overt renal tubular injury, we observed intracellular accumulation of the glycosylphosphatidylinositol-anchored protein uromodulin (UMOD) and gradual loss of Na+ K+ 2Cl- cotransporter from the apical membrane of the thick ascending limb epithelia. The UMOD accumulation coincided with expansion of endoplasmic reticulum (ER) tubules and activation of ER stress and unfolded protein response pathways in Myh9&10-cKO kidneys. We conclude that NM2 proteins are required for localization and transport of UMOD and loss of function results in accumulation of UMOD and ER stress-mediated progressive renal tubulointerstitial disease. These observations establish cell type-specific role(s) for NM2 proteins in regulation of specialized renal epithelial transport pathways and reveal the possibility that human kidney disease associated with MYH9 mutations could be of renal epithelial origin.

Notch signaling regulates Akap12 expression and primary cilia length during renal tubule morphogenesis.

Alagille syndrome patients present with loss of function mutations in either JAG1 or NOTCH2. About 40%-50% of patients have kidney abnormalities, and frequently display multicystic, dysplastic kidneys. Additionally, gain-of-function mutations in NOTCH2 are associated with cystic kidneys in Hajdu-Cheney syndrome patients. How perturbations in Notch signaling cause renal tubular cysts remains unclear. Here, we have determined that reduced Notch signaling mediated transcription by ectopic expression of dominant-negative mastermind-like (dnMaml) peptide in the nephrogenic epithelia from after the s-shaped body formation and in the developing collecting ducts results in proximal tubular and collecting duct cysts, respectively. An acute inhibition of Notch signaling for two days during kidney development is sufficient to disrupt tubule formation, and significantly increases Akap12 expression. Ectopic expression of Akap12 in renal epithelia results in abnormally long primary cilia similar to that observed in Notch-signaling-deficient epithelia. Both loss of Notch signaling and elevated Akap12 expression disrupt the ability of renal epithelial cells to form spherical structures with a single lumen when grown embedded in matrix. Interestingly, Akap12 can inhibit Notch signaling mediated transcription, which likely explains how both loss of Notch signaling and ectopic expression of Akap12 result in similar renal epithelial abnormalities. We conclude that Notch signaling regulates Akap12 expression while also ensuring normal primary cilia length and renal epithelial morphogenesis, and suggest that one aspect of diseases associated with defective Notch signaling, such as Alagille syndrome, maybe mechanistically related to ciliopathies.

Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis.

BACKGROUND: Notch signaling is required during kidney development for nephron formation and principal cell fate selection within the collecting ducts. Whether Notch signaling is required in the adult kidney to maintain epithelial diversity, or whether its loss can trigger principal cell transdifferentiation (which could explain acquired diabetes insipidus in patients receiving lithium) is unclear. METHODS: To investigate whether loss of Notch signaling can trigger principal cells to lose their identity, we genetically inactivated Notch1 and Notch2, inactivated the Notch signaling target Hes1, or induced expression of a Notch signaling inhibitor in all of the nephron segments and collecting ducts in mice after kidney development. We examined renal function and cell type composition of control littermates and mice with conditional Notch signaling inactivation in adult renal epithelia. In addition, we traced the fate of genetically labeled adult kidney collecting duct principal cells after Hes1 inactivation or lithium treatment. RESULTS: Notch signaling was required for maintenance of Aqp2-expressing cells in distal nephron and collecting duct segments in adult kidneys. Fate tracing revealed mature principal cells in the inner stripe of the outer medulla converted to intercalated cells after genetic inactivation of Hes1 and, to a lesser extent, lithium treatment. Hes1 ensured repression of Foxi1 to prevent the intercalated cell program from turning on in mature Aqp2+ cell types. CONCLUSIONS: Notch signaling viaHes1 regulates maintenance of mature renal epithelial cell states. Loss of Notch signaling or use of lithium can trigger transdifferentiation of mature principal cells to intercalated cells in adult kidneys.

Self-assembly of photoactive TiO2-cyclodextrin wires.

Cyclodextrins appear to act as bifunctional linkers when interacting with anatase TiO2 particles under UV light, resulting in super long TiO2-containing wires. These assemblies display mechanical flexibility, stable electronics, and rapid response/long lifetime under photoinduced current.