Lupus-Prone Mice Resist Immune Regulation and Transplant Tolerance Induction.

The strongly immunogenic environment in autoimmune diseases such as lupus may pose a stringent barrier to transplantation. Despite available murine models of lupus, transplant tolerance in this setting has yet to be fully investigated in highly penetrant genetic models of disease. Such studies are of clear clinical importance because lupus is a transplant indication in which transplanted kidneys have a substantially increased risk of rejection including a role for recurrent nephritis. In the fully penetrant B6.SLE123 mouse, we determined that CD4 T follicular helper and germinal center B cells were significantly expanded compared with healthy controls. We traced this expansion to resistance of effector CD4 T and B cells in B6.SLE123 mice to regulation by either CD4 T regulatory cells (CD4Tregs) or CD8 T regulatory cells (CD8Tregs), despite demonstrating normal function by Tregs in this strain. Finally, we determined that B6.SLE123 mice resist anti-CD45RB-mediated tolerance induction to foreign islet allografts, even in the absence of islet autoimmunity. Overall, B6.SLE123 lupus-prone mice are highly resistant to transplant tolerance induction, which provides a new model of failed tolerance in autoimmunity that may elucidate barriers to clinical transplantation in lupus through further cellular and genetic dissection.

Formation of chiral branched nanowires by the Eshelby Twist.

Manipulating the morphology of inorganic nanostructures, such as their chirality and branching structure, has been actively pursued as a means of controlling their electrical, optical and mechanical properties. Notable examples of chiral inorganic nanostructures include carbon nanotubes, gold multishell nanowires, mesoporous nanowires and helical nanowires. Branched nanostructures have also been studied and been shown to have interesting properties for energy harvesting and nanoelectronics. Combining both chiral and branching motifs into nanostructures might provide new materials properties. Here we show a chiral branched PbSe nanowire structure, which is formed by a vapour-liquid-solid branching from a central nanowire with an axial screw dislocation. The chirality is caused by the elastic strain of the axial screw dislocation, which produces a corresponding Eshelby Twist in the nanowires. In addition to opening up new opportunities for tailoring the properties of nanomaterials, these chiral branched nanowires also provide a direct visualization of the Eshelby Twist.

Domain wall resistivity in SrRuO3.

SrRuO3 is an itinerant ferromagnet with T(c) approximately 150 K. When SrRuO3 is cooled through T(c) in zero applied magnetic field, a stripe domain structure appears whose orientation is uniquely determined by the large uniaxial magnetocrystalline anisotropy. We find that the ferromagnetic domain walls clearly enhance the resistivity of SrRuO3 and that the enhancement has different temperature dependence for currents parallel and perpendicular to the domain walls. We discuss possible interpretations of our results.

WT1 modulates apoptosis by transcriptionally upregulating the bcl-2 proto-oncogene.

The Wilms' tumor suppressor gene, WT1, encodes a zinc finger transcription factor that has been demonstrated to negatively regulate several growth factor and cognate receptor genes. However, inconsistent with its tumor suppressor function, WT1 has also been demonstrated to be required to inhibit programmed cell death in vitro and in vivo. Moreover, anaplastic Wilms' tumors, which typically express wild-type WT1, display extreme resistance to chemotherapeutic agents that kill tumor cells through the induction of apoptosis. Although p53 mutations in anaplastic Wilms' tumors have been associated with chemoresistance, this event is believed to occur late during tumor progression. Therefore, since dysregulated WT1 expression occurs relatively early in Wilms' tumors, we hypothesized that WT1 was required to transcriptionally upregulate genes that provide a cell survival advantage to tumor cells. Here we demonstrate that sporadic Wilms' tumors coexpress WT1 and the anti-apoptotic Bcl-2 protein. Using rhabdoid cell lines overexpressing WT1, we show that WT1 activates the endogenous bcl-2 gene through a transcriptional mechanism. Transient transfections and electromobility shift assays demonstrate that WT1 positively stimulates the bcl-2 promoter through a direct interaction. Moreover, WT1 expressing cells displaying upregulated Bcl-2 were found to be resistant to apoptosis induced by staurosporine, vincristine and doxorubicine. These data suggest that in certain cellular contexts, WT1 exhibits oncogenic potential through the transcriptional upregulation of anti-apoptotic genes such as bcl-2.

A-Axis--Oriented YBa2Cu3O7/PrBa2Cu3O7 Superlattices.

A modulated structure has been fabricated from high transition temperature superconductors where the individual CuO(2) planes are composed of alternating superconducting and insulating strips. This structure is made by growing a-axis-oriented YBa(2)Cu(3)O(7)/PrBa(2)Cu(3)O(7) superlattices by 90 degrees off-axis sputtering on (100)SrTiO(3) and (100)LaAlO(3) substrates. Superlattice modulation is observed to a modulation wavelength of 24 angstroms (12 angstroms-YBa(2)Cu(3)O(7)/12 angstroms-PrBa(2)Cu(3)O(7)), both by x-ray diffraction and by cross-sectional transmission electron microscopy. Rutherford backscattering spectroscopy indicates a high degree of crystalline perfection with a channeling minimum yield of 3 percent. Quasi-one-dimensional conductivity should be obtainable in these structures.

Epitaxial and Smooth Films of a-Axis YBa2Cu3O7.

YBa(2)Cu(3)O(7) films have been grown epitaxially on SrTiO(3) (100) and LaAlO(3) (100) substrates with nearly pure a-axis orientation and with transition temperature T(c) (R = 0) of 85 K. A unique feature of these films is their smooth surface. These smooth surfaces enable the growth of short-period superlattices with well-defined modulations. The films are untwinned and the grains grow with their c-axis along one of two perpendicular directions on the substrate ([100] or [010]). The fabrication of sandwich-type Josephson junctions with good characteristics may now be possible because unlike c-axis-oriented films, the superconducting coherence length of these smooth films is appreciably large perpendicular to their surfaces.

Direct observation of structural defects in laser-deposited superconducting y-ba-cu-o thin films.

The defect structure of in situ pulsed, laser-deposited, thin films of the high-transition temperature superconductor Y-Ba-Cu-O has been observed directly by atomic resolution electron microscopy. In a thin film with the nominal composition YBa(2)Cu(3)O(7) (123), stacking defects corresponding to the cationic stoichiometry of the 248, 247, and 224 compounds have been observed. Other defects observed include edge dislocations and antiphase boundaries. These defects, which are related to the nonequilibrium processing conditions, are likely to be responsible for the higher critical currents observed in these films as compared to single crystals.

TEM study of the central dark line in enamel crystallites.

The dark line which is observed in enamel crystallites represents a planar defect involving a single 100 plane of the hydroxyapatite structure. It may occur in the majority of crystals throughout the enamel, although it is only observed in specific diffraction conditions. Its presence may be related both to the formation and growth of crystallites in the developing tooth and to the manner in which the crystallites dissolve during caries. TEM studies show clearly that the central defect is not a dislocation, stacking fault or lattice twin boundary. They further indicate that it cannot represent a structural twin boundary. The remaining possibilities are that it represents a substitution in the HAP lattice, most likely involving carbonate ion, or a separate compatible calcium phosphate phase.