Synthetic analogues of Fe(ii)-Fe(iii) minerals containing a pentagonal 'Cairo' magnetic lattice.

Versiliaite and apuanite are two minerals containing Fe(2+) and Fe(3+) in a low-dimensional structure exhibiting chains of edge-linked FeO6 octahedra. The chemistry of these minerals has not been fully examined because of their rarity. We demonstrate that chemical synthesis of these minerals is possible to allow measurement of their magnetic properties and a more complete description of their structural features using neutron powder diffraction. We also show that chemical manipulation is possible to provide isostructural phases with different chemical compositions.

Dysfunction of the stress-responsive FOXC1 transcription factor contributes to the earlier-onset glaucoma observed in Axenfeld-Rieger syndrome patients.

Mutations in the Forkhead Box C1 (FOXC1) transcription factor gene are associated with Axenfeld-Rieger syndrome (ARS), a developmental disorder affecting structures in the anterior segment of the eye. Approximately 75% of ARS patients with FOXC1 mutations develop earlier-onset glaucoma. Constant exposure of the trabecular meshwork (TM), located in the anterior segment of the eye, to oxidative stress is predicted to be a risk factor for developing glaucoma. Stress-induced death of TM cells results in dysfunction of the TM, leading to elevated intraocular pressure, which is a major risk factor for developing glaucoma. FOXC1 is predicted to maintain homeostasis in TM cells by regulating genes that are important for stress response. In this study, we show that a member of the heat-shock 70 family of proteins, HSPA6, is a target gene of FOXC1. HSPA6 protein, which is only induced under severe oxidative stress conditions, has a protective function in human trabecular meshwork (HTM) cells. We also show that FOXC1 is anti-apoptotic as knocking down FOXC1 significantly decreases HTM cell viability. In addition, we show that FOXC1 itself responds to stress as exposure of cells to H2O2-induced oxidative stress reduces FOXC1 levels and activity. Conditions that decrease FOXC1 function, such as exposure of cells to oxidative stress and FOXC1 ARS mutations, compromise the ability of TM cells to effectively respond to environmental stresses. Dysfunction of FOXC1 contributes to the death of TM cells, an important step in the development of glaucoma.

Magnetic interaction in ferrous antimonite, FeSb2O4, and some derivatives.

Ferrous antimonite, FeSb(2)O(4), which is isostructural with Pb(3)O(4), and some lead- and cobalt-doped variants of composition FeSb(1.5)Pb(0.5)O(4) and Co(0.5)Fe(0.5)Sb(1.5)Pb(0.5)O(4) have been examined by (57)Fe and (121)Sb Mössbauer spectroscopy. Antimony is present as Sb(3+). The presence of Pb(2+) on the antimony site induces partial oxidation of Fe(2+) to Fe(3+). There is no Verwey-type transition in which electrons are shared between iron in different oxidation states. The quasi-one-dimensional magnetic structure gives rise to situations in which weakly coupled Fe(2+) ions can coexist in a non-magnetic state alongside Fe(3+) ions in a magnetically ordered state.

BRCA1 and GATA3 corepress FOXC1 to inhibit the pathogenesis of basal-like breast cancers.

In this study we describe a novel interaction between the breast/ovarian tumor suppressor gene BRCA1 and the transcription factor GATA3, an interaction, which is important for normal breast differentiation. We show that the BRCA1-GATA3 interaction is important for the repression of genes associated with triple-negative and basal-like breast cancer (BLBCs) including FOXC1, and that GATA3 interacts with a C-terminal region of BRCA1. We demonstrate that FOXC1 is an essential survival factor maintaining the proliferation of BLBCs cell lines. We define the mechanistic basis of this corepression and identify the GATA3-binding site within the FOXC1 distal promoter region. We show that BRCA1 and GATA3 interact on the FOXC1 promoter and that BRCA1 requires GATA3 for recruitment to this region. This interaction requires fully functional BRCA1 as a mutant BRCA1 protein is unable to localize to the FOXC1 promoter or repress FOXC1 expression. We demonstrate that this BRCA1-GATA3 repression complex is not a FOXC1-specific phenomenon as a number of other genes associated with BLBCs such as FOXC2, CXCL1 and p-cadherin were also repressed in a similar manner. Finally, we demonstrate the importance of our findings by showing that loss of GATA3 expression or aberrant FOXC1 expression contributes to the drug resistance and epithelial-to-mesenchymal transition-like phenotypes associated with aggressive BLBCs.

Magnetic order in FeCr(2)S(4)-type chalcogenide spinels.

The thiospinels of composition FeCr(2)S(4) and Fe(1+x)Cr(2-2x)Sn(x)S(4) with 0

Positive and negative regulation of myogenic differentiation of C2C12 cells by isoforms of the multiple homeodomain zinc finger transcription factor ATBF1.

The ATBF1 gene encodes two protein isoforms, the 404-kDa ATBF1-A, possessing four homeodomains and 23 zinc fingers, and the 306-kDa ATBF1-B, lacking a 920-amino acid N-terminal region of ATBF1-A which contains 5 zinc fingers. In vitro, ATBF1-A was expressed in proliferating C2C12 myoblasts, but its expression levels decreased upon induction of myogenic differentiation in low serum medium. Forced expression of ATBF1-A in C2C12 cells resulted in repression of MyoD and myogenin expression and elevation of Id3 and cyclin D1 expression, leading to inhibition of myogenic differentiation in low serum. In contrast, transfection of C2C12 cells with the ATBF1-B isoform led to an acceleration of myogenic differentiation, as indicated by an earlier onset of myosin heavy chain expression and formation of a higher percentage of multinucleated myotubes. The fourth homeodomain of ATBF1-A bound to an AT-rich element adjacent to the E1 E-box of the muscle regulatory factor 4 promoter mediating transcriptional repression. The ATBF1-A-specific N-terminal region possesses general transcription repressor activity. These results suggest that ATBF1-A plays a role in the maintenance of the undifferentiated myoblast state, and its down-regulation is a prerequisite to initiate terminal differentiation of C2C12 cells.

Analyses of the effects that disease-causing missense mutations have on the structure and function of the winged-helix protein FOXC1.

Five missense mutations of the winged-helix FOXC1 transcription factor, found in patients with Axenfeld-Rieger (AR) malformations, were investigated for their effects on FOXC1 structure and function. Molecular modeling of the FOXC1 forkhead domain predicted that the missense mutations did not alter FOXC1 structure. Biochemical analyses indicated that, whereas all mutant proteins correctly localize to the cell nucleus, the I87M mutation reduced FOXC1-protein levels. DNA-binding experiments revealed that, although the S82T and S131L mutations decreased DNA binding, the F112S and I126M mutations did not. However, the F112S and I126M mutations decrease the transactivation ability of FOXC1. All the FOXC1 mutations had the net effect of reducing FOXC1 transactivation ability. These results indicate that the FOXC1 forkhead domain contains separable DNA-binding and transactivation functions. In addition, these findings demonstrate that reduced stability, DNA binding, or transactivation, all causing a decrease in the ability of FOXC1 to transactivate genes, can underlie AR malformations.

Microcratering within the lunar regolith--a theory and observation.

Since the Apollo 11 mission to the moon, there has been substantial analysis of the lunar rocks and soil grains, utilizing more recent advances in electron probe technologies. It is the objective of this research to revisit the theories concerning the microcratering within the lunar regolith. Recent theories have included the idea that the microcratering phenomenon was caused by meteoric impacting onto the lunar surface during early lunar history. Other theories have suggested that the microcratering was a result of secondary ejector associated with micrometeoric and meteoric impact. This research team suggests that microcratering may have been associated with primordial dust during and before the formation of our solar system.