There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich ataxia (FA). This disease is due to decreased expression of the mitochondrial protein, frataxin, which leads to alterations in mitochondrial iron (Fe) metabolism. The identification of potentially toxic mitochondrial Fe deposits in FA suggests Fe plays a role in its pathogenesis. Studies using the muscle creatine kinase (MCK) conditional frataxin knockout mouse that mirrors the disease have demonstrated frataxin deletion alters cardiac Fe metabolism. Indeed, there are pronounced changes in Fe trafficking away from the cytosol to the mitochondrion, leading to a cytosolic Fe deficiency. Considering Fe deficiency can induce apoptosis and cell death, we examined the effect of dietary Fe supplementation, which led to body Fe loading and limited the cardiac hypertrophy in MCK mutants. Furthermore, this study indicates a unique effect of heart and skeletal muscle-specific frataxin deletion on systemic Fe metabolism. Namely, frataxin deletion induces a signaling mechanism to increase systemic Fe levels and Fe loading in tissues where frataxin expression is intact (i.e., liver, kidney, and spleen). Examining the mutant heart, native size-exclusion chromatography, transmission electron microscopy, Mössbauer spectroscopy, and magnetic susceptibility measurements demonstrated that in the absence of frataxin, mitochondria contained biomineral Fe aggregates, which were distinctly different from isolated mammalian ferritin molecules. These mitochondrial aggregates of Fe, phosphorus, and sulfur, probably contribute to the oxidative stress and pathology observed in the absence of frataxin.

Hydrothermal iron-rich crusts have been recovered from a number of hot spot volcanos including Crough Seamount, Pitcairn Volcanos 2 and 1, Cyana Seamount, Teahitia, Moua Pihaa, and Macdonald Seamount in the S. W. Pacific. Mineralogically, the crusts consists of ferrihydrite with traces of the weathering products of volcanic ash (feldspar, nontronite, pyroxene, and serpentinite). The iron oxyhydroxide phase has a mean particle size of 3-4 nm indicating rapid deposition. Electron microprobe studies have revealed the presence of filamentous iron-silica deposits within the crusts reflecting the possible bacterial oxidation of iron from the Downloaded by [North Carolina State University] at 11:41 12 April 2015 46 P. Stoffers et al. hydrothermal fluids. The crusts display wide variability in composition both between individual sampling stations and between seamounts. Endmember analysis shows that the compositional data can be resolved into three endmembers: a Fe-rich endmember, a light and heavy rare earth element endmember, and a Ba (barite)-rich endmember. The Fe-rich endmember appears to contain very low concentrations of most trace elements. For bulk samples, the composition of the iron-rich crusts reflects dilution of the iron oxyhydroxide phase by volcanic ash and, to a lesser extent, a hydrogenous component. This is illustrated by the wide variability in SiO 2 (11.1-71.3%) and Mn (0.01-1.21%) contents of the crusts. For iron-rich crusts containing greater than 40% Fe, the Pitcairn crusts display lower contents of Pb, Ba, Mo, U, Th, As, and rare earth elements (REE) and lower cerium anomalies than those from Teahitia. REE profiles of crusts from each of the hot spot volcanoes are characterized by small negative cerium anomalies but pronounced positive europium anomalies. The low average La/Fe ratios of the crusts from the various seamounts (47-572 X 10 -6 ) and positive Eu anomalies of the crusts suggest rapid deposition of the iron oxyhydroxide near the hydrothermal vent. The high Fe/Mn ratio of vent fluids at hot spot volcanoes (8.5-5.6) may account for the formation of these iron-rich crusts. The present data indicate that there may be differences in the nature of the iron-rich crusts based on the depth of occurrence. This influences the temperature of the venting hydrothermal fluids and the possibility of occurrence of submarine phreatomagmatic eruptions.

This letter re-examines a recently published calculation of the forces exerted on a membrane ion channel by a cation passing through in the presence of an externally applied magnetic field. We show here, in contradiction to the originally published calculation, that the forces generated due to the Lorentz force of the magnetic field on the cation are negligible compared with the forces required to activate an ion channel protein conformation change associated with the gating of the channel.

Bone marrow, spleen, liver and kidney proton transverse relaxation rates (R2), together with cardiac R2* from patients with sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNH) and non-transfusion dependent thalassemia (NTDT) have been compared with a control group. Increased liver and bone marrow R2 values for the three groups of patients in comparison with the controls have been found. SCD and PNH patients also present an increased spleen R2 in comparison with the controls. The simultaneous measurement of R2 values for several tissue types by magnetic resonance imaging (MRI) has allowed the identification of iron distribution patterns in diseases associated with iron imbalance. Preferential liver iron loading is found in the highly transfused SCD patients, while the low transfused ones present a preferential iron loading of the spleen. Similar to the highly transfused SCD group, PNH patients preferentially accumulate iron in the liver. A reduced spleen iron accumulation in comparison with the liver and bone marrow loading has been found in NTDT patients, presumably related to the differential increased intestinal iron absorption. The correlation between serum ferritin and tissue R2 is moderate to good for the liver, spleen and bone marrow in SCD and PNH patients. However, serum ferritin does not correlate with NTDT liver R2, spleen R2 or heart R2*. As opposed to serum ferritin measurements, tissue R2 values are a more direct measurement of each tissue’s iron loading. This kind of determination will allow a better understanding of the different patterns of tissue iron biodistribution in diseases predisposed to tissue iron accumulation.

Iron oxide biomineralization in the radula teeth of the common limpet ( Patella vulgata ) has been studied by Mössbauer spectroscopy and high resolution transmission electron microscopy. The results indicate that the teeth comprise two iron-containing phases: (i) a superparamagnetic, microcrystalline and poorly ordered goethite-like component located essentially within the tooth bases; and (ii) stoichiometric well-ordered goethite crystals of acicular morphology sited within the tooth cusps. The goethite crystals are initially deposited in the form of long thin fibrous single crystals elongated along the [001] direction and with extensive irregularities in crystal thickness. Mature crystals often show morphological distortions that are not associated with localized structural imperfections or domain boundaries. The implications of these results in terms of tooth development are discussed.