Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced qacute renal failure

The effect of acute renal failure (ARF) induced by ischemia/reperfusion (I/R) of rat kidney on the expression of organic anion transporters (OATs) was examined. The level of serum indoxyl sulfate (IS), a uremic toxin and substrate of OATs in renal tubules, shows a marked increase with the progression of ARF. However, this increase was significantly attenuated by ingestion of cobalt. The level of mRNA and protein of both rOAT1 and rOAT3 were markedly depressed in the ischemic kidney. The uptake of p-aminohippuric acid (PAH) and estrone sulfate (ES) by renal slices of ischemic rats was significantly reduced compared to control rats. Renal slices taken from ischemic rats treated with cobalt displayed significantly elevated levels of ES uptake. Cobalt intake did not affect PAH uptake, indicating the functional restoration of rOAT3 but not rOAT1. The expression of Na+/K+-ATPase was markedly depressed in the ischemic kidney, suggesting that the inward Na+ gradient in renal tubular cells had collapsed, thereby reducing the outward gradient of α-ketoglutarate, a driving force of both rOATs. The decreased expression of Na+/K+-ATPase was significantly restored by cobalt treatment. Our results suggest that the downregulation of renal rOAT1 and rOAT3 could be responsible for the increase in serum IS level of ischemic rats. Cobalt treatment has a significant protective effect on ischemia-induced ARF, being accompanied by the restoration of rOAT3 and/or Na+/K+-ATPase function

Incommensurate spin correlations induced by magnetic Fe ions substituted into overdoped Bi1.75Pb0.35Sr1.90CuO6+z

Spin correlations in the overdoped region of Bi1.75Pb0.35Sr1.90CuO6+z have been explored with Fe-doped single crystals characterized by neutron scattering, muon-spin-rotation (muSR) spectroscopy, and magnetic susceptibility measurements. Static incommensurate spin correlations induced by the Fe spins are revealed by elastic neutron scattering. The resultant incommensurability delta is unexpectedly large (~0.2 r.l.u.), as compared with delta ~ 1/8 in overdoped superconductor La2-xSrxCuO4. Intriguingly, the large delta in this overdoped region is close to the hole concentration p. This result is reminiscent of the delta ~ p trend observed in underdoped La2-xSrxCuO4; however, it is inconsistent with the saturation of delta in the latter compound in the overdoped regime. While our findings in Fe-doped Bi1.75Pb0.35Sr1.90CuO6+z support the commonality of incommensurate spin correlations in high-Tc cuprate superconductors, they also suggest that the magnetic response might be dominated by a distinct mechanism in the overdoped region.Comment: 4 pages, 5 figures. Revision in introduction, discussion, and conclusion

Spin-polarized Zener tunneling in (Ga,Mn)As

We investigate spin-polarized inter-band tunneling through measurement of (Ga,Mn)As based Zener tunnel diode. By placing the diode under reverse bias, electron spin polarization is transferred from the valence band of p-type (Ga,Mn)As to the conduction band of an adjacent n-GaAs layer. The resulting current is monitored by injection into a quantum well light emitting diode whose electroluminescence polarization is found to track the magnetization of the (Ga,Mn)As layer as a function of both temperature and magnetic field.Comment: 11 pages, 4 figures. Submitted, Physical Review B15 Rapid Communication

Cardiac Transcription Factor Nkx2.5 Is Downregulated under Excessive O-GlcNAcylation Condition

Post-translational modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is linked the development of diabetic cardiomyopathy. We investigated whether Nkx2.5 protein, a cardiac transcription factor, is regulated by O-GlcNAc. Recombinant Nkx2.5 (myc-Nkx2.5) proteins were reduced by treatment with the O-GlcNAcase inhibitors STZ and O-(2-acetamido-2-deoxy-D-glucopyroanosylidene)-amino-N-phenylcarbamate; PUGNAC) as well as the overexpression of recombinant O-GlcNAc transferase (OGT-flag). Co-immunoprecipitation analysis revealed that myc-Nkx2.5 and OGT-flag proteins interacted and myc-Nkx2.5 proteins were modified by O-GlcNAc. In addition, Nkx2.5 proteins were reduced in the heart tissue of streptozotocin (STZ)-induced diabetic mice and O-GlcNAc modification of Nkx2.5 protein increased in diabetic heart tissue compared with non-diabetic heart. Thus, excessive O-GlcNAcylation causes downregulation of Nkx2.5, which may be an underlying contributing factor for the development of diabetic cardiomyopathy

A quantitatively-modeled homozygosity mapping algorithm, qHomozygosityMapping, utilizing whole genome single nucleotide polymorphism genotyping data

Homozygosity mapping is a powerful procedure that is capable of detecting recessive disease-causing genes in a few patients from families with a history of inbreeding. We report here a homozygosity mapping algorithm for high-density single nucleotide polymorphism arrays that is able to (i) correct genotyping errors, (ii) search for autozygous segments genome-wide through regions with runs of homozygous SNPs, (iii) check the validity of the inbreeding history, and (iv) calculate the probability of the disease-causing gene being located in the regions identified. The genotyping error correction restored an average of 94.2% of the total length of all regions with run of homozygous SNPs, and 99.9% of the total length of them that were longer than 2 cM. At the end of the analysis, we would know the probability that regions identified contain a disease-causing gene, and we would be able to determine how much effort should be devoted to scrutinizing the regions. We confirmed the power of this algorithm using 6 patients with Siiyama-type α1-antitrypsin deficiency, a rare autosomal recessive disease in Japan. Our procedure will accelerate the identification of disease-causing genes using high-density SNP array data

Theory of spin-polarized bipolar transport in magnetic p-n junctions

The interplay between spin and charge transport in electrically and magnetically inhomogeneous semiconductor systems is investigated theoretically. In particular, the theory of spin-polarized bipolar transport in magnetic p-n junctions is formulated, generalizing the classic Shockley model. The theory assumes that in the depletion layer the nonequilibrium chemical potentials of spin up and spin down carriers are constant and carrier recombination and spin relaxation are inhibited. Under the general conditions of an applied bias and externally injected (source) spin, the model formulates analytically carrier and spin transport in magnetic p-n junctions at low bias. The evaluation of the carrier and spin densities at the depletion layer establishes the necessary boundary conditions for solving the diffusive transport equations in the bulk regions separately, thus greatly simplifying the problem. The carrier and spin density and current profiles in the bulk regions are calculated and the I-V characteristics of the junction are obtained. It is demonstrated that spin injection through the depletion layer of a magnetic p-n junction is not possible unless nonequilibrium spin accumulates in the bulk regions--either by external spin injection or by the application of a large bias. Implications of the theory for majority spin injection across the depletion layer, minority spin pumping and spin amplification, giant magnetoresistance, spin-voltaic effect, biasing electrode spin injection, and magnetic drift in the bulk regions are discussed in details, and illustrated using the example of a GaAs based magnetic p-n junction.Comment: 36 pages, 11 figures, 2 table

Homozygosity Mapping on Homozygosity Haplotype Analysis to Detect Recessive Disease-Causing Genes from a Small Number of Unrelated, Outbred Patients

Genes involved in disease that are not common are often difficult to identify; a method that pinpoints them from a small number of unrelated patients will be of great help. In order to establish such a method that detects recessive genes identical-by-descent, we modified homozygosity mapping (HM) so that it is constructed on the basis of homozygosity haplotype (HM on HH) analysis. An analysis using 6 unrelated patients with Siiyama-type α1-antitrypsin deficiency, a disease caused by a founder gene, the correct gene locus was pinpointed from data of any 2 patients (length: 1.2–21.8 centimorgans, median: 1.6 centimorgans). For a test population in which these 6 patients and 54 healthy subjects were scrambled, the approach accurately identified these 6 patients and pinpointed the locus to a 1.4-centimorgan fragment. Analyses using synthetic data revealed that the analysis works well for IBD fragment derived from a most recent common ancestor (MRCA) who existed less than 60 generations ago. The analysis is unsuitable for the genes with a frequency in general population more than 0.1. Thus, HM on HH analysis is a powerful technique, applicable to a small number of patients not known to be related, and will accelerate the identification of disease-causing genes for recessive conditions

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio