Abnormal small heat shock protein interactions involving neuropathy-associated HSP22 (HSPB8) mutants

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154632/1/fsb2fj065911fje.pd

Mobilization of putative high-proliferative-potential endothelial colony-forming cells during antihypertensive treatment in patients with essential hypertension

Recent studies have shown that in response to vascular damage or ischemia, bone marrow-derived endothelial progenitor cells (EPCs) are recruited into the circulation. To investigate whether antihypertensive treatment has an influence on the number of circulating EPCs, patients with essential hypertension were treated either with the angiotensin receptor antagonist telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks. At baseline and after 3 and 6 weeks of treatment, EPCs were identified and quantified by fluorescence-activated cell sorting (FACS) analysis and by their capacity to generate colony-forming units of the endothelial lineage (CFU-EC) in a methylcellulose-based assay. During treatment, patients in the nisoldipine groups, but not in the telmisartan group, showed a significant mobilization of EPCs, which in part had the capacity to generate large-sized colonies comprising more than 1,000 cells. Moreover, a remarkable correlation between the number of CFU-EC and the number of circulating CD133(+)/CD34(+)/CD146(+) cells was observed, thereby providing strong evidence that cells with this phenotype represent functional EPCs. No correlation was found between the numbers of CFU-EC and the blood pressure levels at any time point during the treatment. Hence, nisoldipine-induced mobilization of EPCs might represent a novel mechanism by which this antihypertensive compound independently of its blood pressure-lowering effect contributes to vasoprotection in patients with essential hypertension

Impact of strain on electronic defects in (Mg,Zn)O thin films

We have investigated the impact of strain on the incorporation and the properties of extended and point defects in (Mg,Zn)O thin films by means of photoluminescence, X-ray diffraction, deep-level transient spectroscopy (DLTS), and deep-level optical spectroscopy. The recombination line Y2, previously detected in ZnO thin films grown on an Al-doped ZnO buffer layer and attributed to tensile strain, was exclusively found in (Mg,Zn)O samples being under tensile strain and is absent in relaxed or compressively strained thin films. Furthermore a structural defect E3′ can be detected via DLTS measurements and is only incorporated in tensile strained samples. Finally it is shown that the omnipresent deep-level E3 in ZnO can only be optically recharged in relaxed ZnO samples

Asymmetric Dimethylarginine Determines the Improvement of Endothelium-Dependent Vasodilation by Simvastatin Effect of Combination With Oral L-Arginine

ObjectivesWe hypothesized that the level of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase (eNOS), might determine the endothelial effects of statins.BackgroundEndothelial NO synthase is up-regulated by statins. However, statins failed to improve endothelial function in some studies. Asymmetric dimethylarginine inhibits eNOS by a mechanism that is reversible by L-arginine.MethodsNinety-eight clinically asymptomatic elderly subjects had their plasma ADMA levels screened. Those in the highest (high ADMA, n = 15) and lowest quartiles of the ADMA distribution (low ADMA, n = 13) were eligible to receive, in a randomized order, simvastatin (40 mg/day), L-arginine (3 g/day), or a combination of both, each for 3 weeks. Endothelium-dependent vasodilation (EDD) was assessed by brachial artery ultrasound.ResultsSimvastatin had no effect on EDD in subjects with high ADMA (6.2 ± 1.2% vs. 6.1 ± 0.9%), whereas simvastatin plus L-arginine significantly improved EDD (9.8 ± 1.5% vs. 5.3 ± 0.8%; p < 0.01). In subjects with low ADMA, simvastatin improved endothelial function when given alone (9.5 ± 3.2% vs. 6.1 ± 3.8%; p < 0.001) or in combination with L-arginine (9.0 ± 3.1% vs. 6.3 ± 3.3%; p = 0.001). L-arginine alone improved endothelial function in both groups. Endothelium-independent vasodilation was not affected.ConclusionsSimvastatin does not enhance endothelial function in subjects with elevated ADMA, whereas it does so in patients with low ADMA. Combination of simvastatin with oral L-arginine improves endothelial function in subjects with high ADMA, but has no additional effect in subjects with low ADMA. As NO-mediated effects may play a major role in the therapeutic effects of statins, ADMA concentration is an important factor that influences the “pleiotropic” effects of simvastatin

Ternary silicides Sclr4Si2 and RERh4Si2 (RE = Sc, Y, Tb-Lu) and quaternary derivatives RERh4Si2-xSnx (RE = Y, Nd, Sm, Gd-Lu) - structure, chemical bonding and solid state NMR spectroscopy

The silicides ScIr4Si2 and RERh4Si2 (RE=Sc, Y, Tb-Lu) and silicide stannides RERh4Si2–xSnx (RE=Y, Nd, Sm, Gd-Lu) were synthesized from the elements by arc-melting and subsequent annealing. The new compounds crystallize with the orthorhombic YRh4Ge2 type structure, space group Pnma. They were characterized by X-ray powder patterns and several structures were refined from single crystal X-ray diffractometer data. The main structural motifs of this series of silicides are tricapped trigonal prisms formed by the transition metal and rare earth atoms. One of the two crystallographically independent silicon sites allows for formation of solid solutions with tin, exemplarily studied for ErRh4Si2–xSnx. Electronic structure calculations reveal strong covalent Rh–Si bonding as the main stability factor. Multinuclear (29Si, 45Sc, and 89Y) magic-angle spinning (MAS) NMR spectra of the structure representatives with diamagnetic rare-earth elements (Sc, Y, Lu) are found to be consistent with the crystallographic data and specifically confirm the selective substitution of Sn in the Si2 sites in the quaternary compounds YRh4SiSn and LuRh4SiSn

The sperm outer dense fiber protein is the 10th member of the superfamily of mammalian small stress proteins

Nine proteins have been assigned to date to the superfamily of mammalian small heat shock proteins (sHsps): Hsp27 (HspB1, Hsp25), myotonic dystrophy protein kinase–binding protein (MKBP) (HspB2), HspB3, αA-crystallin (HspB4), αB-crystallin (HspB5), Hsp20 (p20, HspB6), cardiovascular heat shock protein (cvHsp [HspB7]), Hsp22 (HspB8), and HspB9. The most pronounced structural feature of sHsps is the α-crystallin domain, a conserved stretch of approximately 80 amino acid residues in the C-terminal half of the molecule. Using the α-crystallin domain of human Hsp27 as query in a BLAST search, we found sequence similarity with another mammalian protein, the sperm outer dense fiber protein (ODFP). ODFP occurs exclusively in the axoneme of sperm cells. Multiple alignment of human ODFP with the other human sHsps reveals that the primary structure of ODFP fits into the sequence pattern that is typical for this protein superfamily: α-crystallin domain (conserved), N-terminal domain (less conserved), central region (variable), and C-terminal tails (variable). In a phylogenetic analysis of 167 proteins of the sHsp superfamily, using Bayesian inference, mammalian ODFPs form a clade and are nested within previously identified sHsps, some of which have been implicated in cytoskeletal functions. Both the multiple alignment and the phylogeny suggest that ODFP is the 10th member of the superfamily of mammalian sHsps, and we propose to name it HspB10 in analogy with the other sHsps. The C-terminal tail of HspB10 has a remarkable low-complexity structure consisting of 10 repeats of the motif C-X-P. A BLAST search using the C-terminal tail as query revealed similarity with sequence elements in a number of Drosophila male sperm proteins, and mammalian type I keratins and cornifin-α. Taken together, the following findings suggest a specialized role of HspB10 in cytoskeleton: (1) the exclusive location in sperm cell tails, (2) the phylogenetic relationship with sHsps implicated in cytoskeletal functions, and (3) the partial similarity with cytoskeletal proteins

Impact of strain on electronic defects in (Mg,Zn)O thin films

We have investigated the impact of strain on the incorporation and the properties of extended and point defects in (Mg,Zn)O thin films by means of photoluminescence, X-ray diffraction, deep-level transient spectroscopy (DLTS), and deep-level optical spectroscopy. The recombination line Y2, previously detected in ZnO thin films grown on an Al-doped ZnO buffer layer and attributed to tensile strain, was exclusively found in (Mg,Zn)O samples being under tensile strain and is absent in relaxed or compressively strained thin films. Furthermore a structural defect E3′ can be detected via DLTS measurements and is only incorporated in tensile strained samples. Finally it is shown that the omnipresent deep-level E3 in ZnO can only be optically recharged in relaxed ZnO samples