mtDNA and mitochondrial stress signaling in human diseases: A special issue

: The completion of the Special Issue dedicated to "mtDNA and mitochondrial stress signaling in human diseases" requests a final overall look to highlight the most valuable findings among the many presented data [...]

Adiabatic normal zone development in MgB2 superconductors

A-priori knowledge of the normal zone development in MgB/sub 2/ conductors is essential for quench protection of applications. Therefore the normal zone propagation in a monofilament MgB/sub 2//Fe conductor under near-adiabatic conditions at 4.2 K has been measured and simulated. The results show normal zone propagation velocities up to several meters per second. In addition, by including the voltage-current relation into the computational model, the influence of the n-value on the normal zone propagation is determined. The simulations show that lower n-values suppress the normal zone propagation velocity due to lower heat generation in the MgB/sub 2/ filaments

Strong enhancement of Jc in binary and alloyed in-situ MgB2 wires by a new approach: Cold high pressure densification

Cold high pressure densification (CHPD) is presented as a new way to substantially enhance the critical current density of in situ MgB2 wires at 4.2 and 20 K at fields between 5 and 14 T. The results on two binary MgB2 wires and an alloyed wire with 10 wt.% B4C are presented The strongest enhancement was measured at 20K, where cold densification at 1.85 GPa on a binary Fe/MgB2 wire raised both Jcpara and Jcperp by more than 300% at 5T, while Birr was enhanced by 0.7 T. At 4.2K, the enhancement of Jc was smaller, but still reached 53% at 10 T. After applying pressures up to 6.5 GPa, the mass density dm of the unreacted (B+Mg) mixture inside the filaments reached 96% of the theoretical density. After reaction under atmospheric pressure, this corresponds to a highest mass density df in the MgB2 filaments of 73%. After reaction, the electrical resistance of wires submitted to cold densification was found to decrease, reflecting an improved connectivity. A quantitative correlation between filament mass density and the physical properties was established. Monofilamentary rectangular wires with aspect ratios a/b < 1.25 based on low energy ball milled powders exhibited very low anisotropy ratios, Gamma = Jcpara/Jcperp being < 1.4 at 4.2 K and 10T. The present results can be generalized to alloyed MgB2 wires, as demonstrated on a wire with B4C additives. Based on the present data, it follows that cold densification has the potential of further improving the highest Jcpara and Jcperp values reported so far for in situ MgB2 tapes and wires with SiC and C additives. Investigations are under work in our laboratory to determine whether the densification method CHPD can be applied to longer wire or tape lengths.Comment: Submitted to Superconductors Science and Technolog

Deletion of OGG1 Results in a Differential Signature of Oxidized Purine Base Damage in mtDNA Regions

Mitochondrial oxidative stress accumulates with aging and age-related diseases and induces alterations in mitochondrial DNA (mtDNA) content. Since mtDNA qualitative alterations are also associated with aging, repair of mtDNA damage is of great importance. The most relevant form of DNA repair in this context is base excision repair (BER), which removes oxidized bases such as 8-oxoguanine (8-oxoG) and thymine glycol through the action of the mitochondrial isoform of the specific 8-oxoG DNA glycosylase/apurinic or apyrimidinic (AP) lyase (OGG1) or the endonuclease III homolog (NTH1). Mouse strains lacking OGG1 (OGG1/) or NTH1 (NTH1/) were analyzed for mtDNA alterations. Interestingly, both knockout strains presented a significant increase in mtDNA content, suggestive of a compensatory mtDNA replication. The mtDNA “common deletion” was not detected in either knockout mouse strain, likely because of the young age of the mice. Formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites accumulated in mtDNA from OGG1/ but not from NTH1/ mice. Interestingly, the D-loop region was most severely aected by the absence of OGG1, suggesting that this region may be a hotspot for oxidative damage. Thus, we speculate that mtDNA alterations may send a stress message to evoke cell changes through a retrograde mitochondrial–nucleus communication

Prospects for Improving the Intrinsic and Extrinsic Properties of Magnesium Diboride Superconducting Strands

The magnetic and transport properties of magnesium diboride films represent performance goals yet to be attained by powder-processed bulk samples and conductors. Such performance limits are still out of the reach of even the best magnesium diboride magnet wire. In discussing the present status and prospects for improving the performance of powder-based wire we focus attention on (1) the intrinsic (intragrain) superconducting properties of magnesium diboride, Hc2 and flux pinning, (2) factors that control the efficiency with which current is transported from grain-to-grain in the conductor, an extrinsic (intergrain) property. With regard to Item-(1), the role of dopants in Hc2 enhancement is discussed and examples presented. On the other hand their roles in increasing Jc, both via Hc2 enhancement as well as direct fluxoid/pining-center interaction, are discussed and a comprehensive survey of Hc2 dopants and flux-pinning additives is presented. Current transport through the powder-processed wire (an extrinsic property) is partially blocked by the inherent granularity of the material itself and the chemical or other properties of the intergrain surfaces. These and other such results indicate that in many cases less than 15% of the conductor's cross sectional area is able to carry transport current. It is pointed out that densification in association with the elimination of grain-boundary blocking phases would yield five-to ten-fold increases in Jc in relevant regimes, enabling the performance of magnesium diboride in selected applications to compete with that of Nb-Sn

Hollow carbon spheres as an efficient dopant for enhancing critical current density of MgB2 based tapes

A significant enhancement of Jc and Hirr in MgB2 tapes has been achieved by the in situ powder-in-tube method utilizing hollow carbon spheres (HCS) as dopants. At 4.2 K, the transport Jc for the 850C sintered samples reached 3.1x10^4, and 1.4x10^4 A/cm^2 at 10 and 12 T, respectively, and were better than those of optimal nano-SiC doped tapes. Furthermore, the Hirr for doped sample was raised up to 16.8 T at 10 K due to the carbon substitution effect. The results demonstrate that HCS is one of the most promising dopants besides nano-carbon and SiC for the enhancement of current capacity for MgB2 in high fields.Comment: 14 pages, 5 figure

The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Qualitative and quantitative changes in human mitochondrial DNA (mtDNA) have been implicated in various cancer types. A 4,977 bp deletion in the major arch of the mitochondrial genome is one of the most common mutations associated with a variety of human diseases and aging.</p> <p>Methods</p> <p>We conducted a comprehensive study on clinical features and mtDNA of 104 colorectal cancer patients in the Wenzhou area of China. In particular, using a quantitative real time PCR method, we analyzed the 4,977 bp deletion and mtDNA content in tumor tissues and paired non-tumor areas from these patients.</p> <p>Results</p> <p>We found that the 4,977 bp deletion was more likely to be present in patients of younger age (≤65 years, p = 0.027). In patients with the 4,977 bp deletion, the deletion level decreased as the cancer stage advanced (p = 0.031). Moreover, mtDNA copy number in tumor tissues of patients with this deletion increased, both compared with that in adjacent non-tumor tissues and with in tumors of patients without the deletion. Such mtDNA content increase correlated with the levels of the 4,977 bp deletion and with cancer stage (p < 0.001).</p> <p>Conclusions</p> <p>Our study indicates that the mtDNA 4,977 bp deletion may play a role in the early stage of colorectal cancer, and it is also implicated in alteration of mtDNA content in cancer cells.</p

Mitochondrial Dysfunction and Apoptosis in Cumulus Cells of Type I Diabetic Mice

Impaired oocyte quality has been demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects on the oocyte are poorly understood. Cumulus cells are in direct contact with the oocyte via gap junctions and provide essential nutrients to support oocyte development. In this study, we investigated the effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency of fragmented mitochondria, a decreased transmembrane potential and an aggregated distribution of mitochondria in cumulus cells from diabetic mice. Furthermore, while mitochondrial biogenesis in cumulus cells was induced by maternal diabetes, their metabolic function was disrupted as evidenced by lower ATP and citrate levels. Moreover, we present evidence suggesting that the mitochondrial impairments induced by maternal diabetes, at least in part, lead to cumulus cell apoptosis through the release of cytochrome c. Together the deleterious effects on cumulus cells may disrupt trophic and signaling interactions with the oocyte, contributing to oocyte incompetence and thus poor pregnancy outcomes in diabetic females

Aberrant Mitochondrial Homeostasis in the Skeletal Muscle of Sedentary Older Adults

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; ♀  =  ♂). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging