We construct the non-linear Kaluza-Klein ansätze describing the embeddings of the U (1) 3 , U (1) 4 and U (1) 2 truncations of D = 5, D = 4 and D = 7 gauged supergravities into the type IIB string and M-theory. These enable one to oxidise any associated lower dimensional solutions to D = 10 or D = 11. In particular, we use these general ansätze to embed the charged AdS 5 , AdS 4 and AdS 7 black hole solutions in ten and eleven dimensions.The charges for the black holes with toroidal horizons may be interpreted as the angular momenta of D3-branes, M2-branes and M5-branes spinning in the transverse dimensions, in their near-horizon decoupling limits. The horizons of the black holes coincide with the worldvolumes of the branes. The Kaluza-Klein ansätze also allow the black holes with spherical or hyperbolic horizons to be reinterpreted in D = 10 or D = 11. IntroductionAnti-de Sitter black hole solutions of gauged extended supergravities [1] are currently attracting a good deal of attention [2,3,4,5,6,7,8,9,10,11,12] due, in large part, to the correspondence between anti-de Sitter space and conformal field theories on its boundary [13,14,15,16]. These gauged extended supergravities can arise as the massless modes of various Kaluza-Klein compactifications of both D = 11 and D = 10 supergravities. The three examples studied in the paper will be gauged D = 4, N = 8 SO(8) supergravity [17, 18] arising from D = 11 supergravity on S 7 [19, 20] whose black hole solutions are discussed in [7]; gauged D = 5, N = 8 SO(6) supergravity [21, 22] arising from Type IIB supergravity on S 5 [23, 24, 25] whose black hole solutions are discussed in [2, 6]; and gauged D = 7, N = 4 SO(5) supergravity [21, 26] arising from D = 11 supergravity on S 4 [27]whose black hole solutions are given in section 4.2 and in [9,28]. 1 In the absence of the black holes, these three AdS compactifications are singled out as arising from the near-horizon geometry of the extremal non-rotating M2, D3 and M5 branes [29,30,31,32]. One of our goals will be to embed these known lower-dimensional black hole solutions into ten or eleven dimensions, thus allowing a higher dimensional interpretation in terms of rotating M2, D3 and M5-branes.Since these gauged supergravity theories may be obtained by consistently truncating the massive modes of the full Kaluza-Klein theories, it follows that all solutions of the lower-dimensional theories will also be solutions of the higher-dimensional ones [33,34]. In principle, therefore, once we know the Kaluza-Klein ansatz for the massless sector, it ought to be straightforward to read off the higher dimensional solutions. It practice, however, this is a formidable task. The correct massless ansatz for the S 7 compactification took many years to finalize [35,36], and is still highly implicit, while for the S 5 and S 4 compactifications, the complete massless ansätze are still unknown. For our present purposes, it suffices to consider truncations of the gauged supergravities to include only gauge fields in the Cartan subalgebras ...

The human mitochondrial 12S ribosomal RNA (rRNA) A1555G mutation has been associated with aminoglycoside-induced and nonsyndromic deafness in many families worldwide. Our previous investigation revealed that the A1555G mutation is a primary factor underlying the development of deafness but is not sufficient to produce a deafness phenotype. However, it has been proposed that nuclear-modifier genes modulate the phenotypic manifestation of the A1555G mutation. Here, we identified the nuclear-modifier gene TRMU, which encodes a highly conserved mitochondrial protein related to transfer RNA (tRNA) modification. Genotyping analysis of TRMU in 613 subjects from 1 Arab-Israeli kindred, 210 European (Italian pedigrees and Spanish pedigrees) families, and 31 Chinese pedigrees carrying the A1555G or the C1494T mutation revealed a missense mutation (G28T) altering an invariant amino acid residue (A10S) in the evolutionarily conserved N-terminal region of the TRMU protein. Interestingly, all 18 Arab-Israeli/Italian-Spanish matrilineal relatives carrying both the TRMU A10S and 12S rRNA A1555G mutations exhibited prelingual profound deafness. Functional analysis showed that this mutation did not affect importation of TRMU precursors into mitochondria. However, the homozygous A10S mutation leads to a marked failure in mitochondrial tRNA metabolisms, specifically reducing the steady-state levels of mitochondrial tRNA. As a consequence, these defects contribute to the impairment of mitochondrial-protein synthesis. Resultant biochemical defects aggravate the mitochondrial dysfunction associated with the A1555G mutation, exceeding the threshold for expressing the deafness phenotype. These findings indicate that the mutated TRMU, acting as a modifier factor, modulates the phenotypic manifestation of the deafness-associated 12S rRNA mutations.

Mitochondria are ubiquitous organelles in eukaryotic cells whose primary function is to generate energy supplies in the form of ATP through oxidative phosphorylation. As the entry point for most electrons into the respiratory chain, NADH:ubiquinone oxidoreductase, or complex I, is the largest and least understood component of the mitochondrial oxidative phosphorylation system. Substantial progress has been made in recent years in understanding its subunit composition, its assembly, the interaction among complex I and other respiratory components, and its role in oxidative stress and apoptosis. This review provides an updated overview of the structure of complex I, as well as its cellular functions, and discusses the implication of complex I dysfunction in various human diseases.

Alterations in oxidative phosphorylation resulting from mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA (mtDNA) mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

Transient cerebral ischemia leads to endoplasmic reticulum (ER) stress. However, the contributions of ER stress to cerebral ischemia are not clear. To address this issue, the ER stress activators tunicamycin (TM) and thapsigargin (TG) were administered to transient middle cerebral artery occluded (tMCAO) mice and oxygen-glucose deprivation-reperfusion (OGD-Rep.)-treated neurons. Both TM and TG showed significant protection against ischemia-induced brain injury, as revealed by reduced brain infarct volume and increased glucose uptake rate in ischemic tissue. In OGD-Rep.-treated neurons, 4-PBA, the ER stress releasing mechanism, counteracted the neuronal protection of TM and TG, which also supports a protective role of ER stress in transient brain ischemia. Knocking down the ER stress sensor Eif2s1, which is further activated by TM and TG, reduced the OGD-Rep.-induced neuronal cell death. In addition, both TM and TG prevented PARK2 loss, promoted its recruitment to mitochondria, and activated mitophagy during reperfusion after ischemia. The neuroprotection of TM and TG was reversed by autophagy inhibition (3-methyladenine and Atg7 knockdown) as well as Park2 silencing. The neuroprotection was also diminished in Park2(+/-) mice. Moreover, Eif2s1 and downstream Atf4 silencing reduced PARK2 expression, impaired mitophagy induction, and counteracted the neuroprotection. Taken together, the present investigation demonstrates that the ER stress induced by TM and TG protects against the transient ischemic brain injury. The PARK2-mediated mitophagy may be underlying the protection of ER stress. These findings may provide a new strategy to rescue ischemic brains by inducing mitophagy through ER stress activation.

Mitochondrial alteration has been long proposed to play a major role in tumorigenesis. Recently, mitochondrial DNA (mtDNA) mutations have been found in a variety of cancer cells. In this study, we examined the contribution of mtDNA mutation and mitochondrial dysfunction in tumorigenesis first using human cell lines carrying a frame-shift at NADH dehydrogenase (respiratory complex I) subunit 5 gene (ND5); the same homoplasmic mutation was also identified in a human colorectal cancer cell line earlier. With increasing mutant ND5 mtDNA content, respiratory function including oxygen consumption and ATP generation through oxidative phosphorylation declined progressively, while lactate production and dependence on glucose increased. Interestingly, the reactive oxygen species (ROS) levels and apoptosis exhibited antagonistic pleiotropy associated with mitochondrial defects. Furthermore, the anchorage-dependence phenotype and tumor-forming capacity of cells carrying wild-type and mutant mtDNA were tested by growth assay in soft agar and subcutaneous implantation of the cells in nude mice. Surprisingly, the cell line carrying the heteroplasmic ND5 mtDNA mutation showed significantly enhanced tumor growth, while cells with homoplasmic form of the same mutation inhibited tumor formation. Similar results were obtained from the analysis of a series of mouse cell lines carrying a nonsense mutation at ND5 gene. Our results indicate that the mtDNA mutations might play an important role in the early stage of cancer development, possibly through alteration of ROS generation and apoptosis.

An elastic-shell-based theory for calculating the thermal conductance of graphene ribbons of arbitrary width w is presented. The analysis of vibrational modes of a continuum thin plate leads to a general equation for ballistic conductance sigma. At low temperature, it yields a power law sigma approximately T(beta), where the exponent beta varies with the ribbon width w from beta = 1 for a narrow ribbon (sigma approximately T, as a four-channel quantum wire) to beta = (3)/(2) (sigma approximately wT(3/2)) in the limit of wider graphene sheets. The ballistic results can be augmented by the phenomenological value of a phonon mean free path to account for scattering and agree well with the reported experimental observations.

We herein report the design of a dumbbell-shaped DNA probe that integrates target-binding, amplification and signaling within one multifunctional design. The dumbbell probe can initiate rolling circle amplification (D-RCA) in the presence of specific microRNA (miRNA) targets. This D-RCA-based miRNA strategy allows quantification of miRNA with very low quantity of RNA samples. The femtomolar sensitivity of D-RCA compares favorably with other existing technologies. More significantly, the dynamic range of D-RCA is extremely large, covering eight orders of magnitude. We also demonstrate miRNA quantification with this highly sensitive and inexpensive D-RCA strategy in clinical samples.