The identification of mitochondrial DNA variants in glioblastoma multiforme

Background: Mitochondrial DNA (mtDNA) encodes key proteins of the electron transfer chain (ETC), which produces ATP through oxidative phosphorylation (OXPHOS) and is essential for cells to perform specialised functions. Tumor-initiating cells use aerobic glycolysis, a combination of glycolysis and low levels of OXPHOS, to promote rapid cell proliferation and tumor growth. Glioblastoma multiforme (GBM) is an aggressively malignant brain tumor and mitochondria have been proposed to play a vital role in GBM tumorigenesis. Results: Using next generation sequencing and high resolution melt analysis, we identified a large number of mtDNA variants within coding and non-coding regions of GBM cell lines and predicted their disease-causing potential through in silico modeling. The frequency of variants was greatest in the D-loop and origin of light strand replication in non-coding regions. ND6 was the most susceptible coding gene to mutation whilst ND4 had the highest frequency of mutation. Both genes encode subunits of complex I of the ETC. These variants were not detected in unaffected brain samples and many have not been previously reported. Depletion of HSR-GBM1 cells to varying degrees of their mtDNA followed by transplantation into immunedeficient mice resulted in the repopulation of the same variants during tumorigenesis. Likewise, de novo variants identified in other GBM cell lines were also incorporated. Nevertheless, ND4 and ND6 were still the most affected genes. We confirmed the presence of these variants in high grade gliomas. Conclusions: These novel variants contribute to GBM by rendering the ETC. partially dysfunctional. This restricts metabolism to anaerobic glycolysis and promotes cell proliferation

A non-invasive technique for standing surgical repair of urinary bladder rupture in a post-partum mare: a case report

An 11-year-old mare presented 36 hours after foaling with a ruptured bladder. Uroperitoneum was diagnosed on ultrasound and from the creatinine concentration of the peritoneal fluid. Bladder endoscopy demonstrated tissue necrosis and a rent in the dorsocranial aspect of the bladder. Following stabilisation, including abdominal drainage and lavage, the mare was taken to standing surgery. Under continuous sedation and epidural anaesthesia, and after surgical preparation, a Balfour retractor was placed in the vagina. Using sterile lubricant and moderate force, it was possible to insert a hand into the bladder. The tear was easily palpable on the dorsal portion of the bladder. Two fingers were inserted through the tear and used to provide traction to evert the bladder completely into the vagina where it could grasped with the surgeons other hand to prevent further trauma. A second surgeon could then visualise the entire tear and repaired this using a single layer of size zero PDS suture in a single continuous pattern. As soon as the bladder was repaired, it was replaced via the urethra. The mare did well after surgery and was discharged after 48 hours, apparently normal

Age-related changes to the neural correlates of working memory which emerge after midlife

Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40-60 years) and an older group (61-82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance. © 2014 Macpherson, White, Ellis, Stough, Camfield, Silberstein and Pipingas

Scalable microaccordion mesh for deformable and stretchable metallic films

Elastically deformable materials can be created from rigids sheets through patterning appropriate meshes which can locally bend and flex. We demonstrate how micro-accordion patterns can be fabricated across large areas using three-beam interference lithography. Our resulting mesh induces a large and robust elasticity within any rigid material film. Gold coating the micro-accordion produces stretchable conducting films. Conductivity changes are negligible when the sample is stretched reversibly up to 30% and no major defects are introduced, in comparison to continuous sheets which quickly tear. Scaling analysis shows that our method is suited to further miniaturisation and large- scale fabrication of stretchable functional films. It thus opens routes to stretchable interconnects in electronic, photonic and sensing applications, as well as a wide variety of other deformable structures.We are grateful for funding from the Cambridge NanoDTC, ERC LINASS 320503 and UK EPSRC grants EP/G060649/1, EP/G037221/1, EP/L027151/1 and EP/L015978/1, as well as Nokia Research. RWB thanks Queens’ College Cambridge for financial support.This is the author accepted manuscript. The final version is available from APS via http://dx.doi.org/10.1103/PhysRevApplied.4.04400

Bifunctional chalcogen linkers for the stepwise generation of multimetallic assemblies and functionalized nanoparticles

The disulfide ligand (SC6H4CO2H-4)2 acts as a simple but versatile linker for a range of group 8 transition metals through reaction of the oxygen donors. This leads to a range of homobimetallic ruthenium and osmium alkenyl compounds, [{M(CH═CHR)(CO)(PPh3)2(O2CC6H4S-4)}2] (M = Ru, Os; R = C6H4Me-4). Additional metal-based functionality can be added through the use of precursors incorporating rhenium bipyridine units (R = (bpy)ReCl(CO)3). The more robust diphosphine ligands in [{Ru(dppm)2(O2CC6H4S-4)}2](2+) (dppm = diphenylphosphinomethane) allow reduction of the disulfide bond with sodium borohydride to yield the thiol complex [Ru(O2CC6H4SH-4)(dppm)2](+). This complex reacts with [AuCl(PPh3)] to afford the bimetallic compound [Ru(dppm)2(O2CC6H4S-4)Au(PPh3)](+). However, an improved route to the same and related heterobimetallic compounds is provided by the reaction of cis-[RuCl2(dppm)2] with [Au(SC6H4CO2H-4)(L)] (L = PPh3, PCy3, PMe3, IDip) in the presence of base and NH4PF6 (IDip = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). The heterotrimetallic compound [Au(SC6H4CO2Ru(dppm)2)2](+) is accessible through the reaction of the homoleptic gold(I) dithiolate [Au(SC6H4CO2H-4)2]PPN (PPN = bis(triphenylphosphine)iminium) with cis-[RuCl2(dppm)2]. Without departure from the same methodology, greater complexity can be incorporated into the system to provide the penta- and heptametallic assemblies [(dppf){AuSC6H4CO2Ru(dppm)2}2](2+) and [(dppf){AuSC6H4CO2Os(CH═CH-bpyReCl(CO)3)(CO)(PPh3)2}2]. The same stepwise approach provides the dinuclear organometallic complexes [(L)Au(SC6H4CO2-4)M(CH═CHC6H4Me-4)(CO)(PPh3)2] (M = Ru, Os; L = PPh3, IDip). Complexes containing three metals from different groups of the periodic table [(L)Au(SC6H4CO2-4)M{CH═CH-bpyReCl(CO)3}(CO)(PPh3)2] (M = Ru, Os) can also be prepared, with one ruthenium example (L = PPh3) being structurally characterized. In order to illustrate the versatility of this approach, the synthesis and characterization (IR and NMR spectroscopy, TEM, EDS, and TGA) of the functionalized gold and palladium nanoparticles Au@[SC6H4CO2Ru(dppm)2](+) and Pd@[SC6H4CO2Ru(dppm)2](+) is reported

XMM-Newton and Chandra Observations of Abell 2626: Interacting Radio Jets and Cooling Core with Jet Precession?

We present a detailed analysis of the XMM-Newton and Chandra observations of Abell 2626 focused on the X-ray and radio interactions. Within the region of the radio mini-halo (~70 kpc), there are substructures which are probably produced by the central radio source and the cooling core. We find that there is no obvious correlation between the radio bars and the X-ray image. The morphology of Abell 2626 is more complex than that of the standard X-ray radio bubbles seen in other cool core clusters. Thus, Abell 2626 provides a challenge to models for the cooling flow -- radio source interaction. We identified two soft X-ray (0.3--2 keV) peaks with the two central cD nuclei; one of them has an associated hard X-ray (2--10 keV) point source. We suggest that the two symmetric radio bars can be explained by two precessing jets ejected from an AGN. Beyond the central regions, we find two extended X-ray sources to the southwest and northeast of the cluster center which are apparently associated with merging subclusters. The main Abell 2626 cluster and these two subclusters are extended along the direction of the Perseus-Pegasus supercluster, and we suggest that Abell 2626 is preferentially accreting subclusters and groups from this large-scale structure filament. We also find an extended X-ray source associated with the cluster S0 galaxy IC 5337; the morphology of this source suggests that it is infalling from the west, and is not associated with the southwest subcluster, as had been previously suggested.Comment: 26 pages, 16 figures, Accepted for publication in the Astrophysical Journal, We highly recommend to download a highly resolution version of the paper, which is available at http://www.astro.virginia.edu/~kw6k/publication/a2626/a2626.pdf.g

Fabrication-tolerant active-passive integration scheme for vertically-coupled microring resonators

The large-scale photonic integration of microring resonators in three dimensions made possible by recent developments in vertical coupling and wafer bonding technology is shown to be sensitive to lateral mask misalignment for the ring and bus waveguides introduced during the fabrication process. For a typical 20-µm radius, vertically coupled microring calculations reveal a linear relationship between deviation in the coupling coefficient and lateral misalignment. A coupling coefficient reduction of 50% is predicted for a lateral misalignment of 0.3 µm, which is typical for an alignment accuracy limited by the current state-of-the-art mask alignment process. The use of a wide multimode bus waveguide is proposed to ameliorate this alignment sensitivity. The mode-expanded bus waveguide, together with its physically wider structure, reduces the dependence of modal overlap and coupling length on precise alignment, resulting in significantly relaxed fabrication tolerance. Deviation of coupling coefficient decreases by an order of magnitude for the new ring coupler geometry, where a sole reduction of 5% is obtained for the same amount of misalignment. The implications of the proposed structure are subsequently investigated for microring laser performance. The differential slope efficiency is shown to be at least five times less sensitive to lateral misalignment for the proposed structure within a small misalignment regime. This readily adaptable coupler geometry based on existing vertical coupling architectures is transferable to any fabrication scheme with multiple waveguide layers coupled vertically, and is of particular importance to microring resonators with small radii