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

NICMOS Snapshot Survey of Damped Lyman Alpha Quasars

We image 19 quasars with 22 damped Lyman alpha (DLA) systems using the F160W filter and the Near-Infrared Camera and Multiobject Spectrograph aboard the Hubble Space Telescope, in both direct and coronagraphic modes. We reach 5 sigma detection limits of ~H=22 in the majority of our images. We compare our observations to the observed Lyman-break population of high-redshift galaxies, as well as Bruzual & Charlot evolutionary models of present-day galaxies redshifted to the distances of the absorption systems. We predict H magnitudes for our DLAs, assuming they are producing stars like an L* Lyman-break galaxy (LBG) at their redshift. Comparing these predictions to our sensitivity, we find that we should be able to detect a galaxy around 0.5-1.0 L* (LBG) for most of our observations. We find only one new possible candidate, that near LBQS0010-0012. This scarcity of candidates leads us to the conclusion that most DLA systems are not drawn from a normal LBG luminosity function nor a local galaxy luminosity function placed at these high redshifts.Comment: 31 pages, 8 figures, Accepted for Feb. 10 issue of Ap

NICMOS Imaging of the Host Galaxies of z ~ 2 - 3 Radio-Quiet Quasars

We have made a deep NICMOS imaging study of a sample of 5 z ~ 2 - 3 radio-quiet quasars with low absolute nuclear luminosities, and we have detected apparent host galaxies in all of these. Most of the hosts have luminosities approximately equal to present-day L*, with a range from 0.2 L* to about 4 L*. These host galaxies have magnitudes and sizes consistent with those of the Lyman break galaxies at similar redshifts and at similar rest wavelengths, but are about two magnitudes fainter than high-z powerful radio galaxies. The hosts of our high-z sample are comparable to or less luminous than the hosts of the low-z RQQs with similar nuclear absolute magnitudes. However, the high z galaxies are more compact than the hosts of the low z quasars, and probably have only 10 - 20% of the stellar mass of their low-z counterparts. Application of the M(bulge)/M(BH) relation found for present-day spheroids to the stellar masses implied for the high z host galaxies would indicate that they contain black holes with masses around 10^8 Msolar. Comparison to their nuclear magnitudes implies accretion rates that are near or at the Eddington limit. Although these high z hosts already contain supermassive black holes, the galaxies will need to grow significantly to evolve into present-day L* galaxies. These results are basically consistent with theoretical predictions for the hierarchical buildup of the galaxy host and its relation to the central supermassive black hole.Comment: 25 pages, 13 figures, accepted for publication in Ap

The response of soil microbial diversity and abundance to long-term application of biosolids

The disposal of biosolids poses a major environmental and economic problem. Agricultural use is generally regarded as the best means of disposal. However, its impact on soil ecosystems remains uncertain. Biosolids can improve soil properties by supplying nutrients and increasing organic matter content but there is also a potentially detrimental effect arising from the introduction of heavy metals into soils. To assess the balance between these competing effects on soil health, we investigated soil bacterial and fungal diversity and community structure at a site that has been dedicated to the disposal of sewage sludge for over 100 years. Terminal restriction fragment length polymorphism (T-RFLP) was used to characterize the soil microbial communities. The most important contaminants at the site were Ni, Cu, Zn, Cd, and Pb. Concentrations were highly correlated and Zn concentration was adopted as a good indicator of the overall (historical) biosolids loading. A biosolids loading, equivalent to 700–1000 mg kg−1 Zn appeared to be optimal for maximum bacterial and fungal diversity. This markedly exceeds the maximum soil Zn concentration of 300 mg kg−1permitted under the current UK Sludge (use in agriculture) Regulations. Redundancy analysis (RDA) suggested that the soil microbial communities had been altered in response to the accumulation of trace metals, especially Zn, Cd, and Cu. We believe this is the first time the trade-off between positive and negative effects of long term (>100 years) biosolids disposal on soil microorganisms have been observed in the field situation

Using LiDAR to Link Forest Canopy Structure with Bat Activity and Insect Occurrence: Preliminary Findings

Bats are an imperiled, yet ecologically-important group of vertebrate predators. Our ongoing research focuses on testing hypotheses about the relationships between the effects of fire on canopy structure and insect prey availability, and how these factors relate to use of foraging space by bats during the pre- and post-hibernation periods at Mammoth Cave National Park (MCNP). LiDAR-derived data (October 2010) were intersected with spatially explicit sampling of bat and insect populations (2010-2011) in order to characterize relationships between canopy structure, insect abundance, and bat activity. A canonical correspondence analysis for bat data suggested that forest canopy structure has a strong relationship with bat activity, particularly for species that echolocate at higher frequencies. Less variation was accounted for in a canonical correspondence analysis of insect occurrence. Even so, this analysis still demonstrated that variation in forest canopy structure influences the insect community at MCNP, albeit in varied ways for specific orders of insects

The shape of motion perception: Global pooling of transformational apparent motion

Transformational apparent motion (TAM) is a visual phenomenon highlighting the utility of form information in motion processing. In TAM, smooth apparent motion is perceived when shapes in certain spatiotemporal arrangements change. It has been argued tha

Experimental heatwaves compromise sperm function and cause transgenerational damage in a model insect

Climate change is affecting biodiversity, but proximate drivers remain poorly understood. Here, we examine how experimental heatwaves impact on reproduction in an insect system. Male sensitivity to heat is recognised in endotherms, but ectotherms have received limited attention, despite comprising most of biodiversity and being more influenced by temperature variation. Using a flour beetle model system, we find that heatwave conditions (5 to 7 °C above optimum for 5 days) damaged male, but not female, reproduction. Heatwaves reduce male fertility and sperm competitiveness, and successive heatwaves almost sterilise males. Heatwaves reduce sperm production, viability, and migration through the female. Inseminated sperm in female storage are also damaged by heatwaves. Finally, we discover transgenerational impacts, with reduced reproductive potential and lifespan of offspring when fathered by males, or sperm, that had experienced heatwaves. This male reproductive damage under heatwave conditions provides one potential driver behind biodiversity declines and contractions through global warming

The C-Band All-Sky Survey: Instrument design, status, and first-look data

The C-Band All-Sky Survey (C-BASS) aims to produce sensitive, all-sky maps of diffuse Galactic emission at 5 GHz in total intensity and linear polarization. These maps will be used (with other surveys) to separate the several astrophysical components contributing to microwave emission, and in particular will allow an accurate map of synchrotron emission to be produced for the subtraction of foregrounds from measurements of the polarized Cosmic Microwave Background. We describe the design of the analog instrument, the optics of our 6.1 m dish at the Owens Valley Radio Observatory, the status of observations, and first-look data.Comment: 10 pages, 11 figures, published in Proceedings of SPIE MIllimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010), Vol. 7741, 77411I-1 - 77411I-1