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

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

High speed solid rotor permanent magnet machines: concept and design

This paper proposes a novel solid rotor topology for an Interior Permanent Magnet (IPM) machine, adopted in this case for an aircraft starter-generator design. The key challenge in the design is to satisfy two operating conditions which are: a high torque at start and a high speed at cruise. Conventional IPM topologies which are highly capable of extended field weakening are found to be limited at high speed due to structural constraints associated with the rotor material. To adopt the IPM concept for high speed operation, it is proposed to adopt a rotor constructed from semi-magnetic stainless steel, which has a higher yield strength than laminated silicon steel. To maintain minimal stress levels and also minimize the resultant eddy current losses due to the lack of laminations, different approaches are considered and studied. Finally, to achieve a better tradeoff between the structural and electromagnetic constraints, a novel slitted approach is implemented on the rotor. The proposed rotor topology is verified using electromagnetic, static structural and dynamic structural Finite Element (FE) analyses. An experiment is performed to confirm the feasibility of the proposed rotor. It is shown that the proposed solid rotor concept for an IPM fulfils the design requirements whilst satisfying the structural, thermal and magnetic limitations

Prediction of a neuropeptidome for the eyestalk ganglia of the lobster Homarus americanus using a tissue-specific de novo assembled transcriptome

In silico transcriptome mining is a powerful tool for crustacean peptidome prediction. Using homology-based BLAST searches and a simple bioinformatics workflow, large peptidomes have recently been predicted for a variety of crustaceans, including the lobster, Homarus americanus. Interestingly, no in silico studies have been conducted on the eyestalk ganglia (lamina ganglionaris, medulla externa, medulla interna and medulla terminalis) of the lobster, although the eyestalk is the location of a major neuroendocrine complex, i.e., the X-organ-sinus gland system. Here, an H. americanus eyestalk ganglia-specific transcriptome was produced using the de novo assembler Trinity. This transcriptome was generated from 130,973,220 Illumina reads and consists of 147,542 unique contigs. Eighty-nine neuropeptide-encoding transcripts were identified from this dataset, allowing for the deduction of 62 distinct pre/preprohormones. Two hundred sixty-two neuropeptides were predicted from this set of precursors; the peptides include members of the adipokinetic hormone-corazonin-like peptide, allatostatin A, allatostatin B, allatostatin C, bursicon α, CCHamide, corazonin, crustacean cardioactive peptide, crustacean hyperglycemic hormone (CHH), CHH precursor-related peptide, diuretic hormone 31, diuretic hormone 44, eclosion hormone, elevenin, FMRFamide-like peptide, glycoprotein hormone α2, glycoprotein hormone β5, GSEFLamide, intocin, leucokinin, molt-inhibiting hormone, myosuppressin, neuroparsin, neuropeptide F, orcokinin, orcomyotropin, pigment dispersing hormone, proctolin, pyrokinin, red pigment concentrating hormone, RYamide, short neuropeptide F, SIFamide, sulfakinin, tachykinin-related peptide and trissin families. The predicted peptides expand the H. americanus eyestalk ganglia neuropeptidome approximately 7-fold, and include 78 peptides new to the lobster. The transcriptome and predicted neuropeptidome described here provide new resources for investigating peptidergic signaling within/from the lobster eyestalk ganglia

The Evolution of the Galaxy Stellar Mass Function at z= 4-8: A Steepening Low-mass-end Slope with Increasing Redshift

We present galaxy stellar mass functions (GSMFs) at $z=$ 4-8 from a rest-frame ultraviolet (UV) selected sample of $\sim$4500 galaxies, found via photometric redshifts over an area of $\sim$280 arcmin$^2$ in the CANDELS/GOODS fields and the Hubble Ultra Deep Field. The deepest Spitzer/IRAC data yet-to-date and the relatively large volume allow us to place a better constraint at both the low- and high-mass ends of the GSMFs compared to previous space-based studies from pre-CANDELS observations. Supplemented by a stacking analysis, we find a linear correlation between the rest-frame UV absolute magnitude at 1500 \AA\ ($M_{\rm UV}$) and logarithmic stellar mass ($\log M_*$) that holds for galaxies with $\log(M_*/M_{\odot}) \lesssim 10$. We use simulations to validate our method of measuring the slope of the $\log M_*$-$M_{\rm UV}$ relation, finding that the bias is minimized with a hybrid technique combining photometry of individual bright galaxies with stacked photometry for faint galaxies. The resultant measured slopes do not significantly evolve over $z=$ 4-8, while the normalization of the trend exhibits a weak evolution toward lower masses at higher redshift. We combine the $\log M_*$-$M_{\rm UV}$ distribution with observed rest-frame UV luminosity functions at each redshift to derive the GSMFs, finding that the low-mass-end slope becomes steeper with increasing redshift from $\alpha=-1.55^{+0.08}_{-0.07}$ at $z=4$ to $\alpha=-2.25^{+0.72}_{-0.35}$ at $z=8$. The inferred stellar mass density, when integrated over $M_*=10^8$-$10^{13} M_{\odot}$, increases by a factor of $10^{+30}_{-2}$ between $z=7$ and $z=4$ and is in good agreement with the time integral of the cosmic star formation rate density.Comment: 27 pages, 17 figures, ApJ, in pres

Algorithms for Olfactory Search across Species

Localizing the sources of stimuli is essential. Most organisms cannot eat, mate, or escape without knowing where the relevant stimuli originate. For many, if not most, animals, olfaction plays an essential role in search. While microorganismal chemotaxis is relatively well understood, in larger animals the algorithms and mechanisms of olfactory search remain mysterious. In this symposium, we will present recent advances in our understanding of olfactory search in flies and rodents. Despite their different sizes and behaviors, both species must solve similar problems, including meeting the challenges of turbulent airflow, sampling the environment to optimize olfactory information, and incorporating odor information into broader navigational systems

The mass evolution of the first galaxies: stellar mass functions and star formation rates at 4<z<74 < z < 7 in the CANDELS GOODS-South field

We measure new estimates for the galaxy stellar mass function and star formation rates for samples of galaxies at $z \sim 4,~5,~6~\&~7$ using data in the CANDELS GOODS South field. The deep near-infrared observations allow us to construct the stellar mass function at $z \geq 6$ directly for the first time. We estimate stellar masses for our sample by fitting the observed spectral energy distributions with synthetic stellar populations, including nebular line and continuum emission. The observed UV luminosity functions for the samples are consistent with previous observations, however we find that the observed $M_{UV}$ - M$_{*}$ relation has a shallow slope more consistent with a constant mass to light ratio and a normalisation which evolves with redshift. Our stellar mass functions have steep low-mass slopes ($\alpha \approx -1.9$), steeper than previously observed at these redshifts and closer to that of the UV luminosity function. Integrating our new mass functions, we find the observed stellar mass density evolves from $\log_{10} \rho_{*} = 6.64^{+0.58}_{-0.89}$ at $z \sim 7$ to $7.36\pm0.06$ $\text{M}_{\odot} \text{Mpc}^{-3}$ at $z \sim 4$. Finally, combining the measured UV continuum slopes ($\beta$) with their rest-frame UV luminosities, we calculate dust corrected star-formation rates (SFR) for our sample. We find the specific star-formation rate for a fixed stellar mass increases with redshift whilst the global SFR density falls rapidly over this period. Our new SFR density estimates are higher than previously observed at this redshift.Comment: 28 pages, 23 figures, 2 appendices. Accepted for publication in MNRAS, August 7 201

Sexual selection protects against extinction

Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring1. It has been theorized that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load2,3,4. Under sexual selection, competition between (usually) males and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which is contingent to mutation load, then sexually selected filtering through ‘genic capture’5 could offset the costs of sex because it provides genetic benefits to populations. Here we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for 6 to 7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress.We thank the Natural Environment Research Council and the Leverhulme Trust for financial support, D. Edward for statistical advice and colleagues at the 2013 Biology of Sperm meeting for comments that improved analytical design and interpretation.Peer reviewedPeer Reviewe

The Unusual Infrared Object HDF-N J123656.3+621322

We describe an object in the Hubble Deep Field North with very unusual near-infrared properties. It is readily visible in Hubble Space Telescope NICMOS images at 1.6um and from the ground at 2.2um, but is undetected (with signal-to-noise <~ 2) in very deep WFPC2 and NICMOS data from 0.3 to 1.1um. The f_nu flux density drops by a factor >~ 8.3 (97.7% confidence) from 1.6 to 1.1um. The object is compact but may be slightly resolved in the NICMOS 1.6um image. In a low-resolution, near-infrared spectrogram, we find a possible emission line at 1.643um, but a reobservation at higher spectral resolution failed to confirm the line, leaving its reality in doubt. We consider various hypotheses for the nature of this object. Its colors are unlike those of known galactic stars, except perhaps the most extreme carbon stars or Mira variables with thick circumstellar dust shells. It does not appear to be possible to explain its spectral energy distribution as that of a normal galaxy at any redshift without additional opacity from either dust or intergalactic neutral hydrogen. The colors can be matched by those of a dusty galaxy at z >~ 2, by a maximally old elliptical galaxy at z >~ 3 (perhaps with some additional reddening), or by an object at z >~ 10 whose optical and 1.1um light have been suppressed by the intergalactic medium. Under the latter hypothesis, if the luminosity results from stars and not an AGN, the object would resemble a classical, unobscured protogalaxy, with a star formation rate >~ 100 M_sun/yr. Such UV-bright objects are evidently rare at 2 < z < 12.5, however, with a space density several hundred times lower than that of present-day L* galaxies.Comment: Accepted for publication in the Astrophysical Journal. 27 pages, LaTeX, with 7 figures (8 files); citations & references updated + minor format change