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

Ionization-induced asymmetric self-phase modulation and universal modulational instability in gas-filled hollow-core photonic crystal fibers

We study theoretically the propagation of relatively long pulses with ionizing intensities in a hollow-core photonic crystal fiber filled with a Raman-inactive gas. Due to photoionization, previously unknown types of asymmetric self-phase modulation and `universal' modulational instabilities existing in both normal and anomalous dispersion regions appear. We also show that it is possible to spontaneously generate a plasma-induced continuum of blueshifting solitons, opening up new possibilities for pushing supercontinuum generation towards shorter and shorter wavelengths.Comment: 5 pages, 4 figure

Population Structure of Mountain Plover as Determined Us ing Nuclear Microsatellites

Moountainuntai Plloverove (Charadrius montanus) is a specie s of conservation concern that has experienced significant habitat loss an d population decline. This, couple d with previous observation s that the species exhibits strong fidelity to breeding grounds, suggests that breeding population s may be genetically differentiate d an d possibly suffer from reduced genetic variation associate d with relatively small population sizes. A previous genetic study comparing mitochondrial DNA sequences of plover s in Montana and Colorado found high level s of genetic variability and very little genetic differentiation among breeding locale s. Because mitochondrial DNA can track only female movement s an d is sample d from only one locus, we used 14 nu clear micro satellite lo ci to further examine population structure, there by bot h documenting male movement s and providing a more comprehensive vie w of genetic structure. We found no significant differences among breeding population s. The most likely number of unique genetic clusters was one, suggesting that all sampled breeding locations comprise a single relatively homogenous gene pool. Level s of genetic diversity was similar across all four population s, with the greatest diver sit y in the southern plains population. We speculate that the lack of detectable genetic differentiation among population s is due to sufficient gene flow among breeding population s that might en sue if at least some pair bon ds are formed when birds form mixed flocks on wintering grounds. This study corroborate s and expands upon the findings of a previous mitochondrial DNA study providing a more comprehensive vie w of Mountain Plover population structure

Acclimation, Adaptation, Traits and Trade-Offs in Plankton Functional Type Models: Reconciling Terminology for Biology and Modelling

We propose definitions in terminology to enhance ongoing collaborations between biologists and modellers on plankton ecology. Organism functional type should refer to commonality in ecology not biogeochemistry; the latter is largely an emergent property of the former, while alignment with ecology is also consistent with usage in terrestrial science. Adaptation should be confined, as in genetics, to consideration of species inter-generational change; most so-called adaptive plankton models are thus acclimative, modifying vital rates in response to stimuli. Trait trade-off approaches should ideally only be considered for describing intra-generational interactions; in applications between generations, and certainly between unrelated species, such concepts should be avoided. We suggest that systems biology approaches, through to complex adaptive/acclimative systems modelling, with explicit modelling of feedback processes (which we suggest should define mechanistic models), would provide realistic and flexible bases upon which to develop descriptions of functional type models

GPflux: A Library for Deep Gaussian Processes

We introduce GPflux, a Python library for Bayesian deep learning with a strong emphasis on deep Gaussian processes (DGPs). Implementing DGPs is a challenging endeavour due to the various mathematical subtleties that arise when dealing with multivariate Gaussian distributions and the complex bookkeeping of indices. To date, there are no actively maintained, open-sourced and extendable libraries available that support research activities in this area. GPflux aims to fill this gap by providing a library with state-of-the-art DGP algorithms, as well as building blocks for implementing novel Bayesian and GP-based hierarchical models and inference schemes. GPflux is compatible with and built on top of the Keras deep learning eco-system. This enables practitioners to leverage tools from the deep learning community for building and training customised Bayesian models, and create hierarchical models that consist of Bayesian and standard neural network layers in a single coherent framework. GPflux relies on GPflow for most of its GP objects and operations, which makes it an efficient, modular and extensible library, while having a lean codebase

The oxidative stress adaptor p66Shc is required for permanent embryo arrest in vitro

<p>Abstract</p> <p>Background</p> <p>Excessive developmental failure occurs during the first week of <it>in vitro </it>embryo development due to elevated levels of cell death and arrest. We hypothesize that permanently arrested embryos enter a stress-induced "senescence-like" state that is dependent on the oxidative stress-adaptor and lifespan determinant protein p66Shc. The aim of this study was to selectively diminish p66Shc gene expression in bovine oocytes and embryos using post-transcriptional gene silencing by RNA-mediated interference to study the effects of p66Shc knockdown on <it>in vitro </it>fertilized bovine embryos.</p> <p>Results</p> <p>Approximately 12,000–24,000 short hairpin (sh)RNAi molecules specific for p66Shc were microinjected into bovine germinal vesicle stage oocytes or zygotes. Experiments were comprised of a control group undergoing IVF alone and two groups microinjected with and without p66Shc shRNAi molecules prior to IVF. The amount of p66Shc mRNA quantified by Real Time PCR was significantly (P < 0.001) lowered upon p66Shc shRNAi microinjection. This reduction was selective for p66Shc mRNA, as both histone H2a and p53 mRNA levels were not altered. The relative signal strength of p66Shc immuno-fluorescence revealed a significant reduction in the number of pixels for p66Shc shRNAi microinjected groups compared to controls (P < 0.05). A significant decrease (P < 0.001) in the incidence of arrested embryos upon p66Shc shRNAi microinjection was detected compared to IVF and microinjected controls along with significant reductions (P < 0.001) in both cleavage divisions and blastocyst development. No significant differences in p66Shc mRNA levels (P = 0.314) were observed among the three groups at the blastocyst stage.</p> <p>Conclusion</p> <p>These results show that p66Shc is involved in the regulation of embryo development specifically in mediating early cleavage arrest and facilitating development to the blastocyst stage for in vitro produced bovine embryos.</p

Long range transport of ultra cold atoms in a far-detuned 1D optical lattice

We present a novel method to transport ultra cold atoms in a focused optical lattice over macroscopic distances of many Rayleigh ranges. With this method ultra cold atoms were transported over 5 cm in 250 ms without significant atom loss or heating. By translating the interference pattern together with the beam geometry the trap parameters are maintained over the full transport range. Thus, the presented method is well suited for tightly focused optical lattices that have sufficient trap depth only close to the focus. Tight focusing is usually required for far-detuned optical traps or traps that require high laser intensity for other reasons. The transport time is short and thus compatible with the operation of an optical lattice clock in which atoms are probed in a well designed environment spatially separated from the preparation and detection region.Comment: 14 pages, 6 figure

ePedagogy as a threshold concept: a reflection on a programme for Science Teaching Assistants

A Science Teaching Assistant (TA) Programme, at the University of the Western Cape (UWC), focused on preparing promising lecturers. A key component of this programme was the contribution by the Centre for Innovative Education and Communication Technologies (CIECT), which promoted the pedagogical adoption of eTools to assist development of Science TAs. A questionnaire enabled TAs to reflect on the eTools and CIECT’s sessions. The authors reflect on academic developer roles in higher education. Within CIECT’s contribution, ePedagogy was identified as a threshold concept that the TAs found challenging, but that could lead to transformed and improved teaching and learning