Neurofibromin knockdown in glioma cell lines is associated with changes in cytokine and chemokine secretion in vitro.

The neurofibromin-1 tumor suppressor gene (NF1) is altered in approximately 20% of sporadic glioblastoma (GBM) cases. NF1 deficient GBM frequently shows a mesenchymal gene expression signature, suggesting a relationship between NF1 status and the tumor microenvironment. To identify changes in the production of secreted cytokines/chemokines in NF1 deficient glioma, we applied cytokine arrays to conditioned media from a panel of three GBM cell lines after siRNA-mediated NF1 knockdown. We identified increased secretion of platelet-derived growth factor AA (PDGF-AA), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8), and endoglin (ENG) in different subsets of these cell lines. Secretion was associated with induction of the corresponding messenger RNA, suggesting a mechanism involving transcriptional upregulation. By contrast, in non-transformed immortalized normal human astrocytes, PDGF-AA secretion was increased upon NF1 knockdown, while secreted CHI3L1, ENG, and IL-8 were reduced or unchanged. Analysis of The Cancer Genome Atlas confirmed a relationship between glioma NF1 status and ENG and CHI3L1 in tumor samples. Overall, this study identifies candidate changes in secreted proteins from NF1 deficient glioma cells that could influence the tumor microenvironment, and suggests a direct link between NF1 loss and increased tumor cell production of CHI3L1 and endoglin, two factors implicated in mesenchymal identity in glioblastoma

Impact of surface-polish on the angular and wavelength dependence of fiber focal ratio degradation

We present measurements of how multimode fiber focal-ratio degradation (FRD) and throughput vary with levels of fiber surface polish from 60 to 0.5 micron grit. Measurements used full-beam and laser injection methods at wavelengths between 0.4 and 0.8 microns on 17 meter lengths of Polymicro FBP 300 and 400 micron core fiber. Full-beam injection probed input focal-ratios between f/3 and f/13.5, while laser injection allowed us to isolate FRD at discrete injection angles up to 17 degrees (f/1.6 marginal ray). We find (1) FRD effects decrease as grit size decreases, with the largest gains in beam quality occurring at grit sizes above 5 microns; (2) total throughput increases as grit size decreases, reaching 90% at 790 nm with the finest polishing levels; (3) total throughput is higher at redder wavelengths for coarser polishing grit, indicating surface-scattering as the primary source of loss. We also quantify the angular dependence of FRD as a function of polishing level. Our results indicate that a commonly adopted micro-bending model for FRD is a poor descriptor of the observed phenomenon.Comment: 10 pages, 7 figures, presented at SPIE Astronomical Telescopes and Instrumentation, July 201

Numerical Chromosomal Instability Mediates Susceptibility to Radiation Treatment

The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated radiation therapy. However, the mechanism for this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads to mitotic chromosome segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell lines. These mitotic errors generate an abundance of micronuclei that predispose chromosomes to subsequent catastrophic pulverization thereby independently amplifying radiation-induced genome damage. Experimentally suppressing whole-chromosome missegregation reduces downstream chromosomal defects and significantly increases the viability of irradiated mitotic cells. Further, orthotopically transplanted human glioblastoma tumours in which chromosome missegregation rates have been reduced are rendered markedly more resistant to IR, exhibiting diminished markers of cell death in response to treatment. This work identifies a novel mitotic pathway for radiation-induced genome damage, which occurs outside of the primary nucleus and augments chromosomal breaks. This relationship between radiation treatment and whole-chromosome missegregation can be exploited to modulate therapeutic response in a clinically relevant manner

The role of fine sediment characteristics and body size on the vertical movement of a freshwater amphipod

1. Sedimentation and clogging (colmation) of interstitial pore spaces with fine sediment particles is widely considered to be one of the most significant threats to lotic ecosystem functioning. This paper presents the results of a running water mesocosm study examining the effect of benthic and hyporheic fine sediment loading and particle size on the vertical movement and distribution of the freshwater amphipod Gammarus pulex. 2. A gradient of fine sediment loading and different particle sizes were used to examine the ability of G. pulex from two body size classes to access and migrate vertically within subsurface sediments. 3. We tested three hypotheses: i) sediment loading would modify the distribution of G. pulex by limiting vertical movement; ii) the deposition of large particles and heterogenous sediments would limit the vertical movement of individuals more than homogeneous fine grained sediments; and iii) large bodied individuals would be prevented from migrating vertically with increasing sediment loading and particle size / heterogeneity. 4. Sediment loading, particle size and heterogeneity of deposited sediment had a significant effect on the vertical movement of individuals, with heterogeneous sand (0.125 - 4 mm) acting as the strongest barrier to the vertical movement of individuals through the infilling and clogging of interstitial spaces followed by coarse (1 - 4mm) and fine sand (0.125 - 4 mm). 5. Fine sediment loading and particle size acted as a filter on body size and limited the ability of large bodied individuals to migrate vertically to a greater extent than small bodied individuals. 6. This study demonstrates that the effects of fine sediment on habitat availability and faunal movement is dependent on both sedimentological characteristics and an individual’s body size. The results illustrate the importance of both abiotic and biotic factors when evaluating the ecological 66 effects of fine sediment deposition

Using Spectral and Cross-Spectral Analysis to Identify Patterns and Synchrony in Couples\u27 Sexual Desire

Sexual desire discrepancy is one of the most frequently reported sexual concerns for individuals and couples and has been shown to be negatively associated with sexual and relationship satisfaction. Sexual desire has increasingly been examined as a state-like construct that ebbs and flows, but little is known about whether there are patterns in the fluctuation of sexual desire. Utilizing spectral and cross-spectral analysis, we transformed 30 days of dyadic daily diary data for perceived levels of sexual desire for a non-clinical sample of 133 couples (266 individuals) into the frequency domain to identify shared periodic state fluctuations in sexual desire. Spectral analysis is a technique commonly used in physics and engineering that allows time series data to be analyzed for the presence of regular cycles of fluctuation. Cross-spectral analysis allows for dyadic data to be analyzed for shared rates of fluctuation between partners as well as the degree of (a)synchrony (or phase shift) between these fluctuations. Men and women were found to exhibit fluctuations in sexual desire at various frequencies including rates of once and twice per month, and to have sexual desire that was unlikely to fluctuate over periods of three days or less and therefore exhibited persistence. Similar patterns of fluctuation were exhibited within couples and these patterns were found to be largely synchronous. While instances of desire discrepancy may arise due to differences in rates of sexual desire fluctuation and random fluctuations, such instances may be normal for romantic relationships. The results have important implications for researchers, clinicians, and educators in that they corroborate the supposition that sexual desire ebbs and flows and suggest that it does so with predictable regularity