Microarray analysis of pathways involved in bladder cancer invasion and metastasis.

MDHypoxia-inducible genes have been linked to the aggressive phenotype of cancer. However, nearly all work on hypoxia-regulated genes has been conducted in vitro on cell lines. Here the hypoxia transcriptome in primary human bladder cancer was investigated using cIDNA microarrays to compare genes induced by hypoxia in vitro in bladder cancer cell line EJ28 with genes upregulated on an in vivo array of 39 bladder tumours (27 Ta/T1 12 T2-T4). mRNA array fold-changes were correlated with carbonic anhydrase IX (CA IX) staining and necrosis of tumours as surrogate markers of hypoxia. Of 6000 genes 32 were repeatedly hypoxia-inducible in vitro more than 2-fold, five of which were novel, including lactate transporter SLC16A3 and RNAse 4. Eight of 32 hypoxia-inducible genes in vitro were also upregulated on the vivo array. Vascular endothelial growth factor (VEGF) mRNA was upregulated 2-fold by hypoxia and 2 to 18-fold in 31/39 tumours. Also up regulated on both arrays was GLUT 1 mRNA, and fold changes on the in vivo genearray significantly correlated with CA IX staining of tumours (p=0.008). However Insulin-like growth factor binding protein 3 (IGFBP-3) mRNA was the most strongly differentially expressed gene in both arrays and its upregulation was confirmed in the urine of bladder cancer patients (n=157, p<0.01) and in cell line supernatants. Angiogenin was also upregulated in urine of bladder cancer patients. Selected genes upregulated by hypoxia (HIF la, HIF 2a, CA IX and NIP3) were studied by immunohistochemistry for their prognostic significance and association with necrosis in 98 cystectomy specimens. Normal human urothelial cells were also grown in culture and a hypoxia genearray profile compared with EJ28, peripheral blood monocytes and T-cells. This thesis studies the prevalence of hypoxia and necrosis in bladder cancer, its relationship with prognosis, genes associated with the hypoxic phenotype and hypoxia related molecular pathways

The “Soluble” Adenylyl Cyclase in Sperm Mediates Multiple Signaling Events Required for Fertilization

SummaryMammalian fertilization is dependent upon a series of bicarbonate-induced, cAMP-dependent processes sperm undergo as they “capacitate,” i.e., acquire the ability to fertilize eggs. Male mice lacking the bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC), the predominant source of cAMP in male germ cells, are infertile, as the sperm are immotile. Membrane-permeable cAMP analogs are reported to rescue the motility defect, but we now show that these “rescued” null sperm were not hyperactive, displayed flagellar angulation, and remained unable to fertilize eggs in vitro. These deficits uncover a requirement for sAC during spermatogenesis and/or epididymal maturation and reveal limitations inherent in studying sAC function using knockout mice. To circumvent this restriction, we identified a specific sAC inhibitor that allowed temporal control over sAC activity. This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC

The Murchison Widefield Array: Design Overview

The Murchison Widefield Array (MWA) is a dipole-based aperture array synthesis telescope designed to operate in the 80-300 MHz frequency range. It is capable of a wide range of science investigations, but is initially focused on three key science projects. These are detection and characterization of 3-dimensional brightness temperature fluctuations in the 21cm line of neutral hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10, solar imaging and remote sensing of the inner heliosphere via propagation effects on signals from distant background sources,and high-sensitivity exploration of the variable radio sky. The array design features 8192 dual-polarization broad-band active dipoles, arranged into 512 tiles comprising 16 dipoles each. The tiles are quasi-randomly distributed over an aperture 1.5km in diameter, with a small number of outliers extending to 3km. All tile-tile baselines are correlated in custom FPGA-based hardware, yielding a Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point spread function (PSF) quality. The correlated data are calibrated in real time using novel position-dependent self-calibration algorithms. The array is located in the Murchison region of outback Western Australia. This region is characterized by extremely low population density and a superbly radio-quiet environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings of the IEE

Evolution of Anolis Lizard Dewlap Diversity

BACKGROUND: The dewlaps of Anolis lizards provide a classic example of a complex signaling system whose function and evolution is poorly understood. Dewlaps are flaps of skin beneath the chin that are extended and combined with head and body movements for visual signals and displays. They exhibit extensive morphological variation and are one of two cladistic features uniting anoles, yet little is known regarding their function and evolution. We quantified the diversity of anole dewlaps, investigated whether dewlap morphology was informative regarding phylogenetic relationships, and tested two separate hypotheses: (A) similar Anolis habitat specialists possess similar dewlap configurations (Ecomorph Convergence hypothesis), and (B) sympatric species differ in their dewlap morphologies to a greater extent than expected by chance (Species Recognition hypothesis). METHODOLOGY/PRINCIPAL FINDINGS: We found that dewlap configurations (sizes, patterns and colors) exhibit substantial diversity, but that most are easily categorized into six patterns that incorporate one to three of 13 recognizable colors. Dewlap morphology is not phylogenetically informative and, like other features of anoles, exhibits convergence in configurations. We found no support for the Ecomorph Convergence hypothesis; species using the same structural habitat were no more similar in dewlap configuration than expected by chance. With one exception, all sympatric species in four communities differ in dewlap configuration. However, this provides only weak support for the Species Recognition hypothesis because, due to the great diversity in dewlap configurations observed across each island, few cases of sympatric species with identical dewlaps would be expected to co-occur by chance alone. CONCLUSIONS/SIGNIFICANCE: Despite previous thought, most dewlaps exhibit easily characterizable patterns and colorations. Nevertheless, dewlap variation is extensive and explanations for the origin and evolution of this diversity are lacking. Our data do not support two hypothesized explanations for this diversity, but others such as sexual selection remain to be tested

First spectroscopic imaging observations of the sun at low radio frequencies with the Murchison Widefield Array Prototype

We present the first spectroscopic images of solar radio transients from the prototype for the Murchison Widefield Array, observed on 2010 March 27. Our observations span the instantaneous frequency band 170.9- 201.6 MHz. Though our observing period is characterized as a period of "low" to "medium" activity, one broadband emission feature and numerous short-lived, narrowband, non-thermal emission features are evident. Our data represent a significant advance in low radio frequency solar imaging, enabling us to follow the spatial, spectral, and temporal evolution of events simultaneously and in unprecedented detail. The rich variety of features seen here reaffirms the coronal diagnostic capability of low radio frequency emission and provides an early glimpse of the nature of radio observations that will become available as the next generation of low-frequency radio interferometers come online over the next few years

Impediments to effective altruism: the role of subjective preferences in charitable giving

Charity could do the most good if every dollar donated went to causes that produced the greatest welfare gains. In line with this proposition, the “Effective Altruism” movement seeks to provide individuals with information regarding the effectiveness of charities in hopes that they will donate to organizations that maximize the social return of their donation. This paper investigates the extent to which presenting effectiveness information leads people to choose more effective charities. We find that even when effectiveness information is made easily comparable across options, it has a limited impact on choice. Specifically, people frequently choose less effective charity options when those options represent more subjectively preferred causes. In contrast to making a personal donation decision, outcome metrics are used to a much greater extent when choosing financial investments and when allocating aid resources as an agent of an organization. Implications for Effective Altruism are discussed

Data from: Convergent evolution in the territorial communication of a classic adaptive radiation: Caribbean Anolis lizards

To demonstrate adaptive convergent evolution, it must be shown that shared phenotypes have evolved independently in different lineages and that a credible selection pressure underlies adaptive evolution. There are a number of robust examples of adaptive convergence in morphology for which both these criteria have been met, but examples from animal behaviour have rarely been tested as rigorously. Adaptive convergence should be common in behaviour, especially behaviour used for communication, because the environment often shapes the evolution of signal design. In this study we report on the origins of a shared design of a territorial display among Anolis species of lizards from two island radiations in the Caribbean. These lizards perform an elaborate display that consists of a complex series of headbobs and dewlap extensions. The way in which these movements are incorporated into displays is generally species specific, but species on the islands of Jamaica and Puerto Rico also share fundamental aspects in display design, resulting in two general display types. We confirm these display types are convergent (the consequence of independent evolution on each island) and provide evidence that the convergence was driven by selection for enhanced signal efficiency. Our study shows how adaptation to common environmental variables can drive the evolution of adaptive, convergent signals in distantly related species

Data from: Adaptation and plasticity of animal communication in fluctuating environments

Adaptations that facilitate the reception of long-range signals under challenging conditions are expected to generate signal diversity when species communicate in different habitats. While we have a general understanding of how individual communicating animals cope with conditions influencing signal detection, the extent to which plasticity and evolutionary changes in signal characteristics contribute to interspecific differences in signaling behavior is unclear. We quantified the visual displays of free-living lizards and environmental variables known to influence display detection for multiple species from two separate island radiations. We found evidence of both adaptive evolution and adaptive plasticity in display characteristics as a function of environmental conditions, but plasticity accounted for most of the observed differences in display behavior across species. At the same time, prominent differences between the two island radiations existed in aspects of signaling behavior, unrelated to the environment. Past evolutionary events have therefore played an important role in shaping the way lizards adjust their signals to challenges in present-day environments. In addition to showing how plasticity contributes to interspecific differences in communication signals, our findings suggest the vagaries of evolution can in itself lead to signal variation between species