Targeted mutagenesis in a human-parasitic nematode.

Parasitic nematodes infect over 1 billion people worldwide and cause some of the most common neglected tropical diseases. Despite their prevalence, our understanding of the biology of parasitic nematodes has been limited by the lack of tools for genetic intervention. In particular, it has not yet been possible to generate targeted gene disruptions and mutant phenotypes in any parasitic nematode. Here, we report the development of a method for introducing CRISPR-Cas9-mediated gene disruptions in the human-parasitic threadworm Strongyloides stercoralis. We disrupted the S. stercoralis twitchin gene unc-22, resulting in nematodes with severe motility defects. Ss-unc-22 mutations were resolved by homology-directed repair when a repair template was provided. Omission of a repair template resulted in deletions at the target locus. Ss-unc-22 mutations were heritable; we passed Ss-unc-22 mutants through a host and successfully recovered mutant progeny. Using a similar approach, we also disrupted the unc-22 gene of the rat-parasitic nematode Strongyloides ratti. Our results demonstrate the applicability of CRISPR-Cas9 to parasitic nematodes, and thereby enable future studies of gene function in these medically relevant but previously genetically intractable parasites

Microfluidics for Hydrodynamics Investigations of Sand Dollar Larvae

The life cycle of most marine invertebrates includes a planktonic larval stage before metamorphosis to bottom-dwelling adulthood. During larval stage, ciliary-mediated activity enables feeding (capture unicellular algae) and transport of materials (oxygen) required for the larva's growth, development, and successful metamorphosis. Investigating the underlying hydrodynamics of these behaviors is valuable for addressing fundamental biological questions (e.g., phenotypic plasticity) and advancing engineering applications. In this work, we combined microfluidics and fluorescence microscopy as a miniaturized PIV (mPIV) to study ciliary-medicated hydrodynamics during suspension feeding in sand dollar larvae (Dendraster excentricus). First, we confirmed the approach's feasibility by examining the underlying hydrodynamics (vortex patterns) for low- and high-fed larvae. Next, ciliary hydrodynamics were tracked from 11 days post-fertilization (DPF) to 20 DPF for 21 low-fed larvae. Microfluidics enabled the examination of baseline activities (without external flow) and behaviors in the presence of environmental cues (external flow). A library of qualitative vortex patterns and quantitative hydrodynamics was generated and shared as a stand alone repository. Results from mPIV (velocities) were used to examine the role of ciliary activity in transporting materials (oxygen). Given the laminar flow and the viscosity-dominated environments surrounding the larvae, overcoming the diffusive boundary layer is critical for the organism's survival. Peclet number analysis for oxygen transport suggested that ciliary velocities help overcome the diffusion dominated transport (max Pe numbers between 30-60). Microfluidics serving as mPIV provided a scalable and accessible approach for investigating the ciliary hydrodynamics of marine organisms.Comment: 21 pages and 11 figures (videos not included

The SAMI Galaxy Survey: the intrinsic shape of kinematically selected galaxies

Using the stellar kinematic maps and ancillary imaging data from the Sydney AAO Multi Integral field (SAMI) Galaxy Survey, the intrinsic shape of kinematically-selected samples of galaxies is inferred. We implement an efficient and optimised algorithm to fit the intrinsic shape of galaxies using an established method to simultaneously invert the distributions of apparent ellipticities and kinematic misalignments. The algorithm output compares favourably with previous studies of the intrinsic shape of galaxies based on imaging alone and our re-analysis of the ATLAS3D data. Our results indicate that most galaxies are oblate axisymmetric. We show empirically that the intrinsic shape of galaxies varies as a function of their rotational support as measured by the "spin" parameter proxy Lambda_Re. In particular, low spin systems have a higher occurrence of triaxiality, while high spin systems are more intrinsically flattened and axisymmetric. The intrinsic shape of galaxies is linked to their formation and merger histories. Galaxies with high spin values have intrinsic shapes consistent with dissipational minor mergers, while the intrinsic shape of low-spin systems is consistent with dissipationless multi-merger assembly histories. This range in assembly histories inferred from intrinsic shapes is broadly consistent with expectations from cosmological simulations.Comment: 15 pages, 11 figures, MNRAS in prin

The SAMI Galaxy Survey: Asymmetry in Gas Kinematics and its links to Stellar Mass and Star Formation

We study the properties of kinematically disturbed galaxies in the SAMI Galaxy Survey using a quantitative criterion, based on kinemetry (Krajnovic et al.). The approach, similar to the application of kinemetry by Shapiro et al. uses ionised gas kinematics, probed by H{\alpha} emission. By this method 23+/-7% of our 360-galaxy sub-sample of the SAMI Galaxy Survey are kinematically asymmetric. Visual classifications agree with our kinemetric results for 90% of asymmetric and 95% of normal galaxies. We find stellar mass and kinematic asymmetry are inversely correlated and that kinematic asymmetry is both more frequent and stronger in low-mass galaxies. This builds on previous studies that found high fractions of kinematic asymmetry in low mass galaxies using a variety of different methods. Concentration of star forma- tion and kinematic disturbance are found to be correlated, confirming results found in previous work. This effect is stronger for high mass galaxies (log(M*) > 10) and indicates that kinematic disturbance is linked to centrally concentrated star formation. Comparison of the inner (within 0.5Re) and outer H{\alpha} equivalent widths of asymmetric and normal galaxies shows a small but significant increase in inner equivalent width for asymmetric galaxies.Comment: 29 pages, 21 figure

The Sydney-AAO Multi-object Integral field spectrograph (SAMI)

We demonstrate a novel technology that combines the power of the multi-object spectrograph with the spatial multiplex advantage of an integral field spectrograph (IFS). The Sydney-AAO Multi-object IFS (SAMI) is a prototype wide-field system at the Anglo-Australian Telescope (AAT) that allows 13 imaging fibre bundles ("hexabundles") to be deployed over a 1-degree diameter field of view. Each hexabundle comprises 61 lightly-fused multimode fibres with reduced cladding and yields a 75 percent filling factor. Each fibre core diameter subtends 1.6 arcseconds on the sky and each hexabundle has a field of view of 15 arcseconds diameter. The fibres are fed to the flexible AAOmega double-beam spectrograph, which can be used at a range of spectral resolutions (R=lambda/delta(lambda) ~ 1700-13000) over the optical spectrum (3700-9500A). We present the first spectroscopic results obtained with SAMI for a sample of galaxies at z~0.05. We discuss the prospects of implementing hexabundles at a much higher multiplex over wider fields of view in order to carry out spatially--resolved spectroscopic surveys of 10^4 to 10^5 galaxies.Comment: 24 pages, 16 figures. Accepted by MNRA

Measuring cosmic density of neutral hydrogen via stacking the DINGO-VLA data

We use the 21-cm emission-line data from the Deep Investigation of Neutral Gas Origin-Very Large Array (DINGO-VLA) project to study the atomic hydrogen gas H I of the Universe at redshifts z \u3c 0.1. Results are obtained using a stacking analysis, combining the H I signals from 3622 galaxies extracted from 267 VLA pointings in the G09 field of the Galaxy and Mass Assembly Survey (GAMA). Rather than using a traditional one-dimensional spectral stacking method, a three-dimensional cubelet stacking method is used to enable deconvolution and the accurate recovery of average galaxy fluxes from this high-resolution interferometric data set. By probing down to galactic scales, this experiment also overcomes confusion corrections that have been necessary to include in previous single-dish studies. After stacking and deconvolution, we obtain a 30σ H I mass measurement from the stacked spectrum, indicating an average H I mass of MHI=(1.67±0.18)×109 M⊙ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eMHI=(1.67±0.18)×109 M⊙MHI=(1.67±0.18)×109 M⊙⁠. The corresponding cosmic density of neutral atomic hydrogen is ΩHI=(0.38±0.04)×10−3 role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eΩHI=(0.38±0.04)×10−3ΩHI=(0.38±0.04)×10−3 at redshift of z = 0.051. These values are in good agreement with earlier results, implying there is no significant evolution of ΩHI role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; border: 0px; font-variant: inherit; font-stretch: inherit; line-height: normal; font-family: inherit; vertical-align: baseline; display: inline; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative; \u3eΩHIΩHI at lower redshifts

Meta-Analysis of Studies Analyzing the Role of Human Papillomavirus in the Development of Bladder Carcinoma

Journal Article;PURPOSE We aimed to ascertain the degree of association between bladder cancer and human papillomavirus (HPV) infection. MATERIALS AND METHODS We performed a meta-analysis of observational studies with cases and controls with publication dates up to January 2011. The PubMed electronic database was searched by using the key words "bladder cancer and virus." Twenty-one articles were selected that met the required methodological criteria. We implemented an internal quality control system to verify the selected search method. We analyzed the pooled effect of all the studies and also analyzed the techniques used as follows: 1) studies with DNA-based techniques, among which we found studies with polymerase chain reaction (PCR)-based techniques and 2) studies with non-PCR-based techniques, and studies with non-DNA-based techniques. RESULTS Taking into account the 21 studies that were included in the meta-analysis, we obtained a heterogeneity chi-squared value of Q(exp)=26.45 (p=0.383). The pooled odds ratio (OR) was 2.13 (95% confidence interval [CI], 1.54 to 2.95), which points to a significant effect between HPV and bladder cancer. Twenty studies assessed the presence of DNA. The overall effect showed a significant relationship between virus presence and bladder cancer, with a pooled OR of 2.19 (95% CI, 1.40 to 3.43). Of the other six studies, four examined the virus's capsid antigen and two detected antibodies in serum by Western blot. The estimated pooled OR in this group was 2.11 (95% CI, 1.27 to 3.51), which confirmed the relationship between the presence of virus and cancer. CONCLUSIONS The pooled OR value showed a moderate relationship between viral infection and bladder tumors.Ye

Measurements of Six-Body Hadronic Decays of the D^0 Charmed Meson

Using data collected by the FOCUS experiment at Fermilab, we report the discovery of the decay modes D^0 --> K- pi+ pi+ pi+ pi- pi- and D^0 --> pi+ pi+ pi+ pi- pi- pi-. With a sample of 48 +/- 10 reconstructed D^0 --> K- pi+ pi+ pi+ pi- pi- decays and 149 +/- 17 reconstructed D^0 --> pi+ pi+ pi+ pi- pi- pi- decays, we measure the following relative branching ratios: ${\Gamma (D^0 \to K^- \pi^+ \pi^+ \pi^+ \pi^- \pi^-) / \Gamma (D^0 \to K^- \pi^+ \pi^+ \pi^-)} = (2.70 \pm 0.58 \pm 0.38) \times 10^{-3}$ ${\Gamma (D^0 \to \pi^+ \pi^+ \pi^+ \pi^- \pi^- \pi^-) / \Gamma (D^0 \to K^- \pi^+ \pi^+ \pi^-)} = (5.23 \pm 0.59 \pm 1.35) \times 10^{-3}$ ${\Gamma (D^0 \to \pi^+ \pi^+ \pi^+ \pi^- \pi^- \pi^-) / \Gamma (D^0 \to K^- \pi^+ \pi^+ \pi^+ \pi^- \pi^-)} = 1.93 \pm 0.47 \pm 0.48$ The first errors are statistical and the second are systematic. The branching fraction of the Cabibbo suppressed six-body decay mode is measured to be a factor of two higher than the branching fraction of the Cabibbo favored six-body decay mode.Comment: To be submitted to Phys. Lett.

Measurement of the Ratio of the Vector to Pseudoscalar Charm Semileptonic Decay Rate \Gamma(D+ > ANTI-K*0 mu+ nu)/\Gamma(D+ > ANTI-K0 mu+ nu)

Using a high statistics sample of photo-produced charm particles from the FOCUS experiment at Fermilab, we report on the measurement of the ratio of semileptonic rates \Gamma(D+ > ANTI-K pi mu+ nu)/\Gamma(D+ > ANTI-K0 mu+ nu)= 0.625 +/- 0.045 +/- 0.034. Allowing for the K pi S-wave interference measured previously by FOCUS, we extract the vector to pseudoscalar ratio \Gamma(D+ > ANTI-K*0 mu+ nu)/\Gamma(D+ > ANTI-K0 mu+ nu)= 0.594 +/- 0.043 +/- 0.033 and the ratio \Gamma(D+ > ANTI-K0 mu+ nu)/\Gamma(D+ > K- pi+ pi+)= 1.019 +/- 0.076 +/- 0.065. Our results show a lower ratio for \Gamma(D > K* \ell nu})/\Gamma(D > K \ell nu) than has been reported recently and indicate the current world average branching fractions for the decays D+ >ANTI-K0(mu+, e+) nu are low. Using the PDG world average for B(D+ > K- pi+ pi+) we extract B(D+ > ANIT-K0 mu+ nu)=(9.27 +/- 0.69 +/- 0.59 +/- 0.61)%.Comment: 15 pages, 1 figur