The X-linked Retinitis Pigmentosa protein RP2 facilitates traffic of cilia target proteins

Photoreceptors are specialized ciliated sensory neurons and aberrant traffic of proteins to the outer segment causes photoreceptor cell death. RP2 is a GTPase activating protein (GAP) for the small GTPase Arl3 and both proteins facilitate protein trafficking to primary cilia. We used GST-RP2 pull down from retinal lysates and identified the Gβ subunit of transducin (Gβ1) as a novel RP2 interacting protein. RP2 competes with Gγ1 for Gβ1 binding and does not interact with the Gβ:Gγ heterodimer. In SK-N-SH cells, overexpression of Gβ1 resulted in the cytoplasmic accumulation of the protein, whereas co-expression of Gβ1 with either RP2 or Gγ1 restored membrane association of Gβ1. Depletion of RP2 in ARPE19 cells by siRNA resulted in a shift of Gβ1 from the membrane to the cytosol, confirming that RP2 facilitates the membrane association of Gβ1. This shift in Gβ1 localization was rescued by Gγ1 overexpression. Membrane targeting of Gβ1 required RP2 N-terminal myristoylation and occurs via the co-factor C (TBCC) homology domain. The interaction was disrupted by the pathogenic RP2 mutation R118H, which blocks Arl3 GAP activity. Arl3-Q71L competed with Gβ1 for RP2 binding suggesting that RP2 GAP activity on Arl3 would release Gβ1. RP2 stimulated the association of Gβ1 with Rab11, an important GTPase for post-Golgi vesicle trafficking of photoreceptor proteins. Collectively our data support a role for RP2 in facilitating membrane association and traffic of Gβ1. Combined with other recent evidence, this suggests that RP2 may co-operate with Arl3 and its effectors in cilia associated trafficking of G proteins

A neuronal network of mitochondrial dynamics regulates metastasis.

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater membrane dynamics and heightened cell invasion. Therefore, a SNPH network regulates metastatic competence and may provide a therapeutic target in cancer

Resonant Magnetic Vortices

By using the complex angular momentum method, we provide a semiclassical analysis of electron scattering by a magnetic vortex of Aharonov-Bohm-type. Regge poles of the $S$-matrix are associated with surface waves orbiting around the vortex and supported by a magnetic field discontinuity. Rapid variations of sharp characteristic shapes can be observed on scattering cross sections. They correspond to quasibound states which are Breit-Wigner-type resonances associated with surface waves and which can be considered as quantum analogues of acoustic whispering-gallery modes. Such a resonant magnetic vortex could provide a new kind of artificial atom while the semiclassical approach developed here could be profitably extended in various areas of the physics of vortices.Comment: 6 pages, 7 figure

A comparative assessment of the economic benefits from shale gas extraction in the Karoo, South Africa

It has been said that the development of a shale gas industry could be a ‘game changer’ for South Africa. Proponents of shale gas tend to emphasise the benefits, whilst opponents emphasise the environmental costs. This paper is an attempt to inform the policy debate by highlighting both the potential economic benefits and environmental costs. To date, the Econometrix report (published in 2012) provides the only estimate of the economic impacts that may emanate from developing the Karoo’s shale gas. The report uses a Keynesian multiplier model to estimate the impacts. The analysis performed in this paper estimates the economic impacts using a Computable General Equilibrium (CGE) modelling approach, and the results are compared to the findings of the Econometrix report. In doing so, this paper provides an expanded view of the potential economic impact. Accordingly, this paper provides a number of findings on the estimated economic impact of shale gas extraction – based on the application of an economy-wide impact modelling methodology – which should be of interest to both opponents and proponents of the shale gas industry. By including all possible results, such as a boost in public sector jobs and an analysis of the impact on consumer prices and jobs in other sectors, this paper expands the current understanding of the likely impact of shale gas extraction in the Karoo of South Africa.Key words: shale gas extraction, economy-wide modelling, CGE, exhaustible resources

The Hall Effect and the Specific Resistance of Thin Silver Films

The Hall Effect of ordinary metals may be expressed by the equation E=HIa/e where E = the Hall Effect, I= the primary current, e= the thickness of the conductor and a= a constant whose value in silver lies between.00083 to.00090. In the present investigation the above equation was found to hold in thin silver films, and that has a value of.00084

The Dependence of the Resistance of Silver Films upon the Method of Deposition

Most observers investigating the specific resistance in thin metallic films have found that it decreases rapidly with time. In the present investigation Brashear\u27s process of obtaining silver films was followed

Harvard Personal Genome Project: lessons from participatory public research

Background: Since its initiation in 2005, the Harvard Personal Genome Project has enrolled thousands of volunteers interested in publicly sharing their genome, health and trait data. Because these data are highly identifiable, we use an ‘open consent’ framework that purposefully excludes promises about privacy and requires participants to demonstrate comprehension prior to enrollment. Discussion Our model of non-anonymous, public genomes has led us to a highly participatory model of researcher-participant communication and interaction. The participants, who are highly committed volunteers, self-pursue and donate research-relevant datasets, and are actively engaged in conversations with both our staff and other Personal Genome Project participants. We have quantitatively assessed these communications and donations, and report our experiences with returning research-grade whole genome data to participants. We also observe some of the community growth and discussion that has occurred related to our project. Summary We find that public non-anonymous data is valuable and leads to a participatory research model, which we encourage others to consider. The implementation of this model is greatly facilitated by web-based tools and methods and participant education. Project results are long-term proactive participant involvement and the growth of a community that benefits both researchers and participants

An asymptotic form of the reciprocity theorem with applications in x-ray scattering

The emission of electromagnetic waves from a source within or near a non-trivial medium (with or without boundaries, crystalline or amorphous, with inhomogeneities, absorption and so on) is sometimes studied using the reciprocity principle. This is a variation of the method of Green's functions. If one is only interested in the asymptotic radiation fields the generality of these methods may actually be a shortcoming: obtaining expressions valid for the uninteresting near fields is not just a wasted effort but may be prohibitively difficult. In this work we obtain a modified form the reciprocity principle which gives the asymptotic radiation field directly. The method may be used to obtain the radiation from a prescribed source, and also to study scattering problems. To illustrate the power of the method we study a few pedagogical examples and then, as a more challenging application we tackle two related problems. We calculate the specular reflection of x rays by a rough surface and by a smoothly graded surface taking polarization effects into account. In conventional treatments of reflection x rays are treated as scalar waves, polarization effects are neglected. This is a good approximation at grazing incidence but becomes increasingly questionable for soft x rays and UV at higher incidence angles. PACs: 61.10.Dp, 61.10.Kw, 03.50.DeComment: 19 pages, 4 figure

Improved Measurement of the Positive Muon Lifetime and Determination of the Fermi Constant

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau_mu = 2.197013(24) us, is in excellent agreement with the previous world average. The new world average tau_mu = 2.197019(21) us determines the Fermi constant G_F = 1.166371(6) x 10^-5 GeV^-2 (5 ppm). Additionally, the precision measurement of the positive muon lifetime is needed to determine the nucleon pseudoscalar coupling g_P.Comment: As published version (PRL, July 2007

A Computational Channel Model for Magnetic Induction-Based Subsurface Applications

There are many underground applications based on magnetic fields generated by an oscillating magnetic source. For them, a magnetic dipole in a three-layered region with upper semi-infinite air layer can be a convenient idealization used for their planning, development, and operation. Solutions are in the form of the well-known Sommerfeld integral expressions that can be evaluated by numerical methods. A set of field expressions to be numerically evaluated by an efficient algorithm are not collected comprehensively yet, or at least in a directly usable form. In this paper, the explicit magnetic field solutions for the vertical magnetic dipole and the horizontal magnetic dipole for a general source-observer location are derived from the Hertz vector. They can be properly combined to model the problem of a tilted magnetic dipole source for horizontally or inclined stratified media. As a result, a complete set of integral equations of the Sommerfeld type valid from the near zone to the far zone are formulated. A method for numerical evaluation of the field expressions for high accurate computations is described. The numerical results are validated using the finite element method for all the possible source-receiver configurations and three well-spanned frequencies of typical subsurface applications. Both numerical solutions agree according to the normalized root-mean-square error-based fit metric. Numerical results for two cases of study are presented to see its usefulness for subsurface applications. A MATLAB implementation of the mathematical description outlined in this paper and the proposed evaluation method is freely available for download