The Trypanosome Rab-Related Proteins RabX1 and RabX2 Play No Role in IntraCellular Trafficking but May Be Involved in Fly Infectivity

BACKGROUND: Rab GTPases constitute the largest subgroup of the Ras superfamily and are primarily involved in vesicle targeting. The full extent of Rab family function is unexplored. Several divergent Rab-like proteins are known but few have been characterized. In Trypanosoma brucei there are sixteen Rab genes, but RabX1, RabX2 and RabX3 are divergent within canonical sequence regions. Where known, trypanosome Rab functions are broadly conserved when orthologous relationships may be robustly established, but specific functions for RabX1, X2 and X3 have yet to be determined. RabX1 and RabX2 originated via tandem duplication and subcellular localization places RabX1 at the endoplasmic reticulum, while RabX2 is at the Golgi complex, suggesting distinct functions. We wished to determine whether RabX1 and RabX2 are involved in vesicle transport or other cellular processes. METHODOLOGY/PRINCIPAL FINDINGS: Using comparative genomics we find that RabX1 and RabX2 are restricted to trypanosomatids. Gene knockout indicates that RabX1 and RabX2 are non-essential. Simultaneous RNAi knockdown of both RabX1 and RabX2, while partial, was also non-lethal and may suggest non-redundant function, consistent with the distinct locations of the proteins. Analysis of the knockout cell lines unexpectedly failed to uncover a defect in exocytosis, endocytosis or in the morphology or location of multiple markers for the endomembrane system, suggesting that neither RabX1 nor RabX2 has a major role in intracellular transport. However, it was apparent that RabX1 and RabX2 knockout cells displayed somewhat enhanced survival within flies. CONCLUSIONS/SIGNIFICANCE: RabX1 and RabX2, two members of the trypanosome Rab subfamily, were shown to have no major detectable role in intracellular transport, despite the localization of each gene product to highly specific endomembrane compartments. These data extend the functional scope of Rab proteins in trypanosomes to include non-canonical roles in differentiation-associated processes in protozoa

Deformation and Depinning of Superconducting Vortices from Artificial Defects: A Ginzburg-Landau Study

Using Ginzburg-Landau theory, we have performed detailed studies of vortices in the presence of artificial defect arrays, for a thin film geometry. We show that when a vortex approaches the vicinity of a defect, an abrupt transition occurs in which the vortex core develops a ``string'' extending to the defect boundary, while simultaneously the supercurrents and associated magnetic flux spread out and engulf the defect. Current induced depinning of vortices is shown to be dominated by the core string distortion in typical experimental situations. Experimental consequences of this unusual depinning behavior are discussed.Comment: 10 pages,9 figure

Biogeographic ranges do not support niche theory in radiating Canary Island plant clades

Aim: Ecological niche concepts, in combination with biogeographic history, underlie our understanding of biogeographic ranges. Two pillars of this understanding are competitive displacement and niche conservatism. The competitive displacement hypothesis holds that very similar (e.g. closely related) co-occurring species should diverge, forced apart by competition. In contrast, according to the niche conservatism hypothesis, closely related species should have similar niches. If these are fundamental structuring forces, they should be detectable when comparing the climatic niches of endemic species in radiating clades in oceanic archipelagos, where closely related species exist in both sympatry and allopatry and the species' entire ranges are known. We took advantage of this natural experimental system to test whether the climatic niche relationships predicted by the two hypotheses are found. Location: Canary Islands. Methods: For the plant clades Aeonium, Argyranthemum, Descurainia, Echium, Lotus and Sonchus, separately, we tested relationships between phylogenetic distance and climatic niche differentiation (in temperature, precipitation and their combination), using a high-resolution dataset. We also tested for niche conservatism using Blomberg's K and Pagel's λ. We compared climatic niche differentiation between pairs of species existing in sympatry with that for pairs of species in allopatry. For each comparison, we focused on the climatic niche space available to both species. Results: The relationships between phylogenetic distance and climatic niche differentiation were mostly non-significant; some weak but significant positive relationships were found, mainly for Aeonium and Sonchus. Where differences between sympatry and allopatry were found, niche differentiation tended to be greater in allopatry. Main conclusions: The expectations from niche conservatism were frequently not met; instead our results suggest considerable climatic niche lability. All significant differences in climatic niche differentiation were opposite to the predictions from competitive displacement. These forces may be less important in structuring biogeographic ranges than is commonly thought, at least on islands

Crackling Noise, Power Spectra and Disorder Induced Critical Scaling

Crackling noise is observed in many disordered non-equilibrium systems in response to slowly changing external conditions. Examples range from Barkhausen noise in magnets to acoustic emission in martensites to earthquakes. Using the non-equilibrium random field Ising model, we derive universal scaling predictions for the dependence of the associated power spectra on the disorder and field sweep rate, near an underlying disorder-induced non-equilibrium critical point. Our theory applies to certain systems in which the crackling noise results from avalanche-like response to a (slowly) increasing external driving force, and is characterized by a broad power law scaling regime of the power spectra. We compute the critical exponents and discuss the relevance of the results to experiments.Comment: 27 Latex Pages, 14 eps figure

PACIFIC-R: First real-world study of patients with unresectable, stage III NSCLC treated with durvalumab after chemoradiotherapy

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NUP-1 Is a Large Coiled-Coil Nucleoskeletal Protein in Trypanosomes with Lamin-Like Functions

NUP1, the first example of a nuclear lamin analog in nonmetazoans, performs roles similar to those of lamins in maintaining the structure and organization of the nucleus in Trypanosoma brucei

On the Testing of Seismicity Models

Recently a likelihood-based methodology has been developed by the Collaboratory for the Study of Earthquake Predictability (CSEP) with a view to testing and ranking seismicity models. We analyze this approach from the standpoint of possible applications to hazard analysis. We arrive at the conclusion that model testing can be made more efficient by focusing on some integral characteristics of the seismicity distribution. This is achieved either in the likelihood framework but with economical and physically reasonable coarsening of the phase space or by choosing a suitable measure of closeness between empirical and model seismicity rate in this space.Comment: To appear at Acta Geophysic

Atomic X-ray Spectroscopy of Accreting Black Holes

Current astrophysical research suggests that the most persistently luminous objects in the Universe are powered by the flow of matter through accretion disks onto black holes. Accretion disk systems are observed to emit copious radiation across the electromagnetic spectrum, each energy band providing access to rather distinct regimes of physical conditions and geometric scale. X-ray emission probes the innermost regions of the accretion disk, where relativistic effects prevail. While this has been known for decades, it also has been acknowledged that inferring physical conditions in the relativistic regime from the behavior of the X-ray continuum is problematic and not satisfactorily constraining. With the discovery in the 1990s of iron X-ray lines bearing signatures of relativistic distortion came the hope that such emission would more firmly constrain models of disk accretion near black holes, as well as provide observational criteria by which to test general relativity in the strong field limit. Here we provide an introduction to this phenomenon. While the presentation is intended to be primarily tutorial in nature, we aim also to acquaint the reader with trends in current research. To achieve these ends, we present the basic applications of general relativity that pertain to X-ray spectroscopic observations of black hole accretion disk systems, focusing on the Schwarzschild and Kerr solutions to the Einstein field equations. To this we add treatments of the fundamental concepts associated with the theoretical and modeling aspects of accretion disks, as well as relevant topics from observational and theoretical X-ray spectroscopy.Comment: 63 pages, 21 figures, Einstein Centennial Review Article, Canadian Journal of Physics, in pres

O-Health-Edu: a vision for oral health professional education in Europe

This consensus paper reports on the process of developing a renewed vision for Oral Health Professional (OHP) education across Europe, and forms part of a larger EU-funded collaborative Erasmus+ project, “O-Health-Edu.” The vision aligns with the World Health Organisation milestones (2016) and resolutions (2021), and EU4Health programme (2020) objectives - and projects 20 years into the future, to 2040. This longitudinal vision takes a multi-stakeholder perspective to deliver OHP education that acts in the best interests of both students and patients, and sits within the context of a wider strategy for general health. Included, it is an infographic to help communicate the vision to various stakeholders of OHP education

Active Galactic Nuclei at the Crossroads of Astrophysics

Over the last five decades, AGN studies have produced a number of spectacular examples of synergies and multifaceted approaches in astrophysics. The field of AGN research now spans the entire spectral range and covers more than twelve orders of magnitude in the spatial and temporal domains. The next generation of astrophysical facilities will open up new possibilities for AGN studies, especially in the areas of high-resolution and high-fidelity imaging and spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These studies will address in detail a number of critical issues in AGN research such as processes in the immediate vicinity of supermassive black holes, physical conditions of broad-line and narrow-line regions, formation and evolution of accretion disks and relativistic outflows, and the connection between nuclear activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical Symposia Serie