A Genome Assembly-Integrated Dog 1 Mb BAC Microarray: A Cytogenetic Resource for Canine Cancer Studies and Comparative Genomic Analysis

Molecular cytogenetic studies have been instrumental in defining the nature of numerical and structural chromosome changes in human cancers, but their significance remains to be fully understood. The emergence of high quality genome assemblies for several model organisms provides exciting opportunities to develop novel genome-integrated molecular cytogenetic resources that now permit a comparative approach to evaluating the relevance of tumor-associated chromosome aberrations, both within and between species. We have used the dog genome sequence assembly to identify a framework panel of 2,097 bacterial artificial chromosome (BAC) clones, selected at intervals of approximately one megabase. Each clone has been evaluated by multicolor fluorescence in situ hybridization (FISH) to confirm its unique cytogenetic location in concordance with its reported position in the genome assembly, providing new information on the organization of the dog genome. This panel of BAC clones also represents a powerful cytogenetic resource with numerous potential applications. We have used the clone set to develop a genome-wide microarray for comparative genomic hybridization (aCGH) analysis, and demonstrate its application in detection of tumor-associated DNA copy number aberrations (CNAs) including single copy deletions and amplifications, regional aneuploidy and whole chromosome aneuploidy. We also show how individual clones selected from the BAC panel can be used as FISH probes in direct evaluation of tumor karyotypes, to verify and explore CNAs detected using aCGH analysis. This cytogenetically validated, genome integrated BAC clone panel has enormous potential for aiding gene discovery through a comparative approach to molecular oncology.Organismic and Evolutionary Biolog

Effectiveness of global optimisation and direct kinematics in predicting surgical outcome in children with cerebral palsy

Multibody optimisation approaches have not seen much use in routine clinical applications despite evidence of improvements in modelling through a reduction in soft tissue artifacts compared to the standard gait analysis technique of direct kinematics. To inform clinical use, this study investigated the consistency with which both approaches predicted post-surgical outcomes, using changes in Gait Profile Score (GPS) when compared to a clinical assessment of outcome that did not include the 3D gait data. Retrospective three-dimensional motion capture data were utilised from 34 typically developing children and 26 children with cerebral palsy who underwent femoral derotation osteotomies as part of Single Event Multi-Level Surgeries. Results indicated that while, as expected, the GPS estimated from the two methods were numerically different, they were strongly correlated (Spearman’s ρ = 0.93), and no significant differences were observed between their estimations of change in GPS after surgery. The two scores equivalently classified a worsening or improvement in the gait quality in 93% of the cases. When compared with the clinical classification of responders versus non-responders to the intervention, an equivalent performance was found for the two approaches, with 27/41 and 28/41 cases in agreement with the clinical judgement for multibody optimisation and direct kinematics, respectively. With this equivalent performance to the direct kinematics approach and the benefit of being less sensitive to skin artefact and allowing additional analysis such as estimation of musculotendon lengths and joint contact forces, multibody optimisation has the potential to improve the clinical decision-making process in children with cerebral palsy

Impact of early exposure to a cafeteria diet on prefrontal cortex monoamines and novel object recognition in adolescent rats

© 2019 Elsevier B.V. The prefrontal cortex (PFC) undergoes protracted postnatal development such that its structure and behavioural function may be profoundly altered by environmental factors. Here we investigate the effect of lactational dietary manipulations on novel object recognition (NOR) learning and PFC monoamine neurotransmitter metabolism in early adolescent rats. To this end, Wistar rat dams were fed a high caloric cafeteria diet (CD) during lactation and resultant 24–26 day old offspring exposed to NOR testing and simultaneous PFC dopamine and serotonin metabolism measurement. In the second NOR choice trial where one familiar and one novel object were presented controls explored the novel preferentially to the familiar object both after a 5 min (P < 0.001) or 30 min (P < 0.05) inter-trial intervals (ITI). By contrast, offspring from dams fed on lactational CD failed to show any significant preference for the novel object at either time point. Compared with chow fed controls, their average exploration ratio of the novel object was lower after the 5 min ITI (P < 0.05). Following a 60 min ITI, neither CD nor control offspring showed a preference for the novel object. PFC dopamine metabolism was significantly reduced in the CD group (P < 0.001), whereas serotonin metabolism was increased (P < 0.001). These results suggest that an obesogenic lactational diet can have a detrimental impact on cognition in adolescent offspring associated with aberrant PFC serotonin and dopamine metabolism

Turbulent Control of the Star Formation Efficiency

Supersonic turbulence plays a dual role in molecular clouds: On one hand, it contributes to the global support of the clouds, while on the other it promotes the formation of small-scale density fluctuations, identifiable with clumps and cores. Within these, the local Jeans length \Ljc is reduced, and collapse ensues if \Ljc becomes smaller than the clump size and the magnetic support is insufficient (i.e., the core is ``magnetically supercritical''); otherwise, the clumps do not collapse and are expected to re-expand and disperse on a few free-fall times. This case may correspond to a fraction of the observed starless cores. The star formation efficiency (SFE, the fraction of the cloud's mass that ends up in collapsed objects) is smaller than unity because the mass contained in collapsing clumps is smaller than the total cloud mass. However, in non-magnetic numerical simulations with realistic Mach numbers and turbulence driving scales, the SFE is still larger than observational estimates. The presence of a magnetic field, even if magnetically supercritical, appears to further reduce the SFE, but by reducing the probability of core formation rather than by delaying the collapse of individual cores, as was formerly thought. Precise quantification of these effects as a function of global cloud parameters is still needed.Comment: Invited review for the conference "IMF@50: the Initial Mass Function 50 Years Later", to be published by Kluwer Academic Publishers, eds. E. Corbelli, F. Palla, and H. Zinnecke

Effect of a liquid Phase on Superplasticity of 2-moI%-Y 2 0 3 -StabiIlzed Tetragonal Zirconla Polycrystals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66013/1/j.1151-2916.1990.tb09806.x.pd

General Relativistic MHD Jets

Magnetic fields connecting the immediate environs of rotating black holes to large distances appear to be the most promising mechanism for launching relativistic jets, an idea first developed by Blandford and Znajek in the mid-1970s. To enable an understanding of this process, we provide a brief introduction to dynamics and electromagnetism in the spacetime near black holes. We then present a brief summary of the classical Blandford-Znajek mechanism and its conceptual foundations. Recently, it has become possible to study these effects in much greater detail using numerical simulation. After discussing which aspects of the problem can be handled well by numerical means and which aspects remain beyond the grasp of such methods, we summarize their results so far. Simulations have confirmed that processes akin to the classical Blandford-Znajek mechanism can launch powerful electromagnetically-dominated jets, and have shown how the jet luminosity can be related to black hole spin and concurrent accretion rate. However, they have also shown that the luminosity and variability of jets can depend strongly on magnetic field geometry. We close with a discussion of several important open questions.Comment: 21 pages, 2 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009

Magnetoluminescence

Pulsar Wind Nebulae, Blazars, Gamma Ray Bursts and Magnetars all contain regions where the electromagnetic energy density greatly exceeds the plasma energy density. These sources exhibit dramatic flaring activity where the electromagnetic energy distributed over large volumes, appears to be converted efficiently into high energy particles and gamma-rays. We call this general process magnetoluminescence. Global requirements on the underlying, extreme particle acceleration processes are described and the likely importance of relativistic beaming in enhancing the observed radiation from a flare is emphasized. Recent research on fluid descriptions of unstable electromagnetic configurations are summarized and progress on the associated kinetic simulations that are needed to account for the acceleration and radiation is discussed. Future observational, simulation and experimental opportunities are briefly summarized.Comment: To appear in "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release" of the Space Science Reviews serie

Revealing uncertainty in the status of biodiversity change

Biodiversity faces unprecedented threats from rapid global change1. Signals of biodiversity change come from time-series abundance datasets for thousands of species over large geographic and temporal scales. Analyses of these biodiversity datasets have pointed to varied trends in abundance, including increases and decreases. However, these analyses have not fully accounted for spatial, temporal and phylogenetic structures in the data. Here, using a new statistical framework, we show across ten high-profile biodiversity datasets2,3,4,5,6,7,8,9,10,11 that increases and decreases under existing approaches vanish once spatial, temporal and phylogenetic structures are accounted for. This is a consequence of existing approaches severely underestimating trend uncertainty and sometimes misestimating the trend direction. Under our revised average abundance trends that appropriately recognize uncertainty, we failed to observe a single increasing or decreasing trend at 95% credible intervals in our ten datasets. This emphasizes how little is known about biodiversity change across vast spatial and taxonomic scales. Despite this uncertainty at vast scales, we reveal improved local-scale prediction accuracy by accounting for spatial, temporal and phylogenetic structures. Improved prediction offers hope of estimating biodiversity change at policy-relevant scales, guiding adaptive conservation responses

Low-mass pre--main-sequence stars in the Magellanic Clouds

[Abridged] The stellar Initial Mass Function (IMF) suggests that sub-solar stars form in very large numbers. Most attractive places for catching low-mass star formation in the act are young stellar clusters and associations, still (half-)embedded in star-forming regions. The low-mass stars in such regions are still in their pre--main-sequence (PMS) evolutionary phase. The peculiar nature of these objects and the contamination of their samples by the evolved populations of the Galactic disk impose demanding observational techniques for the detection of complete numbers of PMS stars in the Milky Way. The Magellanic Clouds, the companion galaxies to our own, demonstrate an exceptional star formation activity. The low extinction and stellar field contamination in star-forming regions of these galaxies imply a more efficient detection of low-mass PMS stars than in the Milky Way, but their distance from us make the application of special detection techniques unfeasible. Nonetheless, imaging with the Hubble Space Telescope yield the discovery of solar and sub-solar PMS stars in the Magellanic Clouds from photometry alone. Unprecedented numbers of such objects are identified as the low-mass stellar content of their star-forming regions, changing completely our picture of young stellar systems outside the Milky Way, and extending the extragalactic stellar IMF below the persisting threshold of a few solar masses. This review presents the recent developments in the investigation of PMS stars in the Magellanic Clouds, with special focus on the limitations by single-epoch photometry that can only be circumvented by the detailed study of the observable behavior of these stars in the color-magnitude diagram. The achieved characterization of the low-mass PMS stars in the Magellanic Clouds allowed thus a more comprehensive understanding of the star formation process in our neighboring galaxies.Comment: Review paper, 26 pages (in LaTeX style for Springer journals), 4 figures. Accepted for publication in Space Science Review