60 research outputs found

    Human Patient-Derived Brain Tumor Models to Recapitulate Ependymoma Tumor Vasculature.

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    Despite in vivo malignancy, ependymoma lacks cell culture models, thus limiting therapy development. Here, we used a tunable three-dimensional (3D) culture system to approximate the ependymoma microenvironment for recapitulating a patient\u27s tumor in vitro. Our data showed that the inclusion of VEGF in serum-free, mixed neural and endothelial cell culture media supported the in vitro growth of all four ependymoma patient samples. The growth was driven by Nestin and Ki67 double-positive cells in a putative cancer stem cell niche, which was manifested as rosette-looking clusters in 2D and spheroids in 3D. The effects of extracellular matrix (ECM) such as collagen or Matrigel superseded that of the media conditions, with Matrigel resulting in the greater enrichment of Nestin-positive cells. When mixed with endothelial cells, the 3D co-culture models developed capillary networks resembling the in vivo ependymoma vasculature. The transcriptomic analysis of two patient cases demonstrated the separation of in vitro cultures by individual patients, with one patient\u27s culture samples closely clustered with the primary tumor tissue. While VEGF was found to be necessary for preserving the transcriptomic features of in vitro cultures, the presence of endothelial cells shifted the gene\u27s expression patterns, especially genes associated with ECM remodeling. The homeobox genes were mostly affected in the 3D in vitro models compared to the primary tumor tissue and between different 3D formats. These findings provide a basis for understanding the ependymoma microenvironment and enabling the further development of patient-derived in vitro ependymoma models for personalized medicine

    Bolocam Survey for 1.1 mm Dust Continuum Emission in the c2d Legacy Clouds. II. Ophiuchus

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    We present a large-scale millimeter continuum map of the Ophiuchus molecular cloud. Nearly 11 square degrees, including all of the area in the cloud with visual extinction more than 3 magnitudes, was mapped at 1.1 mm with Bolocam on the Caltech Submillimeter Observatory (CSO). By design, the map also covers the region mapped in the infrared with the Spitzer Space Telescope. We detect 44 definite sources, and a few likely sources are also seen along a filament in the eastern streamer. The map indicates that dense cores in Ophiuchus are very clustered and often found in filaments within the cloud. Most sources are round, as measured at the half power point, but elongated when measured at lower contour levels, suggesting spherical sources lying within filaments. The masses, for an assumed dust temperature of 10 K, range from 0.24 to 3.9 solar masses, with a mean value of 0.96 solar masses. The total mass in distinct cores is 42 solar masses, 0.5 to 2% of the total cloud mass, and the total mass above 4 sigma is about 80 solar masses. The mean densities in the cores are quite high, with an average of 1.6 x 10^6 per cc, suggesting short free-fall times. The core mass distribution can be fitted with a power law with slope of 2.1 plus or minus 0.3 for M>0.5 solar masses, similar to that found in other regions, but slightly shallower than that of some determinations of the local IMF. In agreement with previous studies, our survey shows that dense cores account for a very small fraction of the cloud volume and total mass. They are nearly all confined to regions with visual extinction at least 9 mag, a lower threshold than found previously.Comment: 47 pages, 16 figures, accepted for Ap

    FusorSV: an algorithm for optimally combining data from multiple structural variation detection methods.

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    Comprehensive and accurate identification of structural variations (SVs) from next generation sequencing data remains a major challenge. We develop FusorSV, which uses a data mining approach to assess performance and merge callsets from an ensemble of SV-calling algorithms. It includes a fusion model built using analysis of 27 deep-coverage human genomes from the 1000 Genomes Project. We identify 843 novel SV calls that were not reported by the 1000 Genomes Project for these 27 samples. Experimental validation of a subset of these calls yields a validation rate of 86.7%. FusorSV is available at https://github.com/TheJacksonLaboratory/SVE . Genome Biol 2018 Mar 20; 19(1):38

    The Twin-Arginine Translocation Pathway in α-Proteobacteria Is Functionally Preserved Irrespective of Genomic and Regulatory Divergence

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    The twin-arginine translocation (Tat) pathway exports fully folded proteins out of the cytoplasm of Gram-negative and Gram-positive bacteria. Although much progress has been made in unraveling the molecular mechanism and biochemical characterization of the Tat system, little is known concerning its functionality and biological role to confer adaptive skills, symbiosis or pathogenesis in the α-proteobacteria class. A comparative genomic analysis in the α-proteobacteria class confirmed the presence of tatA, tatB, and tatC genes in almost all genomes, but significant variations in gene synteny and rearrangements were found in the order Rickettsiales with respect to the typically described operon organization. Transcription of tat genes was confirmed for Anaplasma marginale str. St. Maries and Brucella abortus 2308, two α-proteobacteria with full and partial intracellular lifestyles, respectively. The tat genes of A. marginale are scattered throughout the genome, in contrast to the more generalized operon organization. Particularly, tatA showed an approximately 20-fold increase in mRNA levels relative to tatB and tatC. We showed Tat functionality in B. abortus 2308 for the first time, and confirmed conservation of functionality in A. marginale. We present the first experimental description of the Tat system in the Anaplasmataceae and Brucellaceae families. In particular, in A. marginale Tat functionality is conserved despite operon splitting as a consequence of genome rearrangements. Further studies will be required to understand how the proper stoichiometry of the Tat protein complex and its biological role are achieved. In addition, the predicted substrates might be the evidence of role of the Tat translocation system in the transition process from a free-living to a parasitic lifestyle in these α-proteobacteria

    A super-linear 'radio-AGN main sequence' links mean radio-AGN power and galaxy stellar mass since z similar to 3

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    Mapping the average active galactic nucleus (AGN) luminosity across galaxy populations and over time reveals important clues regarding the interplay between supermassive black hole and galaxy growth. This paper presents the demography, mean power, and cosmic evolution of radio AGN across star-forming galaxies (SFGs) of different stellar masses (M).We exploit deep VLA-COSMOS 3 GHz data to build the rest-frame 1.4 GHz AGN luminosity functions at 0:1 z 4:5 hosted in SFGs. Splitting the AGN luminosity function into different M bins reveals that, at all redshifts, radio AGN are both more frequent and more luminous in higher M than in lower M galaxies. The cumulative kinetic luminosity density exerted by radio AGN in SFGs peaks at z 2, and it is mostly driven by galaxies with 10:5 log(M=M ) < 11. Averaging the cumulative radio AGN activity across all SFGs at each (M,z) results in a ‘radio-AGN main sequence’ that links the time-averaged radio-AGN power hLAGN 1:4 i and galaxy stellar mass, in the form: log h[LAGN 1:4 /WHz1]i = (20.97 0.16) + (2.51 0.34) log(1+z) + (1.41 0.09) (log[M /M ] – 10). The super-linear dependence on M , at fixed redshift, suggests enhanced radio-AGN activity in more massive SFGs as compared to star formation. We ascribe this enhancement to both a higher radio AGN duty cycle and a brighter radio-AGN phase in more massive SFGs. A remarkably consistent M dependence is seen for the evolving X-ray AGN population in SFGs. This similarity is interpreted as possibly driven by secular cold gas accretion fuelling both radio and X-ray AGN activity in a similar fashion over the galaxy’s lifetime.The Cosmic Dawn Center (DAWN) is funded by the Danish National Research Foundation, the Villum Fonden, European Union’s Horizon research and innovation program under the Marie Skłodowska-Curie grant and the Italian Ministry of University and Research.http://www.hanspub.org/Journal/AAS.htmlam2023Physic

    Raspberry Pi nest cameras: An affordable tool for remote behavioral and conservation monitoring of bird nests.

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    Funder: Cardiff UniversityFunder: Project CASE partner ‐ Eco‐explore Community Interest CompanyBespoke (custom-built) Raspberry Pi cameras are increasingly popular research tools in the fields of behavioral ecology and conservation, because of their comparative flexibility in programmable settings, ability to be paired with other sensors, and because they are typically cheaper than commercially built models.Here, we describe a novel, Raspberry Pi-based camera system that is fully portable and yet weatherproof-especially to humidity and salt spray. The camera was paired with a passive infrared sensor, to create a movement-triggered camera capable of recording videos over a 24-hr period. We describe an example deployment involving "retro-fitting" these cameras into artificial nest boxes on Praia Islet, Azores archipelago, Portugal, to monitor the behaviors and interspecific interactions of two sympatric species of storm-petrel (Monteiro's storm-petrel Hydrobates monteiroi and Madeiran storm-petrel Hydrobates castro) during their respective breeding seasons.Of the 138 deployments, 70% of all deployments were deemed to be "Successful" (Successful was defined as continuous footage being recorded for more than one hour without an interruption), which equated to 87% of the individual 30-s videos. The bespoke cameras proved to be easily portable between 54 different nests and reasonably weatherproof (~14% of deployments classed as "Partial" or "Failure" deployments were specifically due to the weather/humidity), and we make further trouble-shooting suggestions to mitigate additional weather-related failures.Here, we have shown that this system is fully portable and capable of coping with salt spray and humidity, and consequently, the camera-build methods and scripts could be applied easily to many different species that also utilize cavities, burrows, and artificial nests, and can potentially be adapted for other wildlife monitoring situations to provide novel insights into species-specific daily cycles of behaviors and interspecies interactions
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