Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Author Correction: A consensus-based transparency checklist.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Fast Visuomotor Processing of Redundant Targets: The Role of the Right Temporo-Parietal Junction

Parallel processing of multiple sensory stimuli is critical for efficient, successful interaction with the environment. An experimental approach to studying parallel processing in sensorimotor integration is to examine reaction times to multiple copies of the same stimulus. Reaction times to bilateral copies of light flashes are faster than to single, unilateral light flashes. These faster responses may be due to ‘statistical facilitation’ between independent processing streams engaged by the two copies of the light flash. On some trials, however, reaction times are faster than predicted by statistical facilitation. This indicates that a neural ‘coactivation’ of the two processing streams must have occurred. Here we use fMRI to investigate the neural locus of this coactivation. Subjects responded manually to the detection of unilateral light flashes presented to the left or right visual hemifield, and to the detection of bilateral light flashes. We compared the bilateral trials where subjects' reaction times exceeded the limit predicted by statistical facilitation to bilateral trials that did not exceed the limit. Activity in the right temporo-parietal junction was higher in those bilateral trials that showed coactivation than in those that did not. These results suggest the neural coactivation observed in visuomotor integration occurs at a cognitive rather than sensory or motor stage of processing

The neural correlates of social attention: automatic orienting to social and nonsocial cues

Previous evidence suggests that directional social cues (e.g., eye gaze) cause automatic shifts in attention toward gaze direction. It has been proposed that automatic attentional orienting driven by social cues (social orienting) involves a different neural network from automatic orienting driven by nonsocial cues. However, previous neuroimaging studies on social orienting have only compared gaze cues to symbolic cues, which typically engage top-down mechanisms. Therefore, we directly compared the neural activity involved in social orienting to that involved in purely automatic nonsocial orienting. Twenty participants performed a spatial cueing task consisting of social (gaze) cues and automatic nonsocial (peripheral squares) cues presented at short and long stimulus (cue-to-target) onset asynchronies (SOA), while undergoing fMRI. Behaviorally, a facilitation effect was found for both cue types at the short SOA, while an inhibitory effect (inhibition of return: IOR) was found only for nonsocial cues at the long SOA. Imaging results demonstrated that social and nonsocial cues recruited a largely overlapping fronto-parietal network. In addition, social cueing evoked greater activity in occipito-temporal regions at both SOAs, while nonsocial cueing recruited greater subcortical activity, but only for the long SOA (when IOR was found). A control experiment, including central arrow cues, confirmed that the occipito-temporal activity was at least in part due to the social nature of the cue and not simply to the location of presentation (central vs. peripheral). These results suggest an evolutionary trajectory for automatic orienting, from predominantly subcortical mechanisms for nonsocial orienting to predominantly cortical mechanisms for social orienting

Analyses of an Expressed Sequence Tag Library from Taenia solium, Cysticerca

A method used to describe expressed genes at a specific stage in an organism is an EST library. In this method mRNA from a specific organism is isolated, transcribed into cDNA and sequenced. The sequence will derive from the 5′-end of the cDNA. The library will not have sequences from all genes, especially if they are expressed in low amounts or not at all in the studied stage. Also the library will mostly not contain full length sequences from genes, but expression patterns can be established. If EST libraries are made from different stages of the same organisms these libraries can be compared and differently expressed genes can be identified. Described here is an analysis of an EST library from the pig cysticerca which is thought to be similar to the stage giving the human neglected disease neurocysticercosis. Novel genes together with putative drug targets are examples of data presented

A consensus-based transparency checklist

We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository

Origins Space Telescope: Baseline mission concept

The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the Universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared (IR) wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of the Herschel Space Observatory, the largest telescope flown in space to date. We describe the baseline concept for Origins recommended to the 2020 US Decadal Survey in Astronomy and Astrophysics. The baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (Mid-Infrared Spectrometer and Camera Transit spectrometer) will measure the spectra of transiting exoplanets in the 2.8 to 20 μm wavelength range and offer unprecedented spectrophotometric precision, enabling definitive exoplanet biosignature detections. The far-IR imager polarimeter will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer will cover wavelengths from 25 to 588 μm, making wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch, while the cryothermal system design leverages James Webb Space Telescope technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins\u27 natural background-limited sensitivity