Glioblastoma vulnerability to neddylation inhibition is dependent on PTEN status, and dysregulation of the cell cycle and DNA replication.

Background: Neddylation (NAE) inhibition, affecting posttranslational protein function and turnover, is a promising therapeutic approach to cancer. We report the cytotoxic vulnerability to NAE inhibitors in a subset of glioblastoma (GBM) preclinical models and identify genetic alterations and biological processes underlying differential response.

Methods: GBM DNA sequencing and transcriptomic data were queried for genes associated with response to NAE inhibition; candidates were validated by molecular techniques.

Droplet Hi-C for Fast and Scalable Profiling of Chromatin Architecture in Single Cells.

Comprehensive analysis of chromatin architecture is crucial for understanding the gene regulatory programs during development and in disease pathogenesis, yet current methods often inadequately address the unique challenges presented by analysis of heterogeneous tissue samples. Here, we introduce Droplet Hi-C, which employs a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture at single-cell resolution from the mouse cortex and analyzed gene regulatory programs in major cortical cell types.

Glioblastoma Mesenchymal Transition and Invasion are Dependent on a NF-κB/BRD2 Chromatin Complex.

Glioblastoma (GBM) represents the most aggressive subtype of glioma, noted for its profound invasiveness and molecular heterogeneity. The mesenchymal (MES) transcriptomic subtype is frequently associated with therapy resistance, rapid recurrence, and increased tumor-associated macrophages. Notably, activation of the NF-κB pathway and alterations in the gene are both associated with this malignant transition.

Linking variation in planktonic primary production to coral reef fish growth and condition.

Within low-nutrient tropical oceans, islands and atolls with higher primary production support higher fish biomass and reef organism abundance. External energy subsidies can be delivered onto reefs via a range of physical mechanisms. However, the influence of spatial variation in primary production on reef fish growth and condition is largely unknown.

Towards an Adaptive Clinical Transcription System for In-Situ Transcribing of Patient Encounter Information.

Electronic patient charts are essential for follow-up and multi-disciplinary care, but either take up an exorbitant amount of time during the patient encounter using a key-stroke entry system, or suffer from poor recall when made long after the encounter. Transcribing in-situ, natural dictations by the clinician, recorded during the encounter, with minimal workflow impact, is a promising solution. However, human transcription requires significant manual resources, whereas automated transcription currently lacks the accuracy for specialized clinical language.

Maximization of fitness by phenological and phenotypic plasticity in range expanding rabbitfishes (Siganidae).

Global warming is modifying the phenology, life-history traits and biogeography of species around the world. Evidence of these effects have increased over recent decades; however, we still have a poor understanding of the possible outcomes of their interplay across global climatic gradients, hindering our ability to accurately predict the consequences of climate change in populations and ecosystems. We examined the effect that changes in biogeography can have on the life-history traits of two of the most successful range-extending fish species in the world: the tropical rabbitfishes Siganus fuscescens and Siganus rivulatus.

PTEN loss drives resistance to the neddylation inhibitor MLN4924 in glioblastoma and can be overcome with TOP2A inhibitors.

Background: Neddylation inhibition, affecting posttranslational protein function and turnover, is a promising therapeutic approach to cancer. We report vulnerability to MLN4924 or pevonedistat (a neddylation inhibitor) in a subset of glioblastoma (GBM) preclinical models and identify biomarkers, mechanisms, and signatures of differential response.

Methods: GBM sequencing data were queried for genes associated with MLN4924 response status; candidates were validated by molecular techniques.

Pediatric ED departmental complexity: a different approach to the concept of ED crowding.

Objective: Emergency department (ED) crowding is a significant problem in Canada and internationally and is associated with the potential for patient harm. Although pediatric patients represent a significant proportion of overall ED visits, there is limited research on pediatric ED crowding. The Canadian Association of Emergency Physicians defines department crowding as a mismatch between the required and available resources to provide timely emergency care.

Distinct pathways of homologous recombination controlled by the SWS1-SWSAP1-SPIDR complex.

Homology-directed repair (HDR), a critical DNA repair pathway in mammalian cells, is complex, leading to multiple outcomes with different impacts on genomic integrity. However, the factors that control these different outcomes are often not well understood. Here we show that SWS1-SWSAP1-SPIDR controls distinct types of HDR.

Natural nutrient subsidies alter demographic rates in a functionally important coral-reef fish.

By improving resource quality, cross-ecosystem nutrient subsidies may boost demographic rates of consumers in recipient ecosystems, which in turn can affect population and community dynamics. However, empirical studies on how nutrient subsidies simultaneously affect multiple demographic rates are lacking, in part because humans have disrupted the majority of these natural flows. Here, we compare the demographics of a sex-changing parrotfish (Chlorurus sordidus) between reefs where cross-ecosystem nutrients provided by seabirds are available versus nearby reefs where invasive, predatory rats have removed seabird populations.

Revisiting the paradigm of shark-driven trophic cascades in coral reef ecosystems.

Global overfishing of higher-level predators has caused cascading effects to lower trophic levels in many marine ecosystems. On coral reefs, which support highly diverse food webs, the degree to which top-down trophic cascades can occur remains equivocal. Using extensive survey data from coral reefs across the relatively unfished northern Great Barrier Reef (nGBR), we quantified the role of reef sharks in structuring coral reef fish assemblages.

Comparative demography of commercially important species of coral grouper, Plectropomus leopardus and P. laevis, from Australia's great barrier reef and Coral Sea marine parks.

Understanding the spatial and environmental variation in demographic processes of fisheries target species, such as coral grouper (Genus: Plectropomus), is important for establishing effective management and conservation strategies. Herein we compare the demography of Plectropomus leopardus and P. laevis between Australia's Great Barrier Reef Marine Park (GBRMP), which has been subject to sustained and extensive fishing pressure, and the oceanic atolls of Australia's Coral Sea Marine Park (CSMP), where there is very limited fishing for reef fishes.

Synchronous biological feedbacks in parrotfishes associated with pantropical coral bleaching.

Biological feedbacks generated through patterns of disturbance are vital for sustaining ecosystem states. Recent ocean warming and thermal anomalies have caused pantropical episodes of coral bleaching, which has led to widespread coral mortality and a range of subsequent effects on coral reef communities. Although the response of many reef-associated fishes to major disturbance events on coral reefs is negative (e.

Demographic plasticity facilitates ecological and economic resilience in a commercially important reef fish.

Variation in life-history characteristics is evident within and across animal populations. Such variation is mediated by environmental gradients and reflects metabolic constraints or trade-offs that enhance reproductive outputs. While generalizations of life-history relationships across species provide a framework for predicting vulnerability to overexploitation, deciphering patterns of intraspecific variation may also enable recognition of peculiar features of populations that facilitate ecological resilience.

Validation and refinement of a clinical decision rule for the use of computed tomography in children with minor head injury in the emergency department.

Background: There is uncertainty about which children with minor head injury need to undergo computed tomography (CT). We sought to prospectively validate the accuracy and potential for refinement of a previously derived decision rule, Canadian Assessment of Tomography for Childhood Head injury (CATCH), to guide CT use in children with minor head injury.

Methods: This multicentre cohort study in 9 Canadian pediatric emergency departments prospectively enrolled children with blunt head trauma presenting with a Glasgow Coma Scale score of 13-15 and loss of consciousness, amnesia, disorientation, persistent vomiting or irritability.

Comparative demography of commercially-harvested snappers and an emperor from American Samoa.

The age-based life history of two commercially-important species of snapper (Lutjanidae) and one emperor (Lethrinidae) were characterized from the nearshore fishery of Tutuila, American Samoa. Examination of sagittal otoliths across multiple months and years confirmed the annual deposition of increments and highlighted marked variation in life-history patterns among the three meso-predator species. The humpback red snapper is a medium-bodied gonochoristic species which exhibits striking sexual dimorphism in length-at-age and consequent growth trajectories and has a life span estimated to be at least 27 years.

Bottom-up processes mediated by social systems drive demographic traits of coral-reef fishes.

Ectotherms exhibit considerable plasticity in their life-history traits. This plasticity can reflect variability in environmental and social factors, but the causes of observed patterns are often obscured with increasing spatial scales. We surveyed dichromatic parrotfishes across the northern Great Barrier Reef to examine variation in body size distributions and concomitant size at sex change (L ) against hypotheses of directional influence from biotic and abiotic factors known to affect demography.

Age-based and reproductive biology of the Pacific Longnose Parrotfish from Guam.

The Pacific longnose parrotfish (Valenciennes 1840) represents a prime fishery resource throughout much of the tropical Pacific. In this study, we sampled the species from the Guam commercial fishery market across five consecutive years to characterize reproductive and age-based demographic information imperative for informed fishery management. Compared with other parrotfishes, this species was found to be large-bodied, but has only a moderate life span of 10 + years.

The impact of individual and combined abiotic factors on daily otolith growth in a coral reef fish.

Coral reefs are increasingly subjected to both local and global stressors, however, there is limited information on how reef organisms respond to their combined effects under natural conditions. This field study examined the growth response of the damselfish Neopomacentrus bankieri to the individual and combined effects of multiple abiotic factors. Turbidity, temperature, tidal movement, and wave action were recorded every 10 minutes for four months, after which the daily otolith growth of N.

Scalp Hematoma Characteristics Associated With Intracranial Injury in Pediatric Minor Head Injury.

Objectives: Minor head trauma accounts for a significant proportion of pediatric emergency department (ED) visits. In children younger than 24 months, scalp hematomas are thought to be associated with the presence of intracranial injury (ICI). We investigated which scalp hematoma characteristics were associated with increased odds of ICI in children less than 17 years who presented to the ED following minor head injury and whether an underlying linear skull fracture may explain this relationship.