Drug screening to target nuclear orphan receptor NR4A2 for cancer therapeutics.

Background: Our previous study suggested NR4A2, a subfamily member of orphan nuclear receptors, is essential for survival of human cancer cells such as mucoepidermoid carcinoma (MEC).

Methods: We conducted high throughput drug screening for NR4A2 inhibitors as a novel therapeutic modality. Positive screening was performed using a luciferase reporter vector containing NR4A2 binding sequence, and a CRE-reporter control vector was used to eliminate false positives.

Non-surgical transient cerebellar mutism-case report and systematic review.

Introduction: Transient cerebellar mutism has been well recognized in literature as a complication of posterior fossa tumor resection. It is marked by profound impairment of fluency, articulation, and modulation of speech, irritability and autistic features and typically resolves within days to months. Underlying pathophysiology is debated, but currently unknown.

GPCRs: Emerging anti-cancer drug targets.

G protein-coupled receptors (GPCRs) constitute the largest and most diverse protein family in the human genome with over 800 members identified to date. They play critical roles in numerous cellular and physiological processes, including cell proliferation, differentiation, neurotransmission, development and apoptosis. Consequently, aberrant receptor activity has been demonstrated in numerous disorders/diseases, and as a result GPCRs have become the most successful drug target class in pharmaceuticals treating a wide variety of indications such as pain, inflammation, neurobiological and metabolic disorders.

Nestlings reduce their predation risk by attending to predator-information encoded within conspecific alarm calls.

Predation is one of the main threats to altricial nestlings, with predators often locating nests via eavesdropping on begging signals. Nestlings may be able to adjust their begging based on the current level of risk by monitoring both intra- and interspecific alarm calls near the nest. We show that noisy miner (Manorina melanocephala) nestlings can differentiate between terrestrial and aerial alarm calls of their own species, as they suppressed begging behaviour for longer in response to terrestrial rather than aerial alarm calls.

Identifying the nature of impairments in executive functioning and working memory of children with severe difficulties in arithmetic.

An age-matched achievement-matched design was used to examine whether the executive functioning and working memory impairments exhibited by children with severe difficulties in arithmetic (SDA) are better viewed as developmental lags or as cognitive deficits. Three groups of children were included: 20 SDA children, 20 typically achieving children (CM) matched in chronological age with the SDA children, and 20 younger typically achieving children (AM) matched in achievement with the SDA group. While children with SDA did not exhibit impairments in color-word inhibition and verbal working memory, they did demonstrate impairments in shifting, quantity-digits inhibition, and visuospatial working memory.

Recalling and Intending to Enact Health Recommendations: Optimal Number of Prescribed Behaviors in Multibehavior Messages.

Two experiments investigated the effects of the number of health recommendations (e.g., quit smoking; relax for a day) contained in a health-promotion message on recommendation recall and intentions to enact the recommendations.

The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion.

Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX 'interactome' in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins with potential roles in tumor progression.

The acoustic repertoire and behavioural context of the vocalisations of a nocturnal dasyurid, the eastern quoll (Dasyurus viverrinus).

Defining an acoustic repertoire is essential to understanding vocal signalling and communicative interactions within a species. Currently, quantitative and statistical definition is lacking for the vocalisations of many dasyurids, an important group of small to medium-sized marsupials from Australasia that includes the eastern quoll (Dasyurus viverrinus), a species of conservation concern. Beyond generating a better understanding of this species' social interactions, determining an acoustic repertoire will further improve detection rates and inference of vocalisations gathered by automated bioacoustic recorders.

Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils.

Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered.

Explicit calculation of nuclear-magnetic-resonance relaxation rates in small pores to elucidate molecular-scale fluid dynamics.

Nuclear-magnetic-resonance (NMR) spin-lattice (T_{1}^{-1}) and spin-spin (T_{2}^{-1}) relaxation rate measurements can act as effective nondestructive probes of the nanoscale dynamics of ^{1}H spins in porous media. In particular, fast-field-cycling T_{1}^{-1} dispersion measurements contain information on the dynamics of diffusing spins over time scales spanning many orders of magnitude. Previously published experimental T_{1}^{-1} dispersions from a plaster paste, synthetic saponite, mortar, and oil-bearing shale are reanalyzed using a model and associated theory which describe the relaxation rate contributions due to the interaction between spin ensembles in quasi-two-dimensional pores.

Nuclear-magnetic-resonance relaxation due to the translational diffusion of fluid confined to quasi-two-dimensional pores.

Nuclear-magnetic-resonance (NMR) relaxation experimentation is an effective technique for nondestructively probing the dynamics of proton-bearing fluids in porous media. The frequency-dependent relaxation rate T_{1}^{-1} can yield a wealth of information on the fluid dynamics within the pore provided data can be fit to a suitable spin diffusion model. A spin diffusion model yields the dipolar correlation function G(t) describing the relative translational motion of pairs of ^{1}H spins which then can be Fourier transformed to yield T_{1}^{-1}.

KK-92A, a novel GABA receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats.

Rationale: GABA receptors (GABAR) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABAR positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABA receptor agonists such as baclofen.

Objectives: The present study was aimed at developing novel, selective, and potent GABAR PAMs with efficacy on abuse-related effects of nicotine.

GABA receptor allosteric modulators exhibit pathway-dependent and species-selective activity.

Positive modulation of the GABA receptor (GABAR) represents a potentially useful therapeutic approach for the treatment of nicotine addiction. The positive allosteric modulators (PAMs) of GABAR GS39783 and BHF177 enhance GABA-stimulated [S]GTP S-binding, and have shown efficacy in a rodent nicotine self-administration procedure reflecting aspects of nicotine dependence. Interestingly, the structural related analog, NVP998, had no effect on nicotine self-administration in rats despite demonstrating similar pharmacokinetic properties.

Correction to 'Young relicts and old relicts: a novel palaeoendemic vertebrate from the Australian Central Uplands'.

[This corrects the article DOI: 10.1098/rsos.160018.

Googling concussion care in the USA: a critical appraisal of online concussion healthcare providers.

Aim: To examine the online personnel and practice profiles of concussion healthcare providers in the USA.

Methods: We conducted independent, blinded, Google Internet searches for concussion healthcare providers using the terms 'concussion clinic' and 'concussion program' and each American state and completed a critical appraisal of healthcare personnel and services at these websites.

Results: A total of 184 concussion healthcare providers were identified.

Fluorescence High-Throughput Screening for Inhibitors of TonB Action.

Gram-negative bacteria acquire ferric siderophores through TonB-dependent outer membrane transporters (TBDT). By fluorescence spectroscopic hgh-throughput screening (FLHTS), we identified inhibitors of TonB-dependent ferric enterobactin (FeEnt) uptake through FepA (EcoFepA). Among 165 inhibitors found in a primary screen of 17,441 compounds, we evaluated 20 in secondary tests: TonB-dependent ferric siderophore uptake and colicin killing and proton motive force-dependent lactose transport.

Tetraspanin 8 is a novel regulator of ILK-driven β1 integrin adhesion and signaling in invasive melanoma cells.

Melanoma is well known for its propensity for lethal metastasis and resistance to most current therapies. Tumor progression and drug resistance depend to a large extent on the interplay between tumor cells and the surrounding matrix. We previously identified Tetraspanin 8 (Tspan8) as a critical mediator of melanoma invasion, whose expression is absent in healthy skin.

Habitat as a mediator of mesopredator-driven mammal extinction.

A prevailing view in dryland systems is that mammals are constrained by the scarcity of fertile soils and primary productivity. An alternative view is that predation is a primary driver of mammal assemblages, especially in Australia, where 2 introduced mesopredators-feral cat (Felis catus) and red fox (Vulpes vulpes)-are responsible for severe declines of dryland mammals. We evaluated productivity and predation as drivers of native mammal assemblage structure in dryland Australia.

National Perspectives on the Training of Neurosurgery Residents in Stereotactic Radiosurgery.

Despite the critical role played by neurosurgeons in performing radiosurgery, neurosurgery residents in Canada have limited exposure to radiosurgery during their training. A survey of neurosurgery residents and faculty along with radiation oncology faculty was conducted to analyze perspectives regarding incorporating formal radiosurgery training into the neurosurgery residency curriculum Methods: An online survey platform was employed. Descriptive statistics were used to summarize center and respondent characteristics.

Gray free-energy multiphase lattice Boltzmann model with effective transport and wetting properties.

The paper shows that it is possible to combine the free-energy lattice Boltzmann approach to multiphase modeling of fluids involving both liquid and vapor with the partial bounce back lattice Boltzmann approach to modeling effective media. Effective media models are designed to mimic the properties of porous materials with porosity much finer than the scale of the simulation lattice. In the partial bounce-back approach, an effective media parameter or bounce-back fraction controls fluid transport.

Young relicts and old relicts: a novel palaeoendemic vertebrate from the Australian Central Uplands.

Climatic change, and in particular aridification, has played a dominant role in shaping Southern Hemisphere biotas since the mid-Neogene. In Australia, ancient and geologically stable ranges within the vast arid zone have functioned as refugia for populations of mesic taxa extirpated from surrounding areas, yet the extent to which relicts may be linked to major aridification events before or after the Pliocene has not been examined in detail. Here we use molecular phylogenetic and morphological data to show that isolated populations of saxicoline geckos in the genus from the Australian Central Uplands, formerly confounded as a single taxon, actually comprise two divergent species with contrasting histories of isolation.

Multidisciplinary Management of Pediatric Sports-Related Concussion.

Objectives: To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population.

Methods: We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon.