Shane sensitivity

The insect steroid hormone ecdysone plays a critical role in insect development. Several recent studies have shown that ecdysone enters cells through Organic Anion Transporting Polypeptides (OATPs) in insects such as flies and mosquitoes. However, the conservation of this mechanism across other arthropods and the role of this transporter in canonical ecdysone pathways are less well studied. Herein we functionally characterized the putative ecdysone importer (EcI) from two major agricultural moth pests: Helicoverpa armigera (cotton bollworm) and Spodoptera frugiperda (fall armyworm)...

RATIONALE: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches...

Increased tetrahydrobiopterin (BH4) generated in injured sensory neurons contributes to increased pain sensitivity and its persistence. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the de novo BH4 synthetic pathway, and human single-nucleotide polymorphism studies, together with mouse genetic modeling, have demonstrated that decreased GCH1 leads to both reduced BH4 and pain. However, little is known about the regulation of Gch1 expression upon nerve injury and whether this could be modulated as an analgesic therapeutic intervention...

Opsin-3 ( Opn3 , encephalopsin) was the first nonvisual opsin gene discovered in mammals. Since then, several Opn3 functions have been described, and in two cases (adipose tissue, smooth muscle) light sensing activity is implicated. In addition to peripheral tissues, Opn3 is robustly expressed within the central nervous system, for which it derives its name. Despite this expression, no studies have investigated developmental or adult CNS consequences of Opn3 loss-of-function. Here, the behavioral consequences of mice deficient in Opn3 were investigated...

The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints1,2 . Targeted gene editing has the potential to overcome these limitations and enhance T cell therapeutic function3-10 . Here we performed multiple genome-wide CRISPR knock-out screens under different immunosuppressive conditions to identify genes that can be targeted to prevent T cell dysfunction. These screens converged on RASA2, a RAS GTPase-activating protein (RasGAP) that we identify as a signalling checkpoint in human T cells, which is downregulated upon acute T cell receptor stimulation and can increase gradually with chronic antigen exposure...

Ferroptosis is a non-apoptotic cell death mechanism characterized by the generation of lipid peroxides. While many effectors in the ferroptosis pathway have been mapped, its epitranscriptional regulation is not yet fully understood. Ferroptosis can be induced via system xCT inhibition (Class I) or GPX4 inhibition (Class II). Previous works have revealed important differences in cellular response to different ferroptosis inducers. Importantly, blocking mRNA transcription or translation appears to protect cells against Class I ferroptosis inducing agents but not Class II...

Magic angle spinning nuclear magnetic resonance spectroscopy experiments are widely employed in the characterization of solid media. The approach is incredibly versatile but deleteriously suffers from low sensitivity, which may be alleviated by adopting dynamic nuclear polarization methods, resulting in large signal enhancements. Paramagnetic metal ions such as Gd3+ have recently shown promising results as polarizing agents for 1 H, 13 C, and 15 N nuclear spins. We demonstrate that the widely available and inexpensive chemical agent Gd(NO3 )3 achieves significant signal enhancements for the 13 C and 15 N nuclear sites of [2-13 C,15 N]glycine at 9...

BACKGROUND: The Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5) was developed to evaluate children between 5 and 12 years of age for a suspected concussion. However, limited empirical evidence exists demonstrating the value of the Child SCAT5 for acute concussion assessment. Therefore, the purpose of our study was to examine differences and assess the diagnostic properties of Child SCAT5 scores among concussed and non-concussed middle school children on the same day as a suspected concussion...

Nurses and doctors must be culturally competent to care for transgender patients. However, there is little time dedicated to lesbian, gay, bisexual, transgender and queer plus (LGBTQ+) health in undergraduate and postgraduate nursing and medicine education and healthcare professionals often lack the competence and skills to treat transgender patients sensitively. At Queen's University Belfast, a transgender awareness training session was developed to enhance the cultural competence of nursing and medicine students and academic staff...

BACKGROUND: With a significant increase in utilisation of computed tomography (CT), inappropriate imaging is a significant concern. Manual justification audits of radiology referrals are time-consuming and require financial resources. We aimed to retrospectively audit justification of brain CT referrals by applying natural language processing and traditional machine learning (ML) techniques to predict their justification based on the audit outcomes. METHODS: Two human experts retrospectively analysed justification of 375 adult brain CT referrals performed in a tertiary referral hospital during the 2019 calendar year, using a cloud-based platform for structured referring...

Background: Size-based assessments are inaccurate indicators of tumor response in soft-tissue sarcoma (STS), motivating the requirement for new response imaging biomarkers for this rare and heterogeneous disease. In this study, we assess the test-retest repeatability of radiomic features from MR diffusion-weighted imaging (DWI) and derived maps of apparent diffusion coefficient (ADC) in retroperitoneal STS and compare baseline repeatability with changes in radiomic features following radiotherapy (RT)...

STUDY DESIGN: Prospective cohort study. BACKGROUND: The cervical rotation lateral flexion (CRLF) test is frequently used in clinical practice to determine whether a thrust manipulation targeting the first rib should be performed. OBJECTIVES: To evaluate the predictive validity of the CRLF test and manual examination in determining whether patients with neck pain are likely to benefit from manipulative treatment to the first and second rib...

ISSUE ADDRESSED: This study reports outcomes from initial steps taken to promote cultural proficiency among our next generation, nonclinical health workforce, including addressing any tendencies towards stereotyping, biases and discrimination, when redeveloping and Indigenising curricula. METHODS: This qualitative study involved purposive sampling of undergraduate students enrolled in a final-year health promotion unit (subject), as well as staff within the Faculty of Health...

TaqMan probe based quantitative polymerase reaction (TaqMan qPCR) is a robust and reliable technique for detecting and quantifying target DNA copies. Quantitative molecular diagnosis of genetically diverse single stranded DNA (ssDNA) virus such as Pigeon circovirus (PiCV) can be challenging owing to difficulties in primer binding or low abundance of template DNA copies in clinical specimens. Several methods have been described for the detection of PiCV, being qPCR the most simple and reliable. As far as is known, two qPCR systems described until now are based on SYBR green...

Exposure to organic contaminants in house dust is linked to the development or exacerbation of many allergic and immune disorders. In this work, we evaluate the effects of organic contaminants on different cell bioenergetics endpoints using five different cell lines (16HBE14o-, NuLi-1, A549, THP-1 and HepG2), and examine its effects on lung epithelial cells using conventional 2D and 3D (air-liquid interface/ALI) models. Proposed rapid bioenergetic assays relies on a quick, 40 min, exposure protocol that provides equivalent dose-response curves for ATP production, spare respiratory capacity, and cell respiration...

BACKGROUND: South Africa's rates of psychiatric morbidity are among the highest in sub-Saharan Africa and are foregrounded by the country's long history of political violence during apartheid. Growing evidence suggests that in utero stress exposure is a potent developmental risk factor for future mental illness risk, yet the extent to which the psychiatric effects of prenatal stress impact the next generation are unknown. We evaluate the intergenerational effects of prenatal stress experienced during apartheid on psychiatric morbidity among children at ages 17-18 and also assess the moderating effects of maternal age, social support, and past household adversity...

TP53 (p53) is mutated in 80-90% of cases of triple-negative breast cancer (TNBC). Statins, which are widely used to treat elevated cholesterol, have recently been shown to degrade mutant p53 protein and exhibit anti-cancer activity. The aim of this work was to evaluate the potential of statins in the treatment of TNBC. The anti-proliferative effects of 2 widely used statins were investigated on a panel of 15 cell lines representing the different molecular subtypes of breast cancer. Significantly lower IC50 values were found in triple-negative (TN) than in non-TN cell lines (atorvastatin, p < 0...

PURPOSE: To (i): examine whether maternal dietary inflammation assessed using the dietary inflammatory index (DII) is associated with gestational weight gain (GWG) and delivery outcomes in urban South African women from the Soweto First 1000-Day Study (S1000); and (ii): explore whether serum high-sensitivity c-reactive protein (hs-CRP) levels mediate these associations. METHODS: Energy-adjusted-DII (E-DII™) scores were calculated for 478 pregnant women using a quantitative food frequency questionnaire...

The long-term sustainability of the offshore wind industry requires the development of appropriate investigative methods to enable less conservative and more cost-effective geotechnical engineering design. Here we describe the novel use of distributed acoustic sensing (DAS) as part of an integrated approach for the geophysical and geotechnical assessment of the shallow subsurface for offshore construction. DAS was used to acquire active Scholte-wave seismic data at several locations in the vicinity of a planned windfarm development near Dundalk Bay, Irish Sea...

OBJECTIVE: To assess the accuracy and marginal value of quantitative D-dimer testing for diagnosing venom-induced consumption coagulopathy (VICC) in people bitten by Australian snakes. DESIGN, SETTING: Analysis of data for suspected and confirmed cases of snakebite collected prospectively by the Australian Snakebite Project, 2005-2019, from 200 hospitals across Australia. PARTICIPANTS: 1363 patients for whom D-dimer was quantitatively assessed within 24 hours of suspected or confirmed snakebite...