Invest Ophthalmol Vis Sci
January 2024
Purpose: NRL is an influential transcription factor and central to animal modeling in ophthalmology. Disrupting NRL abrogates rod development and produces an excess of S-cones (also known as "UV cones" or "short-wavelength-sensitive1 [SWS1] cones"). Strikingly, mutations in zebrafish tbx2b produce the exact opposite phenotypes (excess rods and loss of SWS1 cones).
View Article and Find Full Text PDFAdvances in understanding the physiologic functions of the tumor necrosis factor superfamily (TNFSF) of ligands, receptors, and signaling networks are providing deeper insight into pathogenesis of infectious and autoimmune diseases and cancer. LIGHT (TNFSF14) has emerged as an important modulator of critical innate and adaptive immune responses. LIGHT and its signaling receptors, herpesvirus entry mediator (TNFRSF14), and lymphotoxin β receptor, form an immune regulatory network with two co-receptors of herpesvirus entry mediator, checkpoint inhibitor B and T lymphocyte attenuator, and CD160.
View Article and Find Full Text PDFBACKGROUNDSevere coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune response, which can result in cytokine-release syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19-associated ARDS have elevated free serum levels of the cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT; also known as TNFSF14). Such patients may benefit from LIGHT-neutralization therapy.
View Article and Find Full Text PDFCellular Prion Protein (PrP) is a well-studied protein as the substrate for various progressive untreatable neurodegenerative diseases. Normal functions of PrP are poorly understood, though recent proteomic and transcriptomic approaches have begun to reveal common themes. We use our compound and knockout mutant zebrafish at three days post fertilization to take a transcriptomic approach to investigating potentially conserved PrP functions during development.
View Article and Find Full Text PDFJ Exp Psychol Gen
September 2021
In most misinformation studies, participants are exposed to a to-be-remembered event and then subsequently given misinformation in textual form. This misinformation impacts people's ability to accurately report the initial event. In this article, we present 2 experiments that explored a different approach to presenting misinformation.
View Article and Find Full Text PDFThe transcription factor NRL (neural retina leucine zipper) has been canonized as the master regulator of photoreceptor cell fate in the retina. NRL is necessary and sufficient to specify rod cell fate and to preclude cone cell fate in mice. By engineering zebrafish, we tested if NRL function has conserved roles beyond mammals or beyond nocturnal species, i.
View Article and Find Full Text PDFMany coronavirus disease 2019 (COVID-19) patients demonstrate lethal respiratory complications caused by cytokine release syndrome (CRS). Multiple cytokines have been implicated in CRS, but levels of tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) have not been previously measured in this setting. In this study, we observed significantly elevated serum LIGHT levels in hospitalized COVID-19 patients compared to healthy age- and gender-matched control patients.
View Article and Find Full Text PDFObjectives: To investigate longitudinal trajectory of SARS-CoV-2 neutralising antibodies and the performance of serological assays in diagnosing prior infection and predicting serum neutralisation titres with time Design Retrospective longitudinal analysis of a COVID19 case cohort . Setting NHS outpatient clinics Participants Individuals with RT-PCR diagnosed SARS-CoV-2 infection that did not require hospitalization Main outcome measures The sensitivity with which prior infection was detected and quantitative antibody titres were assessed using four SARS-CoV-2 serologic assay platforms. Two platforms employed SARS-CoV-2 spike (S) based antigens and two employed nucleocapsid (N) based antigens.
View Article and Find Full Text PDFβ-Thalassemia intermedia is a disorder characterized by ineffective erythropoiesis (IE), anemia, splenomegaly, and systemic iron overload. Novel approaches are being explored based on the modulation of pathways that reduce iron absorption (ie, using hepcidin activators like Tmprss6-antisense oligonucleotides [ASOs]) or increase erythropoiesis (by erythropoietin [EPO] administration or modulating the ability of transferrin receptor 2 [Tfr2] to control red blood cell [RBC] synthesis). Targeting Tmprss6 messenger RNA by Tmprss6-ASO was proven to be effective in improving IE and splenomegaly by inducing iron restriction.
View Article and Find Full Text PDFIt has been proposed that Amyloid β Precursor Protein (APP) might act as a rheostat controlling neuronal excitability, but mechanisms have remained untested. APP and its catabolite Aβ are known to impact upon synapse function and dysfunction via their interaction with the prion protein (PrP), suggesting a candidate pathway. Here we test if PrP is required for this APP function in vivo, perhaps via modulating mGluR5 ion channels.
View Article and Find Full Text PDFis commercially available marine algae used for animal feed, human nutrient supplements, and biodiesel. The is one of five genera of haptophytes that produces unique, long-chain lipids known as alkenones that are promising new ingredients for green cosmetics, personal care products and pharmaceutical delivery. However, there is a lack of toxicity data for alkenones in animals, thus limiting their use in humans.
View Article and Find Full Text PDFQ J Exp Psychol (Hove)
March 2020
We learn regularities in the world around us, frequently without conscious effort, a phenomenon known as implicit learning. These regularities are often impossible to verbalise. One example of implicit learning is , in which participants learn a rule set combining two factors, such as lexical frequency and concreteness.
View Article and Find Full Text PDFPigmentary glaucoma (PG) is a common glaucoma subtype that results from release of pigment from the iris, called pigment dispersion syndrome (PDS), and its deposition throughout the anterior chamber of the eye. Although PG has a substantial heritable component, no causative genes have yet been identified. We used whole exome sequencing of two independent pedigrees to identify two premelanosome protein (PMEL) variants associated with heritable PDS/PG.
View Article and Find Full Text PDFBackground: Trastuzumab is a monoclonal antibody which demonstrates efficacy for HER2 positive breast cancer patients. Recently, an increased incidence of brain metastasis in trastuzumab-treated patients has been reported. The reason for this may be the effectiveness of systemic trastuzumab allowing patients to survive longer thus providing time for brain metastases to develop, along with the lack of penetration of systemic therapies through the blood brain barrier.
View Article and Find Full Text PDFTwo experiments are presented, which explore the presence of a distinctiveness advantage when recognising unfamiliar voices. In Experiment 1, distinctive voices were recognised significantly better, and with greater confidence, in a sequential same/different matching task compared with typical voices. These effects were replicated and extended in Experiment 2, as distinctive voices were recognised better even under challenging listening conditions imposed by nonsense sentences and temporal reversal.
View Article and Find Full Text PDFNormally folded prion protein (PrP) and its functions in healthy brains remain underappreciated compared with the intense study of its misfolded forms ("prions," PrP) during the pathobiology of prion diseases. This impedes the development of therapeutic strategies in Alzheimer's and prion diseases. Disrupting the zebrafish homologs of PrP has provided novel insights; however, mutagenesis of the zebrafish paralog did not recapitulate previous dramatic developmental phenotypes, suggesting redundancy with the paralog.
View Article and Find Full Text PDFBackground: Rheumatoid arthritis (RA) is a symmetric inflammatory polyarthritis associated with high concentrations of pro-inflammatory, cytokines including tumor necrosis factor (TNF)-α. Adalimumab is a monoclonal antibody (mAb) that binds TNF-α, and is widely used to treat RA. Despite its proven clinical efficacy, adalimumab and other therapeutic mAbs have disadvantages, including the requirement for repeated bolus injections and the appearance of treatment limiting anti-drug antibodies.
View Article and Find Full Text PDFJ Exp Psychol Hum Percept Perform
June 2017
We report 4 experiments investigating auditory hindsight bias-the tendency to overestimate the intelligibility of distorted auditory stimuli after learning their identity. An associative priming manipulation was used to vary the amount of processing fluency independently of prior target knowledge. For hypothetical designs, in which hindsight judgments are made for peers in foresight, we predicted that judgments would be based on processing fluency and that hindsight bias would be greater in the unrelated- compared to related-prime context (differential-fluency hypothesis).
View Article and Find Full Text PDFUnderstanding the relationship between physiological measurements from human subjects and their demographic data is important within both the biometric and forensic domains. In this paper we explore the relationship between measurements of the human hand and a range of demographic features. We assess the ability of linear regression and machine learning classifiers to predict demographics from hand features, thereby providing evidence on both the strength of relationship and the key features underpinning this relationship.
View Article and Find Full Text PDFProtein drugs are currently delivered by bolus injection and although treatment frequently is successful, these methods also have major drawbacks, which call for the development of alternative technologies allowing prolonged delivery of these drugs. We developed a new ex vivo gene therapy platform called Transduced Autologous Restorative Gene Therapy (TARGT) for sustained long term production and secretion of autologous therapeutic proteins. A biopsy of dermal tissue taken from the patient is transduced ex vivo with a viral vector encoding the required gene under a constitutive promoter.
View Article and Find Full Text PDFTwo experiments are presented to explore the limits when matching a sample to a suspect utilising the hand as a novel biometric. The results of Experiment 1 revealed that novice participants were able to match hands at above-chance levels as viewpoint changed. Notably, a moderate change in viewpoint had no notable effect, but a more substantial change in viewpoint affected performance significantly.
View Article and Find Full Text PDFRecent literature has raised the suggestion that voice recognition runs in parallel to face recognition. As a result, a prediction can be made that voices should prime faces and faces should prime voices. A traditional associative priming paradigm was used in two studies to explore within-modality priming and cross-modality priming.
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