Taste Perception and Coding in Drosophila

AbstractBackground: Discrimination between edible and contaminated foods is crucial for the survival of animals. In Drosophila, a family of gustatory receptors (GRs) expressed in taste neurons is thought to mediate the recognition of sugars and bitter compounds, thereby controlling feeding behavior.Results: We have characterized in detail the expression of eight Gr genes in the labial palps, the fly's main taste organ. These genes fall into two distinct groups: seven of them, including Gr66a, are expressed in 22 or fewer taste neurons in each labial palp. Additional experiments show that many of these genes are coexpressed in partially overlapping sets of neurons. In contrast, Gr5a, which encodes a receptor for trehalose, is expressed in a distinct and larger set of taste neurons associated with most chemosensory sensilla, including taste pegs. Mapping the axonal targets of cells expressing Gr66a and Gr5a reveals distinct projection patterns for these two groups of neurons in the brain. Moreover, tetanus toxin-mediated inactivation of Gr66a- or Gr5a-expressing cells shows that these two sets of neurons mediate distinct taste modalities—the perception of bitter (caffeine) and sweet (trehalose) taste, respectively.Conclusion: Discrimination between two taste modalities—sweet and bitter—requires specific sets of gustatory receptor neurons that express different Gr genes. Unlike the Drosophila olfactory system, where each neuron expresses a single olfactory receptor gene, taste neurons can express multiple receptors and do so in a complex Gr gene code that is unique for small sets of neurons

Anionic multiblock core cross-linked star copolymers via RAFT polymerization

Poly(2-acrylamido-2-methylpropane sulfonic acid) is a polyelectrolyte currently used in numerous industrial applications. Herein, we report the use of reversible addition fragmentation chain transfer (RAFT) polymerization to prepare a range of well-defined homopolymers and block copolymers of 2-acrylamido-2-methylpropane sulfonic acid (AMPS®) and either N-hydroxyethyl acrylamide (HEAm) or 4-acryloylmorpholine (NAM) as a comonomer. We also describe the one-pot synthesis of multiblock core cross-linked star copolymers of AMPS® and HEAm with low dispersities (<1.3). The influence of several parameters such as the cross-linker type, cross-linker to chain transfer agent (CTA) ratio, arm length and composition on the polymerization efficiency are investigated

Sulfonated copolymers as heparin-mimicking stabilizer of fibroblast growth factor : size, architecture, and monomer distribution effects

Fibroblast growth factors (FGF) are involved in a wide range of biological processes such as cell proliferation and differentiation. In living organisms, the binding of FGF to its receptors are mediated through electrostatic interactions between FGF and naturally occurring heparin. Despite its prevalent use in medicine, heparin carries notable limitations, namely; its extraction from natural sources (expensive, low yield and extensive purification), viral contamination, and batch-to-batch heterogeneity. In this work a range of synthetic homopolymers and copolymers of sodium 2-acrylamido-2-methylpropane sulfonate (AMPS®) were evaluated as potential FGF stabilisers. This was studied by measuring the proliferation of BaF3-FR1c cells, as a model assay, and the results will be compared with the natural stabilisation and activation of FGF by heparin. This study explores the structure-activity relationship of these polysulfonated polymers with a focus on the effect of molecular weight, co-monomer type, charge dispersion and polymer architecture on protein stabilisation

We want it to be a culture”: Children and young people’s perceptions of what underpins and undermines education-based wellbeing provision"

Background: Provision that aims to promote the social, emotional, and mental wellbeing of children and young people (including their mental health) is increasingly implemented in education settings. As researchers, policymakers, and practitioners explore the complexities of promotion and prevention provision in practice, it is critical that we include and amplify children and young people’s perspectives. In the current study, we explore children and young people’s perceptions of the values, conditions, foundations that underpin effective social, emotional, and mental wellbeing provision. Methods: We engaged in remote focus groups with 49 children and young people aged 6–17 years across diverse settings and backgrounds, using a storybook in which participants constructed wellbeing provision for a fictional setting. Analysis: Using reflexive thematic analysis, we constructed six main themes presenting participants’ perceptions: 1) recognising and facilitating the setting as a caring social community; 2) enabling wellbeing to be a central setting priority; 3) facilitating strong relationships with staff who understand and care about wellbeing; 4) engaging children and young people as active partners; 5) adapting to collective and individual needs; and 6) being discreet and sensitive to vulnerability. Conclusions: Our analysis presents a vision from children and young people of an integrated systems approach to wellbeing provision, with a relational, participatory culture in which wellbeing and student needs are prioritised. However, our participants identified a range of tensions that risk undermining efforts to promote wellbeing. Achieving children and young people’s vision for an integrated culture of wellbeing will require critical reflection and change to address the current challenges faced by education settings and staff.<br/

Pain in malignant pleural mesothelioma: a prospective characterisation study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is associated with severe pain. The underlying neurobiology of this is complex. The primary aim of this study was to characterize pain in MPM. METHODS: This study was undertaken as part of a trial examining radiotherapy for the treatment of pain in MPM (ISRCTN 10644347). Patients had MPM with associated pain for which radiotherapy was planned and a worst pain score ≥ 4/10. The following assessments were undertaken: clinical neuropathic pain assessment, Brief Pain Inventory (BPI), Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Short form of the McGill Pain Questionnaire (SF-MPQ), and Quantitative Sensory Testing (QST). The relationship of these characteristics and response to radiotherapy was assessed. Unless stated, medians and interquartile range (IQR) are used. RESULTS: Thirty-seven patients were recruited. Average pain and worst pain was 4 (4-6) and 8 (6-8), respectively. Higher average pain and higher worst pain scores were associated with higher interference scores on the BPI, P &lt; 0.001 and P &lt; 0.0005. Twenty patients (54%) had a clinical diagnosis of neuropathic pain, and of these, only six patients (40%) screened positively for neuropathic pain using the LANSS. Patients with a high LANSS also had higher BPI and SF-MPQs. The presence of neuropathic pain (clinically or by LANSS) did not predict response to radiotherapy, P &lt; 0.05. The SF-MPQ scores were higher in those with abnormal cool sensation on QST (P = 0.016). CONCLUSION: Pain in mesothelioma varies among patients and may have neuropathic components. An adequate pain assessment is necessary to guide the clinician in the appropriate choice of analgesics

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

Characteristics of patients who had a stroke not initially identified during emergency prehospital assessment: a systematic review

Background Around 25% of stroke patients do not present with typical ‘Face, Arm, Speech’ symptoms at onset, and are challenging for emergency medical services (EMS) to identify. The aim of this systematic review was to identify the characteristics of acute stroke presentations associated with inaccurate EMS identification (false negatives). Method We performed a systematic search of MEDLINE, EMBASE, CINAHL and PubMed from 1995 to September 2019 using key terms: stroke, Emergency Medical Services, paramedics, identification and assessment. Studies included: Stroke patients or patient records; ≥ 18 years, any stroke type; prehospital assessment undertaken by health professionals including paramedics or technicians; data reported on prehospital diagnostic accuracy and/or presenting symptoms. Data were extracted and study quality assessed by two researchers using the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2) tool. Results Of 845 studies initially identified, 21 observational studies met the inclusion criteria. Of the 6934 stroke and Transient Ischaemic Attack (TIA) patients included, there were 1774 (26%) false negative patients (range from 4 (2%) to 247 (52%)). Commonly documented symptoms in false negative cases were speech problems (n=107; 13% to 28%), nausea/vomiting (n=94; 8% to 38%), dizziness (n=86; 23% to 27%), changes in mental status (n=51; 8% to 25%) and visual disturbance/impairment (n=43; 13% to 28%). Conclusion Speech problems and posterior circulation symptoms were the most commonly documented symptoms amongst stroke presentations that were not correctly identified by EMS (false negatives). However, the addition of further symptoms to stroke screening tools requires valuation of subsequent sensitivity and specificity, training needs, and possible overuse of high priority resources

Psychological interventions for weight reduction and sustained weight reduction in adults with overweight and obesity: a scoping review protocol

Introduction: Overweight and obesity are growing public health problems worldwide. Both diet and physical activity have been the primary interventions for weight reduction over the past decade. With increasing rates of overweight and obesity, it is evident that a primary focus on diet and exercise has not resulted in sustained obesity reduction within the global population. There is now a case to explore other weight management strategies, focusing on psychological factors that may underpin overweight and obesity. Psychological therapy interventions are gaining recognition for their effectiveness in addressing underlying emotional factors and promoting weight loss. However, there is a dearth of literature that has mapped the types of psychological interventions and the characteristics of these interventions as a means of achieving weight reduction and sustained weight reduction in adults with overweight or obesity. Methods and analysis: The review will combine the methodology outlined by Arksey and O’Malley with the PRISMA-ScR guidelines. A total of six databases will be searched using a comprehensive search strategy. Intervention studies will be included if participants are 18 years and over, classified as overweight or obese (≥BMI 25kg/m2), and have received a psychological therapy intervention. The review will exclude studies that are not available in English, not full text, none peer reviewed or combine a lifestyle and/or pharmacological intervention with a psychological intervention. Data will be synthesised using a narrative synthesis approach. Ethics and dissemination: Ethical approval is not required to conduct this scoping review. The findings will be disseminated through journal publication(s), social media, and a lay summary for key stakeholders

Exploring precision polymers to fine-tune magnetic resonance imaging properties of iron oxide nanoparticles

The use of bio-polymers as stabilising agents for iron oxide-based negative magnetic resonance imaging (MRI) contrast agents has become popular in recent years, however the wide polydispersity of biologically-derived and commercially available polymers limits the ability to produce truly tuneable and reproducible behaviour, a major challenge in this area. In this work, stable colloids of iron oxide nanoparticles were prepared utilising precision-engineered bio-polymer mimics, poly(2-acrylamido-2-methylpropane sodium sulfonate) (P(AMPS)) polymers, with controlled narrow polydispersity molecular weights, as templating stabilisers. In addition to producing magnetic colloids with excellent MRI contrast capabilities (r values reaching 434.2 mM  s at 25 °C and 23 MHz, several times higher than similar commercial analogues), variable field relaxometry provided unexpected important insights into the dynamic environment of the hydrated materials, and hence their exceptional MRI behaviour. Thanks to the polymer's templating backbone and flexible conformation in aqueous suspension, nanocomposites appear to behave as "multi-core" clustered species, enhancing interparticle interactions whilst retaining water diffusion, boosting relaxation properties at low frequency. This clustering behaviour, evidenced by small-angle X-ray scattering, and strong relaxometric response, was fine-tuned using the well-defined molecular weight polymer species with precise iron to polymer ratios. By also showing negligible haemolytic activity, these nanocomposites exhibit considerable potential for MRI diagnostics. [Abstract copyright: Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

De novo designed peptide and protein hairpins self‐assemble into sheets and nanoparticles

AFM, TEM, fluorescence microscopy image files and spectral data published in DOI:10.1002/smll.202100472. Preprint of this is available at bioRxiv DOI:10.1101/2020.08.14.25146