Cyclooxygenase-2 and prostaglandin E(2)(PGE(2)) receptor messenger RNAs are affected by bovine oocyte maturation time and cumulus-oocyte complex quality, and PGE(2) induces moderate expansion of the bovine cumulus in vitro.

Expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) receptor 2 (EP2) are necessary for rodent cumulus expansion in vivo. Prostaglandin E(2) receptor 3 (EP3) has been detected in bovine preovulatory follicles and corpora lutea. The current experiments examined the effect of PGE(2) on bovine cumulus expansion in vitro and expression of COX-2, EP1, EP2, EP3, and EP4 mRNAs in bovine cumulus-oocyte complexes (COCs) at 0, 6, 12, 18, and 24 h time points during maturation in vitro. Concentrations of PGE(2) above 50 ng/ml resulted in moderate cumulus expansion of bovine COCs, but expansion did not occur in the absence of serum. COX-2 mRNA expression increased in bovine COCs at 6 h and 12 h of maturation, then decreased. EP2 mRNA was detectable by reverse transcription-polymerase chain reaction at all time points. EP3 mRNA expression increased in COCs from 0 to 6 h and remained at this higher level through the culture period. Very low levels of EP4 mRNA expression were detectable, but EP1 was not detected in bovine COCs. Because EP receptor mRNAs and COX-2 mRNA are expressed in bovine COCs, there exists the potential for a prostaglandin autocrine/paracrine regulatory pathway during oocyte maturation. Differential expression of the EP3 mRNA among varying COC classes indicates that this gene product may be a useful marker of oocyte competence. Although the PGE(2) pathway is involved in cumulus expansion, serum factors are required to mediate PGE(2)-induced expansion

Circularly polarized colour reflection from helicoidal structures in the beetle Plusiotis boucardi

Copyright © 2007 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. This is the published version of an article published in New Journal of Physics Vol. 9, article 99. DOI: 10.1088/1367-2630/9/4/099A detailed optical study of the iridescent outer-shell of the beetle Plusiotis boucardi has revealed a novel microstructure which controls both the polarization and wavelength of reflected light. A previously unreported hexagonal array across the integument of the beetle exhibits highly localized regions of reflection of only red and green left-handed circularly-polarized light. Optical and transmission electron microscopy (TEM) imaging reveals the origin of this effect as an array of 'bowl-shaped' recesses on the elytra that are formed from a dual-pitch helicoidal layer. Reflectivity spectra collected from the beetle are compared to theoretical data produced using a multi-layer optics model for modelling chiral, optically anisotropic media such as cholesteric liquid crystals. Excellent agreement is obtained between data and theory produced using a model that incorporates an upper isotropic layer (of cuticular wax), followed by a short pitch (310 (± 1) nm) overlying a longer pitch (370 (±1) nm) helicoidal layer of optically anisotropic material. These layers are backed by an absorbing underlayer. Synthetic replication of this form of structure may provide a route to the fabrication of tuneable micro-mirrors for optical applications

Mineral-PET: Kimberlite sorting by nuclear-medical technology

A revolutionary new technology for diamond bearing rock sorting which has its roots in medical-nuclear physics has been taken through a substantial part of the R&D phase. This has led to the construction of the technology demonstrator. Experiments using the technology demonstrator and experiments at a hospital have established the scientific and technological viability of the project

Making it work for me: beliefs about making a personal health record relevant and useable.

BACKGROUND: A Personal Health Record (PHR) is an electronic record that individuals use to manage and share their health information, e.g. data from their medical records and data collected by apps. However, engagement with their record can be low if people do not find it beneficial to their health, wellbeing or interactions with health and other services. We have explored the beliefs potential users have about a PHR, how it could be made personally relevant, and barriers to its use. METHODS: A qualitative design comprising eight focus groups, each with 6-8 participants. Groups included adults with long-term health conditions, young people, physically active adults, data experts, and members of the voluntary sector. Each group lasted 60-90 min, was audio recorded and transcribed verbatim. We analysed the data using thematic analysis to address the question "What are people's beliefs about making a Personal Health Record have relevance and impact?" RESULTS: We found four themes. Making it work for me is about how to encourage individuals to actively engage with their PHR. I control my information is about individuals deciding what to share and who to share it with. My concerns is about individuals' concerns about information security and if and how their information will be acted upon. Potential impact shows the potential benefits of a PHR such as increasing self-efficacy, uptake of health-protective behaviours, and professionals taking a more holistic approach to providing care and facilitating behaviour change. CONCLUSIONS: Our research shows the functionality that a PHR requires in order for people to engage with it. Interactive functions and integration with lifestyle and health apps are particularly important. A PHR could increase the effectiveness of behaviour change apps by specifying evidence-based behaviour change techniques that apps should incorporate. A PHR has the potential to increase health-protective behaviours and facilitate a more person-driven health and social care system. It could support patients to take responsibility for self-managing their health and treatment regimens, as well as helping patients to play a more active role when care transfers across boundaries of responsibility

Reconstruction of Genome-Scale Active Metabolic Networks for 69 Human Cell Types and 16 Cancer Types Using INIT

Development of high throughput analytical methods has given physicians the potential access to extensive and patient-specific data sets, such as gene sequences, gene expression profiles or metabolite footprints. This opens for a new approach in health care, which is both personalized and based on system-level analysis. Genome-scale metabolic networks provide a mechanistic description of the relationships between different genes, which is valuable for the analysis and interpretation of large experimental data-sets. Here we describe the generation of genome-scale active metabolic networks for 69 different cell types and 16 cancer types using the INIT (Integrative Network Inference for Tissues) algorithm. The INIT algorithm uses cell type specific information about protein abundances contained in the Human Proteome Atlas as the main source of evidence. The generated models constitute the first step towards establishing a Human Metabolic Atlas, which will be a comprehensive description (accessible online) of the metabolism of different human cell types, and will allow for tissue-level and organism-level simulations in order to achieve a better understanding of complex diseases. A comparative analysis between the active metabolic networks of cancer types and healthy cell types allowed for identification of cancer-specific metabolic features that constitute generic potential drug targets for cancer treatment

Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR

Tanya M Laidlaw1,2 *, Andrew Menzies-Gow3 *, Scott Caveney,4 Joseph K Han,5 Nicole Martin,6,7 Elliot Israel,8 Jason K Lee,9,10 Jean-Pierre Llanos,11 Neil Martin,12,13 Ayman Megally,14 Bhavini Parikh,14 Sylvia Vong,15 Tobias Welte,16 Jonathan Corren17 1Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA, USA; 2Department of Medicine, Harvard Medical School, Boston, MA, USA; 3Royal Brompton and Harefield Hospitals, School of Immunology and Microbial Sciences, King’s College London, London, UK; 4Global Development, Inflammation, R&D, Amgen, Thousand Oaks, CA, USA; 5Department of Otolaryngology, Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, VA, USA; 6Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA; 7Cytel Inc, Waltham, MA, USA; 8Divisions of Pulmonary and Critical Care Medicine and Allergy and Clinical Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 9Evidence Based Medical Educator Inc., Toronto, ON, Canada; 10Toronto Allergy and Asthma Clinic, Toronto, ON, Canada; 11Global Medical Affairs, Amgen, Thousand Oaks, CA, USA; 12Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 13University of Leicester, Leicester, UK; 14Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 15Translational Science and Experimental Medicine, Early Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA; 16Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany; 17David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA*These authors contributed equally to this workCorrespondence: Tanya M Laidlaw, Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, 60 Fenwood Road, Boston, MA, 02115, USA, Email [email protected]: Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control versus placebo in adults and adolescents with severe, uncontrolled asthma. We assessed the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR.Methods: Patients with severe asthma (N=1059) were randomized (1:1) and received tezepelumab 210 mg or placebo every 4 weeks subcutaneously for 52 weeks. Prespecified exploratory analyses included: AAER over 52 weeks and changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second, Sino-Nasal Outcome Test (SNOT)-22 scores, and asthma control and health-related quality life (HRQoL) outcomes in NP subgroups. Changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase-10 (MMP-10), and serum interleukin (IL)-5, IL-6, IL-8 and IL-13 were assessed (post hoc).Results: Tezepelumab reduced the AAER over 52 weeks versus placebo by 85% (95% confidence interval [CI]: 72, 92; n=118) and 51% (95% CI: 40, 60; n=941) in patients with and without NPs, respectively. At week 52, tezepelumab improved lung function, asthma control and HRQoL versus placebo in patients with and without NPs. Tezepelumab reduced SNOT-22 total scores (least-squares mean difference versus placebo [95% CI]) in patients with NPs at 28 weeks (– 12.57 points [– 19.40, – 5.73]) and 52 weeks (– 10.58 points [– 17.75, – 3.41]). At week 52, tezepelumab reduced blood eosinophil counts and FeNO, IgE, IL-5, IL-13, EDN and MMP-10 levels versus placebo, irrespective of NP status.Conclusion: Tezepelumab resulted in clinically meaningful improvements in sino-nasal symptoms and asthma outcomes in patients with severe asthma with comorbid NPs.Graphical Abstract: Plain Language Summary: Asthma is a long-term condition caused by ongoing inflammation of the lower airways. The main symptoms are difficulty breathing, coughing, wheezing and shortness of breath. Approximately 41% of patients with severe asthma also have chronic rhinosinusitis with nasal polyps, a condition that affects the upper airways and sinuses. Nasal polyps are painless soft growths inside your nose that can keep growing if not treated. Symptoms include nasal congestion with mucus, facial pain and a reduced sense of smell or taste. People with both severe asthma and nasal polyps often have severe symptoms.Thymic stromal lymphopoietin (TSLP) is a signaling molecule released by cells lining the airways in response to airborne triggers, such as smoke, pollen and viruses. TSLP activates several pathways that cause inflammation in the airways, leading to asthma symptoms. Tezepelumab is a biologic treatment that targets the very start of these inflammatory pathways by blocking TSLP.The 1-year-long clinical trial called “NAVIGATOR” reported that tezepelumab reduced asthma attacks and improved lung function and asthma symptom control compared with placebo in patients with severe asthma that was not controlled with their current medicines. This analysis of data from NAVIGATOR looked at patients with both severe asthma and nasal polyps, showing that tezepelumab treatment improved sino-nasal symptoms compared with placebo. Tezepelumab also reduced asthma attacks and improved asthma symptoms, regardless of a patient’s medical history of nasal polyps. The effects of tezepelumab in patients with severe nasal polyps are being investigated in another clinical trial called “WAYPOINT”.Keywords: chronic rhinosinusitis, nasal polyps, SNOT-22, thymic stromal lymphopoieti

Circular Polarization Vision of Scarab Beetles

International audienceIn this chapter the occurrence of circularly polarized (CP) light in nature (both in the abiotic and biotic optical environment) is surveyed. We deal with the reason and the possible adaptive significance of CP light reflected from the exocuticle of many beetle species belonging to the Scarabaeoidea. This unique feature of the insect exocuticle seems to have evolved only in scarabaeoids. The imaging polarimetry of circularly polarizing scarab beetles and its results are reviewed. The alleged CP sensitivity in Chrysina gloriosa scarabs is briefly discussed. Finally, the experimental evidence for the lack of CP vision in the scarab species Anomala dubia, A. vitis (Coleoptera, Scarabaeidae, Rutelinae), Cetonia aurata, and Protaetia cuprea (Coleoptera, Scarabaeidae, Cetoniinae) with circularly polarizing exocuticle is presented