Investigating Peripheral Innervation and Epithelial Development in Embryonic Chicken Lungs

Studies have begun to determine the impact of peripheral nerve development on epithelial morphogenesis in branching organs, such as the salivary gland and lung. While most of these studies have used embryonic mice as the model organism, studying this interplay in embryonic chicken lungs is an uncharted research area. Thus, this thesis investigates the interaction between peripheral innervation and epithelial development using embryonic chicken lungs as a model system. First, I characterized nerve development in relation to the epithelium, both qualitatively and quantitatively, using whole-mount fluorescent staining. Subsequently, I used two different drugs to manipulate the acetylcholine neurotransmitter pathway; this pathway has been previously studied in embryonic mouse lungs and salivary glands. I performed these pharmacological manipulations through in vitro cultured explant experiments, and in ovo microinjection experiments. Lastly, I used RNA-sequencing to examine the differential expression of nerve-related genes between the following stages of embryonic lung development: E5 (1-3 buds) and E6 (several buds and extended branches). By studying the impact of peripheral innervation on epithelial development in embryonic chicken lungs, mechanisms that can serve as prevention and treatment targets for underdeveloped lung diseases can be identified

Vaccine hesitancy and attitude towards vaccination among parents of children between 1-5 years of age attending a tertiary care hospital in Chennai, India

Introduction: Vaccination is an effective public health intervention; however, coverage of vaccination is declining in states like Tamil Nadu which have good health indicators. Objective: To evaluate the presence of vaccine hesitancy among parents of children between 1 and 5 years of age attending the paediatric out patient department of a tertiary care hospital in Chennai and to assess its relationship with attitudes towards vaccines. Material & Methods: A cross sectional questionnaire-based survey was conducted among 100 consecutively sampled parents of children between 1 and 5 years of age attending a tertiary care paediatric out-patient department. The Parental Attitude towards Childhood Vaccines scale of vaccine hesitancy and the Beliefs and Attitudes towards Childhood Vaccines scale were used to measure vaccine hesitancy and beliefs and attitudes towards vaccination respectively. The data were analysed descriptively and statistical correlation between vaccination attitudes and vaccination hesitancy were studied. Results: In the predominantly urban, educated, working class population, the prevalence of vaccine hesitancy was 21%. But all the children had received complete vaccination appropriate for age. The major drivers for vaccine hesitancy were suspicions about newer vaccines, concerns about adverse effects of vaccines and the perception that there is no need for vaccines against uncommon diseases. The vaccine hesitancy scores were negatively correlated with the vaccine attitude scores (R = -0.266; p = 0.007). Conclusion: Vaccine hesitancy is present among the sampled mothers and is influenced mainly by concerns regarding safety of newer vaccines. Vaccine hesitancy needs to be clearly addressed for strengthening the Universal Immunization Program

Creating Controlled Thickness Gradients in Polymer Thin Films via Flowcoating

Flowcoating is a popular technique for generating thin (5–200 nm), substrate-supported polymer films. In this process, a reservoir of coating fluid is held between the horizontal substrate and a nearly horizontal blade above the substrate; a film of fluid is drawn out of the reservoir by moving the substrate. Accelerating the substrate produces a film with a thickness gradient, particularly useful for high-throughput measurements where film thickness is an important parameter. The present work compares experimental film thickness profiles with a model based on a Landau–Levich treatment to identify the experimental parameters which govern film thickness. The key parameters are the capillary number and the radius of curvature of the reservoir’s static meniscus, which is set by the blade angle, gap height, solution reservoir volume, and contact angles of the fluid with the blade and substrate. The results show excellent quantitative agreement with the first-principles model; the model thus provides a design approach which allows a user to produce polymer thin films of virtually any desired thickness profile

Transplantation elicits a clonally diverse CD8+ T cell response that is comprised of potent CD43+ effectors

Summary: CD8+ T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. Using MHC class I tetramers, we find that allogeneic CD8+ T cells are present at an elevated naive precursor frequency relative to other epitopes, only modestly increase in number after grafting, and maintain high T cell receptor diversity throughout the immune response. While antigen-specific effector CD8+ T cells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defines potent effectors after transplantation. Activated CD43+ effector T cells maintain high expression of the coreceptor induced T cell costimulator (ICOS) in the presence of CTLA-4 immunoglobulin (Ig), and dual CTLA-4 Ig/anti-ICOS treatment prolongs graft survival. These data demonstrate that graft-specific CD8+ T cells have a distinct response profile relative to anti-pathogen CD8+ T cells and that CD43 and ICOS are critical surface receptors that define potent effector CD8+ T cell populations that form after transplantation

Unbiased discovery of autoantibodies associated with severe COVID-19 via genome-scale self-assembled DNA-barcoded protein libraries

Pathogenic autoreactive antibodies that may be associated with life-threatening coronavirus disease 2019 (COVID-19) remain to be identified. Here, we show that self-assembled genome-scale libraries of full-length proteins covalently coupled to unique DNA barcodes for analysis by sequencing can be used for the unbiased identification of autoreactive antibodies in plasma samples. By screening 11,076 DNA-barcoded proteins expressed from a sequence-verified human ORFeome library, the method, which we named MIPSA (for Molecular Indexing of Proteins by Self-Assembly), allowed us to detect circulating neutralizing type-I and type-III interferon (IFN) autoantibodies in five plasma samples from 55 patients with life-threatening COVID-19. In addition to identifying neutralizing type-I IFN-α and IFN-ω autoantibodies and other previously known autoreactive antibodies in patient plasma, MIPSA enabled the detection of as yet unidentified neutralizing type-III anti-IFN-λ3 autoantibodies that were not seen in healthy plasma samples or in convalescent plasma from ten non-hospitalized individuals with COVID-19. The low cost and simple workflow of MIPSA will facilitate unbiased high-throughput analyses of protein-antibody, protein-protein and protein-small-molecule interactions

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license