Mechanisms of Degranulation in Neutrophils

Neutrophils are critical inflammatory cells that cause tissue damage in a range of diseases and disorders. Being bone marrow-derived white blood cells, they migrate from the bloodstream to sites of tissue inflammation in response to chemotactic signals and induce inflammation by undergoing receptor-mediated respiratory burst and degranulation. Degranulation from neutrophils has been implicated as a major causative factor in pulmonary disorders, including severe asphyxic episodes of asthma. However, the mechanisms that control neutrophil degranulation are not well understood. Recent observations indicate that granule release from neutrophils depends on activation of intracellular signalling pathways, including β-arrestins, the Rho guanosine triphosphatase Rac2, soluble NSF attachment protein (SNAP) receptors, the src family of tyrosine kinases, and the tyrosine phosphatase MEG2. Some of these observations suggest that degranulation from neutrophils is selective and depends on nonredundant signalling pathways. This review focuses on new findings from the literature on the mechanisms that control the release of granule-derived mediators from neutrophils

Gender Differences in the Relationships between Research Impact and Compensation and Promotion: A Case Study Among PhD/PharmD

We examine whether the effects of research impact on faculty compensation and promotion to full professor differ for male and female associate and full professors in the Faculty of Medicine & Dentistry at the University of Alberta. We exclude faculty with MDs and DDSs and proxy for research impact using the faculty member’s h-index, where h represents the number of publications that have been cited at least h times. We find that while the compensation of male faculty members increases by 0.6% for every one-unit increase in the h-index, the compensation of female faculty is essentially uncorrelated with their h-indices. We likewise find that for female faculty to be promoted to full professor they have to have higher research impact proxies than their male peers. Our findings highlight the urgent need for more research on the gendered relationships between research impact and career rewards among faculty.Nous avons évalué l’impact de la recherche sur la rémunération du corps professoral et la promotion au rang de professeur titulaire, entre les professeurs agrégés et titulaires hommes et femmes de la Faculté de médecine et de dentisterie de l’Université de l’Alberta. Nous avons exclu les professeurs cliniciens ayant un doctorat en médecine (MD) ou un doctorat en médecine dentaire (DDSs). L’impact de la recherche a été évalué à l’aide de l’indice h de chaque membre du corps professoral, oùh représente le nombre de publications qui ont été citées au moins h fois. Nous constatons ainsi que tandis que la rémunération des hommes augmente en moyenne de 0,6 % pour chaque augmentation d’une unité de l’indice h, la rémunération des femmes est essentiellement non corrélée avec leurs indices h. Nous constatons également que les professeures atteignent la parité pour la  promotion au poste de professeur titulaire avec les professeurs masculins équivalents à des indicateursd’impact de la recherche considérablement supérieurs aux valeurs médianes normalement attendues pour une promotion au poste de professeur titulaire. Nos résultats mettent en évidence le besoin urgent de plus de recherches sur les relations entre le genre et l’impact de la recherche sur l’avancement de la carrière chez les professeurs-chercheurs

Are Advanced Practice Registered Nurses In Mississippi Participating In Practices That Advocate The Nursing Profession

Previous research studies have focused on patient outcomes related to healthcare interventions, but there is little research available regarding nurses’ involvement in activities that would advance the profession. Advanced Practice Registered Nurses’ (APRN) contributions to the healthcare system lead to direct improvement of patient outcomes through research, mentoring new professionals, and participating in professional organizations. The theoretical motivation behind the study is Ray’s Theory of Bureaucratic Caring that proposed healthcare personnel consider incorporation of the business aspects of healthcare to propel nursing into the future. Ray dared nurses to become leaders in the field, understand the corporate aspects of health care, evolve bedside nursing through research activity, and build future nurse leaders with political and mentorship works. The study considers characteristics Ray demanded nurses take to control the future of the profession and advance the nurse’s role in healthcare. The study will assess current level of involvement of APRNs in three activities that directly advance the profession. Survey questions will address demographic information and the degree of participation in the three specific activities. The study will use a quantitative approach through randomized surveys distributed through face-to-face encounters, Survey Monkey, social media, and email. Inclusion criteria is limited to practicing APRNs within any specialty with a master’s level education or higher

Proteomic analysis of secretagogue-stimulated neutrophils implicates a role for actin and actin-interacting proteins in Rac2-mediated granule exocytosis

<p>Abstract</p> <p>Background</p> <p>Neutrophils are abundant leukocytes that play a primary role in defence against pathogens. Neutrophils enter sites of infection where they eliminate pathogens via phagocytosis and the release of antimicrobial mediators via degranulation. Rho GTPases, particularly Rac2, play a key role in neutrophil degranulation. The purpose of this study was to identify Rac2-dependent changes in protein abundance in stimulated neutrophils.</p> <p>Methods</p> <p>We performed a proteomic analysis on secretagogue-stimulated bone marrow neutrophils that were isolated from wild-type and Rac2^-/-mice. Protein abundance was analyzed by 2-dimensional SDS-PAGE of fluorescently labelled samples which allowed the detection ~3500 proteins.</p> <p>Results</p> <p>We identified 22 proteins that showed significant changes in abundance after secretagogue-stimulation of wild-type neutrophils, which did not occur in neutrophils isolated from Rac2^-/-mice. As expected, the abundance of several granule proteins was reduced in wild-type cells; this did not occur in Rac2^-/-neutrophils which confirms the requirement for Rac2 in degranulation. We also found changes in abundance of many actin remodelling proteins including coronin-1A, β-actin and the F-actin capping protein, (CapZ-β). Coronin-1A showed elevated levels of several isoforms after stimulation of neutrophils from wild-type, but not from Rac2^-/-mice. These isoforms were immunoreactive with anti-phospho-threonine antibodies, suggesting that neutrophil stimulation triggers a Rac2-dependent kinase cascade that results in the phosphorylation of coronin-1A.</p> <p>Conclusion</p> <p>The control of Rac2-mediated degranulation in neutrophils likely functions through actin remodelling via activation of several actin-binding proteins. We found coronin-1A to be a novel downstream effector protein of this pathway that is threonine phosphorylated in response to secretagogue stimulation.</p

Interleukin‐5 drives glycolysis and reactive oxygen species‐dependent citric acid cycling by eosinophils

Introduction Eosinophils have been long implicated in antiparasite immunity and allergic diseases and, more recently, in regulating adipose tissue homeostasis. The metabolic processes that govern eosinophils, particularly upon activation, are unknown. Methods Peripheral blood eosinophils were isolated for the analysis of metabolic processes using extracellular flux analysis and individual metabolites by stable isotope tracer analysis coupled to gas chromatography‐mass spectrometry following treatment with IL‐3, IL‐5 or granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Eosinophil metabolism was elucidated using pharmacological inhibitors. Results Human eosinophils engage a largely glycolytic metabolism but also employ mitochondrial metabolism. Cytokine stimulation generates citric acid cycle (TCA) intermediates from both glucose and glutamine revealing this previously unknown role for mitochondria upon eosinophil activation. We further show that the metabolic programme driven by IL‐5 is dependent on the STAT5/PI3K/Akt signalling axis and that nicotinamide adenine dinucleotide phosphate oxidase (NOX)‐dependent ROS production might be a driver of mitochondrial metabolism upon eosinophil activation. Conclusion We demonstrate for the first time that eosinophils are capable of metabolic plasticity, evidenced by increased glucose‐derived lactate production upon ROS inhibition. Collectively, this study reveals a role for both glycolysis and mitochondrial metabolism in cytokine‐stimulated eosinophils. Selective targeting of eosinophil metabolism may be of therapeutic benefit in eosinophil‐mediated diseases and regulation of tissue homeostasis

Il meticciato nell'Italia contemporanea. Storia, memorie e cultura di massa.

L'idea diffusa degli "italiani brava gente" e della diversit\ue0 della nostra storia rispetto alla storia USA, segnata da razzismo istituzionale, si fonda sul silenziamento del passato coloniale e razzista italiano. Il ripudio della categoria di razza da parte dell'Italia repubblicana e la smentita scientifica dell'esistenza biologica della categoria non hanno cancellato la presenza della razza, formazione storico-culturale che paradossalmente esiste e non esiste. Priva di referenti oggettivi nella realt\ue0, la razza produce in essa effetti significativi, opera sia come categoria sociale e strumento di esclusione, sia come costruzione simbolica e istanza identitaria. A fronte del silenziamento del meticciato storico nell'uso pubblico della storia e nella memoria nazionali del secondo dopoguerra, il saggio sottolinea la presenza diffusa del meticciato nei prodotti della cultura di massa italiani contemporanei e ne indaga i significati con gli strumenti degli studi critici sulla razza e in prospettiva comparata tra Italia e Stati Uniti

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine