The history of pediatric allergy in Europe – From a working group to ESPACI and SP‐EAACI

A Working Group on Pediatric Allergology was formed in 1984, which rapidly developed to become the European Society on Pediatric Allergology and Clinical Immunology (ESPACI) in 1988 with its own journal, Pediatric Allergology and Immunology. ESPACI worked together with the European Academy of Allergology and Clinical Immunology (EAACI) to form a Section of Pediatrics within EAACI (SP‐EAACI) in 1996. The ESPACI and the SP‐EAACI formally merged in 2001. Within the EAACI organization, the Pediatric Section has continued to grow. The Pediatric Section is working to develop pediatric allergology across Europe, focusing on postgraduate education, facilitating the research agenda and advocating for children and adolescents with allergies.     

Budding of filamentous and non-filamentous influenza A virus occurs via a VPS4 and VPS28-independent pathway

The mechanism of membrane scission during influenza A virus budding has been the subject of controversy. We confirm that influenza M1 binds VPS28, a subunit of the ESCRT-1 complex. However, confocal microscopy of infected cells showed no marked colocalisation between M1 and VPS28 or VPS4 ESCRT proteins, or relocalisation of the cellular proteins. Trafficking of HA and M1 appeared normal when endosomal sorting was impaired by expression of inactive VPS4. Overexpression of either isoform of VPS28 or wildtype or dominant negative VPS4 proteins did not alter production of filamentous virions. SiRNA depletion of endogenous VPS28 had no significant effect on influenza virus replication. Furthermore, cells expressing wildtype or dominant-negative VPS4 replicated filamentous and non-filamentous strains of influenza to similar titres, indicating that influenza release is VPS4-independent. Overall, we see no role for the ESCRT pathway in influenza virus budding and the significance of the M1–VPS28 interaction remains to be determined.     

Role of nucleocapsid protein of hantaviruses in intracellular traffic of viral glycoproteins

To understand the role of nucleocapsid protein (NP) of hantaviruses in viral assembly, the effect of NP on intracellular traffic of viral glycoproteins Gn and Gc was investigated. Double staining of viral and host proteins in Hantaan virus (HTNV)-infected Vero E6 cells showed that Gn and Gc were localized to cis-Golgi, in which virus particles are thought to be formed. When HTNV Gn and Gc were expressed by a plasmid encoding glycoprotein precursor (GPC), which is posttranslationaly cleaved into Gn and Gc, Gn was localized to cis-Golgi, whereas Gc showed diffuse distribution in the cytoplasm in 32.9% of Gc-positive cells. The ratio of the diffused Gc-positive cells was significantly decreased to 15.0% by co-expression of HTNV NP. Co-expression of HTNV GPC with NPs of other hantaviruses, such as Seoul virus, Puumala virus and Sin Nombre virus, also reduced the ratios of diffused Gc-positive cells to 13.5%, 25.2%, and 11.6%, respectively. Among amino- and carboxyl-terminally truncated HTNV NPs, NP75-429, NP116-429, NP1-333, NP1-233, and NP1-155 possessed activity to reduce the ratio of diffused Gc-positive cells, while NP155-429 and NP1-116 did not. NP30-429 has partial activity. These results indicate that amino acid region 116–155 of NP is important for the activity, although amino acid region 1-30 is partially related. Truncation of the HTNV Gc cytoplasmic tail caused an increase in diffused Gc-positive cells. In addition, the effect of coexpression of HTNV NP was weakened. These results suggest that HTNV NP has a role to promote Golgi localization of Gc through a mechanism possibly mediated by the Gc cytoplasmic tail.     

Winnicott and Gender Madness

This essay draws on Winnicott's deep insights developed in a series of texts over the last decade of his life and addressing questions of gender and sexuality, as these phenomena shape and are shaped by core experiences in the evolution of intersubjectivity. Interweaving Winnicott's work with that of Loewald, Laplanche and Matte Blanco, the essay speculates about possible developmental processes through which complex and shifting gender identifications intersect and interact with experiences of sexuality and desiring. The essay tracks Winnicott's evolving ideas about gender and madness and opens a way of thinking about one process by which gender may emerge, in a complex, ‘softly assembled’ encounter with desire and being desired. This approach also seeks to reframe and expand the current move in gender theory ‘from etiology to teleology’. The term ‘etiology’ locates us in causation, diagnosis and the sites of pathology, and I think we should continue to be wary of the intrusion of these socially driven biases and ideas into reflections about sexuality and gender in development.     

Overlapping and independent structural roles for human papillomavirus type 16 L2 conserved cysteines

Cryoelectron microscopy images of HPV16 pseudovirions (PsV) depict that each pentamer of L1 can be occluded with a monomer of L2. Further research suggests that an N-terminal external loop of L2 exists, which is the target of neutralizing and cross-neutralizing antibodies. Here we show that N-terminal L2 cysteine residues, Cys22 and Cys28, have overlapping and independent structural roles, which affect both early- and late-stage assembly events. Substitution of either cysteine residue enhances infectivity markedly in comparison to wild-type HPV16. However, only Cys22Ser 20-day virions become nearly as stable as wild type. In addition, Cys22Ser, and Cys22,28Ser 20-day virions have lost their susceptibility to neutralization by anti-L2 antibodies, whereas Cys28Ser 20-day virions remain partially susceptible. These results suggest that Cys28 is necessary for late-stage stabilization of capsids, while Cys22 is necessary for proper display of L2 neutralizing epitopes.     

HIV-1 matrix organizes as a hexamer of trimers on membranes containing phosphatidylinositol-(4,5)-bisphosphate

The human immunodeficiency virus type 1 (HIV-1) matrix (MA) protein represents the N-terminal domain of the HIV-1 precursor Gag (PrGag) protein and carries an N-terminal myristate (Myr) group. HIV-1 MA fosters PrGag membrane binding, as well as assembly of envelope (Env) proteins into virus particles, and recent studies have shown that HIV-1 MA preferentially directs virus assembly at plasma membrane sites enriched in cholesterol and phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P₂). To characterize the membrane binding of MA and PrGag proteins, we have examined how Myr-MA proteins, and proteins composed of Myr-MA and its neighbor Gag capsid (CA) protein associate on membranes containing cholesterol and PI[4,5]P₂. Our results indicate that Myr-MA assembles as a hexamer of trimers on such membranes, and imply that MA trimers interconnect CA hexamer rings in immature virus particles. Our observations suggest a model for the organization of PrGag proteins, and for MA-Env protein interactions.     

Dissection and identification of regions required to form pseudoparticles by the interaction between the nucleocapsid (N) and membrane (M) proteins of SARS coronavirus

When expressed in mammalian cells, the nucleocapsid (N) and membrane (M) proteins of the severe acute respiratory syndrome coronavirus (SARS-CoV) are sufficient to form pseudoparticles. To identify region(s) of the N molecule required for pseudoparticle formation, we performed biochemical analysis of the interaction of N mutants and M in HEK293 cells. Using a peptide library derived from N, we found that amino acids 101-115 constituted a novel binding site for M. We examined the ability of N mutants to interact with M and form pseudoparticles, and our observations indicated that M bound to NΔ(101-115), N1-150, N151-300, and N301-422, but not to N1-150Δ(101-115). However, pseudoparticles were formed when NΔ(101-115) or N301-422, but not N1-150 or N151-300, were expressed with M in HEK293 cells. These results indicated that the minimum portion of N required for the interaction with M and pseudoparticle formation consists of amino acids 301-422.     

Global Vaccine Action Plan Lessons Learned II: Stakeholder Perspectives

IntroductionThe Global Vaccine Action Plan (GVAP), unanimously endorsed by the World Health Assembly in 2012, defined an ambitious strategy to improve immunization. At the end of the decade, significant progress has been made but four of the five GVAP goals are likely to be missed. This report describes a set of surveys and interviews relating to GVAP, conducted to inform the immunization strategy for the next decade.MethodsThree surveys and two sets of semi-structured interviews were conducted from 2017 to 2019. Respondents consisted of immunization stakeholders at global, regional, and country levels, and included individuals who had been involved in the development and implementation of GVAP or its monitoring, evaluation and accountability (M&E/A) process; national immunization managers; academics; and personnel from non-governmental organizations and civil society organizations.ResultsThe surveys and interviews gave consistent results. They highlighted the value of GVAP in increasing visibility for immunization and the benefits of the GVAP M&E/A framework. The main limitations of GVAP were identified as the limited ownership by countries and other stakeholders leading to incomplete implementation of the strategy and poor accountability for achieving GVAP targets.DiscussionThese results informed the review of GVAP and the development of its successor strategy, the Immunization Agenda 2030. In addition, these surveys and interviews identified two challenges in assessing the value of GVAP: the need to rely exclusively on stakeholder perspectives and difficulties in attributing benefits. These challenges are inherent in evaluating an over-arching strategy such as GVAP and should be factored into interpretation of the results.     

Evaluation of ergonomic physical risk factors in a truck manufacturing plant: case study in SCANIA Production Angers

The aims of this study were 1) to assess the ergonomic physical risk factors from practitioner’s viewpoint in a truck assembly plant with an in-house observational method and the NIOSH lifting equation, and 2) to compare the results of both methods and their differences. The in-house ergonomic observational method for truck assembly i.e. the SCANIA Ergonomics Standard (SES) and the NIOSH lifting equation were applied to evaluate physical risk factors and lifting of loads by operators. Both risk assessment approaches revealed various levels of risk, ranging from low to high. Two workstations were identified by the SES method as high risk. The NIOSH lifting index (LI) was greater than two for four lifting tasks. The results of the SES method disagreed with the NIOSH lifting equation for lifting tasks. Moreover, meaningful variations in ergonomic risk patterns were found for various truck models at each workstation. These results provide a better understanding of the physical ergonomic exposure from practitioner’s point of view in the automotive assembly plant.     

流水线作业工人心理负荷与神经行为功能的研究

通过对２８１名流水线作业工人和１７２名非流水线工人的工作心理负荷和神经行为功能的调查研究发现，流水线工作的心理负荷大于非流水线工作，主要表现在自主性、整体性、反馈性、决定能力、意义感和满意感上，特别是自主性和满意感；流水线作业工人的反应时间延长，其工作心理负荷与神经行为功能之间存在极显著的负相关，提示流水线作业工人具有明显负荷特征，并可引起神经行为功能的改变。