Generation of precision-cut slice cultures of human placenta.

We present a protocol to generate an advanced ex vivo model of human placenta. We use a vibrating tissue slicer to obtain precision-cut slices representative of the entire thickness of human placenta. This approach delivers standardized cultures with a preserved microstructure and cellular composition comparable to the native tissue. We applied this system to study SARS-CoV-2 infection at the maternal-fetal interface. Moreover, this system can be used to investigate the basic functions of the human placenta in health and disease. For complete details on the use and execution of this protocol, please refer to Fahmi et al. (2021)

Correction: Absence of Zika virus among pregnant women in Vietnam in 2008.

International audienc

Exploring the Potential of Using Carbonyl Sulfide to Track the Urban Biosphere Signal

Unidad de excelencia María de Maeztu CEX2019-000940-MCities are implementing additional urban green as a means to capture CO and become more carbon neutral. However, cities are complex systems where anthropogenic and natural components of the CO budget interact with each other, and the ability to measure the efficacy of such measures is still not properly addressed. There is still a high degree of uncertainty in determining the contribution of the vegetation signal, which furthermore confounds the use of CO mole fraction measurements for inferring anthropogenic emissions of CO. Carbonyl sulfide (OCS) is a tracer of photosynthesis which can aid in constraining the biosphere signal. This study explores the potential of using OCS to track the urban biosphere signal. We used the Sulfur Transport and dEposition Model (STEM) to simulate the OCS concentrations and the Carnegie Ames Stanford Approach ecosystem model to simulate global CO fluxes over the Bay Area of San Francisco during March 2015. Two observation towers provided measurements of OCS and CO: The Sutro tower in San Francisco (upwind from the area of study providing background observations), and a tower located at Sandia National Laboratories in Livermore (downwind of the highly urbanized San Francisco region). Our results show that the STEM model works better under stable marine influence, and that the boundary layer height and entrainment are driving the diurnal changes in OCS and CO at the downwind Sandia site. However, the STEM model needs to better represent the transport and boundary layer variability, and improved estimates of gross primary productivity for characterizing the urban biosphere signal are needed

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype.

Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and animal models are urgently needed. Here, we characterize Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in hamsters, ferrets and hACE2-expressing mice, and immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In hamsters, Delta shows dominance over Omicron-BA.1, and in ferrets Omicron-BA.1 infection is abortive. In hACE2-knock-in mice, Delta and a Delta spike clone also show dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observe Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of replication and pathogenicity. Finally, the Omicron-BA.1 spike clone is less well-controlled by mRNA-vaccination in K18-hACE2-mice and becomes more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA. 1 phenotype

Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and animal models are urgently needed. Here, we characterize Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in hamsters, ferrets and hACE2-expressing mice, and immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In hamsters, Delta shows dominance over Omicron-BA.1, and in ferrets Omicron-BA.1 infection is abortive. In hACE2-knock-in mice, Delta and a Delta spike clone also show dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observe Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of replication and pathogenicity. Finally, the Omicron-BA.1 spike clone is less well-controlled by mRNA-vaccination in K18-hACE2-mice and becomes more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance

Absence of Zika virus among pregnant women in Vietnam in 2008.

BACKGROUND Despite being first identified in 1947, Zika virus-related outbreaks were first described starting from 2007 culminating with the 2015 Latin American outbreak. Hypotheses indicate that the virus has been circulating in Asia for decades, but reports are scarce. METHODS We performed serological analysis and screened placental samples isolated in 2008 for the presence of Zika virus from pregnant women in Ho Chi Minh City (Vietnam). RESULTS None of the placental samples was positive for Zika virus. Four serum samples out of 176 (2.3%) specifically inhibited Zika virus, with variable degrees of cross-reactivity with other flaviviruses. While one of the four samples inhibited only Zika virus, cross-reactivity with other flaviviruses not included in the study could not be ruled out. CONCLUSION Our results support the conclusion that the virus was not present among pregnant women in the Vietnamese largest city during the initial phases of the epidemic wave

SARS-CoV-2 can infect and propagate in human placenta explants.

The ongoing SARS-CoV-2 pandemic continues to lead to high morbidity and mortality. During pregnancy, severe maternal and neonatal outcomes and placental pathological changes have been described. We evaluate SARS-CoV-2 infection at the maternal-fetal interface using precision-cut slices (PCSs) of human placenta. Remarkably, exposure of placenta PCSs to SARS-CoV-2 leads to a full replication cycle with infectious virus release. Moreover, the susceptibility of placental tissue to SARS-CoV-2 replication relates to the expression levels of ACE2. Viral proteins and/or viral RNA are detected in syncytiotrophoblasts, cytotrophoblasts, villous stroma, and possibly Hofbauer cells. While SARS-CoV-2 infection of placenta PCSs does not cause a detectable cytotoxicity or a pro-inflammatory cytokine response, an upregulation of one order of magnitude of interferon type III transcripts is measured. In conclusion, our data demonstrate the capacity of SARS-CoV-2 to infect and propagate in human placenta and constitute a basis for further investigation of SARS-CoV-2 biology at the maternal-fetal interface

The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis.

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4+ and CD8+ T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity

The lexicography of German

This chapter discusses the main dictionaries of the German language as it is spoken and written in Germany, and also German as it is spoken and written in Austria, Switzerland, the eastern fringes of Belgium, and South Tyrol. It also briefly describes Pennsylvania German. Corpora and other language resources used in German dictionary-making are also presented. Finally, there is a discussion of some current issues in German lexicography, as well as future prospects