Age-related decline of de novo T cell responsiveness as a cause of COVID-19 severity

To the Editor, So far, little attention has been paid to the link between immunosenescence and the dramatic mortality rate of coronavirus disease 2019 (COVID-19) in older age groups. Indeed, the number of cases of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is very low among children and teenagers, in contrast to the increased frequency in adults and the elderly, who are also more at risk of developing very serious symptoms and death (Guan et al. 2020; Wu and McGoogan 2020). As shown in Fig. 1, a similar epidemiological profile was observed during previous coronavirus (severe acute respiratory syndrome coronavirus 1, SARS-CoV-1, and Middle east respiratory syndrome coronavirus, MERS-CoV) outbreaks (Jia et al. 2009; Salamatbakhsh et al. 2019). Notably, the same trend was also noted during West Nile virus and, with some exceptions in very young children, Ebolavirus outbreaks (Bower et al. 2016; Hayes et al. 2005). Likely this phenomenon is multifactorial. For instance, in elderly individuals with severe COVID-19, associated comorbidities are much more prevalent (Guan et al. 2020). In addition, the progressive accumulation of senescent cells during life may play a role in the vulnerability of old people to COVID-19, resulting in reduced functionality of the organs, such as the lungs, and facilitating conditions for the development of fibrosis. Moreover, senescent cells can generate a pro-inflammatory environment, referred to as SASP (for senescence-associated secretory phenotype), which includes many inflammatory cytokines (e.g., interleukin-6) and contributes to the basal hyperinflammatory status characteristic of the old person. This hyperinflammatory status might influence the expression of ACE2, CD147, cyclophilins, CD26, and other CoV-associated molecules in human tissues, thus favoring viral entry (Radzikowska et al. 2020). It likely also constitutes an already unbalanced pro-inflammatory background, on which the development of an exacerbated inflammatory response and acute respiratory distress syndrome may be facilitated upon SARS-CoV-2 infection

Time-sensitive autonomous architectures

Autonomous and software-defined vehicles (ASDVs) feature highly complex systems, coupling safety-critical and non-critical components such as infotainment. These systems require the highest connectivity, both inside the vehicle and with the outside world. An effective solution for network communication lies in Time-Sensitive Networking (TSN) which enables high-bandwidth and low-latency communications in a mixed-criticality environment. In this work, we present Time-Sensitive Autonomous Architectures (TSAA) to enable TSN in ASDVs. The software architecture is based on a hypervisor providing strong isolation and virtual access to TSN for virtual machines (VMs). TSAA latest iteration includes an autonomous car controlled by two Xilinx accelerators and a multiport TSN switch. We discuss the engineering challenges and the performance evaluation of the project demonstrator. In addition, we propose a Proof-of-Concept design of virtualized TSN to enable multiple VMs executing on a single board taking advantage of the inherent guarantees offered by TSN

Anomalous spectral weight in photoemission spectra of the hole doped Haldane chain Y2-xSrxBaNiO5

In this paper, we present photoemission experiments on the hole doped Haldane chain compound $Y_{2-x}Sr_xBaNiO_5$. By using the photon energy dependence of the photoemission cross section, we identified the symmetry of the first ionisation states (d type). Hole doping in this system leads to a significant increase in the spectral weight at the top of the valence band without any change in the vicinity of the Fermi energy. This behavior, not observed in other charge transfer oxides at low doping level, could result from the inhomogeneous character of the doped system and from a Ni 3d-O 2p hybridization enhancement due to the shortening of the relevant Ni-O distance in the localized hole-doped regions.Comment: 5 pages, 4 figure

Silagem de soja no enriquecimento de dietas compostas por silagem de ponta de cana-de-açúcar. 1 - Consumo de nutrientes.

Conduziu-se o estudo com o objetivo de avaliar o desempenho de ovinos alimentados com dietas compostas por silagem da ponta de cana-de-açúcar enriquecida com silagem de soja. Foram utilizados 24 cordeiros da raça Morada Nova com idade média de 75 dias e peso vivo médio de 16,98 kg ± 2,62 kg. Avaliaram-se as seguintes dietas: T1= 20% de silagem da ponta de cana + 80% de concentrado; T2= 20% de silagem da ponta de cana + 30% de silagem de soja + 50% de concentrado; T3= 20% de silagem da ponta de cana + 60% de silagem de soja + 20% de concentrado. O delineamento experimental foi o de blocos completos casualizados, com oito repetições. Foram avaliados os consumos de matéria seca, proteína bruta, nitrogênio contido na fibra em detergente neutro (nFDN) e na fibra em detergente ácido (nFDA). Dietas compostas por silagem de ponta de cana-de-açúcar enriquecida com silagem de soja + concentrado proporcionam maior consumo de nutrientes. A utilização de silagem de soja para enriquecer o teor protéico de dietas compostas por silagem de ponta de cana-de-açúcar fica na dependência do custo para aquisição de concentrado protéico ou produção de proteína na propriedade por meio da ensilagem da planta de soja

Hpv-specific systemic antibody responses and memory b cells are independently maintained up to 6 years and in a vaccine-specific manner following immunization with cervarix and gardasil in adolescent and young adult women in vaccination programs in Italy

Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV- 11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view

HIV-1 Tat protein modulates the generation of cytotoxic T cell epitopes by modifying proteasome composition and enzymatic activity

Tat, the trans activation protein of HIV, is produced early upon infection to promote and expand HIV replication and transmission. However, Tat appears to also have effects on target cells, which may affect Ag recognition both during infection and after vaccination. In particular, Tat targets dendritic cells and induces their maturation and Ag-presenting functions, increasing Th1 T cell responses. We show in this work that Tat modifies the catalytic subunit composition of immunoproteasomes in B and T cells either expressing Tat or treated with exogenous biological active Tat protein. In particular, Tat up-regulates latent membrane protein 7 and multicatalytic endopeptidase complex like-1 subunits and down-modulates the latent membrane protein 2 subunit. These changes correlate with the increase of all three major proteolytic activities of the proteasome and result in a more efficient generation and presentation of subdominant MHC-I-binding CTL epitopes of heterologous Ags. Thus, Tat modifies the Ag processing and modulates the generation of CTL epitopes. This may have an impact on both the control of virally infected cells during HIV-1 infection and the use of Tat for vaccination strategies