Primary Human mDC1, mDC2, and pDC Dendritic Cells Are Differentially Infected and Activated by Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) causes recurrent infections throughout life. Vaccine development may depend upon understanding the molecular basis for induction of ineffective immunity. Because dendritic cells (DCs) are critically involved in early responses to infection, their interaction with RSV may determine the immunological outcome of RSV infection. Therefore, we investigated the ability of RSV to infect and activate primary mDCs and pDCs using recombinant RSV expressing green fluorescent protein (GFP). At a multiplicity of infection of 5, initial studies demonstrated ∼6.8% of mDC1 and ∼0.9% pDCs were infected. We extended these studies to include CD1c−CD141+ mDC2, finding mDC2 infected at similar frequencies as mDC1. Both infected and uninfected cells upregulated phenotypic markers of maturation. Divalent cations were required for infection and maturation, but maturation did not require viral replication. There is evidence that attachment and entry/replication processes exert distinct effects on DC activation. Cell-specific patterns of RSV-induced maturation and cytokine production were detected in mDC1, mDC2, and pDC. We also demonstrate for the first time that RSV induces significant TIMP-2 production in all DC subsets. Defining the influence of RSV on the function of selected DC subsets may improve the likelihood of achieving protective vaccine-induced immunity

Historical culture and peace. How older generations address the need of younger generations to learn about theier in-group past

This chapter has three aims. First, it aims to disentangle social denial of in-group responsibilities for intergroup violence from other types of silence about intergroup violence. Secondly, it argues that intergenerational narratives which omit information about in-group responsibilities for violence that occurred before the birth of younger generations are highly risky to the descendants of perpetrators. Finally, it emphasises the importance of exploring in greater depth the understudied moment when a literal social denial about past in-group war crimes is exposed. To support these aims, the chapter presents results from a recent mixed methods, quasi-experimental study, which used between- and within-subject comparisons. The study asked young Italian university students to read an explicit text (“detailed text”) vs. a more nuanced one (“mild text”) about Italian war crimes occurring during the colonial invasion of Ethiopia. Data were collected before reading the text, during the reading and after it. Texts were constructed by manipulating the wording of a single historical narrative, taken from a textbook currently used in Italian high schools. The inclusion of this information in Italian history textbooks is quite recent, taking place approximately 70 years after the end of the war. Prior to this a widespread social denial silenced these crimes and as a result they were largely ignored in general social discourse. Results showed that participants reacted not only to the new information received but also to the way in which it was conveyed. The detailed narrative, by frankly taking a moral stance on past violence (a strategy that we named, after classic works of Foucault, 1983, parrhesia), provoked a better understanding of information, together with an increase of negative group-based moral emotions. Interestingly, while collective guilt did not differ between participants exposed to a detailed or a mild text, moral emotions distancing young participants from the responsibilities of older generations increased when these crimes were clearly exposed

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10−8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer