Caspase-Dependent Inhibition of Mousepox Replication by gzmB

BACKGROUND: Ectromelia virus is a natural mouse pathogen, causing mousepox. The cytotoxic T (Tc) cell granule serine-protease, granzyme B, is important for its control, but the underlying mechanism is unknown. Using ex vivo virus immune Tc cells, we have previously shown that granzyme B is able to activate several independent pro-apoptotic pathways, including those mediated by Bid/Bak/Bax and caspases-3/-7, in target cells pulsed with Tc cell determinants. METHODS AND FINDINGS: Here we analysed the physiological relevance of those pro-apoptotic pathways in ectromelia infection, by incubating ectromelia-immune ex vivo Tc cells from granzyme A deficient (GzmB(+) Tc cells) or granzyme A and granzyme B deficient (GzmAxB(-/-) Tc cell) mice with ectromelia-infected target cells. We found that gzmB-induced apoptosis was totally blocked in ectromelia infected or peptide pulsed cells lacking caspases-3/-7. However ectromelia inhibited only partially apoptosis in cells deficient for Bid/Bak/Bax and not at all when both pathways were operative suggesting that the virus is able to interfere with apoptosis induced by gzmB in case not all pathways are activated. Importantly, inhibition of viral replication in vitro, as seen with wild type cells, was not affected by the lack of Bid/Bak/Bax but was significantly reduced in caspase-3/-7-deficient cells. Both caspase dependent processes were strictly dependent on gzmB, since Tc cells, lacking both gzms, neither induced apoptosis nor reduced viral titers. SIGNIFICANCE: Out findings present the first evidence on the biological importance of the independent gzmB-inducible pro-apoptotic pathways in a physiological relevant virus infection model

Joint action aesthetics

Synchronized movement is a ubiquitous feature of dance and music performance. Much research into the evolutionary origins of these cultural practices has focused on why humans perform rather than watch or listen to dance and music. In this study, we show that movement synchrony among a group of performers predicts the aesthetic appreciation of live dance performances. We developed a choreography that continuously manipulated group synchronization using a defined movement vocabulary based on arm swinging, walking and running. The choreography was performed live to four audiences, as we continuously tracked the performers’ movements, and the spectators’ affective responses. We computed dynamic synchrony among performers using cross recurrence analysis of data from wrist accelerometers, and implicit measures of arousal from spectators’ heart rates. Additionally, a subset of spectators provided continuous ratings of enjoyment and perceived synchrony using tablet computers. Granger causality analyses demonstrate predictive relationships between synchrony, enjoyment ratings and spectator arousal, if audiences form a collectively consistent positive or negative aesthetic evaluation. Controlling for the influence of overall movement acceleration and visual change, we show that dance communicates group coordination via coupled movement dynamics among a group of performers. Our findings are in line with an evolutionary function of dance–and perhaps all performing arts–in transmitting social signals between groups of people. Human movement is the common denominator of dance, music and theatre. Acknowledging the time-sensitive and immediate nature of the performer-spectator relationship, our study makes a significant step towards an aesthetics of joint actions in the performing arts

Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice

The DNA-binding protein PRDM9 directs positioning of the double strand breaks (DSBs) initiating meiotic recombination, in mice and humans. PRDM9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized PRDM9’s DNA-binding domain in C57BL/6 mice. This change repositions DSB hotspots and completely restores fertility in male hybrids. We show that alteration of one Prdm9 allele impacts the behaviour of DSBs controlled by the other allele at chromosome-wide scales. These effects correlate strongly with the degree to which each PRDM9 variant binds both homologues at the DSB sites it controls. Furthermore, higher genome-wide levels of such “symmetric” PRDM9 binding associate with increasing fertility measures and comparisons of individual hotspots suggest binding symmetry plays a downstream role in the recombination process. These findings reveal that subspecies-specific degradation of PRDM9 binding sites by meiotic drive, which steadily increases asymmetric PRDM9 binding, has impacts beyond simply changing hotspot positions, and strongly support a direct involvement in hybrid infertility. Because such meiotic drive occurs across mammals, PRDM9 may play a wider, yet transient, role in early stages of speciation

Nation, College, Wartime: Archaeology at a WWI Student Army Training Corps Camp at New Hampshire College

During World War I, the U.S. War Department contracted with 157 universities to form the National Army Training Detachments whose mission was to train college-age draftees in 66 critical army trades (subsequently the Student Army Training Corps). This program is an overlooked part of First World War history and has received little to no archaeological inquiry. This paper investigates the New Hampshire College camp. Working between documentary and archaeological materials, this paper explores how the interrelated duties of educational institutions, businesses, government, and individuals merged with an American wartime imagined community here but also how in their lived experiences of the camp, people materialized the complications of balancing citizenship, difference, duty, and nation. The social lives of the lower-rank men who inhabited these camps, the composite communities formed at them, and the impact of the government’s assertion of control over institutions of higher education all carry material ramifications that deserve further investigation