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We previously reported that laboratory mice from all global vendors are frequently colonized with Staphylococcus aureus ( S. aureus ). Genotyping of a snap sample of murine S. aureus isolates from Charles River, US, showed that mice were predominantly colonized with methicillin-sensitive CC88 strains. Here, we expanded our view and investigated whether laboratory mice from other global animal facilities are colonized with similar strains or novel S. aureus lineages, and whether the murine S. aureus isolates show features of host adaptation. In total, we genotyped 230 S. aureus isolates from various vendor facilities of laboratory mice around the globe (Charles River facilities in the USA, Canada, France, and Germany; another US facility) and university- or company-associated breeding facilities in Germany, China and New Zealand. Spa typing was performed to analyse the clonal relationship of the isolates. Moreover, multiplex PCRs were performed for human-specific virulence factors, the immune-evasion cluster (IEC) and superantigen genes (SAg). We found a total of 58 different spa types that clustered into 15 clonal complexes (CCs). Three of these S. aureus lineages had spread globally among laboratory mice and accounted for three quarters of the isolates: CC1 (13.5%), CC15 (14.3%), and CC88 (47.0%). Compared to human colonizing isolates of the same lineages, the murine isolates frequently lacked IEC genes and SAg genes on mobile genetic elements, implying long-term adaptation to the murine host. In conclusion, laboratory mice from various vendors are colonized with host-adapted S. aureus -strains of a few lineages, predominantly the CC88 lineage. S. aureus researchers must be cautioned that S. aureus colonization might be a relevant confounder in infection and vaccination studies and are therefore advised to screen their mice before experimentation. [ABSTRACT FROM AUTHOR]

The synchronous paradigm provides a logical abstraction of time for reactive system design which allows automatic synthesis of embedded systems that behave in a predictable, timely, and reactive manner. According to the synchrony hypothesis, a synchronous model reacts to inputs by generating outputs that are immediately made available to the environment. While synchrony greatly simplifies the design of complex systems in general, it can sometimes lead to causal cycles. In these cases, constructiveness is a key property to guarantee that the output of each reaction can still be always algorithmically determined. Polychrony deviates from perfect synchrony by using a partially ordered, i.e., a relational model of time. It encompasses the behaviors of (implicitly) multi-clocked data-flow networks of synchronous modules and can analyze and synthesize them as GALS systems or Kahn process networks (KPNs). In this paper, we present a unified constructive semantic framework using structured operational semantics, which encompasses both the constructive behavior of synchronous modules and the multi-clocked behavior of polychronous networks. Along the way, we define the very first executable operational semantics of the polychronous language Signal . [ABSTRACT FROM AUTHOR]

If loose-housed farrowing systems are to be an alternative to traditional farrowing crates, it is important that they can deliver the same production results as can be achieved in farrowing crates under commercial conditions. The aim of this study was to compare preweaning mortality in farrowing crates and free farrowing pens (FF-pens) within herds that had both systems. The study was conducted over 2 years in three commercial Danish herds that had FF-pens as well as traditional farrowing crates in their farrowing unit. Piglet mortality was analysed in two periods: before litter equalisation and after litter equalisation. Linear models were used to analyse effects of housing (crate or pen), herd (Herd A, B or C), parity (parities 1, 2, 3 to 4 or 5 to 8) as well as the effect of number of total born piglets on mortality before litter equalisation, and the effect of equalised litter size on piglet mortality after litter equalisation. All corresponding interactions were included in the models. Before litter equalisation piglet mortality was higher (P<0.001) in pens (13.7%) than in crates (11.8%). Similarly, piglet mortality after litter equalisation was higher in pens than in crates in all three herds, but the difference between pens and crates were dissimilar (P<0.05) in the different herds. In addition, piglet mortality, both before (P<0.001) and after litter equalisation (P<0.001), grew with increasing parity of the sows. Mortality before litter equalisation moreover increased with increasing number of total born piglets per litter (P<0.001), and mortality after equalisation increased when equalised litter size increased (P<0.001). No significant interactions were detected between housing and parity or housing and litter size for any of the analysed variables. In conclusion, there is knowledge how to design pens for free farrowing; but this study showed a higher preweaning mortality in the FF-pen. Nonetheless a noteworthy proportion of the sows in the FF-pens delivered results comparable to those farrowing in crates. This indicates that FF-pens are not yet a robust type of housing for farrowing sows. [ABSTRACT FROM PUBLISHER]

Abstract: The role of CD8+ T cells in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is still unclear. We describe here significantly reduced disease activity of EAE both in Lewis rats depleted of CD8+ T cells by monoclonal antibodies and CD8 knockout rats, which was accompanied by reduced leukocyte infiltration into the spinal cord. We detected myelin basic protein (MBP)-specific CD4+ T cells in peripheral lymphoid organs of CD8-depleted animals which, however, failed to differentiate into interferon-γ-producing effector cells. Our results indicate that CD8+ T cells interact with myelin-specific CD4+ T cells early in EAE enabling them to differentiate into pathogenic effector cells. [Copyright &y& Elsevier]