Distinct Types of Fibrocyte Can Differentiate from Mononuclear Cells in the Presence and Absence of Serum

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Syk-dependent Phosphorylation of CLEC-2: A Novel Mechanism of Hem-Immunoreceptor Tyrosine-Based Activation Motif Signaling

The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro

Livestock Judges Training Provides Hands-On Experience

The judging of a market animal at a fair is the highlight of a youth-owned livestock project. Livestock judges are hired to evaluate youth projects at fairs. They are critical ambassadors for agriculture and influence countless youths and adults. Judges must be knowledgeable about current animal evaluation methods that support youth development. The circle of knowledgeable individuals qualified to evaluate animal projects is limited in the Intermountain West, making it difficult to find skilled judges. This necessitates hiring unqualified or untrained judges, limiting the educational experiences for participating youths. The Intermountain Livestock Judges Training was developed to train and update youth livestock judges

Trusted source, trusted information, trusted support:The role of trust in resident emergency response

If you were to ask people about their ideal, best case scenario response of people in a building fire, it might be something akin to everyone in the building instantly becoming aware of the fire, immediately following the fire safety guidance for their building, and ultimately everyone coming out of the incident unscathed because the correct procedures were followed. This article lays out some of the reasons why people may not react this way. We show that trust is critical to understanding why people may delay response to a threat, and crucially why they might not follow the safety guidance

Who and what is trusted in fire incidents?:The role of trust in guidance and guidance creators in resident response to fire incidents in high-rise residential buildings

Ensuring that residents of high-rise residential buildings follow fire safety guidance in emergencies is important to facilitate safe response. However, little prior research has explored how willingness to follow fire safety guidance is impacted by trust in the guidance itself and trust in the creators of the guidance. The research presented herein hypothesised that the relationship between perceived clarity of the guidance and self-reported willingness to follow the guidance in an emergency would be mediated by both trust in the guidance and trust in the creators of the guidance. An online survey (N = 769) with residents of UK high-rise residential buildings was conducted to examine the relationship between participants’ perceived clarity of their building’s fire safety guidance (both to stay put and evacuate) and their self-reported willingness to follow it. Specifically, we explored how this relationship was impacted by trust in the guidance itself and the providers of the guidance. Parallel mediation analyses showed that the relationship between the perceived clarity of the guidance to and willingness to follow it operated through trust in the guidance and trust in the creators of the guidance. The results replicate previous research on group processes in emergencies but highlight the importance of addressing how views of guidance, its creators, building safety as well as physical constraints may influence emergency response

Exploring Children’s Attitudes towards Digital Good/Bad through hybrid arts practices. Final Project Report.

This report shares the findings of a project funded by the Economic and Social Research Council’s (ESRC) Digital Good Network that sought to explore children’s attitudes towards notions of digital good and conversely digital bad through hybrid arts practice. The project built on our previous work that has centred on one or more emerging technologies, exploring what this might mean in terms of children’s entertainment, play, education and/or health. To tie in with the wider Network’s provocation about whether a digital good society is possible and if so what it would look like, we connected our ideas to a project we previously undertook called Countermeasures (Main & Yamada-Rice, 2022), which taught children about digital sensors, the data they can collect about them and used speculative design (Dunne & Raby, 2014) to create tools to subvert/block them. In that project we focused on four technologies: smart watches, phones, speakers and Nintendo Switch Game Consoles.The Digital Good/Bad project, as we nicknamed, it was broader seeking 9-13-year-oldsattitudes towards notions of digital good/bad and knowledge of how these may differ from adults. We believe that understanding children\u27s ideas/ knowledge is crucial in shaping our collective vision and actions, towards how technologies and software are developed, taught and generally included in their lives