Constructive pointfree topology eliminates non-constructive representation theorems from Riesz space theory

In Riesz space theory it is good practice to avoid representation theorems which depend on the axiom of choice. Here we present a general methodology to do this using pointfree topology. To illustrate the technique we show that almost f-algebras are commutative. The proof is obtained relatively straightforward from the proof by Buskes and van Rooij by using the pointfree Stone-Yosida representation theorem by Coquand and Spitters

Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.

Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone

Promoting Diverse Youth's Career Development through Informal Science Learning: The Role of Inclusivity and Belonging

This is the final version. Available on open access from Springer via the DOI in this recordLittle research has examined the associations between perceived inclusivity within informal science learning sites, youth program belonging and perceptions of program career preparation. This study explored relations between these factors at three timepoints (T1 = start of program, T2 = 3 months and T3 = 12 months after start). Participants were a diverse sample of 209 adolescents participating in STEM youth programs within informal science learning sites situated in the United States and United Kingdom (70% females: M age = 15.27, SD age = 1.60), with 53.1% British and 64.1% non-White. Path analysis revealed that only perceptions of inclusivity for own social identity group (i.e., gender, ethnicity) at T1 were associated with T2 STEM youth program belonging. There was a significant indirect effect of T1 perceptions of inclusivity for one's own social identity groups on T3 perceptions of program career preparation via T2 program belonging. This study highlights that, over time, perceptions of inclusivity around youth's own social identity groups (i.e., gender and ethnicity/culture) are related to a sense of youth program belonging, which in turn is later associated with perceptions of program career preparation.National Science Foundation (NSF)Wellcome TrustEconomic and Social Research Council (ESRC

A 'Different Class'? Homophily and Heterophily in the Social Class Networks of Britpop

Social network analysis is increasingly recognised as a useful way to explore music scenes. In this article we examine the individuals who were the cultural workforce that comprised the 'Britpop' music scene of the 1990s. The focus of our analysis is homophily and heterophily to determine whether the clusters of friendships and working relationships of those who were ‘best connected’ in the scene were patterned by original social class position. We find that Britpop's 'whole network' is heterophilic but its 'sub-networks' are more likely to be social class homophilic. The sub-networks that remain heterophilic are likely to be united by other common experiences that brought individuals in the network to the same social spaces. We suggest that our findings on Britpop might be generalised to the composition of other music scenes, cultural workforces and aggregations of young people. Our study differs from research on, first, British ‘indie music’ and social class which focusses upon the construction, representation and performance of social location rather than the relationships it might shape (such as Wiseman-Trowse, 2008) and second, the pioneering social network analyses of music scenes (such as Crossley 2008; 2009; 2015; Crossley et. al 2014) which currently lacks the explicit emphasis on social class

Lipopolysaccharide Renders Transgenic Mice Expressing Human Serum Amyloid P Component Sensitive to Shiga Toxin 2

Transgenic C57BL/6 mice expressing human serum amyloid P component (HuSAP) are resistant to Shiga toxin 2 (Stx2) at dosages that are lethal in HuSAP-negative wild-type mice. However, it is well established that Stx2 initiates extra-intestinal complications such as the haemolytic-uremic syndrome despite the presence of HuSAP in human sera. We now demonstrate that co-administering purified Escherichia coli O55 lipopolysaccharide (LPS), at a dosage of 300 ng/g body weight, to HuSAP-transgenic mice increases their susceptibility to the lethal effects of Stx2. The enhanced susceptibility to Stx2 correlated with an increased expression of genes encoding the pro-inflammatory cytokine TNFα and chemokines of the CXC and CC families in the kidneys of LPS-treated mice, 48 hours after the Stx2/LPS challenge. Co-administering the glucocorticoid dexamethasone, but not the LPS neutralizing cationic peptide LL-37, protected LPS-sensitized HuSAP-transgenic mice from lethal doses of Stx2. Dexamethasone protection was specifically associated with decreased expression of the same inflammatory mediators (CXC and CC-type chemokines and TNFα) linked to enhanced susceptibility caused by LPS. The studies reveal further details about the complex cascade of host-related events that are initiated by Stx2 as well as establish a new animal model system in which to investigate strategies for diminishing serious Stx2-mediated complications in humans infected with enterohemorrhagic E. coli strains

Reciprocal Associations Between Science Efficacy, STEM Identity and Scientist Career Interest Among Adolescent Girls within the Context of Informal Science Learning

This is the final version. Available on open access from Springer via the DOI in this recordLimited research has explored the longitudinal pathway to youth career interests via identity and efficacy together. This study examined the longitudinal associations between science efficacy, STEM (science, technology, engineering and math) identity, and scientist career interest among girls who are historically considered as an underrepresented group among scientists. The sample included 308 girls (M age = 15.22, SD age = 1.66; 42.8% White) from six STEM youth programs, each at a different informal science learning site within the U.K. and the U.S. Longitudinal structural equation modelling demonstrated that science efficacy consistently predicted STEM identity and scientist career interest, and similarly, STEM identity consistently predicted science efficacy over a two-year period. Scientist career interest at 12 months predicted science efficacy at 24 months. The coefficients of efficacy predicting STEM identity and scientist career interest were significantly larger compared to STEM identity and scientist career interest in predicting science efficacy from 12 months to 24 months. Further mediation analysis supported a significant pathway from STEM identity at 3 months to scientist career interest at 24 months via 12-month science efficacy. The findings highlight that science efficacy and STEM identity for girls relate to their scientist career interest and these longitudinal associations are reciprocal. This study suggests that science efficacy and STEM identity mutually influence each other, and enhancing science efficacy and STEM identity is key to promoting adolescents' interest in being a scientist.Wellcome TrustNational Science Foundation (NSF)Economic and Social Research Council (ESRC

Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection

Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC) into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease

Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (−60–75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum

Peer Toy Play as a Gateway to Children’s Gender Flexibility: The Effect of (Counter)Stereotypic Portrayals of Peers in Children’s Magazines

Extensive evidence has documented the gender stereotypic content of children’s media, and media is recognized as an important socializing agent for young children. Yet, the precise impact of children’s media on the endorsement of gender-typed attitudes and behaviors has received less scholarly attention. We investigated the impact of stereotypic and counter-stereotypic peers pictured in children’s magazines on children’s gender flexibility around toy play and preferences, playmate choice, and social exclusion behavior (n = 82, age 4–7 years-old). British children were randomly assigned to view a picture of a peer-age boy and girl in a magazine playing with either a gender stereotypic or counter-stereotypic toy. In the stereotypic condition, the pictured girl was shown with a toy pony and the pictured boy was shown with a toy car; these toys were reversed in the counter-stereotypic condition. Results revealed significantly greater gender flexibility around toy play and playmate choices among children in the counterstereotypic condition compared to the stereotypic condition, and boys in the stereotypic condition were more accepting of gender-based exclusion than were girls. However, there was no difference in children’s own toy preferences between the stereotypic and counter-stereotypic condition, with children preferring more gender-typed toys overall. Implications of the findings for media, education, and parenting practices are discussed, and the potential for counterstereotypic media portrayals of toy play to shape the gender socialization of young children is explored