Heterogeneity among Isolates Reveals that Fitness in Low Oxygen Correlates with Aspergillus fumigatus Virulence

Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population that occupies a variety of niches, has extensive genetic diversity, and exhibits virulence heterogeneity in a number of animal models of invasive pulmonary aspergillosis (IPA). However, mechanisms explaining differences in virulence among A. fumigatus isolates remain enigmatic. Here, we report a significant difference in virulence of two common lab strains, CEA10 and AF293, in the murine triamcinolone immunosuppression model of IPA, in which we previously identified severe low oxygen microenvironments surrounding fungal lesions. Therefore, we hypothesize that the ability to thrive within these lesions of low oxygen promotes virulence of A. fumigatus in this model. To test this hypothesis, we performed in vitro fitness and in vivo virulence analyses in the triamcinolone murine model of IPA with 14 environmental and clinical isolates of A. fumigatus Among these isolates, we observed a strong correlation between fitness in low oxygen in vitro and virulence. In further support of our hypothesis, experimental evolution of AF293, a strain that exhibits reduced fitness in low oxygen and reduced virulence in the triamcinolone model of IPA, results in a strain (EVOL20) that has increased hypoxia fitness and a corresponding increase in virulence. Thus, the ability to thrive in low oxygen correlates with virulence of A. fumigatus isolates in the context of steroid-mediated murin

Injury Scores and Spatial Responses of Wolves Following Capture: Cable Restraints Versus Foothold Traps

Wolves (Canis lupus) have been captured with foothold traps for several decades to equip them with radiocollars for population monitoring. However, trapping in most areas is limited to spring, summer, and autumn as cold winter temperatures can lead to frozen appendages in trapped animals. In addition, conflicts arise when domestic dogs encounter these traps in nonwinter seasons. An alternative capture method is the use of cable restraint devices (modified neck snares) in the winter. We evaluated injury scores, movement patterns, and space use of wolves captured in cable restraint devices and foothold traps in north‐central Minnesota, USA, during 2012–2016. Injury scores did not differ between capture techniques; however, movement patterns and space use were different. We found that the movement away from the capture site appeared to plateau by approximately 8–10 days for wolves captured by either foothold traps or cable restraints, but wolves captured in traps travelled farther away. Daily movement rates reached an asymptote approximately 14 days earlier for wolves captured with cable restraints as compared with wolves caught with foothold traps. We found the space use among wolves caught with cable restraint devices plateaued in a shorter time frame than wolves caught with foothold traps whether using days since capture (38 days earlier) or number of locations (149 locations earlier). When we controlled for seasonal effects and the presence of a capture using locational data collected 6 months later, there was no difference in space use. We concluded that wolves captured in cable restraints recovered more quickly from the capture and resumed space use and activity patterns more rapidly than wolves captured with foothold traps. Published 2019. This article is a U.S. Government work and is in the public domain in the USA

Do Community Structural Characteristics Moderate the Association Between Mental Health and the Frequency and Severity of Violent-Behavioral Outcomes in Community Respondents?

In this prospective study, we examined the association between three types of mental health symptom clusters (i.e., psychotic, internalizing, and externalizing) and the frequency and severity of violent-behavioral outcomes, and whether community disadvantage, residential instability, and criminogenic facility density moderated these associations. Study data were derived from 258 community-dwelling adults nested in 60 postal forward sortation areas (FSAs) in a large metropolitan area in Western Canada who were assessed twice over a 6-month period. In addition, census and administrative data were obtained on the same areas. Controlling for sociodemographic characteristics (i.e., age, gender, ethnicity, relationship status, and employment status), lifetime history of violent-behavioral outcomes, and community structural characteristics, internalizing and externalizing mental health symptoms were significantly positively associated with the frequency and severity of subsequent violence perpetration and with the severity of subsequent violent victimization. Several significant interactions were observed: internalizing symptoms increased the risk of frequent and severe violence perpetration in FSAs with high but not low disadvantage, and externalizing symptoms increased the risk of frequent violent victimization in FSAs with a high but not low criminogenic facility density. Only the interactive association of internalizing symptoms and community disadvantage with the severity of violence perpetration, however, remained significant after Bonferroni correction was applied. These findings provide tentative support that associations between mental health and violent-behavioral outcomes can vary with community context. The implication of these findings for assessing and managing violent-behavioral outcomes in the community is discussed

Coral Identification Guide NAFO Area

Accurate reporting of benthic corals is increasingly important for mapping distributions and for the continued development of sustainable fisheries under the ecosystem approach. This coral identification guide is intended to help those on-board commercial and research fishing vessels to identify and record the various species of coral likely to be commonly encountered in fishing trawls. The guide is clear and simple to use, and will provide names to the majority of these beautiful bottomdwelling animals. The photographs are typically of caught specimens taken on the deck, as this gives the best picture of what is actually seen. Sadly, we rarely personally see corals in their natural habitat, except by looking at films and photos taken by deep underwater cameras

CaMKK2 as an emerging treatment target for bipolar disorder

Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme. CaMKK2 is highly enriched in brain neurons and regulates energy metabolism and neuronal processes that underpin higher order functions such as long-term memory, mood, and other affective functions. Loss-of-function polymorphisms and a rare missense mutation in human CAMKK2 are associated with bipolar disorder, and genetic deletion of Camkk2 in mice causes bipolar-like behaviours similar to those in patients. Furthermore, these behaviours are ameliorated by lithium, which increases CaMKK2 activity. In this review, we discuss multiple convergent lines of evidence that support targeting of CaMKK2 as a new treatment strategy for bipolar disorder

Integrating solutions to adapt cities for climate change

Record climate extremes are reducing urban liveability, compounding inequality, and threatening infrastructure. Adaptation measures that integrate technological, nature-based, and social solutions can provide multiple co-benefits to address complex socioecological issues in cities while increasing resilience to potential impacts. However, there remain many challenges to developing and implementing integrated solutions. In this Viewpoint, we consider the value of integrating across the three solution sets, the challenges and potential enablers for integrating solution sets, and present examples of challenges and adopted solutions in three cities with different urban contexts and climates (Freiburg, Germany; Durban, South Africa; and Singapore). We conclude with a discussion of research directions and provide a road map to identify the actions that enable successful implementation of integrated climate solutions. We highlight the need for more systematic research that targets enabling environments for integration; achieving integrated solutions in different contexts to avoid maladaptation; simultaneously improving liveability, sustainability, and equality; and replicating via transfer and scale-up of local solutions. Cities in systematically disadvantaged countries (sometimes referred to as the Global South) are central to future urban development and must be prioritised. Helping decision makers and communities understand the potential opportunities associated with integrated solutions for climate change will encourage urgent and deliberate strides towards adapting cities to the dynamic climate reality.TM was supported by the US National Science Foundation through grants #1444755, #1927167, and #193493 to participate in the writing of the Viewpoint. BBL received funding from CSIRO Land & Water and the Julius Career Awar

The Concussion Recognition Tool 5th Edition (CRT5): Background and rationale

The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically trained individuals to recognise the signs and symptoms of possible sport-related concussion and provides guidance for removing an athlete from play/sport and to seek medical attention. This paper presents the development of the CRT5 and highlights the differences between the CRT5 and prior versions of the instrument

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases