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Mosquito‐borne diseases contribute substantially to the global burden of disease, and are strongly influenced by environmental conditions. Ongoing and rapid environmental change necessitates improved understanding of the response of mosquito‐borne diseases to environmental factors like temperature, and novel approaches to mapping and monitoring risk. Recent development of trait‐based mechanistic models has improved understanding of the temperature dependence of transmission, but model predictions remain challenging to validate in the field. Using West Nile virus (WNV) as a case study, we illustrate the use of a novel remote sensing‐based approach to mapping temperature‐dependent mosquito and viral traits at high spatial resolution and across the diurnal cycle. We validate the approach using mosquito and WNV surveillance data controlling for other key factors in the ecology of WNV, finding strong agreement between temperature‐dependent traits and field‐based metrics of risk. Moreover, we find that WNV infection rate in mosquitos exhibits a unimodal relationship with temperature, peaking at ~24.6–25.2°C, in the middle of the 95% credible interval of optimal temperature for transmission of WNV predicted by trait‐based mechanistic models. This study represents one of the highest resolution validations of trait‐based model predictions, and illustrates the utility of a novel remote sensing approach to predicting mosquito‐borne disease risk. [ABSTRACT FROM AUTHOR]

Accurate identification of agricultural pests is a major component of integrated pest management. The seedcorn maggot, Delia platura (Meigen) (Diptera: Anthomyiidae), is a cosmopolitan polyphagous pest species that may be found in high numbers in numerous crops. Two morphologically identical genetic lines of D. platura (H and N) with distinct distributions were recently identified. To date, no study has investigated the reproductive compatibility of the two lines and thus the possibility that they may actually be two unique biological entities. A previous study described the reproductive traits of the two lines and suggested that H‐line females are highly selective toward the male with which they mate, pointing to a possible pre‐mating isolation mechanism between the lines. Using laboratory‐reared colonies originating from the Montérégie region in Québec, Canada, this study investigates the reproductive compatibility of the two D. platura lines. We found that only one of 30 H‐line females was inseminated by an N‐line male, further suggesting mate choice as a pre‐mating isolation mechanism between the lines. However, N‐line females were readily inseminated by H‐line males, suggesting a lack of pre‐mating isolation in this type of cross. The eggs laid by N‐line females mated with H‐line males had a lower hatching rate than the ones laid by females of intraline crosses, suggesting either post‐mating pre‐zygotic or post‐zygotic partial isolation. However, the larvae that did hatch had a comparable developmental success to those from intraline crosses in terms of survival and developmental time from larval hatching to adult emergence, pupal mass, and adult sex ratio, suggesting a lack of post‐zygotic isolation for these life stages. Considering the different biological traits of the two lines, we suggest the use of the 'biotype' terminology to designate the two biological entities and discuss their implications for integrated pest management. [ABSTRACT FROM AUTHOR]

Src homology 3 (SH3) domains play a critical role in mediating protein–protein interactions (PPIs) involved in cell proliferation, migration, and the cytoskeleton. Despite their abundance in the human proteome, the functions and molecular interactions of many SH3 domains remain unknown, and this is in part due to the lack of SH3-domain-specific reagents available for their study. Affimer proteins have been developed as affinity reagents targeting a diverse range of targets, including those involved in PPIs. In this study, Affimer proteins were isolated against both the N- and C-terminal SH3 domains (NSH3 and CSH3) of growth-factor-receptor-bound protein 2 (Grb2), an adapter protein that provides a critical link between cell surface receptors and Ras signalling pathways. Targeting the CSH3 alone for the inhibition of PPIs appeared sufficient for curtailing Ras signalling in mammalian cell lines stimulated with human epidermal growth factor (EGF), which conflicts with the notion that the predominant interactions with Ras activating Son of sevenless (SOS) occur via the NSH3 domain. This result supports a model in which allosteric mechanisms involved in Grb2-SOS1 interaction modulate Ras activation. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies. The Hippo signalling pathway is important in HPV+ cancers, with the downstream effector YAP playing a pro-oncogenic role. In contrast, the significance of its paralogue TAZ remains largely uncharacterised in these cancers. We demonstrate that TAZ is dysregulated in a HPV-type dependent manner by a distinct mechanism to that of YAP and controls proliferation via alternative cellular targets. Analysis of cervical cancer cell lines and patient biopsies revealed that TAZ expression was only significantly increased in HPV18+ and HPV18-like cells and TAZ knockdown reduced proliferation, migration and invasion only in HPV18+ cells. RNA-sequencing of HPV18+ cervical cells revealed that YAP and TAZ have distinct targets, suggesting they promote carcinogenesis by different mechanisms. Thus, in HPV18+ cancers, YAP and TAZ play non-redundant roles. This analysis identified TOGARAM2 as a previously uncharacterised TAZ target and demonstrates its role as a key effector of TAZ-mediated proliferation, migration and invasion in HPV18+ cancers. The Hippo pathway transcription factors YAP and TAZ are often thought to play redundant roles in cancer progression. Here, Patterson et al demonstrate that TAZ is specifically required in HPV18+ cervical cancer, a subtype associated with worse prognosis. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the in vivo administration of soil-derived bacteria with anti-inflammatory and immunoregulatory properties, such as Mycobacterium vaccae NCTC 11659, can prevent a stress-induced shift toward an inflammatory M1 microglial immunophenotype and microglial priming in the central nervous system (CNS). It remains unclear whether M. vaccae NCTC 11659 can act directly on microglia to mediate these effects. This study was designed to determine the effects of M. vaccae NCTC 11659 on the polarization of naïve BV-2 cells, a murine microglial cell line, and BV-2 cells subsequently challenged with lipopolysaccharide (LPS). Briefly, murine BV-2 cells were exposed to 100 µg/mL whole-cell, heat-killed M. vaccae NCTC 11659 or sterile borate-buffered saline (BBS) vehicle, followed, 24 h later, by exposure to 0.250 µg/mL LPS (Escherichia coli 0111: B4; n = 3) in cell culture media vehicle (CMV) or a CMV control condition. Twenty-four hours after the LPS or CMV challenge, cells were harvested to isolate total RNA. An analysis using the NanoString platform revealed that, by itself, M. vaccae NCTC 11659 had an "adjuvant-like" effect, while exposure to LPS increased the expression of mRNAs encoding proinflammatory cytokines, chemokine ligands, the C3 component of complement, and components of inflammasome signaling such as Nlrp3. Among LPS-challenged cells, M. vaccae NCTC 11659 had limited effects on differential gene expression using a threshold of 1.5-fold change. A subset of genes was assessed using real-time reverse transcription polymerase chain reaction (real-time RT-PCR), including Arg1, Ccl2, Il1b, Il6, Nlrp3, and Tnf. Based on the analysis using real-time RT-PCR, M. vaccae NCTC 11659 by itself again induced "adjuvant-like" effects, increasing the expression of Il1b, Il6, and Tnf while decreasing the expression of Arg1. LPS by itself increased the expression of Ccl2, Il1b, Il6, Nlrp3, and Tnf while decreasing the expression of Arg1. Among LPS-challenged cells, M. vaccae NCTC 11659 enhanced LPS-induced increases in the expression of Nlrp3 and Tnf, consistent with microglial priming. In contrast, among LPS-challenged cells, although M. vaccae NCTC 11659 did not fully prevent the effects of LPS relative to vehicle-treated control conditions, it increased Arg1 mRNA expression, suggesting that M. vaccae NCTC 11659 induces an atypical microglial phenotype. Thus, M. vaccae NCTC 11659 acutely (within 48 h) induced immune-activating and microglial-priming effects when applied directly to murine BV-2 microglial cells, in contrast to its long-term anti-inflammatory and immunoregulatory effects observed on the CNS when whole-cell, heat-killed preparations of M. vaccae NCTC 11659 were given peripherally in vivo. [ABSTRACT FROM AUTHOR]

This paper explores the gendered politics of care in global environmental activism. Drawing on interviews with 96 Extinction Rebellion activists worldwide and a close analysis of 10 older women within this dataset, we contend that 'care' both replicated and contradicted the patriarchal order. Older women in Extinction Rebellion have often been relied upon to take on much of the caring labour involved in the maintenance of the movement at local and national levels. However, care also involved these women undertaking powerful—and empowering—forms of political action, often grounded in their knowledge and experience of organising social justice movements over decades. In contrast to prior research in the area, we found that women's participation in leadership roles within the movement against climate change appears to have increased over time. Using Sara Ahmed's (2004) concept of affective economies, we argue that the emotion of care came to be accumulated and attached to older women within Extinction Rebellion, producing inequalities in expectations for who would 'care for the movement' while also opening up opportunities for empowerment. [ABSTRACT FROM AUTHOR]

Pro-inflammatory immune responses are rapidly suppressed during blood-stage malaria but the molecular mechanisms driving this regulation are still incompletely understood. In this study, we show that the co-inhibitory receptors TIGIT and PD-1 are upregulated and co-expressed by antigen-specific CD4 + T cells (ovalbumin-specific OT-II cells) during non-lethal Plasmodium yoelii expressing ovalbumin ( Py NL -OVA ) blood-stage infection. Synergistic blockade of TIGIT and PD-L1, but not individual blockade of each receptor, during the early stages of infection significantly improved parasite control during the peak stages (days 10-15) of infection. Mechanistically, this protection was correlated with significantly increased plasma levels of IFN-γ, TNF, and IL-2, and an increase in the frequencies of IFN-γ-producing antigen-specific T-bet + CD4 + T cells (OT-II cells), but not antigen-specific CD8 + T cells (OT-I cells), along with expansion of the splenic red pulp and monocyte-derived macrophage populations. Collectively, our study identifies a novel role for TIGIT in combination with the PD1-PD-L1 axis in regulating specific components of the pro-inflammatory immune response and restricting parasite control during the acute stages of blood-stage Py NL infection.