One major concern related to climate change is that elevated temperatures will drive increases in parasite outbreaks. Increasing temperature is known to alter host traits and host-parasite ...interactions, but we know relatively little about how these are connected mechanistically-that is, about how warmer temperatures impact the relationship between epidemiologically relevant host traits and infection outcomes. Here, we used a zooplankton-fungus (
) disease system to experimentally investigate how temperature impacted physical barriers to infection and cellular immune responses. We found that
reared at warmer temperatures had more robust physical barriers to infection but decreased cellular immune responses during the initial infection process. Infected hosts at warmer temperatures also suffered greater reductions in fecundity and lifespan. Furthermore, the relationship between a key trait-gut epithelium thickness, a physical barrier-and the likelihood of terminal infection reversed at warmer temperatures. Together, our results highlight the complex ways that temperatures can modulate host-parasite interactions and show that different defense components can have qualitatively different responses to warmer temperatures, highlighting the importance of considering key host traits when predicting disease dynamics in a warmer world. This article is part of the theme issue 'Infectious disease ecology and evolution in a changing world'.
We report our experience using a biodegradable calcium sulphate antibiotic carrier containing tobramycin in the surgical management of patients with chronic osteomyelitis. The patients were reviewed ...to determine the rate of recurrent infection, the filling of bony defects, and any problems with wound healing. A total of 193 patients (195 cases) with a mean age of 46.1 years (16.1 to 82.0) underwent surgery. According to the Cierny-Mader classification of osteomyelitis there were 12 type I, 1 type II, 144 type III and 38 type IV cases. The mean follow-up was 3.7 years (1.3 to 7.1) with recurrent infection occurring in 18 cases (9.2%) at a mean of 10.3 months post-operatively (1 to 25.0). After further treatment the infection resolved in 191 cases (97.9%). Prolonged wound ooze (longer than two weeks post-operatively) occurred in 30 cases (15.4%) in which there were no recurrent infection. Radiographic assessment at final follow-up showed no filling of the defect with bone in 67 (36.6%), partial filling in 108 (59.0%) and complete filling in eight (4.4%). A fracture occurred in nine (4.6%) of the treated osteomyelitic segments at a mean of 1.9 years (0.4 to 4.9) after operation. We conclude that Osteoset T is helpful in the management of patients with chronic osteomyelitis, but the filling of the defect in bone is variable. Prolonged wound ooze is usually self-limiting and not associated with recurrent infection.
This study investigated the role of children's gender stereotypes and peer playmate experiences in shaping their desire to play with peers who hold counterstereotypical preferences (e.g., a boy who ...likes dolls or a girl who likes trucks). Children (N = 95; 46 girls, 49 boys; 67% White, 18% Black, 8% Latinx, 4% Asian, 3% other; median household income = $US97,810) who were 4 to 8 years old (M = 6.11 years old, SD = 1.34) were interviewed about their gender stereotypes about toy preferences, how often they engage in counterstereotypical playmate experiences, and their desire to play with peers who hold counterstereotypical toy preferences. Children with less gender stereotype-consistent expectations reported more playmate experiences with children who played with toys that were gender counterstereotypical compared to children with more gender stereotype-consistent expectations. Additionally, children with less gender stereotype-consistent expectations reported a greater desire to play with peers who held counterstereotypical toy preferences compared to children with more gender stereotype-consistent expectations. Younger children's reported playmate experiences with peers who liked toys that were gender counterstereotypical and their desire to play with these peers were strongly related to their gender stereotypical expectations (and more so than for older children). Together, these findings indicate that children's gender stereotypes and peer playmate experiences are related to their desire to play with peers who hold counterstereotypical toy preferences, highlighting the importance of facilitating diverse friendships for promoting inclusive orientations in childhood.
The role that human papillomavirus (HPV) oncogenes play in suppressing responses to immunotherapy in cancer deserves further investigation. In particular, the effects of HPV E5 remain poorly ...understood relative to E6 and E7. Here, we demonstrate that HPV E5 is a negative regulator of anti-viral interferon (IFN) response pathways, antigen processing, and antigen presentation. Using head and neck cancer as a model, we identify that E5 decreases expression and function of the immunoproteasome and that the immunoproteasome, but not the constitutive proteasome, is associated with improved overall survival in patients. Moreover, immunopeptidome analysis reveals that HPV E5 restricts the repertoire of antigens presented on the cell surface, likely contributing to immune escape. Mechanistically, we discover a direct interaction between E5 and stimulator of interferon genes (STING), which suppresses downstream IFN signaling. Taken together, these findings identify a powerful molecular mechanism by which HPV E5 limits immune detection and mediates resistance to immunotherapy.
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•HPV E5 downregulates anti-viral type I interferon response pathways•HPV E5 binds STING and MAVS to inhibit downstream type I IFN signaling•HPV E5 limits the MHC class I antigen repertoire by suppressing the immunoproteasome
Miyauchi et al. report that the HPV E5 oncoprotein functions as a powerful negative regulator of anti-viral response pathways by blocking STING and MAVS and inhibiting the immunoproteasome. This study reveals a mechanism of action of E5 that enables virally infected cancer cells to escape host immune surveillance.
Heterozygous genetic variants within the
gene show a strong association with increased Alzheimer's disease (AD) risk. Amyloid beta-depositing mouse models haploinsufficient or null for
have ...identified important relationships among TREM2, microglia, and AD pathology; however, results are challenging to interpret in the context of varying microglial phenotypes and disease progression. We hypothesized that acute
reduction may alter amyloid pathology and microglial responses independent of genetic
deletion in mouse models. We developed antisense oligonucleotides (ASOs) that potently but transiently lower
messenger RNA throughout the brain and administered them to APP/PS1 mice at varying stages of plaque pathology. Late-stage ASO-mediated
knockdown significantly reduced plaque deposition and attenuated microglial association around plaque deposits when evaluated 1 mo after ASO injection. Changes in microglial gene signatures 1 wk after ASO administration and phagocytosis measured in ASO-treated cells together indicate that microglia may be activated with short-term
reduction. These results suggest a time- and/or dose-dependent role for TREM2 in mediating plaque deposition and microglial responses in which loss of TREM2 function may be beneficial for microglial activation and plaque removal in an acute context.
Energetic electron precipitation (EEP) associated with pulsating aurora can transfer greater than 30 keV electrons from the outer radiation belt region into the upper atmosphere and can deplete ...atmospheric ozone via collisions that produce NOx and HOx molecules. Our knowledge of exactly how EEP occurs is incomplete. Previous studies have shown that pitch angle scattering between electrons and lower‐band chorus waves can cause pulsating aurora associated with EEP and that substorms play an important role. In this work, we quantify the timescale of chorus wave decay following substorms and compare that to previously determined timescales. We find that the chorus decay e‐folding time varies based on magnetic local time (MLT), magnetic latitude, and wave frequency. The shortest timescales occur for lower‐band chorus in the 21 to 9 MLT region and compares, within uncertainty, to the energetic pulsating aurora timescale of Troyer et al. (2022, https://doi.org/10.3389/fspas.2022.1032552) for energetic pulsating aurora. We are able to further support this connection by modeling our findings in a quasi‐linear diffusion simulation. These results provide observations of how chorus waves behave after substorms and add additional statistical evidence linking energetic pulsating aurora to substorm driven lower‐band chorus waves.
Key Points
Chorus waves exponentially decay with a timescale on the order of an hour in the quiet period following substorms
This decay timescale varies based on magnetic local time, magnetic latitude, and wave frequency
Lower‐band chorus waves between 21 and 5 magnetic local time decay with a similar timescale to energetic pulsating aurora electrons after substorms
Between the 2006 and 2014 editions of CSA S6, significant changes were made to the simplified method of analysis (SMA) for all girder bridges, including transverse wood deck on wood girder bridges. ...The load-distribution predictions became more conservative, resulting in both load-limit posting of existing bridges and increased cost for bridge construction, repair, and replacement. In this paper, we examine the load distribution for the timber bridge inventory in NS. Finite-element models are developed and rigorously validated; a parametric study, consisting of 204 bridges, is performed; current SMA equations are evaluated; and new equations for the truck-load distribution width are derived. The new equations bring SMA predictions of the longitudinal bending moment for transverse wood deck on wood girder bridges into line with currently expected safety-index levels. Corrected bias factors and coefficients of variation for live-load analysis/evaluation in conjunction with CSA S6 are presented.
To describe a novel technique for direct perfluorocarbon liquid (PFCL)-silicone oil exchange that aims to reduce the inherent risk of intraoperative intraocular pressure spike.
We use the ...conventional setup for passive PFCL-silicone exchange, but intentionally create a mismatch between the passive PFCL aspiration and the active silicone injection that favors the PFCL extrusion. This is achieved by converting one port to a large gauge one-23 or 20-gauge.
We did not note the occurrence of high intraocular pressure spikes with this technique as noted by disk pallor or attenuated vessels.
A hybrid 23/25-gauge technique for direct PFCL-silicone oil exchange is safe and reduces the risk of intraoperative intraocular pressure spike.
There are over 220 identified genotypes of Human papillomavirus (HPV), and the HPV genome encodes 3 major oncogenes, E5, E6, and E7. Conservation and divergence in protein sequence and function ...between low-risk versus high-risk oncogenic HPV genotypes has not been fully characterized. Here, we used modern computational and structural folding algorithms to perform a comparative analysis of HPV E5, E6, and E7 between multiple low risk and high risk genotypes. We first identified significantly greater sequence divergence in E5 between low- and high-risk genotypes compared to E6 and E7. Next, we used AlphaFold to model the structure of papillomavirus proteins and complexes with high confidence, including some with no established consensus structure. We observed that HPV E5, but not E6 or E7, had a dramatically different 3D structure between low-risk and high-risk genotypes. To our knowledge, this is the first comparative analysis of HPV proteins using Alphafold artificial intelligence (AI) system. The marked differences in E5 sequence and structure in high-risk HPVs may contribute in important and underappreciated ways to the development of HPV-associated cancers.
Transgenerational plasticity can help organisms respond rapidly to changing environments. Most prior studies of transgenerational plasticity in host–parasite interactions have focused on the host, ...leaving us with a limited understanding of transgenerational plasticity of parasites. We tested whether exposure to elevated temperatures while spores are developing can modify the ability of those spores to infect new hosts, as well as the growth and virulence of the next generation of parasites in the new host. We exposed Daphnia dentifera to its naturally co-occurring fungal parasite Metschnikowia bicuspidata, rearing the parasite at cooler (20°C) or warmer (24°C) temperatures and then, factorially, using those spores to infect at 20 and 24°C. Infections by parasites reared at warmer past temperatures produced more mature spores, but only when the current infections were at cooler temperatures. Moreover, the percentage of mature spores was impacted by both rearing and current temperatures, and was highest for infections with spores reared in a warmer environment that infected hosts in a cooler environment. In contrast, virulence was influenced only by current temperatures. These results demonstrate transgenerational plasticity of parasites in response to temperature changes, with fitness impacts that are dependent on both past and current environments.
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