A human STAT1 gain-of-function mutation impairs CD8 + T cell responses against gammaherpesvirus 68

Autosomal dominant STAT1 mutations in humans have been associated with chronic mucocutaneous candidiasis (CMC), as well as with increased susceptibility to herpesvirus infections. Prior studies have focused on mucosal and Th17-mediated immunity agains

Groundcover community assembly in high-diversity pine savannas: seed arrival and fire-generated environmental filtering

Environmental filtering—abiotic and biotic constraints on the demographic performance of individual organisms—is a widespread mechanism of selection in communities. A given individual is “filtered out” (i.e., selectively removed) when environmental conditions or disturbances like fires preclude its survival and reproduction. Although interactions between these filters and dispersal from the regional species pool are thought to determine much about species composition locally, there have been relatively few studies of dispersal × filtering interactions in species-rich communities and fewer still where fire is also a primary selective agent. We experimentally manipulated dispersal and filtering by fire (pre-fire fuel loads and post-fire ash) in species-rich groundcover communities of the longleaf pine ecosystem. We tested four predictions: (1) That species richness would increase with biologically realistic dispersal (seed addition); (2) that the immediate effect of increased fuels in burned communities would be to decrease species richness, whereas the longer-term effects of increased fuels would be to open recruitment opportunities in the groundcover, increase species richness, and increase individual performance (growth) of immigrating species; (3) that adding ash would increase species richness; and (4) that increased dispersal would generate larger increases in species richness in plots with increased fuels compared to plots with decreased fuels. We found that dispersal interacted with complex fire-generated filtering during and after fires. Dispersal increased species richness more in burned communities with increased and decreased fuels compared to burned controls. Moreover, individuals of immigrating species generally grew to larger sizes in burned communities with increased fuels compared to burned controls. In contrast to dispersal and fuels, ash had no effect on species richness directly or in combination with other treatments. We conclude that filtering occurs both during fires and in the post-fire environment and that these influences interact with dispersal such that the consequences are only fully revealed when all are considered in combination. Our experiment highlights the importance of considering the dynamic interplay of dispersal and selection in the assembly of species-rich communities

Associations between lifetime potentially traumatic events and chronic physical conditions in the South African Stress and Health Survey: a cross-sectional study

Background: This study examined the association between the type, and cumulative number of lifetime potentially traumatic events (PTEs), and chronic physical conditions, in a South African sample. PTE exposures have been associated with an increased risk for a wide range of chronic physical conditions, but it is unclear whether psychiatric disorders mediate this association. Given the established differences in trauma occurrence, and the epidemiology of posttraumatic stress disorder (PTSD) in South Africa relative to other countries, examining associations between PTEs and chronic physical conditions, particularly while accounting for psychiatric comorbidity is important. Methods: Data were drawn from the South African Stress and Health Study, a cross-sectional population-representative study of psychological and physical health of South African adults. Twenty-seven PTEs, based on the World Health Organization Composite International Diagnostic Interview Version 3.0, DSM-IV PTSD module were grouped into seven PTE types (war events, physical violence, sexual violence, accidents, unexpected death of a loved one, network events, and witnessing PTEs). Five clusters of physical conditions (cardiovascular, arthritis, respiratory, chronic pain, and other health conditions) were examined. Logistic regressions assessed the odds of reporting a physical condition in relation to type and cumulative number of PTEs. Cochran-Armitage test for trend was used to examine dose-response effect of cumulative PTEs on physical conditions. Results: After adjusting for sociodemographic variables and psychiatric disorders, respondents with any PTE had increased odds of all assessed physical conditions, ranging between 1.48 (95 % CI: 1.06–2.07) for arthritis and 2.07 (95 % CI: 1.57–2.73) for respiratory conditions, compared to those without PTE exposure. Sexual violence, physical violence, unexpected death of a loved one, and network PTEs significantly increased the odds of all or nearly all the physical conditions assessed. There was a dose-response relationship between number of PTEs and increased odds of all physical conditions. Conclusions: Results from this study, the first in an African general population, are consistent with other population-based studies; PTEs confer a broad-spectrum risk for chronic physical conditions, independent of psychiatric disorders. These risks increase with each cumulative PTE exposure. Clinically, comprehensive evaluations for risk of mental and physical health morbidities should be considered among PTE survivors

A Mouse Model of Zika Virus Pathogenesis

SummaryThe ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barré syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3−/− Irf5−/− Irf7−/− triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor (Ifnar1−/−) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3−/−, Irf5−/−, and Mavs−/− knockout mice exhibited no overt illness. Ifnar1−/− mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1−/− mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis

Does pyrogenicity protect burning plants?

Pyrogenic plants dominate many fire-prone ecosystems. Their prevalence suggests some advantage to their enhanced flammability, but researchers have had difficulty tying pyrogenicity to individual-level advantages. Based on our review, we propose that enhanced flammability in fire-prone ecosystems should protect the belowground organs and nearby propagules of certain individual plants during fires. We base this hypothesis on five points: (1) organs and propagules by which many fire-adapted plants survive fires are vulnerable to elevated soil temperatures during fires; (2) the degree to which burning plant fuels heat the soil depends mainly on residence times of fires and on fuel location relative to the soil; (3) fires and fire effects are locally heterogeneous, meaning that individual plants can affect local soil heating via their fuels; (4) how a plant burns can thus affect its fitness; and (5) in many cases, natural selection in fire-prone habitats should therefore favor plants that burn rapidly and retain fuels off the ground. We predict an advantage of enhanced flammability for plants whose fuels influence local fire characteristics and whose regenerative tissues or propagules are affected by local variation in fires. Our pyrogenicity as protection hypothesis has the potential to apply to a range of life histories. We discuss implications for ecological and evolutionary theory and suggest considerations for testing the hypothesis. © 2010 by the Ecological Society of America

Fuels and fires influence vegetation via above- and below-ground pathways in a high-diversity plant community

1. Fire strongly influences plant populations and communities around the world, making it an important agent of plant evolution. Fire influences vegetation through multiple pathways, both above- and belowground. Few studies have yet attempted to tie these pathways together in a mechanistic way through soil heating even though the importance of soil heating for plants in fire-prone ecosystems is increasingly recognized. 2. Here we combine an experimental approach with structural equation modelling (SEM) to simultaneously examine multiple pathways through which fire might influence herbaceous vegetation. In a high-diversity longleaf pine groundcover community in Louisiana, USA, we manipulated fine-fuel biomass and monitored the resulting fires with high-resolution thermocouples placed in vertical profile above- and belowground. 3. We predicted that vegetation response to burning would be inversely related to fuel load owing to relationships among fuels, fire temperature, duration and soil heating. 4. We found that fuel manipulations altered fire properties and vegetation responses, of which soil heating proved to be a highly accurate predictor. Fire duration acting through soil heating was important for vegetation response in our SEMs, whereas fire temperature was not. 5. Our results indicate that in this herbaceous plant community, fire duration is a good predictor of soil heating and therefore of vegetation response to fire. Soil heating may be the key determinant of vegetation response to fire in ecosystems wherein plants persist by resprouting or reseeding from soil-stored propagules. 6. Synthesis. Our SEMs demonstrate how the complex pathways through which fires influence plant community structure and dynamics can be examined simultaneously. Comparative studies of these pathways across different communities will provide important insights into the ecology, evolution and conservation of fire-prone ecosystems

Combined anti-inflammatory and neuroprotective treatments have the potential to impact disease phenotypes in Cln3−/− mice

Batten disease, or juvenile NCL, is a fatal neurodegenerative disorder that occurs due to mutations in the CLN3 gene. Because the function of CLN3 remains unclear, experimental therapies for JNCL have largely concentrated upon the targeting of downstream pathomechanisms. Neuron loss is preceded by localized glial activation, and in this proof-of-concept study we have investigated whether targeting this innate immune response with ibuprofen in combination with the neuroprotective agent lamotrigine improves the previously documented beneficial effects of immunosuppressants alone. Drugs were administered daily to symptomatic Cln3 -/- mice over a 3 month period, starting at 6 months of age, and their impact was assessed using both behavioral and neuropathological outcome measures. During the treatment period, the combination of ibuprofen and lamotrigine significantly improved the performance of Cln3 -/- mice on the vertical pole test, slowing the disease-associated decline, but had less of an impact upon their rotarod performance. There were also moderate and regionally dependent effects upon astrocyte activation that were most pronounced for ibuprofen alone, but there was no overt effect upon microglial activation. Administering such treatments for longer periods will enable testing for any impact upon the neuron loss that occurs later in disease progression. Given the partial efficacy of these treatments, it will be important to test further drugs of this type in order to find more effective combinations

HSV-1 and Zika virus but not SARS-CoV-2 replicate in the human cornea and are restricted by corneal type III interferon

Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. In human corneal explants, blockade of IFNλR1 enhances replication of ZIKV and HSV-1 but not SARS-CoV-2. In addition to an antiviral role for IFNλR1 in the cornea, our results suggest that the human cornea does not support SARS-CoV-2 infection despite expression of ACE2, a SARS-CoV-2 receptor, in the human corneal epithelium