Mosquito ageing modulates the development, virulence and transmission potential of pathogens.

Host age variation is a striking source of heterogeneity that can shape the evolution and transmission dynamic of pathogens. Compared with vertebrate systems, our understanding of the impact of host age on invertebrate-pathogen interactions remains limited. We examined the influence of mosquito age on key life-history traits driving human malaria transmission. Females of Anopheles coluzzii, a major malaria vector, belonging to three age classes (4-, 8- and 12-day-old), were experimentally infected with Plasmodium falciparum field isolates. Our findings revealed reduced competence in 12-day-old mosquitoes, characterized by lower oocyst/sporozoite rates and intensities compared with younger mosquitoes. Despite shorter median longevities in older age classes, infected 12-day-old mosquitoes exhibited improved survival, suggesting that the infection might act as a fountain of youth for older mosquitoes specifically. The timing of sporozoite appearance in the salivary glands remained consistent across mosquito age classes, with an extrinsic incubation period of approximately 13 days. Integrating these results into an epidemiological model revealed a lower vectorial capacity for older mosquitoes compared with younger ones, albeit still substantial owing to extended longevity in the presence of infection. Considering age heterogeneity provides valuable insights for ecological and epidemiological studies, informing targeted control strategies to mitigate pathogen transmission.

Understanding systemic racism: Anti-Blackness, white supremacy, racial capitalism, and the re/creation of white space and time.

In this article, the authors explain systemic racism through a racial-spatial framework wherein anti-Blackness, white supremacy, and racial capitalism interlock to create and recreate white space and time. Through the creation of private property, institutional inequities become embedded and structured for the benefit of white people. The framework provides a way to conceptualize how our geographies are racialized and how time is often used against Black and non-Black people of Color. In contrast to white experiences of feeling "in-place" almost everywhere, Black and non-Black people of Color continually experience displacement and dispossession of both their place and their time. This racial-spatial onto-epistemology is derived from the knowledge and experiences of Black, Indigenous, Latinx, Asian, and other non-Black people of Color, and how they have learned through acculturation, racial trauma, and micro-aggressions to thrive in white spaces and contend with racism such as time-theft. The authors posit that through reclaiming space and time, Black and non-Black people of Color can imagine and practice possibilities that center their lived experiences and knowledge as well as elevate their communities. Recognizing the importance of reclaiming space and time, the authors encourage counseling psychology researchers, educators, and practitioners to consider their positionalities with respect to systemic racism and the advantages it confers to white people. Through the process of creating counterspaces and using counterstorytelling, practitioners may help clients develop healing and nurturing ecologies that challenge the perniciousness of systemic racism. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

New insights into the Immune TME of adult-type diffuse gliomas.

PURPOSE OF REVIEW: Adult-type diffuse gliomas are highly heterogeneous tumors. Bulk transcriptome analyses suggested that the composition of the tumor microenvironment (TME) corresponds to genetic and clinical features. In this review, we highlight novel findings on the intratumoral heterogeneity of IDH-wildtype and IDH-mutant gliomas characterized at single-cell resolution, and emphasize the mechanisms shaping the immune TME and therapeutic implications. RECENT FINDINGS: Emergent evidence indicates that in addition to genetic drivers, epigenetic mechanisms and microenvironmental factors influence the glioma subtypes. Interactions between glioma and immune cells contribute to immune evasion, particularly in aggressive tumors. Spatial and temporal heterogeneity of malignant and immune cell subpopulations is high in recurrent gliomas. IDH-wildtype and IDH-mutant tumors display distinctive changes in their myeloid and lymphoid compartments, and D-2HG produced by IDH-mutant cells impacts the immune TME. SUMMARY: The comprehensive dissection of the intratumoral ecosystem of human gliomas using single-cell and spatial transcriptomic approaches advances our understanding of the mechanisms underlying the immunosuppressed state of the TME, supports the prognostic value of tumor-associated macrophages and microglial cells, and sheds light on novel therapeutic options.

An epi-evolutionary model for predicting the adaptation of spore-producing pathogens to quantitative resistance in heterogeneous environments.

We have modeled the evolutionary epidemiology of spore-producing plant pathogens in heterogeneous environments sown with several cultivars carrying quantitative resistances. The model explicitly tracks the infection-age structure and genetic composition of the pathogen population. Each strain is characterized by pathogenicity traits determining its infection efficiency and a time-varying sporulation curve taking into account lesion aging. We first derived a general expression of the basic reproduction number R 0 for fungal pathogens in heterogeneous environments. We show that the evolutionary attractors of the model coincide with local maxima of R 0 only if the infection efficiency is the same on all host types. We then studied the contribution of three basic resistance characteristics (the pathogenicity trait targeted, resistance effectiveness, and adaptation cost), in interaction with the deployment strategy (proportion of fields sown with a resistant cultivar), to (i) pathogen diversification at equilibrium and (ii) the shaping of transient dynamics from evolutionary and epidemiological perspectives. We show that quantitative resistance affecting only the sporulation curve will always lead to a monomorphic population, whereas dimorphism (i.e., pathogen diversification) can occur if resistance alters infection efficiency, notably with high adaptation costs and proportions of the resistant cultivar. Accordingly, the choice of the quantitative resistance genes operated by plant breeders is a driver of pathogen diversification. From an evolutionary perspective, the time to emergence of the evolutionary attractor best adapted to the resistant cultivar tends to be shorter when resistance affects infection efficiency than when it affects sporulation. Conversely, from an epidemiological perspective, epidemiological control is always greater when the resistance affects infection efficiency. This highlights the difficulty of defining deployment strategies for quantitative resistance simultaneously maximizing epidemiological and evolutionary outcomes.

Age-structured non-pharmaceutical interventions for optimal control of COVID-19 epidemic.

In an epidemic, individuals can widely differ in the way they spread the infection depending on their age or on the number of days they have been infected for. In the absence of pharmaceutical interventions such as a vaccine or treatment, non-pharmaceutical interventions (e.g. physical or social distancing) are essential to mitigate the pandemic. We develop an original approach to identify the optimal age-stratified control strategy to implement as a function of the time since the onset of the epidemic. This is based on a model with a double continuous structure in terms of host age and time since infection. By applying optimal control theory to this model, we identify a solution that minimizes deaths and costs associated with the implementation of the control strategy itself. We also implement this strategy for three countries with contrasted age distributions (Burkina-Faso, France, and Vietnam). Overall, the optimal strategy varies throughout the epidemic, with a more intense control early on, and depending on host age, with a stronger control for the older population, except in the scenario where the cost associated with the control is low. In the latter scenario, we find strong differences across countries because the control extends to the younger population for France and Vietnam 2 to 3 months after the onset of the epidemic, but not for Burkina Faso. Finally, we show that the optimal control strategy strongly outperforms a constant uniform control exerted over the whole population or over its younger fraction. This improved understanding of the effect of age-based control interventions opens new perspectives for the field, especially for age-based contact tracing.

Striatal circuit development and its alterations in Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder that usually starts during midlife with progressive alterations of motor and cognitive functions. The disease is caused by a CAG repeat expansion within the huntingtin gene leading to severe striatal neurodegeneration. Recent studies conducted on pre-HD children highlight early striatal developmental alterations starting as soon as 6 years old, the earliest age assessed. These findings, in line with data from mouse models of HD, raise the questions of when during development do the first disease-related striatal alterations emerge and whether they contribute to the later appearance of the neurodegenerative features of the disease. In this review we will describe the different stages of striatal network development and then discuss recent evidence for its alterations in rodent models of the disease. We argue that a better understanding of the striatum's development should help in assessing aberrant neurodevelopmental processes linked to the HD mutation.

From gestation to weaning: Combining robust design and multi-event models unveils cost of lactation in a large herbivore.

The cost of current reproduction on survival or future reproduction is one of the most studied trade-offs governing resource distribution between fitness components. Results have often been clouded, however, by the existence of individual heterogeneity, with high-quality individuals able to allocate energy to several functions simultaneously, at no apparent cost. Surprisingly, it has also rarely been assessed within a breeding season by breaking down the various reproductive efforts of females from gestation to weaning, even though resource availability and energy requirements vary greatly. We filled this gap by using an intensively monitored population of Pyrenean chamois and by expanding a new methodological approach integrating robust design in a multi-event framework. We distinguished females that gave birth or not, and among reproducing females whether they lost their kid or successfully raised it until weaning. We estimated spring and summer juvenile survival, investigated whether gestation, lactation or weaning incurred costs on the next reproductive occasion, and assessed how individual heterogeneity influenced the detection of such costs. Contrary to expectations if trade-offs occur, we found a positive relationship between gestation and adult survival suggesting that non-breeding females are in poor condition. Costs of reproduction were expressed through negative relationships between lactation and both subsequent breeding probability and spring juvenile survival. Such costs could be detected only once individual heterogeneity (assessed as two groups contrasting good vs. poor breeders) and time variations in juvenile survival were accounted for. Early lactation decreased the probability of future reproduction, providing quantitative evidence of the fitness cost of this period recognized as the most energetically demanding in female mammals and critical for neonatal survival. The new approach employed made it possible to estimate two components of kid survival that are often considered practically unavailable in free-ranging populations, and also revealed that reproductive costs appeared only when contrasting the different stages of reproductive effort. From an evolutionary perspective, our findings stressed the importance of the temporal resolution at which reproductive cost is studied, and also provided insights on the reproductive period during which internal and external factors would be expected to have the greatest fitness impact.