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\"Charmed by Betty Crocker, who has been an icon in American cooking for nearly a century yet still represents a certain style of modern super-woman who can do it all, the Shannons were compelled to take on a cooking challenge: they set out to prove that any recipe could be re-created to satisy even the pickiest eaters, whether they be vegan, vegetarian, or carnivore\"--P. [4] of cover.

CAKE 1½ cups sugar ½ cup (1 stick) vegan margarine, such as Earth Balance, softened 1 Tbs. applesauce 1 Tbs. egg replacer, such as Ener-G 2½ cups all-purpose flour 1 tsp. baking soda 1 tsp. salt 1 14-oz. can coconut milk 3 Tbs. limoncello 2 Tbs. grated lemon zest Candied lemon slices for garnish, optional GLAZE ¼ cup Earth Balance margarine, softened 2 cups confectioners' sugar ¼ cup limoncello 2 Tbs. grated lemon zest 1 | Preheat oven to 325°F- Spray Bundt pan with cooking spray. 2 | To make Cake: Cream sugar and margarine in bowl with electric mixer.

MISS MIRAMON still sat at her desk, thinking.

Miss Miramon still sat at her desk thinking.

Dendritic cells play a key role in processing and presenting antigens to naïve T cells to prime adaptive immunity. Circadian rhythms are known to regulate many aspects of immunity; however, the role of circadian rhythms in dendritic cell function is still unclear. Here, we show greater T cell responses when mice are immunised in the middle of their rest versus their active phase. We find a circadian rhythm in antigen processing that correlates with rhythms in both mitochondrial morphology and metabolism, dependent on the molecular clock gene, Bmal1 . Using Mdivi-1, a compound that promotes mitochondrial fusion, we are able to rescue the circadian deficit in antigen processing and mechanistically link mitochondrial morphology and antigen processing. Furthermore, we find that circadian changes in mitochondrial Ca 2+ are central to the circadian regulation of antigen processing. Our results indicate that rhythmic changes in mitochondrial calcium, which are associated with changes in mitochondrial morphology, regulate antigen processing. Circadian rhythms are known to impact a range of biological processes including in the immune system. Here the authors show how circadian rhythms modulate the T cell response to vaccination via regulation of dendritic cell metabolism.

The transcription factor BMAL1 is a clock protein that generates daily or circadian rhythms in physiological functions including the inflammatory response of macrophages. Intracellular metabolic pathways direct the macrophage inflammatory response, however whether the clock is impacting intracellular metabolism to direct this response is unclear. Specific metabolic reprogramming of macrophages controls the production of the potent pro-inflammatory cytokine IL-1β. We now describe that the macrophage molecular clock, through Bmal1 , regulates the uptake of glucose, its flux through glycolysis and the Krebs cycle, including the production of the metabolite succinate to drive Il-1β production. We further demonstrate that BMAL1 modulates the level and localisation of the glycolytic enzyme PKM2, which in turn activates STAT3 to further drive Il-1β mRNA expression. Overall, this work demonstrates that BMAL1 is a key metabolic sensor in macrophages, and its deficiency leads to a metabolic shift of enhanced glycolysis and mitochondrial respiration, leading to a heightened pro-inflammatory state. These data provide insight into the control of macrophage driven inflammation by the molecular clock, and the potential for time-based therapeutics against a range of chronic inflammatory diseases.

Background Rare diseases (i.e., incidence of <1/2000) are individually uncommon, but collectively these 10,000 conditions affect an estimated 473 million people globally, and approximately 70% of rare diseases manifest in childhood. Despite this global impact, 90% of rare diseases lack effective treatment. Treatments for rare diseases are often identified through clinical trials. Identifying parents’ knowledge needs and preferences regarding pediatric rare disease clinical trials is an important aspect of empowering parents, improving clinical research practices, and potentially improving recruitment to these vital trials. The aim of the scoping review is to determine the extent, range, and characteristics of the evidence on the knowledge needs and preferences of parents regarding pediatric rare disease clinical trials. Methods A scoping review will be conducted to identify sources of literature on the topic. A systematic search strategy co-developed with a research librarian will be conducted in six databases (Medline, EMBASE, CINAHL, Scopus, Web of Science, and PsycINFO). Gray literature will be searched via Google, Perplexity AI, the ProQuest Dissertations & Theses Global database, and relevant rare disease organizational websites. Abstract and full-text screening will be conducted by two reviewers independently. Studies in English will be included regardless of study design, date of publication, or location of study/publication. Study quality will be appraised using the Mixed Methods Appraisal Tool. Data will be extracted including study characteristics, population, phenomena under investigation, and knowledge needs and preferences identified. Analysis will involve a descriptive numerical summary and qualitative content analysis. Findings will be presented in evidence tables, and patterns, themes, and gaps across the data will be reported using a narrative approach. Discussion This review will provide an overview of the existing literature regarding parents’ knowledge needs and preferences about pediatric rare disease clinical trials. The findings of this review will inform future research and the development of knowledge translation resources for parents of children with rare diseases. Systematic review registration This protocol has been registered in Open Science Framework (registration: https://doi.org/10.17605/OSF.IO/QXR8G ).

Batrachochytrium dendrobatidis (Bd) is the most catastrophic wildlife pathogen, associated with severe amphibian population declines or the extinction of over 500 species. Bd has the potential to influence the structure and dynamics of amphibian populations in multiple and compounding ways, yet few studies have investigated how Bd effects vary in communities with differential susceptibility. Here, we used temporal data from amphibian communities in temperate Tasmania, Australia, comprising four co‐occurring species: the brown treefrog ( Litoria ewingii ), Tasmanian treefrog ( L. burrowsae ), common froglet ( Crinia signifera ), and Tasmanian froglet ( C. tasmaniensis ). Previous laboratory trials indicated L. burrowsae and C. tasmaniensis are susceptible to Bd, whereas L. ewingii and C. signifera act as reservoirs. Using Bayesian Markov chain Monte Carlo models, we tested whether Bd presence, the presence of reservoirs, or same‐genus species influenced susceptible species across sites and years. Contrary to expectations—that Bd and reservoir hosts destabilise amphibian communities—we found no evidence of population declines in L. burrowsae or C. tasmaniensis . Instead, species appeared to coexist in a relatively stable community structure, despite Bd presence. Our findings suggest that susceptibility identified by laboratory trials might not reliably predict field disease outcomes in this system, owing to an absence of relevant extrinsic environmental variables. We postulate that pond conditions in which amphibian communities in our study occur, characterised by low temperature and pH, limit Bd growth and survival, creating a refuge from its effects. These results highlight the importance of ecological and environmental context when assessing disease impacts in wild multi‐host communities, and also that climate change may threaten community resilience.

Four ways archaeologists have tried to gain insights into how flintknapping creates lithic variability are fracture mechanics, controlled experimentation, replication and attribute studies of lithic assemblages. Fracture mechanics has the advantage of drawing more directly on first principles derived from physics and material sciences, but its relevance to controlled experimentation, replication and lithic studies more generally has been limited. Controlled experiments have the advantage of being able to isolate and quantify the contribution of individual variables to knapping outcomes, and the results of these experiments have provided models of flake formation that when applied to the archaeological record of flintknapping have provided insights into past behavior. Here we develop a linkage between fracture mechanics and the results of previous controlled experiments to increase their combined explanatory and predictive power. We do this by documenting the influence of Herztian cone formation, a constant in fracture mechanics, on flake platforms. We find that the platform width is a function of the Hertzian cone constant angle and the geometry of the platform edge. This finding strengthens the foundation of one of the more influential models emerging from the controlled experiments. With additional work, this should make it possible to merge more of the experimental results into a more comprehensive model of flake formation.