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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.

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.

The molecular mechanisms regulating the zonal distribution of metabolism in liver are incompletely understood. Here we use single nuclei genomics techniques to examine the spatial transcriptional function of transcription factor 7-like 2 (TCF7L2) in mouse liver, and determine the consequences of TCF7L2 transcriptional inactivation on the metabolic architecture of the liver and the function of zonated metabolic pathways. We report that while Tcf7l2 mRNA expression is ubiquitous across the liver lobule, accessibility of the consensus TCF/LEF DNA binding motif is restricted to pericentral (PC) hepatocytes in zone 3. In mice expressing functionally inactive TCF7L2 in liver, PC hepatocyte-specific gene expression is absent, which we demonstrate promotes hepatic cholesterol accumulation, impaired bile acid synthesis, disruption to glutamine/glutamate homeostasis and pronounced dietary-induced hepatic fibrosis. In summary, TCF7L2 is a key regulator of hepatic zonal gene expression and regulates several zonated metabolic pathways that may contribute to the development of fibrotic liver disease. This study identifies transcription factor 7-like 2 (TCF7L2) as a key regulator of hepatic metabolic zonation, and demonstrates that disruption to the transcriptional activity of TCF7L2 exacerbates the development of dietary-induced hepatic fibrosis.

PHOTOS 5 DIAGRAM; ) This page was one of six written by Stuart Williams. He left the note in his room at his Hollywood apartment on Friday before going on a rampage that left three dead and two injured. (color) Williams Amanda Scheiber, wounded and bleeding , called 911 for help. Staff photo/Judy Sloan Reich RESCUERS: Officers who participated in Friday's events are [Don Huneke], left, [Jimmy Vogel], [William Ferguson], [Mike Browne], [Anthony Fernandez], [Jason Thomas] and [Daniel Dunn]. Staff graphic/Jon-Paul Dumont Diagram shows the method used by the police to rescue Amanda Scheiber. 911 TRANSCRIPT 911: Where did he shoot you at? Amanda Scheiber: I don't know if it's near the heart or what? It's in my chest somewhere. I'm bleeding. 911: Okay ma'am. Stay on the phone with me.Okay ma'am. Scheiber: I'm pregnant. 911: Is he white or black? Scheiber: White. 911: Why did he shoot you? Scheiber: I don't know. Hurry, please hurry. TRANSCRIPT OF 911 TAPE 911: Do you have an emergency? What's wrong? First victim: (Amanda Scheiber) I'm at 1776 Polk St. 911: Okay Scheiber: I've been shot. 911: You've been shot. Scheiber: Yes. 911: Who shot you ma'am? Scheiber: I don't know, I don't know who he is. He's shooting other people. 911: Okay, where is he now? Scheiber: He's in the building somewhere. I don't know. 911: What apartment are you in? Scheiber: I'm in the office. I'm the manager. 911: You're the manager? Scheiber: Uh-huh. 911: Where did he shoot you at? Scheiber: I don't know if it's through the heart or what? It's in my chest somewhere. I'm bleeding. 911: Okay ma'am. Stay on the phone with me. Okay ma'am. Scheiber: I'm pregnant. 911: Is he white or black? Scheiber: White. 911: Why did he shoot you? Scheiber: I don't know. Hurry, please hurry. 911: Hold on. How many months are you? Scheiber: Three months and one week. 911: You don't know why he shot you? Scheiber: No, I don't. 911: Did he shoot anybody else. Scheiber: I heard five shots. 911: What is he wearing? Scheiber: A blue hat and glasses. 911: Hold on. You don't know why he shot you? Scheiber: No, I don't. 911: What's your name? Scheiber: Amanda. 911: What is it? Scheiber: Amanda. 911: Amanda. Okay, give me a description of him. He's a white male. Hello, hello, hello Scheiber: Yes. Shot was fired and a second one was fired. 911: He's a white male. Scheiber: Please hurry. 911: Ma'am, he's a white male, okay. What is he wearing? Scheiber: Blue. 911: Blue what? Amanda Scheiber's portion of the tape ends. A call by [Jelena Marjanovic] begins. 911: Ma'am, do you need the police to rescue you? Marjanovic: Hello. 911: Hello. Marjanovic: Please, 1776 Polk St.. Some guy shot me with a gun here. I'm shot. Please hurry up. 911: You're shot. Marjanovic: Yes, two people. One lady down the aisle. I tried to walk in and he shot me. I'm bleeding. Please come. 911: Stay on the phone. Where are you? Marjanovic: I'm in front of the building, inside. Please come I'm shot, 1776 Polk St. 911: Where are you shot? Marjanovic: In front door, I don't know. 911: Okay, but you got shot. Marjanovic: Yeah. 911: Do you know what the male was wearing? Marjanovic: Hello? 911: Do you know what the male was wearing? Marjanovic: Hello? 911: What was he wearing? Who shot you?