EXTH-08. REPLACEMENT OF MICROGLIA BY BRAIN-ENGRAFTED MACROPHAGES PREVENTS MEMORY DEFICITS AFTER THERAPEUTIC WHOLE-BRAIN IRRADIATION

Abstract Microglia have a distinct origin compared to blood circulating myeloid cells. Under normal physiological conditions, microglia are maintained by self-renewal, independent of hematopoietic progenitors. Following genetic or pharmacologic depletion, newborn microglia derive from the local residual pool and quickly repopulate the entire brain. The depletion of brain resident microglia during therapeutic whole-brain irradiation fully prevents irradiation-induced synaptic loss and recognition memory deficits but the mechanisms driving these protective effects are unknown. Here, we demonstrate that after CSF-1R inhibitor-mediated microglia depletion and therapeutic whole-brain irradiation, circulating monocytes engraft into the brain and replace the microglia pool. These monocyte-derived brain-engrafted macrophages have reduced phagocytic activity compared to microglia from irradiated brains, but similar to locally repopulated microglia without brain irradiation. Transcriptome comparisons reveal that brain-engrafted macrophages have both monocyte and embryonic microglia signatures. These results suggest that monocyte-derived brain-engrafted macrophages represent a novel therapeutic avenue for the treatment of brain radiotherapy-induced cognitive deficits

The bioaccessibility of folate in breads and the stability of folate vitamers during in vitro digestion

Both the liberation and stability of endogenous folate are relevant to the bioaccessibility of folate. Since folates are unstable, in addition to studying the natural folate content in foods, bioaccessibility should be considered. To understand folate changes during digestion, a mixture of standard folate compounds was subjected to a static in vitro gastrointestinal digestion assay. Next, different types of bread were analysed to study how food matrices influence folate bioaccessibility. Folates were identified and quantitated by a UHPLC-PDA/FL method. Folic acid and 10-formylfolic acid were stable throughout the digestion, and the conversions among formyl folates and 5,10-methenyltetrahydrofolate were triggered at the gastric phase. Tetrahydrofolate began to degrade during the oral phase and was lost completely during the gastric phase. During the intestinal phase, 5-methyltetrahydrofolate began to degrade and suffered a 60% loss. With bread matrices, folate conversions and the decrease of reduced folates were also common, but the extent of changes varied. Generally, rye breads had the highest (80–120%) bioaccessibility of folate, while oat breads had the lowest (31–102%). The high proportion of 5-methyltetrahydrofolate could result in low bioaccessibility because of its relatively low stability during digestion in bread matrices. An increase in 10-formylfolic acid content was observed for all the breads, but 10-formyldihydrofolate seemed to be more stable in rye breads than in oat and wheat breads. The results showed that folates undergo significant changes during digestion and that food matrices could be modified to affect these changes towards better folate bioaccessibility.Peer reviewe

Bioaccessibility of Folate in Faba Bean, Oat, Rye and Wheat Matrices

Cereals and legumes are rich in folate. However, due to the instability of folate, processing and digestion can induce significant folate loss. In this paper, folate bioaccessibility of faba bean, oat, rye and wheat flours and pastes was studied using a static in vitro digestion model. Folate bioaccessibility depended on food matrices, varying from 42% to 67% in flours and from 40% to 123% in pastes. Digestion was associated with the inter conversion of formyl folates, as well as the increase of oxidised vitamers and decrease of reduced vitamers. Especially in faba bean, 5-methyltetrahydrofolate showed surprisingly good stability both in digestion and heat treatment, resulting in high bioaccessibility. The physiological concentration of ascorbic acid did not stabilise folate in digestion; however, a higher level helped to maintain reduced vitamers. Heat treatment (10-min paste making) could improve folate bioaccessibility by liberating folate from the food matrices and by altering folate vitamer distribution.Peer reviewe

5-Methyltetrahydrofolate Is a Crucial Factor in Determining the Bioaccessibility of Folate in Bread

This study investigated the bioaccessibility of folate in wheat bread baked with different ingredients and processing methods. Next, different matrices were spiked with 5-methyltetrahydrofolate, gallic acid (GA), or both to investigate the stability of 5-methyltetrahydrofolate during in vitro digestion. The folate bioaccessibility in bread varied from 44 to 96%. The inclusion of whole-grain or faba bean flour significantly improved both folate content and bioaccessibility. Baking with yeast increased the folate content by 145% in bread but decreased folate bioaccessibility compared to the bread without added yeast because of the instability of 5-methyltetrahydrofolate. Spiking experiments confirmed oxidation as a critical reason for 5-methyltetrahydrofolate loss during digestion. However, GA protected this vitamer from degradation. Additionally, 5-methyltetrahydrofolate was less stable in whole-grain wheat matrices than other matrices. This study demonstrated that the stability of 5-methyltetrahydrofolate is crucial for folate bioaccessibility in bread, and methods for stabilizing this vitamer should be further studied.Peer reviewe

Vermont Agriculture and Food System Plan 2020 -- A Review of Recommendations (Part One)

Key Findings in reviewing the Vermont Agriculture and Food System Plan: 1. All recommendations in this review have been coded into eight thematic categories to be used more effectively by stakeholders. 2. We identify four clusters of recommendations to assist stakeholders in understanding the relationships between categories and enabling understanding of the various stakeholders and resources necessary to implement recommendations from different briefs 3. 87% of recommendations either request direct funding for an initiative or recommend a capital expenditure. With financial challenges amidst COVID-19, we highlight eight recommendations for a Vermont Food System that could move forward without financial resources. 4. In the future, giving authors a guide for writing recommendations would make them easier to categorize and implement

Traffic restrictions during the 2008 Olympic Games reduced urban heat intensity and extent in Beijing

Satellite thermal remote sensing has been utilized to examine the urban heat dynamics in relation to the urban traffic restriction policy. During the 2008 Olympic Games in Beijing, the traffic volume was approximately cut off by half through the road space rationing. Based on daily MODIS satellite thermal observations on the surface temperature, statistical models were developed to analyze the contribution of traffic volume reduction to the urban heat intensity and spatial extent. Our analyses show that cutting off half of the traffic volume has led to a marked decrease in the mean surface temperature by 1.5–2.4 °C and shrinkage of the heat extent by 820 km2 in Beijing. This research suggests that the impact of urban traffic on heat intensity is considerably larger than previously thought, and the management of urban traffic and vehicle fossil fuel use should be included in the future urban heat mitigation plan

A New SFF Process for Functional Ceramic Components

SRI International in collaboration with Saint-Gobain/Norton Industrial Ceramics Corporation and Allison Engine Company is developing a new SFF process, Direct Photo Shaping, for the fabrication of functional ceramic components. The process is based on the layerby-layer photocuring of ceramic slurries containing monomers curable by visible light. Each layer is photoimaged by a liquid crystal display (LCD) or a digital light processing (DLP) projection system. After binder removal and sintering, the properties of silicon nitride tiles prepared according to the Dire~t Photo Shaping process were found to be comparable to properties of tiles formed by conventional methods.Mechanical Engineerin

Production and temperature sensitivity of long chain alkenones in the cultured haptophyte Pseudoisochrysis paradoxa

The alkenone unsaturation index (U<sub>37</sub><sup>K</sup> or U<sub>37</sub><sup>K′</sup>) serves as a critical tool for reconstructing temperature in marine environments. Lacustrine haptophyte algae are genetically distinct from their ubiquitous and well studied marine counterparts, and the unknown species-specific genetic imprints on long chain alkenone production by lacustrine species have hindered the widespread application of the U37<sup>K</sup> temperature proxy to lake sediment records. The haptophyte Pseudoisochrysis paradoxa produces alkenones but its U37<sup>K</sup> calibration has never been determined. It has an alkenone fingerprint abundant in tetraunsaturated alkenones, a hallmark of lacustrine environments. We present here the first calibration of the U37<sup>K</sup> index to temperature for a culture of P. paradoxa. We found that the U37<sup>K</sup> index accurately captured the alkenone response to temperature whereas the U37<sup>K′</sup> index failed to do so, with U37<sup>K′</sup> values below 0.08 projecting to two different temperature values. Our results add a fifth species-specific U37<sup>K</sup> calibration and provide another line of evidence that different haptophyte species require different U37<sup>K</sup> calibrations. The findings also highlight the necessary inclusion of the C<sub>37:4</sub> alkenone when reconstructing temperatures from P. paradoxa-derived alkenone records