Project description:A koji mold Aspergillus kawachii is used for making a Japanese distilled spirit, shochu. During making shochu, A. kawachii is grown in a solid-state culture comprised of steamed grains such as rice or barley, termed koji, to convert the starch to glucose and also to produce citric acid. During this process, cultivation temperature of A. kawachii is generally controlled by raising to 40M-BM-0C and then lowering to 30M-BM-0C. The cultivation at 40M-BM-0C and the following at lower temperature of 30M-BM-0C has important roles in the elevated activity of amylase and starting an accumulation of a large amount of citric acid, respectively. In this study, we investigated the effect of temperature on the gene expression of A. kawachii when barley was used as ingredient for making koji. The results of DNA microarray and gene ontology analysis showed that the expression of genes involved in the metabolic processes of glycerol, trehalose, and pentose phosphate that branch from glycolysis was down-regulated by shifting the cultivation temperature from 40M-BM-0C from 30M-BM-0C. In addition, reduction in the expression of the genes related with heat shock responses and increasing in the expression of the genes related with amino acid transport after the temperature lowering were found to be significant change. These results suggested that the cultivation at 40M-BM-0C is stressful event for the A. kawachii and the heat adaption lead to the depression of citric acid accumulation through activation of the branching pathways from glycolysis. The gene expression profile obtained in this study will help to understand the gene regulation during koji-making process to optimize A. kawachii as industrial microorganism. Gene expression of Aspergillus kawachii in barley koji was measured at 25, 26.5, and 44 hours at two different temperature control. Three independent experiments were performed at each time (25, 26.5, or 44 hours) using different barley koji for each expreriment.

Project description:Challenges arise when treatment to improve maternal health brings the possibility of risk to fetal health. The coronavirus disease 2019 (COVID-19) vaccine is the most recent, but hardly the only, example. Because pregnant patients are often specifically excluded from trials of new therapies, this is often the dilemma that patients and providers face when considering new treatments. In this study, we used the COVID-19 vaccine as an exemplar to question the broader issue of how society, in general, and obstetricians, in particular, should balance obligations to pregnant women's right of access to new therapeutic agents with the physician's desire to protect the fetus from potential risks. We will argue that in almost all circumstances (with few exceptions, as will also be discussed), maternal benefit and respect for autonomy create the uncertainty that absent safety data bring. Consequently, if pregnant women choose to try new interventions and treatments, such as the COVID-19 vaccination, they should be offered those new regimens and their decision supported. In addition, we will argue that the right solution to avoid the dilemma of absent data is to include pregnant individuals in clinical trials studying new treatments, drugs, and other therapies. We will also discuss the basis for our opinion, which are mainstream obstetrical ethics, precedents in law (supreme court ruling that forbids companies to exclude women from jobs that might pose a risk to the fetus), and historic events (thalidomide). The ethical framework includes the supposition that sacrifice to improve fetal outcome is a virtue and not a mandate. Denying a pregnant patient treatment because of threats to their life can create absurd and paradoxical consequences. Either requiring abortion or premature delivery before proceeding with treatments to optimize maternal health, or risking a patient's own life and ability to parent a child by delaying treatment brings clear and significant risks to fetal and/or neonatal outcomes. With rare exceptions, properly and ethically balancing such consequential actions cannot be undertaken without considering the values and goals of the pregnant patient. Therefore, active participation of both the pregnant patient and their physician in shared decision making is needed.

Project description:The ability to differentiate between threat and safety cues is essential for adaptive behavior, yet this process is disrupted in psychiatric disorders such as post-traumatic stress disorder (PTSD), where safety cues fail to suppress fear expression. To uncover the neurobiological mechanisms of safety learning, we compared safety conditioning (SC) and contextual fear conditioning (CFC) in the infralimbic cortex (IL) of the medial prefrontal cortex (mPFC) across recent and remote memory retrieval in mice. We identify a novel mechanism whereby safety learning promotes neuro-glial interactions that may facilitate plasticity in the mPFC. SC promotes long-term suppression of contextual fear compared to CFC. At remote retrieval, SC animals show increased IL parvalbumin (PV) interneuron activity and reduced perineuronal net (PNN) density, suggesting that extracellular matrix (ECM) remodeling could support enhanced plasticity in this group. We further identify a critical role for oligodendrocyte lineage cells (OLCs) in PNN remodeling. Notably, safety retrieval recruits satellite oligodendrocyte lineage cells (i.e., satOlig2+ cells) to PV interneurons. In SC animals, this recruitment correlates with reduced PNN accumulation around PV-satOlig2 pairs, whereas CFC animals exhibit increased PNN density at remote retrieval. Open-source single-cell RNA sequencing reveals that oligodendrocyte precursor cells (OPCs) express PNN-building genes, mature oligodendrocytes (OLs) express PNN-degrading genes, and newly-formed oligodendrocytes (NFOLs) express both. Bulk RNAseq from SC animals shows reduced expression of OPC-related structural genes and increased expression of OL-related PNN-degrading genes in the mPFC. Notably, satOlig2 cells recruited during remote safety retrieval are predominantly CC1+ mature satellite OLs (satOLs), which we hypothesize degrade PNNs through expression of PNN degradation enzymes. Optogenetic inhibition of PV activity during safety learning blocks satOlig2 recruitment, maturation, and PNN degradation while restoring long-term contextual fear expression. These findings suggest a role for satOlig2 cells in promoting safety learning through dynamic PNN regulation. By maintaining PV interneuron activity and excitatory-inhibitory balance, satOlig2 cells may facilitate PNN remodeling, in support of fear suppression and adaptive behavior. This study provides critical insights into the mechanisms of safety learning and highlights potential OL- and ECM-based therapeutic targets for PTSD and related psychiatric disorders.

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Making Safety Decisions for a Sunscreen Active Ingredient Using Next-Generation Risk Assessment: Benzophenone-4 Case Study

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