病院に勤務する若年管理栄養士の精神的ストレス

Aim: Although the stress levels of medical doctors and nurses have often been studied, those of hospital registered dietitians （HRDs） have not. In the present study, we examined the levels of psychological stress of young HRDs in comparison with registered dietitians working at places other than hospitals（other registered dietitians; ORDs）.Methods: The subjects were 343 female registered dieticians （RDs） who graduated from Yasuda Women’s University in Hiroshima. The questionnaires were sent to them by mail. The General Health Questionnaire 30 （GHQ-30） was used to evaluate their levels of psychological stress. Their levels of satisfaction with work-life balance（WLB） were also examined.Results: Of the 343 subjects, 197 returned the questionnaires. Among them, 47 subjects were excluded from the analysis due to missing information. Thus, data from 150 subjects（44 HRDs and 106 ORDs） were used for the analysis. The total GHQ-30 score of HRDs was similar to that reported for other healthcare professionals and was significantly higher than that of ORDs（P = 0.03）. The total GHQ-30 score significantly correlated with the levels of satisfaction with one factor of WLB（personal activities, e.g. hobbies） in HRDs but not in ORDs.Conclusions: The present study demonstrated for the first time that the stress levels of HRDs are as high as those of other healthcare professionals

UCP1-dependent and UCP1-independent metabolic changes induced by acute cold exposure in brown adipose tissue of mice

Background: Brown adipose tissue (BAT) is a site of metabolic thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1) and represents a target for a therapeutic intervention in obesity. Cold exposure activates UCP1-mediated thermogenesis in BAT and causes drastic changes in glucose, lipid, and amino acid metabolism; however, the relationship between these metabolic changes and UCP1-mediated thermogenesis is not fully understood. Methods: We conducted metabolomic and GeneChip array analyses of BAT after 4-h exposure to cold temperature (10 °C) in wild-type (WT) and UCP1-KO mice. Results: Cold exposure largely increased metabolites of the glycolysis pathway and lactic acid levels in WT, but not in UCP1-KO, mice, indicating that aerobic glycolysis is enhanced as a consequence of UCP1-mediated thermogenesis. GeneChip array analysis of BAT revealed that there were 2865 genes upregulated by cold exposure in WT mice, and 838 of these were upregulated and 74 were downregulated in UCP1-KO mice. Pathway analysis revealed the enrichment of genes involved in fatty acid (FA) β oxidation and triglyceride (TG) synthesis in both WT and UCP1-KO mice, suggesting that these metabolic pathways were enhanced by cold exposure independently of UCP1-mediated thermogenesis. FA and cholesterol biosynthesis pathways were enhanced only in UCP1-KO mice. Cold exposure also significantly increased the BAT content of proline, tryptophan, and phenylalanine amino acids in both WT and UCP1-KO mice. In WT mice, cold exposure significantly increased glutamine content and enhanced the expression of genes related to glutamine metabolism. Surprisingly, aspartate was almost completely depleted after cold exposure in UCP1-KO mice. Gene expression analysis suggested that aspartate was actively utilized after cold exposure both in WT and UCP1-KO mice, but it was replenished from intracellular N-acetyl-aspartate in WT mice. Conclusions: These results revealed that cold exposure induces UCP1-mediated thermogenesis-dependent glucose utilization and UCP1-independent active lipid metabolism in BAT. In addition, cold exposure largely affects amino acid metabolism in BAT, especially UCP1-dependently enhances glutamine utilization. These results contribute a comprehensive understanding of UCP1-mediated thermogenesis-dependent and thermogenesis-independent metabolism in BAT

過剰なグルテン除去が与える影響について

　グルテンは、小麦などの麦類に含まれる蛋白質の一種であり、米国ではグルテンを含まない食品を「グルテンフリー（以下、GF）」と表示している。GFと表示された食品（以下、GF食品）を用いた食生活は（以下GF食）、セリアック病などの治療に用いられている。近年、欧米においてGF食は健康に有用である、さらには痩身にも有用であるとの情報が拡散し、グルテンを避ける必要がない者がGF食を取り入れる傾向がある。これをうけて日本でも同様の情報が拡散しGF食品が増加してきた。本研究では、グルテンを避ける必要がない者がGFを選択した場合、非GFと比較して、摂取する栄養量にどのような差異が生じるかを明らかにすることを目的とした。本研究では、GF食/非GF食として最もポピュラーだと思われるパンを試料とした。　結果、グルテンを避ける必要がない者がGFパンを長期的かつ日常的に選択した場合、非GFパンを選択した場合と比較して、食物繊維や鉄の不足および脂質の過剰といった悪影響が出る可能性があることがわかった

Temperature Changes in Brown Adipocytes Detected with a Bimaterial Microcantilever

AbstractMammalian cells must produce heat to maintain body temperature and support other biological activities. Methods to measure a cell’s thermogenic ability by inserting a thermometer into the cell or measuring the rate of oxygen consumption in a closed vessel can disturb its natural state. Here, we developed a noninvasive system for measuring a cell’s heat production with a bimaterial microcantilever. This method is suitable for investigating the heat-generating properties of cells in their native state, because changes in cell temperature can be measured from the bending of the microcantilever, without damaging the cell and restricting its supply of dissolved oxygen. Thus, we were able to measure increases in cell temperature of <1 K in a small number of murine brown adipocytes (n = 4–7 cells) stimulated with norepinephrine, and observed a slow increase in temperature over several hours. This long-term heat production suggests that, in addition to converting fatty acids into heat energy, brown adipocytes may also adjust protein expression to raise their own temperature, to generate more heat. We expect this bimaterial microcantilever system to prove useful for determining a cell’s state by measuring thermal characteristics

Algal protein kinase, Triacylglycerol Accumulation Regulator 1, modulates cell viability and gametogenesis in carbon/nitrogen imbalanced conditions

Nutrient-deprived microalgae accumulate triacylglycerol (TAG) in lipid droplets. A dual-specificity tyrosine phosphorylation-regulated kinase, TAG accumulation regulator 1 (TAR1) has been shown to be required for acetate-dependent TAG accumulation and the degradation of chlorophyll and photosynthesis-related proteins in photomixotrophic nitrogen (N)-deficient conditions (Kajikawa et al. 2015). However, this previous report only examined particular condition. Here, we report that in photoautotrophic N-deficient conditions, tar1-1 cells, with a mutation in the TAR1 gene, maintained higher levels of cell viability and lower levels of hydrogen peroxide generation and accumulated higher levels of TAG and starch compared with those of wild-type (WT) cells with bubbling of air containing 5% carbon dioxide. Transcriptomic analyses suggested that genes involved in the scavenging of reactive oxygen species are not repressed in tar1-1 cells. In contrast, the mating efficiency and mRNA levels of key regulatory genes for gametogenesis, MID, MTD, and FUS, were suppressed in tar1-1 cells. Among the TAR1-dependent phosphopeptides deduced by phosphoproteomic analysis, protein kinases and enzymes related to N assimilation and carbon (C) metabolism are of particular interest. Characterization of these putative downstream factors may elucidate the molecular pathway whereby TAR1 mediates cellular propagation and C and N metabolism in C/N-imbalanced stress conditions

On the Correlation between Hydration of the Stratum Corneum and the Nutritional Status of Dialysis Patients

　Stratum corneum (SC) prevents evaporation of internal moisture and maintains dermal flexibility and fluidity. Malnutrition is known to decrease SC hydration, but involvement of nutritional status in SC hydration of dialysis patients is unclear. In this study, we examined the association between SC hydration and nutritional status on dialysis patients. We studied 16 control subjects and 81 dialysis patients to examine SC hydration of the neck, upper arm and lower leg. In the 81 patients, we measured serum albumin (Alb), transferrin, geriatric nutritional risk index (GNRI) and normalized protein catabolic rate (nPCR). We then classified the dialysis patients into a 21-patients group, with both Alb ≥ 3.6 g/dl and nPCR ≥ 0.9 g/kg/ day, and a 60-patients group with either Alb ＜3.6 g/dl or nPCR ＜0.9 g/kg/day. SC hydration in the lower leg and the Alb value in the 81 patients were significantly lower than those in the control subjects. SC hydration in the upper arm and lower leg and the values of transferrin and GNRI in the 60-patients group were significantly lower than those in the 21-patients group. This study demonstrates for the first time that nutritional status is correlated with maintenance of SC hydration on dialysis patients

Disease-Association Analysis of an Inflammation-Related Feedback Loop

SummaryThe IL-6-triggered positive feedback loop for NFκB signaling (or the IL-6 amplifier/Inflammation amplifier) was originally discovered as a synergistic-activation signal that follows IL-17/IL-6 stimulation in nonimmune cells. Subsequent results from animal models have shown that the amplifier is activated by stimulation of NFκB and STAT3 and induces chemokines and inflammation via an NFκB loop. However, its role in human diseases is unclear. Here, we combined two genome-wide mouse screens with SNP-based disease association studies, revealing 1,700 genes related to the IL-6 amplifier, 202 of which showed 492 indications of association with ailments beyond autoimmune diseases. We followed up on ErbB1 from our list. Blocking ErbB1 signaling suppressed the IL-6 amplifier, whereas the expression of epiregulin, an ErbB1 ligand, was higher in patients with inflammatory diseases. These results indicate that the IL-6 amplifier is indeed associated with human diseases and disorders and that the identified genes may make for potential therapeutic targets

製パン関連企業勤務者におけるグルテンフリー食の認知度

グルテンフリー食によって、影響を受けると思われる製パン企業とその関連企業に勤務する成人男女82名を対象に、グルテンフリー食に関する認知度についてgoogleフォームを利用したweb調査を実施した。グルテンフリー食を認知している人は79名（96.3%）であった。グルテンフリー食を治療食とする小麦関連疾患のうち、セリアック病、小麦不耐症に関する認知度はそれぞれ52名（63.4%）、46名（56.1%）で、グルテンフリー食の認知度に比べると低かった。これら2つの小麦関連疾患の認知度とグルテンフリー食に期待する効果には関連が見られ、小麦関連疾患を認知していない群では、グルテンフリー食に対して「減量に効果がある」との誤った効果を期待している人が多かった。製パン企業とその関連企業に勤務する人でも、グルテンフリー食に関する正しい知識が不足により、科学的根拠のない情報の影響を受ける可能性が示唆された

Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain

Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear’s vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes

Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies. Furthermore, the neutralizing potency of vaccinee plasma samples against mutant viruses we obtained or circulating viruses differed among individuals. These findings suggest that genetic backgrounds of vaccinees influence the recognition of neutralizing epitopes