Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells

Genetically identical cells in a uniform external environment can exhibit different phenotypes, which are often masked by conventional measurements that average over cell populations. Although most studies on this topic have used microorganisms, differentiated mammalian cells have rarely been explored. Here, we report that only approximately 40% of clonal human embryonic kidney 293 cells respond with an intracellular Ca2+ increase when ryanodine receptor Ca2+ release channels in the endoplasmic reticulum are maximally activated by caffeine. On the other hand, the expression levels of ryanodine receptor showed a unimodal distribution. We showed that the difference in the caffeine sensitivity depends on a critical balance between Ca2+ release and Ca2+ uptake activities, which is amplified by the regenerative nature of the Ca2+ release mechanism. Furthermore, individual cells switched between the caffeine-sensitive and caffeine-insensitive states with an average transition time of approximately 65 h, suggestive of temporal fluctuation in endogenous protein expression levels associated with caffeine response. These results suggest the significance of regenerative mechanisms that amplify protein expression noise and induce cell-to-cell phenotypic variation in mammalian cells

乳房ソナゾイド造影超音波における背景乳腺の造影効果についての検討

Purpose: The objective of this study was to retrospectively evaluate the association between background parenchymal enhancement (BPE) on contrast-enhanced ultrasound (CEUS) with Sonazoid® and patient characteristics. Additionally, background parenchymal tissues with the high-contrast effect were pathologically observed compared to those showing the low-contrast effect. Methods: A total of 65 patients who underwent breast CEUS with Sonazoid® between January 2010 and November 2013 were enrolled. Regions of interest (ROIs) were put on the tumor and on the background parenchymal tissue. The dB values during the nonenhanced time and at peak contrast enhancement were measured based on the time intensity curve (TIC) drawn by the ROI. The differences in the dB values of pre- and post-enhanced time were obtained separately for ROIs on the tumor and ROIs on the parenchymal tissue. The patient characteristics studied were age, menstrual status, mammographic density, BPE on magnetic resonance imaging (MRI), and pathological diagnoses of breast tumors. Results: There was a weak negative correlation between BPE on CEUS and age. As for the contrast effect of parenchymal tissue, there was a significant difference between the menstruating and menopausal groups. There was no significant difference among the levels of mammographic density, and among the degrees of contrast effect on MRI. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status. The parenchymal tissue with the low-contrast effect showed pathological atrophy. Conclusion: The degree of BPE on CEUS appeared related to age, menstruating or menopausal, and atrophy of breast tissue. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status.博士（医学）・乙第1508号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020.© The Japan Society of Ultrasonics in Medicine 2020.This is a post-peer-review, pre-copyedit version of an article published in Journal of medical ultrasonics. The final authenticated version is available online at: https://doi.org/10.1007/s10396-020-01052-4

Trace element and isotopic characteristics of inclusions in the Yamato ordinary chondrites Y-75097, Y-793241 and Y-794046

Igneous inclusions and hosts of the Yamato ordinary chondrites Y-75097 (L6), Y-793241 (L6) and Y-794046 (H5) were analyzed for lithophile trace elements, and Rb-Sr, rare gas and oxygen isotopes, together with preliminary petrographic examinations. On a three oxygen-isotope plot, all the inclusions lie near the H-chondrite field. The Y-75097 host and inclusion were severely shocked and the Rb-Sr systematics were disturbed by a 500Ma event which was defined by the K-Ar age. The Y-793241 host and inclusion are unshocked and have an old K-Ar age of 4270±170Ma and undisturbed Rb-Sr systematics for the bulk meteorite. Both Y-75097 and Y-793241 inclusions have similar chemical compositions and mineral assemblages consisting mainly of olivine (Fa_), and minor plagioclase (An_), chlor-apatite, merrillite and chromite. Olivines in both inclusions equilibrated with those of their L6 hosts. The two inclusion mantles consisting of mainly olivine and plagioclase show a highly fractionated REE pattern with middle REE depletion and a large positive Eu anomaly (50-100 times chondritic) (V-shaped). A model calculation suggests that this remarkable REE fractionation was produced by thermal equilibration with the phosphate-rich cores of inclusions during the igneous formation and the metamorphic event. The Y-794046 inclusion comprises abundant anhedral olivines (Fa_), fractured pyroxenes (Fs_) and microcrystalline plagioclase (An_Ab_Or_). The inclusion did not equilibrate with its host which has less Fe-rich olivines (Fa_) and more Fe in pyroxenes (Fs_). The inclusion shows an unfractionated REE pattern. We suggest that the three inclusions formed by melting of differentiated precursor materials carrying unfractionated REE. They were then incorporated into the L-or H-chondrite parent bodies and subjected to the early thermal metamorphism, which eventually overprinted the fractionated REE in the Y-75097 and Y-793241 inclusions by solid/solid equilibrium partitioning. The Y-794046 inclusion was subjected to less extensive equilibration, so that REE abundances remained unfractionated

A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice

A combination of genetic and environmental factors can cause autoimmune disease in animals. SKG mice, which are genetically prone to develop autoimmune arthritis, fail to develop the disease under a microbially clean condition, despite active thymic production of arthritogenic autoimmune T cells and their persistence in the periphery. However, in the clean environment, a single intraperitoneal injection of zymosan, a crude fungal β-glucan, or purified β-glucans such as curdlan and laminarin can trigger severe chronic arthritis in SKG mice, but only transient arthritis in normal mice. Blockade of Dectin-1, a major β-glucan receptor, can prevent SKG arthritis triggered by β-glucans, which strongly activate dendritic cells in vitro in a Dectin-1–dependent but Toll-like receptor-independent manner. Furthermore, antibiotic treatment against fungi can prevent SKG arthritis in an arthritis-prone microbial environment. Multiple injections of polyinosinic-polycytidylic acid double-stranded RNA also elicit mild arthritis in SKG mice. Thus, specific microbes, including fungi and viruses, may evoke autoimmune arthritis such as rheumatoid arthritis by stimulating innate immunity in individuals who harbor potentially arthritogenic autoimmune T cells as a result of genetic anomalies or variations

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1)大量調理における献立作成時の食塩量の計算値と喫食時の実測値は,料理毎ではばらつきがみられた。 2)献立毎にみると計算値と実測値の比率は平均が0.99となり,ほぼ一致していた。 3)喫食量の調査結果は,料理毎にみると「全部食べた」の平均が86.6%と高い値であった。献立毎にみると「全部食べた」の平均は,A・C・D・Eが88%前後で,Bは79.5%とやや低かった。 4)喫食量から個人別に食塩の摂取量を求めるとかなりの差があった。 5)塩味の嗜好調査結果は,ほとんどの料理について70%以上の者が「ちょうど良い」塩味と感じており,点数化した平均点は3.0前後「ちょうど良い」に集中していた。 6)トマトの前菜風サラダ」の塩味嗜好は,ドレッシングの酸味や,分量,混ざり具合,時間の経過などによって,ばらつきが生じた。 7)スープ4種のうち,実の多いスープは,実の旨味やかくし味で,塩分濃度0.7%で「ちょうど良い」と答えたものが多かった。 8)「コーンピラフ」は塩分濃度が0.64%で「少しうすい」,「菜飯」は0.76%で「ちょうど良い」となり,塩分濃度の差は僅かであるのに嗜好度の差は大であった。 9)献立作成時の調味料(塩分)の割合と喫食時の実測値(塩分濃度)の差は料理によってかなり異なったが,これは調理操作,調味料の塩分含有量の違い,食品に含まれる塩分などが要因であると考えられた。 10)献立作成時の食塩量の計算値と喫食時の食塩摂取量は,種々の要因により差が生じるので,調理過程で味を確認し,さらに嗜好調査の結果を生かし,栄養素の偏りのない献立を作製する工夫が重要である

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1)女子短大生49名の3日間食事記録について栄養素等摂取量を算出した。対象の状況は,年齢18.3±0.5歳,身長157.2±4.5cm,体重52.9±7.9kg,BMI21.4±3.0,最高血圧113±13.6mmHg,最低血圧64±7.8mmHgである。2)個人データ(3日間平均値)でみた栄養素等摂取状況では脂質,ビタミンA,B_1,B_2は充足し,カルシウム,鉄,ビタミンCは3～4割不足していた。食塩摂取量は7.7gであった。3)朝・昼・夕食別摂取量は,朝食はビタミンB_1だけが充足し,昼食は全ての栄養素が2割不足した。夕食は3食の内最も良いが,朝・昼と同様にカルシウム,鉄,ビタミンCが不足した。4)1日のPFC比はF比が適正比率の25%を上回り,朝・昼・夕食別では昼食が朝食・夕食に比べてC比が高く,主食に偏っていた。5)エネルギー摂取量とたんぱく質摂取量との間には有意に相関関係があった。脂質摂取量とでは有意な関係はなかった。6)穀類エネルギー量は770kcalで,1日摂取エネルギー量の48.7%にあたり適正であった。7)脂肪酸の摂取量は飽和脂肪酸が10.1±4.7g,一価不飽和脂肪酸が12.4±4.5g,多価不飽和脂肪酸が10.0±3.6gであり,その比は3 : 4 : 3で適正であった。8)動物・植物・魚類由来の脂肪割合は,8 : 12 : 1で適正比率の4 : 5 : 1に比べて魚類由来の脂肪摂取が極めて少なかった。9)動物性たんぱく質量は22.7gであり,たんぱく質摂取量の42.2%で適正であった。10)BMI別栄養等摂取量は「やせ」ほど充足率が低い。BMIとエネルギー摂取量に有意な相関関係はみられなかった。11)間食で占める栄養素等摂取量は1日の摂取量の3～10%であった。エネルギー量の最大値は1日の61.5%であった。12)食物繊維の摂取量は9.8±4.1gとかなり低く,充足率は50%を下回った。昼・朝・夕食の順に多く,夕食ではいも類・野菜類の摂取頻度が高い。排便習慣との関わりは,排便間隔の長い者や不規則な者の方が毎日排便する者に比べて食物繊維の摂取量は少ない。13)3日間の平均値では日差が不明なので延べ147日分の傾向をみると,どの栄養素等摂取量も偏差が大きくなった。PFC比ではF比が6.5～56.0%と差があった。脂肪酸S : M : PではSの最大値が36.2g,Pの最大値が32.Ogであり,それぞれの比率は適正比とはかけ離れていた。問題点は脂肪エネルギー比が高いことと,ミネラル類,ビタミン類,食物繊維が不足していることである。14)改善策は,意識・食行動・運動・昼食・排便・食品の選び方・調理についてそれぞれ提案したが,最も大切なのは個人の動機付けと,実行継続して習慣化させることであると強調する