A CASE OF RUPTURED MITRAL VALVE ANEURYSM DUE TO INFECTIVE ENDOCARDITIS

58-year-old woman with aortic regurgitation was admitted to our hospi- tal because of high grade fever. She had infective endocarditis and an aneurysm of the anterior mitral leaflet. Doppler echocardiography indicated a ruptured mitral valve aneurysm. Aortic regurgitant flow along the anterior mitral leaflet was suspected to have contributed to mitral valve endocarditis, aneurysm formation and rupture. She was initially treated with high-dose intravenous penicillin, but congestive heart failure worsened. Mitral valve replacement was then successfully performed

Impaired Function is a Common Feature of Neuropathy‐Associated Glycyl‐t RNA Synthetase Mutations

C harcot– M arie– T ooth disease type 2 D ( CMT 2 D ) is an autosomal‐dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl‐t RNA synthetase ( GARS ) gene cause CMT 2 D . GARS is a member of the ubiquitously expressed aminoacyl‐ tRNA synthetase ( ARS ) family and is responsible for charging t RNA with glycine. To date, 13 GARS mutations have been identified in patients with CMT disease. While functional studies have revealed loss‐of‐function characteristics, only four GARS mutations have been rigorously studied. Here, we report the functional evaluation of nine CMT ‐associated GARS mutations in t RNA charging, yeast complementation, and subcellular localization assays. Our results demonstrate that impaired function is a common characteristic of CMT ‐associated GARS mutations. Additionally, one mutation previously associated with CMT disease (p. S er581 L eu) does not demonstrate impaired function, was identified in the general population, and failed to segregate with disease in two newly identified families with CMT disease. Thus, we propose that this variant is not a disease‐causing mutation. Together, our data indicate that impaired function is a key component of GARS ‐mediated CMT disease and emphasize the need for careful genetic and functional evaluation before implicating a variant in disease onset.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109288/1/humu22681.pd

Inactivation of the Influenza Virus by a Supplemental Fermented Plant Product (Manda Koso)

Manda Koso is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that are fermented for more than 3 years. We hypothesized that the FPP can prevent infection by influenza virus and human norovirus. Therefore, we investigated the effects of the FPP on influenza virus and feline calicivirus, a surrogate of human norovirus. We found that 10% FPP inactivated the influenza virus but not the feline calicivirus. Inhibition of the influenza virus was highly concentration-dependent: 1% and 0.3% FPP showed reduced inactivation efficacy. The effects of the FPP on the influenza virus-infected cells were investigated by addition of the FPP to the culture medium after virus infection. No suppressive effect of the FPP on influenza replication in MDCK cells was observed. The results showed that the FPP could inactivate influenza virus by affecting the virus particles

Osteoclasts adapt to physioxia perturbation through DNA demethylation

Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two-photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia-inducible factor activity. We observe that hypoxia decreases ten-eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen-dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.Nishikawa K., Seno S., Yoshihara T., et al. Osteoclasts adapt to physioxia perturbation through DNA demethylation. EMBO Reports 22, e53035 (2021); https://doi.org/10.15252/embr.202153035

SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production

SOCS1 is required to restrict IFN-γ and IL-17 expression and maintain Foxp3 expression in and function of regulatory T cells

Design Strategies of Fluorescent Biosensors Based on Biological Macromolecular Receptors

Fluorescent biosensors to detect the bona fide events of biologically important molecules in living cells are increasingly demanded in the field of molecular cell biology. Recent advances in the development of fluorescent biosensors have made an outstanding contribution to elucidating not only the roles of individual biomolecules, but also the dynamic intracellular relationships between these molecules. However, rational design strategies of fluorescent biosensors are not as mature as they look. An insatiable request for the establishment of a more universal and versatile strategy continues to provide an attractive alternative, so-called modular strategy, which permits facile preparation of biosensors with tailored characteristics by a simple combination of a receptor and a signal transducer. This review describes an overview of the progress in design strategies of fluorescent biosensors, such as auto-fluorescent protein-based biosensors, protein-based biosensors covalently modified with synthetic fluorophores, and signaling aptamers, and highlights the insight into how a given receptor is converted to a fluorescent biosensor. Furthermore, we will demonstrate a significance of the modular strategy for the sensor design

サービングサイズ オ モチイタ カンイ ショクモツ セッシュリョウ チョウサホウ ノ カイハツ

近年,生活習慣病の深刻化に伴い,管理栄養士に高度な専門知識や技能が求められるようになった。対象者の食行動の変容を目的とした栄養教育の過程で,栄養状態や食習慣の十分な把握は重要であり,実際に個人または集団レベルでの食物および栄養摂取量評価のために食事調査が行われている。その方法は多種類あるが,我々は個人および集団を対象とし,簡便かつ調査者および被調査者の負担が軽く,より正確な摂取状況を把握する方法としてサービングサイズを用いた簡易食物摂取量調査法を開発するために,20歳代女子大生に見合った簡易記録法(以下,簡易法)I,IIを作成し,段階的調査を行った。簡易法の摂取栄養量の算出のため,食品群別荷重平均成分表(以下,荷重平均成分表)を作成し,24時間秤量法(以下,秤量法)との整合性をはかり,精度を高める検討をした。秤量法と簡易法の一回目の検討の結果,食品群では調味料類を除いて有意な差は認められなかったが,食品摂取量の間に相違がみられた。栄養素では,ナトリウム(以下,Na)を除いて有意な差は認められなかった。両調査法間の相関関係は,全ての食品群で有意な正の相関がみられた。栄養素では,レチノール当量を除いて有意な正の相関が認められた。しかし,簡易法の摂取量と秤量法のそれとの間の近似をはかるために,1日の目標量を訂正し,両調査法の二度目の検討を行った。調査IIの結果,食品群では嗜好飲料類を除いて有意な差は認めらなかった。両調査法による食品摂取量は,目標量に対する充足率80∿120%を示し,近似値が認められた。栄養素では,鉄(以下,Fe),レチノール当量,ビタミンC(以下,VC)を除いて有意な差は認められなかった。両調査法間の相関関係は,嗜好飲料類を除く全ての食品群で有意であった。また,全ての栄養素で有意な正の相関が認められた

サイボウナイ ジョウホウ デンタツ ブッシツ カシカ ノ タメ ノ リアルタイム センサー ノ カイハツ

京都大学0048新制・課程博士博士(エネルギー科学)甲第15009号エネ博第211号新制||エネ||47(附属図書館)27459UT51-2009-R733京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻(主査)教授 森井 孝, 教授 木下 正弘, 准教授 佐川 尚学位規則第4条第1項該当Doctor of Energy ScienceKyoto UniversityDA