PLEIAD/SIMC1/C5orf25, a Novel Autolysis Regulator for a Skeletal-Muscle-Specific Calpain, CAPN3, Scaffolds a CAPN3 Substrate, CTBP1

AbstractCAPN3/p94/calpain-3 is a skeletal-muscle-specific member of the calpain protease family. Multiple muscle cell functions have been reported for CAPN3, and mutations in this protease cause limb-girdle muscular dystrophy type 2A. Little is known about the molecular mechanisms that allow CAPN3 to be so multifunctional. One hypothesis is that the very rapid and exhaustive autolytic activity of CAPN3 needs to be suppressed by dynamic molecular interactions for specific periods of time. The previously identified interaction between CAPN3 and connectin/titin, a giant molecule in muscle sarcomeres, supports this assumption; however, the regulatory mechanisms of non-sarcomere-associated CAPN3 are unknown. Here, we report that a novel CAPN3-binding protein, PLEIAD [Platform element for inhibition of autolytic degradation; originally called SIMC1/C5orf25 (SUMO-interacting motif containing protein 1/chromosome 5 open reading frame 25)], suppresses the protease activity of CAPN3. Database analyses showed that PLEIAD homologs, like CAPN3 homologs, are evolutionarily conserved in vertebrates. Furthermore, we found that PLEIAD also interacts with CTBP1 (C-terminal binding protein 1), a transcriptional co-regulator, and CTBP1 is proteolyzed in COS7 cells expressing CAPN3. The identified cleavage sites in CTBP1 suggested that it undergoes functional modification upon its proteolysis by CAPN3, as well as by conventional calpains. These results indicate that PLEIAD can shift its major function from CAPN3 suppression to CAPN3-substrate recruitment, depending on the cellular context. Taken together, our data suggest that PLEIAD is a novel regulatory scaffold for CAPN3, as reflected in its name

College Students’ Perceptions of Intimate Partner Violence: A Comparative Study of Japan, China, and the United States

An investigation of cross-cultural differences between the United States, Japan, and China in perceptions of male to female intimate partner violence, and in the extent to which gender and traditional attitudes toward women related to these perceptions. College students (n = 943) read two fictitious scenarios describing marital and dating violence. MANOVA results showed gender differences in the perceptions of violence between the three countries. Male participants had more traditional attitudes toward women and placed more blame on female victims. The magnitude of the difference between women’s and men’s scores was much smaller for Japanese students than for American and Chinese students. Hierarchical multiple regression analyses demonstrated that the effects of respondent gender were reduced when traditional attitudes toward women were taken into account. Differences in beliefs about appropriate gender roles still exist among college students in these countries and may be related to socially tolerant attitudes toward violence against women

Circadian protection against bacterial skin infection by epidermal CXCL14-mediated innate immunity

体内時計は夜間に自然免疫を発動 --皮膚ケモカインによる自然免疫機構--. 京都大学プレスリリース. 2022-06-16.Biological clocks set for skin immunity. 京都大学プレスリリース. 2022-06-21.The epidermis is the outermost layer of the skin and the body’s primary barrier to external pathogens; however, the early epidermal immune response remains to be mechanistically understood. We show that the chemokine CXCL14, produced by epidermal keratinocytes, exhibits robust circadian fluctuations and initiates innate immunity. Clearance of the skin pathogen Staphylococcus aureus in nocturnal mice was associated with CXCL14 expression, which was high during subjective daytime and low at night. In contrast, in marmosets, a diurnal primate, circadian CXCL14 expression was reversed. Rhythmically expressed CXCL14 binds to S. aureus DNA and induces inflammatory cytokine production by activating Toll-like receptor (TLR)9-dependent innate pathways in dendritic cells and macrophages underneath the epidermis. CXCL14 also promoted phagocytosis by macrophages in a TLR9-independent manner. These data indicate that circadian production of the epidermal chemokine CXCL14 rhythmically suppresses skin bacterial proliferation in mammals by activating the innate immune system

Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus

Synchronous oscillations of thousands of cellular clocks in the suprachiasmatic nucleus (SCN), the circadian centre, are coordinated by precisely timed cell–cell communication, the principle of which is largely unknown. Here we show that the amount of RGS16 (regulator of G protein signalling 16), a protein known to inactivate Gαi, increases at a selective circadian time to allow time-dependent activation of intracellular cyclic AMP signalling in the SCN. Gene ablation of Rgs16 leads to the loss of circadian production of cAMP and as a result lengthens circadian period of behavioural rhythm. The temporally precise regulation of the cAMP signal by clock-controlled RGS16 is needed for the dorsomedial SCN to maintain a normal phase-relationship to the ventrolateral SCN. Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24 h rhythm in behaviour

Comprehensive survey of p94/calpain 3 substrates by comparative proteomics – Possible regulation of protein synthesis by p94

Calpain represents a family of Ca2+-dependent cytosolic cysteine proteases found in almost all eukaryotes and some bacteria, and is involved in a variety of biological phenomena, including brain function. Several substrates of calpain are aggressively proteolyzed under pathological conditions, e.g., in neurodegenerating processes, fodrin is proteolyzed by calpain. Because very small amounts of substrate are proteolyzed by calpain under normal biological conditions, the molecular identities of calpain substrates are largely unknown. In this study, an extensive survey of the substrates of p94/calpain 3 in COS7 cells was executed using iTRAQ™ labeling and 2-D LC-MALDI analysis. p94 was used because: (i) several p94 splicing variants are expressed in brain tissue even though p94 itself is a skeletal-muscle-specific calpain, and (ii) it exhibits Ca2+-independent activity in COS cells, which makes it useful for evaluating the effects of p94 protease activity on proteins without perturbing the cells. Our approach revealed several novel protein substrates for p94, including the substrates of conventional calpains, components of the protein synthesis system, and enzymes of the glycolytic pathway. The results demonstrate the usefulness and sensitivity of this approach for mining calpain substrates. A combination of this method with other analytical methods would contribute to elucidation of the biological relevance of the calpain family

地域に根付く米国ホスピスのフィールドワーク：ボランティアとの協働からみた本邦の看護教育についての考察

Portland, Oregon, has attracted attention in Japan as the “most desirable city to live in the United States” and “a model of urban development.” The purpose of this study was to examine nursing education in Japan through care that supports people who live and die in the community by visiting the Hopewell House Hospice in Portland. The hospice is run by approximately 70 volunteers and facility staff who provide facility care for 11 beds and about 150 home care patients. From fieldwork conducted at the facility and from an interview with the volunteer staff manager who was a former midwife and nursing manager, we found that the users and the staff themselves have “a special place called a bed,” a “record of their personality and health,” and “prayer and hope”. In addition, the nurses relied on their ingenuity to manage their environment and provide continuous care in order to reach the end stage while keeping the patient connected to the community, which facilitated feelings of joy. Nursing practice in the Hopewell House Hospice was influenced by the climate of the region and the culture of the local residents, so there was an overlap between life and death, which we believe should be incorporated into nursing education in Japan.論

A Research on a New Science Curriculum Development Based on ‘Nature Of Science’ Ⅲ : Reconstruction of a Coherence Science Curriculum from Elementary School to Upper Secondary School

本研究は，新しい科学観を取り入れた小学校から高等学校までの理科カリキュラムを開発することを目的としており，今年度は３年次にあたる。これまでの成果と課題をもとに，初等・中等教育で一貫して「科学の本質」を学ぶためのフレームワーク構築に向け，小学校から高等学校を通じて系統的に取り扱うことが可能な内容について検討を行った。 中学校における実践からは，理科教師が，科学者コミュニティーによる知，政策決定者や教師たちによる教えるべき知，児童・生徒の発達段階や文脈などを考慮した教える知，について可能な限り熟知する必要があることが示唆された。また，論証活動を行う際の，教師の振る舞い方も重要であることも明らかとなった。 また，小学校における実践では，学年による差異はあるものの，見たことや考えたことの違いを次第に意識化させることによって，観察や実験等のレポートの書き方の指導にも繋がることが明らかとなった。 以上の実践より，科学の本質を初等・中等教育で一貫して教えるためには，これまでの実践の視点の変容に基づく教師による授業方略の在り方や投げ込み的教材を使用する教師の意図が，いかに重要であるかを示唆している。This study develops a new science curriculum for elementary to upper secondary schools which include the concept of the “Nature of Science”. We examined possible content to build a systematic framework for mentioned above science education. The practice at junior high school shows that teachers should be familiar with scholarly knowledge, knowledge to be taught by the policy makers and teachers, and taught knowledge which students understand through learning along with the students’ ages and contexts. The teacher’s behavior in argumentation by pupils is also important. The practice at elementary school shows that perceptions of the crucial distinction between inference and observation lead students to write good reports. These practices exemplify that teaching Nature of Science consistently to elementary and lower secondary students should largely depend on the teachers’ methods of instruction and what material they develop from a new viewpoint

Hypertrophic pyloric stenosis treated with co-administration of nitroglycerin and atropine sulfate

Hypertrophic pyloric stenosis (HPS) is a common infantile disease that causes a transit pyloric disorder. For the treatment of this disorder, intravenous atropine sulfate (AS) has been reported to be effective. However, AS treatment is ineffective in some cases, and these cases require surgical treatment. Recently, it has been reported that the co-administration of nitroglycerin (NTG) and AS is more effective than the administration of AS alone. Herein, we present two cases of infants with HPS treated using percutaneous NTG along with intravenous AS. Both cases were refractory to intravenous AS alone. After additional administrations of percutaneous NTG, their vomiting was rapidly resolved. These cases highlight the effectiveness of the co-administration of NTG and AS for HPS. Keywords: Hypertrophic pyloric stenosis, Nitroglycerin, Atropine sulfate, Infan