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Biomedical subjects

Eiji Goto

Publications and source records attributed to Eiji Goto.

14 recordsLinked to original sources
PubMed2006

A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics.

In this study, we have identified a novel mitochondrial ubiquitin ligase, designated MITOL, which is localized in the mitochondrial outer membrane. MITOL possesses a Plant Homeo-Domain (PHD) motif responsible for E3 ubiquitin ligase activity and predicted four-transmembrane domains. MITOL displayed a rapid degradation by autoubiquitination activity in a PHD-dependent manner. HeLa cells stably expressing a MITOL mutant lacking ubiquitin ligase activity or MITOL-deficient cells by small interfering RNA showed an aberrant mitochondrial morphology such as fragmentation, suggesting the enhancement of mitochondrial fission by MITOL dysfunction. Indeed, a dominant-negative expression of Drp1 mutant blocked mitochondrial fragmentation induced by MITOL depletion. We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1. Pulse-chase experiment showed that MITOL overexpression increased turnover of these fission proteins. In addition, overexpression phenotype of hFis1 could be reverted by MITOL co-overexpression. Our finding indicates that MITOL plays a critical role in mitochondrial dynamics through the control of mitochondrial fission proteins.

Amino Acid Sequence↗
PubMed2006

Inhibition of MHC class II expression and immune responses by c-MIR.

We previously reported a novel E3 ubiquitin ligase (E3), designated as c-MIR, which targets B7-2 to lysosomal degradation and down-regulates the B7-2 surface expression through ubiquitination of its cytoplasmic tail. B7-2 is well known as a costimulatory molecule for Ag presentation, suggesting that the manipulation of c-MIR expression modulates immune responses in vivo. To examine this hypothesis, we generated genetically modified mice in which c-MIR was expressed under an invariant chain (Ii) promoter. Dendritic cells derived from genetically engineered mice showed low ability to present Ags. In addition, these mice showed resistance to the onset of experimental autoimmune encephalomyelitis and an impaired development of CD4 T cells in the thymus and the periphery. These findings led us to conclude that MHC class II (MHC II) is an additional target for c-MIR. Indeed, forced expression of c-MIR in several B cell lines down-regulated the surface expression of MHC II, and down-regulation was found to depend on the presence of a single lysine residue in the cytoplasmic tail of the I-A beta-chain. In a reconstitution system using 293T cells, we found that the lysine residue at position 225 in the I-A beta-chain was ubiquitinated by c-MIR. To our knowledge, c-MIR is the first example of an E3 that is capable of inhibiting MHC II expression. Our findings suggest that c-MIR might potently regulate immune responses in vivo.

Amino Acid Sequence↗
PubMed2006

A novel family of membrane-bound E3 ubiquitin ligases.

A novel E3 ubiquitin ligase family that consists of viral E3 ubiquitin ligases (E3s) and their mammalian homologues was recently discovered. These novel E3s are membrane-bound molecules that share the secondary structure and catalytic domain for E3 activity. All family members have two transmembrane regions at the center and a RING-CH domain at the amino terminus. Forced expression of these novel E3s has been shown to reduce the surface expression of various membrane proteins through ubiquitination of target molecules. Initial examples of viral E3s were identified in Kaposi's sarcoma associated herpesvirus (KSHV) and murine gamma-herpesvirus 68 (MHV-68) and have been designated as modulator of immune recognition (MIR) 1, 2 and mK3, respectively. MIR 1, 2 and mK3 are able to down-regulate MHC class I molecule expression, and mK3 is required to establish an effective latent viral infection in vivo. The first characterized mammalian homologue to MIR 1, 2 and mK3 is c-MIR/MARCH VIII. Forced expression of c-MIR/MARCH VIII down-regulates B7-2, a co-stimulatory molecule important for antigen presentation. Subsequently, several mammalian molecules related to c-MIR/MARCH VIII have been characterized and named as membrane associated RING-CH (MARCH) family. However, the precise physiological function of MARCH family members remains as yet unknown.

Cell Membrane↗
PubMed2006

An overview of challenges in modeling heat and mass transfer for living on Mars.

Engineering a life-support system for living on Mars requires the modeling of heat and mass transfer. This report describes the analysis of heat and mass transfer phenomena in a greenhouse dome, which is being designed as a pressurized life-support system for agricultural production on Mars. In this Martian greenhouse, solar energy will be converted into chemical energy in plant biomass. Agricultural products will be harvested for food and plant cultivation, and waste materials will be processed in a composting microbial ecosystem. Transpired water from plants will be condensed and recycled. In our thermal design and analysis for the Martian greenhouse, we addressed the question of whether temperature and pressure would be maintained in the appropriate range for humans as well as plants. Energy flow and material circulation should be controlled to provide an artificial ecological system on Mars. In our analysis, we assumed that the greenhouse would be maintained at a subatmospheric pressure under 1/3-G gravitational force with 1/2 solar light intensity on Earth. Convection of atmospheric gases will be induced inside the greenhouse, primarily by heating from sunlight. Microclimate (thermal and gas species structure) could be generated locally around plant bodies, which would affect gas transport. Potential effects of those environmental factors are discussed on the phenomena including plant growth and plant physiology and focusing on transport processes. Fire safety is a crucial issue and we evaluate its impact on the total gas pressure in the greenhouse dome.

Agriculture↗
PubMed2006

Heat and gas exchanges between plants and atmosphere under microgravity conditions.

Fundamental studies were conducted to develop a facility having an adequate air circulation system for growing healthy plants over a long term under microgravity conditions in space. To clarify the effects of gravity on heat and gas exchanges between plant leaves and the ambient air, surface temperatures and net photosynthetic rates of barley leaves were evaluated at gravity levels of 0.01, 1.0, and 2.0 g for 20 sec each during parabolic airplane flights. Thermal images were captured using infrared thermography at an air temperature of 22 degrees C, a relative humidity of 18%, and an irradiance of 260 W/m2. The net photosynthetic rates were determined by means of a chamber method with an infrared gas analyzer at an air temperature of 20 degrees C, a relative humidity of 50%, and photosynthetic photon fluxes (PPFDs) of 250 and 500 micromol/m2/sec. Mean leaf temperatures increased by 1.9 degrees C with decreasing gravity levels from 1.0 to 0.01 g and decreased by 0.6 degrees C with increasing gravity levels from 1.0 to 2.0 g. The increase in leaf temperatures was greater at the regions closer to the leaf tip and at most 2.5 degrees C over 20 sec as gravity decreased from 1.0 to 0.01 g. The net photosynthetic rate decreased by 20% with decreasing gravity levels from 1.0 to 0.01 g and increased by 10% with increasing gravity levels from 1.0 to 2.0 g at a PPFD of 500 micromol/m2/sec. The heat and gas exchanges between leaves and the ambient air were suppressed more at the lower gravity levels. The retardation would be caused by heat and gas transfers with less heat convection. Restricted free air convection under microgravity conditions in space would limit plant growth by retarding heat and gas exchanges between leaves and the ambient air.

Acceleration↗
PubMed2005

Medical student abuse during clinical clerkships in Japan.

OBJECTIVE: To assess the prevalence of medical student abuse during clinical clerkships in Japan. DESIGN: A cross-sectional questionnaire survey. SETTING: Six medical schools in Japan. PARTICIPANTS: Final year (sixth-year) and fifth-year medical students in the period from September 2003 to January 2004. From a total of 559 students solicited, 304 (54.4%) returned the questionnaire, and 276 (49.4%: 178 male and 98 female) completed it. MEASUREMENTS: Prevalence of medical student abuse in 5 categories: verbal abuse, physical abuse, academic abuse, sexual harassment, and gender discrimination; differences in abusive experience between male and female students; types of alleged abusers; reporting abusive experiences to authorities; and emotional effects of abusive experiences. RESULTS: Medical student abuse was reported by 68.5% of the respondents. Verbal abuse was the most frequently experienced abuse (male students 52.8%, female students 63.3%). Sexual harassment was experienced significantly more often (P<.001) by female students (54.1%) than by male students (14.6%). Faculty members were most often reported as abusers (45.2% of cases). Abuse occurred most frequently during surgical rotations (42.0% of cases), followed by internal medicine (25.1%) and anesthesia rotations (21.8%). Very few abused students reported their abusive experiences to authorities (8.5%). The most frequent emotional response to abuse was anger (27.1% of cases). CONCLUSIONS: Although experience of abuse during clinical clerkships is common among medical students in Japan, the concept of "medical student abuse" is not yet familiar to Japanese. To improve the learning environment, medical educators need to take action to resolve this serious issue.

Cross-Sectional Studies↗
PubMed2004

Photosynthetic characteristics of rice leaves grown under red light with or without supplemental blue light.

In rice plants grown under red light supplemented with blue light (red/blue-light PPFD ratio was 4/1), photosynthetic rates per unit leaf area measured under white light at 1,600 and 250 micromol m-2) s-1 were higher than those in the plants grown under red light alone. The higher photosynthetic rates were associated with higher total N content of leaves, which was accompanied by larger amounts of key components of photosynthesis-limiting processes, including Rubisco, Cyt f, Chl and LHCII. These results suggested that the increase in total N content of leaves induced by supplemental blue light enhanced both light-saturated and light-limited photosynthesis.

Chlorophyll↗
PubMed2003

c-MIR, a human E3 ubiquitin ligase, is a functional homolog of herpesvirus proteins MIR1 and MIR2 and has similar activity.

Kaposi's sarcoma associated-herpes virus encodes two proteins, MIR (modulator of immune recognition) 1 and 2, which are involved in the evasion of host immunity. MIR1 and 2 have been shown to function as an E3 ubiquitin ligase for immune recognition-related molecules (e.g. major histocompatibility complex class I, B7-2, and ICAM-1) through the BKS (bovine herpesvirus 4, Kaposi's sarcoma associated-herpes virus, and Swinepox virus) subclass of plant homeodomain (PHD) domain, termed the BKS-PHD domain. Here we show that the human genome also encodes a novel BKS-PHD domain-containing protein that functions as an E3 ubiquitin ligase and whose putative substrate is the B7-2 co-stimulatory molecule. This novel E3 ubiquitin ligase was designated as c-MIR (cellular MIR) based on its functional and structural similarity to MIR1 and 2. Forced expression of c-MIR induced specific down-regulation of B7-2 surface expression through ubiquitination, rapid endocytosis, and lysosomal degradation of the target molecule. This specific targeting was dependent upon the binding of c-MIR to B7-2. Replacing the BKS-PHD domain of MIR1 with the corresponding domain of c-MIR did not alter MIR1 function. The discovery of c-MIR, a novel E3 ubiquitin ligase, highlights the possibility that viral immune regulatory proteins originated in the host genome and presents unique functions of BKS-PHD domain-containing proteins in mammals.

Amino Acid Sequence↗
PubMed2003

Seed production of Arabidopsis thaliana under hypobaric conditions.

In the present study, we examined carbohydrate contents of Arabidopsis thaliana seeds during seed development under hypobaric conditions in order to characterize the mechanism of low pressure-induced seed damage, and to determine critical pressures for seed development under low total and/or low oxygen partial pressures. We analyzed contents of starch, sucrose, glucose, and fructose in seeds at different developmental stages at 101 kPa total pressure with 21 kPa O2 partial pressure (control conditions), and at various low pressure conditions (23 kPa Ptot/21 kPa pO2, 101 kPa Ptot/2 kPa pO2, 53 kPa Ptot/2 kPa pO2, 23 kPa Ptot/2 kPa pO2, 12 kPa Ptot/10 kPa pO2, and 12 kPa Ptot/2 kPa pO2). Our results indicate that maintaining an adequate oxygen partial pressure inside the siliques is necessary for seed production under hypobaric conditions.

Arabidopsis↗
PubMed2002

Accuracy and reliability of wrist-cuff devices for self-measurement of blood pressure.

OBJECT: Self-measurement of blood pressure (BP) might offer some advantages in diagnosis and therapeutic evaluation and in patient management of hypertension. Recently, wrist-cuff devices for self-measurement of BP have gained more than one-third of the world market share. In the present study, we validated wrist-cuff devices and compared the results between wrist- and arm-cuff devices. The factors affecting the accuracy of wrist-cuff devices were also studied. METHOD: The research group to assess the validity of automated blood pressure measuring device consisted of 13 institutes in Japan, which validated two wrist-cuff devices (WC-1 and WC-2) and two arm-cuff devices (AC-1 and AC-2). They used a crossover method, where the comparison was done between auscultation, by two observers by means of a double stethoscope on one arm and the device on the opposite arm or wrist. RESULTS: There was good inter-observer agreement for the auscultation method in each institute (systolic blood pressure (SBP), -0.1 +/- 2.8 mmHg; diastolic blood pressure (DBP), -0.1 +/- 2.6 mmHg, n = 498). The mean difference between auscultation and the device was minimal both in arm-cuff devices (mean difference for AC-1, 2.2/1.9 mmHg, n = 97 and for AC-2, 5.1/2.9 mmHg, n = 136, SBP/DBP) and wrist-cuff devices (mean difference for WC-1, -2.1/1.2 mmHg, n = 173 mmHg and for WC-2, -2.3/-5.6 mmHg, n = 92). The standard deviation of the difference (SDD) in wrist-cuff devices, however (SDD for WC-1, 9.7/7.3 mmHg and for WC-2, 10.2/8.6 mmHg), was larger than that of the arm-cuff devices (SDD for AC-1, 5.6/6.6 mmHg and for AC-2, 6.3/5.1 mmHg). Grading of AC-1 and AC-2 based on criteria of British Hypertension Society was A/A and B/A, respectively, while that of WC-1 and WC-2 was C/B and D/B, respectively. Using the same validation protocol, the results of validation for one device were divergent in each institute. In wrist-cuff devices, the BP value obtained in palmar flexion was significantly higher and that obtained in palmar dorsiflexion was significantly lower than that in palmar extension. In some cases, finger plethysmogram did not disappear during maximum inflation of the wrist-cuff (congruent with 250 mmHg), even in palmar extension and especially in palmar flexion, suggesting incomplete obstruction of radial and/or ulnar arteries during inflation. CONCLUSION: The results suggest that wrist-cuff devices in the present form are inadequate for self-measurement of blood pressure and, thus, are inadequate for general use or clinical and practical use. However, there is much possibility in wrist-cuff device and the accuracy and reliability of wrist-cuff device are warranted by an improvement of technology.

Adolescent↗