Reverse genetic studies of mitochondrial DNA-based diseases using a mouse model

In the situation that it would not be able to produce model animals for mitochondrial diseases caused by mitochondrial DNA (mtDNA) with pathogenic mutations, we succeeded in generating mice with pathogenic deletion mutant mtDNA (ΔmtDNA), named “mito-mice”, by direct introduction of mitochondria with ΔmtDNA into mouse zygotes. In the mito-mice, accumulation of ΔmtDNA induced mitochondrial respiration defects in various tissues, resulting in mitochondrial disease phenotypes, such as low body weight, lactic acidosis, ischemia, myopathy, heart block, deafness, male infertility, and renal failure. Thus, mito-mice are the first model animal for mtDNA-based diseases, and the mice could be valuable for understanding precise pathogeneses and testing therapies of mitochondrial diseases. In the present review, we summarized reverse genetic studies using the mito-mice

Untyping Typed Algebras and Colouring Cyclic Linear Logic

We prove "untyping" theorems: in some typed theories (semirings, Kleene algebras, residuated lattices, involutive residuated lattices), typed equations can be derived from the underlying untyped equations. As a consequence, the corresponding untyped decision procedures can be extended for free to the typed settings. Some of these theorems are obtained via a detour through fragments of cyclic linear logic, and give rise to a substantial optimisation of standard proof search algorithms.Comment: 21

The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine

It has been more than 25 years since HGF was discovered as a mitogen of hepatocytes. HGF is produced by stromal cells, and stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its receptor, c-Met. In fetal stages, HGF-neutralization, or c-Met gene destruction, leads to hypoplasia of many organs, indicating that HGF signals are essential for organ development. Endogenous HGF is required for self-repair of injured livers, kidneys, lungs and so on. In addition, HGF exerts protective effects on epithelial and non-epithelial organs (including the heart and brain) via anti-apoptotic and anti-inflammatory signals. During organ diseases, plasma HGF levels significantly increased, while anti-HGF antibody infusion accelerated tissue destruction in rodents. Thus, endogenous HGF is required for minimization of diseases, while insufficient production of HGF leads to organ failure. This is the reason why HGF supplementation produces therapeutic outcomes under pathological conditions. Moreover, emerging studies delineated key roles of HGF during tumor metastasis, while HGF-antagonism leads to anti-tumor outcomes. Taken together, HGF-based molecules, including HGF-variants, HGF-fragments and c-Met-binders are available as regenerative or anti-tumor drugs. Molecular analysis of the HGF-c-Met system could provide bridges between basic biology and clinical medicine

Dosimetric evaluation of Acuros XB Advanced Dose Calculation algorithm in heterogeneous media

<p>Abstract</p> <p>Background</p> <p>A study was realised to evaluate and determine relative figures of merit of a new algorithm for photon dose calculation when applied to inhomogeneous media.</p> <p>Methods</p> <p>The new Acuros XB algorithm implemented in the Varian Eclipse treatment planning system was compared against a Monte Carlo method (VMC++), and the Analytical Anisotropic Algorithm (AAA). The study was carried out in virtual phantoms characterized by simple geometrical structures. An insert of different material and density was included in a phantom built of skeletal-muscle and HU = 0 (setting "A"): Normal Lung (lung, 0.198 g/cm³); Light Lung (lung, 0.035 g/cm³); Bone (bone, 1.798 g/cm³); another phantom (setting "B") was built of adipose material and including thin layers of bone (1.85 g/cm³), adipose (0.92 g/cm³), cartilage (1.4745 g/cm³), air (0.0012 g/cm³). Investigations were performed for 6 and 15 MV photon beams, and for a large (13 × 13 cm²) and a small (2.8 × 13 cm²) field.</p> <p>Results</p> <p>Results are provided in terms of depth dose curves, transverse profiles and Gamma analysis (3 mm/3% and 2 mm/2% distance to agreement/dose difference criteria) in planes parallel to the beam central axis; Monte Carlo simulations were assumed as reference. Acuros XB gave an average gamma agreement, with a 3 mm/3% criteria, of 100%, 86% and 100% for Normal Lung, Light Lung and Bone settings, respectively, and dose to medium calculations. The same figures were 86%, 11% and 100% for AAA, where only dose rescaled to water calculations are possible.</p> <p>Conclusions</p> <p>In conclusion, Acuros XB algorithm provides a valid and accurate alternative to Monte Carlo calculations for heterogeneity management.</p

Effect of obesity on intraoperative bleeding volume in open gastrectomy with D2 lymph-node dissection for gastric cancer

<p>Abstract</p> <p>Background</p> <p>To investigate the effect of obesity on open gastrectomy with D2 lymph-node dissection.</p> <p>Methods</p> <p>Between January 2005 and March 2007, 100 patients with preoperatively diagnosed gastric cancer who underwent open gastrectomy with D2 lymph-node dissection were enrolled in this study. Of these, 61 patients underwent open distal gastrectomy (ODG) and 39 patients underwent open total gastrectomy (OTG). Patients were classified as having a high body-mass index (BMI; ≥ 25.0 kg/m²; <it>n </it>= 21) or a normal BMI (<25.0 kg/m²; <it>n </it>= 79). The visceral fat area (VFA) and subcutaneous fat area (SFA) were assessed as identifiers of obesity using FatScan software. Patients were classified as having a high VFA (≥ 100 cm²; <it>n </it>= 34) or a normal VFA (<100 cm²; <it>n </it>= 66). The relationship between obesity and short-term patient outcomes after open gastrectomy was evaluated. Patients were classified as having high intraoperative blood loss (IBL; ≥ 300 ml; <it>n </it>= 42) or low IBL (<300 ml; <it>n </it>= 58). Univariate and multivariate analyses were used to identify predictive factors for high IBL.</p> <p>Results</p> <p>Significantly increased IBL was seen in the following: patients with high BMI versus normal BMI; patients with gastric cancer in the upper third of the stomach versus gastric cancer in the middle or lower third of the stomach; patients who underwent OTG versus ODG; patients who underwent splenectomy versus no splenectomy; and patients with high VFA versus low VFA. BMI and VFA were significantly greater in the high IBL group than in the low IBL group. There was no significant difference in morbidity between the high IBL group and the low IBL group. Multivariate analysis revealed that patient age, OTG and high BMI or high VFA independently predicted high IBL.</p> <p>Conclusion</p> <p>It is necessary to perform operative manipulations with particular care in patients with high BMI or high VFA in order to reduce the IBL during D2 gastrectomy.</p

Clinical consequences of road traffic injuries among the elderly in Japan

<p>Abstract</p> <p>Background</p> <p>Road traffic injuries among the elderly have recently become a public health issue; therefore, we investigated the clinical characteristics of such injuries among the elderly in Japan.</p> <p>Methods</p> <p>A retrospective study was performed using data from a medium-sized hospital emergency department. Data were extracted from medical records for one year, and patients were categorized into groups ages 18-64, 65-74 and 75+. Variables included demographic characteristics, injury circumstances, and nature of injury. Univariate and bivariate descriptive statistical analyses were performed, and multivariate logistic regression was used to evaluate injury severity and hospital admission by age groups.</p> <p>Results</p> <p>A total of 1,656 patients were studied. Patients aged 65+ had more chest wall injury, intracranial injury, lower extremity fracture, and intrathoracic injury than patients aged 18-64.</p> <p>Conclusions</p> <p>Injury circumstances and nature of injuries associated with traffic incidents showed different patterns by age groups, particularly among the elderly.</p

Subaru Studies of the Cosmic Dawn

An overview on the current status of the census of the early universe population is given. Observational surveys of high redshift objects provide direct opportunities to study the early epoch of the Universe. The target population included are Lyman Alpha Emitters (LAE), Lyman Break Galaxies (LBG), gravitationally lensed galaxies, quasars and gamma-ray bursts (GRB). The basic properties of these objects and the methods used to study them are reviewed. The present paper highlights the fact that the Subaru Telescope group made significant contributions in this field of science to elucidate the epoch of the cosmic dawn and to improve the understanding of how and when infant galaxies evolve into mature ones.Comment: 14 pages, 11 figures, accepted for publication in the Proceedings of the Japan Academy, Series

Substance use and sexual behaviours of Japanese men who have sex with men: A nationwide internet survey conducted in Japan

BACKGROUND: Japanese men who have sex with men (MSM), especially those living in large metropolitan areas such as Tokyo and Osaka, are facing a growing HIV/AIDS epidemic. Although the Internet is used as a new venue for meeting sex partners, it can also serve as a useful research tool for investigating the risk behaviours of Japanese MSM. This Internet survey explored the extent of substance use and its association with sexual risk behaviours among Japanese MSM. METHODS: Between 28 February 2003 and 16 May 2003 MSM were recruited through 57 Japanese gay-oriented Web sites, gay magazines, and Internet mailing lists. Participants completed a structured questionnaire anonymously through the Internet. RESULTS: In total, 2,062 Japanese MSM completed the questionnaire. The average age of participants was 29.0 years and 70.5% identified as gay, 20.8% as bisexual, and 8.7% as other. Overall, 34.5% reported never using a substance, 45% reported ever using one type of substance (lifetime reported single substance users), and 19.6% had used more than 1 type of substance (lifetime reported multiple substance users) in their lifetimes. The substances most commonly used were amyl nitrite (63.2%), 5-methoxy-N, N-diisopropyltryptamine (5MEO-DIPT) (9.3%), and marijuana (5.7%). In the multivariate analysis, unprotected anal intercourse, having had 6 or more sexual partners, visiting a sex club/gay venue in the previous 6 months, a lower education level, and being 30 to 39 years of age were associated with both lifetime single and lifetime multiple substance use. Lifetime reported multiple substance use was also correlated with having a casual sex partner, having symptoms of depression, being diagnosed as HIV-positive, and greater HIV/AIDS-related knowledge. CONCLUSION: This is the first Internet-based research focused on the sexual and substance use behaviours of MSM in Asia. Our findings suggest a compelling need for prevention interventions to reduce HIV risk-related substance use behaviours among Japanese MSM. The results also suggest that the Internet is potentially a useful tool for collecting behavioural data and promoting prevention interventions among this population

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA

We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5– 20 deg2 requires at least three detectors of sensitivity within a factor of ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone