身体支援ロボット工学の基盤となるシナジー解析と関節トルク積算エネルギーの相補的活用による運動軌道解析法に関する研究

九州工業大学博士学位論文（要旨）学位記番号：生工博甲第265号 学位授与年月日平成28年3月25

Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery

The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT).Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed.All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P  LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission

Phylogeography and Population Structure Analysis Reveal Diversity by Gene Flow and Mutation in Ustilago segetum (Pers.) Roussel tritici Causing Loose Smut of Wheat

Ustilago segetum (Pers.) Roussel tritici (UST) causes loose smut of wheat account for considerable grain yield losses globally. For effective management, knowledge of its genetic variability and population structure is a prerequisite. In this study, UST isolates sampled from four different wheat growing zones of India were analyzed using the second largest subunit of the RNA polymerase II (RPB2) and a set of sixteen neutral simple sequence repeats (SSRs) markers. Among the 112 UST isolates genotyped, 98 haplotypes were identified. All the isolates were categorized into two groups (K = 2), each consisting of isolates from different sampling sites, on the basis of unweighted paired-grouping method with arithmetic averages (UPGMA) and the Bayesian analysis of population structure. The positive and significant index of association (IA = 1.169) and standardized index of association (rBarD = 0.075) indicate population is of non-random mating type. Analysis of molecular variance showed that the highest variance component is among isolates (91%), with significantly low genetic differentiation variation among regions (8%) (Fst = 0.012). Recombination (Rm = 0) was not detected. The results showed that UST isolates have a clonal genetic structure with limited genetic differentiation and human arbitrated gene flow and mutations are the prime evolutionary processes determining its genetic structure. These findings will be helpful in devising management strategy especially for selection and breeding of resistant wheat cultivars

Dopunska prehrana ribljim uljem poboljšala je funkciju jajnika, koncepciju i određene reprodukcijske pokazatelje kod kobila pasmine marvari

We investigated the effect of dietary fish oil supplementation on the development of the ovarian follicles, corpus luteum (CL), conceptus and certain reproductive events in Marwari mares, since it is reported to improve reproduction in cows. Accordingly, non-lactating mares (n = 20) were randomly assigned into two groups (10 per group) and fed either the control diet (CTR) or a diet enriched with fish oil (FOS) to supplement n-3 polyunsaturated fatty acids (PUFA) at the rate of 64 mg/kg body weight/day for 70 days or until 45 days post-ovulation in the mares that became pregnant. Estrus was detected using a teaser and insemination was performed using frozen thawed semen in the experimental mares. Development of the ovarian follicle, CL and conceptus were recorded using trans-rectal ultrasonography. Plasma concentrations of progesterone and estradiol were estimated by radioimmunoassay. In the FOS group, the diameter of the largest follicle from day 4 of estrus until ovulation, and the diameter of the CL on day 7 post-ovulation (D7PO) were greater (P<0.05). However, on day 15 post-ovulation (D15PO), the CL diameter increased significantly in the pregnant mares. Dietary fish oil significantly improved the development of the embryo as evidenced by an increase in the diameter of the embryonic vesicle on day 15 post-ovulation (D15PO), and the embryo proper on day 28 post ovulation (D28PO). Further, the mean plasma estradiol concentration was higher on the day of estrus onset (P<0.05) and day 4 of estrus (P<0.01) in the FOS group. Similarly, dietary fish oil significantly increased the plasma progesterone on D15PO in the pregnant mares (P<0.01). Although the duration of estrus was shorter by 19 hours (P<0.05), the length of the estrous cycle did not vary in the FOS group. A non-significant increase in the pregnancy rate was observed in the mares that received fish oil. It was concluded that dietary fish oil supplementation improved ovarian function and embryonic development in the Marwari mares.Na temelju prethodnih izvješća o poboljšanju reprodukcije krava, kod kobila pasmine marvari istražili smo učinak ribljeg ulja kao prehrambenog dodatka na razvoj folikula jajnika, žutog tijela, koncepcije i određenih reprodukcijskih pokazatelja. U skladu s ciljem, 20 kobila koje nisu bile u laktaciji je metodom slučajnog izbora podijeljeno u dvije skupine s po 10 kobila. Za razliku od kontrolne skupine, kobile u eksperimentalnoj skupini hranjene su obrokom obogaćenim ribljim uljem u obliku dodatka koji je sadržavao n-3 polinezasićene masne kiseline (PUFA), u dnevnoj količini od 64 mg na jedan kg tjelesne mase. Eksperiment je trajao 70 dana, odnosno za kobile koje su ostale gravidne do 45 dana nakon ovulacije. Estrus je praćen teaserom, a osjemenjivanje je provedeno zamrznutim sjemenom. Razvoj folikula jajnika i žutih tijela te gravidnosti praćeni su transrektalnim ultrazvukom. Koncentracija progesterona i estradiola u plazmi procijenjena je radioimunološkom metodom. U eksperimentalnoj skupini utvrđen je veći (P<0,05) promjer najvećeg folikula od 4. dana estrusa do ovulacije i veći promjer žutog tijela 7. dan nakon ovulacije. No, 15. dan nakon ovulacije promjer žutih tijela bio je signifikantno povećan kod gravidnih kobila. Obrok obogaćen ribljim uljem signifikantno je poboljšao razvoj embrija, što se očitovalo povećanjem promjera embrionalne vezikule 15. dan nakon ovulacije i povećanjem embrija 28. dan nakon ovulacije. Nadalje, u eksperimentalnoj skupini kobila srednja koncentracija estradiola u plazmi bila je veća na dan početka estrusa (P<0,05) i 4. dan estrusa (P<0,01). Slično tome, obrok obogaćen ribljim uljem kod gravidnih je kobila signifikantno (P<0,01) povećao progesteron u plazmi 15. dan nakon ovulacije. U kobila eksperimentalne skupine je, uz varijacije estrusnog ciklusa, utvrđeno i za 19 sati kraće trajanje estrusa (P<0,05). Povećana stopa gravidnosti kod kobila dohranjivanih ribljim uljem nije bila signifikantna. Zaključeno je da je hranidba s dodatkom ribljeg ulja kod kobila pasmine marvari poboljšala funkciju jajnika i razvoj embrija

Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Methods Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes. Results Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05). Conclusions/interpretation Our study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (&lt; 5 years, 5–10 years, 10–20 years, and &gt; 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (&lt; 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs &gt; 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (&lt; 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs &gt; 20 years: 0.62), and only surgeons with &gt; 20 years of experience did not have substantial reliability on assessment 2 (&lt; 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs &gt; 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe