Discovery and fine mapping of serum protein loci through transethnic meta-analysis.

Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p < 5 × 10(-8)) for serum albumin (HPN-SCN1B, GCKR-FNDC4, SERPINF2-WDR81, TNFRSF11A-ZCCHC2, FRMD5-WDR76, and RPS11-FCGRT, in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein (TNFRS13B, 6q21.3, and ELL2, in up to 25,539 European-ancestry and 10,168 Japanese individuals). We observed little evidence of heterogeneity in allelic effects at these loci between groups of European and Japanese ancestry but obtained substantial improvements in the resolution of fine mapping of potential causal variants by leveraging transethnic differences in the distribution of linkage disequilibrium. We demonstrated a functional role for the most strongly associated serum albumin locus, HPN, for which Hpn knockout mice manifest low plasma albumin concentrations. Other loci associated with serum albumin harbor genes related to ribosome function, protein translation, and proteasomal degradation, whereas those associated with serum total protein include genes related to immune function. Our results highlight the advantages of transethnic meta-analysis for the discovery and fine mapping of complex trait loci and have provided initial insights into the underlying genetic architecture of serum protein concentrations and their association with human disease.

Collection of Canadian periodical clippings and Peninsular Game Club of St. Catharines broadside, 1874, [1910-1950]

Items include: 13 small poems clipped from newspapers. None of the poems list authors. Most of the poems are based on life lessons. Clippings of short stories which appear to have come from a St. Catharines newspaper. The stories include anecdotes, humour and medical advice. There is no author listed on any of the stories. 2 coloured sewing machine advertisements each measuring 9 cm. x 13 cm. and 9 cm. x 14 cm. 1 broadside measuring 27 cm. x 37 cm. and posted by the Peninsular Game Club of St. Catharines. The broadside is a copy of the game laws of 1874 with a warning that breach of these laws will bring rigorous prosecution.

Biostatistical evaluation and Management of sciaenid fishery with particular reference to Otolithes ruber (Schneider, 1801) andJohnieops sina (Cuvier, 1830) of Konkan coast

Fish, a natural resource, has received great attention from all over the world. since it provides a cheap protein, employment and income to the millions of people for centuries. So fishermen, industrialist and multinationals are trying to exploit the marine resources to their maximum benefit by using modern craft, advance fishing equipments and efficient gear. Fishery resources in the open system particularly in oceans, were considered to be unlimited. However, recent developments in the innovation of efficient craft and gear using well tested material fitted with modern equipments that have greatly enhanced the mobility of craft, agility of gear and the ability of equipments to locate fishery resources have proved otherwise. Hence as the exploitation increases with more effort entering the fishery, the catch per unit of fishing effort starts to decline due to the limitness of the resources. The heavy fishing pressure in the recent past led to commercial extinction of a number of stocks such as. the North Sea herring, California sardine, Japanese Sardine and Peruvian anchovy (FAO. 1968: Gulland, 1974). In India, seer fish from Palk-Bay declined due to uncontrolled fishing (Devaraj 1983).

The bi-cultural option for international human resource management: the Japanese/Brazilian Nikkeijin example

This paper reports on an important subgroup of international boundary-spanners – immigrants and second or third generation migrants from the MNC's home country living in the subsidiary host country. We take as our example the Nikkeijin (Japanese immigrants and their descendants) in Brazil. Such bi-cultural people are a largely unexplored source of boundary-spanning internationally competent talent for multinational enterprises. Using two different surveys, we find that this group is recognized as a source of talent by Japanese MNCs, but that their HRM practices are not appropriate to attract and use them in their global talent management programmes.

Barriers to environmental management in clusters of small businesses in Brazil and Japan: from a lack of knowledge to a decline in traditional knowledge

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Autoimmunity does not contribute to the highly prevalent glucose metabolism disturbances in a Japanese Brazilian population

The Japanese Brazilian population has one of the highest prevalences of diabetes worldwide. Despite being non-obese according to standard definitions, their body fat distribution is typically central. We investigated whether a subset of these subjects had autoantibodies that would suggest a slowly progressive form of type 1 diabetes. A total of 721 Japanese Brazilians (386 men) in the 30- to 60-year age group underwent clinical examination and laboratory procedures, including a 75-g oral glucose tolerance test and determinations of serum autoantibodies. Antibodies to glutamic acid decarboxylase (GADab) were determined by radioimmunoassay and to thyroglobulin (TGab) and thyroperoxidase (TPOab) by flow-cytometry assays. Mean body mass index was 25.2 ± 3.8 kg/m2, but waist circumference was elevated according to the Asian standards. Diabetes, impaired glucose tolerance, and impaired fasting glycemia were found in 31%, 22%, and 22%, respectively, and 53% of the subjects had metabolic syndrome. Glutamic acid decarboxylase (GADab) was positive in 4.72%, TGab in 9.6%, and TPOab in 10% of the whole sample. When participants were stratified according to the presence of thyroid antibodies, similar frequencies of GADab were found in positive and negative groups. The prevalence rates of glucose metabolism disturbances did not differ between GADab positive and negative groups. Our data did not support the view that autoimmune injury could contribute to the high prevalence of diabetes seen in Japanese Brazilians, and the presence of co-morbidities included in the spectrum of metabolic syndrome favors the classification as type 2 diabetes.

Flying geese or sitting ducks? Transnationals and industry in developing countries

Includes bibliography

The restructuring of the Brazilian industrial groups between 1980 and 1993

Includes bibliography

Pharmacogenetic polymorphisms in Brazilian-born, first-generation japanese descendants

Brazil hosts the largest Japanese community outside Japan, estimated at 1.5 million individuals, one third of whom are first-generation, Brazilian-born with native Japanese parents. This large community provides a unique opportunity for comparative studies of the distribution of pharmacogenetic polymorphisms in native Japanese versus their Brazilian-born descendants. Functional polymorphisms in genes that modulate drug disposition (CYP2C9, CYP2C19 and GSTM3) or response (VKORC1) and that differ significantly in frequency in native Japanese versus Brazilians with no Japanese ancestry were selected for the present study. Healthy subjects (200 native Japanese and 126 first-generation Japanese descendants) living in agricultural colonies were enrolled. Individual DNA was genotyped using RFLP (GSTM3*A/B) or TaqMan Detection System assays (CYP2C9*2 and *3; CYP2C19*2 and *3; VKORC1 3673G>A, 5808T>G, 6853G>C, and 9041G>A). No difference was detected in the frequency of these pharmacogenetic polymorphisms between native Japanese and first-generation Japanese descendants. In contrast, significant differences in the frequency of each polymorphism were observed between native or first-generation Japanese and Brazilians with no Japanese ancestry. The VKORC1 3673G>A, 6853G>C and 9041G>A single nucleotide polymorphisms were in linkage disequilibrium in both native and first-generation Japanese living in Brazil. The striking similarity in the frequency of clinically relevant pharmacogenetic polymorphisms between Brazilian-born Japanese descendants and native Japanese suggests that the former may be recruited for clinical trials designed to generate bridging data for the Japanese population in the context of the International Conference on Harmonization.

Performance of cucumber hybrids cultivated in coconut fiber and soil

The objective of this work was to evaluate the performance of three Japanese group cucumber hybrids, which were cultivated in two cultivation systems. The experiment was designed in a split-plot randomized block design with two cultivation systems (coconut fiber and soil) for commercial Japanese cucumber hybrids ('Tsuyataro', 'Yoshinari' and 'Nankyoku'). After harvesting the cucumbers, we evaluated the number of marketable fruits per plant, the average fruit length, the mean fruit diameter, the bottom fruit diameter, the marketable production of fruits per plant and the marketable yield per hectare. There were significant interactions between the cultivation system and the hybrid, as indicated by the number of marketable fruits. The Nankyoku hybrid had the highest average (14.54 fruits pl(-1)), although it did not differ from the Yoshinari hybrid when grown in coconut fiber. In soil culture, the Yoshinari hybrid had the highest average number of fruits per plant (10.12 fruits pl(-1)) and did not differ from the Tsuyataro hybrid. Cultivation in coconut fiber provided better results for production traits and plant productivity. 'Yoshinari' and 'Nankyoku' were the most productive hybrids. Based on the cucumber cultivation results from a protected environment, the cultivation of hybrid Japanese cucumbers and Yoshinari and Nankyoku hybrids in coconut fiber is recommended.

[Old and new interventional therapies in the treatment of symptomatic benign prostate hyperplasia (BPH)]

Benign Prostatic Hyperplasia is a common entity among the aging male population. Its prevalence is increasing with age and is around 80% in the over 80-years old. The androgen-estrogen ratio changes in favor of the estrogens, which leads to a growth of prostatic tissue, presenting histologically as hyperplasia. BPH can cause irritative or obstructive symptoms or both. Nowadays we speak of bladder storage or bladder voiding symptoms, summarised as LUTS (Lower Urinary Tract Symptoms). LUTS has a structural and a functional component, the structural being caused by the size of the adenoma itself the functional depending on the muscle tone of the bladder neck and the prostatic urethra. To investigate LUTS, we use validated symptom scores, sonography for residual urine and eventually a urodynamic evaluation. There are 3 grades of BPH. The indication for an interventional therapy is relative in BPH II, and absolute in BPH III. Prior to treatment, other diseases mimicking the same symptoms, have to be ruled out and adequatly treated. Electro-resection of the prostate (TUR-P) remains the standard therapy and the benchmark any new technology has to compete with. TUR-P has good short- and longterm results, but can be associated with a considerable perioperative morbidity, and the learning curve for the operator is long. The most promising of the newer techniques is the Holmium-Laser-Enucleation of the prostate (Laser-TUR-P), showing at least identical short- and median-term results, but a lower perioperative morbidity than TUR-P For several minimally-invasive techniques, indications are limited. TUMT TUNA, WIT and laser-coagulation all produce a coagulation necrosis of the prostatic tissue by thermic damage with secondary tissue shrinking. Urodynamic results however, are not comparable to TUR-P or Laser-TUR-P, and significantly more secondary interventions within 2 to 5 years are required. Minimal-invasive techniques present a favorable alternative for younger patients without complications of BPH, and for older patients with relevant comorbidities, and can usually be performed under local anaesthesia. The morbidity is low and further therapies remain possible later, if necessary.

Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics

PURPOSE To explore whether population-related pharmacogenomics contribute to differences in patient outcomes between clinical trials performed in Japan and the United States, given similar study designs, eligibility criteria, staging, and treatment regimens. METHODS We prospectively designed and conducted three phase III trials (Four-Arm Cooperative Study, LC00-03, and S0003) in advanced-stage, non-small-cell lung cancer, each with a common arm of paclitaxel plus carboplatin. Genomic DNA was collected from patients in LC00-03 and S0003 who received paclitaxel (225 mg/m(2)) and carboplatin (area under the concentration-time curve, 6). Genotypic variants of CYP3A4, CYP3A5, CYP2C8, NR1I2-206, ABCB1, ERCC1, and ERCC2 were analyzed by pyrosequencing or by PCR restriction fragment length polymorphism. Results were assessed by Cox model for survival and by logistic regression for response and toxicity. Results Clinical results were similar in the two Japanese trials, and were significantly different from the US trial, for survival, neutropenia, febrile neutropenia, and anemia. There was a significant difference between Japanese and US patients in genotypic distribution for CYP3A4*1B (P = .01), CYP3A5*3C (P = .03), ERCC1 118 (P < .0001), ERCC2 K751Q (P < .001), and CYP2C8 R139K (P = .01). Genotypic associations were observed between CYP3A4*1B for progression-free survival (hazard ratio [HR], 0.36; 95% CI, 0.14 to 0.94; P = .04) and ERCC2 K751Q for response (HR, 0.33; 95% CI, 0.13 to 0.83; P = .02). For grade 4 neutropenia, the HR for ABCB1 3425C-->T was 1.84 (95% CI, 0.77 to 4.48; P = .19). CONCLUSION Differences in allelic distribution for genes involved in paclitaxel disposition or DNA repair were observed between Japanese and US patients. In an exploratory analysis, genotype-related associations with patient outcomes were observed for CYP3A4*1B and ERCC2 K751Q. This common-arm approach facilitates the prospective study of population-related pharmacogenomics in which ethnic differences in antineoplastic drug disposition are anticipated.

A longitudinal comparison of cardiovascular disease risk factors among children and adolescents in the U.S. and Japan: Project HeartBeat!

Blood cholesterol and blood pressure development in childhood and adolescence have important impact on the future adult level of cholesterol and blood pressure, and on increased risk of cardiovascular diseases. The U.S. has higher mortality rates of coronary heart diseases than Japan. A longitudinal comparison in children of risk factor development in the two countries provides more understanding about the causes of cardiovascular disease and its prevention. Such comparisons have not been reported in the past. ^ In Project HeartBeat!, 506 non-Hispanic white, 136 black and 369 Japanese children participated in the study in the U.S. and Japan from 1991 to 1995. A synthetic cohort of ages 8 to 18 years was composed by three cohorts with starting ages at 8, 11, and 14. A multilevel regression model was used for data analysis. ^ The study revealed that the Japanese children had significantly higher slopes of mean total cholesterol (TC) and high density lipoprotein (HDL) cholesterol levels than the U.S. children after adjusting for age and sex. The mean TC level of Japanese children was not significantly different from white and black children. The mean HDL level of Japanese children was significantly higher than white and black children after adjusting for age and sex. The ratio of HDL/TC in Japanese children was significantly higher than in U.S. whites, but not significantly different from the black children. The Japanese group had significantly lower mean diastolic blood pressure phase IV (DBP4) and phase V (DBP5) than the two U.S. groups. The Japanese group also showed significantly higher slopes in systolic blood pressure, DBP5 and DBP4 during the study period than both U.S. groups. The differences were independent from height and body mass index. ^ The study provided the first longitudinal comparison of blood cholesterol and blood pressure between the U.S. and Japanese children and adolescents. It revealed the dynamic process of these factors in the three ethnic groups. ^

Early metacognitive abilities: The interplay of monitoring and control processes in 5- to 7-year-old children

The goal of the current investigation was to compare two monitoring processes (judgments of learning [JOLs] and confidence judgments [CJs]) and their corresponding control processes (allocation of study time and selection of answers to maximize accuracy, respectively) in 5- to 7-year-old children (N=101). Children learned the meaning of Japanese characters and provided JOLs after a study phase and CJs after a memory test. They were given the opportunity to control their learning in self-paced study phases, and to control their accuracy by placing correct answers into a treasure chest and incorrect answers into a trash can. All three age groups gave significantly higher CJs for correct compared to incorrect answers, with no age-related differences in the magnitude of this difference, suggesting robust metacognitive monitoring skills in children as young as 5. Furthermore, a link between JOLs and study time was found in the 6- and 7-year-olds, such that children spent more time studying items with low JOLs compared to items with high JOLs. Also, 6- and 7-year-olds but not 5-year-olds spent more time studying difficult items compared to easier items. Moreover, age-related improvements were found in children's use of CJs to guide their selection of answers: although children as young as 5 placed their most confident answers in the treasure chest and least confident answers in the trash can, this pattern was more robust in older children. Overall, results support the view that some metacognitive judgments may be acted upon with greater ease than others among young children.