Search

Accumulating epidemiological evidence indicates a strong clinical association between obesity and an increased risk of cancer. The global pandemic of obesity indicates a public health trend towards a substantial increase in cancer incidence and mortality. However, the mechanisms that link obesity to cancer remain incompletely understood. The fruit fly Drosophila melanogaster has been increasingly used to model an expanding spectrum of human diseases. Fly models provide a genetically simpler system that is ideal for use as a first step towards dissecting disease interactions. Recently, the combining of fly models of diet-induced obesity with models of cancer has provided a novel model system in which to study the biological mechanisms that underlie the connections between obesity and cancer. In this Review, I summarize recent advances, made using Drosophila, in our understanding of the interplay between diet, obesity, insulin resistance and cancer. I also discuss how the biological mechanisms and therapeutic targets that have been identified in fly studies could be utilized to develop preventative interventions and treatment strategies for obesity-associated cancers., Summary: This Review highlights a Drosophila model of diet-induced obesity and cancer, and how these two models are combined to study the interplay between obesity and cancer.

The subjects were 354 fifth graders. They had one or two siblings and the differences of their grades ranged from one to four. If they had two siblings, they were asked to rate their siblings whose age were closer to theirs than the other ones. The questionnaire contained three parts; the first was their dominance in four conflict situations, the second was a sentiment toward siblings, and the third was a frequency of interpersonal behaviors that included interpersonal conflicts what are called "quarrels", and usual contacts in daily activities. Scales of the sentiment, the interpersonal conflicts, and the usual contacts had reasonable reliabilities. Siblings were divided into five groups by dominance type; self-dominant, equal, other-dominant, no-conflict, and inconsistency. In general, the sentiment correlated negatively with the frequency of quarrels and positively with the frequency of usual contacts, and the frequency of quarrels did not correlate with the usual contacts. Dividing into the elder and the younger groups, it was found that in both the other-dominant type of the elder group and the self-dominant type of the younger group, the sentiment negatively correlated with the frequency of quarrels. On the other hand, in both the self-dominant type of the elder group and the other-dominant type of the younger group, the sentiment did not indicate a significant correlation with the frequency of quarrels. Futhermore, in the equal type of the elder group, the frequency of quarrels negatively correlated with the frequency of the usual contacts. These findings were discussed in terms of the dominance types of siblings., 国立情報学研究所で電子化したコンテンツを使用している。

In the present investigation, we tried to examine longitudinally a process in which interpersonal relations were formed and developed in classrooms among like-sexed students who had been perfectly strange one another previously. In our opinion, interpersonal relation is two-sided composed of sentiment relation and power relation. Here we are concerned solely with the former, and employ P's relation toward O, instead of that between P and O, as a unit of analysis. We defined the sentiment relation as P's attitude toward O, composed of three components - cognitive, feeling, and action tendency. Our principal aim is to make clear how the relation would be formed at the very early stage of the encounter, and how it would be devopled along with amount of interactions between P and O increased. Data on the feeling component, on which our attention is focused, will be compared with those on cognitive and action tendency components. Participants of the investigation were eighty-four students who had entered the University Junior High School in April, 1979. They were assinged into two classrooms. In describing findings in the following, however, we treat a sub-class composed of students of either sex as a group. The following "tests" were administered: (1) SMT-1, in which the participants were asked to rate each of their like-sexed classmates on a 101-point-scale according to their favorableness. (2) SMT-2, in which they were asked to infer each classmate's rating him/her on SMT-1. (3) PPI, in which they were asked to rate personality of each of their classmates on eight seven-point-scales. (4) IAS, in which they reported the extent to which they contacted personally with each of the classmates during the past one week in five situations on a three-point-scale. (5) Ten other tests of personality, interests, and adjustments, etc. Tests (1), (2), and (4) were administered about once a week, totally fourteen or thirteen times through the period covering fifteen weeks from the entrance. Test (3) was repeated every two weeks, totally seven times, while the remaining ten tests were given just once through the period. Major findings obtained are as follows: 1. The sentiment relations were found to be differentiated to a considerable degree even at the very early stage. Average rating scores of SMT-1 increased remarkably at the earlier stages. From about Week-5 on, however, they remained at nearly constant levels. Stability in individual rating scores and in choice statuses, which was derived from average rating score individuals received, tended to become higher as the stage progressed. Accuracy in perceiving score given him/herself by each of classmates showed no improvements through the various stages, on the contrary to our anticipation. 2. Two factors were extracted by factoring data on perceiving the classmates' personality: "dynamism" and "evaluation." The rating scores on PPI were relatively stable throughout the whole stages. Considerable correlations were found between PPI and SMT-1. 3. Increase in the amount of interactions among individuals measured by IAS was notable during the earlier stages. Correlations between IAS and SMT-1, were found to be the higher, the earlier the stages. 4. Even at the very early stage, patterns of sociometric relation in the four groups were structured to a marked extent. Generally speaking, network structure of low level was prevalent at the earlier stages, while that of high level was common at the later stages. The developing process was, however, neither monotonous nor irreversable. Depending on various idiosyncratic factors, the actual process of structuring of each of the four groups was really individual., 国立情報学研究所で電子化したコンテンツを使用している。

The present study has two purposes. The first is to investigate the differential effects of interview vs. questionnaire method upon personality impression ratings. The second is to cast some lights upon the importance of using not only a "like-dislike" scale but also some scales which represent important personality dimensions. Ninety-nine female undergraduates served as subjects in the interview method. They were given one of three sets of stimulus each of which is composed of two personality traits, and asked to describe orally impressions of each of three stimulus-persons (SP) who were described by each of two traits and by both two traits. Then they were asked to rate impressions of each SP on ten personality-rating scales (7-points) and a "like-dislike" scale (21-points) After description followed by ratings of the first, of the second, and of the third SP, they were asked to answer the questions about changes of denotation of each trait when presented in a set from presented alone, and to rate the relative degree of contribution of the two traits in making impressions of the two-size SP, difficulty of making images of SPs in mind, and the degree of relatedness of the two traits. In the questionnaire method, subjects were two hundreds and fifteen female undergraduates. They were given two sets and were asked to rate six SPs on twelve rating scales, which were composed of the same eleven scales as in the interview method and 7-points "like-dislike" scale. Stimulus sets were also the same as in the interview method. They were not asked to describe SPs verbally. The rersults obtained are as follows : (1) 11 rating scales were classified into three groups, referring results obtained by means of factor analysis. They were designated as the social desirability scales (4 scales), the activity scales (2), and others (5), respectively. (2) Three response patterns were discriminated in terms of the relationship among the three rating values in the set : the averaging, the additive, and the odd. The odd pattern which were unaccountable by any of linear models, appeared more frequently in the interview than the questionnaire method. The rest were, on the other hand, observed more frequently in the questionnaire than in the interview method. (3) Fitness of data obtained to the simple averaging model was better in the questionnaire than in the interview method. (4) The odd pattern appeared more frequently and fitness to the simple averging model was worse in the social desirability scales than in the activity scales., 国立情報学研究所で電子化したコンテンツを使用している。

This study examines what relation people assume between physiognomic and personality characteristics and why they have such assumed relations, through more direct method than the one in the former study. Twenty-five pairs of opposite physiognomic characteristics (A-A^^^-) and 10 pairs of opposite personality traits (X-X^^^-) were used. They made two hundred and fifty combinations of physiognomic pair-personality pair, which were devided into ten groups of twenty-five combinations by Latin square. Thirty-four, thirty-five, or thirty-six subjects (female university students) were assigned to each group. On each combination of physiognomy pair-personality pair, subjects were asked at first to draw a line between the words printed if they believe that there was any relation between a physiognomic characteristic and a personality trait, and then to describe the reason for the relation. Subjects were instructed to imagine a person of the same sex and age to them. The results are as follows. 1) One hundred and thirty-four combinations of the overall (54.0%) showed significant assumed relation. This figure is lower than that obtained in former study which used rating method. However, current and former studies presented quite consistent results in spite of their different methods. One hundred and ninty-three of overall combinations (77.2%) were consistent and only one combination was inconsistent between both studies in their assumed relations. 2) From overall combination, ten which showed strong relations in one direction, and six combinations which showed relations in two direction evenly were selected for the content analysis of reasons for the assumed relations. From preliminary analysis of these sixteen combinations, six categories of the type for the reasoning were established. They were Intuition, Induction, Metaphor, Mediation, Logic, and Evaluation/Affection types. Seven judges classified 334 descriptions written on these 16 combinations into six categories. The proportion of the number of agreed judgements between a couple of judges were ranged between 53.7% and 80.9%, and 69.1% as average. This suggests that six categories may be reliably used for classification of the reasoning for the assumed relations. 3) Subjects seemed to have difficulty in describing the reasons. Such verbal description may be not adequate to elucidate the implicit relations between physiognomic and personality characteristics. Subjects' descriptions of the reasons for assumed relations and interpretations of their descriptions in terms of six categories were fully presented., 国立情報学研究所で電子化したコンテンツを使用している。

The present investigation aims at, as a first step for exploring implicit personality theories one holds, examining which physiognomic features are, in general, assumed to be related to which personality traits. Female undergraduates served as Ss. Two questionnaires were administered to separate samples. In Questionnaire I, Ss were made to rate some of the stimulus persons (SPs) on twenty-five seven-point scales described by two mutually antonymous physiognomic features each. SPs were described by one of twenty personality traits, composing ten pairs : the two are counterparts. N of Ss was 253. In addition, some Ss rated the identical SPs twice with an interval of a week on the scales, the purpose being to check the reliability of the rating. In Questionnaire II, stimuli and rating scales used in Questionnaire I were reversed; SPs described by single physiognomic features were rated on personality scales. N of Ss was 251. In the both questionnaires, no stimuli composing any pair were presented to the same Ss. Major findings obtained are as follows : 1. In order to check reliability, correlation coefficients between test and retest were calculated for each SP and for each scale. Median r's for ten SPs ranged from .34 to .53,being by no means so high. 2. There are 250 combinations of 25 physiognomic features and 10 personality traits. In many of them, significant differences were found between average rating scores of SPs described by counterparts of the stimulus-pair. The percentages of combinations with such significant difference were 88.4 in Questionnaire I, 84.8 in Questionnaire II, and 78.0 in the both questionnaires combined. These percentages are unexpectedly high, meaning that the assumed relationship between the physiognomic features and the personality traits is strong enough. 3. From a factor analysis of ratings on the 25 physiognomic scales, four factors were extracted. They were interpreted as follows : the largeness of eyes, the slender frame, the sharpness of the face and the loosely closed mouth. In a similar way, three factors were extracted from the ratings on the 10 personality scales : sociability, passiveness, and indiscretion. 4. According to their factor-loadings to the factors, physiognomic scales were classified into four, and personality scales into three, groups. Some coordinations between the both kinds of groups were observed : unsociability with sharpness of the face, passiveness with smallness of eyes and slender frame, and indiscretion with loosely closed mouth. 5. "The Method of Quantification III" developed by C. Hayashi was applied to the data in Questionnaire I. A similar coordination was observed between the groups of physiognomic scales and those of personality scales., 国立情報学研究所で電子化したコンテンツを使用している。

This research is designed to examine the effects of photographed faces as the firsts tep to study the process : "how to form impression through person's appearance." Aims of the present study are as follows : 1. To clarify the differences of the impression between color pictures and black & white ones. 2. To select some typical pictures for future researches which are dissimilar to each other. Ss are college females : 123 persons in the first investigation, and 89 in the second. Procedure is devided into the following four steps. 1. To collect 90 pictures each of color and black & white of female students. 2. To use 25 bipolar adjectives with 7 points as the rating scales of the impression. 3. 90 pictures are devided into 15 sets. Some Ss are presented with a color set first (C-1) and a black & white one next (W-2). The rest are presented reversely (W-1,C-2). 4. For the first set of pictures only, besides making a check at a point on the rating scales, Ss are also asked to decide the degree of the certainty of their rating. Major results obtained are as follows : 1. When examining the inter-correlations between 6 pictures in each set, we find the average correlation insignificant, This means that Ss tended to rate not stereotypically but differentially. 2. There is a significant interrelation between the ratings in the two investigations. In the both Ss' group, average intercorrelations are significant. In addition, most of the correlations between two ratings of each subject are significant. 3. The mean of the certainty of the colored is not different from that of balck & white, The variance among 25 scales is small. The certainty is weak on the middle of the scale, getting stronger towards both polars. 4. Ninety pictures are classified into 4 groups by means of both a method of hierarchical clustering and a factor analysis. The correspondence between the both methods is pretty good. Profiles of the four representative pictures are presented, amog which will be seen differences to a large extent., 国立情報学研究所で電子化したコンテンツを使用している。

A complex and bi-directional interaction exists between a tumour and its host. By treating cancer as a systemic disease, and leveraging the genetic tractability of Drosophila melanogaster, work throughout this thesis explores the nature of the tumour-host interaction. By combining Drosophila models of high sugar diet (HSD)-induced obesity and Ras/Src-driven tumourigenesis, I have established a model of ‘cachexia-like’ systemic muscle wasting. This model system has provided an excellent opportunity to explore the metabolic/nutritional interplay between tumourigenesis, HSD-induced obesity, and host systemic muscle wasting. This thesis specifically addresses two questions. Firstly, how does a tumour impact host systemic metabolism? And secondly, how do host metabolic alterations and their associated effects on systemic nutrient availability, impact tumour growth? I identify Branchless (Bnl), a Drosophila Fibroblast Growth Factor (FGF), as a tumour- and hostderived mediator of systemic muscle wasting. I highlight a perturbed systemic metabolic profile, characterised by amino acid mobilisation and elevated levels of circulating amino acids as one of the key consequences of systemic muscle wasting. This altered systemic amino acid profile has functional effects on tumour growth; elevated levels of circulating L-proline promote tumour growth via tumour-autonomous SLC36-family amino acid transporter expression. This establishes a tumour-host circuitry which requires two levels of coordination: (i) at the whole organism level— by promoting cachexia-like muscle wasting and systemic amino acid availability, and (ii) at the tumour-autonomous level—by modulating amino acid transporter repertoire. Furthermore, I highlight our approach of combining mechanistic insights from whole-animal Drosophila studies, with human cancer database analysis and human in vitro data to rationally target the nutrient vulnerabilities of tumourigenesis. Overall, this uncovers a novel concept and mechanism by which tumours exploit extracellular nutrients in response to systemic muscle wasting. This work therefore represents a new layer of tumour-host metabolic crosstalk which adds to our ever-growing appreciation of the intricacies of tumour-host interaction. Open Access

Simple carbohydrates constitute a big part of our everyday diet, as significant consumption increases have occurred in recent decades. This has coincided with a dramatic rise in people suffering from metabolic disorders, such as diabetes and obesity. However, the genetic factors ensuring a healthy response to sugar intake remain poorly understood. To keep blood glucose in a healthy range even upon overnight fasting or following a rich meal, animals need to be able to adapt quickly. In a healthy organism, high sugar intake leads to rapid conversion of excess sugars into stored glycogen and triacylglycerols, while starvation triggers glucose production through gluconeogenesis and glycogen breakdown. To cope with these fluctuating nutritional conditions organisms possess glucose-sensing mechanisms. Such pathways have a key role in monitoring changes in cellular and organismal nutrient status and readjusting animal physiology accordingly to maintain homeostasis. Intracellular sugar metabolites are sensed by the conserved Mondo family transcription factors (TFs)(MondoA and MondoB/ChREBP in mammals, Mondo in Drosophila), which act together with TF Mlx. Together, they control the expression of metabolic target genes by binding to the carbohydrate response elements present in their promoters. The known Mondo-Mlx targets include genes involved in carbohydrate metabolism and biosynthesis of fatty acids. Yet, the physiological output of these transcription factors has remained largely elusive. As these TFs are very well conserved in Drosophila, this model organism has been used in this thesis to understand the physiological role of Mondo-Mlx and their target genes in vivo. We show that Mondo-Mlx interact in the fly and are crucial for dietary sugar tolerance. Loss of either transcription factor leads to impaired growth and lethality upon high sugar diet. We further characterize the mlx mutant phenotype to reveal high circulating glucose, and increased glycogen levels. We uncover transcriptional repressor Cabut as a direct target of Mondo-Mlx. The Cabut promoter is directly bound by Mondo-Mlx in a sugar-dependent manner. Loss of Cabut similarly results in dietary sugar intolerance, pointing to a crucial function in carbohydrate metabolism. Mondo-Mlx through Cabut are essential for repressing the expression of pepck – the rate limiting gene in gluconeogenesis and glyceroneogenesis. A failure to regulate this step results in pepck over-expression, leading to several fold higher levels of circulating glycerol, and pupal lethality of mlx mutants. Moreover, we reveal that Cabut interconnects nutrient sensing with the circadian clock, and contributes to circadian gene expression oscillation. We also identify Salt inducible kinase 3 (SIK3) as a direct transcriptional target of Mondo-Mlx required for dietary sugar tolerance. Moreover, we show that the activity of the rate-limiting enzyme in the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD), is increased following sugar feeding. The sugar-augmented increase in G6PD activity is achieved through SIK3-dependent activating G6PD phosphorylation. Collectively, Mondo-Mlx-mediated transcriptional upregulation, as well as SIK3-dependent phosphorylation promote G6PD enzyme activity in response to high high sugar diet. The increased G6PD activity is required for elevating NADPH/NADP+ ratio in order to reduce glutathione in high sugar conditions. We determine that upregulating G6PD activity through Mondo-Mlx and SIK3 is essential for redox balance maintenance, and dietary sugar tolerance. In sum, thesis demonstrates that maintaining redox balance, directing the flow of carbon backbones, and regulating the expression of metabolic circadian genes is essential for dietary sugar tolerance. We highlight the central role of Mondo-Mlx in orchestrating the necessary transcriptional response required for safe glucose utilization, and ultimately, for maintaining metabolic homeostasis. Yksinkertaiset hiilihydraatit, sokerit, ovat merkittävä osa päivittäistä ravintoamme ja sokerien kulutus on lisääntynyt huomattavasti viime vuosikymmeninä. Samanaikaisesti metabolisten sairauksien, kuten diabeteksen ja lihavuuden, esiintyvyys on lisääntynyt voimakkaasti. Ymmärrämme kuitenkin edelleen huonosti, miten yksilön geenit vaikuttavat ruuan sokerien aiheuttamiin terveysriskeihin. Eläimet pystyvät nopeasti sopeuttamaan elimistönsä aineenvaihdunnan muuttuviin ravitsemusolosuhteisiin. Näinollen esimerkiksi veren glukoosi pysyy tasapainossa aterian jälkeen. Tämä on mahdollista, koska elimistössä on ns. glukoosinaistintamekanismeja, jotka toimivat hormonaalisesti (esim. insuliini ja glukagoni) tai paikallisesti solujen sisällä. Nämä mekanismit reagoivat elimistön muuttuviin glukoosipitoisuuksiin ja muuttavat eläimen fysiologiaa niin, että aineenvaihdunnan tasapaino palautuu. Solun sisäisen glukoosinaistinnan kulmakiviä ovat Mondo-transkriptiotekijät ChREBP (MondoB) ja MondoA, jotka toimivat yhdessä Mlx transkriptiotekijän kanssa. ChREBP/MondoA-Mlx-kompleksi aktivoituu solunsisäisen glukoosin lisääntyessä ja se säätelee monia aineenvaihduntaan vaikuttavia geenejä. Monet aineenvaihdunnan säätelyyn vaikuttavat mekanismit ovat evoluutiossa hyvin säilyneitä, joten ne ovat samankaltaisia ihmisellä ja yksinkertaisemmilla eläimillä, kuten banaanikärpäsellä (Drosophila melanogaster). Tämä mahdollistaa aineenvaihdunnan säätelyn perusmekanismien tutkimisen käyttäen Drosophilaa tutkimusmallina. Myös Drosophilalla on solunsisäinen glukoosinaistintajärjestelmä, joka on hieman yksinkertaisempi kuin ihmisellä: Drosophilalla on yksi Mondo-transkriptiotekijä ja yksi Mlx. Niiden toimintaa ei ollut juurikaan aiemmin tutkittu. Tässä väitöstyössä osoitimme, että Drosophilan Mondo ja Mlx muodostavat yhdessä samanlaisen kompleksin kuin ihmisellä. Lisäksi havaitsimme, että toiminnallinen Mondo-Mlx kompleksi on välttämätön edellytys Drosophilan kyvylle säilyä hengissä sokeripitoisella ravinnolla. Lisäksi löysimme useita Mondo-Mlx:n säätelemiä tekijöitä, jotka osallistuvat solunsisäiseen glukoosinaistintaan. Yksi näistä on transkriptiotekijä Cabut, joka vaikuttaa solunsisäiseen glukoosiaineenvaihduntaan inhiboimalla gluko- ja glyseroneogeneesiä. Lisäksi Cabut toimii yhdistävänä linkkinä glukoosiaineenvaihdunnan ja vuorokausirytmin säätelyn välillä. Toinen löytämämme Mondo-Mlx:n kohdegeeni on SIK3, joka on aineenvaihduntaa säätelevä kinaasi. Me havaitsimme, että SIK3 säätelee solujen hapetus-pelkistys-tasapainoa, mikä puolestaan on keskeinen säätelykohde eläinten sokerinsietokyvyn kannalta. Yhteenvetona, tässä työssä on löydetty uusia säätelyverkostoja, jotka mahdollistavat eläimen fysiologisen adaptoitumisen sokeripitoiseen ravintoon. Koska väitöstyössä tutkitut säätelijät ovat evoluutiossa hyvin säilyneitä, saavuttamamme tieto saattaa olla tärkeää myös ihmisen aineenvaihduntasairauksien näkökulmasta.