The lifespan of an organism is determined by a complex array of genetic, environmental and nutritional factors. Yet single gene manipulations have been shown to significantly extend lifespan in several model organisms. Of all the genes that have been studied thus far, components of the insulin/IGF-1 signaling (IIS) pathway have emerged as the most robust regulators of longevity. In addition, IIS also regulates development, energy metabolism and the response to stress in a conserved manner. In Caenorhabditis elegans, signaling through this pathway is initiated by activation of the insulin/IGF-1 receptor tyrosine kinase DAF-2, which then activates a PI3-kinase signaling pathway involving additional downstream serine/threonine kinases such as PDK-1, AKT-1, AKT-2 and SGK-1. The concerted action of these kinases results in the negative regulation of the single FOXO transcription factor homolog DAF-16. Under reduced signaling conditions, active DAF-16 is able to translocate into the nucleus and regulate the expression of hundreds of genes regulating longevity, stress resistance, metabolism and development. The PTEN phosphatase homolog DAF-18, which antagonizes IIS at the level of PI3-kinase, is a major negative regulator of the pathway. However, not much was known about additional phosphatases that negatively regulated the kinases in the pathway. Dephosphorylation is a critical regulatory mechanism by which cellular signaling homeostasis is maintained. Aberrant hyper-activation of growth factor signaling pathways, including IIS, has been implicated in several cancers. In addition, deregulation of IIS is also closely linked to Type II diabetes. Therefore, the identification phosphatases that balance kinase activity will provide a better understanding of the regulation of the IIS pathway under normal as well as disease conditions. A directed RNAi screen using dauer diapause was conducted in our lab to identify serine/threonine phosphatases that modulated IIS. My work in the Tissenbaum Lab has primarily focused on characterization of the top three candidates from this screen, the genes pptr-1, pdp-1 and fem-2. From these studies, we have also uncovered novel crosstalk between the IIS and TGF-β signaling pathways. In Chapter 2, we demonstrate that PPTR-1, a PP2A phosphatase regulatory subunit negatively regulates the IIS pathway by modulating AKT-1 dephosphorylation. PPTR-1 modulates several outputs of IIS similar to DAF-18. In addition, PPTR-1 co-localizes and physically interacts with its substrate, AKT-1. PPTR-1 modulates dephosphorylation of AKT-1 at a conserved threonine site and we show the molecular conservation of this interaction in mammalian adipocytes. Ultimately, this negative regulation by PPTR-1 results in increased DAF-16 nuclear localization and transcriptional activity. Next, in Chapter 3, we show how PDP-1 is a novel link between the IIS and TGF-β signaling pathways. Similar to DAF-18 and PPTR-1, PDP-1 regulates multiple outputs of the IIS pathway and promotes DAF-16 activity. Interestingly, PDP-1 acts at the level of DAF-8 and DAF-14, two R-SMAD proteins that function in a TGF-β pathway. Our data suggests that PDP-1 may negatively regulate TGF-β signaling to downregulate the expression of several insulin(s). Without the insulin ligands, there is less activation of the IIS pathway, and DAF-16 is more active, thereby promoting transcription of genes that act to enhance longevity and stress resistance. In Chapter 4, we investigate possible crosstalk between IIS and the TGF-β signaling pathways, as the latter was previously considered as a parallel independent pathway. From our studies on PDP-1, we knew that this phosphatase, despite acting in the TGF-β pathway, was a robust modulator of multiple outputs of IIS. Using double mutant combinations as well as RNAi we unravel complex and extensive crosstalk between the two pathways. Importantly, our results suggest that DAF-16 is likely to be the most downstream component of the two pathways. In Chapter 5, we describe genetic characterization of fem-2, and its regulation of the IIS pathway. RNAi of fem-2 results in robust suppression of dauer formation, similar to pptr-1 and pdp-1 RNAi but this phenotype is only observed in the e1370 allele of daf-2. While knockdown of pptr-1 and pdp-1 suppress dauer formation of additional alleles of daf-2, fem-2 RNAi has no effect. These results reveal a complex genetic interaction between fem-2 and the daf-2 receptor. Taken together, our results identify several novel regulators of IIS that modulate this pathway by distinct mechanisms.

A qualitative study of the experiences and observations of 4 art therapists and 2 program directors who facilitated Camp Suzanne, a week-long art-based therapeutic program for incarcerated mothers and their children in a federal prison in California. Research on psychotherapy, art therapy, and family therapy in prison environments, with a focus on parent-child dyads, Attachment Theory, and various techniques for creating sustainable therapy with separated family units, including tele-mental health and evidence-based military protocols, informed the interviews. The research participants were interviewed individually and created art regarding the subjects of Attachment Theory with incarcerated-mother-child dyads and longevity considerations for the program. Emergent themes in the data included the impact of art-making on attachment and a variety of observable attachment styles, as well as obstacles to both attachment and longevity of Camp Suzanne. Some of the obstacles addressed include systemic challenges, continuity of care, location concerns, external support (for facilitators and for incarcerated-mother-child dyads), as well as preparatory support (psychoeducation). Various implications of these obstacles are discussed.

This phenomenological study examined the experiences of women in midlife. The primary purpose of the study was to develop and describe a model of health promotion that will facilitate self-care of women in midlife to support them in the attainment of wholeness. A theory-generative, qualitative, explorative, descriptive and contextual design was utilized to achieve the objectives of the study, namely to explore and describe women's experience of midlife transition; classify concepts of the model; describe the structure and process of a model for support of women during midlife transition, and develop guidelines for operationalization of the model. The study was undertaken in one of the northwest states of the United States of America. Purposive sampling of eight women included women between the ages of 40 and 55 years of age. Women who had undergone surgical menopause were excluded as the influence of prolonged hormone replacement therapy was seen as a bias. Data was collected by using an unstructured interview technique. Data was analyzed according to Tesch's protocol (in Cresswell, 1994:155). Guba's model (in Krefting 1991:215) was utilized to ensure the trustworthiness of the study. Ethical issues were considered throughout and these are reflected in chapter one of the thesis. The study identified two themes: (1) how the women experienced midlife and (2) how they managed it. The experiences of midlife were expressed in physical, psychosocial and spiritual changes while the management of the process was accomplished in two ways, namely self-care and the services of healthcare professionals. The researcher identified that health promotion was essential to facilitate the self-care practices of women in midlife. Essential and related attributes of health promotion were identified, analyzed and synthesized to define health promotion. The process of health promotion was then defined with a description of the structure and process of the model. Concepts identified were classified, defined and placed into relationship statements after which the model was described and evaluated. Guidelines to operationalize the model were then formulated to assist health professionals to support women in self-care for the attainment of wholeness. / Health Studies / D.Litt et Phil (Health Studies)

The concept of population ageing is a development issue that has received much attention due to the demographic transition that is occurring globally, marked by declining levels of fertility and mortality. Therefore, the implications of population ageing for older persons within the context of Social Development was examined from the perspective of government and non government officials. The study was confined to older persons and the policies and programmes implemented by the Department of Social Development. The study employed an exploratory research design within a qualitative paradigm. Semi-structured interviews and a questionnaire were distributed to officials in the nine provinces. Thirty six questionnaires were received and qualitative methods of data analysis were used to analyse and interpret the data. The main finding of the study is that there is congruence in what government officials and the non government officials view as implications for older persons. Central to this is that the issue of ageing does not receive attention on the agenda of government. The top five priorities for older persons are healthy ageing, economic security, community/home based care services for older persons, having care and support systems for older persons and an improved quality of life/poverty alleviation. Based on the demographic determinants of population ageing, the findings are that there will be an increased demand for services for older persons which might place a strain on the social assistance and health care programmes. The issue of ageing was viewed positively as an opportunity by government officials and pessimistically as a challenge by NGO’s. The most common problems in old age is a reliance on the younger generation and or the state for their care and support, abuse, high levels of illiteracy and the burden of care for their children and grandchildren. The future older person is likely to be in better health and better educated than the older person of today if the necessary public investments are made now in these areas. The study makes recommendations for the adoption of a South African plan of action on ageing, inter-sectoral budgeting, development of specialised programmes, review of current policies and legislation for older persons, strengthening the partnership with the NGO sector and facilitating ageing mainstreaming within government programmes. / Sociology / M.A. (Social Development)

L’allongement de la durée de la vie humaine et le déficit du rapport démographique constituent de véritables défis pour les systèmes sociaux des États membres. Pour y faire face, les législateurs doivent à la fois développer une politique de protection des plus jeunes dans le cadre des relations professionnelles, tout en revisitant les logiques des seuils d’âge notamment au regard de la fin de ces relations. Cette étude a vocation à s’interroger sur l’existence d’un concept de l’âge. Fort d’une histoire culturelle, confortée par une analyse du phénomène physiologique du vieillissement par le législateur, le critère de l’âge entretient des liens particuliers avec les principes généraux du droit de l’Union, tel que le principe de la dignité humaine et le principe de l’égalité de traitement. Malgré tout, le critère de l’âge conserve une ambivalence certaine, mise en exergue à travers le principe général du droit de l’Union de non-discrimination à raison de l’âge. Cette ambivalence se manifeste plus fortement encore à l’issue des relations professionnelles, posant ainsi la question de la place de l’âge à la fin de la vie active. Ce curseur au soutien du pacte intergénérationnel, conditionnant le bénéfice de la liquidation de la pension, connaît actuellement un renouveau, dépassant les frontières des États membres. Une convergence dans le traitement de la vieillesse se crée, tendant au développement de nouvelles solidarités dans le cadre de l’entreprise (régimes professionnels d’entreprise). Il s’agit en outre de favoriser la poursuite de l’activité à un âge élevé (relèvement de l’âge légal de la retraite, décote, surcote, encadrement des régimes dérogatoires, prohibition des ruptures de la relation de travail fondée sur l’âge…) et de repenser les rapports entre les relations de travail et l’âge (cumul emploi - retraite, retraite progressive…). Ce faisant, les législateurs promeuvent un traitement de l’âge qui s’inscrit dans la problématique générale de la longévité humaine en Europe / Dealing with longer life expectancy and demographic deficit is currently a huge challenge for the social system of European member states. To face this challenge, it is necessary for legislators to develop a dedicated protection policy for the young people in a business relationship context and, at the same time, to redefine age limits policy especially in business relationship termination situation.. The presented study focuses on the factuality of the « age » concept. Based on cultural history, confirmed by the legislator analysis of the physiological aging, « age » criterion is closely linked to general principles in E.U. legislation like, for example, the human dignity and the equal treatment. However, the « age » criterion still remains ambivalent which is underlined by the non-discrimination principle. This ambiguity is emphasized in business relationships which leads to the influence of the « age » in an ending working life situation. This intergenerational pact support, which influence the proceed of the pension liquidation, is currently experiencing a revival beyond E.U. member state boundaries. A converging point is achieved in old-age treatment which leads to new solidarity development schemes inside companies (like for example the company occupational scheme). An important objective is to promote the pursuance of a professional activity in order to retire later (increasing in the statutory retirement age, increment or reduce of the retirement pension, restriction of derogations, proscription of business relationship breaches if they are based on age, …) and to redefine the connection between age and business relationships (combined work and retirement, phased retirement, …). By this way, legislators promote a human longevity based age treatment in Europe

In this study, buckwheat (Fagopyrum esculentum Moench) and alyssum (Lobularia maritima (L.)) flowers were used to examine the effect of floral resources on the efficacy of the leafroller parasitoid Dolichogenidea tasmanica (Cameron) in vineyards. This was done by assessing the influence of these flowers on parasitoid abundance and parasitism rate, and by investigating the consequences of this for leafroller abundance. In laboratory experiments, alyssum flowers were used to investigate the effect of floral food on the longevity, fecundity and sex ratio of D. tasmanica. Dolichogenidea tasmanica comprised more than 95 % of parasitoids reared from field collected leafrollers in this study. The abundance of D. tasmanica during the 1999-2000 growing season was very low compared with previous studies, possibly due to the very low abundance of its leafroller hosts during the experiment. The number of males of this species on yellow sticky traps was increased (although not significantly) when buckwheat flowers were planted in a Marlborough vineyard; however, the number of female D. tasmanica on traps was no greater with flowers than without. The abundance of another leafroller parasitoid, Glyptapanteles demeter (Wilkinson)(Hymenoptera: Braconidae), on traps was also not significantly affected by the presence of buckwheat flowers, although females of this species were caught in greater numbers in the control than in buckwheat plots. Naturally-occurring leafrollers were collected from three vineyard sites in Marlborough, and one in Canterbury during the 2000-2001 season to assess the effect of buckwheat and alyssum flowers on parasitism rate. Parasitism rate more than doubled in the presence of buckwheat at one of the Marlborough vineyards, but alyssum had no effect on parasitism rate in Canterbury. A leafroller release/recover method, used when naturally-occurring leafrollers were too scarce to collect, was unable to detect any effect of buckwheat or alyssum on parasitism rate. Mean parasitism rates of approximately 20 % were common in Marlborough, although rates ranged from 0 % to 45 % across the three vineyard sites in that region. In Canterbury in April, mean parasitism rates were approximately 40 % (Chapter 4). Rates were higher on upper canopy leaves (40-60 %) compared with lower canopy leaves and bunches (0-25 %). Leafroller abundance was apparently not affected by the presence of buckwheat in Marlborough, or alyssum in Canterbury. Buckwheat did, however, significantly reduce the amount of leafroller evidence (webbed leafroller feeding sites on leaves or in bunches) in Marlborough, suggesting that the presence of these flowers may reduce leafroller populations. Leafrollers infested less than 0.1 % of Cabernet Sauvignon leaves throughout the 1999-2000 growing season, but increased in abundance in bunches to infest a maximum of 0.5 % of bunches in late March in Marlborough. In Pinot Noir vines in the 2000-2001 season, leafroller abundance was also low, although sampling was not conducted late in the season when abundance reaches a peak. In Riesling vines in Canterbury, between 1.5 % and 2.5 % of bunches were infested with leafrollers in April. In the laboratory, alyssum flowers significantly increased the longevity and lifetime fecundity of D. tasmanica compared with a no-flower treatment. However, daily fecundity was not increased by the availability of food, suggesting that the greater lifetime fecundity was related to increases in longevity. Parasitoids were also able to obtain nutrients from whitefly honeydew, which resulted in similar longevity and daily fecundity to those when alyssum flowers were present. The availability of food had a significant effect on the offspring sex ratio of D. tasmanica. Parasitoids reared from naturally-occurring leafrollers produced an equal sex ratio, assumed to be the evolutionarily stable strategy (ESS) for this species. In the laboratory, this ESS was observed only when parasitoids had access to alyssum flowers. Without food, or with honeydew only, sex ratios were strongly male-biased. In the field, floral resources affected the sex ratio of D. tasmanica only when this species was reared from leafrollers released and recovered in Marlborough. In that experiment, buckwheat shifted the sex ratio in favour of female production from the equal sex ratio found in control plots. No firm explanations can be given to account for these results, due to a lack of research in this area. Possible mechanisms for the changes in sex ratio with flowers are discussed. This study demonstrated that flowers are an important source of nutrients for D. tasmanica, influencing the longevity, fecundity and offspring sex ratio of this species. However, only some of the field experiments were able to show any positive effect of the provision of floral resources on parasitoid abundance or parasitism rate. More information is needed on the role these parasitoids, and other natural enemies, play in regulating leafroller populations in New Zealand vineyards, and on how they use floral resources in the field, before recommendations can be made regarding the adoption of this technology by growers.

科学研究費補助金 研究種目:一般研究(C) 課題番号:03660013 研究代表者:田代 亨 研究期間:1991-1992年度

This phenomenological study examined the experiences of women in midlife. The primary purpose of the study was to develop and describe a model of health promotion that will facilitate self-care of women in midlife to support them in the attainment of wholeness. A theory-generative, qualitative, explorative, descriptive and contextual design was utilized to achieve the objectives of the study, namely to explore and describe women's experience of midlife transition; classify concepts of the model; describe the structure and process of a model for support of women during midlife transition, and develop guidelines for operationalization of the model. The study was undertaken in one of the northwest states of the United States of America. Purposive sampling of eight women included women between the ages of 40 and 55 years of age. Women who had undergone surgical menopause were excluded as the influence of prolonged hormone replacement therapy was seen as a bias. Data was collected by using an unstructured interview technique. Data was analyzed according to Tesch's protocol (in Cresswell, 1994:155). Guba's model (in Krefting 1991:215) was utilized to ensure the trustworthiness of the study. Ethical issues were considered throughout and these are reflected in chapter one of the thesis. The study identified two themes: (1) how the women experienced midlife and (2) how they managed it. The experiences of midlife were expressed in physical, psychosocial and spiritual changes while the management of the process was accomplished in two ways, namely self-care and the services of healthcare professionals. The researcher identified that health promotion was essential to facilitate the self-care practices of women in midlife. Essential and related attributes of health promotion were identified, analyzed and synthesized to define health promotion. The process of health promotion was then defined with a description of the structure and process of the model. Concepts identified were classified, defined and placed into relationship statements after which the model was described and evaluated. Guidelines to operationalize the model were then formulated to assist health professionals to support women in self-care for the attainment of wholeness. / Health Studies / D.Litt et Phil (Health Studies)

The concept of population ageing is a development issue that has received much attention due to the demographic transition that is occurring globally, marked by declining levels of fertility and mortality. Therefore, the implications of population ageing for older persons within the context of Social Development was examined from the perspective of government and non government officials. The study was confined to older persons and the policies and programmes implemented by the Department of Social Development. The study employed an exploratory research design within a qualitative paradigm. Semi-structured interviews and a questionnaire were distributed to officials in the nine provinces. Thirty six questionnaires were received and qualitative methods of data analysis were used to analyse and interpret the data. The main finding of the study is that there is congruence in what government officials and the non government officials view as implications for older persons. Central to this is that the issue of ageing does not receive attention on the agenda of government. The top five priorities for older persons are healthy ageing, economic security, community/home based care services for older persons, having care and support systems for older persons and an improved quality of life/poverty alleviation. Based on the demographic determinants of population ageing, the findings are that there will be an increased demand for services for older persons which might place a strain on the social assistance and health care programmes. The issue of ageing was viewed positively as an opportunity by government officials and pessimistically as a challenge by NGO’s. The most common problems in old age is a reliance on the younger generation and or the state for their care and support, abuse, high levels of illiteracy and the burden of care for their children and grandchildren. The future older person is likely to be in better health and better educated than the older person of today if the necessary public investments are made now in these areas. The study makes recommendations for the adoption of a South African plan of action on ageing, inter-sectoral budgeting, development of specialised programmes, review of current policies and legislation for older persons, strengthening the partnership with the NGO sector and facilitating ageing mainstreaming within government programmes. / Sociology / M.A. (Development Studies)

No description available.