Preschoolers’ Executive Control and Diurnal Cortisol as Mediators of the Relations of Prenatal Stress to Child Adjustment

Thesis (Ph.D.)--University of Washington, 2016-08

Aflatoxin B1 and M1 Degradation by Lac2 from Pleurotus pulmonarius and Redox Mediators

Laccases (LCs) are multicopper oxidases that find application as versatile biocatalysts for the green bioremediation of environmental pollutants and xenobiotics. In this study we elucidate the degrading activity of Lac2 pure enzyme form Pleurotus pulmonarius towards aflatoxin B1 (AFB1) and M1 (AFM1). LC enzyme was purified using three chromatographic steps and identified as Lac2 through zymogram and LC-MS/MS. The degradation assays were performed in vitro at 25 °C for 72 h in buffer solution. AFB1 degradation by Lac2 direct oxidation was 23%. Toxin degradation was also investigated in the presence of three redox mediators, (2,2′-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid]) (ABTS) and two naturally-occurring phenols, acetosyringone (AS) and syringaldehyde (SA). The direct effect of the enzyme and the mediated action of Lac2 with redox mediators univocally proved the correlation between Lac2 activity and aflatoxins degradation. The degradation of AFB1 was enhanced by the addition of all mediators at 10 mM, with AS being the most effective (90% of degradation). AFM1 was completely degraded by Lac2 with all mediators at 10 mM. The novelty of this study relies on the identification of a pure enzyme as capable of degrading AFB1 and, for the first time, AFM1, and on the evidence that the mechanism of an effective degradation occurs via the mediation of natural phenolic compounds. These results opened new perspective for Lac2 application in the food and feed supply chains as a biotransforming agent of AFB1 and AFM1.

Tutors as mediators of exchange student experiences: evaluation of the international student tutor system at the University of Turku

As academic student mobility is increasing, improving the functionality of international operations is recognised as a competitive advantage at tertiary education institutions. Although many scholars have researched the experiences of exchange students, the role of student tutors and their contribution to exchange students’ experiences is still an unknown factor. This research examines international tutoring at the University of Turku, and aims to understand better the way tutoring contributes to exchange experiences and to explore the functionality of the tutor system and discover areas for improvements. To achieve these goals, the research seeks to answer the fundamental research question: What is the role of tutors in mediating exchange experiences? The theoretical framework combines literature on mediating exchange experiences, the phenomenon of studying abroad, the process of adaptation, the importance of cross-cultural communication, and the role of student tutors as mediators. Based on the literature review, a theoretical model for studying the mediation of exchange experiences is introduced. The model’s applicability and validity is examined through a case study. Three methods were used in the empirical research: surveys, participant observations, and interviews. These methods provided extensive data from three major parties of the tutor system: tutors, exchange students, and the international office. The findings of the research reveal that tutoring – instrumental leading and social and cultural mediating – generates both negative and positive experiences depending on the individuals’ expectations, motivations, relationships, and the nature of the tutoring. Although functional, there are a few weaknesses in the tutor system. Tutors tend to act as effective instrumental leaders, but often fail to create a friendship and contribute to the exchange students’ experience through social and cultural mediation, which is significantly more important in the exchange students’ overall experience in terms of building networks, adapting, gaining emotional experiences, and achieving the stage of personal development and mental change. Based on the weaknesses, three improvements are suggested: (1) increasing comprehensive sharing of information, effective communication, and collective cooperation, (2) emphasising the importance of social and cultural mediation and increasing the frequency of interaction between tutors and exchange students, and (3) improving the recruitment and training, revising the process of reporting and rewarding, and finally, enhancing services and coordination.

Toward Self-Organising Service Communities

This paper discusses a framework in which catalog service communities are built, linked for interaction, and constantly monitored and adapted over time. A catalog service community (represented as a peer node in a peer-to-peer network) in our system can be viewed as domain specific data integration mediators representing the domain knowledge and the registry information. The query routing among communities is performed to identify a set of data sources that are relevant to answering a given query. The system monitors the interactions between the communities to discover patterns that may lead to restructuring of the network (e.g., irrelevant peers removed, new relationships created, etc.).

Situating Design Research within Social Framework

This paper explores the expertise in industrial (product) design and contribution of knowledge generated trough the design research. Within this approach the research is situated within the social structure that constitutes people, activity, context and culture where an artifact is seen to be a mediator for the generation of new knowledge and its application. The paper concludes about the importance of research and practice integration and points out that situating the research around the artifacts, as mediators of knowledge, is transferable to Human-Computer Interaction field and any other area of the design research

The Financial Benefit For Insurers : Mediate in Personal Injuries Disputes

Resolving insurance disputes can focus only on quantum. Where insurers adopt integrative solutions they can enjoy cost savings and higher customer satisfaction. An integratively managed process can expand the negotiation options. The potential inherent in plaintiff’s emotions to resolve matters on an emotional basis, rather than an economic one, is explored. Using research, the author demonstrates how mediations are more likely to obtain integrative outcomes than unmediated conferences. Using a combination of governmental reports, published studies and academic publications, the paper demonstrates how mediation is more likely to foster an environment where the parties communicate and cooperate. Research is employed to demonstrate where mediators can reduce hostilities, in circumstances where negotiating parties alone would likely fail. Generally the paper constructs an argument to support the proposition that mediation can offer insurers an effective mechanism to reduce costs and increase customer satisfaction. INTRODUCTION Mediation can offer insurers an effective mechanism to reduce costs and increase customer satisfaction. This paper will first demonstrate the differences between distributive and integrative outcomes. It is argued insurer’s interest can be far better served through obtaining an integrative solution. The paper explains how the mediator can assist both parties to obtain an integrative outcome. Simultaneously the paper explores the extreme difficulties conference participants face in obtaining an integrative outcome without a mediator in an adversarial climate. The mediator’s ability to assist in the facilitation of integrative information exchange, defuse hostilities and reality check expectations is discussed. The mediator’s ability to facilitate in this area is compared to the inability of conference participants to achieve similar results. This paper concludes, the potential financial benefit offered by integrative solutions, combined with the ability of mediation to deliver such outcomes where unmediated conferences cannot deliver, leads to the recommendation that insurers opt for a mediation to best serve their commercial interests.

Sharing knowledge at work : macro, social and relational individual influences on individual behavior

The impact of relations between an organization and its workers and the relations among workers on individual knowledge generation and sharing practices has not, to date, been addressed in an integrated way. This paper discusses the findings of a study analyzing issues at macro, locally-constructed and micro levels in a public sector organization, to identify and integrate the complex sets of mediators. Key factors were found to include (a) the contested nature of the process of knowledge construction, (b) the worker’s experience of the organization’s internal environment, (c) how the organization is understood to value knowledge sharing, (d) relations with colleagues, and (e) the perceived outcomes of knowledge sharing behaviors. Implications for practice are discussed.

Impulsivity and positive psychotic symptoms influence hostility in methamphetamine users

Methamphetamine (MA) use is associated with hostility, aggression, and positive psychotic symptoms. However, little is known of the processes or mechanisms that underlie this relationship. The present research was designed to investigate putative mediating and moderating variables between MA dependence and hostility in a sample of injecting MA users (N=237). Both positive symptoms of psychosis and higher levels of impulsivity functioned as mediators and moderators of this relationship. This pattern of findings suggests that MA use leads to greater hostility by increasing positive psychotic symptoms that contribute to a perception of the environment as a hostile and threatening place as well as by increasing impulsivity. Those who were high in positive symptoms and high in impulsivity were the most hostile. Individual differences in impulsivity and positive psychotic symptoms should be taken into account in the assessment and management of MA dependence.

Kallikrein-related peptidase 4 activation of protease-activated receptor family members and association with prostate cancer

Two areas of particular importance in prostate cancer progression are primary tumour development and metastasis. These processes involve a number of physiological events, the mediators of which are still being discovered and characterised. Serine proteases have been shown to play a major role in cancer invasion and metastasis. The recently discovered phenomenon of their activation of a receptor family known as the protease activated receptors (PARs) has extended their physiological role to that of signaling molecule. Several serine proteases are expressed by malignant prostate cancer cells, including members of the kallikreinrelated peptidase (KLK) serine protease family, and increasingly these are being shown to be associated with prostate cancer progression. KLK4 is highly expressed in the prostate and expression levels increase during prostate cancer progression. Critically, recent studies have implicated KLK4 in processes associated with cancer. For example, the ectopic over-expression of KLK4 in prostate cancer cell lines results in an increased ability of these cells to form colonies, proliferate and migrate. In addition, it has been demonstrated that KLK4 is a potential mediator of cellular interactions between prostate cancer cells and osteoblasts (bone forming cells). The ability of KLK4 to influence cellular behaviour is believed to be through the selective cleavage of specific substrates. Identification of relevant in vivo substrates of KLK4 is critical to understanding the pathophysiological roles of this enzyme. Significantly, recent reports have demonstrated that several members of the KLK family are able to activate PARs. The PARs are relatively new members of the seven transmembrane domain containing G protein coupled receptor (GPCR) family. PARs are activated through proteolytic cleavage of their N-terminus by serine proteases, the resulting nascent N-terminal binds intramolecularly to initiate receptor activation. PARs are involved in a number of patho-physiological processes, including vascular repair and inflammation, and a growing body of evidence suggests roles in cancer. While expression of PAR family members has been documented in several types of cancers, including prostate, the role of these GPCRs in prostate cancer development and progression is yet to be examined. Interestingly, several studies have suggested potential roles in cellular invasion through the induction of cytoskeletal reorganisation and expression of basement membrane-degrading enzymes. Accordingly, this program of research focussed on the activation of the PARs by the prostate cancer associated enzyme KLK4, cellular processing of activated PARs and the expression pattern of receptor and agonist in prostate cancer. For these studies KLK4 was purified from the conditioned media of stably transfected Sf9 insect cells expressing a construct containing the complete human KLK4 coding sequence in frame with a V5 epitope and poly-histidine encoding sequences. The first aspect of this study was the further characterisation of this recombinant zymogen form of KLK4. The recombinant KLK4 zymogen was demonstrated to be activatable by the metalloendopeptidase thermolysin and amino terminal sequencing indicated that thermolysin activated KLK4 had the predicted N-terminus of mature active KLK4 (31IINED). Critically, removal of the pro-region successfully generated a catalytically active enzyme, with comparable activity to a previously published recombinant KLK4 produced from S2 insect cells. The second aspect of this study was the activation of the PARs by KLK4 and the initiation of signal transduction. This study demonstrated that KLK4 can activate PAR-1 and PAR-2 to mobilise intracellular Ca2+, but failed to activate PAR-4. Further, KLK4 activated PAR-1 and PAR-2 over distinct concentration ranges, with KLK4 activation and mobilisation of Ca2+ demonstrating higher efficacy through PAR-2. Thus, the remainder of this study focussed on PAR-2. KLK4 was demonstrated to directly cleave a synthetic peptide that mimicked the PAR-2 Nterminal activation sequence. Further, KLK4 mediated Ca2+ mobilisation through PAR-2 was accompanied by the initiation of the extra-cellular regulated kinase (ERK) cascade. The specificity of intracellular signaling mediated through PAR-2 by KLK4 activation was demonstrated by siRNA mediated protein depletion, with a reduction in PAR-2 protein levels correlating to a reduction in KLK4 mediated Ca2+mobilisation and ERK phosphorylation. The third aspect of this study examined cellular processing of KLK4 activated PAR- 2 in a prostate cancer cell line. PAR-2 was demonstrated to be expressed by five prostate derived cell lines including the prostate cancer cell line PC-3. It was also demonstrated by flow cytometry and confocal microscopy analyses that activation of PC-3 cell surface PAR-2 by KLK4 leads to internalisation of this receptor in a time dependent manner. Critically, in vivo relevance of the interaction between KLK4 and PAR-2 was established by the observation of the co-expression of receptor and agonist in primary prostate cancer and prostate cancer bone lesion samples by immunohistochemical analysis. Based on the results of this study a number of exciting future studies have been proposed, including, delineating differences in KLK4 cellular signaling via PAR-1 and PAR-2 and the role of PAR-1 and PAR-2 activation by KLK4 in prostate cancer cells and bone cells in prostate cancer progression.

Diagramming the interior

Mark Taylor's new essay assesses the impact of the diagram on interior design from the late 19th century to the present. Taylor identifies the pop-cultural discourse of advice writing in both books and magazines as a starting point for his analysis. Drawing on diverse sources, his analysis focuses on texts relating to the dynamics of use and flexibility by Catherine Beecher, Harriet Beecher Stowe, Melusina Fay Peirce, Mary Haweis and Christine Frederick among others. The examples in these texts use the home, domestic housekeeping and kitchens as the sites and practices of intervention through which interior design innovations can be enacted. Taylor's analysis identified the innovations in both the social and the political aspects of space and the critique of static space behind these seemingly amateurish and innocuous texts. Identifying these contributions as early precursors of Modernism's open-plan and flexible, dynamic spaces, Taylor also interprets them with a critical concern for the oppositions and hierarchies that can exist in spatial design, and which are the hallmarks of recent Postmodern, phenomenological approaches to interior design and its theorisations. The progressive and subversive "paradigms for living" implicit in these diagrams can be argued to present a model of greater economic, social and political equality as well as representing a more balanced set of power relations in the home. Progressing through the 20th century to the present, Taylor's analysis shifts byond the dressed body and on to the more intimate rituals of the revealed body to further examine how diagrams of the interior, and the interior as a set of diagrams, are also mediators, sites and grounds for the design of social and sexual intimacy. Through a consideration of the link between design, indentity and intimacy (whether of the invisible, fashioned or sexualised body), the diagrms of interiors are reconfigured as radical and critical tools for an animate, material and emancipatory "redressing" of the balance between the body, identity, sexuality, gender, function, mis(use), aesthetics and the interior.

Ghrelin and obestatin concentrations during puberty: Relationships with adiposity, nutrition and physical activity

Ghrelin and obestatin are two peptides associated with appetite control and the regulation of energy balance in adults. It is intuitive that they have an important role in growth and development during puberty. Therefore, it is acknowledged that these peptides, in addition to others, form part of the substrate underlying energy homeostasis which in turn will contribute to body weight regulation and could explain changes in energy balance during puberty. Both peptides originate from the stomach; hence, it is intuitive that they are involved in generating signals from tissue stores which influence food intake. This could be manifested via alterations in the drive to eat (i.e. hunger), eating behaviors and appetite regulation. Furthermore, there is some evidence that these peptides might also be associated with physical activity behaviors and metabolism. Anecdotally, children and adolescents experience behavioral and metabolic changes during growth and development which will be associated with physiological changes.

Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism

Leukocytes are critical effectors of inflammation and tumor biology. Chemokine-like factors produced by such inflammatory sites are key mediators of tumor growth that activate leukocytic recruitment and tumor infiltration and suppress immune surveillance. Here we report that the endocrine peptide hormone, relaxin, is a regulator of leukocyte biology with properties important in recruitment to sites of inflammation. This study uses the human monocytic cell line THP-1 and normal human peripheral blood mononuclear cells to define a novel role for relaxin in regulation of leukocyte adhesion and migration. Our studies indicate that relaxin promotes adenylate cyclase activation, substrate adhesion, and migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7-dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur primarily in non-adherent cells. Relaxin stimulation results in increased substrate adhesion and increased migratory activity of leukocytes. In addition, relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte chemoattractant protein-1. These responses in THP-1 and peripheral blood mononuclear cells are relaxin dose-dependent and proportional to cAMP accumulation. We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs. In summary, we provide evidence that relaxin is a novel leukocyte stimulatory agent with properties affecting adhesion and chemomigration

The relationship between substrate metabolism, exercise and appetite control : does glycogen availability influence the motivation to eat, energy intake or food choice?

The way in which metabolic fuels are utilised can alter the expression of behaviour in the interests of regulating energy balance and fuel availability. This is consistent with the notion that the regulation of appetite is a psychobiological process, in which physiological mediators act as drivers of behaviour. The glycogenostatic theory suggests that glycogen availability is central in eliciting negative feedback signals to restore energy homeostasis. Due to its limited storage capacity, carbohydrate availability is tightly regulated and its restoration is a high metabolic priority following depletion. It has been proposed that such depletion may act as a biological cue to stimulate compensatory energy intake in an effort to restore availability. Due to the increased energy demand, aerobic exercise may act as a biological cue to trigger compensatory eating as a result of perturbations to muscle and liver glycogen stores. However, studies manipulating glycogen availability over short-term periods (1-3 days) using exercise, diet or both have often produced equivocal findings. There is limited but growing evidence to suggest that carbohydrate balance is involved in the short-term regulation of food intake, with a negative carbohydrate balance having been shown to predict greater ad libitum feeding. Furthermore, a negative carbohydrate balance has been shown to be predictive of weight gain. However, further research is needed to support these findings as the current research in this area is limited. In addition, the specific neural or hormonal signal through which carbohydrate availability could regulate energy intake is at present unknown. Identification of this signal or pathway is imperative if a casual relationship is to be established. Without this, the possibility remains that the associations found between carbohydrate balance and food intake are incidental.

Empathy, neutrality and emotional intelligence: a balancing act for the emotional Einstein

Emotions play a central role in mediation as they help to define the scope and direction of a conflict. When a party to mediation expresses (and hence entrusts) their emotions to those present in a mediation, a mediator must do more than simply listen - they must attend to these emotions. Mediator empathy is an essential skill for communicating to a party that their feelings have been heard and understood, but it can lead mediators into trouble. Whilst there might exist a theoretical divide between the notions of empathy and sympathy, the very best characteristics of mediators (caring and compassionate nature) may see empathy and sympathy merge - resulting in challenges to mediator neutrality. This article first outlines the semantic difference between empathy and sympathy and the role that intrapsychic conflict can play in the convergence of these behavioural phenomena. It then defines emotional intelligence in the context of a mediation, suggesting that only the most emotionally intelligent mediators are able to emotionally connect with the parties, but maintain an impression of impartiality – the quality of remaining ‘attached yet detached’ to the process. It is argued that these emotionally intelligent mediators have the common qualities of strong self-awareness and emotional self-regulation.