UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression

Bromati CR, Lellis-Santos C, Yamanaka TS, Nogueira TC, Leonelli M, Caperuto LC, Gorjao R, Leite AR, Anhe GF, Bordin S. UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression. Am J Physiol Regul Integr Comp Physiol 300: R92-R100, 2011. First published November 10, 2010; doi:10.1152/ajpregu.00169.2010.-Endocrine pancreas from pregnant rats undergoes several adaptations that comprise increase in beta-cell number, mass and insulin secretion, and reduction of apoptosis. Lactogens are the main hormones that account for these changes. Maternal pancreas, however, returns to a nonpregnant state just after the delivery. The precise mechanism by which this reversal occurs is not settled but, in spite of high lactogen levels, a transient increase in apoptosis was already reported as early as the 3rd day of lactation (L3). Our results revealed that maternal islets displayed a transient increase in DNA fragmentation at L3, in parallel with decreased RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation (pAKT), a known prosurvival kinase. Wortmannin completely abolished the prosurvival action of prolactin (PRL) in cultured islets. Decreased pAKT in L3-islets correlated with increased Tribble 3 (TRB3) expression, a pseudokinase inhibitor of AKT. PERK and eIF2 alpha phosphorylation transiently increased in islets from rats at the first day after delivery, followed by an increase in immunoglobulin heavy chain-binding protein (BiP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islets from L3 rats. Chromatin immunoprecipitation (ChIP) and Re-ChIP experiments further confirmed increased binding of the heterodimer ATF4/CHOP to the TRB3 promoter in L3 islets. Treatment with PBA, a chemical chaperone that inhibits UPR, restored pAKT levels and inhibited the increase in apoptosis found in L3. Moreover, PBA reduced CHOP and TRB3 levels in beta-cell from L3 rats. Altogether, our study collects compelling evidence that UPR underlies the physiological and transient increase in beta-cell apoptosis after delivery. The UPR is likely to counteract prosurvival actions of PRL by reducing pAKT through ATF4/CHOP-induced TRB3 expression.

Glucocorticoids in Vivo Induce Both Insulin Hypersecretion and Enhanced Glucose Sensitivity of Stimulus-Secretion Coupling in Isolated Rat Islets

Although glucocorticoids are widely used as antiinflammatory agents in clinical therapies, they may cause serious side effects that include insulin resistance and hyperinsulinemia. To study the potential functional adaptations of the islet of Langerhans to in vivo glucocorticoid treatment, adult Wistar rats received dexamethasone (DEX) for 5 consecutive days, whereas controls (CTL) received only saline. The analysis of insulin release in freshly isolated islets showed an enhanced secretion in response to glucose in DEX-treated rats. The study of Ca(2+) signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca(2+) signals were found between both groups with tolbutamide or KCl, indicating that the alterations were probably related to metabolism. Thus, mitochondrial function was explored by monitoring oxidation of nicotinamide dinucleotide phosphate autofluorescence and mitochondrial membrane potential. Both parameters revealed a higher response to glucose in islets from DEX-treated rats. The mRNA and protein content of glucose transporter-2, glucokinase, and pyruvate kinase was similar in both groups, indicating that changes in these proteins were probably not involved in the increased mitochondrial function. Additionally, we explored the status of Ca(2+)-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase C alpha as well as an increased response of the phospholipase C/inositol 1,4,5-triphosphate pathway in DEX-treated rats. Finally, an increased number of docked secretory granules were observed in the beta-cells of DEX animals using transmission electron microscopy. Thus, these results demonstrate that islets from glucocorticoid-treated rats develop several adaptations that lead to an enhanced stimulus-secretion coupling and secretory capacity. (Endocrinology 151: 85-95, 2010)

Genesis of quantum nonlocality

We revisit the problem of an otherwise classical particle immersed in the zero-point radiation field, with the purpose of tracing the origin of the nonlocality characteristic of Schrodinger`s equation. The Fokker-Planck-type equation in the particles phase-space leads to an infinite hierarchy of equations in configuration space. In the radiationless limit the first two equations decouple from the rest. The first is the continuity equation: the second one, for the particle flux, contains a nonlocal term due to the momentum fluctuations impressed by the field. These equations are shown to lead to Schrodinger`s equation. Nonlocality (obtained here for the one-particle system) appears thus as a property of the description, not of Nature. (C) 2011 Elsevier B.V. All rights reserved.

Aminoacetone, a putative endogenous source of methylglyoxal, causes oxidative stress and death to insulin-producing RINm5f cells

Aminoacetone (AA), triose phosphates, and acetone are putative endogenous sources of potentially cytotoxic and genotoxic methylglyoxal (MG), which has been reported to be augmented in the plasma of diabetic patients. In these patients, accumulation of MG derived from aminoacetone, a threonine and glycine catabolite, is inferred from the observed concomitant endothelial overexpression of circulating semicarbazide-sensitive amine oxidases. These copper-dependent enzymes catalyze the oxidation of primary amines, such as AA and methylamine, by molecular oxygen, to the corresponding aldehydes, NH4+ ion and H2O2. We recently reported that AA aerobic oxidation to MG also takes place immediately upon addition of catalytic amounts of copper and iron ions. Taking into account that (i) MG and H2O2 are reportedly cytotoxic to insulin-producing cell lineages such as RINm5f and that (ii) the metal-catalyzed oxidation of AA is propagated by O-2(center dot-) radical anion, we decided to investigate the possible pro-oxidant action of AA on these cells taken here as a reliable model system for pancreatic beta-cells. Indeed, we show that AA (0.10-5.0 mM) administration to RINm5f cultures induces cell death. Ferrous (50-300 mu M) and Fe3+ ion (100 mu M) addition to the cell cultures had no effect, whereas Cu2+ (5.0-100 mu M) significantly increased cell death. Supplementation of the AA- and Cu2+-containing culture medium with antioxidants, such as catalase (5.0 mu M), superoxide dismutase (SOD, 50 U/mL), and N-acetylcysteine (NAC, 5.0 mM) led to partial protection. mRNA expression of MnSOD, CuZnSOD, glutathione peroxidase, and glutathione reductase, but not of catalase, is higher in cells treated with AA (0.50-1.0 mM) plus Cu2+ ions (10-50 mu M) relative to control cultures. This may imply higher activity of antioxidant enzymes C, in RINm5f AA-treated cells. In addition, we have found that AA (0.50-1.0 mM) Plus Cu2+ (100 mu M) (i) increase RINm5f cytosolic calcium; (ii) promote DNA fragmentation; and (iii) increase the pro-apoptotic (Bax)/antiapoptotic (Bcl-2) ratio at the level of mRNA expression. In conclusion, although both normal and pathological concentrations of AA are probably much lower than those used here, it is tempting to propose that excess AA in diabetic patients may drive oxidative damage and eventually the death of pancreatic beta-cells.

Facile Synthesis of Koser`s Reagent and Derivatives from Iodine or Aryl Iodides

The first one-pot synthesis of neutral and electron-rich [hydroxy(tosyloxy)iodo]arenes (HTIBs) from iodine and arenes is presented, thereby avoiding the need for expensive iodine(III) precursors. A large set of including a polyfluorinated analogue, can be obtained from the corresponding aryl iodide under the same conditions. The reaction proceeds under mild conditions, without excess reagents, and is fast and high-yielding. Together, the two presented routes give access to a wide range of HTIBs, which are useful reagents in a variety of synthetic transformations.

Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice

Aromatherapy uses essential oils (EOs) for several medical purposes, including relaxation. The association between the use of aromas and a decrease in anxiety could be a valuable instrument in managing anxiety in an ever increasing anxiogenic daily life style. Linalool is a monoterpene commonly found as the major volatile component of EOs in several aromatic plant species. Adding to previously reported sedative effects of inhaled linalool, the aim of this study was to investigate the effects of inhaled linalool on anxiety, aggressiveness and social interaction in mice. Additionally, we investigated the effects of inhaled linalool on the acquisition phase of a step-down memory task in mice. Inhaled linalool showed anxiolytic properties in the light/dark test, increased social interaction and decreased aggressive behavior; impaired memory was only seen the higher dose of linalool. These results strengthen the suggestion that inhaling linalool rich essential oils can be useful as a mean to attain relaxation and counteract anxiety. (C) 2009 Elsevier GmbH. All rights reserved.

Museum Personalized : The impact of floor staff on an exhibition - A holistic approach

The current paper presents a study conducted at The National Museum of Science and Technology in Stockholm to investigate the exhibition “Antarctica – that’s cool” from its first concept to the first workshop that is held in the exhibition. The focus is on the influence of floor staff on an exhibition and workshops as learning facilities in museums. Findings, based on visitor observation and the exhibition building process, go into the characteristics of low-budget productions and discuss the importance of staff on the exhibition floor for museums as life-long learning facilities. The holistic approach of the study provides deep insights into the complex interplay of visitors, staff and exhibitions. The results can be used for future exhibition building processes and educational programs in museums and should strengthen the museum’s position as life-long learning facility in nowadays society.

The Evolution of a Responsibility to Protect in Africa : The African Unions Emerging Peace and Security Regime

The thesis focuses on, and tries to evaluate, the role that the African Union (AU) plays in protecting the peace and security on the African continent. The thesis takes an interdisciplinary approach to the topic by both utilizing international relations and international law theories. The two disciplines are combined in an attempt to understand the evolution of the AU’s commitment to the pragmatist doctrine: responsibility to protect (R2P). The AU charter is considered to be the first international law document to cover R2P as it allows the AU to interfere in the internal affairs of its member states. The R2P doctrine was evolved around the notion of a need to arrive at a consensus in regard to the right to intervene in the face of humanitarian emergencies. A part of the post-Cold War shift in UN behaviour has been to support local solutions to local problems. Hereby the UN acts in collaboration with regional organizations, such as the AU, to achieve the shared aspirations to maintain international peace and security without getting directly involved on the ground. The R2P takes a more holistic and long-term approach to interventions by including an awareness of the need to address the root causes of the crisis in order to prevent future resurrections of conflicts. The doctrine also acknowledges the responsibility of the international community and the intervening parties to actively participate in the rebuilding of the post-conflict state. This requires sustained and well planned support to ensure the development of a stable society.While the AU is committed to implementing R2P, many of the AU’s members are struggling, both ideologically and practically, to uphold the foundations on which legitimate intervention rests, such as the protection of human rights and good governance. The fact that many members are also among the poorest countries in the world adds to the challenges facing the AU. A lack of human and material resources leads to a situation where few countries are willing, or able, to support a long-term commitment to humanitarian interventions. Bad planning and unclear mandates also limit the effectiveness of the interventions. This leaves the AU strongly dependent on regional powerbrokers such as Nigeria and South Africa, which in itself creates new problems in regard to the motivations behind interventions. The current AU charter does not provide sufficient checks and balances to ensure that national interests are not furthered through humanitarian interventions. The lack of resources within the AU also generates worries over what pressure foreign nations and other international actors apply through donor funding. It is impossible for the principle of “local solutions for local problems? to gain ground while this donor conditionality exists.The future of the AU peace and security regime is not established since it still is a work in progress. The direction that these developments will take depends on a wide verity of factors, many of which are beyond the immediate control of the AU.

International conference site selection criteria : And a case study of Stockholm as an international conference city

The purpose of this thesis is to identify the destination site selection criteria for internationalconferences from the perspectives of the three main players of the conference industry,conference buyers (organizers and delegates) and suppliers. Additionally, the researchidentifies the strengths and weaknesses of the congress cities of Stockholm and Vienna.Through a comparison with Vienna, the top city for hosting international conferences, a roadmap for Stockholm has been designed, to strengthen its congress tourism opportunities, thus,obtaining a higher status as an international congress city. This qualitative research hascombined both primary and secondary data methods, through semi-standardized expertinterviews and secondary studies respectively, to fulfil the study’s aim. The data have beenanalysed by applying the techniques of qualitative content analysis; the secondary dataadopting an inductive approach according to Mayring (2003) while the expert interviewsusing a deductive approach according to Meuser & Nagel (2009). The conclusions of thesecondary data have been further compared and contrasted with the outcomes of the primarydata, to propose fresh discoveries, clarifications, and concepts related to the site selectioncriteria for international conferences, and for the congress tourism industry of Stockholm. Theresearch discusses the discoveries of the site selection criteria, the implications of thestrengths and weaknesses of Stockholm in comparison to Vienna, recommendations forStockholm via a road map, and future research areas in detail. The findings andrecommendation, not only provide specific steps and inceptions that Stockholm as aninternational conference city can apply, but also propose findings, which can aid conferencebuyers and suppliers to cooperate, to strengthen their marketing strategies and developsuccessful international conferences and destinations to help achieve a greater competitiveadvantage.

PANA V : Evaluation of a Literacy Project

PANA V Evaluation of a Literacy ProjectSUMMARY AND CONCLUSIONSThis evaluation set out to explore the impact of the literacy work carried out through PANA V. It focussed on clarifying effects such as empowerment and poverty reduction in relation to the civil society. Two specific objectives were to evaluate the methodological approach and the didactic materials and to evaluate the sustainability of the project.Although the focus of the evaluation has been PANA V, the project has been evaluated in its context, as one in a series of five projects located in Rwanda ten years after the war and genocide. The conclusion will consider future plans in this field.The evaluator has striven to create a holistic picture of the effects of the project, although the given time for the evaluation was short. Only three weeks were spent in the field study and only ten days in the actual field. Although there were some organisational and logistic problems, as is common when carrying out a study like this in a poor country, many literacy sites were visited and quite many participators were interviewed. The overall impression from the study is overwhelmingly positive. So many people commit themselves in this task of teaching Rwandans reading, writing and numeracy. Despite harsh conditions learners strive to learn and group leaders devote themselves to the task. Many leaders on different levels try their very best to manage their difficult and demanding task. The main objective was to explore the impact of the project on poverty reduction, particularly on empowerment and strategies for everyday life. Women were to be regarded particularly. From the results it is clear that the project has a strong, positive impact both on poverty reduction and empowerment of marginalised groups. Among those who have benefited from the alphabetisation are mainly women. Unfortunately, when it comes to leaders in PANA, who may also be said to have benefited from the project, only a small minority is women. This is something that is recommended that it be reconsidered inside the organisation. As a majority of the targeted learners are women, and as the economic and social situation of women in Rwanda is generally weak, this is a question that I recommend the Pentesostal church and ADEPR to look particularly into. With many women being single breadwinners of their households, it is important that also women get access to positions that may bring benefits of different kind.It is also clear that the project has positive effects for the civil society. In the present situation in Rwanda, during the process of reconciliation and rapid progress, basic education for the poor majority is a democratic issue. In a country with a plethora of internet-cafés in the capital and a small minority that use cars and mobile-telephones to communicate nation-wide, it is of outmost importance that the majority acquires basic education, of which literacy is a central part. To strengthen the civil society in Rwanda literacy is important. One central issue is then that Rwanda develops toward becoming a country where literacy is used for the benefit of the citizens and it is a democratic issue that all citizens get an opportunity to participate. Crucial for this is that strong efforts are put into primary schools nation-wide. Literacy projects for adults, like PANA, may only complement these efforts, but they constitute important and necessary complements. Other relevant ways to promote literacy are campaigns in Radio and TV and through cultural events such as festivals, music and theatre. News papers, magazines and books are natural parts of such campaigns as well as adult education. As stated under the results not much can be said about the didactics in this evaluation. On the whole the methodology and the materials fill their function well and receive a high reputation. As people learn to read and write under very simple conditions, obviously the approach is appropriate. A few suggestions may be given from the study:•Focus groups leaders’ attention on clearness, that they show very clearly what is to be read. Good structuring is probably of great importance for many learners.•Make clear what is tested in the tests and consider the possibility to use a holistic test that would be more congruent with the methodology. The possibility to use only one grade, pass, would enable a more practical test, such as reading a short, relevant text, writing something relevant and solving practical mathematic problems. Avoid tests that demand school knowledge.•Avoid using methaphors such as “fight against illiteracy” and connections between illiteracy/literacy and darkness/light. It is not true that illiteracy causes bad things and that literacy only brings good. •Be prepared that it may be more difficult in the future to achieve the goals as it may be the case that the early learners where the ones who achieved easily. The goal of “literacy in six month” in PANA will probably hold only for some learners but also those who do not manage in six months need literacy skills.A third objective was to secure sustainability. As for sustainability of the project in itself, and of the literacy process, the main conclusion is that there is a good potential. The commitment and devotedness among many involved in PANA proves good. One weakness is individual leaders in ADEPR who do not see this as an important task for the Pentecostal church in Rwanda. Other weaknesses are the unwillingness to mention explicitly the wish, for example among group leaders, to get some kind of incentive and the fear of loosing believers by cooperation with other organisations. A higher degree of transparency in this issue would probably solve some irritations and tensions.As for the sustainability of the literacy skills much may be done to improve. The acquired skills seem to be comparably relevant. The level achieved, and the level tested, may be defined as basic literacy skills, consisting of basic reading, writing and numeracy skills. However, these skills are very restricted and there is a high risk that the skills will decline, which means that there is a high risk that people will forget how to read and write because of lack of exercising. From these conclusions a few suggestions for future development will be given.

The Role of Motivational Strategies in the Upper Elementary Classroom : A systematic literature review about teacher strategies that promote self-confidence, motivation and a conducive learning environment

The aim of this literature review is to investigate which strategies teachers use to motivate pupils to communicate orally in English. The literature review also investigates how these teacher strategies affect pupils. The methodology used for this investigation is a systematic literature review. Various databases have been used when searching for literature. Scientific articles and theses have been searched for. They have also been read and analyzed before they have become a part of this review. The results indicate that some teachers feel insecure when speaking English. Therefore Swedish is spoken in many language classrooms. Teachers speaking in front of the class is the traditional way of teaching, and it does not seem to be a strategy who influences pupils positively. If teachers speak the target language among pupils they often get more motivated and focused pupils who feel comfortable speaking English. Young pupils are fast learners. By exposing them to the English language in early ages they receive great opportunities to learn a foreign language and strengthen their self-confidence. Drama, songs and rhymes are preferable strategies to use when teaching young learners. What position teachers decide to take in the classroom is also a significant element when teaching foreign languages.

Assumptions of retail price strategy and price tactic decisions

This licentiate thesis sets out to analyse how a retail price decision frame can be understood. It is argued that it is possible to view price determination within retailing by determining the level of rationality and using behavioural theories. In this way, it is possible to use assumptions derived from economics and marketing to establish a decision frame. By taking a management perspective, it is possible to take into consideration how it is assumed that the retailer should strategically manage price decisions, which decisions might be assumed to be price decisions, and which decisions can be assumed to be under the control of the retailer. Theoretically, this licentiate thesis has its foundations in different assumptions about decision frames regarding the level of information collected, the goal of the decisions, and the outcomes of the decisions. Since the concepts that are to be analysed within this thesis are price decisions, the latter part of the theory discusses price decision in specific: sequential price decisions, at the point of the decision, and trade-offs when making a decision. Here, it is evident that a conceptual decision frame that is intended to illustrate price decisions includes several aspects: several decision alternatives and what assumptions of rationality that can be made in relation to the decision frame. A semi-structured literature review was conducted. As a result, it became apparent that two important things in the decision frame were unclear: time assumptions regarding the decisions and the amount of information that is assumed in relation to the different decision alternatives. By using the same articles that were used to adjust the decision frame, a topical study was made in order to determine the time specific assumptions, as well as the analytical level based on the assumed information necessary for individual decision alternatives. This, together with an experimental study, was necessary to be able to discuss the consequences of the rationality assumption. When the retail literature is analysed for the level of rationality and consequences of assuming certain assumptions of rationality, three main things becomes apparent. First, the level of rationality or the assumptions of rationality are seldom made or accounted for in the literature. In fact, there are indications that perfect and bounded rationality assumptions are used simultaneously within studies. Second, although bounded rationality is a recognised theoretical perspective, very few articles seem to use these assumptions. Third, since the outcome of a price decision seems to provide no incremental sale, it is questionable which assumptions of rationality that should be used. It might even be the case that no assumptions of rationality at all should be used. In a broader perspective, the findings from this licentiate thesis show that the assumptions of rationality within retail research is unclear. There is an imbalance between the perspectives used, where the main assumptions seem to be concentrated to perfect rationality. However, it is suggested that by clarifying which assumptions of rationality that is used and using bounded rationality assumptions within research would result in a clearer picture of the multifaceted price decisions that could be assumed within retailing. The theoretical contribution of this thesis mainly surround the identification of how the level of rationality provides limiting assumptions within retail research. Furthermore, since indications show that learning might not occur within this specific context it is questioned whether the basic learning assumption within bounded rationality should be used in this context.

Self-reported conflict management competence among nursing students on the point of graduating and registered nurses with professional experience

Objective: It has been shown that specific competence is necessary for preventing and managing conflicts in healthcare settings. The aim of this descriptive and correlation study was to investigate and compare the self-reported conflict management competence (CMC) of nursing students who were on the point of graduating (NSPGs), and the CMC of registered nurses (RNs) with professional experience. Methods: The data collection, which consisted of soliciting answers to items measuring CMC in the Nurse Professional Competence (NPC) Scale, was performed as a purposive selection of 11 higher education institutions (HEIs) in Sweden. Three CMC items from the NPC Scale were answered by a total of 569 nursing students who were on the point of graduating and 227 RN registered nurses with professional experience. Results: No significant differences between NSPGs and RNs were found, and both groups showed a similar score pattern, with the lowest score for the item: “How do you perceive your ability to develop the group and strengthen competence in conflict management and problem-solving, based on knowledge of group dynamics?”. RNs with long professional experience (>24 months) rated their overall CMC as significantly better than RNs with short (<24 months) professional experience did (p = .05). NSPGs who had experience of international studies during their nursing education reported higher CMC, compared with those who did not have this experience (p = .03). RNs who reported a high degree of utilisation of CMC during the previous month scored higher regarding self-reported overall CMC (p < .0001). Conclusions: Experience of international studies during nursing education, or long professional experience, resulted in higher self-reported CMC. Hence, the CMC items in the NPC Scale can be suitable for identifying self-reported conflict management competence among NSPGs and RNs