Deletion of Tumor Necrosis Factor-alpha Receptor 1 (TNFR1) Protects against Diet-induced Obesity by Means of Increased Thermogenesis

In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-alpha (TNF-alpha) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most of TNF-alpha inflammatory signals are delivered by TNF receptor 1 (R1); however, the role played by this receptor in the context of obesity-associated inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1 KO) mice are protected from diet-induced obesity due to increased thermogenesis. Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less body mass despite increased caloric intake. Visceral adiposity and mean adipocyte diameter are reduced and blood concentrations of insulin and leptin are lower. Protection from hypothalamic leptin resistance is evidenced by increased leptin-induced suppression of food intake and preserved activation of leptin signal transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO mice present a significantly increased expression of the thermogenesis-related neurotransmitter, TRH. Further evidence of increased thermogenesis includes increased O(2) consumption in respirometry measurements, increased expressions of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and increased O(2) consumption by isolated skeletal muscle fiber mitochondria. This demonstrates that TNF-alpha signaling through TNFR1 is an important mechanism involved in obesity-associated defective thermogenesis.

Opposite effects of fasting on TGF-beta 3 and T beta RI distribution in the gastric mucosa of suckling and early weanling rats

Objective: Our aim was to evaluate the effects of a dietary regimen (suckling or early weaning) and feeding status (fed or fasted) on the distribution of transforming growth factor-beta 3 (TGF-beta 3) and TGF receptor-I (T beta RI) in the gastric epithelium of pups Methods: Wistar rats were used At 15 d, half of the pups were separated from dams and fed with hydrated powered chow On day 17, suckling and early weanling rats were subjected to fasting (17 h). Four different conditions were established. suckling fed and fasted and early weanling fed and fasted At 18 d stomachs were collected under anesthesia and were fixed in 4% formaldehyde for immunohistochemistry The number of immunostained epithelial cells per microscopic field was determined for TGF-beta 3 and T beta RI in longitudinal sections from the gastric mucosa Results: We found that during suckling, fasting reduced the number of immunolabeled cells per field of both molecules when compared with the fed group (P < 0.05), whereas in early weaning, food restriction increased TGF-beta 3 and T beta RI distributions (P < 0.05) We also observed that TGF-beta 3 and T beta RI were more concentrated in parietal cells in the upper gland in suckling pups, whereas after early weaning these were displaced to parietal and chief cells at the bottom of the gland Conclusion: Suckling and early weaning directly influence TGF-beta 3 and T beta RI distributions in the gastric epithelium in response to fasting, such that early weaning anticipates the effects observed in adult rats. Furthermore, the differential concentrations of TGF-beta 3 and T beta RI indicate that they might be important for cell proliferation events in growth control (C) 2010 Elsevier Inc. All rights reserved

Early weaning accelerates the differentiation of mucous neck cells in rat gastric mucosa: Possible role of TGF alpha/EGFR

The development of the gastric mucosa is controlled by hormones, growth factors and feeding behavior. Early weaning (EW), which means the abrupt interruption of suckling, increases proliferation and differentiation in the rat gastric epithelium. Transforming growth factor alpha(TGF alpha) is secreted in the stomach, binds to the epidermal growth factor receptor( EGFR) and may control cell proliferation, differentiation and migration. Here, we investigated the influence of suckling-weaning transition on the differentiation of mucous neck cells in the stomach and its association to the expression of TGF alpha and EGFR. Fifteen-day-old Wistar rats were divided into two groups: suckling( control), in which pups were kept with the dam, and early weaning( EW), in which rats were separated from their mother and fed with hydrated powdered chow. TGF alpha and EGFR levels were increased at 18 days in EW animals compared to control ones (p<0.05). Histochemical reactions with Periodic Acid-Schiff reagent+Alcian Blue or Bandeiraea simplicifolia II lectin were used to stain the mucous neck cells and showed an increase in this cell population throughout EW, which was more pronounced at 17 days when compared to suckling pups (p<0.05). These morphological results were confirmed by RT-PCR for mucin 6. The levels of mucin 6 mRNA were higher in EW animals from the 16th to the 18th day(1-3 days post-weaning) when compared to the respective control group. Inhibition of EGFR through AG1478 administration to EW animals prevented the expansion of mucous neck cell population induced by EW (p<0.05). Therefore, early weaning up regulated TGF alpha/EGFR expression and induced differentiation of mucous neck cells. Moreover, we showed that EGFR takes part in the maturation of this cell population. We conclude that regular suckling-weaning transition is crucial to guarantee the development of the gastric mucosa. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.

Micronutrient prenatal supplementation prevents the development of hypertension and vascular endothelial damage induced by intrauterine malnutrition

Aims: The premise that intrauterine malnutrition plays an important role in the development of cardiovascular and renal diseases implies that these disorders can be programmed during fetal life. Here, we analyzed the hypothesis that supplementation with mixed antioxidant vitamins and essential mineral in early life could prevent later elevation of blood pressure and vascular and renal dysfunction associated with intrauterine malnutrition. Main methods: For this, female Wistar rats were randomly divided into three groups on day 1 of pregnancy: control fed standard chow ad libitum; restricted group fed 50% of the ad libitum intake and a restricted plus micronutrient cocktail group treated daily with a combination of micronutrient (selenium, folate, vitamin C and vitamin E) by oral gavage. Key findings: In adult offspring, renal function and glomerular number were impaired by intrauterine malnutrition. and the prenatal micronutrient treatment did not prevent it. However, increased blood pressure and reduced endothelium-dependent vasodilation were prevented by the micronutrient prenatal treatment. Intrauterine malnutrition also led to reduced NO production associated with increased superoxide generation, and these parameters were fully normalized by this prenatal treatment. Significance: Our current findings indicate that programming alterations during fetal life can be prevented by interventions during the prenatal period, and that disturbance in availability of both antioxidant vitamins and mineral may play a crucial role in determining the occurrence of long-term cardiovascular injury. (C) 2009 Elsevier Inc. All rights reserved.

Sleep deprivation of rats: The hyperphagic response is real

Study Objectives: Chronic sleep deprivation of rats causes hyperphagia without body weight gain. Sleep deprivation hyperphagia is prompted by changes in pathways governing food intake; hyperphagia may be adaptive to sleep deprivation hypermetabolism. A recent paper suggested that sleep deprivation might inhibit ability of rats to increase food intake and that hyperphagia may be an artifact of uncorrected chow spillage. To resolve this, a palatable liquid diet (Ensure) was used where spillage is insignificant. Design: Sleep deprivation of male Sprague Dawley rats was enforced for 10 days by the flowerpot/platform paradigm. Daily food intake and body weight were measured. On day 10, rats were transcardially perfused for analysis of hypothalamic mRNA expression of the orexigen, neuropeptide Y (NPY). Setting: Morgan State University, sleep deprivation and transcardial perfusion; University of Maryland, NPY in situ hybridization and analysis. Measurements and Results: Using a liquid diet for accurate daily measurements, there was no change in food intake in the first 5 days of sleep deprivation. Importantly, from days 6-10 it increased significantly, peaking at 29% above baseline. Control rats steadily gained weight but sleep-deprived rats did not. Hypothalamic NPY mRNA levels were positively correlated to stimulation of food intake and negatively correlated with changes in body weight. Conclusion: Sleep deprivation hyperphagia may not be apparent over the short term (i.e., <= 5 days), but when extended beyond 6 days, it is readily observed. The timing of changes in body weight and food intake suggests that the negative energy balance induced by sleep deprivation prompts the neural changes that evoke hyperphagia.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 mu M epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.

Actitudes hacia el catalán : un estudio sociolingüístico de principiantes del catalán en Barcelona

This study focuses on the Catalan language of Catalonia, a region located in the east of Spain. There are many immigrants living in this region who decide to learn the Catalan language in hope of finding a job or to integrate in the Catalan society. The main aim of this study was to discover the types of language attitudes the beginners of Catalan show towards this language (general, instrumental and integrative attitudes). Language attitudes are of importance because it can indicate the “health” of a minority language, such as is usually considered Catalan. The method applied was direct, where the informants had to answer a written questionnaire. The results of the study show positive attitudes towards the Catalan language and its general use in Catalonia. The main conclusions of the study were that the informants showed positive and slightly more instrumental attitudes towards Catalan, indicating that the main motive of learning the language was more of practical use than integrative motives.

Inte bara jämställdhet : Beslutet om föräldraledighet, moderskaps- och faderskapsidealoch idéer om barns bästa

More than gender equality. Decisions on parental leave and ideals around motherhood, fatherhood and the best interest of the child On the basis of 40 semi-structured interviews, this study discusses decision making processes regarding parental leave among nascent first-time middle-class parents in Sweden. We analyze motives and ideas behind the couples’ plans and decisions and how decisions on parental leave were made. We furthermore show how the decision making processes can be discussed in relation to the institutional context. The results show that ideals and norms of gender equality are accompanied by gendered divisions of work and care and a partially traditional view on motherhood and fatherhood. Contrary to previous studies, we do not find a clear link between gender equal ideals and explicit negotiations. An equal division of parental leave is, in some couples, taken for granted to such an extent that the decision on how to divide the leave is taken implicitly rather than explicitly. Decisions on division of parental leave are not isolated processes. Rather, ideals and norms around motherhood, fatherhood, gender equality and not least what is ‘in the best interest of the child’ constitute part of the context in which these decision making processes take place.

Att leva och sälja sin dröm : Livsstilsföretagaren mellan familjeliv, marknadoch politisk retorik

Living and selling a dream: Lifestyle entrepreneurship in the intersection between family, market and political rhetoric The article focuses on lifestyle entrepreneurship, characterised by a balancing work between personal lifestyle motives and economic motives. It builds on a qualitative study of business owners who have realized a life dream of starting a countryside business in the tourism and hospitality industry in Sweden. Through the notion of ”balancing work”, the analysis focuses on the tension between a personal life sphere and a market. In particular, the analysis highlights how the notion of ”the life dream” emerges as a narrative practice of self-realization, simultaneously as it is offered as an experience product. The analysis demonstrates how the entrepreneurs balance between personal stories of togetherness and marketing practices, between images of right and wrong commodification, and between constraining working conditions and a popular image of the successful entrepreneur, reinforced by a political discourse on rural entrepreneurship. It is concluded that balancing work between personal identities and economic practices is a practice of valuation, offering new insights into working conditions and markets situated in the intersection between markets and personal life spheres.

Fan Culture as an Informal Learning Environment : Presentation of a NGL project

Fan culture is a subculture that has developed explosively on the internet over the last decades. Fans are creating their own films, translations, fiction, fan art, blogs, role play and also various forms that are all based on familiar popular culture creations like TV-series, bestsellers, anime, manga stories and games. In our project, we analyze two of these subculture genres, fan fiction and scanlation. Amateurs, and sometimes professional writers, create new stories by adapting and developing existing storylines and characters from the original. In this way, a "network" of texts occurs, and writers step into an intertextual dialogue with established writers such as JK Rowling (Harry Potter) and Stephanie Meyer (Twilight). Literary reception and creation then merge into a rich reciprocal creative activity which includes comments and feedback from the participators in the community. The critical attitude of the fans regarding quality and the frustration at waiting for the official translation of manga books led to the development of scanlation, which is an amateur translation of manga distributed on the internet.  Today, young internet users get involved in conceptual discussions of intertextuality and narrative structures through fan activity. In the case of scanlation, the scanlators practice the skills and techniques of translating in an informal environment. This phenomenon of participatory culture has been observed by scholars and it is concluded that they contribute to the development of a student’s literacy and foreign language skills. Furthermore, there is no doubt that the fandom related to Japanese cultural products such as manga, anime and videogames is one of the strong motives for foreign students to start learning Japanese. This is something to take into pedagogical consideration when we develop web-based courses. Fan fiction and fan culture make it ​​possible to have an intensive transcultural dialogue between participators throughout the world and is of great interest when studying the interaction between formal and informal learning that puts the student in focus

The Passionate Combining Entrepreneurs

Entrepreneurs are portrayed as salient drivers of regional development and for a number of years nascent entrepreneurs have been studied in a large number of countries as part of the Global Entrepreneurship Monitor project and the Panel Study of Entrepreneurial Dynamics. Scholars have devoted much effort to investigating factors that determine how individuals engage in entrepreneurial activities, with most of the discussion limited to business start-ups. However, since this type of project does not follow identical nascent entrepreneurs over time, limited knowledge exists about their development and whether they stay in this nascent phase for a long time. In practice, it is common for entrepreneurs to run a business and at the same time work in wage work, so-called combining entrepreneurs. In Sweden, almost half of all business owners combine wage work with a business. However, not all combining entrepreneurs will eventually decide to leave the wage work and invest fully in the business. Consequently, much research has focused on the first step of entering entrepreneurship full time, but less has focused on the second step, the transition from the combining phase to full-time self-employment. The aim of this thesis is therefore to contribute to the theory of entrepreneurship by gaining a deeper understanding of combining entrepreneurs and their motives and intentions.   In the context of combining entrepreneurs, the theory of identity, resources and choice overload has been used to examine how entrepreneurs’ age (when starting the business), entrepreneurial tenure (the length of engagement in the side-business), hours spent (weekly involvement in the side-business), involvement in entrepreneurial teams (leading the business with one or more partners) and involvement in networks (business networks) influence their passion for engaging in entrepreneurship while sustaining wage work. Different categories of combining entrepreneurs and their intentions have also been examined.   A survey was administered to 1457 entrepreneurs within the creative sector in two counties in Sweden (Gävleborgs County and Jämtlands County). Since there were no separate mailing lists to only combining entrepreneurs, the survey was sent to all entrepreneurs within the chosen industry and counties. The total response rate was 33.5 percent and of them 57.6 percent combined, yielding 262 combining entrepreneurs who answered the questionnaire. The survey was then followed up with eight focus group interviews and two single interviews to validate the answers from the questionnaire.   The results indicate three types of combining entrepreneurs: nascent – with the intention to leave the combining phase for a transition into full-time self-employment, lifestyle – with the intention to stay in the combining phase, and occasional – with the intention to leave the combining phase for full-time wage work and close down the business. Transitioning fully to self-employment increases with the individual’s age. Also, a positive interactive effect exists with involvement in entrepreneurial networks. The results also indicate that the ability to work with something one is passionate about is the top motive for combining wage work with a side-business. Passion is also more likely to be the main motive behind the combining form among individuals who are older at business start-up, but passion is less likely to be the main motive behind the combining form among individuals who spend more time on the business. The longer the individual has had the side-business, the less likely passion is the main motive behind the combining form, and passion is less likely to be the main motive among those who are part of an entrepreneurial team.

Modelling the Provenance of Data in Autonomous Systems

Determining the provenance of data, i.e. the process that led to that data, is vital in many disciplines. For example, in science, the process that produced a given result must be demonstrably rigorous for the result to be deemed reliable. A provenance system supports applications in recording adequate documentation about process executions to answer queries regarding provenance, and provides functionality to perform those queries. Several provenance systems are being developed, but all focus on systems in which the components are textitreactive, for example Web Services that act on the basis of a request, job submission system, etc. This limitation means that questions regarding the motives of autonomous actors, or textitagents, in such systems remain unanswerable in the general case. Such questions include: who was ultimately responsible for a given effect, what was their reason for initiating the process and does the effect of a process match what was intended to occur by those initiating the process? In this paper, we address this limitation by integrating two solutions: a generic, re-usable framework for representing the provenance of data in service-oriented architectures and a model for describing the goal-oriented delegation and engagement of agents in multi-agent systems. Using these solutions, we present algorithms to answer common questions regarding responsibility and success of a process and evaluate the approach with a simulated healthcare example.

A Complexity Based Model for Quantifying Forensic Evidential Probabilities

An operational complexity model (OCM) is proposed to enable the complexity of both the cognitive and the computational components of a process to be determined. From the complexity of formation of a set of traces via a specified route a measure of the probability of that route can be determined. By determining the complexities of alternative routes leading to the formation of the same set of traces, the odds ratio indicating the relative plausibility of the alternative routes can be found. An illustrative application to a BitTorrent piracy case is presented, and the results obtained suggest that the OCM is capable of providing a realistic estimate of the odds ratio for two competing hypotheses. It is also demonstrated that the OCM can be straightforwardly refined to encompass a variety of circumstances.

Exploration of the idea of the horse in graphics and sculpture

The exploration of the idea of the horse is a very complex and open quest. Primarily it entails some conception of what the idea of the horse is. In choosing to title the project as such, I was attempting to indicate that what was of major interest to me was the representation of those qualities of the horse which are abstract and intangible as well as the physical qualities of the horse. Because of this interest, much of my work is concerned with movement, gesture, and the effects of structure, or lack thereof, on movement and gesture.