Obesity induced by neonatal treatment with monosodium glutamate impairs microvascular reactivity in adult rats: Role of NO and prostanoids

Background and aim: given that obesity is an independent risk factor for the development of cardiovascular diseases we decided to investigate the mechanisms involved in microvascular dysfunction using a monosodium glutamate (MSG)-induced model of obesity, which allows us to work on both normotensive and normoglycemic conditions. Methods and results: Male offspring of Wistar rats received MSG from the second to the sixth day after birth. Sixteen-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia and insulin resistance, with no alteration in glycemia and blood pressure. The effect of norepinephrine (NE), which was increased in MSG rats, was potentiated by L-nitro arginine methyl ester (L-NAME) or tetraethylammonium (TEA) and was reversed by indomethacin and NS-398. Sensitivity to acetylcholine (ACh), which was reduced in MSG rats, was further impaired by L-NAME or TEA, and was corrected by indomethacin, NS-398 and tetrahydrobiopterin (BH4). MSG rats displayed increased endothelium-independent relaxation to sodium nitroprusside. A reduced prostacyclin/tromboxane ratio was found in the mesenteric beds of MSG rats. Mesenteric arterioles of MSG rats also displayed reduced nitric oxide (NO) production along with increased reactive oxygen species (ROS) generation; these were corrected by BH4 and either L-NAME or superoxide dismutase, respectively. The protein expression of eNOS and cyclooxygenase (COX)-2 was increased in mesenteric arterioles from MSG rats. Conclusion: Obesity/insulin resistance has a detrimental impact on vascular function. Reduced NO bioavailability and increased ROS generation from uncoupled eNOS and imbalanced release of COX products from COX-2 play a critical role in the development of these vascular alterations (C) 2010 Elsevier B.V. All rights reserved.

Role of a Novel Tetrodotoxin-Resistant Sodium Channel in the Nitrergic Relaxation of Corpus Cavernosum from the South American Rattlesnake Crotalus Durissus Terrificus

Introduction. Coitus in snakes may last up to 28 hours; however, the mechanisms involved are unknown. Aim. To evaluate the relevance of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) system in snake corpus cavernosum reactivity. Methods. Hemipenes were removed from anesthetized South American rattlesnakes (Crotalus durissus terrificus) and studied by light and scanning electronic microscopy. Isolated Crotalus corpora cavernosa (CCC) were dissected from the non-spiny region of the hemipenises, and tissue reactivity was assessed in organ baths. Main Outcome Measures. Cumulative concentration-response curves were constructed for acetylcholine (ACh), sodium nitroprusside (SNP), 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272), and tadalafil in CCC precontracted with phenylephrine. Relaxation induced by electrical field stimulation (EFS) was also done in the absence and presence of N omega nitro-L-arginine methyl ester (L-NAME; 100 mu M), 1H-[1, 2, 4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mu M) and tetrodotoxin (TTX; 1 mu M). Results. The hemipenes consisted of two functionally concentric corpora cavernosa, one of them containing radiating bundles of smooth muscle fibers (confirmed by alpha-actin immunostaining). Endothelial and neural nitric oxide synthases were present in the endothelium and neural structures, respectively; whereas soluble guanylate cyclase and PDE5 were expressed in trabecular smooth muscle. ACh and SNP relaxed isolated CCC, with the relaxations being markedly reduced by L-NAME and ODQ, respectively. BAY 41-2272 and tadalafil caused sustained relaxations with potency (pEC(50)) values of 5.84 +/- 0.17 and 5.10 +/- 0.08 (N = 3-4), respectively. In precontracted CCC, EFS caused frequency-dependent relaxations that lasted three times longer than those in mammalian CC. Although these relaxations were almost abolished by either L-NAME or ODQ, they were unaffected by TTX. In contrast, EFS-induced relaxations in marmoset CC were abolished by TTX. Conclusions. Rattlesnake CC relaxation is mediated by the NO-cGMP-PDE5 pathway in a manner similar to mammals. The novel TTX-resistant Na channel identified here may be responsible for the slow response of smooth muscle following nerve stimulation and could explain the extraordinary duration of snake coitus. Capel RO, Monica FZ, Porto M, Barillas S, Muscara MN, Teixeira SA, Arruda AMM, Pissinatti, L, Pissinatti A, Schenka AA, Antunes E, Nahoum C, Cogo JC, de Oliveira MA, and De Nucci G. Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus. J Sex Med 2011;8:1616-1625.

Early Phase of Allergic Airway Inflammation in Diabetic Rats: Role of Insulin on the Signaling Pathways and Mediators

Background: Allergic lung inflammation is impaired in diabetic rats and is restored by insulin treatment. In the present study we investigated the effect of insulin on the signaling pathways triggered by allergic inflammation in the lung and the release of selected mediators. Methods: Diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days) and matching controls were sensitized by s.c. injections of ovalbumin (OA) in aluminium hydroxide, 14 days before OA (1 mg/0.4 ml) or saline intratracheal challenge. A group of diabetic rats were treated with neutral protamine Hagedorn insulin (NPH, 4 IU, s.c.), 2 h before the OA challenge. Six hours after the challenge, bronchoalveolar lavage (BAL) was performed for mediator release and lung tissue was homogenized for Western blotting analysis of signaling pathways. Results: Relative to non-diabetic rats, the diabetic rats exhibited a significant reduction in OA-induced phosphorylation of the extracellular signal-regulated kinase (ERK, 59%), p38 (53%), protein kinase B (Akt, 46%), protein kinase C (PKC)-alpha (63%) and PKC-delta (38%) in lung homogenates following the antigen challenge. Activation of the NF-kappa B p65 subunit and phosphorylation of I kappa B alpha were almost suppressed in diabetic rats. Reduced expression of inducible nitric oxide synthase (iNOS, 32%) and cyclooxygenase-2 (COX-2, 46%) in the lung homogenates was also observed. The BAL concentration of prostaglandin (PG)-E(2), nitric oxide (NO) and interleukin (IL)-6 was reduced in diabetic rats (74%, 44% and 65%, respectively), whereas the cytokine-induced neutrophil chemoattractant (CINC)-2 concentration was not different from the control animals. Treatment of diabetic rats with insulin completely or partially restored all of these parameters. This protocol of insulin treatment only partially reduced the blood glucose levels. Conclusion: The data presented show that insulin regulates MAPK, PI3K, PKC and NF-kappa B pathways, the expression of the inducible enzymes iNOS and COX-2, and the levels of NO, PGE(2) and IL-6 in the early phase of allergic lung inflammation in diabetic rats. It is suggested that insulin is required for optimal transduction of the intracellular signals that follow allergic stimulation. Copyright (C) 2010 S. Karger AG, Basel

Toll-like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate ovalbumin-specific allergic airway disease: role of MyD88 adaptor molecule and interleukin-12/interferon-gamma axis

Background Epidemiological and experimental data suggest that bacteria] lipopolysaccharides (LPS) can either protect from or exacerbate allergic asthma. Lipopolysaccharides trigger immune responses through toll-like receptor 4 (TLR4) that in turn activates two major signalling pathways via either MyD88 or TRIF adaptor proteins. The LPS is a pro-Type 1 T helper cells (Th 1) adjuvant while aluminium hydroxide (alum) is a strong Type 2 T helper cells (Th2) adjuvant, but the effect of the mixing of both adjuvants on the development of lung allergy has not been investigated. Objective We determined whether natural (LPS) or synthetic (ER-803022) TLR4 agonists adsorbed onto alum adjuvant affect allergen sensitization and development of airway allergic disease. To dissect LPS-induced molecular pathways, we used TLR4-, MyD88-, TRIF-, or IL-12/IFN-gamma-deficient mice. Methods Mice were sensitized with subcutaneous injections of ovalbumin (OVA) with or without TLR4 agonists co-adsorbed onto alum and challenged with intranasally with OVA. The development of allergic lung disease was evaluated 24 h after last OVA challenge. Results Sensitization with OVA plus LPS co-adsorbed onto alum impaired in dose-dependent manner OVA-induced Th2-mediated allergic responses such as airway eosinophilia, type-2 cytokines secretion, airway hyper-reactivity, mucus hyper production and serum levels of IgE or IgG1 anaphylactic antibodies. Although the levels of IgG2a, Th1 -affiliated isotype increased, investigation into the lung-specific effects revealed that LPS did not induce a Th1 pattern of inflammation. Lipopolysaccharides impaired the development of Th2 immunity, signaling via TLR4 and MyD88 molecules and via the IL-12/IFN-gamma axis, but not through TRIF pathway. Moreover, the synthetic TLR4 agonists that proved to have a less systemic inflammatory response than LPS also protected against allergic asthma development. Conclusion Toll-like receptor 4 agonists co-adsorbed with allergen onto alum down-modulate allergic lung disease and prevent the development of polarized T cell-mediated airway inflammation.

Phosphoproteomics Profiling Suggests a Role for Nuclear beta IPKC in Transcription Processes of Undifferentiated Murine Embryonic Stem Cells

Protein kinase C (PKC) plays a key role in embryonic stem cell (ESC) proliferation, self-renewal and differentiation However, the function of specific PKC Isoenzymes have yet to be determined Of the PKCs expressed in undifferentiated ESCs, beta IPKC was the only isoenzyme abundantly expressed in the nuclei To investigate the role of beta IPKC in these cells, we employed a phosphoproteomics strategy and used two classical (cPKC) peptide modulators and one beta IPKC-specific inhibitor peptide We identified 13 nuclear proteins that are direct or indirect beta IPKC substrates in undifferentiated ESCs These proteins are known to be involved in regulating transcription, splicing, and chromatin remodeling during proliferation and differentiation Inhibiting beta IPKC had no effect on DNA synthesis in undifferentiated ESCs However, upon differentiation many cells seized to express beta IPKC and beta IPKC was frequently found in the cytoplasm Taken together, our results suggest that beta IPKC takes part in the processes that maintain ESCs in their undifferentiated state

Time-dependent increases in ouabain-sensitive Na(+), K(+)-ATPase activity in aortas from diabetic rats: The role of prostanoids and protein kinase C

Aims: Na(+), K(+)-ATPase activity contributes to the regulation of vascular contractility and it has been suggested that vascular Na(+), K(+)-ATPase activity may be altered during the progression of diabetes; however the mechanisms involved in the altered Na(+), K(+)-ATPase activity changes remain unclear. Thus, the aim of the present study was to evaluate ouabain-sensitive Na(+), K(+)-ATPase activity and the mechanism(s) responsible for any alterations on this activity in aortas from 1- and 4-week streptozotocin-pretreated (50 mg kg(-1), i.v.) rats. Main methods: Aortic rings were used to evaluate the relaxation induced by KCl (1-10 mM) in the presence and absence of ouabain (0.1 mmol/L) as an index of ouabain-sensitive Na(+), K(+)-ATPase activity. Protein expression of COX-2 and p-PKC-beta II in aortas were also investigated. Key findings: Ouabain-sensitive Na(+), K(+)-ATPase activity was unaltered following 1-week of streptozotocin administration, but was increased in the 4-week diabetic aorta (27%). Endothelium removal or nitric oxide synthase inhibition with L-NAME decreased ouabain-sensitive Na(+), K(+)-ATPase activity only in control aortas. In denuded aortic rings, indomethacin. NS-398, ridogrel or Go-6976 normalized ouabain-sensitive Na(+), K(+)-ATPase activity in 4-week diabetic rats. In addition, COX-2 (51%) and p-PKC-beta II (59%) protein expression were increased in 4-week diabetic aortas compared to controls. Significance: In conclusion, diabetes led to a time-dependent increase in ouabain-sensitive Na(+), K(+)-ATPase activity. The main mechanism involved in this activation is the release of TxA(2)/PGH(2) by COX-2 in smooth muscle cells, linked to activation of the PKC pathway. (C) 2010 Elsevier Inc. All rights reserved.

Analytic Methods for the Logic of Proofs

The logic of proofs (lp) was proposed as Gdels missed link between Intuitionistic and S4-proofs, but so far the tableau-based methods proposed for lp have not explored this closeness with S4 and contain rules whose analycity is not immediately evident. We study possible formulations of analytic tableau proof methods for lp that preserve the subformula property. Two sound and complete tableau decision methods of increasing degree of analycity are proposed, KELP and preKELP. The latter is particularly inspired on S4-proofs. The crucial role of proof constants in the structure of lp-proofs methods is analysed. In particular, a method for the abduction of proof constant specifications in strongly analytic preKELP proofs is presented; abduction heuristics and the complexity of the method are discussed.

AMIN domains have a predicted role in localization of diverse periplasmic protein complexes

We describe AMIN (Amidase N-terminal domain), a novel protein domain found specifically in bacterial periplasmic proteins. AMIN domains are widely distributed among peptidoglycan hydrolases and transporter protein families. Based on experimental data, contextual information and phyletic profiles, we suggest that AMIN domains mediate the targeting of periplasmic or extracellular proteins to specific regions of the bacterial envelope.

Implementation and role of device management Solutions to the end users

This research is based on consumer complaints with respect to recently purchased consumer electronics. This research document will investigate the instances of development and device management as a tool used to aid consumer and manage consumer’s mobile products in order to resolve issues in or before the consumers is aware one exists. The problem at the present time is that mobile devices are becoming very advanced pieces of technology, and not all manufacturers and network providers have kept up the support element of End users. As such, the subject of the research is to investigate how device management could possibly be used as a method to promote research and development of mobile devices, and provide a better experience for the consumer. The wireless world is becoming increasingly complex as revenue opportunities are driven by new and innovative data services. We can no longer expect the customer to have the knowledge or ability to configure their own device. Device Management platforms can address the challenges of device configuration and support through new enabling technologies. Leveraging these technologies will allow a network operator to reduce the cost of subscriber ownership, drive increased ARPU (Average Revenue per User) by removing barriers to adoption, reduce churn by improving the customer experience and increase customer loyalty. DM technologies provide a flexible and powerful management method but are managing the same device features that have historically been configured manually through call centers or by the end user making changes directly on the device. For this reason DM technologies must be treated as part of a wider support solution. The traditional requirement for discovery, fault finding, troubleshooting and diagnosis are still as relevant with DM as they are in the current human support environment yet the current generation of solutions do little to address this problem. In the deployment of an effective Device Management solution the network operator must consider the integration of the DM platform, interfacing with many areas of the business, supported by knowledge of the relationship between devices, applications, solutions and services maintained on an ongoing basis. Complementing the DM solution with published device information, setup guides, training material and web based tools will ensure the quality of the customer experience, ensuring that problems are completely resolved, driving data usage by focusing customer education on the use of the wireless service In this way device management becomes a tool used both internally within the network or device vendor and by the customer themselves, with each user empowered to effectively manage the device without any prior knowledge or experience, confident that changes they apply will be relevant, accurate, stable and compatible. The value offered by an effective DM solution with an expert knowledge service will become a significant differentiator for the network operator in an ever competitive wireless market. This research document is intended to highlight some of the issues the industry faces as device management technologies become more prevalent, and offers some potential solutions to simplify the increasingly complex task of managing devices on the network, where device management can be used as a tool to aid customer relations and manage customer’s mobile products in order to resolve issues before the user is aware one exists. The research is broken down into the following, Customer Relationship Management, Device management, the role of knowledge with the DM, Companies that have successfully implemented device management, and the future of device management and CRM. And it also consists of questionnaires aimed at technical support agents and mobile device users. Interview was carried out with CRM managers within support centre to further the evidence gathered. To conclude, the document is to consider the advantages and disadvantages of device management and attempt to determine the influence it will have over customer support centre, and what methods could be used to implement it.

Translation, Communication and 'Learning' : Experiences from teaching a master program in Viet Nam

In Vietnam, as in other Asian countries, co-operation with foreign universities plays an important role for the development of higher education. This paper is based on personal experiences from teaching a Swedish Master Programme in Education Science at Vietnam National University in Hanoi. Using theories developed by Lev Vygotsky and Donald Schon, the programme is explored as an inter-cultural learning process. Three aspects are focused upon. Firstly, the fact that communication between students and teachers is conducted with the help of translators who support both teachers and students in their attempt to understand and make themselves understood. Secondly, the expressed need to connect the ideas and techniques which are studied in the programme to the students´ professional worlds. Thirdly, the need to construct a framework wherein the students can inquire into their own situations and to encourage them to try new and more productive ways to deal with problems they are confronted with.

The role of entrepreneurial networking on internationalization of a micro-sized Born Global Swedish fashion company : A narrative ethnographic research

Background: In recent studies a lot of attention is drawn to the connection between networking and entrepreneurship. Many scholars consider successful business and networking inseparable. Taking into consideration the topicality of the two notions discussed above the authors of this thesis decided to conduct the research dedicated to these phenomena in the field that interests them most – in the field of Swedish fashion. Purpose: The purpose of the thesis is to gain a deeper insight into entrepreneur’s experiences to point out the role of entrepreneurial networking in the process of internationalization of a micro-sized Swedish fashion company and to contribute to the research in this field by telling its unique story. Method: To achieve the purpose of the research a narrative ethnographic research was conducted. This research strategy was chosen because it suits the purpose best by giving an opportunity to get fresh insights into the field of entrepreneurial networking from the point of view of the entrepreneur. The data collected has a narrative nature therefore narrative analysis is used to present it. The methods of gathering the data are face-to-face interview and documents. Conclusion: we can define the most important role of entrepreneurial networking on the internationalization process of Odeur as an effective accelerator and a tool to fulfil the knowledge and expertise gaps in certain areas through other actors in the network.

A Story of English Language Learning – How Can Children’s Literature be Used in Teaching Vocabulary to Young English Language Learners? : - A Literature Review

This study aims to find research relating to the use of children’s literature to promote vocabulary development in young children, particularly English language learners in Sweden. The main questions address how (methods) children’s literature can be used and why (reasons) children’s literature is often recommended for the teaching of vocabulary to young learners. The study also aims to explore reasons against the use of children’s literature in vocabulary teaching found in previous research. A systematic literature review was carried out, including results from five empirical studies. The studies involved native speakers, second language learners and foreign language learners from various backgrounds. The results suggest that while research has shown children’s literature to be a good tool to use with young learners, careful lesson planning needs to be carried out. Direct instruction and scaffolding using pictures, technology and gestures is recommended. Hence, the teacher plays an important part for the vocabulary development using children’s literature in the classroom.

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.

Role of headmasters, teachers and supervisors in knowledge transfer about occupational health and safety to pupils in vocational education

Background Young people are at an increased risk for illness in working life. The authorities stipulate certain goals for training in occupational health and safety (OHS) in vocational schools. A previous study concluded that pupils in vocational education had limited knowledge in the prevention of health risks at work. The aim of the current study, therefore, was to study how OHS training is organized in school and in workplace-based learning (WPL).   Method The study design featured a qualitative approach, which included interviews with 12 headmasters, 20 teachers, and 20 supervisors at companies in which the pupils had their WPL. The study was conducted at 10 upper secondary schools, located in Central Sweden, that were graduating pupils in four vocational programs.   Result The interviews with headmasters, teachers, and supervisors indicate a staggered picture of how pupils are prepared for safe work. The headmasters generally give teachers the responsibility for how goals should be reached. Teaching is very much based on risk factors that are present in the workshops and on teachers’ own experiences and knowledge. The teaching during WPL also lacks the systematic training in OHS as well as in the traditional classroom environment.   Conclusion Teachers and supervisors did not plan the training in OHS in accordance with the provisions of systematic work environment management. Instead, the teachers based the training on their own experiences. Most of the supervisors did not get information from the schools as to what should be included when introducing OHS issues in WPL.

The Key Role of the School Principal’s Leadership in the Schooling of Newly Arrived Immigrant Pupils in Sweden : Experiences from an Interactive Action Research Project

When newly immigrated children and young people begin school in Sweden, certain challengesarise. These may result from weak Swedish-language skills and different schooling backgrounds,as well as organizational and pedagogical limitations in the schools. This generates demands onschool leaders to lead and develop the organization and teachers competences to meet these pupils’needs. This situation was behind the initiation of the project “New Immigrants and Learning—Competence Development for Teachers and School Principals.” The project ran in schools infour Swedish municipalities, its aim was to develop leadership, organizational and pedagogicalskills that would facilitate the schooling and integration of newly arrived pupils. This article aimsto describe and discuss a Participant Action Research (PAR) based on a think tank and researchcircles, drawing special attention to the role of the school leaders. It will also examine whether theresearch circles and the project overall served to develop educational and intercultural leadership,organizational conditions, collegial learning, pedagogical methods and competence in terms ofschooling for this pupil group.