Journal Staff

Inhibitors of the catalytic activity of the 20S proteasome are cytotoxic to tumor cells and are currently in clinical use for treatment of multiple myeloma, whilst the deubiquitinase activity associated with the 19S regulatory subunit of the proteasome is also a valid target for anti-cancer drugs. The mechanisms underlying the therapeutic efficacy of these drugs and their selective toxicity towards cancer cells are not known. Here, we show that increasing the cellular levels of proteasome substrates using an inhibitor of Sec61-mediated protein translocation significantly increases the extent of apoptosis that is induced by inhibition of proteasomal deubiquitinase activity in both cancer derived and non-transformed cell lines. Our results suggest that increased generation of misfolded proteasome substrates may contribute to the mechanism(s) underlying the increased sensitivity of tumor cells to inhibitors of the ubiquitin-proteasome system

Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation

Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates, resulting in alterations in autophagy. However, the consequences of impaired autophagy for neuronal function remain poorly understood. In this study, we used cell culture and mouse models of huntingtin protein aggregation as well as post-mortem material from patients with Huntington’s disease to demonstrate that Argonaute-2 (AGO2) accumulates in the presence of neuronal protein aggregates and that this is due to impaired autophagy. Accumulation of AGO2, a key factor of the RNA-induced silencing complex that executes microRNA functions, results in global alterations of microRNA levels and activity. Together, these results demonstrate that impaired autophagy found in neurodegenerative diseases not only influences protein aggregation but also directly contributes to global alterations of intracellular post-transcriptional networks

The HOG Pathway Dictates the Short-Term Translational Response after Hyperosmotic Shock

In the global osmoshock translational response in yeast, some gene products were translationally mobilized without transcriptional up-regulation. Conversely, other transcriptionally up-regulated mRNAs were translationally inhibited. Analogous changes occurred on the protein level. These translational responses were strongly dependent on Hog1 and Rck2

Utbildningsradion : what is it and what do they have to offer?

Det här arbetets syfte är att ge den intresserade en del information om Utbildningsradion eller UR. Vad är UR? Vad kan Utbildningsradion erbjuda lärare i årskurs 4-9 och vad har denna yrkesgrupp för attityd till UR? Jag anser att det material som UR distribuerar i media har ett viktigt syfte och jag har haft för avsikt att påvisa att det både är kvalitativt och pedagogiskt. Resultatet av undersökningen visar att lärare har en positiv attityd till Utbildningsradion

11beta-hydroxysteroid dehydrogenase type 1 as a pharmacological target in metabolic disease

The metabolic syndrome is a collection of associated disorders, affected by lifestyle, genetic predisposition and environment, and emerges as a consequence of the Western society lifestyle. It describes a variety of cardiovascular and atherosclerotic risk factors including insulin resistance, obesity, dyslipidemia and arterial hypertension. The connection between insulin resistance and diabetes mellitus type 2 has been well established, and the major abnormalities are peripheral insulin resistance, beta-cell dysfunction and increased endogenous glucose production. Glucocorticoids have received considerable interest among the many factors that play a role in the metabolic syndrome. Excess glucocorticoid levels cause glucose intolerance and insulin resistance, as demonstrated by the clinical picture of Cushing s syndrome, which closely resembles the metabolic syndrome. A further understanding of the disease mechanisms behind the metabolic syndrome is essential to diminish its increasing impact on health of the Western population. Novel pharmacological treatment strategies based on modulation of glucocorticoid function is a feasible approach to combat this metabolic disease. Glucocorticoids are steroid hormones that belong to the superfamily of ligand-activated nuclear receptors. An emerging concept describes tissue-specific metabolic reactions that many hormones undergo, including steroids, resulting in a pre-receptor control mechanism. The OH/keto group on the C11-position in glucocorticoids determines if the steroid can activate its receptor or is inert . The enzyme responsible for this conversion of glucocorticoids is 11beta-hydroxysteroid dehydrogenase (11beta-HSD). Two different isozymes of 11beta-HSD (11beta-HSD1 and 11beta-HSD2) are described. Their functions are to activate and inactivate glucocorticoids in a tissue-dependent manner. 11beta-HSD1 mediates activation of the glucocorticoid precursor cortisone (in humans) to the active glucocorticoid receptor ligand cortisol. It is widely expressed in central and peripheral tissues involved in glucose and carbohydrate metabolism, including liver and adipose tissue. Because of the beneficial effects of reduced tissue glucocorticoid levels in the metabolic syndrome and related disorders, 11beta-HSD1 is a pursued target of pharmacological intervention. The aims of the study were to investigate structure-function relationships and functional effects of 11beta-HSD1. The results show that the hydrophobic enzyme 11beta-HSD1 can be expressed with high activity as a full length, membrane bound enzyme in the yeast system Pichia pastoris and can be purified as a soluble, N-terminally truncated form expressed in E.coli, by using metal-chelate chromatography. The full-length and truncated enzymes have equivalent enzymatic properties in regard to glucocorticoid metabolism. 11beta-HSD1 orthologs from human, rat, mouse and guinea pig show considerable inter-species variations as inferred by primary structure determinations and inhibitor characterization. A 11beta-HSD1 selective arylsulfonamidothiazole inhibitor class was investigated and is currently developed as a promising tool for the treatment of insulinresistance. Several derivatives were analyzed and show a high degree of species selectivity, with different inhibitor mechanisms and low nM affinities towards the human enzyme. 11beta-HSD1 mediates glucocorticoid-activation in pancreatic islets of Langerhans, and thereby regulates glucose-stimulated insulin secretion. Whereas glucocorticoids suppress insulin secretion in the insulin resistant ob/ob mouse model, they increase insulin release in lean mice. Hence it is postulated that the known beneficial effects of 11beta-HSD1-inhibition in the pharmacological treatment of diabetes mellitus can be extended to include improved insulin release in diabetic mice. Glucocorticoid-activation in lean mice may at an early phase lead to increased insulin secretion and priming of the â-cells to stress-adaptation, whereas long-term exposure leads to a decrease in insulin secretion. A novel role of 11beta-HSD1 in 7-oxosterol metabolism was discovered and investigated using recombinant 11beta-HSD1 orthologs. The enzymatic origin of endogenous 7beta-OH-cholesterol in humans is assigned to 11beta- HSD1, possibly pointing to an involvement in atherosclerosis. Species differences in 7-oxysterol metabolism can be explained on the basis of 11beta-HSD1 specificities

Lärares perspektiv på arbete med elever i matematiksvårigheter och speciallärarens roll i processen.

Syftet med studien är att få fördjupad kunskap om och förståelse av arbete kring elever i matematiksvårigheter, samt speciallärarens roll i problemlösningsprocessen. Det är en kvalitativ studie där speciallärare, specialpedagoger och klasslärare som alla arbetar med elever i matematiksvårigheter intervjuats. I studien har 14 lärare intervjuats för att synliggöra deras tankar och få svar på studiens frågeställningar kring matematiksvårigheter, identifiering och åtgärder. Resultatet visar att matematiksvårigheter är komplext och svårt att definiera. Elevers svårigheter förstås på en mängd olika sätt så som organisation och lärmiljö, färdigheter i matematik, koncentration och minnessvårigheter samt motivation. Identifieringen av matematiksvårigheter sker löpande i undervisningen men också genom tester och i samtal. De åtgärder som sätts in då en elev visar sig ha svårigheter skiftar, men vanligtvis sker förändringar i lärmiljön. Specialläraren har en betydelsefull roll som "spindeln i nätet" i arbetet kring elever i matematiksvårigheter. Specialläraren beskrivs vara den som ser helheten och kan organisera stöd utifrån de behov som finns på skolan, samt ha en stödjande funktion för såväl elever, lärare som föräldrar. Arbetet med elever i matematiksvårigheter är komplext och specialläraren har i samarbete med övrig personal en viktig uppgift att fylla för att identifiera svårigheter, ge stöd i elevers matematiklärande men framför allt förebygga så att svårigheter i matematik inte uppstår

Neuro Muskulär Elektrisk Stimulering (NMES) som behandlingsmetod hos strokepatienter med droppfot

Validerat; 20101217 (root

Neuro Muskulär Elektrisk Stimulering (NMES) som behandlingsmetod hos strokepatienter med droppfot

Validerat; 20101217 (root

Sjuksköterskors erfarenheter av samarbetet mellan slutenvård och kommunal sjukvård kring den äldre patienten.

ABSTRAKT Bakgrund: De mest sjuka/sköra äldre är en ökande grupp patienter som ofta hamnar i kläm då missförstånd uppstår vid övergång mellan slutenvård och kommunal sjukvård. Tidigare forskning har visat att bland annat bristande informationsöverföring mellan instanser är en av de mest förekommande orsakerna till vårdskador. Att samarbetet mellan dessa två primära vårdinstanser fungerar är av största vikt för god patientsäkerhet. Syfte: att undersöka sjuksköterskors erfarenheter av samarbetet mellan slutenvården och kommunal sjukvård kring den äldre patienten. Metod: En kvalitativ metod valdes för att undersöka sjuksköterskors erfarenheter av samarbetet mellan slutenvård och kommunal sjukvård. Sammanlagt 27 sjuksköterskor från både kommunal sjukvård och slutenvård svarade på en elektronisk enkät via e-post. Deras svar analyserades med en kvalitativ innehållsanalys. Resultat: Sjuksköterskor från både slutenvården och den kommunala sjukvården anser att ett bättre samarbete måste till för att öka patientsäkerheten. Brister finns i samarbetet framför allt kring läkemedelshantering, kommunikation och informationsöverföring. De upplever även att förståelsen för varandras verksamheter bör öka. Som förbättringsförslag ges utbildning och hospitering för att öka sjuksköterskornas kompetens för det gemensamma kommunikationsverktyget och bättre förståelse för de olika verksamheterna. Slutsats: Samarbetet mellan kommunal sjukvård och slutenvård kan bli bättre och patientsäkerheten öka om läkemedelshanteringen säkras, bra planer görs upp med och för patienten och om informationsöverföringen sker korrekt. Då möjliggörs ett gott samarbetet och vårdens övergångar blir inte lika märkbara för patienten. Det befintliga kommunikationsverktyget, om det används till fullo, är ett bra stöd i detta.ABSTRACT Background: The frail and/or sick elderly are a growing group of patients who are often caught in between healthcare instances when misunderstandings occur in transition between inpatient and municipal healthcare providers. Previous research has shown that, among other things, lack of information between instances are one of the most common causes of preventable harm. Improved cooperation between these two primary health facilities work is of paramount importance for patient safety. Aim: The aim of the study was to examine nurses experiences of cooperation between inpatient care and municipal healthcare concerning geriatric patients. Method: A qualitative method was chosen to investigate the nurses' experience of cooperation between inpatient care and municipal healthcare. A total of 27 nurses from both municipal and inpatient answered an electronic questionnaire via e-mail. Their answers were analyzed using qualitative content analysis. Results: Nurses from both inpatient care and municipal healthcare believes that the cooperation is in need of improvement in order to increase patient safety. Shortcomings occur in cooperation, especially regarding medicinal management, communication and information transfer. They are also under the impression that an increased understanding of each other's work situations are crucial. Suggestions of improvement are increased education within the common communicational tool and also visits to each other’s workplaces to increase the understanding of the different work situations. Conclusion: An increased and improved cooperation between municipal healthcare and inpatient care can improve patient safety if medicinal management and transference is secured, better care plans are set up with and for the patient, and also that information transfer is conducted properly. These things will enable a good cooperation and transition of caregiver will not be as noticeable to the patient. The existing tool for communication, if used to its full extent, is a great support in doing this