1,8-Cineol inhibits nuclear translocation of NF-κB p65 and NF-κB-dependent transcriptional activity

Natural plant-derived products are commonly applied to treat a broad range of human diseases, including cancer as well as chronic and acute airway inflammation. In this regard, the monoterpene oxide 1,8-cineol, the active ingredient of the clinically approved drug Soledum®, is well-established for the therapy of airway diseases, such as chronic sinusitis and bronchitis, chronic obstructive pulmonary disease and bronchial asthma. Although clinical trials underline the beneficial effects of 1,8-cineol in treating inflammatory diseases, the molecular mode of action still remains unclear. Here, we demonstrate for the first time a 1,8-cineol-depending reduction of NF-κB-activity in human cell lines U373 and HeLa upon stimulation using lipopolysaccharides (LPS). Immunocytochemistry further revealed a reduced nuclear translocation of NF-κB p65, while qPCR and western blot analyses showed strongly attenuated expression of NF-κB target genes. Treatment with 1,8-cineol further led to increased protein levels of IκBα in an IKK-independent matter, while FRET-analyses showed restoring of LPS-associated loss of interaction between NF-κB p65 and IκBα. We likewise observed reduced amounts of phosphorylated c-Jun N-terminal kinase 1/2 protein in U373 cells after exposure to 1,8-cineol. In addition, 1,8-cineol led to decreased amount of nuclear NF-κB p65 and reduction of its target gene IκBα at protein level in human peripheral blood mononuclear cells. Our findings suggest a novel mode of action of 1,8-cineol through inhibition of nuclear NF-κB p65 translocation via IκBα resulting in decreased levels of proinflammatory NF-κB target genes and may therefore broaden the field of clinical application of this natural drug for treating inflammatory diseases.

Culture bag systems for clinical applications of adult human neural crest-derived stem cells

Introduction Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags. Methods We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using Afc-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosphatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs. Results When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as adipocytes positive in Oil Red O assays. Bag culture further did not affect the potential of ITSCs to undergo differentiation into neuroectodermal cell types coexpressing β-III-tubulin and MAP2 and exhibiting the capability for synaptic vesicle recycling. Conclusions Here, we report for the first time the successful cultivation of human NCSCs within cGMP-grade Afc-FEP bags using a human blood plasma-supplemented medium. Our findings particularly demonstrate the unchanged differentiation capability and genetic stability of the cultivated NCSCs, suggesting the great potential of this culture system for future medical applications in the field of regenerative medicine.

Stay calm! Regulating emotional responses by implementation intentions: assessing the impact on physiological and subjective arousal

Implementation intention (IMP) has recently been highlighted as an effective emotion regulatory strategy (Schweiger Gallo et al., 2009). Most studies examining the effectiveness of IMPs to regulate emotion have relied on self-report measures of emotional change. In two studies we employed electrodermal activity (EDA) and heart rate (HR) in addition to arousal ratings (AR) to assess the impact of an IMP on emotional responses. In Study 1, 60 participants viewed neutral and two types of negative pictures (weapon vs. non-weapon) under the IMP “If I see a weapon, then I will stay calm and relaxed!” or no self-regulatory instructions (Control). In Study 2, additionally to the Control and IMP conditions, participants completed the picture task either under goal intention (GI) to stay calm and relaxed or warning instructions highlighting that some pictures contain weapons. In both studies, participants showed lower EDA, reduced HR deceleration and lower AR to the weapon pictures compared to the non-weapon pictures. In Study 2, the IMP was associated with lower EDA compared to the GI condition for the weapon pictures, but not compared to the weapon pictures in the Warning condition. AR were lower for IMP compared to GI and Warning conditions for the weapon pictures.

Impact of Northern Hemisphere snow on the Arctic Ocean in a climate model

A present day control integration performed with the Hadley Centre's coupled climate model HadGEM1.2 experiences a large salinity bias in the Arctic Ocean when compared to in situ observations. Such a large salinity bias may have implications for both Arctic and Atlantic Ocean circulation. Large differences are seen between the runoff in HadGEM and the observations from the Global Runoff Data Centre, in particular in the Lena catchment, which could account for this salinity bias. We suggest that this discrepancy in runoff is, at least in part, due to a lack of snow accumulation in the model. The model climatology is very different to those obtained by remote sensing, such as the Global Snow Water Equivalent Climatology (NSIDC) and GlobSnow (ESA).

Diversity in a honey bee pathogen: first report of a third master variant of the Deformed Wing Virus quasispecies

Treatment of emerging RNA viruses is hampered by the high mutation and replication rates that enable these viruses to operate as a quasispecies. Declining honey bee populations have been attributed to the ectoparasitic mite Varroa destructor and its affiliation with Deformed Wing Virus (DWV). In the current study we use next-generation sequencing to investigate the DWV quasispecies in an apiary known to suffer from overwintering colony losses. We show that the DWV species complex is made up of three master variants. Our results indicate that a new DWV Type C variant is distinct from the previously described types A and B, but together they form a distinct clade compared with other members of the Iflaviridae. The molecular clock estimation predicts that Type C diverged from the other variants ~319 years ago. The discovery of a new master variant of DWV has important implications for the positive identification of the true pathogen within global honey bee populations.

Farmer attitudes and livestock disease: exploring citizenship behaviour and peer monitoring across two BVD control schemes in the UK

The eradication of BVD in the UK is technically possible but appears to be socially untenable. The following study explored farmer attitudes to BVD control schemes in relation to advice networks and information sharing, shared aims and goals, motivation and benefits of membership, notions of BVD as a priority disease and attitudes toward regulation. Two concepts from the organisational management literature framed the study: citizenship behaviour where actions of individuals support the collective good (but are not explicitly recognised as such) and peer to peer monitoring (where individuals evaluate other’s behaviour). Farmers from two BVD control schemes in the UK participated in the study: Orkney Livestock Association BVD Eradication Scheme and Norfolk and Suffolk Cattle Breeders Association BVD Eradication Scheme. In total 162 farmers participated in the research (109 in-scheme and 53 out of scheme). The findings revealed that group helping and information sharing among scheme members was low with a positive BVD status subject to social censure. Peer monitoring in the form of gossip with regard to the animal health status of other farms was high. Interestingly, farmers across both schemes supported greater regulation with regard to animal health, largely due to the mistrust of fellow farmers following voluntary disease control measures. While group cohesiveness varied across the two schemes, without continued financial inducements, longer-term sustainability is questionable

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Evolutionary patterns in neotropical Helieae (Gentianaceae): evidence from morphology, chloroplast and nuclear DNA sequences

Parsimony-based phylogenetic analyses of the neotropical tribe Helieae (Gentianaceae) are presented, including 22 of the 23 genera and 60 species. This study is based on data from morphology, palynology, and seed micromorphology (127 structural characters), and DNA sequences (matK, trnL intron, ITS). Phylogenetic reconstructions based on ITS and morphology provided the greatest resolution, morphological data further helping to tentatively place several taxa for which DNA was not available (Celiantha, Lagenanthus, Rogersonanthus, Roraimaea, Senaea, Sipapoantha, Zonanthus). Celiantha, Prepusa and Senaea together appear as the sister clade to the rest of Helieae. The remainder of Helieae is largely divided into two large subclades, the Macrocarpaea subclade and the Symbolanthus subclade. The first subclade includes Macrocarpaea, sister to Chorisepalum, Tochia, and Zonanthus. Irlbachia and Neblinantha are placed as sisters to the Symbolanthus subclade, which includes Aripuana, Calolisianthus, Chelonanthus, Helia, Lagenanthus, Lehmanniella, Purdieanthus, Rogersonanthus, Roraimaea, Sipapoantha, and symbolanthus. Generic-level polyphyly is detected in Chelonanthus and Irlbachia. Evolution of morphological characters is discussed, and new pollen and seed characters are evaluated for the first time in a combined morphological-molecular phylogenetic analysis.

Cell coupling in mouse pancreatic beta-cells measured in intact islets of Langerhans

The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified beta-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent beta-cells. Using a combination of current- and voltage-clamp recordings, the total gap junctional conductance between beta-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell ( due to the. ring of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of beta-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to -55 mV) gave rise to a slow capacitive current indicative of coupling between beta-cells, but not in non-beta-cells, with a time constant of 13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a superficial beta-cell in an islet is in electrical contact with six to seven other beta-cells. No evidence for dye coupling was obtained when cells were dialysed with Lucifer yellow even when electrical coupling was apparent. The correction of the measured resting conductance for the contribution of the gap junctional conductance indicated that the whole-cell K(ATP) channel conductance (G(K,ATP)) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at 15 mM glucose with an estimated IC(50) of approximately 4 mM. Theoretical considerations indicate that the coupling between beta-cells within the islet is sufficient to allow propagation of [Ca(2+)](i) waves to spread with a speed of approximately 80 mu m s(-1), similar to that observed experimentally in confocal [Ca(2+)](i) imaging.

GLP-1 Inhibits and Adrenaline Stimulates Glucagon Release by Differential Modulation of N- and L-Type Ca(2+) Channel-Dependent Exocytosis

Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1-10 nM) and high (10 mu M) concentrations of forskolin, respectively. The expression of GLP-1 receptors in a cells is <0.2% of that in beta cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose independent, and does not involve paracrine effects mediated by insulin or somatostatin. GLP-1 is without much effect on a cell electrical activity but selectively inhibits N-type Ca(2+) channels and exocytosis. Adrenaline stimulates a cell electrical activity, increases [Ca(2+)] enhances L-type Ca(2+) channel activity, and accelerates exocytosis. The stimulatory effect is partially PKA independent and reduced in Epac2-deficient islets. We propose that GLP-1 inhibits glucagon secretion by PKA-dependent inhibition of the N-type Ca(2+) channels via a small increase in intracellular cAMP ([cAMP]). Adrenaline stimulates L-type Ca(2+) channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP],.

Neopaleozoic striated surfaces in the granitic basement and clast pavement remains of Salto, SP

Near Guarau Ceramic, localized southwest of Salto city in the State of Sao Paulo, two granite outcrops, distant some tens of meters from each other, display Neopaleozoic striated surfaces. These surfaces are in contact with diamictites from the Itarare Subgroup. The striae correspond to sub parallel grooves with millimetric spacing and depth, oriented about N48E and dipping 12 degrees to 42 degrees towards SE. Observed features and association with diamictites indicate an origin by glacial abrasion due to ice movement from southeast towards northwest. About 1.8 km east of Salto, unconsolidated material containing flat-iron-shaped and striated clasts was found on top of granite outcrops, interpreted as clasts pavement remains.

Undervisning till patienter med diabetes typ 2.Faktorer som påverkar resultatet av egenvården- En systematisk litteraturstudie

Syftet med studien var att belysa vilka faktorer i patientundervisningen som kan påverka resultatet av egenvård för patienter med diabetes typ 2 samt att kartlägga gruppundervisningens betydelse och dess innehåll. Studien baseras på 13 vetenskapliga artiklar daterade från år 1991 och fram till år 2003. Litteraturen har sökts manuellt och via databaserna PubMed, SweMed och Elsevier. Sökorden som använts i olika kombinationer var: education, diabetes type 2, support, obesity, self- management, changes lifestyle, factors affecting, empowerment, diabetes nurse, nurse, individually, group, diabetes typ 2, stöd, sjuksköterska, undervisning och egenvård. Urvalet av de vetenskapliga artiklarna gjordes med tanke på litteraturstudiens syfte och frågeställningar. Resultatet visade att undervisningen bör vara en ständigt pågående process. Kontinuitet, hänsyn, tillgänglighet och stöd av hela diabetesteamet under en längre tid är viktiga faktorer i behandlingen. Andra viktiga faktorer som kan påverka resultatet av egenvård är patientens självkänsla, motivation och upplevd ensamhet. Det är viktigt att undervisarens förhållningssätt varieras och anpassas efter patientens individuella resurser och behov. Undervisningsprogram som innehåller både grupp- och individuell undervisning i kombination med teoretisk- och praktisk undervisning har en positiv betydelse för patientens egenvård. Diskussioner och sociala aktiviteter i grupp, visade sig ha en god inverkan på patientens livsstilsförändringar.

Elektronisk rese- och upplevelseguide, konceptuell modell som nyttjar nationella databaser

Resandet ökar i dagens samhälle och människor söker nya upplevelser och utmaningar. Konkurrensen om besökarna är stor. Med hjälp av den nya informations- och kommunikationstekniken kan en elektronisk rese- och upplevelseguide utgöra ett alternativ i syfte att attrahera besökarna och få dem att stanna längre. Genom tekniken kan intressanta berättelser presenteras med både ljud, bild och video, s k multimedieteknik. För att besökaren ska kunna vara rörlig och samtidigt ta emot information krävs en mobil utrustning som exempelvis en handdator.Denna magisteruppsats i informatik ingår i ett projekt, uppdelat i tre steg. Projektet, som drivs på uppdrag av Vision Vimmerby och Högskolan Dalarna, har som mål att ta fram en elektronisk rese- och upplevelseguide, avsedd för vuxna bilburna besökare i Astrid Lindgrens landskap. Den elektroniska guiden ska presenteras via en handdator som besökare kan hyra vid Turistbyrån i Vimmerby.Målet för uppsatsen, som utgör första fasen av dessa tre, är att redogöra för en konceptuell generell modell för en elektronisk rese- och upplevelseguide. Grundtanken är att modellen lätt ska kunna appliceras på vilket resmål som helst. Förutsättningar för det skapas genom att använda befintliga nationella databaser.Vi har strävat efter att den konceptuella modellen ska vara komponentbaserad så att andra datakällor kan väljas utan att konceptet faller. Vidare har vi analyserat om VITSA-projektets tekniska grundplattform, som innehåller funktionalitet som är anpassad för den här typen av tjänster, är lämplig att använda.I arbetet har vi använt oss av befintliga teorier om mobilitet, tjänster och systemarkitekturer. Parallellt med att de befintliga teorierna har använts, har en strukturell modell för IT-tjänster vidareutvecklats. Vår tanke är att den vidareutvecklade modellen ska inspirera till användning och eventuellt användas som stöd vid fortsatt forskning om IT-tjänster.

Verksamhetsanalys vid ett snickeriföretag – behov av organisationsanpassningvid expansion

Vårt examensarbete i informatik är utfört på ett producerande företag som expanderat och därför sett behov av att förändra sin organisation. Ägarna upplever att personalplanering och tillverkningsplanering är alltför tidskrävande och de hinner inte med viktiga arbetsuppgifter som marknadsföring och företagsutveckling.Examensarbetet har innefattat teoristudier, en analys av företagets verksamhet samt utformning av förändringsförslag för att förbättra företagets organisation. Våra litteraturstudier har bestått av inläsning av teorier om problem som kan uppstå i expanderande företag samt datainsamling genom intervjuer av företagets ägare och några av de anställda. Detta har legat till grund för den verksamhetsanalys vi genomfört med hjälp av delar ur metoden FA/SIM. Denna analys ligger till grund för de förändringsförslag som har arbetats fram.I analysen har problem som rör följande fyra aktiviteter identifierats. - Arbetsledning - Planering - Tillverkning - VaruleveransDe åtgärdsförslag vi anser viktigast att genomföra för att effektivisera och underlätta arbetssituationen för ägare och anställda är att börja registrera ordrar dagligen och införa rutiner för att registrera produktion och lagerhållning. Ytterligare åtgärder är att anställa kvalificerad personal på kontoret samt utbilda fler i personalen i att köra lackeringen.Vi kan konstatera att företagets övergripande problem till stor del orsakas av att organisationen inte anpassats till företagets expansion. Det är vanligt att insikt om detta kommer först när problemen börjar kännas oöverstigliga.

Förstudie av MMS-tjänster för bildöverförd trafikinformation

Vägverket har ett önskemål om att distribuera trafikinformation till trafikanter. Vi fick uppdraget att undersöka om MMS skulle kunna användas i detta syfte. Eftersom MMS är en ny teknik med multimediala egenskaper som kan leverera stora textmängder, bild, ljud och video, beslöt vi oss för att koncentrera oss på de bilder som kommer från Vägverkets trafik- och väglagskameror som finns längs våra vägar.Det finns en stor mängd av möjliga tjänster som kan utvecklas, riktade till olika målgrupper och som strävar till att ge trafikanter ett beslutsunderlag vid val av färdsätt, färdväg eller starttid. Vi valde i arbetet en storstadspendlare som kan få en insikt om hur det ser ut längs vägen till arbetsplatsen. En annan tjänst är till landsvägspendlaren som kan beställa en bild från en känslig vägsträcka under vintertid. Tillsammans med dessa bilder visas ett textmeddelande om hur trafiksituationen ser ut eller vilket väder det är vid kamerans position. Målet med tjänsterna är att förbättra framkomligheten i trafiken och till följd av det, trafiksäkerheten och miljön.Examensarbetet fokuserar på den tjänsteteori och det systemarkitekturarbete som har ingått i magisterutbildningen. Givetvis har vi också utgått från de önskemål samt den infrastruktur som Vägverket har.