185 research outputs found

    GAB2 is involved in differential pi3-kinase signaling by two splice forms of C-kit.

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    The stem cell factor receptor/c-Kit plays an important physiological role in hematopoesis, melanogenesis and gametogenesis. It has also been implicated in numerous human malignancies. Signal transduction pathways shown to be of importance for c-Kit mediated transformation include the PI3-kinase/Akt pathway. We have previously shown that two alternative splice forms of c-Kit, denoted GNNK- and GNNK+ respectively, mediate distinctively different signals. In this study we find that in the hematopoietic cell line Ba/F3, the GNNK- c-Kit mediates a substantially stronger activation of PI3-kinase/Akt than the GNNK+ c-Kit. This difference in signaling was shown to be dependent on the association of the scaffolding protein Gab2 to c-Kit and Src-mediated phosphorylation of Gab2, to be independent of the direct association of PI3-kinase with c-Kit. Furthermore, proliferation and survival of Ba/F3 cells expressing a mutant of c-Kit that fails to bind to PI3-kinase directly was slightly decreased compared to wild-type c-Kit expressing cells. Using siRNA technology we further verified a role of Gab2 in inducing activation of PI3-kinase/Akt downstream of c-Kit. To summarize, we show that PI3-kinase activation by c-Kit is both splice form dependent and cell type specific. Furthermore, activation of PI3-kinase by c-Kit is dependent both on the direct PI3-kinase binding site in c-Kit as well as on the phosphorylation of Gab2. The fact that c-Kit has been found mutated in numerous human malignancies including acute myeloid leukemia and that Gab2 often is overexpressed in acute myeloid leukemia suggests a potential role of Gab2 mediated PI3-kinase activation in transformation

    Arbeidsgivers styringsrett, SĂŠrlig om betydningen av samfunnsutviklingen for styringsrettens innhold

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    Denne oppgaven redegjÞr for hvordan samfunnet sÄ langt har utformet og fremdeles utfordrer styringsrettens innhold. I moderne tid er det sÊrlig den selvregulatoriske vernelovgivningen som pÄvirker styringsrettens innhold og rekkevidde. Reglene om varsling i arbeidsmiljÞloven kapittel 2A behandles nÊrmere for Ä illustrere hva denne type lovgivning medfÞrer for arbeidsgivers utÞvelse av styringsretten.MasteroppgaveJUS399MAJURMAJUR-

    Kengurumetoden: Viktigheten ved tidlig implementering av hud-mot-hud kontakt hos det premature barnet, og faktorer som pÄvirker sykepleierens holdninger knyttet til dette.

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    ‱Bakgrunn: Kengurumetoden dikterer at det premature barnet blir lagt direkte pĂ„ foreldrenes bryst. Det er sykepleierne som legger til rette for hud-mot-hud pĂ„ alle NyfĂždte intensive avdelinger. Deres kunnskap om og holdninger til denne metoden kan pĂ„virke hvor lenge det premature barnet fĂ„r ligge hud-mot-hud, og det finnes flere ulike faktorer som pĂ„virker disse holdningene. ‱Problemstilling: Kengurumetoden: Viktigheten ved tidlig implementering av hud-mot-hud kontakt hos det premature barnet, og faktorer som pĂ„virker sykepleierens holdninger knyttet til dette. ‱Hensikt: Hensikten med oppgaven er Ă„ belyse viktigheten ved tidlig implementering av hud-mot-hud kontakt mellom det premature barnet og dens foreldre, og se nĂŠrmere pĂ„ sykepleierens holdninger og hvilke faktorer som pĂ„virker dem. ‱Metode: Metoden som er blitt benyttet i denne bacheloroppgaven er en integrativ litteraturoversikt. Oppgaven vĂ„r bygger pĂ„ fire utvalgte forskningsartikler, hvor tre av de bygger pĂ„ et kvantitativt studium og den resterende bygger pĂ„ et kvalitativt studium. ‱Resultater: Resultatene i studiene vi har tatt utgangspunkt i, viser til flere helsefremmende faktorer ved tidlig implementering av kengurumetoden, underbygget av tall og statistikker. Dessuten viser de ogsĂ„ til hvilke utfordringer det kan ha for det premature barnet dersom tiltaket ikke implementeres innenfor “the golden hour”. Det er sykepleiernes og foreldrenes holdninger som legger til rette for nĂ„r og hvor mye hud-mot-hud kontakt det premature barnet fĂ„r under oppholdet. Studiene i besvarelsen viser til flere faktorer som har en pĂ„virkning pĂ„ disse holdningene. Det blir belyst at sykepleierne vil ha mer informasjon og kunnskap om kengurumetoden, spesielt et Ăžnske om felles retningslinjer pĂ„ alle NyfĂždte intensive avdelinger

    Kengurumetoden: Viktigheten ved tidlig implementering av hud-mot-hud kontakt hos det premature barnet, og faktorene som pÄvirker sykepleierens holdninger knyttet til dette.

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    ‱ Bakgrunn: Kengurumetoden dikterer at det premature barnet blir lagt direkte pĂ„ foreldrenes bryst. Det er sykepleierne som legger til rette for hud-mot-hud pĂ„ alle NyfĂždte intensive avdelinger. Deres kunnskap om og holdninger til denne metoden kan pĂ„virke hvor lenge det premature barnet fĂ„r ligge hud-mot-hud, og det finnes flere ulike faktorer som pĂ„virker disse holdningene. ‱ Problemstilling: Kengurumetoden: Viktigheten ved tidlig implementering av hud-mot-hud kontakt hos det premature barnet, og faktorer som pĂ„virker sykepleierens holdninger knyttet til dette. ‱ Hensikt: Hensikten med oppgaven er Ă„ belyse viktigheten ved tidlig implementering av hud-mot-hud kontakt mellom det premature barnet og dens foreldre, og se nĂŠrmere pĂ„ sykepleierens holdninger og hvilke faktorer som pĂ„virker dem. ‱ Metode: Metoden som er blitt benyttet i denne bacheloroppgaven er en integrativ litteraturoversikt. Oppgaven vĂ„r bygger pĂ„ fire utvalgte forskningsartikler, hvor tre av de bygger pĂ„ et kvantitativt studium og den resterende bygger pĂ„ et kvalitativt studium. ‱ Resultater: Resultatene i studiene vi har tatt utgangspunkt i, viser til flere helsefremmende faktorer ved tidlig implementering av kengurumetoden, underbygget av tall og statistikker. Dessuten viser de ogsĂ„ til hvilke utfordringer det kan ha for det premature barnet dersom tiltaket ikke implementeres innenfor “the golden hour”. Det er sykepleiernes og foreldrenes holdninger som legger til rette for nĂ„r og hvor mye hud-mot-hud kontakt det premature barnet fĂ„r under oppholdet. Studiene i besvarelsen viser til flere faktorer som har en pĂ„virkning pĂ„ disse holdningene. Det blir belyst at sykepleierne vil ha mer informasjon og kunnskap om kengurumetoden, spesielt et Ăžnske om felles retningslinjer pĂ„ alle NyfĂždte intensive avdelinger

    CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells

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    Glucagon is the main counterregulatory hormone in the body. Still, the mechanism involved in the regulation of glucagon secretion from pancreatic alpha cells remains elusive. Dysregulated glucagon secretion is common in patients with Cystic Fibrosis (CF) that develop CF related diabetes (CFRD). CF is caused by a mutation in the Cl(-) channel Cystic fibrosis transmembrane conductance regulator (CFTR), but whether CFTR is present in human alpha cells and regulate glucagon secretion has not been investigated in detail. Here, both human and mouse alpha cells showed CFTR protein expression, whereas CFTR was absent in somatostatin secreting delta cells. CFTR-current activity induced by cAMP was measured in single alpha cells. Glucagon secretion at different glucose levels and in the presence of forskolin was increased by CFTR-inhibition in human islets, whereas depolarization-induced glucagon secretion was unaffected. CFTR is suggested to mainly regulate the membrane potential through an intrinsic alpha cell effect, as supported by a mathematical model of alpha cell electrophysiology. In conclusion, CFTR channels are present in alpha cells and act as important negative regulators of cAMP-enhanced glucagon secretion through effects on alpha cell membrane potential. Our data support that loss-of-function mutations in CFTR contributes to dysregulated glucagon secretion in CFRD

    Influences of salinity on the physiology and distribution of the Arctic coralline algae, Lithothamnion glaciale (Corallinales, Rhodophyta)

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    In Greenland, free-living red coralline algae contribute to and dominate marine habitats along the coastline. Lithothamnion glaciale dominates coralline algae beds in many regions of the Arctic, but never in GodthĂ„bsfjord, Greenland, where Clathromorphum sp. is dominant. To investigate environmental impacts on coralline algae distribution, calcification and primary productivity were measured in situ during summers of 2015 and 2016, and annual patterns of productivity in L. glaciale were monitored in laboratory-based mesocosm experiments where temperature and salinity were manipulated to mimic high glacial melt. The results of field and cold-room measurements indicate that both L. glaciale and Clathromorphum sp. had low calcification and photosynthetic rates during the Greenland summer (2015 and 2016), with maximum of 1.225 ± 0.17 or 0.002 ± 0.023 ÎŒmol CaCO3 · g-1 · h-1 and -0.007 ±0.003 or -0.004 ± 0.001 mg O2 · L-1 · h-1 in each species respectively. Mesocosm experiments indicate L. glaciale is a seasonal responder; photosynthetic and calcification rates increase with annual light cycles. Furthermore, metabolic processes in L. glaciale were negatively influenced by low salinity; positive growth rates only occurred in marine treatments where individuals accumulated an average of 1.85 ± 1.73 mg · d-1 of biomass through summer. These results indicate high freshwater input to the GodthĂ„bsfjord region may drive the low abundance of L. glaciale, and could decrease species distribution as climate change increases freshwater input to the Arctic marine system via enhanced ice sheet runoff and glacier calving.Peer reviewedFinal Accepted Versio

    Formation and degradation of chaotic terrain in the Galaxias regions of Mars: implications for near-surface storage of ice

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    Galaxias Chaos is a region of low plateaus separated by narrow fractures – a chaotic terrain. Galaxias Mensae and Galaxias Colles are characterised by mesa and knobby terrains of individual landforms, or small assemblages, separated by plains. Galaxias Chaos has been attributed to ground disturbance due to sublimation in shallow subsurface ice-rich deposits, Galaxias Mensae and Galaxias Colles to sublimation and degradation of icy surface materials, without production of chaotic terrain. Liquid water has not been regarded as a product of the degradation of these icy terrains. This paper asks two research questions: (1) what was the total extent of the different modes of landscape degradation, especially chaotic terrain, involved in producing the present landscapes of Galaxias Chaos and Galaxias Mensae–Colles; (2) can the generation of liquid water as a product of landscape degradation be ruled-out? Using a morphological-statistical approach, including power spectrum analysis of relief, our observations and analyses show that present mesa-knobby terrains of Galaxias Mensae–Colles evolved from a landscape that had the same directional pattern and relief as presently found in Galaxias Chaos. This terrain extended across ∌440,000 km2 but ∌22,000 km3 (average thickness, 77 m) have been lost across ∌285,000 km2. This represents a significant loss of ice-bearing deposits. Moreover, this surface degradation was spatially partitioned by landforms associated with elevated ground heating and the transmission of a fluid in the shallow subsurface towards a distal channel. In answer to research question 2, it cannot be determined definitively if the fluid involved was groundwater, generated by the thermal destabilisation of the icy deposits, or low viscosity lava. However, it is likely that the degradation of Galaxias Mensae–Colles was not a consequence of sublimation alone. These findings underscore the significance of cryo-volcanic interactions in the cycling of water between the Martian surface and the atmosphere
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