| 1061. |
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| 1062. |
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| 1063. |
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| 1064. |
- Denwood, G., et al.
(författare)
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Glucose stimulates somatostatin secretion in pancreatic delta-cells by cAMP-dependent intracellular Ca-2+ release
- 2019
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Ingår i: Journal of General Physiology. - : Rockefeller University Press. - 0022-1295 .- 1540-7748. ; 151:9, s. 1094-1115
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Tidskriftsartikel (refereegranskat)abstract
- Somatostatin secretion from pancreatic islet delta-cells is stimulated by elevated glucose levels, but the underlying mechanisms have only partially been elucidated. Here we show that glucose-induced somatostatin secretion (GISS) involves both membrane potential-dependent and -independent pathways. Although glucose-induced electrical activity triggers somatostatin release, the sugar also stimulates GISS via a cAMP-dependent stimulation of CICR and exocytosis of somatostatin. The latter effect is more quantitatively important and in mouse islets depolarized by 70 mM extracellular K+, increasing glucose from 1 mM to 20 mM produced an similar to 3.5-fold stimulation of somatostatin secretion, an effect that was mimicked by the application of the adenylyl cyclase activator forskolin. Inhibiting cAMP-dependent pathways with PKI or ESI-05, which inhibit PKA and exchange protein directly activated by cAMP 2 (Epac2), respectively, reduced glucose/forskolin-induced somatostatin secretion. Ryanodine produced a similar effect that was not additive to that of the PKA or Epac2 inhibitors. Intracellular application of cAMP produced a concentration-dependent stimulation of somatostatin exocytosis and elevation of cytoplasmic Ca2+ ([Ca2+](i)). Both effects were inhibited by ESI-05 and thapsigargin (an inhibitor of SERCA). By contrast, inhibition of PKA suppressed delta-cell exocytosis without affecting [Ca2+](i) . Simultaneous recordings of electrical activity and [Ca2+](i) in delta-cells expressing the genetically encoded Ca2+ indicator GCaMP3 revealed that the majority of glucose-induced [Ca2+](i) spikes did not correlate with delta-cell electrical activity but instead reflected Cat' release from the ER. These spontaneous [Ca2+](i) spikes are resistant to PKI but sensitive to ESI-05 or thapsigargin. We propose that cAMP links an increase in plasma glucose to stimulation of somatostatin secretion by promoting CICR, thus evoking exocytosis of somatostatin-containing secretory vesicles in the delta-cell.
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| 1065. |
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| 1066. |
- Follette, Katherine B., et al.
(författare)
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SEEDS ADAPTIVE OPTICS IMAGING OF THE ASYMMETRIC TRANSITION DISK OPH IRS 48 IN SCATTERED LIGHT
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 798:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first resolved near-infrared imagery of the transition disk Oph IRS 48 (WLY 2-48), which was recently observed with ALMA to have a strongly asymmetric submillimeter flux distribution. H-band polarized intensity images show a similar to 60 AU radius scattered light cavity with two pronounced arcs of emission, one from northeast to southeast and one smaller, fainter, and more distant arc in the northwest. K-band scattered light imagery reveals a similar morphology, but with a clear third arc along the southwestern rim of the disk cavity. This arc meets the northwestern arc at nearly a right angle, revealing the presence of a spiral arm or local surface brightness deficit in the disk, and explaining the east-west brightness asymmetry in the H-band data. We also present 0.8-5.4 mu m IRTF SpeX spectra of this object, which allow us to constrain the spectral class to A0 +/- 1 and measure a low mass accretion rate of 10(-8.5) M-circle dot yr(-1), both consistent with previous estimates. We investigate a variety of reddening laws in order to fit the multiwavelength spectral energy distribution of Oph IRS 48 and find a best fit consistent with a younger, higher luminosity star than previous estimates.
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| 1067. |
- Fornander, Louise, 1984, et al.
(författare)
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Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament
- 2014
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 42:4, s. 2358-2365
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Tidskriftsartikel (refereegranskat)abstract
- The Swi5-Sfr1 heterodimer protein stimulates the Rad51-promoted DNA strand exchange reaction, a crucial step in homologous recombination. To clarify how this accessory protein acts on the strand exchange reaction, we have analyzed how the structure of the primary reaction intermediate, the Rad51/single-stranded DNA (ssDNA) complex filament formed in the presence of ATP, is affected by Swi5-Sfr1. Using flow linear dichroism spectroscopy, we observe that the nucleobases of the ssDNA are more perpendicularly aligned to the filament axis in the presence of Swi5-Sfr1, whereas the bases are more randomly oriented in the absence of Swi5-Sfr1. When using a modified version of the natural protein where the N-terminal part of Sfr1 is deleted, which has no affinity for DNA but maintained ability to stimulate the strand exchange reaction, we still observe the improved perpendicular DNA base orientation. This indicates that Swi5-Sfr1 exerts its activating effect through interaction with the Rad51 filament mainly and not with the DNA. We propose that the role of a coplanar alignment of nucleobases induced by Swi5-Sfr1 in the presynaptic Rad51/ssDNA complex is to facilitate the critical matching with an invading double-stranded DNA, hence stimulating the strand exchange reaction.
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| 1068. |
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| 1069. |
|
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| 1070. |
- Gadjeva, M, et al.
(författare)
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Mannan-binding lectin modulates the response to HSV-2 infection.
- 2004
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 138:2, s. 304-11
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Tidskriftsartikel (refereegranskat)abstract
- Viruses have developed numerous strategies to escape recognition by the immune system. However, some viruses such as herpes simplex virus-2 (HSV-2) are recognized by initiators of the complement system, e.g. mannan-binding lectin (MBL). To study the effects of MBL deficiency during viral infection we have chosen a model of generalized HSV-2 infection. We infected MBL-A and MBL-C double knock-out mice (DKO) with HSV-2 via the intraperitoneal (i.p.) route. DKO mice cleared HSV-2 from the liver less efficiently than the comparable wild-type animals. The impairment to effectively neutralize HSV-2 correlated with compromised liver function as measured by increased plasma levels of alanine-amino transferase. No differences in the viral burden were found in other organs such as spleen or brain. Thus, MBL-mediated protection was limited to the effects of preservation of liver homeostasis. Reconstitution with recombinant human MBL before and during the HSV-2 infection dramatically lowered the viral titres in the liver. Taken together, the data show that MBL modulates the response to HSV-2 in mice by affecting neutralization of the virus. To analyse if MBL plays a role in establishment and progression of human HSV-2 infection we analysed MBL levels in the serum samples from asymptomatic (virus-exposed people who have never displayed symptoms of HSV-2 infection) and symptomatic HSV-2 patients (people with recurrent HSV-2 infections). We found that the frequency of the MBL deficiency (<100 ng/ml) was higher in the symptomatic group and significantly different from that in the asymptomatic group (P = 0.0369). This suggests that lack of MBL-mediated complement activation increases susceptibility to viral infection.
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