Prostaglandin Synthesis in the Feline Adrenal Cortex

Studies were carried out on the feline adrenal gland to ascertain the role of prostaglandins in the mechanism of action of ACTH. Using tritiated arachidonic acid as a prostaglandin (PG) precursor , it was demonstrated by column and thin layer chromatography techniques that isolated trypsinized adrenocortical cells possess an active PG synthetase capable of synthesizing radiolabeled PGE, PGF, and PGA/B-like substances. Concentrations of ACTH (125 - 250 μU) which stimulate steroidogenesis enhanced the conversion of radiolabeled arachidonic acid to PGE, PGF and the PGA/B products extracted from cortical cells and incubation media. PG biosynthesis by isolated cortical cells was studied by radio immunoassay (RIA) using antisera generated against conjugates of PGE2 , PGF1α and PGF2α. PGF2α and PGE2 were identified as the primary PGs released by feline cortical cells, and steroidogenic concentrations of ACTH (50-250 μU) enhanced their release in a dose related manner. Indomethacin (10-5 M) inhibited PG and steroid release, whereas low indomethacin concentrations (10-9 M) potentiated ACTH-evoked PG and steroid release. The steroidogenic response to exogenous PGE2 was not markedly altered by indomethacin. 5 , 8, 11, 14- Eicosatetraynoic acid (ETA) inhibited PGE and PGF release , and elicited a concentration-dependent inhibition of ACTH-induced steroid release. Therefore, there appears to be a functional relationship between PG and steroid release. Such a relationship was further supported by studies on the perfused adrenal gland, which demonstrated that maximal PGF2α release in response to ACTH preceded the maximal steroidogenic response. Moreover, pregnenolone (3 μM) elicited a 30-fold increase in steroid release from isolated cortical cells but failed to augment PGF2α and PGE2 release; this study further supports the concept that PG synthesis occurs prior to the steroidogenic response to ACTH. Cycloheximide did not block the steroidogenic response to pregnenolone, but completely blocked the steroidogenic effects of ACTH. Cycloheximide also depressed basal PGF2α and PGE2 release , while ACTH-facilitated PG release was not significantly impaired. Thus, the enzymes responsible for increasing PG synthesis are activated rather than formed de novo in response to ACTH. Three steroidogenic agents, ACTH, an ACTH analogue NPS-ACTH, and monobutyryl cyclic AMP (BCAMP), increased PGF2α and PGE2 release from isolated adrenocortical cells. Calcium deprivation blocked PG and steroid release evoked by ACTH and NPS-ACTH, but only inhibited PG release elicited by BCAMP without affecting steroid release. These studies suggest a functional role for PGs in the mechanism of action of ACTH. Although the nature of this role remains to be elucidated, it appears to involve some complex interaction with calcium and cyclic nucleotides

The caspase-3-p120-RasGAP module generates a NF-κB repressor in response to cellular stress.

The nuclear factor κB (NF-κB) transcription factor is a master regulator of inflammation. Short-term NF-κB activation is generally beneficial. However, sustained NF-κB might be detrimental, directly causing apoptosis of cells or leading to a persistent damaging inflammatory response. NF-κB activity in stressed cells needs therefore to be controlled for homeostasis maintenance. In mildly stressed cells, caspase-3 cleaves p120 RasGAP, also known as RASA1, into an N-terminal fragment, which we call fragment N. We show here that this fragment is a potent NF-κB inhibitor. Fragment N decreases the transcriptional activity of NF-κB by promoting its export from the nucleus. Cells unable to generate fragment N displayed increased NF-κB activation upon stress. Knock-in mice expressing an uncleavable p120 RasGAP mutant showed exaggerated NF-κB activation when their epidermis was treated with anthralin, a drug used for the treatment of psoriasis. Our study provides biochemical and genetic evidence of the importance of the caspase-3-p120-RasGAP stress-sensing module in the control of stress-induced NF-κB activation

Demonstration of remote optical measurement configuration that correlates to glucose concentration in blood

An optical approach allowing the extraction and the separation of remote vibration sources has recently been proposed. The approach has also been applied for medical related applications as blood pressure and heart beats monitoring. In this paper we demonstrate its capability to monitor glucose concentration in blood stream. The technique is based on the tracking of temporal changes of reflected secondary speckle produced in human skin (wrist) when being illuminated by a laser beam. A temporal change in skin’s vibration profile generated due to blood pulsation is analyzed for estimating the glucose concentration. Experimental tests that were carried out in order to verify the proposed approach showed good match with the change of the glucose level at the positive slope stage as it was obtained from conventional reference measurement

TOI-257b (HD 19916b): A warm sub-saturn orbiting an evolved F-type star

We report the discovery of a warm sub-Saturn, TOI-257b (HD 19916b), based on data from NASA's Transiting Exoplanet Survey Satellite (TESS). The transit signal was detected by TESS and confirmed to be of planetary origin based on radial velocity observations. An analysis of the TESS photometry, the Minerva-Australis, FEROS, and HARPS radial velocities, and the asteroseismic data of the stellar oscillations reveals that TOI-257b has a mass of MP = 0.138 ± 0.023 M J (43.9 ± 7.3, M⊕), a radius of RP = 0.639 ± 0.013 R J (7.16 ± 0.15, R ⊕), bulk density of 0.65+0.12-0.11 (cgs), and period 18.38818 +0.00085 -0.00084 days. TOI-257b orbits a bright (V = 7.612 mag) somewhat evolved late F-type star with M∗ = 1.390 ± 0.046 rm M sun, R∗ = 1.888 ± 0.033 Rsun, Teff = 6075 ± 90 rm K, and vsin i = 11.3 ± 0.5 km s-1. Additionally, we find hints for a second non-transiting sub-Saturn mass planet on a ∼71 day orbit using the radial velocity data. This system joins the ranks of a small number of exoplanet host stars (∼100) that have been characterized with asteroseismology. Warm sub-Saturns are rare in the known sample of exoplanets, and thus the discovery of TOI-257b is important in the context of future work studying the formation and migration history of similar planetary systems

TOI-257b (HD 19916b): a warm sub-saturn orbiting an evolved F-type star

ABSTRACT We report the discovery of a warm sub-Saturn, TOI-257b (HD 19916b), based on data from NASA’s Transiting Exoplanet Survey Satellite (TESS). The transit signal was detected by TESS and confirmed to be of planetary origin based on radial velocity observations. An analysis of the TESS photometry, the Minerva-Australis, FEROS, and HARPS radial velocities, and the asteroseismic data of the stellar oscillations reveals that TOI-257b has a mass of MP = 0.138 ± 0.023 $\rm {M_J}$ (43.9 ± 7.3 $\, M_{\rm \oplus}$), a radius of RP = 0.639 ± 0.013 $\rm {R_J}$ (7.16 ± 0.15 $\, \mathrm{ R}_{\rm \oplus}$), bulk density of $0.65^{+0.12}_{-0.11}$ (cgs), and period $18.38818^{+0.00085}_{-0.00084}$ $\rm {days}$. TOI-257b orbits a bright (V = 7.612 mag) somewhat evolved late F-type star with M* = 1.390 ± 0.046 $\rm {M_{sun}}$, R* = 1.888 ± 0.033 $\rm {R_{sun}}$, Teff = 6075 ± 90 $\rm {K}$, and vsin i = 11.3 ± 0.5 km s−1. Additionally, we find hints for a second non-transiting sub-Saturn mass planet on a ∼71 day orbit using the radial velocity data. This system joins the ranks of a small number of exoplanet host stars (∼100) that have been characterized with asteroseismology. Warm sub-Saturns are rare in the known sample of exoplanets, and thus the discovery of TOI-257b is important in the context of future work studying the formation and migration history of similar planetary systems

Low- and high-density lipoproteins modulate function, apoptosis, and proliferation of primary human and murine pancreatic beta-cells

A low high-density lipoprotein (HDL) plasma concentration and the abundance of small dense low-density lipoproteins (LDL) are risk factors for developing type 2 diabetes. We therefore investigated whether HDL and LDL play a role in the regulation of pancreatic islet cell apoptosis, proliferation and secretory function. Isolated mouse and human islets were exposed to plasma lipoproteins of healthy human donors. In murine and human beta-cells LDL decreased both proliferation and maximal glucose-stimulated insulin secretion. The comparative analysis of beta-cells from wild type and LDL receptor deficient mice revealed that the inhibitory effect of LDL on insulin secretion but not on proliferation requires the LDL receptor. HDL was found to modulate the survival of both human and murine islets by decreasing basal as well as IL-1beta and glucose induced apoptosis. IL-1beta induced beta-cell apoptosis was also inhibited in the presence of either the delipidated protein or the deproteinated lipid moieties of HDL, apolipoprotein A1 (the main protein component of HDL) or sphingosine-1-phosphate (a bioactive sphingolipid mostly carried by HDL). In murine beta-cells, the protective effect of HDL against IL-1beta induced apoptosis was also observed in the absence of the HDL receptor scavenger receptor class B type 1 (SRB1). Our data show that both LDL and HDL affect function or survival of beta-cells and raise the question whether dyslipidemia contributes to beta-cell failure and hence the manifestation and progression of type 2 diabetes mellitus