Pyrolysis-GC×GC-TOFMS to characterize carbonaceous chondrites

Using pyrolysis-GCxGC-TOFMS to analyze organic carbon in carbonaceous chondrites gives a massive increase in both sensitivity and structural information from samples when compared to traditional Py-GC-MS

Glucocorticoid therapy for adrenal insufficiency: nonadherence, concerns and dissatisfaction with information

Objective: Appropriate self‐management of glucocorticoid therapy (GC) is crucial for patients with adrenal insufficiency (AI). We aimed to describe patients’ self‐reported nonadherence to GC, evaluate perceived doubts about need for GC, concerns about adverse effects, and dissatisfaction with information received about GC. Design: Cross‐sectional survey. Patients: Patients prescribed GC for AI (n = 81) from five European countries. Measurements: Online survey including the Medication Adherence Report Scale (MARS), Beliefs about Medicines Questionnaire© (BMQ Specific, adapted for AI) and Satisfaction with Information about Medicines Scale© (Prof Rob Horne; SIMS). Results: Most patients (85·2%) reported a degree of nonadherence to GC. The most frequent types of nonadherence concerned changing the timing of GC doses, for example taking a dose later in the day than advised (37·0%). Few patients doubted their personal need for daily GC, but most reported high concerns about GC including potential weight gain (50·6%), osteoporosis (53·6%) and the continuing risk of adrenal crisis (50·6%). Dissatisfaction with information about GC was frequent, with participants particularly dissatisfied with the amount of information they had received about potential problems with GC. People who expressed dissatisfaction with information about GC, and concerns about its adverse effects were also more likely to report nonadherence (P < 0·05). Conclusions: Nonadherence to treatment, concerns about potential adverse effects and dissatisfaction with the information provided about treatment were frequently reported by this European sample of AI patients. Many AI patients may need additional information about their GC and support to address concerns about GC and facilitate adherence

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

The Presence of GC-C in Extracellular Vesicles Secreted by Colorectal Cancer Cells

Background: Guanylyl Cyclase C (GC-C) is a membrane-bound protein found on intestinal epithelial cells involved in the activation of CFTR. This protein has previously been involved in the development of colorectal cancer. Extracellular vesicles (EVs) are bilayered vesicles of varying size (30 to 1,000 + nm in diameter) that believed to be secreted by all cells in the human body. In the past decade, EVs have garnered attention due to their impact in the field of oncology, where they have been shown to potentially serve as biomarkers for various cancers. In this study, we looked at the EVs secreted by GC-C+ and GC-C- cell lines. We expected GC-C to be present on the EVs secreted by GC-C+ cell lines and that this finding may intake a role for GC-C at tissues distal to the intestinal epithelial cells. Methods: GC-C+ cells lines (T84 and CT26-hGCC) and GC-C- cell lines (SW480 and CT26-WT) were cultured and their media was harvested, then ultracentrifuged to extract the EVs from the media. These EVs were then checked for the presence and absence of various markers (GC-C, Calnexin, TSG101) via Western Blot. Exosome size was assessed via NTA to further provide evidence for the identity of these EVs. Results: Western blot confirmed the presence of TSG101 in both EV types samples, as well as the presence of GC-C in EVs derived from GC-C+ cell lines, but not from GC-C- cell lines. Calnexin was found to be absent in EV samples, excluding the possibility of lysate contamination. NTA analysis confirmed the correct size for the exosomes in sample. Discussion: This study assessed the contents of EVs secreted by colorectal cancer cell lines. Our findings indicate the presence of GC-C on exosomes and microvesicles. Further studies will need to be conducted in order to assess the function of these GC-C+ EVs in the setting of colorectal cancer

The Globular Cluster Population of NGC 7457: Clues to the Evolution of Field S0 Galaxies

In this paper we present the results of a wide-field imaging study of the globular cluster (GC) system of the field S0 galaxy NGC 7457. To derive the global properties of the GC system, we obtained deep BVR images with the WIYN 3.5 m telescope and Minimosaic Imager and studied the GC population of NGC 7457 to a projected radius of approximately 30 kpc. Our ground-based data were combined with archival and published Hubble Space Telescope data to probe the properties of the GC system close to the galaxy center and reduce contamination in the GC candidate sample from foreground stars and background galaxies. We performed surface photometry of NGC 7457 and compared the galaxy's surface brightness profile with the surface density profile of the GC system. The profiles have similar shapes in the inner 1 arcminute (3.9 kpc), but the GC system profile appears to flatten relative to the galaxy light at larger radii. The GC system of NGC 7457 is noticeably elliptical in our images; we measure an ellipticity of 0.66 +/- 0.14 for the GC distribution, which is consistent with our measured ellipticity of the galaxy light. We integrated the radial surface density profile of the GC system to derive a total number of GCs N_GC = 210 +/- 30. The GC specific frequency normalized by the galaxy luminosity and mass are S_N = 3.1 +/- 0.7 and T = 4.8 +/- 1.1, respectively. Comparing the derived GC system properties and other empirical data for NGC 7457 to S0 formation scenarios suggests that this field S0 galaxy may have formed in an unequal-mass merger.Comment: 40 pages, 10 figures, accepted for publication in The Astrophysical Journa

The Globular Cluster System of M60 (NGC 4649). II. Kinematics of the Globular Cluster System

We present a kinematic analysis of the globular cluster (GC) system in the giant elliptical galaxy (gE) M60 in the Virgo cluster. Using the photometric and spectroscopic database of 121 GCs (83 blue GCs and 38 red GCs), we have investigated the kinematics of the GC system. We have found that the M60 GC system shows a significant overall rotation. The rotation amplitude of the blue GCs is slightly smaller than or similar to that of the red GCs, and their angles of rotation axes are similar. The velocity dispersions about the mean velocity and about the best fit rotation curve for the red GCs are marginally larger than those for the blue GCs. Comparison of observed stellar and GC velocity dispersion profiles with those calculated from the stellar mass profile shows that the mass-to-light ratio should be increased as the galactocentric distance increases, indicating the existence of an extended dark matter halo. The entire sample of GCs in M60 is found to have a tangentially biased velocity ellipsoid unlike the GC systems in other gEs. Two subsamples appear to have different velocity ellipsoids. The blue GC system has a modest tangentially biased velocity ellipsoid, while the red GC system has a modest radially biased or an isotropic velocity ellipsoid. From the comparison of the kinematic properties of the M60 GC system to those of other gEs (M87, M49, NGC 1399, NGC 5128, and NGC 4636), it is found that the velocity dispersion of the blue GC system is similar to or larger than that of the red GC system except for M60, and the rotation of the GC system is not negligible. The entire sample of each GC system shows an isotropic velocity ellipsoid except for M60, while the subsamples show diverse velocity ellipsoids. We discuss the implication of these results for the formation models of the GC system in gEs.Comment: 48 pages, 16 figures. To appear in Ap

The G protein-coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination.

The orphan Gα13-coupled receptor P2RY8 is mutated in human germinal center (GC)-derived lymphomas and was recently found to promote B cell association with GCs in a mouse model. Here we establish that P2RY8 promotes clustering of activated B cells within follicles in a follicular dendritic cell (FDC)-dependent manner. Although mice lack a P2RY8 orthologue, we show that mouse GC B cell clustering is also dependent on FDCs acting to support the function of a Gα13-coupled receptor. Mutations in GNA13 and its downstream effector ARHGEF1 are associated with the development of disseminated GC-derived lymphomas. We find that egress of Gna13 mutant GC B cells from lymph nodes in the mouse depends on sphingosine-1-phosphate receptor-3. These findings provide evidence that FDCs promote GC confinement of both human and mouse GC B cells via Gα13-dependent pathways, and they show that dissemination of Gα13-deficient GC B cells additionally requires an egress-promoting receptor