Global Properties of the Globular Cluster Systems of Four Spiral Galaxies

We present results from a wide-field imaging study of the globular cluster (GC) systems of a sample of edge-on, Sb-Sc spiral galaxies ~7-20 Mpc away. This study is part of a larger survey of the ensemble properties of the GC populations of giant galaxies. We imaged the galaxies in BVR filters with large-format CCD detectors on the WIYN 3.5-m telescope, to projected radii of ~20-40 kpc. For four galaxies (NGC 2683, NGC 3556, NGC 4157, and NGC 7331), we quantify the radial distributions of the GC systems and estimate the total number, luminosity- and mass-normalized specific frequencies (S_N and T), and blue (metal-poor) fraction of GCs. A fifth galaxy (NGC 3044) was apparently too distant for us to have detected its GC system. Our S_N for NGC 2683 is 2.5 times smaller than the previously-published value, likely due in part to reduced contamination from non-GCs. For the spiral galaxies analyzed for the survey to date, the average number of GCs is 170+/-40 and the weighted mean values of S_N and T are 0.8+/-0.2 and 1.4+/-0.3. We use the survey data to derive a relationship between radial exent of the GC system and host galaxy mass over a factor of 20 in mass. Finally, we confirm the trend, identified in previous survey papers, of increasing specific frequency of metal-poor GCs with increasing galaxy mass. We compare the data with predictions from a simple model and show that carefully quantifying the numbers of metal-poor GCs in galaxies can constrain the formation redshifts of the GCs and their host galaxies.Comment: 30 pages, including 14 figures and 13 tables; accepted for publication in The Astronomical Journal, Oct 2007 issu

Free versus total serum 25-hydroxyvitamin D in a murine model of colitis

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease have been linked to vitamin D-deficiency. Using a dextran sodium sulphate (DSS)-induced model of IBD we have shown previously that mice raised on vitamin D-deficient diets from weaning have lower serum 25-hydroxyvitamin D (25OHD) levels and develop more severe colitis compared to vitamin D-sufficient counterparts. We have also shown in vitro that immune responses to 25OHD may depend on 'free' rather than total serum concentrations of 25OHD. To investigate the possible effects of free versus total 25OHD on anti-inflammatory immune responses in vivo we have studied DSS-induced colitis in wild type C57BL/6 mice raised from weaning on diets containing vitamin D2 (D2) or vitamin D3 (D3) only (both 1000 IU/kg feed). 25OHD2 has lower binding affinity for the vitamin D binding protein than 25OHD3 which results in higher levels of free 25OHD2 relative to free 25OHD3 in mice raised on a D2-only diet. Total serum 25OHD concentrations, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), showed that D2 mice had significantly lower levels of 25OHD than D3 mice (6.85 ± 2.61 nmol/L vs. 49.16 ± 13.8 nmol/L for D2 and D3 respectively). Despite this, direct ELISA measurement showed no difference in free serum 25OHD levels between D2 and D3 mice (13.62 ± 2.26 pmol/L vs. 14.11 ± 2.24 pmol/L for D2 and D3 respectively). Analysis of DSS-induced colitis also showed no difference in weight loss or disease progression between D2 and D3 mice. These data indicate that despite D2-fed mice being vitamin D-deficient based on serum total 25OHD concentrations, these mice showed no evidence of increased inflammatory colitis disease relative to vitamin D-sufficient D3 mice. We therefore propose that free, rather than total serum 25OHD, may be a better marker of immune responses to vitamin D in vivo

Acute NMDA toxicity in cultured rat cerebellar granule neurons is accompanied by autophagy induction and late onset autophagic cell death phenotype

<p>Abstract</p> <p>Background</p> <p>Autophagy, an intracellular response to stress, is characterized by double membrane cytosolic vesicles called autophagosomes. Prolonged autophagy is known to result in autophagic (Type II) cell death. This study examined the potential role of an autophagic response in cultured cerebellar granule neurons challenged with excitotoxin N-methyl-D-aspartate (NMDA).</p> <p>Results</p> <p>NMDA exposure induced light chain-3 (LC-3)-immunopositive and monodansylcadaverine (MDC) fluorescent dye-labeled autophagosome formation in both cell bodies and neurites as early as 3 hours post-treatment. Elevated levels of Beclin-1 and the autophagosome-targeting LC3-II were also observed following NMDA exposure. Prolonged exposure of the cultures to NMDA (8-24 h) generated MDC-, LC3-positive autophagosomal bodies, concomitant with the neurodegenerative phase of NMDA challenge. Lysosomal inhibition studies also suggest that NMDA-treatment diverted the autophagosome-associated LC3-II from the normal lysosomal degradation pathway. Autophagy inhibitor 3-methyladenine significantly reduced NMDA-induced LC3-II/LC3-I ratio increase, accumulation of autophagosomes, and suppressed NMDA-mediated neuronal death. ATG7 siRNA studies also showed neuroprotective effects following NMDA treatment.</p> <p>Conclusions</p> <p>Collectively, this study shows that autophagy machinery is robustly induced in cultured neurons subjected to prolonged exposure to excitotoxin, while autophagosome clearance by lysosomal pathway might be impaired. Our data further show that prolonged autophagy contributes to cell death in NMDA-mediated excitotoxicity.</p

The open source guild: creating more sustainable enterprise?

© 2017, © Emerald Publishing Limited. Purpose: The purpose of this paper is to report on an action research project with two emergent micro-businesses that explored how their business model connected with the principles of open source. Design/methodology/approach: The authors first gained initial qualitative data to establish the core values of each micro-business, which the authors then explored in the context of open source and business models in two design workshops with each organisation. Findings: The authors developed the open source guild business model, which has the elements of: building a focal micro-business with resources secured through the guild, promoting learning and development through apprenticeship, promoting shared values through a commons of experience and capturing value by protecting key intellectual property. Research limitations/implications: This research was undertaken with two emergent micro-businesses in the North West of England. Further research will be needed to establish the wider applicability of the open source guild model. Practical implications: The open source guild model can be a mechanism for an emergent micro-business to create a community around their values and grow their business without conventional external investment of resources. Originality/value: This research contributes to the literature on business models based on open source and how these models can be sustainable in terms of the quadruple bottom line, which extends the triple bottom line to include personal values and meaning

The Signal Transducer and Activator of Transcription 1 (STAT1) Inhibits Mitochondrial Biogenesis in Liver and Fatty Acid Oxidation in Adipocytes

The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a master regulator of mitochondrial biogenesis. STAT1 binds to the PGC1α promoter in fed mice but not in fasted animals, suggesting that STAT1 inhibited transcription of PGC1α. Since STAT1-/-mice utilized more lipids we examined white adipose tissue (WAT) stores. Contrary to expectations, fasted STAT1-/- mice did not lose lipid from WAT. β-adrenergic stimulation of glycerol release from isolated STAT1-/- WAT was decreased, while activation of hormone sensitive lipase was not changed. These findings suggest that STAT1-/- adipose tissue does not release glycerol and that free fatty acids (FFA) re-esterify back to triglycerides, thus maintaining fat mass in fasted STAT1-/- mice

Creating citizen-consumers? Public service reform and (un)willing selves

About the book: Postmodern theories heralded the "death of the subject", and thereby deeply contested our intuition that we are free and willing selves. In recent times, the (free) will has come under attack yet again. Findings from the neuro- and cognitive sciences claim the concept of will to be scientifically untenable, specifying that it is our brain rather than our 'self' which decides what we want to do. In spite of these challenges however, the willing self has come to take centre stage in our society: juridical and moral practices ascribing guilt, or the organization of everyday life attributing responsibilities, for instance, can hardly be understood without taking recourse to the willing subject. In this vein, the authors address topics such as the genealogy of the concept of willing selves, the discourse on agency in neuroscience and sociology, the political debate on volition within neoliberal and neoconservative regimes, approaches toward novel forms of relational responsibility as well as moral evaluations in conceptualizing autonomy

Obliged to calculate: My School, markets, and equipping parents for calculativeness

This paper argues neoliberal programs of government in education are equipping parents for calculativeness. Regimes of testing and the publication of these results and other organizational data are contributing to a public economy of numbers that increasingly oblige citizens to calculate. Using the notions of calculative and market devices, this paper examines the Australian Government’s My School website, which publishes academic and organizational information about schools, including national test results. While it is often assumed that such performance technologies contribute to neoliberal reform of education through school choice, the paper argues the website is technically limited in its capacity to facilitate the economic calculations and calculated action of parents resulting in school choice. The paper instead opens My School to analysis as a technique of governmental self-formation. Using the theoretical resources of actor-network theory and Foucauldian scholarship, this paper complicates assumptions in the literature about the extent to which My School actually operates as a ‘market mechanism’. It argues My School attempts to cultivate a calculated form of parental educational agency, irreducible to economic market agency

Stat3 oxidation-dependent regulation of gene expression impacts on developmental processes and involves cooperation with Hif-1α

© 2020 Grillo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Reactive oxygen species are bona fide intracellular second messengers that influence cell metabolism and aging by mechanisms that are incompletely resolved. Mitochondria generate superoxide that is dis-mutated to hydrogen peroxide, which in turn oxidises cysteine-based enzymes such as phosphatases, peroxiredoxins and redox-sensitive transcription factors to modulate their activity. Signal Transducer and Activator of Transcription 3 (Stat3) has been shown to participate in an oxidative relay with peroxiredoxin II but the impact of Stat3 oxidation on target gene expression and its biological consequences remain to be established. Thus, we created murine embryonic fibroblasts (MEFs) that express either WTStat3 or a redox-insensitive mutant of Stat3 (Stat3-C3S). The Stat3-C3S cells differed from WT-Stat3 cells in morphology, proliferation and resistance to oxidative stress; in response to cytokine stimulation, they displayed elevated Stat3 tyrosine phosphorylation and Socs3 expression, implying that Stat3-C3S is insensitive to oxidative inhibition. Comparative analysis of global gene expression in WT-Stat3 and Stat3-C3S cells revealed differential expression (DE) of genes both under basal conditions and during oxidative stress. Using differential gene regulation pattern analysis, we identified 199 genes clustered into 10 distinct patterns that were selectively responsive to Stat3 oxidation. GO term analysis identified down-regulated genes to be enriched for tissue/organ development and morphogenesis and up-regulated genes to be enriched for cell-cell adhesion, immune responses and transport related processes. Although most DE gene promoters contain consensus Stat3 inducible elements (SIEs), our chromatin immunoprecipitation (ChIP) and ChIP-seq analyses did not detect Stat3 binding at these sites in control or oxidant-stimulated cells, suggesting that oxidised Stat3 regulates these genes indirectly. Our further computational analysis revealed enrichment of hypoxia response elements (HREs) within DE gene promoters, implying a role for Hif-1. Experimental validation revealed that efficient stabilisation of Hif-1α in response to oxidative stress or hypoxia required an oxidation-competent Stat3 and that depletion of Hif-1α suppressed the inducible expression of Kcnb1, a representative DE gene. Our data suggest that Stat3 and Hif-1α cooperate to regulate genes involved in immune functions and developmental processes in response to oxidative stress