Star Formation in Galaxies Along the Hubble Sequence

Observations of star formation rates (SFRs) in galaxies provide vital clues to the physical nature of the Hubble sequence, and are key probes of the evolutionary properties of galaxies. The focus of this review is on the broad patterns in the star formation properties of galaxies along the Hubble sequence, and their implications for understanding galaxy evolution and the physical processes that drive the evolution. Star formation in the disks and nuclear regions of galaxies are reviewed separately, then discussed within a common interpretive framework. The diagnostic methods used to measure SFRs are also reviewed, and a self-consistent set of SFR calibrations is presented as an aid to workers in the field.Comment: 41 pages, with 9 figures. To appear in Volume 36 of the Annual Review of Astronomy and Astrophysic

Single-Species Microarrays and Comparative Transcriptomics

BACKGROUND: Prefabricated expression microarrays are currently available for only a few species but methods have been proposed to extend their application to comparisons between divergent genomes. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that the hybridization intensity of genomic DNA is a poor basis on which to select unbiased probes on Affymetrix expression arrays for studies of comparative transcriptomics, and that doing so produces spurious results. We used the Affymetrix Xenopus laevis microarray to evaluate expression divergence between X. laevis, X. borealis, and their F1 hybrids. When data are analyzed with probes that interrogate only sequences with confirmed identity in both species, we recover results that differ substantially analyses that use genomic DNA hybridizations to select probes. CONCLUSIONS/SIGNIFICANCE: Our findings have implications for the experimental design of comparative expression studies that use single-species microarrays, and for our understanding of divergent expression in hybrid clawed frogs. These findings also highlight important limitations of single-species microarrays for studies of comparative transcriptomics of polyploid species

PKCδ regulates force signaling during VEGF/CXCL4 induced dissociation of endothelial tubes

Wound healing requires the vasculature to re-establish itself from the severed ends; endothelial cells within capillaries must detach from neighboring cells before they can migrate into the nascent wound bed to initiate angiogenesis. The dissociation of these endothelial capillaries is driven partially by platelets' release of growth factors and cytokines, particularly the chemokine CXCL4/platelet factor-4 (PF4) that increases cell-cell de-adherence. As this retraction is partly mediated by increased transcellular contractility, the protein kinase c-δ/myosin light chain-2 (PKCδ/MLC-2) signaling axis becomes a candidate mechanism to drive endothelial dissociation. We hypothesize that PKCδ activation induces contractility through MLC-2 to promote dissociation of endothelial cords after exposure to platelet-released CXCL4 and VEGF. To investigate this mechanism of contractility, endothelial cells were allowed to form cords following CXCL4 addition to perpetuate cord dissociation. In this study, CXCL4-induced dissociation was reduced by a VEGFR inhibitor (sunitinib malate) and/or PKCδ inhibition. During combined CXCL4+VEGF treatment, increased contractility mediated by MLC-2 that is dependent on PKCδ regulation. As cellular force is transmitted to focal adhesions, zyxin, a focal adhesion protein that is mechano-responsive, was upregulated after PKCδ inhibition. This study suggests that growth factor regulation of PKCδ may be involved in CXCL4-mediated dissociation of endothelial cords. © 2014 Jamison et al

The diversity of reproductive parasites among arthropods: Wolbachia do not walk alone

<p>Abstract</p> <p>Background</p> <p>Inherited bacteria have come to be recognised as important components of arthropod biology. In addition to mutualistic symbioses, a range of other inherited bacteria are known to act either as reproductive parasites or as secondary symbionts. Whilst the incidence of the α-proteobacterium <it>Wolbachia </it>is relatively well established, the current knowledge of other inherited bacteria is much weaker. Here, we tested 136 arthropod species for a range of inherited bacteria known to demonstrate reproductive parasitism, sampling each species more intensively than in past surveys.</p> <p>Results</p> <p>The inclusion of inherited bacteria other than <it>Wolbachia </it>increased the number of infections recorded in our sample from 33 to 57, and the proportion of species infected from 22.8% to 32.4%. Thus, whilst <it>Wolbachia </it>remained the dominant inherited bacterium, it alone was responsible for around half of all inherited infections of the bacteria sampled, with members of the <it>Cardinium</it>, <it>Arsenophonus </it>and <it>Spiroplasma ixodetis </it>clades each occurring in 4% to 7% of all species. The observation that infection was sometimes rare within host populations, and that there was variation in presence of symbionts between populations indicates that our survey will itself underscore incidence.</p> <p>Conclusion</p> <p>This extensive survey demonstrates that at least a third of arthropod species are infected by a diverse assemblage of maternally inherited bacteria that are likely to strongly influence their hosts' biology, and indicates an urgent need to establish the nature of the interaction between non-<it>Wolbachia </it>bacteria and their hosts.</p

Evaluation of pseudoephedrine pharmacy sales before and after mandatory recording requirements in Western Australia: a case study

Background: A community pharmacy real-time electronic recording program, ProjectSTOP, enables Australian community pharmacists to verify pseudoephedrine requests. In Western Australia the program was available for voluntary use from April 2007 and became mandatory November 2010. This case study explores the effectiveness of the program by reviewing the total requests for pseudoephedrine products, and the proportion of requests which were classified as ‘denied sales’ before and after mandatory implementation. Seasonal and annual trends in these measures are also evaluated. Methods: ProjectSTOP data recordings for Western Australia pharmacies between 1 December 2007 and 28 February 2014 were analysed. Data included a de-identified pharmacy number and date of each pseudoephedrine product request. The total number of requests and sale classification (allowed, denied, safety, or not recorded) were calculated for each month/pharmacy. The potential influence of mandatory reporting using ProjectSTOP was investigated using a Regression Discontinuity Design. Correlations between sales from the same pharmacy were taken into account by classifying the pharmacy number as a random effect. The main effects of year (continuous variable), and season (categorical variable) were also included in the model. Results: There was a small but steady decline in the total requests for pseudoephedrine per month per 100,000 population (per pharmacy) from the time of mandatory reporting. The number of denied sales showed a steady increase up until mandatory reporting, after which it showed a significant decline over time. Total sales were heavily influenced by season, as expected (highest in winter, least in summer). The seasonal pattern was less pronounced for denied sales, which were highest in winter and similar across other seasons. The pattern over time for safety sales was similar to that for denied sales, with a clear change occurring around the time of mandatory reporting. Conclusion: Results indicate a decrease in pseudoephedrine product requests in Western Australia community pharmacies. Findings suggest ProjectSTOP has been successful in addressing suspicious sales and potential diversion however ongoing data review is recommended

Drug Discovery for Duchenne Muscular Dystrophy via Utrophin Promoter Activation Screening

Background: Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. Methodology/Principal Findings: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. Conclusions/Significance: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics an

Dysregulated Cytokine Expression by CD4+ T cells from Post-Septic Mice Modulates both Th1 and Th2-Mediated Granulomatous Lung Inflammation

Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative) and TH2-(Schistosoma mansoni egg antigen) driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of TH2 cytokines in TH1 inflammation, and increased production of TH1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression

Gas flows, star formation and galaxy evolution

In the first part of this article we show how observations of the chemical evolution of the Galaxy: G- and K-dwarf numbers as functions of metallicity, and abundances of the light elements, D, Li, Be and B, in both stars and the interstellar medium (ISM), lead to the conclusion that metal poor HI gas has been accreting to the Galactic disc during the whole of its lifetime, and is accreting today at a measurable rate, ~2 Msun per year across the full disc. Estimates of the local star formation rate (SFR) using methods based on stellar activity, support this picture. The best fits to all these data are for models where the accretion rate is constant, or slowly rising with epoch. We explain here how this conclusion, for a galaxy in a small bound group, is not in conflict with graphs such as the Madau plot, which show that the universal SFR has declined steadily from z=1 to the present day. We also show that a model in which disc galaxies in general evolve by accreting major clouds of low metallicity gas from their surroundings can explain many observations, notably that the SFR for whole galaxies tends to show obvious variability, and fractionally more for early than for late types, and yields lower dark to baryonic matter ratios for large disc galaxies than for dwarfs. In the second part of the article we use NGC 1530 as a template object, showing from Fabry-Perot observations of its Halpha emission how strong shear in this strongly barred galaxy acts to inhibit star formation, while compression acts to stimulate it.Comment: 20 pages, 10 figures, to be presented at the "Penetrating Bars through Masks of Cosmic Dust" conference in South Africa, proceedings published by Kluwer, Eds. D.L. Block, K.C. Freeman, I. Puerari, & R. Groes

Murine Pancreatic Adenocarcinoma Reduces Ikaros Expression and Disrupts T Cell Homeostasis

Background Maintenance of T cell immune homeostasis is critical for adequate anti-tumor immunity. The transcription factor Ikaros is essential for lymphocyte development including T cells. Alterations in Ikaros expression occur in blood malignancies in humans and mice. In this study, we investigated the role of Ikaros in regulating T cell immune balance in pancreatic cancer mouse models. Methodology and Principal Findings Using our Panc02 tumor-bearing (TB) mouse model, western blot analysis revealed a reduction in Ikaros proteins while qRT-PCR showed no differences in Ikaros mRNA levels in TB splenocytes compared to control. Treatment of naïve splenocytes with the proteasomal inhibitor, MG132, stabilized Ikaros expression and prevented Ikaros downregulation by Panc02 cells, in vitro. Western blot analyses showed a reduction in protein phosphatase 1 (PP1) and protein kinase CK2 expression in TB splenocytes while CK2 activity was increased. Immunofluorescence microscopy revealed altered punctate staining of Ikaros in TB splenocytes. Flow cytometry revealed a significant decrease in effector CD4+ and CD8+ T cell percentages but increased CD4+CD25+ regulatory T cells in TB splenocytes. Similar alterations in T cell percentages, as well as reduced Ikaros and CK2 but not PP1 expression, were observed in a transgenic, triple mutant (TrM) pancreatic cancer model. Ikaros expression was also reduced in enriched TB CD3+ T cells. MG132 treatment of naïve CD3+ T cells stabilized Ikaros expression in the presence of Panc02 cells. Western blots showed reduced PP1 and CK2 expression in TB CD3+ T cells. Conclusions/Significance The results of this study suggest that the pancreatic tumor microenvironment may cause proteasomal degradation of Ikaros, possibly via dysregulation of PP1 and CK2 expression and activity, respectively. This loss of Ikaros expression may contribute to an imbalance in T cell percentages. Ikaros may potentially be a therapeutic target to restore T cell homeostasis in pancreatic cancer hosts, which may be critical for effective anti-tumor immunity