566 research outputs found

    The Shared Pathoetiological Effects of Particulate Air Pollution and the Social Environment on Fetal-Placental Development

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    Exposure to particulate air pollution and socioeconomic risk factors are shown to be independently associated with adverse pregnancy outcomes; however, their confounding relationship is an epidemiological challenge that requires understanding of their shared etiologic pathways affecting fetal-placental development. The purpose of this paper is to explore the etiological mechanisms associated with exposure to particulate air pollution in contributing to adverse pregnancy outcomes and how these mechanisms intersect with those related to socioeconomic status. Here we review the role of oxidative stress, inflammation and endocrine modification in the pathoetiology of deficient deep placentation and detail how the physical and social environments can act alone and collectively to mediate the established pathology linked to a spectrum of adverse pregnancy outcomes. We review the experimental and epidemiological literature showing that diet/nutrition, smoking, and psychosocial stress share similar pathways with that of particulate air pollution exposure to potentially exasperate the negative effects of either insult alone. Therefore, socially patterned risk factors often treated as nuisance parameters should be explored as potential effect modifiers that may operate at multiple levels of social geography. The degree to which deleterious exposures can be ameliorated or exacerbated via community-level social and environmental characteristics needs further exploration

    Red blood cell folate levels in Canadian Inuit women of childbearing years: influence of food security, body mass index, smoking, education, and vitamin use

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    Background: The benefits of folic acid for prevention of congenital anomalies are well known. For the Inuit of Canada, where vitamin use is low and access to folate-rich foods limited, fortification is likely a major source of intake. We sought to determine whether red blood cell folate (RBCF) levels of Inuit women reached accepted target levels. Methods: The Inuit Health Survey, 2007–2008, included evaluation of RBCF levels among 249 randomly selected non-pregnant women of reproductive age. Using descriptive statistics and linear regression analyses, RBCF levels were assessed and compared across several socio-demographic variables to evaluate the characteristics associated with RBCF status. Results: Mean (SD) RBCF levels of 935.5 nmol/L (± 192) reached proposed target levels (> 906 nmol/L); however, 47% of women had lower than target levels. In bivariate analysis, non-smoking, higher education, higher income, food security, increased body mass index, and vitamin use were each significantly associated with higher RBCF. Increased levels of smoking had a negative association with RBCF levels (− 5.8 nmol/L per cigarette smoked per day (p = 0.001)). A total of 6.8% of women reported taking vitamin supplements, resulting in a 226 nmol/L higher RBCF level on average compared to non-users (p < 0.001). Conclusion: While mean levels of folate reached target levels, this was largely driven by the small number of women taking vitamin supplements. Our results suggest that folate status is often too low in Inuit women of childbearing years. Initiatives to improve food security, culturally relevant education on folate-rich traditional foods, vitamin supplements, and smoking cessation/reduction programs may benefit Inuit women and improve birth outcomes.publishedVersio

    Effects of cardiotrophin on adipocytes

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    Cardiotrophin (CT-1) is a naturally occurring protein member of the interleukin (IL)-6 cytokine family and signals through the gp130/leukemia inhibitory factor receptor (LIFR) heterodimer. The formation of gp130/ LIFR complex triggers the auto/trans-phosphorylation of associated Janus kinases, leading to the activation of Janus kinase/STAT and MAPK (ERK1 and -2) signaling pathways. Since adipocytes express both gp130 and LIFR proteins and are responsive to other IL-6 family cytokines, we examined the effects of CT-1 on 3T3-L1 adipocytes. Our studies have shown that CT-1 administration results in a dose- and time-dependent activation and nuclear translocation of STAT1, -3, -5A, and -5B as well as ERK1 and -2. We also confirmed the ability of CT-1 to induce signaling in fat cells in vivo. Our studies revealed that neither CT-1 nor ciliary neurotrophic factor treatment affected adipocyte differentiation. However, acute CT-1 treatment caused an increase in SOCS-3 mRNA in adipocytes and a transient decrease in peroxisome proliferator-activated receptor γ (PPARγ) mRNA that was regulated by the binding of STAT1 to the PPARγ2 promoter. The effects of CT-1 on SOCS-3 and PPARγ mRNA were independent of MAPK activation. Chronic administration of CT-1 to 3T3-L1 adipocytes resulted in a decrease of both fatty acid synthase and insulin receptor substrate-1 protein expression yet did not effect the expression of a variety of other adipocyte proteins. Moreover, chronic CT-1 treatment resulted in the development of insulin resistance as judged by a decrease in insulin-stimulated glucose uptake. In summary, CT-1 is a potent regulator of signaling in adipocytes in vitro and in vivo, and our current efforts are focused on determining the role of this cardioprotective cytokine on adipocyte physiology

    Altered gene expression and spongiotrophoblast differentiation in placenta from a mouse model of diabetes in pregnancy

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    Aims/hypothesis: Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, e.g. metabolic syndrome and hypertension. We hypothesised that adverse outcomes from diabetic pregnancies may be linked to compromised placental function, and sought to identify cellular and molecular abnormalities in diabetic placenta. Methods: Using a mouse model of diabetic pregnancy, placental gene expression was assayed at mid-gestation and cellular composition analysed at various stages. Genome-wide expression profiling was validated by quantitative PCR and tissue localisation studies were performed to identify cellular correlates of altered gene expression in diabetic placenta. Results: We detected significantly altered gene expression in diabetic placenta for genes expressed in the maternal and those expressed in the embryonic compartments. We also found altered cellular composition of the decidual compartment. In addition, the junctional and labyrinth layers were reduced in diabetic placenta, accompanied by aberrant differentiation of spongiotrophoblast cells. Conclusions/interpretation: Diabetes during pregnancy alters transcriptional profiles in the murine placenta, affecting cells of embryonic and maternal origin, and involving several genes not previously implicated in diabetic pregnancies. The molecular changes and abnormal differentiation of multiple cell types precede impaired growth of junctional zone and labyrinth, and of placenta overall. Regardless of whether these changes represent direct responses to hyperglycaemia or are physiological adaptations, they are likely to play a role in pregnancy complications and outcomes, and to have implications for developmental origins of adult disease. © 2011 Springer-Verlag

    The phylogenetic nomenclature of ornithischian dinosaurs

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    Ornithischians form a large clade of globally distributed Mesozoic dinosaurs, and represent one of their three major radiations. Throughout their evolutionary history, exceeding 134 million years, ornithischians evolved considerable morphological disparity, expressed especially through the cranial and osteodermal features of their most distinguishable representatives. The nearly two-century-long research history on ornithischians has resulted in the recognition of numerous diverse lineages, many of which have been named. Following the formative publications establishing the theoretical foundation of phylogenetic nomenclature throughout the 1980s and 1990s, many of the proposed names of ornithischian clades were provided with phylogenetic definitions. Some of these definitions have proven useful and have not been changed, beyond the way they were formulated, since their introduction. Some names, however, have multiple definitions, making their application ambiguous. Recent implementation of the International Code of Phylogenetic Nomenclature (ICPN, or PhyloCode) offers the opportunity to explore the utility of previously proposed definitions of established taxon names. Since the Articles of the ICPN are not to be applied retroactively, all phylogenetic definitions published prior to its implementation remain informal (and ineffective) in the light of the Code. Here, we revise the nomenclature of ornithischian dinosaur clades; we revisit 76 preexisting ornithischian clade names, review their recent and historical use, and formally establish their phylogenetic definitions. Additionally, we introduce five new clade names: two for robustly supported clades of later-diverging hadrosaurids and ceratopsians, one uniting heterodontosaurids and genasaurs, and two for clades of nodosaurids. Our study marks a key step towards a formal phylogenetic nomenclature of ornithischian dinosaurs. © 2021 Madzia et al

    Census of Self-Obscured Massive Stars in Nearby Galaxies with Spitzer: Implications for Understanding the Progenitors of SN 2008S-Like Transients

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    A new link in the causal mapping between massive stars and potentially fatal explosive transients opened with the 2008 discovery of the dust-obscured progenitors of the luminous outbursts in NGC 6946 and NGC 300. Here we carry out a systematic mid-IR photometric search for massive, luminous, self-obscured stars in four nearby galaxies: M33, NGC 300, M81, and NGC 6946. For detection, we use only the 3.6 micron and 4.5 micron IRAC bands, as these can still be used for multi-epoch Spitzer surveys of nearby galaxies (=<10 Mpc). We combine familiar PSF and aperture-photometry with an innovative application of image subtraction to catalog the self-obscured massive stars in these galaxies. In particular, we verify that stars analogous to the progenitors of the NGC 6946 (SN 2008S) and NGC 300 transients are truly rare in all four galaxies: their number may be as low as ~1 per galaxy at any given moment. This result empirically supports the idea that the dust-enshrouded phase is a very short-lived phenomenon in the lives of many massive stars and that these objects constitute a natural extension of the AGB sequence. We also provide mid-IR catalogs of sources in NGC 300, M81, and NGC 6946.Comment: 21 pages, 15 figures, 11 tables. Accepted by ApJ on April 12, 2010. High resolution figures and full length versions of tables 6, 8 and 10 can be accessed at http://www.astronomy.ohio-state.edu/~khan/redstars

    Late-time Light Curves of Type II Supernovae: Physical Properties of SNe and Their Environment

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    We present BVRIJHK band photometry of 6 core-collapse supernovae, SNe 1999bw, 2002hh, 2003gd, 2004et, 2005cs, and 2006bc measured at late epochs (>2 yrs) based on Hubble Space Telescope (HST), Gemini north, and WIYN telescopes. We also show the JHK lightcurves of a supernova impostor SN 2008S up to day 575. Of our 43 HST observations in total, 36 observations are successful in detecting the light from the SNe alone and measuring magnitudes of all the targets. HST observations show a resolved scattered light echo around SN 2003gd at day 1520 and around SN 2002hh at day 1717. Our Gemini and WIYN observations detected SNe 2002hh and 2004et, as well. Combining our data with previously published data, we show VRIJHK-band lightcurves and estimate decline magnitude rates at each band in 4 different phases. Our prior work on these lightcurves and other data indicate that dust is forming in our targets from day ~300-400, supporting SN dust formation theory. In this paper we focus on other physical properties derived from the late time light curves. We estimate 56Ni masses for our targets (0.5-14 x 10^{-2} Msun) from the bolometric lightcurve of each for days ~150-300 using SN 1987A as a standard (7.5 x 10^{-2} Msun). The flattening or sometimes increasing fluxes in the late time light curves of SNe 2002hh, 2003gd, 2004et and 2006bc indicate the presence of light echos. We estimate the circumstellar hydrogen density of the material causing the light echo and find that SN 2002hh is surrounded by relatively dense materials (n(H) >400 cm^{-3}) and SNe 2003gd and 2004et have densities more typical of the interstellar medium (~1 cm^{-3}). The 56Ni mass appears well correlated with progenitor mass with a slope of 0.31 x 10^{-2}, supporting the previous work by Maeda et al. (2010), who focus on more massive Type II SNe. The dust mass does not appear to be correlated with progenitor mass.Comment: We corrected the 56Ni mass of SN2005cs and Figures 8 (a) and 8 (c

    Defining early steps in <i>Bacillus subtilis</i> biofilm biosynthesis

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    ABSTRACT The Bacillus subtilis extracellular biofilm matrix includes an exopolysaccharide (EPS) that is critical for the architecture and function of the community. To date, our understanding of the biosynthetic machinery and the molecular composition of the EPS of B. subtilis remains unclear and incomplete. This report presents synergistic biochemical and genetic studies built from a foundation of comparative sequence analyses targeted at elucidating the activities of the first two membrane-committed steps in the EPS biosynthetic pathway. By taking this approach, we determined the nucleotide sugar donor and lipid-linked acceptor substrates for the first two enzymes in the B. subtilis biofilm EPS biosynthetic pathway. EpsL catalyzes the first phosphoglycosyl transferase step using uridine diphosphate (UDP)-di-N-acetyl bacillosamine as phospho-sugar donor. EpsD is a predicted GT-B fold (GT4 family) retaining glycosyl transferase that catalyzes the second step in the pathway that utilizes the product of EpsL as an acceptor substrate and UDP-N-acetyl glucosamine as the sugar donor. Thus, the study defines the first two monosaccharides at the reducing end of the growing EPS unit. In doing so, we provide the first evidence of the presence of bacillosamine in an EPS synthesized by a Gram-positive bacterium. IMPORTANCE Biofilms are the communal way of life that microbes adopt to increase survival. Key to our ability to systematically promote or ablate biofilm formation is a detailed understanding of the biofilm matrix macromolecules. Here, we identify the first two essential steps in the Bacillus subtilis biofilm matrix exopolysaccharide (EPS) synthesis pathway. Together, our studies and approaches provide the foundation for the sequential characterization of the steps in EPS biosynthesis, using prior steps to enable chemoenzymatic synthesis of the undecaprenyl diphosphate-linked glycan substrates
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