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

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 destruction and survival of dust in the shell around SN 2008S

SN 2008S erupted in early 2008 in the grand design spiral galaxy NGC 6946. The progenitor was detected by Prieto et al. in Spitzer Space Telescope images taken over the four years prior to the explosion, but was not detected in deep optical images, from which they inferred a self-obscured object with a mass of about 10 Msun. We obtained Spitzer observations of SN 2008S five days after its discovery, as well as coordinated Gemini and Spitzer optical and infrared observations six months after its outburst. We have constructed radiative transfer dust models for the object before and after the outburst, using the same r^-2 density distribution of pre-existing amorphous carbon grains for all epochs and taking light-travel time effects into account for the early post-outburst epoch. We rule out silicate grains as a significant component of the dust around SN 2008S. The inner radius of the dust shell moved outwards from its pre-outburst value of 85 AU to a post-outburst value of 1250 AU, attributable to grain vaporisation by the light flash from SN 2008S. Although this caused the circumstellar extinction to decrease from Av = 15 before the outburst to 0.8 after the outburst, we estimate that less than 2% of the overall circumstellar dust mass was destroyed. The total mass-loss rate from the progenitor star is estimated to have been (0.5-1.0)x10^-4 Msun yr^-1. The derived dust mass-loss rate of 5x10^-7 Msun yr^-1 implies a total dust injection into the ISM of up to 0.01 Msun over the suggested duration of the self-obscured phase. We consider the potential contribution of objects like SN 2008S to the dust enrichment of galaxies.Comment: 9 pages, 7 figures, 3 tables. rv2. To appear in MNRA

The type IIb SN 2008ax: spectral and light curve evolution

We present spectroscopy and photometry of the He-rich supernova (SN) 2008ax. The early-time spectra show prominent P-Cygni H lines, which decrease with time and disappear completely about two months after the explosion. In the same period He I lines become the most prominent spectral features. SN 2008ax displays the ordinary spectral evolution of a type IIb supernova. A stringent pre-discovery limit constrains the time of the shock breakout of SN 2008ax to within only a few hours. Its light curve, which peaks in the B band about 20 days after the explosion, strongly resembles that of other He-rich core-collapse supernovae. The observed evolution of SN 2008ax is consistent with the explosion of a young Wolf-Rayet (of WNL type) star, which had retained a thin, low-mass shell of its original H envelope. The overall characteristics of SN 2008ax are reminiscent of those of SN 1993J, except for a likely smaller H mass. This may account for the findings that the progenitor of SN 2008ax was a WNL star and not a K supergiant as in the case of SN 1993J, that a prominent early-time peak is missing in the light curve of SN 2008ax, and that Halpha is observed at higher velocities in SN 2008ax than in SN 1993J.Comment: 10 pages, including 8 figures and 4 tables. Accepted for publication in MNRA

SN 2008S: an electron capture SN from a super-AGB progenitor?

We present comprehensive photometric and spectroscopic observations of the faint transient SN 2008S discovered in NGC 6946. SN 2008S exhibited slow photometric evolution and almost no spectral variability during the first nine months, implying a high density CS medium. The light curve is similar in shape to that of SN 1998S and SN 1979C, although significantly fainter at maximum light. Our quasi-bolometric lightcurve extends to 300 days and shows a tail phase decay rate consistent with that of ^{56}Co. We propose that this is evidence for an explosion and formation of ^{56}Ni (0.0015 +/- 0.0004 M_Sun). The large MIR flux detected shortly after explosion can be explained by a light echo from pre-exisiting dust. The late NIR flux excess is plausibly due to a combination of warm newly-formed ejecta dust together with shock-heated dust in the CS environment. We reassess the progenitor object detected previously in Spitzer archive images, supplementing this discussion with a model of the MIR spectral energy distribution. This supports the idea of a dusty, optically thick shell around SN 2008S with an inner radius of nearly 90AU and outer radius of 450AU, and an inferred heating source of 3000 K and luminosity of L ~ 10^{4.6} L_Sun. The combination of our monitoring data and the evidence from the progenitor analysis leads us to support the scenario of a weak electron capture supernova explosion in a super-AGB progenitor star (of initial mass 6-8 M_sun) embedded within a thick CS gaseous envelope. We suggest that all of main properties of the electron capture SN phenomenon are observed in SN 2008S and future observations may allow a definitive answer.Comment: accepted for publication in MNRAS (2009 May 7

Mental Health Recovery Narratives and Their Impact on Recipients: Systematic Review and Narrative Synthesis.

OBJECTIVE: Mental health recovery narratives are often shared in peer support work and antistigma campaigns. Internet technology provides access to an almost unlimited number of narratives, and yet little is known about how they affect recipients. The aim of this study was to develop a conceptual framework characterizing the impact of recovery narratives on recipients. METHOD: A systematic review of evidence about the impact of mental health recovery narratives was conducted. Searches used electronic databases ( n = 9), reference tracking, hand-searching of selected journals ( n = 2), grey literature searching, and expert consultation ( n = 7). A conceptual framework was generated through a thematic analysis of included articles, augmented by consultation with a Lived Experience Advisory Panel. RESULTS: In total, 8137 articles were screened. Five articles were included. Forms of impact were connectedness, understanding of recovery, reduction in stigma, validation of personal experience, affective responses, and behavioural responses. Impact was moderated by characteristics of the recipient, context, and narrative. Increases in eating disorder behaviours were identified as a harmful response specific to recipients with eating disorders. CONCLUSIONS: Mental health recovery narratives can promote recovery. Recovery narratives might be useful for clients with limited access to peers and in online interventions targeted at reducing social isolation in rural or remote locations, but support is needed for the processing of the strong emotions that can arise. Caution is needed for use with specific clinical populations. Protocol registration: Prospero-CRD42018090923

derived neutrophil to lymphocyte ratio dnlr change between baseline and cycle 2 is correlated with benefit during immune checkpoint inhibitors ici in advanced non small cell lung cancer nsclc patients

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Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

The Transitional Stripped-Envelope SN 2008ax: Spectral Evolution and Evidence for Large Asphericity

Supernova (SN) 2008ax in NGC 4490 was discovered within hours after shock breakout, presenting the rare opportunity to study a core-collapse SN beginning with the initial envelope-cooling phase immediately following shock breakout. We present an extensive sequence of optical and near-infrared spectra, as well as three epochs of optical spectropolarimetry. Our initial spectra, taken two days after shock breakout, are dominated by hydrogen Balmer lines at high velocity. However, by maximum light, He I lines dominated the optical and near-infrared spectra, which closely resembled those of normal Type Ib supernovae (SNe Ib) such as SN 1999ex. This spectroscopic transition defines Type IIb supernovae, but the strong similarity of SN 2008ax to normal SNe Ib beginning near maximum light, including an absorption feature near 6270A due to H-alpha at high velocities, suggests that many objects classified as SNe Ib in the literature may have ejected similar amounts of hydrogen as SN 2008ax, roughly a few x 0.01 M_sun. Early-time spectropolarimetry (6 and 9 days after shock breakout) revealed strong line polarization modulations of 3.4% across H-alpha, indicating the presence of large asphericities in the outer ejecta. The continuum shares a common polarization angle with the hydrogen, helium, and oxygen lines, while the calcium and iron absorptions are oriented at different angles. This is clear evidence of deviations from axisymmetry even in the outer ejecta. Intrinsic continuum polarization of 0.64% only nine days after shock breakout shows that the outer layers of the ejecta were quite aspherical. A single epoch of late-time spectropolarimetry, as well as the shapes of the nebular line profiles, demonstrate that asphericities extended from the outermost layers all the way down to the center of this SN. [Abridged]Comment: 24 pages, 21 figures, 4 tables, appendix, minor revisions to match version accepted by Ap

Production of IL-27 in multiple sclerosis lesions by astrocytes and myeloid cells: Modulation of local immune responses

The mechanisms whereby human glial cells modulate local immune responses are not fully understood. Interleukin-27 (IL-27), a pleiotropic cytokine, has been shown to dampen the severity of experimental autoimmune encephalomyelitis, but it is still unresolved whether IL-27 plays a role in the human disease multiple sclerosis (MS). IL-27 contribution to local modulation of immune responses in the brain of MS patients was investigated. The expression of IL-27 subunits (EBI3 and p28) and its cognate receptor IL-27R (the gp130 and TCCR chains) was elevated within post-mortem MS brain lesions compared with normal control brains. Moreover, astrocytes (GFAP(+) cells) as well as microglia and macrophages (Iba1(+) cells) were important sources of IL-27. Brain-infiltrating CD4 and CD8 T lymphocytes expressed the IL-27R specific chain (TCCR) implying that these cells could respond to local IL-27 sources. In primary cultures of human astrocytes inflammatory cytokines increased IL-27 production, whereas myeloid cell inflammatory M1 polarization and inflammatory cytokines enhanced IL-27 expression in microglia and macrophages. Astrocytes in postmortem tissues and in vitro expressed IL-27R. Moreover, IL-27 triggered the phosphorylation of the transcription regulator STAT1, but not STAT3 in human astrocytes; indeed IL-27 up-regulated MHC class I expression on astrocytes in a STAT1-dependent manner. These findings demonstrated that IL-27 and its receptor were elevated in MS lesions and that local IL-27 can modulate immune properties of astrocytes and infiltrating immune cells. Thus, therapeutic strategies targeting IL-27 may influence not only peripheral but also local inflammatory responses within the brain of MS patients