UV Imaging Polarimetry of the peculiar Seyfert 2 galaxy Mrk 477

We present the results of UV imaging polarimetry of the Seyfert 2 galaxy Mrk 477 taken by the Faint Object Camera onboard the Hubble Space Telescope (HST). From a previous HST UV image (lambda ~ 2180A), Mrk 477 has been known to have a pointlike bright UV hotspot in the central region, peculiar among nearby Seyfert 2 galaxies. There are also claims of UV/optical variability, unusual for a Seyfert 2 galaxy. Our data show that there is an off-nuclear scattering region ~ 0."6 (~ 500 pc) NE from the hotspot. The data, after the subtraction of the instrumental effect due to this bright hotspot region, might indicate that the scattered light is also detected in the central 0."2 radius region and is extended to a very wide angle. The hotspot location is consistent with the symmetry center of the PA pattern, which represents the location of the hidden nucleus, but our data do not provide a strong upper limit to the distance between the symmetry center and the hotspot. We have obtained high spatial resolution color map of the continuum which shows that the nuclear spiral arm of 0."4 scale (~ 300pc) is significantly bluer than the off-nuclear mirror and the hotspot region. The nature of the hotspot is briefly discussed.Comment: To appear in Ap

UV Imaging Polarimetry of the Seyfert 2 Galaxy Mrk 3

We present UV imaging polarimetry data of the Seyfert 2 galaxy Mrk 3 taken by the Hubble Space Telescope. The polarized flux is found to be extended to ~1 kpc from the nucleus, and the position angles of polarization are centrosymmetric, confirming that the polarization is caused by scattering. We determine the location of the hidden nucleus as the center of this centrosymmetric pattern. From the polarization images taken in two broad bands, we have obtained the color distribution of the polarized flux. Some regions have blue polarized flux, consistent with optically-thin dust scattering, but some bright knots have a color similar to that of Seyfert 1 nucleus. Also, the recent Chandra X-ray observation suggests that the ratio of scattered UV flux to scattered X-ray flux is rather similar to the intrinsic UV/X-ray ratio in a Seyfert 1 nucleus, if the observed extended X-ray continuum is scattered light. While the scattered X-ray would be essentially from electron scattering, the UV slope and UV/X-ray ratio both being similar to Seyfert 1's would lead to two possibilities as to the nature of the UV scatterers. One is that the UV may also be scattered by electrons, in which case the scattering gas is somehow dust-free. The other is that the UV is scattered by dust grains, but the wavelength-independent UV scattering with low efficiency indicated by the UV slope and UV/X-ray ratio would suggest that the grains reside in UV-opaque clouds, or the dust might be mainly composed of large grains and lacks small-grain population.Comment: 15 pages, 8 figures (plus 2 color versions of grayscale figures), To appear in ApJ; minor corrections for the proofs of the manuscrip

Akt promotes Endocardial-Mesenchyme Transition

Endothelial to mesenchyme transition (EndMT) can be observed during the formation of endocardial cushions from the endocardium, the endothelial lining of the atrioventricular canal (AVC), of the developing heart at embryonic day 9.5 (E9.5). Many regulators of the process have been identified; however, the mechanisms driving the initial commitment decision of endothelial cells to EndMT have been difficult to separate from processes required for mesenchymal proliferation and migration. We have several lines of evidence that suggest a central role for Akt signaling in committing endothelial cells to enter EndMT. Akt1 mRNA was restricted to the endocardium of endocardial cushions while they were forming. The PI3K/Akt signaling pathway is necessary for mesenchyme outgrowth, as sprouting was inhibited in AVC explant cultures treated with the PI3K inhibitor LY294002. Furthermore, endothelial marker, VE-cadherin, was downregulated and mesenchyme markers, N-cadherin and Snail, were induced in response to expression of a constitutively active form of Akt1 (myrAkt1) in endothelial cells. Finally, we isolated the function of Akt1 signaling in the commitment to the transition using a transgenic model where myrAkt1 was pulsed only in endocardial cells and turned off after EndMT initiation. In this way, we determined that increased Akt signaling in the endocardium drives EndMT and discounted its other functions in cushion mesenchymal cells

Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units : an international Delphi study

Peer reviewedPublisher PD

Beliefs about Causes of Colon Cancer by English-as-a-Second-Language Chinese Immigrant Women to Canada

Abstract Colon cancer is the second leading cause of cancer death for Canadians

Formation of a TBX20-CASZ1 protein complex is protective against dilated cardiomyopathy and critical for cardiac homeostasis

By the age of 40, one in five adults without symptoms of cardiovascular disease are at risk for developing congestive heart failure. Within this population, dilated cardiomyopathy (DCM) remains one of the leading causes of disease and death, with nearly half of cases genetically determined. Though genetic and high throughput sequencing-based approaches have identified sporadic and inherited mutations in a multitude of genes implicated in cardiomyopathy, how combinations of asymptomatic mutations lead to cardiac failure remains a mystery. Since a number of studies have implicated mutations of the transcription factor TBX20 in congenital heart diseases, we investigated the underlying mechanisms, using an unbiased systems-based screen to identify novel, cardiac-specific binding partners. We demonstrated that TBX20 physically and genetically interacts with the essential transcription factor CASZ1. This interaction is required for survival, as mice heterozygous for both Tbx20 and Casz1 die post-natally as a result of DCM. A Tbx20 mutation associated with human familial DCM sterically interferes with the TBX20-CASZ1 interaction and provides a physical basis for how this human mutation disrupts normal cardiac function. Finally, we employed quantitative proteomic analyses to define the molecular pathways mis-regulated upon disruption of this novel complex. Collectively, our proteomic, biochemical, genetic, and structural studies suggest that the physical interaction between TBX20 and CASZ1 is required for cardiac homeostasis, and further, that reduction or loss of this critical interaction leads to DCM. This work provides strong evidence that DCM can be inherited through a digenic mechanism

Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575

The γ-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of γ-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by γ-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active γ-secretase inhibitor LY-411575 in 10–11 month old APP:PS1 mice with established amyloid pathology and neuritic abnormalities. Neurons expressed YFP allowing fluorescent detection of morphology whereas plaques were labelled with methoxy-XO4. The same identified neurites and plaques were followed in weekly imaging sessions in living mice treated daily (5 mg/kg) for 3 weeks with the compound. Although LY-411575 reduced Aβ levels in plasma and brain, it did not have an effect on the size of existing plaques. There was also no effect on the abnormal neuritic curvature near plaques, or the dystrophies in very close proximity to senile plaques. Our results suggest that therapeutics aimed at inhibition of Aβ generation are less effective for reversal of existing plaques than for prevention of new plaque formation and have no effect on the plaque-mediated neuritic abnormalities, at least under these conditions where Aβ production is suppressed but not completely blocked. Therefore, a combination therapy of Aβ suppression with agents that increase clearance of amyloid and/or prevent neurotoxicity might be needed for a more effective treatment in patients with pre-existing pathology

Perspectives on Extended-Release Naltrexone Induction among Patients Living with HIV and Opioid Use Disorder: A Qualitative Analysis

BACKGROUND: The CHOICES study randomized participants with HIV and opioid use disorder (OUD) to HIV clinic-based extended-release naltrexone (XR-NTX), which requires complete cessation of opioid use, versus treatment-as-usual (i.e., buprenorphine, methadone). Study participants randomized to XR-NTX were interviewed to assess their experiences with successful and unsuccessful XR-NTX induction. METHODS: Semi-structured qualitative interviews were completed with a convenience sample of study participants with HIV and OUD (n = 37) randomized to XR-NTX in five HIV clinics between 2018 and 2019. All participants approached agreed to be interviewed. Interviews were digitally recorded, professionally transcribed, and analyzed using thematic analysis. RESULTS: Participants included women (43%), African Americans (62%) and Hispanics (16%), between 27 to 69 years of age. Individuals who completed XR-NTX induction (n = 20) reported experiencing (1) readiness for change, (2) a supportive environment during withdrawal including comfort medications, and (3) caring interactions with staff. Four contrasting themes emerged among participants (n = 17) who did not complete induction: (1) concern and anxiety about withdrawal including past negative experiences, (2) ambivalence about or reluctance to stop opioids, (3) concerns about XR-NTX effects, and (4) preferences for other medications. CONCLUSIONS: The results highlight opportunities to improve initiation of XR-NTX in high-need groups. Addressing expectations regarding induction may enhance XR-NTX initiation rates. Trial Registration ClinicalTrials.gov: NCT03275350. Registered September 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03275350?term=extended+release+naltrexone&cond=Opioid+Use

wuHMM: a robust algorithm to detect DNA copy number variation using long oligonucleotide microarray data

Copy number variants (CNVs) are currently defined as genomic sequences that are polymorphic in copy number and range in length from 1000 to several million base pairs. Among current array-based CNV detection platforms, long-oligonucleotide arrays promise the highest resolution. However, the performance of currently available analytical tools suffers when applied to these data because of the lower signal:noise ratio inherent in oligonucleotide-based hybridization assays. We have developed wuHMM, an algorithm for mapping CNVs from array comparative genomic hybridization (aCGH) platforms comprised of 385 000 to more than 3 million probes. wuHMM is unique in that it can utilize sequence divergence information to reduce the false positive rate (FPR). We apply wuHMM to 385K-aCGH, 2.1M-aCGH and 3.1M-aCGH experiments comparing the 129X1/SvJ and C57BL/6J inbred mouse genomes. We assess wuHMM's performance on the 385K platform by comparison to the higher resolution platforms and we independently validate 10 CNVs. The method requires no training data and is robust with respect to changes in algorithm parameters. At a FPR of <10%, the algorithm can detect CNVs with five probes on the 385K platform and three on the 2.1M and 3.1M platforms, resulting in effective resolutions of 24 kb, 2–5 kb and 1 kb, respectively