501 research outputs found
Bringing "The Moth" to Light: A Planet-Sculpting Scenario for the HD 61005 Debris Disk
The HD 61005 debris disk ("The Moth") stands out from the growing collection
of spatially resolved circumstellar disks by virtue of its unusual swept-back
morphology, brightness asymmetries, and dust ring offset. Despite several
suggestions for the physical mechanisms creating these features, no definitive
answer has been found. In this work, we demonstrate the plausibility of a
scenario in which the disk material is shaped dynamically by an eccentric,
inclined planet. We present new Keck NIRC2 scattered-light angular differential
imaging of the disk at 1.2-2.3 microns that further constrains its outer
morphology (projected separations of 27-135 AU). We also present complementary
Gemini Planet Imager 1.6 micron total intensity and polarized light detections
that probe down to projected separations less than 10 AU. To test our
planet-sculpting hypothesis, we employed secular perturbation theory to
construct parent body and dust distributions that informed scattered-light
models. We found that this method produced models with morphological and
photometric features similar to those seen in the data, supporting the premise
of a planet-perturbed disk. Briefly, our results indicate a disk parent body
population with a semimajor axis of 40-52 AU and an interior planet with an
eccentricity of at least 0.2. Many permutations of planet mass and semimajor
axis are allowed, ranging from an Earth mass at 35 AU to a Jupiter mass at 5
AU.Comment: Accepted to AJ; added Figure 5 and minor text edit
Youth Employment in Ghana: Conditions and Determinants
Youth employment, and its limitations, is a pertinent problem that most developing nations face. “Youth Employment in Ghana: Conditions and Determinants” is a student-led research project that summarizes and analyzes the conditions of youth employment in Ghana as of 2013. The purpose of this report is to provide a comprehensive analysis of the impacts of individual, household, and community characteristics on youth employment outcomes. This study finds that Ghana’s youth labor issues center around the low quality of jobs rather than unemployment. The findings highlight the issue of gender gap, the importance of family background and community infrastructure in youth labor outcomes
Transcription factors NRF2 and HSF1 have opposing functions in autophagy
Abstract Autophagy plays a critical role in the maintenance of cellular homeostasis by degrading proteins, lipids and organelles. Autophagy is activated in response to stress, but its regulation in the context of other stress response pathways, such as those mediated by heat shock factor 1 (HSF1) and nuclear factor-erythroid 2 p45-related factor 2 (NRF2), is not well understood. We found that the Michael acceptor bis(2-hydoxybenzylidene)acetone (HBB2), a dual activator of NRF2 and HSF1, protects against the development of UV irradiation-mediated cutaneous squamous cell carcinoma in mice. We further show that HBB2 is an inducer of autophagy. In cells, HBB2 increases the levels of the autophagy-cargo protein p62/sequestosome 1, and the lipidated form of microtubule-associated protein light chain 3 isoform B. Activation of autophagy by HBB2 is impaired in NRF2-deficient cells, which have reduced autophagic flux and low basal and induced levels of p62. Conversely, HSF1-deficient cells have increased autophagic flux under both basal as well as HBB2-induced conditions, accompanied by increased p62 levels. Our findings suggest that NRF2 and HSF1 have opposing roles during autophagy, and illustrate the existence of tight mechanistic links between the cellular stress responses
The Peculiar Debris Disk of HD 111520 as Resolved by the Gemini Planet Imager
Using the Gemini Planet Imager (GPI), we have resolved the circumstellar
debris disk around HD 111520 at a projected range of ~30-100 AU in both total
and polarized -band intensity. The disk is seen edge-on at a position angle
of ~165 along the spine of emission. A slight inclination or
asymmetric warping are covariant and alters the interpretation of the observed
disk emission. We employ 3 point spread function (PSF) subtraction methods to
reduce the stellar glare and instrumental artifacts to confirm that there is a
roughly 2:1 brightness asymmetry between the NW and SE extension. This specific
feature makes HD 111520 the most extreme examples of asymmetric debris disks
observed in scattered light among similar highly inclined systems, such as HD
15115 and HD 106906. We further identify a tentative localized brightness
enhancement and scale height enhancement associated with the disk at ~40 AU
away from the star on the SE extension. We also find that the fractional
polarization rises from 10 to 40% from 0.5" to 0.8" from the star. The
combination of large brightness asymmetry and symmetric polarization fraction
leads us to believe that an azimuthal dust density variation is causing the
observed asymmetry.Comment: 9 pages, 8 Figures, 1 table, Accepted to Ap
Pathophysiological role of microRNA-29 in pancreatic cancer stroma
poster abstractBackground: Dense fibrotic stroma associated with pancreatic ductal adenocarcinoma
(PDAC) has been a major obstacle for drug delivery to the tumor bed and may impede
attempts to slow down PDAC progression and metastasis. However, current antistromal
drugs have not improved tumor response to chemotherapy or patient survival.
Thus, a better understanding of the molecular mechanisms associated with tumorstromal
interactions is desperately needed to develop novel anti-stromal therapeutic
approaches. MicroRNAs (miRNAs) are an abundant class of highly conserved, small
non-coding RNAs that function as key regulators of eukaryotic gene expression and
cellular homeostasis. miR-29 is known to play a paramount role in the fibrotic process of
several organs by providing crucial functions downstream of pro-fibrotic signaling
pathways such as TGF-β1 and regulates the expression of extracellular matrix (ECM)
proteins, a major component in the PDAC stroma. Upregulation of TGF-β1 is associated
with PDAC pathogenesis and is known to activate stromal cells. Furthermore, vascular
endothelial growth factor (VEGF) that stimulates tumor angiogenesis is a predicted
target of miR-29. We hypothesize that miR-29 may be misregulated in TGF-β1 activated
PDAC stromal cells and lead to excessive accumulation of ECM proteins and VEGF.
Kwon et al. 2015 Annual AACR Meeting Restored expression of miR-29 could be therapeutically beneficial to modulate tumorstromal interactions.
Methods: Northern blot or qPCR techniques were used to assess miR-29 levels in vitro
stromal cells, murine PDAC model, and PDAC patient biopsies, and stromal
deposition/fibrosis was determined by Sirius red staining. In murine and human PDAC
samples, stromal specific miR-29 expression was determined via in situ hybridization by
co-staining pancreatic tissues with glial fibrillary acidic protein a marker for stromal cells
and miR-29. miR-29 functional studies were conducted by transfection of stroma cells
with synthetic miR-29 mimics and locked nucleic acid, a miR-29 inhibitor, and ECM
protein/VEGF expression was analyzed by western blot analysis. The effect of miR-29
overexpression in stromal cells on cancer colony growth was evaluated by direct coculture
of stromal cells ectopically expressing miR-29 with pancreatic cancer cells, and
subsequently, cancer colony number and stromal accumulation was determined by
crystal violet and sirius red stains respectively.
Results: In both in vitro and in vivo models as well as PDAC patient biopsies, we
observed loss of miR-29 is a common phenomenon of activated stromal cells, and is
associated with a significant increase in ECM and VEGF accumulation. Restored
expression of miR-29 in stromal cells reduced the deposition of matrix proteins, VEGF
expression, and cancer colony formation in direct co-culture.
Conclusion: These results provide insight into the mechanistic role of miR-29 in PDAC
stroma and its potential use as an anti-stromal/angiogenic therapeutic agent
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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