275 research outputs found
Portraying the hosts: Stellar science from planet searches
Information on the full session can be found on this website: https://sites.google.com/site/portrayingthehostscs18/We present a compendium of the splinter session on stellar science from planet searches that was organized as part of the Cool Stars 18 conference. Seven speakers discussed techniques to infer stellar information from radial velocity, transit and microlensing data, as well as new instrumentation and missions designed for planet searches that will provide useful for the study of the cool stars
Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation
BACKGROUND: Cubilin is a peripheral membrane protein that interacts with the integral membrane proteins megalin and amnionless to mediate ligand endocytosis by absorptive epithelia such as the extraembryonic visceral endoderm (VE). RESULTS: Here we report the effects of the genetic deletion of cubilin on mouse embryonic development. Cubilin gene deletion is homozygous embryonic lethal with death occurring between 7.5â13.5 days post coitum (dpc). Cubilin-deficient embryos display developmental retardation and do not advance morphologically beyond the gross appearance of wild-type 8â8.5 dpc embryos. While mesodermal structures such as the allantois and the heart are formed in cubilin mutants, other mesoderm-derived tissues are anomalous or absent. Yolk sac blood islands are formed in cubilin mutants but are unusually large, and the yolk sac blood vessels fail to undergo remodeling. Furthermore, somite formation does not occur in cubilin mutants. Morphological abnormalities of endoderm occur in cubilin mutants and include a stratified epithelium in place of the normally simple columnar VE epithelium and a stratified cuboidal epithelium in place of the normally simple squamous epithelium of the definitive endoderm. Cubilin-deficient VE is also functionally defective, unable to mediate uptake of maternally derived high-density lipoprotein (HDL). CONCLUSION: In summary, cubilin is required for embryonic development and is essential for the formation of somites, definitive endoderm and VE and for the absorptive function of VE including the process of maternal-embryo transport of HDL
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Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway
Cancer cells exhibit metabolic dependencies that distinguish them from their normal counterparts1. Among these addictions is an increased utilization of the amino acid glutamine (Gln) to fuel anabolic processes2. Indeed, the spectrum of Gln-dependent tumors and the mechanisms whereby Gln supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of Gln utilization in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumor growth. While most cells utilize glutamate dehydrogenase (GLUD1) to convert Gln-derived glutamate (Glu) into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid (TCA) cycle, PDAC relies on a distinct pathway to fuel the TCA cycle such that Gln-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate (OAA) by aspartate transaminase (GOT1). Subsequently, this OAA is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as Gln deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of Gln metabolism is mediated by oncogenic Kras, the signature genetic alteration in PDAC, via the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumors
HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma
Background Metabolic changes in tumour cells are used in clinical imaging and may provide potential therapeutic targets. Human papillomavirus (HPV) status is important in classifying head and neck cancers (HNSCC), identifying a distinct clinical phenotype; metabolic differences between these HNSCC subtypes remain poorly understood. Methods We used RNA sequencing to classify the metabolic expression profiles of HPV+ve and HPVâve HNSCC, performed a meta-analysis on FDG-PET imaging characteristics and correlated results with in vitro extracellular flux analysis of HPVâve and HPV+ve HNSCC cell lines. The monocarboxylic acid transporter-1 (MCT1) was identified as a potential metabolic target and tested in functional assays. Results Specific metabolic profiles were associated with HPV status, not limited to carbohydrate metabolism. There was dominance of all energy pathways in HPV-negative disease, with elevated expression of genes associated with glycolysis and oxidative phosphorylation. In vitro analysis confirmed comparative increased rates of oxidative phosphorylation and glycolysis in HPV-negative cell lines. PET SUV(max) scores however were unable to reliably differentiate between HPV-positive and HPV-negative tumours. MCT1 expression was significantly increased in HPV-negative tumours, and inhibition suppressed tumour cell invasion, colony formation and promoted radiosensitivity. Conclusion HPV-positive and negative HNSCC have different metabolic profiles which may have potential therapeutic applications
Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma.
INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.
METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.
RESULTS: Patients underwent pancreaticoduodenectomy (n = 302; 92%), distal (n = 20; 6%), or total pancreatectomy (n = 7; 2%). A total of 108 patients (33%) underwent vascular reconstruction, 301 patients (91%) received neoadjuvant or adjuvant therapy, 157 specimens (48%) were node positive, and margins were microscopically positive in 52 patients (16%). Median overall survival and disease-specific survival was 23.9 and 26.5 months. Eighty-eight patients (27%) survived a minimum of 5 years and had a median overall survival of 11 years. Of these, 21 (24%) experienced recurrence, 7 (8%) after 5 years. Late recurrences occurred most frequently in the lungs, the latest at 6.7 years. Multivariate analysis identified disease-negative lymph nodes (P = .02) and no prior attempt at resection (P = 0.01) as associated with 5-year survival.
CONCLUSIONS: Our 27% actual 5-year survival rate for patients with resected PC is superior to that previously reported, and it is influenced by our emphasis on detailed staging and patient selection, a standardized operative approach, and routine use of multimodality therapy
Very Low-Mass Stellar and Substellar Companions to Solar-Like Stars from MARVELS I: A Low Mass Ratio Stellar Companion to TYC 4110-01037-1 in a 79-day Orbit
TYC 4110-01037-1 has a low-mass stellar companion, whose small mass ratio and
short orbital period are atypical amongst solar-like (Teff ~< 6000 K) binary
systems. Our analysis of TYC 4110-01037-1 reveals it to be a moderately aged
(~<5 Gyr) solar-like star having a mass of 1.07 +/- 0.08 MSun and radius of
0.99 +/- 0.18 RSun. We analyze 32 radial velocity measurements from the
SDSS-III MARVELS survey as well as 6 supporting radial velocity measurements
from the SARG spectrograph on the 3.6m TNG telescope obtained over a period of
~2 years. The best Keplerian orbital fit parameters were found to have a period
of 78.994 +/- 0.012 days, an eccentricity of 0.1095 +/- 0.0023, and a
semi-amplitude of 4199 +/- 11 m/s. We determine the minimum companion mass (if
sin i = 1) to be 97.7 +/- 5.8 MJup. The system's companion to host star mass
ratio, >0.087 +/- 0.003, places it at the lowest end of observed values for
short period stellar companions to solar-like (Teff ~< 6000 K) stars. One
possible way to create such a system would be if a triple-component stellar
multiple broke up into a short period, low q binary during the cluster
dispersal phase of its lifetime. A candidate tertiary body has been identified
in the system via single-epoch, high contrast imagery. If this object is
confirmed to be co-moving, we estimate it would be a dM4 star. We present these
results in the context of our larger-scale effort to constrain the statistics
of low mass stellar and brown dwarf companions to FGK-type stars via the
MARVELS survey.Comment: 22 pages; accepted in A
Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)
\We present the sixth catalog of Kepler candidate planets based on nearly 4
years of high precision photometry. This catalog builds on the legacy of
previous catalogs released by the Kepler project and includes 1493 new Kepler
Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these
candidates have best fit radii <1.5 R_earth. This brings the total number of
KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many
of these new candidates at the low signal-to-noise limit may be false alarms
created by instrumental noise, and discuss our efforts to identify such
objects. We re-evaluate all previously published KOIs with orbital periods of
>50 days to provide a consistently vetted sample that can be used to improve
planet occurrence rate calculations. We discuss the performance of our planet
detection algorithms, and the consistency of our vetting products. The full
catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement
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