Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells

Survivin is a dual functioning protein. It inhibits the apoptosis of cancer cells by inhibiting caspases, and also promotes cancer cell growth by stabilizing microtubules during mitosis. Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG. However, Hsp90 interferes with a number of molecules that up-regulate the intracellular level of survivin, raising the question that clinical use of Hsp90 inhibitors may indirectly induce survivin expression and subsequently enhance cancer anti-drug responses. The purpose of this study is to determine whether targeting Hsp90 can alter survivin expression differently in different cancer cell lines and to explore possible mechanisms that cause the alteration in survivin expression.<br /

Proteomic analysis of rhein-induced cyt: ER stress mediates cell death in breast cancer cells

Rhein is a natural product purified from herbal plants such as Rheum palmatum, which has been shown to have anti-angiogenesis and anti-tumor metastasis properties. However, the biological effects of rhein on the behavior of breast cancers are not completely elucidated. To evaluate whether rhein might be useful in the treatment of breast cancer and its cytotoxic mechanism, we analyzed the impact of rhein treatment on differential protein expression as well as redox regulation in a non-invasive breast cancer cell line, MCF-7, and an invasive breast cancer cell line, MDA-MB-231, using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF mass spectrometry. This proteomic study revealed that 73 proteins were significantly changed in protein expression; while 9 proteins were significantly altered in thiol reactivity in both MCF-7 and MDA-MB-231 cells. The results also demonstrated that rhein-induced cytotoxicity in breast cancer cells mostly involves dysregulation of cytoskeleton regulation, protein folding, the glycolysis pathway and transcription control. A further study also indicated that rhein promotes misfolding of cellular proteins as well as unbalancing of the cellular redox status leading to ER-stress. Our work shows that the current proteomic strategy offers a high-through-put platform to study the molecular mechanisms of rhein-induced cytotoxicity in breast cancer cells. The identified differentially expressed proteins might be further evaluated as potential targets in breast cancer therapy

The Cosmos in its Infancy: JADES Galaxy Candidates at z > 8 in GOODS-S and GOODS-N

© 2024. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We present a catalog of 717 candidate galaxies at z > 8 selected from 125 square arcmin of NIRCam imaging as part of the JWST Advanced Deep Extragalactic Survey (JADES). We combine the full JADES imaging data set with data from the JWST Extragalactic Medium Survey and First Reionization Epoch Spectroscopic COmplete Survey (FRESCO) along with extremely deep existing observations from Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) for a final filter set that includes 15 JWST/NIRCam filters and five HST/ACS filters. The high-redshift galaxy candidates were selected from their estimated photometric redshifts calculated using a template-fitting approach, followed by visual inspection from seven independent reviewers. We explore these candidates in detail, highlighting interesting resolved or extended sources, sources with very red long-wavelength slopes, and our highest-redshift candidates, which extend to z phot ∼ 18. Over 93% of the sources are newly identified from our deep JADES imaging, including 31 new galaxy candidates at z phot > 12. We also investigate potential contamination by stellar objects, and do not find strong evidence from spectral energy distribution fitting that these faint high-redshift galaxy candidates are low-mass stars. Using 42 sources in our sample with measured spectroscopic redshifts from NIRSpec and FRESCO, we find excellent agreement to our photometric redshift estimates, with no catastrophic outliers and an average difference of 〈Δz = z phot − z spec〉 = 0.26. These sources comprise one of the most robust samples for probing the early buildup of galaxies within the first few hundred million years of the Universe’s history.Peer reviewe

The Cosmos in its Infancy: JADES Galaxy Candidates at z > 8 in GOODS-S and GOODS-N

We present a catalog of 717 candidate galaxies at $z > 8$ selected from 125 square arcminutes of NIRCam imaging as part of the JWST Advanced Deep Extragalactic Survey (JADES). We combine the full JADES imaging dataset with data from the JEMS and FRESCO JWST surveys along with extremely deep existing observations from HST/ACS for a final filter set that includes fifteen JWST/NIRCam filters and five HST/ACS filters. The high-redshift galaxy candidates were selected from their estimated photometric redshifts calculated using a template fitting approach, followed by visual inspection from seven independent reviewers. We explore these candidates in detail, highlighting interesting resolved or extended sources, sources with very red long-wavelength slopes, and our highest redshift candidates, which extend to $z_{phot} = 18$. We also investigate potential contamination by stellar objects, and do not find strong evidence from SED fitting that these faint high-redshift galaxy candidates are low-mass stars. Over 93\% of the sources are newly identified from our deep JADES imaging, including 31 new galaxy candidates at $z_{phot} > 12$. Using 42 sources in our sample with measured spectroscopic redshifts from NIRSpec and FRESCO, we find excellent agreement to our photometric redshift estimates, with no catastrophic outliers and an average difference of $\langle \Delta z = z_{phot}- z_{spec} \rangle= 0.26$. These sources comprise one of the most robust samples for probing the early buildup of galaxies within the first few hundred million years of the Universe's history.Comment: v2: 40 pages, 18 figures, submitted to AAS Journals, online data catalog (JADES Deep only) found at https://doi.org/10.5281/zenodo.809252

JADES Imaging of GN-z11: Revealing the Morphology and Environment of a Luminous Galaxy 430 Myr After the Big Bang

We present JWST NIRCam 9-band near-infrared imaging of the luminous $z=10.6$ galaxy GN-z11 from the JWST Advanced Deep Extragalactic Survey (JADES) of the GOODS-N field. We find a spectral energy distribution (SED) entirely consistent with the expected form of a high-redshift galaxy: a clear blue continuum from 1.5 to 4 microns with a complete dropout in F115W. The core of GN-z11 is extremely compact in JWST imaging. We analyze the image with a two-component model, using a point source and a S\'{e}rsic profile that fits to a half-light radius of 200 pc and an index $n=0.9$. We find a low-surface brightness haze about $0.4''$ to the northeast of the galaxy, which is most likely a foreground object but might be a more extended component of GN-z11. At a spectroscopic redshift of 10.60 (Bunker et al. 2023), the comparison of the NIRCam F410M and F444W images spans the Balmer jump. From population synthesis modeling, here assuming no light from an active galactic nucleus, we reproduce the SED of GN-z11, finding a stellar mass of $\sim$$10^{9}~M_{\odot}$, a star-formation rate of $\sim$$20~M_{\odot}~\mathrm{yr}^{-1}$ and a young stellar age of $\sim$$20~\mathrm{Myr}$. As massive galaxies at high redshift are likely to be highly clustered, we search for faint neighbors of GN-z11, finding 9 galaxies out to $\sim$5 comoving Mpc transverse with photometric redshifts consistent with $z=10.6$, and a 10$^{\rm th}$ more tentative dropout only $3''$ away.Comment: Submitted to ApJ; 18 pages, 8 figures; comments welcom

Three Saturn-mass planets transiting F-type stars revealed with TESS and HARPS

While the sample of confirmed exoplanets continues to increase, the population of transiting exoplanets around early-type stars is still limited. These planets allow us to investigate the planet properties and formation pathways over a wide range of stellar masses and study the impact of high irradiation on hot Jupiters orbiting such stars. We report the discovery of TOI-615b, TOI-622b, and TOI-2641b, three Saturn-mass planets transiting main sequence, F-type stars. The planets were identified by the Transiting Exoplanet Survey Satellite (TESS) and confirmed with complementary ground-based and radial velocity observations. TOI-615b is a highly irradiated ($\sim$1277 $F_{\oplus}$) and bloated Saturn-mass planet (1.69$^{+0.05}_{-0.06}$$R_{Jup}$ and 0.43$^{+0.09}_{-0.08}$$M_{Jup}$) in a 4.66 day orbit transiting a 6850 K star. TOI-622b has a radius of 0.82$^{+0.03}_{-0.03}$$R_{Jup}$ and a mass of 0.30$^{+0.07}_{-0.08}$~$M_{Jup}$ in a 6.40 day orbit. Despite its high insolation flux ($\sim$600 $F_{\oplus}$), TOI-622b does not show any evidence of radius inflation. TOI-2641b is a 0.37$^{+0.05}_{-0.04}$$M_{Jup}$ planet in a 4.88 day orbit with a grazing transit (b = 1.04$^{+0.05}_{-0.06 }$) that results in a poorly constrained radius of 1.61$^{+0.46}_{-0.64}$$R_{Jup}$. Additionally, TOI-615b is considered attractive for atmospheric studies via transmission spectroscopy with ground-based spectrographs and $\textit{JWST}$. Future atmospheric and spin-orbit alignment observations are essential since they can provide information on the atmospheric composition, formation and migration of exoplanets across various stellar types.Comment: 16 pages, 17 figures, submitted to A&

Spectroscopy of four metal-poor galaxies beyond redshift ten

Finding and characterising the first galaxies that illuminated the early Universe at cosmic dawn is pivotal to understand the physical conditions and the processes that led to the formation of the first stars. In the first few months of operations, imaging from the James Webb Space Telescope (JWST) have been used to identify tens of candidates of galaxies at redshift (z) greater than 10, less than 450 million years after the Big Bang. However, none of these candidates has yet been confirmed spectroscopically, leaving open the possibility that they are actually low-redshift interlopers. Here we present spectroscopic confirmation and analysis of four galaxies unambiguously detected at redshift 10.3<z<13.2, previously selected from NIRCam imaging. The spectra reveal that these primeval galaxies are extremely metal poor, have masses between 10^7 and a few times 10^8 solar masses, and young ages. The damping wings that shape the continuum close to the Lyman edge are consistent with a fully neutral intergalactic medium at this epoch. These findings demonstrate the rapid emergence of the first generations of galaxies at cosmic dawn.Comment: 32 pages, 9 figures, Submitte

The JADES Origins Field: A New JWST Deep Field in the JADES Second NIRCam Data Release

We summarize the properties and initial data release of the JADES Origins Field (JOF), which will soon be the deepest imaging field yet observed with the James Webb Space Telescope (JWST). This field falls within the GOODS-S region about 8' south-west of the Hubble Ultra Deep Field (HUDF), where it was formed initially in Cycle 1 as a parallel field of HUDF spectroscopic observations within the JWST Advanced Deep Extragalactic Survey (JADES). This imaging will be greatly extended in Cycle 2 program 3215, which will observe the JOF for 5 days in six medium-band filters, seeking robust candidates for z>15 galaxies. This program will also include ultra-deep parallel NIRSpec spectroscopy (up to 104 hours on-source, summing over the dispersion modes) on the HUDF. Cycle 3 observations from program 4540 will add 20 hours of NIRCam slitless spectroscopy to the JOF. With these three campaigns, the JOF will be observed for 380 open-shutter hours with NIRCam using 15 imaging filters and 2 grism bandpasses. Further, parts of the JOF have deep 43 hr MIRI observations in F770W. Taken together, the JOF will soon be one of the most compelling deep fields available with JWST and a powerful window into the early Universe. This paper presents the second data release from JADES, featuring the imaging and catalogs from the year 1 JOF observations.Comment: Submitted to ApJ Supplement. Images and catalogs are available at https://archive.stsci.edu/hlsp/jades . A FITSmap portal to view the images is at https://jades.idies.jhu.ed

JADES NIRSpec Spectroscopy of GN-z11: Lyman-α\alpha emission and possible enhanced nitrogen abundance in a z=10.60z=10.60 luminous galaxy

We present JADES JWST/NIRSpec spectroscopy of GN-z11, the most luminous candidate $z>10$ Lyman break galaxy in the GOODS-North field with $M_{UV}=-21.5$. We derive a redshift of $z=10.603$ (lower than previous determinations) based on multiple emission lines in our low and medium resolution spectra over $0.8-5.3\,\mu$m. We significantly detect the continuum and measure a blue rest-UV spectral slope of $\beta=-2.4$. Remarkably, we see spatially-extended Lyman-$\alpha$ in emission (despite the highly-neutral IGM expected at this early epoch), offset 555 km/s redward of the systemic redshift. From our measurements of collisionally-excited lines of both low- and high-ionization (including [O II] $\lambda3727$, [Ne III] $\lambda 3869$ and C III] $\lambda1909$) we infer a high ionization parameter ($\log U\sim -2$). We detect the rarely-seen N IV] $\lambda1486$ and N III]$\lambda1748$ lines in both our low and medium resolution spectra, with other high ionization lines seen in low resolution spectrum such as He II (blended with O III]) and C IV (with a possible P-Cygni profile). Based on the observed rest-UV line ratios, we cannot conclusively rule out photoionization from AGN. The high C III]/He II ratios, however, suggest a likely star-formation explanation. If the observed emission lines are powered by star formation, then the strong N III] $\lambda1748$ observed may imply an unusually high $N/O$ abundance. Balmer emission lines (H$\gamma$, H$\delta$) are also detected, and if powered by star formation rather than an AGN we infer a star formation rate of $\sim 20-30 M_{\odot}\,\rm yr^{-1}$ (depending on the IMF) and low dust attenuation. Our NIRSpec spectroscopy confirms that GN-z11 is a remarkable galaxy with extreme properties seen 430 Myr after the Big Bang.Comment: Submitted to Astronomy & Astrophysics, 14 pages, 9 figure