Insulin and IGF-1, but not 17β-estradiol, alter the subcellular localization of MIER1α in MCF7 breast carcinoma cells

Background MIER1α is a transcriptional regulator that interacts with estrogen receptor α and inhibits estrogen-stimulated growth of breast carcinoma cells. Interestingly, analysis of MIER1α subcellular localization in breast samples revealed a stepwise shift from the nucleus to the cytoplasm during progression to invasive carcinoma. Previously, we demonstrated that MIER1α is nuclear in MCF7 cells yet it does not contain a nuclear localization signal. Instead MIER1α is targeted to the nucleus through interaction and co-transport with HDAC 1 and 2. Results In this study, we demonstrate that treatment of MCF7 breast carcinoma cells with either insulin or insulin-like growth factor affects the subcellular localization of MIER1α. Both factors reduce the percentage of cells with nuclear MIER1α from 81 and 89 to 41 and 56 %, respectively. Treatment with 17β-estradiol, on the other hand, had no effect and MIER1α remained nuclear. Conclusions Our data demonstrate that insulin and IGF-1 can contribute to loss of nuclear MIER1α in the MCF7 breast carcinoma cell line

The Magellan Evolution of Galaxies Spectroscopic and Ultraviolet Reference Atlas (MEGaSaURA) I: The Sample and the Spectra

We introduce Project MEGaSaURA: The Magellan Evolution of Galaxies Spectroscopic and Ultraviolet Reference Atlas. MEGaSaURA comprises medium-resolution, rest-frame ultraviolet spectroscopy of N=15 bright gravitationally lensed galaxies at redshifts of 1.68$<$z$<$3.6, obtained with the MagE spectrograph on the Magellan telescopes. The spectra cover the observed-frame wavelength range $3200 < \lambda_o < 8280$ \AA ; the average spectral resolving power is R=3300. The median spectrum has a signal-to-noise ratio of $SNR=21$ per resolution element at 5000 \AA . As such, the MEGaSaURA spectra have superior signal-to-noise-ratio and wavelength coverage compared to what COS/HST provides for starburst galaxies in the local universe. This paper describes the sample, the observations, and the data reduction. We compare the measured redshifts for the stars, the ionized gas as traced by nebular lines, and the neutral gas as traced by absorption lines; we find the expected bulk outflow of the neutral gas, and no systemic offset between the redshifts measured from nebular lines and the redshifts measured from the stellar continuum. We provide the MEGaSaURA spectra to the astronomical community through a data release.Comment: Resubmitted to AAS Journals. Data release will accompany journal publication. v2 addresses minor comments from refere

Low-Temperature Photoluminescence Spectroscopy of Solvent-Free PCBM Single-Crystals

PCBM ([6,6]-phenyl-C61-butyric acid methyl ester) is a highly soluble C60 derivative that is extensively used in organic solar cells, enabling power conversion efficiencies above 10%. Here we report, for the first time to the best of our knowledge, the photoluminescence of high-quality solvent-free PCBM crystals between room temperature and 4 K. Interestingly, the PL spectra of these crystals become increasingly structured as the temperature is lowered, with extremely well-resolved emission lines (and a minimum line width of ∼1.3 meV at 1.73 eV). We are able to account for such a structured emission by means of a vibronic coupling model including Franck–Condon, Jahn–Teller and Herzberg–Teller effects. Although optical transitions are not formally forbidden from the low-lying excited states of PCBM, the high symmetry of the electronically active fullerene core limits the intensity of the 0–0 transition, such that Herzberg–Teller transitions which borrow intensity from higher-lying states represent a large part of the observed spectrum. Our simulations suggest that the emissive state of PCBM can be considered as a mixture of the T1g and Hg excited states of C60 and hence that the Hg state plays a larger role in the relaxed excited state of PCBM than in that of C60

A Preliminary Analysis of Anthropogenic and Natural Impacts on a Volcanic Lake Ecosystem in Southern Italy by UAV-Based Monitoring

Lakes play an important role in providing various ecosystem services. However, stressors such as climate change, land use, or land-cover change threaten the ecological functions of lakes. National and international legislations address these threats and establish consistent, long-term monitoring schemes. Remote sensing techniques based on the use of Unmanned Aerial Vehicles (UAV) have recently been demonstrated to provide accurate and low-cost spatio-temporal views for the assessment of the ecological status of aquatic ecosystems and the identification of areas at risk of contamination. Few studies have been carried out so far on the employment of these tools in the monitoring of lakes. Therefore, high-resolution UAV surveys were used to analyse and evaluate natural and anthropogenic impacts on the habitat status of a volcanic lake in a protected area. Five UAV flights took place during a year-long cycle (November 2020 to November 2021) in a volcanic lake located in southern Italy. For each flight performance, an orthomosaic of georeferenced RGB images was obtained, and the different features of interest were monitored and quantified using automated processing in a GIS environment. The UAV images made it possible not only to estimate the flooded shores but also to detect the impact of human-made structures and infrastructures on the lagoon environment. It has been possible to observe how the rapid changes in lake-water level have led to the submersion of about 90.000 m(2) of terrain in winter, causing the fragmentation and degradation of habitats, while the connectivity of the natural ecosystem has been threatened by the presence of the road around the lake. The proposed methodology is rather simple and easily replicable by decision makers and local administrators and can be useful for choosing the best restoration interventions

Differential Splicing Alters Subcellular Localization of the Alpha but not Beta Isoform of the MIER1 Transcriptional Regulator in Breast Cancer Cells

MIER1 was originally identified in a screen for novel fibroblast growth factor activated early response genes. The mier1 gene gives rise to multiple transcripts encoding protein isoforms that differ in their amino (N-) and carboxy (C-) termini. Much of the work to date has focused on the two C-terminal variants, MIER1α and β, both of which have been shown to function as transcriptional repressors. Our previous work revealed a dramatic shift in MIER1α subcellular localization from nuclear in normal breast tissue to cytoplasmic in invasive breast carcinoma, suggesting that loss of nuclear MIER1α may play a role in breast cancer development. In the present study, we investigated whether alternative splicing to include a cassette exon and produce an N–terminal variant of MIER1α affects its subcellular localization in MCF7 breast carcinoma cells. We demonstrate that this cassette exon, exon 3A, encodes a consensus leucine-rich nuclear export signal (NES). Inclusion of this exon in MIER1α to produce the MIER1-3Aα isoform altered its subcellular distribution in MCF7 cells from 81% nuclear to 2% nuclear and this change in localization was abrogated by mutation of critical leucines within the NES. Treatment with leptomycin B (LMB), an inhibitor of the nuclear export receptor CRM1, resulted in a significant increase in the percentage of cells with nuclear MIER1-3Aα, from 4% to 53%, demonstrating that cytoplasmic localization of this isoform was due to CRM1-dependent nuclear export. Inclusion of exon 3A in MIER1β to produce the N-terminal variant MIER1-3Aβ however had little effect on the nuclear targeting of this isoform. Our results demonstrate that alternative splicing to include exon 3A specifically affects the localization pattern of the α isoform

The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein

Background: Mier1 encodes a novel transcriptional regulator and was originally isolated as a fibroblast growth factor early response gene. Two major protein isoforms have been identified, MIER1 and, which differ in their C-terminal sequence. Previously, we demonstrated that both isoforms recruit histone deacetylase 1 (HDAC1) to repress transcription. To further explore the role of MIER1 in chromatin remodeling, we investigated the functional interaction of MIER1 with the histone acetyltransferase (HAT), Creb-binding protein (CBP). Findings: Using GST pull-down assays, we demonstrate that MIER1 interacts with CBP and that this interaction involves the N-terminal half (amino acids 1-283) of MIER1, which includes the acidic activation and ELM2 domains and the C-terminal half (amino acids 1094-2441) of CBP, which includes the bromo-, HAT, C/H3 and glutamine-rich domains. Functional analysis, using HEK293 cells, shows that the CBP bound to MIER1 in vivo has no detectable HAT activity. Histone 4 peptide binding assays demonstrate that this inhibition of HAT activity is not the result of interference with histone binding. Conclusion: Our data indicate that an additional mechanism by which MIER1 could repress transcription involves the inhibition of histone acetyltransferase activity

Lens Model and Time Delay Predictions for the Sextuply Lensed Quasar SDSS J2222+2745

SDSS J2222+2745 is a galaxy cluster at z=0.49, strongly lensing a quasar at z=2.805 into six widely separated images. In recent HST imaging of the field, we identify additional multiply lensed galaxies, and confirm the sixth quasar image that was identified by Dahle et al. (2013). We used the Gemini North telescope to measure a spectroscopic redshift of z=4.56 of one of the secondary lensed galaxies. These data are used to refine the lens model of SDSS J2222+2745, compute the time delay and magnifications of the lensed quasar images, and reconstruct the source image of the quasar host and a second lensed galaxy at z=2.3. This second galaxy also appears in absorption in our Gemini spectra of the lensed quasar, at a projected distance of 34 kpc. Our model is in agreement with the recent time delay measurements of Dahle et al. (2015), who found tAB=47.7+/-6.0 days and tAC=-722+/-24 days. We use the observed time delays to further constrain the model, and find that the model-predicted time delays of the three faint images of the quasar are tAD=502+/-68 days, tAE=611+/-75 days, and tAF=415+/-72 days. We have initiated a follow-up campaign to measure these time delays with Gemini North. Finally, we present initial results from an X-ray monitoring program with Swift, indicating the presence of hard X-ray emission from the lensed quasar, as well as extended X-ray emission from the cluster itself, which is consistent with the lensing mass measurement and the cluster velocity dispersion.Comment: 16 pages, 11 figures; submitted to Ap

Spatially Resolved Patchy Lyman-α\alpha Emission Within the Central Kiloparsec of a Strongly Lensed Quasar Host Galaxy at z = 2.8

We report the detection of extended Lyman-$\alpha$ emission from the host galaxy of SDSS~J2222+2745, a strongly lensed quasar at $z = 2.8$. Spectroscopic follow-up clearly reveals extended Lyman-$\alpha$ in emission between two images of the central active galactic nucleus (AGN). We reconstruct the lensed quasar host galaxy in the source plane by applying a strong lens model to HST imaging, and resolve spatial scales as small as $\sim$200 parsecs. In the source plane we recover the host galaxy morphology to within a few hundred parsecs of the central AGN, and map the extended Lyman-$\alpha$ emission to its physical origin on one side of the host galaxy at radii $\sim$0.5-2 kpc from the central AGN. There are clear morphological differences between the Lyman-$\alpha$ and rest-frame ultraviolet stellar continuum emission from the quasar host galaxy. Furthermore, the relative velocity profiles of quasar Lyman-$\alpha$, host galaxy Lyman-$\alpha$, and metal lines in outflowing gas reveal differences in the absorbing material affecting the AGN and host galaxy. These data indicate the presence of patchy local intervening gas in front of the central quasar and its host galaxy. This interpretation is consistent with the central luminous quasar being obscured across a substantial fraction of its surrounding solid angle, resulting in strong anisotropy in the exposure of the host galaxy to ionizing radiation from the AGN. This work demonstrates the power of strong lensing-assisted studies to probe spatial scales that are currently inaccessible by other means.Comment: Accepted to ApJ Letters; 7 pages, 5 figure

Adapting SAM for CDF

The CDF and D0 experiments probe the high-energy frontier and as they do so have accumulated hundreds of Terabytes of data on the way to petabytes of data over the next two years. The experiments have made a commitment to use the developing Grid based on the SAM system to handle these data. The D0 SAM has been extended for use in CDF as common patterns of design emerged to meet the similar requirements of these experiments. The process by which the merger was achieved is explained with particular emphasis on lessons learned concerning the database design patterns plus realization of the use cases.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 4 pages, pdf format, TUAT00

Leucocyte-and platelet-rich fibrin block: Its use for the treatment of a large cyst with implant-based rehabilitation

The management of critical-size bone defects is still demanding. Recently, autologous platelet concentrates in combination with bone substitute have been applied and reported in a few studies. Our aim is to report the healing of a critical-size alveolar bone defect treated with a new bone regeneration technique by means of L-PRF and L-PRF blocks. A 45-year-old woman presented a large cystic lesion; the extraction of three teeth, a cyst removal procedure, and bone regeneration procedures with L-PRF and L-PRF blocks were planned. The L-PRF block was prepared by mixing a bone substitute with a piece of L-PRF membrane and liquid fibrinogen. Additionally, after bone healing an implant-based rehabilitation was optimally performed. On the basis of the positive results, in terms of bone healing and tissue regeneration in a large bone defect, the application of LPRF and L-PRF blocks, in agreement with the scarce literature, is suggested as a feasible procedure in selected cases