Yin-Yang transcription factor 1 (YY1) is involved in tumor progression, metastasis and has been shown to be elevated in different cancers, including leukemia. The regulatory mechanism underlying YY1 ...expression in leukemia is still not understood. Bioinformatics analysis reveal three Hypoxia-inducible factor 1-alpha (HIF-1α) putative binding sites in the YY1 promoter region. The regulation of YY1 by HIF-1α in leukemia was analyzed. Mutation of the putative YY1 binding sites in a reporter system containing the HIF-1α promoter region and CHIP analysis confirmed that these sites are important for YY1 regulation. Leukemia cell lines showed that both proteins HIF-1α and YY1 are co-expressed under hypoxia. In addition, the expression of mRNA of YY1 was increased after 3 h of hypoxia conditions and affect several target genes expression. In contrast, chemical inhibition of HIF-1α induces downregulation of YY1 and sensitizes cells to chemotherapeutic drugs. The clinical implications of HIF-1α in the regulation of YY1 were investigated by evaluation of expression of HIF-1α and YY1 in 108 peripheral blood samples and by RT-PCR in 46 bone marrow samples of patients with pediatric acute lymphoblastic leukemia (ALL). We found that the expression of HIF-1α positively correlates with YY1 expression in those patients. This is consistent with bioinformatic analyses of several databases. Our findings demonstrate for the first time that YY1 can be transcriptionally regulated by HIF-1α, and a correlation between HIF-1α expression and YY1 was found in ALL clinical samples. Hence, HIF-1α and YY1 may be possible therapeutic target and/or biomarkers of ALL.
A Catalog of M-dwarf Flares with ASAS-SN Rodríguez Martínez, Romy; Lopez, Laura A.; Shappee, Benjamin J. ...
Astrophysical journal/The Astrophysical journal,
04/2020, Letnik:
892, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We analyzed the light curves of 1376 early-to-late, nearby M dwarfs to search for white-light flares using photometry from the All-Sky Automated Survey for Supernovae. We identified 480 M dwarfs with ...at least one potential flare employing a simple statistical algorithm that searches for sudden increases in V-band flux. After more detailed evaluation, we identified 62 individual flares on 62 stars. The event amplitudes range from mag. Using classical flare models, we place lower limits on the flare energies and obtain V-band energies spanning erg. The fraction of flaring stars increases with spectral type, and most flaring stars show moderate to strong H emission. Additionally, we find that 14 of the 62 flaring stars are rotational variables, and they have shorter rotation periods and stronger H emission than nonflaring rotational variable M dwarfs.
We present evidence of diffuse, non-thermal X-ray emission from the superbubble 30 Doradus C (30 Dor C) using hard X-ray images and spectra from NuSTAR observations. For this analysis, we utilize ...data from a 200 ks targeted observation of 30 Dor C as well as 2.8 Ms of serendipitous off-axis observations from the monitoring of nearby SN 1987A. The complete shell of 30 Dor C is detected up to 20 keV, and the young supernova remnant MCSNR J0536−6913 in the southeast of 30 Dor C is not detected above 8 keV. Additionally, six point sources identified in previous Chandra and XMM-Newton investigations have hard X-ray emission coincident with their locations. Joint spectral fits to the NuSTAR and XMM-Newton spectra across the 30 Dor C shell confirm the non-thermal nature of the diffuse emission. Given the best-fit rolloff frequencies of the X-ray spectra, we find maximum electron energies of 70-110 TeV (assuming a B-field strength of 4 G), suggesting 30 Dor C is accelerating particles. Particles are either accelerated via diffusive shock acceleration at locations where the shocks have not stalled behind the H shell, or cosmic-rays are accelerated through repeated acceleration of low-energy particles via turbulence and magnetohydrodynamic waves in the bubble's interior.
Abstract
Rectal cancer is an increasing disease worldwide. The outcomes of its treatment are related to the preoperative characteristics of the patient. The objective of this study was to describe ...sociodemographic, clinical and surgical characteristics and outcomes of patients operated on for rectal cancer at Hospital Universitario Mayor Méderi (HUM) during the period within 2013–2017.A retrospective descriptive cohort-type study was carried out by consulting the clinical records of patients above the age of 18 years with a clinical/histopathological diagnosis of rectal cancer and an institutional follow-up in those who underwent surgery with laparoscopic anterior resection of the rectum carried out by the coloproctology service of the HUM between 2013 and 2017. For statistical analysis, the SPSS V22 program was used.Data from 133 patients were collected during the study period, most of them male, with more frequent involvement of the lower rectum. Complications occurred in 25% of the patients. Conversion rate to open surgery was 8.6%, in-hospital death was associated with cardiovascular comorbidity, corticosteroid uses and with the presence of complications. Sociodemographic characteristics of the patients were similar to the world population. The institution has a low prevalence of anastomotic dehiscence, global complications are comparable with international statistics.
The pathophysiology of anorexia nervosa (AN) and bulimia nervosa (BN) are still poorly understood, but psychobiological models have proposed a key role for disturbances in the neuroendocrines that ...signal hunger and satiety and maintain energy homeostasis. Mounting evidence suggests that many neuroendocrines involved in the regulation of homeostasis and body weight also play integral roles in food reward valuation and learning via their interactions with the mesolimbic dopamine system. Neuroimaging data have associated altered brain reward responses in this system with the dietary restriction and binge eating and purging characteristic of AN and BN. Thus, neuroendocrine dysfunction may contribute to or perpetuate eating disorder symptoms via effects on reward circuitry. This narrative review focuses on reward-related neuroendocrines that are altered in eating disorder populations, including peptide YY, insulin, stress and gonadal hormones, and orexins. We provide an overview of the animal and human literature implicating these neuroendocrines in dopaminergic reward processes and discuss their potential relevance to eating disorder symptomatology and treatment.
•Neuroendocrine disturbances may play a key role in anorexia and bulimia nervosa.•Interactions with dopaminergic reward circuits may promote eating disorder symptoms.•We review peptide YY, insulin, stress and gonadal hormones, and orexin alterations.
Abstract
We measure the molecular gas environment near recent (<100 yr old) supernovae (SNe) using ∼1″ or ≤150 pc resolution CO (2–1) maps from the PHANGS–Atacama Large Millimeter/submillimeter Array ...(ALMA) survey of nearby star-forming galaxies. This is arguably the first such study to approach the scales of individual massive molecular clouds (
M
mol
≳ 10
5.3
M
⊙
). Using the Open Supernova Catalog, we identify 63 SNe within the PHANGS–ALMA footprint. We detect CO (2–1) emission near ∼60% of the sample at 150 pc resolution, compared to ∼35% of map pixels with CO (2–1) emission, and up to ∼95% of the SNe at 1 kpc resolution, compared to ∼80% of map pixels with CO (2–1) emission. We expect the ∼60% of SNe within the same 150 pc beam, as a giant molecular cloud will likely interact with these clouds in the future, consistent with the observation of widespread SN–molecular gas interaction in the Milky Way, while the other ∼40% of SNe without strong CO (2–1) detections will deposit their energy in the diffuse interstellar medium, perhaps helping drive large-scale turbulence or galactic outflows. Broken down by type, we detect CO (2–1) emission at the sites of ∼85% of our 9 stripped-envelope SNe (SESNe), ∼40% of our 34 Type II SNe, and ∼35% of our 13 Type Ia SNe, indicating that SESNe are most closely associated with the brightest CO (2–1) emitting regions in our sample. Our results confirm that SN explosions are not restricted to only the densest gas, and instead exert feedback across a wide range of molecular gas densities.
Abstract High-resolution JWST-MIRI images of nearby spiral galaxies reveal emission with complex substructures that trace dust heated both by massive young stars and the diffuse interstellar ...radiation field. We present high angular (0.″85) and physical resolution (20–80 pc) measurements of the probability distribution function (PDF) of mid-infrared (mid-IR) emission (7.7–21 μ m) from 19 nearby star-forming galaxies from the PHANGS-JWST Cycle 1 Treasury. The PDFs of mid-IR emission from the disks of all 19 galaxies consistently show two distinct components: an approximately lognormal distribution at lower intensities and a high-intensity power law component. These two components only emerge once individual star-forming regions are resolved. Comparing with locations of H ii regions identified from Very Large Telescope/MUSE H α mapping, we infer that the power-law component arises from star-forming regions and thus primarily traces dust heated by young stars. In the continuum-dominated 21 μ m band, the power law is more prominent and contains roughly half of the total flux. At 7.7–11.3 μ m, the power law is suppressed by the destruction of small grains (including PAHs) close to H ii regions, while the lognormal component tracing the dust column in diffuse regions appears more prominent. The width and shape of the lognormal diffuse emission PDFs in galactic disks remain consistent across our sample, implying a lognormal gas column density N (H) ≈ 10 21 cm −2 shaped by supersonic turbulence with typical (isothermal) turbulent Mach numbers ≈5−15. Finally, we describe how the PDFs of galactic disks are assembled from dusty H ii regions and diffuse gas and discuss how the measured PDF parameters correlate with global properties such as star formation rate and gas surface density.
The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease ...(COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect on the SARS-CoV-2 in vitro and in vivo viral load. The in vitro study was conducted in a model of Vero E6 cells, while the in vivo study was an adaptive, two-armed, randomized, prospective, longitudinal, double-blind, multicentric, and phase IIb clinical trial. Our in vitro results revealed that MG effectively inhibits viral replication after 48 h of exposure to the drug, with no cytotoxic effect in doses up to 100 µM. The effect of the MG was also tested against three variants of interest (alpha, delta, and epsilon), showing increased survival rates in cells treated with MG. These results are aligned with our clinical data, which indicates that MG treatment reduces SARS-CoV2-infected patients´ viral load in just 3.3 days and supplementary oxygen requirements compared with the control group. We expect our results can guide efforts to position MG as a therapeutic option for COVID-19 patients.
•Metformin glycinate inhibits SARS-CoV-2 viral replication after 48 h of exposure.•MG increased survival in cells exposed to VOI (alpha, delta, and epsilon).•Patients treated with metformin glycinate reduces SARS-CoV2 viral load in 3.3 days.
Abstract We present a statistical analysis of the local, ≈50–100 pc scale, H α emission at the locations of recent (≤125 yr) supernovae (SNe) in nearby star-forming galaxies. Our sample consists of ...32 SNe in 10 galaxies that are targets of the PHANGS-MUSE survey. We find that 41% (13/32) of these SNe occur coincident with a previously identified H ii region. For comparison, H ii regions cover 32% of the area within ±1 kpc of any recent SN. Contrasting this local covering fraction with the fraction of SNe coincident with H ii regions, we find a statistical excess of 7.6% ± 8.7% of all SNe to be associated with H ii regions. This increases to an excess of 19.2% ± 10.4% when considering only core-collapse SNe (CCSNe). These estimates appear to be in good agreement with qualitative results from new, higher-resolution Hubble Space Telescope H α imaging, which also suggests many CCSNe detonate near but not in H ii regions. Our results appear consistent with the expectation that only a modest fraction of stars explode during the first ≲5 Myr of the life of a stellar population when H α emission is expected to be bright. Of the H ii region associated SNe, 85% (11/13) also have associated detected CO (2–1) emission, indicating the presence of molecular gas. The SNe associated with H ii regions have typical extinctions of A V ∼ 1 mag, consistent with a significant amount of pre-clearing of gas from the region before the SNe explode.
Abstract We present the Physics at High Angular resolution in Nearby GalaxieS (PHANGS)-AstroSat atlas, which contains UV imaging of 31 nearby star-forming galaxies captured by the Ultraviolet Imaging ...Telescope on the AstroSat satellite. The atlas provides a homogeneous data set of far-UV and near-UV maps of galaxies within a distance of 22 Mpc and a median angular resolution of 1.″4 (corresponding to a physical scale between 25 and 160 pc). After subtracting a uniform UV background and accounting for Milky Way extinction, we compare our estimated flux densities to GALEX observations, finding good agreement. We find candidate extended UV disks around the galaxies NGC 6744 and IC 5332. We present the first statistical measurements of the clumping of the UV emission and compare it to the clumping of molecular gas traced with the Atacama Large Millimeter/submillimeter Array (ALMA). We find that bars and spiral arms exhibit the highest degree of clumping, and the molecular gas is even more clumped than the far-UV (FUV) emission in galaxies. We investigate the variation of the ratio of observed FUV to H α in different galactic environments and kiloparsec-sized apertures. We report that ∼65% of the variation of the log 10 (FUV/H α ) can be described through a combination of dust attenuation with star formation history parameters. The PHANGS-AstroSat atlas enhances the multiwavelength coverage of our sample, offering a detailed perspective on star formation. When integrated with PHANGS data sets from ALMA, the Very Large Telescope-MUSE, the Hubble Space Telescope, and JWST, it develops our comprehensive understanding of attenuation curves and dust attenuation in star-forming galaxies.
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