Identification of ZBTB18 as a novel colorectal tumor suppressor gene through genome-wide promoter hypermethylation analysis

Background Cancer initiation and progression are driven by genetic and epigenetic changes. Although genome/exome sequencing has significantly contributed to the characterization of the genetic driver alterations, further investigation is required to systematically identify cancer driver genes regulated by promoter hypermethylation. Results Using genome-wide analysis of promoter methylation in 45 colorectal cancer cell lines, we found that higher overall methylation levels were associated with microsatellite instability (MSI), faster proliferation and absence of APC mutations. Because epigenetically silenced genes could represent important oncogenic drivers, we used mRNA expression profiling of colorectal cancer cell lines and primary tumors to identify a subset of 382 (3.9%) genes for which promoter methylation was negatively associated with gene expression. Remarkably, a significant enrichment in zinc finger proteins was observed, including the transcriptional repressor ZBTB18. Re-introduction of ZBTB18 in colon cancer cells significantly reduced proliferation in vitro and in a subcutaneous xenograft mouse model. Moreover, immunohistochemical analysis revealed that ZBTB18 is frequently lost or reduced in colorectal tumors, and reduced ZBTB18 expression was found to be associated with lymph node metastasis and shorter survival of patients with locally advanced colorectal cancer. Conclusions We identified a set of 382 genes putatively silenced by promoter methylation in colorectal cancer that could significantly contribute to the oncogenic process. Moreover, as a proof of concept, we demonstrate that the epigenetically silenced gene ZBTB18 has tumor suppressor activity and is a novel prognostic marker for patients with locally advanced colorectal cancer.Peer reviewe

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

COSMOGRAIL XVI: Time delays for the quadruply imaged quasar DES J0408-5354 with high-cadence photometric monitoring

We present time-delay measurements for the new quadruply imaged quasar DES J0408-5354, the first quadruply imaged quasar found in the Dark Energy Survey (DES). Our result is made possible by implementing a new observational strategy using almost daily observations with the MPIA 2.2m telescope at La Silla observatory and deep exposures reaching a signal-to-noise ratio of about 1000 per quasar image. This data quality allows us to catch small photometric variations (a few mmag rms) of the quasar, acting on temporal scales much shorter than microlensing, hence making the time delay measurement very robust against microlensing. In only 7 months we measure very accurately one of the time delays in DES J0408-5354: Dt(AB) = -112.1 +- 2.1 days (1.8%) using only the MPIA 2.2m data. In combination with data taken with the 1.2m Euler Swiss telescope, we also measure two delays involving the D component of the system Dt(AD) = -155.5 +- 12.8 days (8.2%) and Dt(BD) = -42.4 +- 17.6 days (41%), where all the error bars include systematics. Turning these time delays into cosmological constraints will require deep HST imaging or ground-based Adaptive Optics (AO), and information on the velocity field of the lensing galaxy.Comment: 9 pages, 5 figures, accepted for publication in Astronomy & Astrophysic

Cosmograil: the cosmological monitoring of gravItational Lenses XVI. Time delays for the quadruply imaged quasar DES J0408-5354 with high-cadence photometric monitoring

FINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESWe present time-delay measurements for the new quadruple imaged quasar DES J0408-5354, the first quadruple imaged quasar found in the Dark Energy Survey (DES). Our result is made possible by implementing a new observational strategy using almost daily observations with the MPIA 2.2 m telescope at La Silla observatory and deep exposures reaching a signal-to-noise ratio of about 1000 per quasar image. This data quality allows us to catch small photometric variations (a few mmag rms) of the quasar, acting on temporal scales much shorter than microlensing, and hence making the time delay measurement very robust against microlensing. In only seven months we very accurately measured one of the time delays in DES J0408-5354: Delta t(AB) = -112.1 +/- 2.1 days (1.8%) using only the MPIA 2.2 m data. In combination with data taken with the 1.2 m Euler Swiss telescope, we also measured two delays involving the D component of the system Delta t(AD) = -155.5 +/- 12.8 days (8.2%) and Delta t(BD) = -42.4 +/- 17.6 days (41%), where all the error bars include systematics. Turning these time delays into cosmological constraints will require deep Hubble Space Telescope (HST) imaging or ground-based adaptive optics (AO), and information on the velocity field of the lensing galaxy.60919FINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESSem informaçãoSem informaçãoSem informaçãoSem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

The STRong lensing insights into the dark energy survey (STRIDES) 2016 follow-up campaign - II. new quasar lenses from double component fitting

FINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESWe report upon the follow-up of 34 candidate lensed quasars found in the Dark Energy Survey using NTTEFOSC, Magellan-IMACS, KECK-ESI, and SOAR-SAMI. These candidates were selected by a combination of double component fitting, morphological assessment, and colour analysis. Most systems followed up are indeed composed of at least one quasar image and 13 with two or more quasar images: two lenses, four projected binaries, and seven nearly identical quasar pairs (NIQs). The two systems confirmed as genuine gravitationally lensed quasars are one quadruple at z(s) = 1.713 and one double at z(s) = 1.515. Lens modelling of these two systems reveals that both systems require very little contribution from the environment to reproduce the image configuration. Nevertheless, small flux anomalies can be observed in one of the images of the quad. Further observations of nine inconclusive systems (including seven NIQs) will allow to confirm (or not) their gravitational lens nature.480450175028FINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Erratum: Is every strong lens model unhappy in its own way? Uniform modelling of a sample of 13 quadruply+ imaged quasars

The paper ‘Is every strong lens model unhappy in its own way? Uniform modelling of a sample of 13 quadruply+ imaged quasars’ was published in MNRAS, 483, 4, 5649–5671 (2019). The coordinate values of the image positions in table 4 were wrongly printed due to a clerical error. At a later stage of writing the manuscript, we have changed the zero-point definition of the lens coordinate systems, but the relative image positions were not accounted for this change of definition while printing out table 4. We provide the updated Table 4 below. This error does not impact any other results of the paper in any way, except for the table itself. We thank Collin Werner and Paul Schechter for helping us identify this error

Is every strong lens model unhappy in its own way? Uniform modelling of a sample of 13 quadruply+ imaged quasars

Strong-gravitational lens systems with quadruply imaged quasars (quads) are unique probes to address several fundamental problems in cosmology and astrophysics. Although they are intrinsically very rare, ongoing and planned wide-field deep-sky surveys are set to discover thousands of such systems in the next decade. It is thus paramount to devise a general framework to model strong-lens systems to cope with this large influx without being limited by expert investigator time. We propose such a general modelling framework (implemented with the publicly available software LENSTRONOMY) and apply it to uniformly model three-band Hubble Space Telescope Wide Field Camera 3 images of 13 quads. This is the largest uniformly modelled sample of quads to date and paves the way for a variety of studies. To illustrate the scientific content of the sample, we investigate the alignment between the mass and light distribution in the deflectors. The position angles of these distributions are well-aligned, except when there is strong external shear. However, we find no correlation between the ellipticity of the light and mass distributions. We also show that the observed flux-ratios between the images depart significantly from the predictions of simple smooth models. The departures are strongest in the bluest band, consistent with microlensing being the dominant cause in addition to millilensing. Future papers will exploit this rich data set in combination with ground-based spectroscopy and time delays to determine quantities such as the Hubble constant, the free streaming length of dark matter, and the normalization of the initial stellar mass function

DES meets Gaia: discovery of strongly lensed quasars from a multiplet search

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROFINEP - FINANCIADORA DE ESTUDOS E PROJETOSWe report the discovery, spectroscopic confirmation, and first lens models of the first, strongly lensed quasars from a combined search in WISE and Gaia-DR1 over the DES footprint. Their Einstein radii span a range between approximate to 2.0 arcsec and approximate to 0.4 arcsec. Two of these (WGD2038-4008, RA = 20: 38: 02.65, Dec. = -40: 08: 14.64; WGD2021-4115, RA = 20: 21: 39.45, Dec. = -41:15:57.11) also have confirmed deflector redshifts. The four-image lens WGD2038-4008, with source and deflector redshifts s = 0.777 +/- 0.001 and z(l) = 0.230 +/- 0.002, respectively, has a deflector with radius R-eff approximate to 3.4 arcsec, stellar mass log(M-star /M-circle dot) = 11.64(-0.43)(+ 0.20), and extended isophotal shape variation. Simple lens models yield Einstein radii R-E = (1.30 +/- 0.04) arcsec, axis ratio q = 0.75 +/- 0.1 (compatible with that of the starlight) and considerable shear-ellipticity degeneracies. The two-image lens WGD2021-4115 has z(s) = 1.390 +/- 0.001 and z(l) = 0.335 +/- 0.002, and Einstein radius R-E = (1.1 +/- 0.1) arcsec, but higher-resolution imaging is needed to accurately separate the deflector and faint quasar image. Analogous lens model degeneracies hold for the other six lenses (J0146-1133, J0150-4041, J0235-2433, J0245-0556, J0259-2338, and J0508-2748) shown in this paper.479443454354CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROFINEP - FINANCIADORA DE ESTUDOS E PROJETOSCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROFINEP - FINANCIADORA DE ESTUDOS E PROJETOSSem informaçãoSem informaçãoSem informaçãoSem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

The STRong lensing Insights into the Dark Energy Survey (STRIDES) 2016 follow-up campaign - I. Overview and classification of candidates selected by two techniques

The primary goals of the STRong lensing Insights into the Dark Energy Survey (STRIDES) collaboration are to measure the dark energy equation of state parameter and the free streaming length of dark matter. To this aim, STRIDES is discovering strongly lensed quasars in the imaging data of the Dark Energy Survey and following them up to measure time delays, high resolution imaging, and spectroscopy sufficient to construct accurate lens models. In this paper, we first present forecasts for STRIDES. Then, we describe the STRIDES classification scheme, and give an overview of the Fall 2016 follow-up campaign. We continue by detailing the results of two selection methods, the Outlier Selection Technique and a morphological algorithm, and presenting lens models of a system, which could possibly be a lensed quasar in an unusual configuration. We conclude with the summary statistics of the Fall 2016 campaign. Including searches presented in companion papers (Anguita et al.; Ostrovski et al.), STRIDES followed up 117 targets identifying 7 new strongly lensed systems, and 7 nearly identical quasars (NIQs), which could be confirmed as lenses by the detection of the lens galaxy. 76 candidates were rejected and 27 remain otherwise inconclusive, for a success rate in the range 6-35\%. This rate is comparable to that of previous searches like SQLS even though the parent dataset of STRIDES is purely photometric and our selection of candidates cannot rely on spectroscopic information

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location