Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression

BACKGROUND: S100 proteins, a multigenic family of non-ubiquitous cytoplasmic Ca(2+)-binding proteins, have been linked to human pathologies in recent years. Dysregulated expression of S100 proteins, including S100A9, has been reported in the epidermis as a response to stress and in association with neoplastic disorders. Recently, we characterized a regulatory element within the S100A9 promotor, referred to as MRE that drives the S100A9 gene expression in a cell type-specific, activation- and differentiation-dependent manner (Kerkhoff et al. (2002) J. Biol. Chem. 277, 41879–41887). RESULTS: In the present study, we investigated transcription factors that bind to MRE. Using the MRE motif for a pull-down assay, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric complex Ku70/Ku80 were identified by mass spectrometry and confirmed by chromatin immunoprecipitation. Furthermore, TPA-induced S100A9 gene expression in HaCaT keratinocytes was blocked after the pharmacologic inhibition of PARP-1 with 1,5-isoquinolinediol (DiQ). CONCLUSION: The candidates, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric complex Ku70/Ku80, are known to participate in inflammatory disorders as well as tumorgenesis. The latter may indicate a possible link between S100 and inflammation-associated cancer

A prospective cohort analysis of residential radon and UV exposures and malignant melanoma mortality in the Swiss population.

BACKGROUND Radon is a radioactive noble gas naturally found in the earth crust that can accumulate in buildings. In addition to lung cancer, alpha particles emitted by radon may contribute to the risk of skin cancer. We evaluated the association between residential radon exposure and skin cancer mortality, over a fifteen year period, taking residential ultra-violet (UV) exposure into account. METHODS We included 4.9 million adults from the Swiss National Cohort. Hazard ratios for melanoma mortality were estimated using Cox proportional hazard models (20+ years old; follow-up 2001-2015). Long-term modelled residential radon and ambient UV exposures were assigned at baseline, and included together in the Cox models. With age as a time scale, models were adjusted for calendar time, sex, marital status, education, mother tongue, socioeconomic position, and occupational environment with potential for UV exposure. Age specific hazard ratios were derived. Effect modification, sensitivity analyses and the shape of the exposure response, as well as secondary analysis using other outcome definitions, were investigated. RESULTS During follow-up (average of 13.6 years), 3,979 melanoma deaths were observed. Associations declined with age, with an adjusted hazard ratio per 100 Bq/m3 radon at age 60 of 1.10 (95% CI: 0.99, 1.23). The dose-response showed an approximate linear trend between the minimum and mean radon exposure of 75 Bq/m3. Having outdoor occupation significantly increased the risk of melanoma mortality associated with UV exposure compared to indoor jobs. Analysis restricted to the last five years of follow-up showed similar results compared to the main analysis. Similar associations were found for mortality from melanoma and non-melanoma skin cancer combined. CONCLUSION With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance

Using Supervised Learning Algorithms as a Follow-Up Method in the Search of Gravitational Waves from Core-Collapse Supernovae

We present a follow-up method based on supervised machine learning (ML) to improve the performance in the search of gravitational wave (GW) bursts from core-collapse supernovae (CCSNe) using the coherent WaveBurst (cWB) pipeline. The ML model discriminates noise from signal events by using a set of reconstruction parameters provided by cWB as features. Detected noise events are discarded yielding a reduction in the false alarm rate (FAR) and the false alarm probability thus enhancing the statistical significance. We tested the proposed method using strain data from the first half of the third observing run of advanced LIGO, and CCSNe GW signals extracted from 3D simulations. The ML model is tuned using a dataset of noise and signal events, and then used to identify and discard noise events in the cWB analyses. Noise and signal reduction levels were examined in single (L1 and H1) and two detector networks (L1H1). The FAR was reduced by a factor of ∼10 to ∼100 resulting in an enhancement in the statistical significance of ∼1σ to ∼2σ, while not impacting the detection efficiencies

Using supervised learning algorithms as a follow-up method in the search of gravitational waves from core-collapse supernovae

We present a follow-up method based on supervised machine learning (ML) to improve the performance in the search of gravitational wave (GW) bursts from core-collapse supernovae (CCSNe) using the coherent WaveBurst (cWB) pipeline. The ML model discriminates noise from signal events by using a set of reconstruction parameters provided by cWB as features. Detected noise events are discarded yielding a reduction in the false alarm rate (FAR) and the false alarm probability thus enhancing the statistical significance. We tested the proposed method using strain data from the first half of the third observing run of advanced LIGO, and CCSNe GW signals extracted from 3D simulations. The ML model is tuned using a dataset of noise and signal events, and then used to identify and discard noise events in the cWB analyses. Noise and signal reduction levels were examined in single (L1 and H1) and two detector network (L1H1). The FAR was reduced by a factor of ∼10 to ∼100 resulting in an enhancement in the statistical significance of ∼1σ to ∼2σ, while not impacting the detection efficiencies

BIOESTIMULADORES DE COLÁGENO NO GERENCIAMENTO DO ENVELHECIMENTO: ARTIGO DE REVISÃO CRÍTICA DE LITERATURA

Os compostos conhecidos como bioestimuladores de colágeno, nomeadamente o ácido poli-L-láctico (PLL A), a hidroxiapatita de cálcio (CaHA) e a policaprolactona (PCL), são polímeros injetáveis que têm a capacidade de estimular a produção de colágeno. Essa estimulação contribui para a melhoria das características da pele, resultando em um rejuvenescimento perceptível externamente. Esses bioestimuladores podem tratar eficazmente problemas como rugas, flacidez, sulcos, manchas, textura irregular e outros efeitos do envelhecimento. Além disso, eles são empregados como preenchedores faciais. O objetivo desta revisão sistemática é avaliar a eficácia e segurança do uso de bioestimuladores faciais no rejuvenescimento facial. A metodologia empregada neste trabalho consiste em pesquisa bibliográfica, adotando uma abordagem qualitativa, básica, exploratória e descritiva. Através dessa abordagem, observa-se que os bioestimuladores desempenham um papel restaurador e suavizante nos efeitos do envelhecimento e outras imperfeições faciais. Eles induzem uma resposta inflamatória que estimula os fibroblastos a produzirem colágeno, combatendo assim os sinais visíveis do envelhecimento facial e promovendo a formação de novos tecidos

Electronic structure, magnetism, and disorder in the Heusler compound Co2_2TiSn

Polycrystalline samples of the half-metallic ferromagnet Heusler compound Co$_2$TiSn have been prepared and studied using bulk techniques (X-ray diffraction and magnetization) as well as local probes ($^{119}$Sn M\"ossbauer spectroscopy and $^{59}$Co nuclear magnetic resonance spectroscopy) in order to determine how disorder affects half-metallic behavior and also, to establish the joint use of M\"ossbauer and NMR spectroscopies as a quantitative probe of local ion ordering in these compounds. Additionally, density functional electronic structure calculations on ordered and partially disordered Co$_2$TiSn compounds have been carried out at a number of different levels of theory in order to simultaneously understand how the particular choice of DFT scheme as well as disorder affect the computed magnetization. Our studies suggest that a sample which seems well-ordered by X-ray diffraction and magnetization measurements can possess up to 10% of antisite (Co/Ti) disordering. Computations similarly suggest that even 12.5% antisite Co/Ti disorder does not destroy the half-metallic character of this material. However, the use of an appropriate level of non-local DFT is crucial.Comment: 11 pages and 5 figure

Observing an intermediate-mass black hole GW190521 with minimal assumptions

On May 21, 2019 the Advanced LIGO and Advanced Virgo detectors observed a gravitationalwave transient GW190521, the heaviest binary black-hole merger detected to date with remnant mass of 142 M⊙ that was published recently. This observation is the first strong evidence for the existence of intermediate-mass black holes. The significance of this observation was determined by the coherent WAVEBURST (cWB) search algorithm, which identified GW190521 with minimal assumptions of its source model. In this paper, we show the performance of cWB for the detection of the binary black-hole mergers without use of the signal templates, describe the details of the GW190521 detection, and establish the consistency of the model-agnostic reconstruction of GW190521 by cWB with the theoretical waveform model of a binary black hole

Tailored enrichment strategy detects low abundant small noncoding RNAs in HIV-1 infected cells

BACKGROUND: The various classes of small noncoding RNAs (sncRNAs) are important regulators of gene expression across divergent types of organisms. While a rapidly increasing number of sncRNAs has been identified over recent years, the isolation of sncRNAs of low abundance remains challenging. Virally encoded sncRNAs, particularly those of RNA viruses, can be expressed at very low levels. This is best illustrated by HIV-1 where virus encoded sncRNAs represent approximately 0.1-1.0% of all sncRNAs in HIV-1 infected cells or were found to be undetected. Thus, we applied a novel, sequence targeted enrichment strategy to capture HIV-1 derived sncRNAs in HIV-1 infected primary CD4+ T-lymphocytes and macrophages that allows a greater than 100-fold enrichment of low abundant sncRNAs. RESULTS: Eight hundred and ninety-two individual HIV-1 sncRNAs were cloned and sequenced from nine different sncRNA libraries derived from five independent experiments. These clones represent up to 90% of all sncRNA clones in the generated libraries. Two hundred and sixteen HIV-1 sncRNAs were distinguishable as unique clones. They are spread throughout the HIV-1 genome, however, forming certain clusters, and almost 10% show an antisense orientation. The length of HIV-1 sncRNAs varies between 16 and 89 nucleotides with an unexpected peak at 31 to 50 nucleotides, thus, longer than cellular microRNAs or short-interfering RNAs (siRNAs). Exemplary HIV-1 sncRNAs were also generated in cells infected with different primary HIV-1 isolates and can inhibit HIV-1 replication. CONCLUSIONS: HIV-1 infected cells generate virally encoded sncRNAs, which might play a role in the HIV-1 life cycle. Furthermore, the enormous capacity to enrich low abundance sncRNAs in a sequence specific manner highly recommends our selection strategy for any type of investigation where origin or target sequences of the sought-after sncRNAs are known

Observing an intermediate-mass black hole GW190521 with minimal assumptions

On May 21, 2019 the Advanced LIGO and Advanced Virgo detectors observed a gravitational-wave transient GW190521, the heaviest binary black-hole merger detected to date with remnant mass of 142 solar masses that was published recently. This observation is the first strong evidence for the existence of intermediate-mass black holes. The significance of this observation was determined by the coherent waveburst (cWB) search algorithm, which identified GW190521 with minimal assumptions of its source model. In this paper, we show the performance of cWB for the detection of the binary black-hole mergers without use of the signal templates, describe the details of the GW190521 detection, and establish the consistency of the model-agnostic reconstruction of GW190521 by cWB with the theoretical waveform model of a binary black hole