Nuclear factor-jB (NF-jB) and p53 critically determine cancer development and progression. Defining the cross talk between these transcription factors can expand our knowledge on molecular mechanisms of tumorigenesis. Here, we show that induction of replicational stress activates NF-jB p65 and triggers its interaction with p53 in the nucleus. Experiments with knockout cells show that p65 and p53 are both required for enhanced NF-jB activity during S-phase checkpoint activation involving ataxiatelangiectasia mutated and checkpoint kinase-1. Accordingly, the pro-inflammatory cytokine tumor necrosis factora (TNF-a) also triggers formation of a transcriptionally active complex containing nuclear p65 and p53 on jB response elements. Gene expression analyses revealed that, independent of NF-jB activation in the cytosol, TNFinduced NF-jB-directed gene expression relies on p53. Hence, p53 is unexpectedly necessary for NF-jB-mediated gene expression induced by atypical and classical stimuli. Remarkably, data from gain-and loss-of function approaches argue that anti-apoptotic NF-jB p65 activity is constitutively evoked by a p53 hot-spot mutant frequently found in tumors. Our observations suggest explanations for the outstanding question why p53 mutations rather than p53 deletions arise in tumors of various origins.

Context. Class II methanol masers are signposts of massive young stellar objects (MYSOs). Recent evidence shows that flares of these masers are driven by MYSO accretion bursts. Thus, maser monitoring can be used to identify such bursts which are hard to discover otherwise. Infrared observations reveal burst-induced changes in the spectral energy distribution (first and foremost a luminosity increase), which provide valuable information on a very intense phase of high-mass star formation. Aims. In mid-January 2019, flaring of the 6.7 GHz CH3OH maser (hereafter maser) of the MYSO G358.93-0.03 (hereafter G358) was reported. The international maser community initiated an extensive observational campaign which revealed extraordinary maser activity and yielded the detection of numerous new masering transitions. Interferometric imaging with the Atacama Large Millimeter/submillimeter Array and the Submillimeter Array resolved the maser emitting core of the star forming region and proved the association of the masers with the brightest continuum source (MM1), which hosts a hot molecular core. These observations, however, failed to detect a significant rise in the (sub)millimeter dust continuum emission. Therefore, we performed near-infrared (NIR) and far-infrared (FIR) observations to prove or disprove whether the CH3OH flare was driven by an accretion burst. Methods. NIR imaging with the Gamma-Ray Burst Optical/Near-infrared Detector has been acquired and integral-field spectroscopy with the Field-Imaging Far-Infrared Line Spectrometer (FIFI-LS) aboard the Stratospheric Observatory for Infrared Astronomy (SOFIA) was carried out on two occasions to detect possible counterparts to the (sub)millimeter sources and compare their photometry to archival measurements. The comparison of pre-burst and burst spectral energy distributions is of crucial importance to judge whether a substantial luminosity increase, caused by an accretion burst, is present and if it triggered the maser flare. Radiative transfer modeling of the spectral energy distribution (SED) of the dust continuum emission at multiple epochs provides valuable information on the bursting MYSO. Results. The FIR fluxes of MM1 measured with FIFI-LS exceed those from Herschel significantly, which clearly confirms the presence of an accretion burst. The second epoch data, taken about 16 months later, still show increased fluxes. Our radiative transfer modeling yielded major burst parameters and suggests that the MYSO features a circumstellar disk which might be transient. From the pre-burst, burst, and post-burst SEDs, conclusions on heating and cooling time-scales could be drawn. Circumstances of the burst-induced maser relocation have been explored. Conclusions. The verification of the accretion burst from G358 is another confirmation that Class II methanol maser flares represent an alert for such events. Thus, monitoring of these masers greatly enhances the chances of identifying MYSOs during periods of intense growth. The few events known to date already indicate that there is a broad range in burst strength and duration as well as environmental characteristics. The G358 event is the shortest and least luminous accretion burst known to date. According to models, bursts of this kind occur most often.

Helicobacter pylori infection is marked by intense production of reactive oxygen species (ROS) through the activation of neutrophils that are constantly attracted to the infected gastric mucosa. Here, gallic acid and its alkyl esters were evaluated as compounds able to act as antimicrobial agents and inhibitors of ROS released by H. pylori-activated neutrophils simultaneously. We found that the higher hydrophobicity caused by esterification of gallic acid led to a significant increase in its ability as a cytotoxic agent against H. pylori, a scavenger of ROS and an inhibitor of NADPH oxidase in neutrophils. Octyl gallate, a widely used food additive, showed the highest antimicrobial activity against H. pylori, with a minimum inhibitory concentration (MIC) value of 125 μg mL, whereas gallic acid had a MIC value higher than 1000 μg mL. The production of superoxide anion radicals was almost 100% abolished by the addition of 10 μM (2.82 μg mL) octyl gallate, whereas gallic acid inhibited around 20%. A similar tendency was also found when measuring the production of hypochlorous acid. The protective effect of the esters was cytochemically confirmed. In conclusion, this study showed that hydrophobicity is a crucial factor to obtain a significant anti-ROS and anti-H. pylori activity. Finally, it highlights octyl gallate, a food additive widely used in the food industry, as a promising molecule in the treatment of H. pylori infection.

This work aims to demonstrate that the gallic acid structure modification to the decyl gallate (G14) compound contributed to increase the antifungal activity against several species of pathogenic fungi, mainly, Candida spp., Cryptococcus spp., Paracoccidioides spp., and Histoplasma capsulatum, according to standardized microdilution method described by Clinical Laboratory Standard Institute (CLSI) documents. Moreover this compound has a particularly good selectivity index value, which makes it an excellent candidate for broad-spectrum antifungal prototype and encourages the continuation of subsequent studies for the discovery of its mechanism of action.