Nucleosomes effectively shield DNA from radiation damage in living cells

Abstract Eukaryotic DNA is organized in nucleosomes, which package DNA and regulate its accessibility to transcription, replication, recombination and repair. Here, we show that in living cells nucleosomes protect DNA from high-energy radiation and reactive oxygen species. We combined sequence-based methods (ATAC-seq and BLISS) to determine the position of both nucleosomes and double strand breaks (DSBs) in the genome of nucleosome-rich malignant mesothelioma cells, and of the same cells partially depleted of nucleosomes. The results were replicated in the human MCF-7 breast carcinoma cell line. We found that, for each genomic sequence, the probability of DSB formation is directly proportional to the fraction of time it is nucleosome-free; DSBs accumulate distal from the nucleosome dyad axis. Nucleosome free regions and promoters of actively transcribed genes are more sensitive to DSB formation, and consequently to mutation. We argue that this may be true for a variety of chemical and physical DNA damaging agents

Effects of crystal morphology on the hot-carrier dynamics in mixed-cation hybrid lead halide perovskites

Ultrafast pump-probe spectroscopies have proved to be an important tool for the investigation of charge carriers dynamics in perovskite materials providing crucial information on the dynamics of the excited carriers, and fundamental in the development of new devices with tailored photovoltaic properties. Fast transient absorbance spectroscopy on mixed-cation hybrid lead halide perovskite samples was used to investigate how the dimensions and the morphology of the per-ovskite crystals embedded in the capping (large crystals) and mesoporous (small crystals) layers affect the hot-carrier dynamics in the first hundreds of femtoseconds as a function of the excitation energy. The comparative study between samples with perovskite deposited on substrates with and without the mesoporous layer has shown how the small crystals preserve the temperature of the carriers for a longer period after the excitation than the large crystals. This study showed how the high sensitivity of the time-resolved spectroscopies in discriminating the transient response due to the different morphology of the crystals embedded in the layers of the same sample can be applied in the general characterization of materials to be used in solar cell devices and large area modules, providing further and valuable information for the optimization and enhancement of stability and efficiency in the power conversion of new perovskite-based devices

Different biological and prognostic breast cancer populations identified by FDG-PET in sentinel node-positive patients: Results and clinical implications after eight-years follow-up

Abstract Background Sentinel node (SN) biopsy is the standard method to evaluate axillary node involvement in breast cancer (BC). Positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG-PET) provides a non-invasive tool to evaluate regional nodes in BC in a metabolic-dependent, biomolecular-related way. In 1999, we initiated a prospective non-randomized study to compare these two methods and to test the hypothesis that FDG-PET results reflect biomolecular characteristics of the primary tumor, thereby yielding valuable prognostic information. Patients and methods A total of 145 cT1N0 BC patients, aged 24–70 years, underwent FDG-PET and lymphoscintigraphy before surgery. SN biopsy was followed in all cases by complete axillary dissection. Pathologic evaluation in tissue sections for involvement of the SN and other non-SN nodes served as the basis of the comparison between FDG-PET imaging and SN biopsy. Results FDG-PET and SN biopsy sensitivity was 72.6% and 88.7%, respectively, and negative predictive values were 80.5% and 92.2%, respectively. A subgroup of more aggressive tumors (ER-GIII, Her2+) was found mainly in the FDG-PET true-positive (FDG-PET+) patients, whereas LuminalA, Mib1 low-rate BCs were significantly undetected ( p = 0.009) in FDG-PET false-negative (FDG-PET−) patients. Kaplan–Meier survival estimates after a median follow-up of more than 8 years showed significantly worse overall survival for FDG-PET+ patients in node-positive (N+) patients ( p = 0.035) as compared to N+/FDG-PET− patients, which overlapped with survival curves of N− and FDG-PET+ or − patients. Conclusions Our findings suggest that FDG-PET results reflect intrinsic biologic features of primary BC tumors and have prognostic value with respect to nodal metastases. FDG-PET false negative cases appear to identify less aggressive indolent metastases. The possibility to identify a subgroup of N+ BC patients with an outcome comparable with N− BC patients could reduce the surgical and adjuvant therapeutic intervention

Substantial Histone Reduction Modulates Genomewide Nucleosomal Occupancy and Global Transcriptional Output

The basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. Nucleosome number in cells was considered fixed, but recently aging yeast and mammalian cells were shown to contain fewer nucleosomes. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker, and variant histones, and a correspondingly reduced number of nucleosomes, possibly because HMGB1 facilitates nucleosome assembly. Yeast nhp6 mutants lacking Nhp6a and -b proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and affects the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform and can be modelled assuming that different nucleosomal sites compete for available histones. Sites with a high propensity to occupation are almost always packaged into nucleosomes both in wild type and nucleosome-depleted cells; nucleosomes on sites with low propensity to occupation are disproportionately lost in nucleosome-depleted cells. We suggest that variation in nucleosome number, by affecting nucleosomal occupancy both genomewide and gene-specifically, constitutes a novel layer of epigenetic regulation

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Sustained Oscillations of NF-κB Produce Distinct Genome Scanning and Gene Expression Profiles

NF-κB is a prototypic stress-responsive transcription factor that acts within a complex regulatory network. The signaling dynamics of endogenous NF-κB in single cells remain poorly understood. To examine real time dynamics in living cells, we monitored NF-κB activities at multiple timescales using GFP-p65 knock-in mouse embryonic fibroblasts. Oscillations in NF-κB were sustained in most cells, with several cycles of transient nuclear translocation after TNF-α stimulation. Mathematical modeling suggests that NF-κB oscillations are selected over other non-oscillatory dynamics by fine-tuning the relative strengths of feedback loops like IκBα. The ability of NF-κB to scan and interact with the genome in vivo remained remarkably constant from early to late cycles, as observed by fluorescence recovery after photobleaching (FRAP). Perturbation of long-term NF-κB oscillations interfered with its short-term interaction with chromatin and balanced transcriptional output, as predicted by the mathematical model. We propose that negative feedback loops do not simply terminate signaling, but rather promote oscillations of NF-κB in the nucleus, and these oscillations are functionally advantageous

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Multilinguisme et variétés linguistiques en Europe à l’aune de l’intelligence artificielle Multilinguismo e variazioni linguistiche in Europa nell’era dell’intelligenza artificiale Multilingualism and Language Varieties in Europe in the Age of Artificial Intelligence

Il presente volume è il frutto di una riflessione interdisciplinare e multilingue maturata attorno a diversi eventi organizzati nell’ambito del panel concernente i diritti e le variazioni linguistiche in Europa nell’era dell’intelligenza artificiale all’interno del progetto Artificial Intelligence for European Integration, promosso dal Centro studi sull’Europa TO-EU dell’Università di Torino e cofinanziato dalla Commissione europea. L’interrogativo iniziale che abbiamo voluto sollevare è se l’IA potesse avere un impatto negativo sulle varietà linguistiche e sul multilinguismo, valore “aggiunto” dell’UE, o se potesse, e in che modo, divenire utile per la promozione di essi. Il volume, interamente inedito, può dirsi tra i primi ad affrontare, almeno in Europa, questo tipo di tematiche.This book is the outcome of an interdisciplinary multilingual reflection carried out on research into linguistic rights, multilingualism and language varieties in Europe in the age of artificial intelligence. It is part of the Artificial Intelligence for European Integration project, promoted by the Centre of European Studies To-EU of the University of Turin and co-financed by the European Commission. Our aim was to investigate more generally the negative and/or positive outcomes of AI on language varieties and multilingualism, the latter a key value for the EU. The result is a volume of original unpublished research being made generally available for the first time, at least in Europe.Ce livre a été élaboré à partir d’une réflexion interdisciplinaire et multilingue qui a été menée dans le cadre d’une recherche sur les droits, le multilinguisme et les variétés linguistiques en Europe à l’aune de l’intelligence artificielle à l’intérieur du projet Artificial Intelligence for European Integration promu par le Centre d’études européennes To-EU de l’Université de Turin et cofinancé par la Commission de l’Union européenne. Notre propos était de réfléchir plus généralement sur les conséquences négatives et/ou positives de l’IA sur les variétés linguistiques et le multilinguisme, ce dernier étant une valeur de l’UE. Ce que nous proposons par ce numéro est un livre inédit qui peut se vanter d’être parmi les premiers à s’occuper de ce type de thématique, du moins en Europe

NF-κB, the Importance of Being Dynamic: Role and Insights in Cancer

In this review, we aim at describing the results obtained in the past years on dynamics features defining NF-&kappa;B regulatory functions, as we believe that these developments might have a transformative effect on the way in which NF-&kappa;B involvement in cancer is studied. We will also describe technical aspects of the studies performed in this context, including the use of different cellular models, culture conditions, microscopy approaches and quantification of the imaging data, balancing their strengths and limitations and pointing out to common features and to some open questions. Our emphasis in the methodology will allow a critical overview of literature and will show how these cutting-edge approaches can contribute to shed light on the involvement of NF-&kappa;B deregulation in tumour onset and progression. We hypothesize that this &ldquo;dynamic point of view&rdquo; can be fruitfully applied to untangle the complex relationship between NF-&kappa;B and cancer and to find new targets to restrain cancer growth