Transcription-replication conflicts: How they occur and how they are resolved

The frequent occurrence of transcription and DNA replication in cells results in many encounters, and thus conflicts, between the transcription and replication machineries. These conflicts constitute a major intrinsic source of genome instability, which is a hallmark of cancer cells. How the replication machinery progresses along a DNA molecule occupied by an RNA polymerase is an old question. Here we review recent data on the biological relevance of transcription-replication conflicts, and the factors and mechanisms that are involved in either preventing or resolving them, mainly in eukaryotes. On the basis of these data, we provide our current view of how transcription can generate obstacles to replication, including torsional stress and non-B DNA structures, and of the different cellular processes that have evolved to solve them

Acoustic resonance tracking in sol gel materials

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Strong and fragile plastic crystals

A pattern of behavior for the structure relaxation time of molecular and ionic liquids, which becomes clear when data at different temperatures are scaled by the glass transition, is reviewed. A similar pattern is then shown, within the limitations of available data, to apply to plastic crystals "Strong plastic crystals are characterized by a temperature-resistant medium-range order which is manifested by a small change in heat capacity at Tg, a single (or narrow distribution of) relaxation time(s) and Arrhenius (or nearly Arrhenius) dependence of the relaxation time on temperature over some fifteen orders of magnitude. For "fragile" plastic crystals whose structures degrade rapidly with temperature, ΔCp at Tg is relatively large, and the relaxation time characteristics are more complex. In the latter, and in intermediate cases, the very long time scale behavior of the orientationally equilibrated heat capacity which ultimately must resolve the Simon-Kauzmann entropy crisis, remains a fundamental problem

Kinetic study of silica gels by a new rheological ultrasonic investigation

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The lncRNA 'UCA1' modulates the response to chemotherapy of ovarian cancer through direct binding to miR-27a-5p and control of UBE2N levels.

International audienceOvarian cancer (OC) is the leading cause of death in patients with gynecologic cancers. Due to late diagnosis and resistance to chemotherapy, the 5-year survival rate in patients with OC is below 40%. We observed that UCA1, a lncRNA previously reported to play an oncogenic role in several malignancies, is overexpressed in the chemoresistant OC cell line OAW42-R compared to their chemotherapy-sensitive counterpart OAW42. Additionally, UCA1 overexpression was related to poor prognosis in two independent patient cohorts. Currently, the molecular mechanisms through which UCA1 acts in OC are poorly understood. We demonstrated that downregulation of the short isoform of UCA1 sensitized OC cells to cisplatin and that UCA1 acted as competing endogenous RNA to miR-27a-5p. Upon UCA1 downregulation, miR-27a-5p downregulated its direct target UBE2N leading to the upregulation of BIM, a proapoptotic protein of the Bcl2 family. The upregulation of BIM is the event responsible for the sensitization of OC cells to cisplatin. In order to model response to therapy in patients with OC, we used several patient-derived organoid cultures, a model faithfully mimicking patient’s response to therapy. Inhibition of UBE2N sensitized patient-derived organoids to platinum salts. In conclusion, response to treatment in patients with OC is regulated by the UCA1/miR-27a-5p/UBE2N axis, where UBE2N inhibition could potentially represent a novel therapeutic strategy to counter chemoresistance in OC

Isochoric thermal conductivity of solid furan

Thermal conductivity of solid furan has been measured at isochoric conditions in the high-temperature orien-tationally-disordered phase I for samples of different densities. Our isochoric data show a gradual increase of ΛV with temperature whereas isobaric thermal conductivity goes down in this temperature range. The above effect is most clearly expressed in furan, where the atoms in the ring plane are not equivalent, as compared with earlier studied C₆H₆ and C₆H₁₂. The increase of ΛV with temperature can be attributed to weakening of the translation-al-orientational interaction which, in turn, leads to a decrease of phonon scattering on rotational excitations. The experimental data are described in terms of a modified Debye model of thermal conductivity with allowance for heat transfer by both low-frequency phonons and ―diffuse‖ modes