Nucleotide Loading Modes of Human RNA Polymerase II as Deciphered by Molecular Simulations.

Mapping the route of nucleoside triphosphate (NTP) entry into the sequestered active site of RNA polymerase (RNAP) has major implications for elucidating the complete nucleotide addition cycle. Constituting a dichotomy that remains to be resolved, two alternatives, direct NTP delivery via the secondary channel (CH2) or selection to downstream sites in the main channel (CH1) prior to catalysis, have been proposed. In this study, accelerated molecular dynamics simulations of freely diffusing NTPs about RNAPII were applied to refine the CH2 model and uncover atomic details on the CH1 model that previously lacked a persuasive structural framework to illustrate its mechanism of action. Diffusion and binding of NTPs to downstream DNA, and the transfer of a preselected NTP to the active site, are simulated for the first time. All-atom simulations further support that CH1 loading is transcription factor IIF (TFIIF) dependent and impacts catalytic isomerization. Altogether, the alternative nucleotide loading systems may allow distinct transcriptional landscapes to be expressed.

[Prevalence of pain in radiotherapy and improvement of its management]. / Prévalence de la douleur en radiothérapie et amélioration de sa prise en charge.

PURPOSE: To assess pain prevalence, its features and its management in a radiotherapy department of a French public general hospital. To highlight strategies to improve pain screening and treatment. METHODS: Designed in conjunction with pain management specialists, a cross-sectional study on pain was carried out. All patients treated in the department being interviewed with a standardised questionnaire during 2 days. RESULTS: Among 91 patients, 63.7% reported pain in daily life. They respectively represented 100%, 85.7% and 83.3% all of the patients treated for brain tumours, for bone metastasis and for head and neck cancers. Only 7.7% of patients reported pain during radiotherapy sessions. Among patients reporting pain, 70.7% received pain relief treatment and 60.8% of them thought this was adequate. While 51.6% of patients knew there was a specialist pain unit in the hospital, only 5.5% were offered a consultation with it. This unit provides non-pharmacological pain management techniques. CONCLUSIONS: This study confirms the importance, the underestimation and undertreatment, of pain management in radiotherapy departments. We recommend using a standardised questionnaire to identify patients at highest risk of pain, and the use of specialised pain relief teams when needed. A radiation therapist could act as a referrer to the pain relief team. Pain management remains teamwork, with links to specialised units.