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Sleep debt accumulates during wakefulness, leading to increased slow wave activity (SWA) during sleep, an encephalographic marker for sleep need. The use-dependent demands of prior wakefulness increase sleep SWA locally. However, the circuitry and molecular identity of this "local sleep" remain unclear. Using pharmacology and optogenetic perturbations together with transcriptomics, we find that cortical brain-derived neurotrophic factor (BDNF) regulates SWA via the activation of tyrosine kinase B (TrkB) receptor and cAMP-response element-binding protein (CREB). We map BDNF/TrkB-induced sleep SWA to layer 5 (L5) pyramidal neurons of the cortex, independent of neuronal firing per se. Using mathematical modeling, we here propose a model of how BDNF's effects on synaptic strength can increase SWA in ways not achieved through increased firing alone. Proteomic analysis further reveals that TrkB activation enriches ubiquitin and proteasome subunits. Together, our study reveals that local SWA control is mediated by BDNF-TrkB-CREB signaling in L5 excitatory cortical neurons., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This in vitro study aimed to assess the impact of incorporating calcium glycerophosphate (CaGP) and sodium fluoride (NaF) in addition to 35% hydrogen peroxide concerning the enamel mechanical and morphological properties., Methods: Specimens of bovine enamel were chosen based on their initial surface hardness (SHi) and subsequently divided into five gel groups (n=12): 1) 35% Hydrogen Peroxide (HP) Gel; 2) HP + 0.1% NaF Gel (HP/NaF); 3) HP + 0.25% CaGP Gel (HP/CaGP); 4) HP + 0.1% NaF + 0.25% CaGP Gel (HP/NaF/CaGP) and 5) HP Blue 35% Gel (HP Blue). The bleaching gels were applied thrice, for 40 min, at intervals of 7 days each. After 21 days, the final surface hardness (SHf), integrated hardness (IH), Polydispersity Index (PdI) and Zeta Potential (Zp), surface roughness (Ra, after and before), and surface/structural analysis by Scanning Electron Microscopy (SEM) were determined. The data were submitted to ANOVA (one-way and two-way) followed by the Student-Newman-Keuls test (α=0.05)., Results: The addition of NaF to HP reduced demineralization by 11.5% in relation to HP (p<0.05). The NaF/CaGP association reduction is 22.8 and 20% higher in comparison to HP/NaF/CaGP and HP Blue, respectively. The IH when the PH/NaF/CaGP bleaching gel was applied, was 14% higher compared to HP and HP Blue groups., Conclusions: It can be concluded that the association of NaF and CaGP with the 35% hydrogen peroxide gel (HP/NaF/CaGP) significantly changed tooth enamel demineralization in terms of surface, depth, roughness, and enamel morphology., (©Operative Dentistry, 2024.)

Percutaneous closure of the left atrial appendage may be indicated in patients with contraindications to anticoagulation therapy, for example, after recurrent gastrointestinal bleeding. It is an effective and safe procedure but is not without complications. We present a patient who presented with severe aortic insufficiency due to migration of the left atrial appendage closure device, which required urgent cardiac surgery for its removal., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Covalent DNA-protein cross-links (DPCs) are toxic DNA lesions that block replication and require repair by multiple pathways. Whether transcription blockage contributes to the toxicity of DPCs and how cells respond when RNA polymerases stall at DPCs is unknown. Here we find that DPC formation arrests transcription and induces ubiquitylation and degradation of RNA polymerase II. Using genetic screens and a method for the genome-wide mapping of DNA-protein adducts, DPC sequencing, we discover that Cockayne syndrome (CS) proteins CSB and CSA provide resistance to DPC-inducing agents by promoting DPC repair in actively transcribed genes. Consequently, CSB- or CSA-deficient cells fail to efficiently restart transcription after induction of DPCs. In contrast, nucleotide excision repair factors that act downstream of CSB and CSA at ultraviolet light-induced DNA lesions are dispensable. Our study describes a transcription-coupled DPC repair pathway and suggests that defects in this pathway may contribute to the unique neurological features of CS., (© 2024. The Author(s).)

Introduction and Purpose: Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data., Methods: Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained., Results: H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease., Conclusions: The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.