Ubiquitination involving G3BP1 mediates strain granule disassembly within a contextspecific way

Overall, our data indicate that blocking hepatocyte division induces biological processes driving the onset of the disease phenotype. It suggests that the decrease in hepatocyte division observed in liver disease may not only be a consequence of fibrosis and inflammation, but also a pathological cue.Statistical learning and probabilistic prediction are fundamental processes in auditory cognition. A prominent computational model of these processes is Prediction by Partial Matching (PPM), a variable-order Markov model that learns by internalizing n-grams from training sequences. this website However, PPM has limitations as a cognitive model in particular, it has a perfect memory that weights all historic observations equally, which is inconsistent with memory capacity constraints and recency effects observed in human cognition. We address these limitations with PPM-Decay, a new variant of PPM that introduces a customizable memory decay kernel. In three studies-one with artificially generated sequences, one with chord sequences from Western music, and one with new behavioral data from an auditory pattern detection experiment-we show how this decay kernel improves the model's predictive performance for sequences whose underlying statistics change over time, and enables the model to capture effects of memory constraints on auditory pattern detection. The resulting model is available in our new open-source R package, ppm (https//github.com/pmcharrison/ppm).Interferon β (IFN-β) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previously shown that in mice, the TRIM33 protein restrains Ifnb1 transcription in activated myeloid cells through an upstream inhibitory sequence called ICE. Here, we show that the deregulation of Ifnb1 expression observed in murine Trim33-/- macrophages correlates with abnormal looping of both ICE and the Ifnb1 gene to a 100 kb downstream region overlapping the Ptplad2/Hacd4 gene. This region is a predicted myeloid super-enhancer in which we could characterize 3 myeloid-specific active enhancers, one of which (E5) increases the response of the Ifnb1 promoter to activation. In humans, the orthologous region contains several single nucleotide polymorphisms (SNPs) known to be associated with decreased expression of IFNB1 in activated monocytes, and loops to the IFNB1 gene. The strongest association is found for the rs12553564 SNP, located in the E5 orthologous region. The minor allele of rs12553564 disrupts a conserved C/EBP-β binding motif, prevents binding of C/EBP-β, and abolishes the activation-induced enhancer activity of E5. Altogether, these results establish a link between a genetic variant preventing binding of a transcription factor and a higher order phenotype, and suggest that the frequent minor allele (around 30% worldwide) might be associated with phenotypes regulated by IFN-β expression in myeloid cells.The pumping of blood through the heart is due to a wave of muscle contractions that are in turn due to a wave of electrical activity initiated at the sinoatrial node. At the cellular level, this wave of electrical activity corresponds to the sequential excitation of electrically coupled cardiac cells. Under some conditions, the normally-long action potentials of cardiac cells are extended even further by small oscillations called early afterdepolarizations (EADs) that can occur either during the plateau phase or repolarizing phase of the action potential. Hence, cellular EADs have been implicated as a driver of potentially lethal cardiac arrhythmias. One of the major determinants of cellular EAD production and repolarization failure is the size of the overlap region between Ca2+ channel activation and inactivation, called the window region. In this article, we interpret the role of the window region in terms of the fast-slow structure of a low-dimensional model for ventricular action potential generation. We demonstrate that the effects of manipulation of the size of the window region can be understood from the point of view of canard theory. We use canard theory to explain why enlarging the size of the window region elicits EADs and why shrinking the window region can eliminate them. We also use the canard mechanism to explain why some manipulations in the size of the window region have a stronger influence on cellular electrical behavior than others. This dynamical viewpoint gives predictive power that is beyond that of the biophysical explanation alone while also uncovering a common mechanism for phenomena observed in experiments on both atrial and ventricular cardiac cells.BACKGROUND This report is of a case of vocal cord ulceration following endotracheal intubation and mechanical ventilation in a patient with severe COVID-19 pneumonia. CASE REPORT A 57-year-old woman was admitted to our hospital (Ospedale Degli Infermi, Biella, Italy) presenting with symptoms of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Reverse transcription real-time polymerase chain reaction from a nasopharyngeal swab, authorized and validated by the World Health Organization, confirmed the diagnosis of SARS-CoV-2 infection. The patient presented with severe respiratory distress and underwent orotracheal intubation for mechanical ventilation. She was extubated after 9 days in the intensive care unit. After extubation, the patient experienced an onset of dysphonia, and was evaluated by the otolaryngologist. The videolaryngoscopy revealed the presence of an ulceration at the level of the left vocal cord. Steroids and proton pump inhibitors were administered as primary therapy for 1 week. Two weeks later, a significant improvement in the patient's voice quality was observed. A second videolaryngoscopy was performed, which displayed healing of the ulcer at the level of the left vocal fold and rapid re-epithelialization. CONCLUSIONS This report has shown that with increasing numbers of cases of severe COVID-19 pneumonia requiring endotracheal intubation and mechanical ventilation, clinical guidelines should be followed to ensure that the incidence of complications such as vocal cord ulceration are as low as possible.