Redundant or separate entities?—roles of Twist1 and Twist2 as molecular switches during gene transcription

Twist1 and Twist2 are highly conserved members of the Twist subfamily of bHLH proteins responsible for the transcriptional regulation of the developmental programs in mesenchymal cell lineages. The regulation of such processes requires that Twist1 and Twist2 function as molecular switches to activate and repress target genes by employing several direct and indirect mechanisms. Modes of action by these proteins include direct DNA binding to conserved E-box sequences and recruitment of coactivators or repressors, sequestration of E-protein modulators, and interruption of proper activator/repressor function through protein–protein interactions. Regulatory outcomes of Twist1 and Twist2 are themselves controlled by spatial-temporal expression, phosphoregulation, dimer choice and cellular localization. Although these two proteins are highly conserved and exhibit similar functions in vitro, emerging literature have demonstrated different roles in vivo. The involvement of Twist1 and Twist2 in a broad spectrum of regulatory pathways highlights the importance of understanding their roles in normal development, homeostasis and disease. Here we focus on the mechanistic models of transcriptional regulation and summarize the similarities and differences between Twist1 and Twist2 in the context of myogenesis, osteogenesis, immune system development and cancer

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Runoff Water Management on Karstic Terrain and Stability of Slopes and Foundations in Northern Spain

Publisher Copyright: © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.This communication analyzes the latest experiences in slope and foundation drainage and runoff water management to improve resilience in roadway infrastructures. The actions resulted from temporary rain and adverse weather conditions during the months of January and February 2012 and 2013, which caused singular damage to several road slopes in Northern Spain. The objective of the repair was to restore road safety and road stability. Regarding runoff water, heavy rains cause loose and scattered stone movements along the slopes of the La Hermida Gorge and in the limestone rocky massifs that make up the Gorge. There are also many karst caves exiting that load their levels to the fullest and produce impressive waterfalls on the road. The energy of these waterfalls was dissipated, and the water curtain was channeled into the Deva River through an innovative solution. With regard to the drainage of slopes and foundations, the action carried out on the slope of the A-8 motorway includes its stabilization by biological engineering. All the actions presented in this article have proven to be valid throughout the last year of road operation. Furthermore, the monitoring system used in full-scale tests for dynamic barriers according to ETAG-27 is reliable to better understand the force transmission mechanism and also for future design purposes.Peer reviewe