The cardiac torsion as a sensitive index of heart pathology: A model study.

The torsional behaviour of the heart (i.e. the mutual rotation of the cardiac base and apex) was proved to be sensitive to alterations of some cardiovascular parameters, i.e. preload, afterload and contractility. Moreover, pathologies which affect the fibers architecture and cardiac geometry were proved to alter the cardiac torsion pattern. For these reasons, cardiac torsion represents a sensitive index of ventricular performance. The aim of this work is to provide further insight into physiological and pathological alterations of the cardiac torsion by means of computational analyses, combining a structural model of the two ventricles with simple lumped parameter models of both the systemic and the pulmonary circulations. Starting from diagnostic images, a 3D anatomy based geometry of the two ventricles was reconstructed. The myocytes orientation in the ventricles was assigned according to literature data and the myocardium was modelled as an anisotropic hyperelastic material. Both the active and the passive phases of the cardiac cycle were modelled, and different clinical conditions were simulated. The results in terms of alterations of the cardiac torsion in the presence of pathologies are in agreement with experimental literature data. The use of a computational approach allowed the investigation of the stresses and strains in the ventricular wall as well as of the global hemodynamic parameters in the presence of the considered pathologies. Furthermore, the model outcomes highlight how for specific pathological conditions, an altered torsional pattern of the ventricles can be present, encouraging the use of the ventricular torsion in the clinical practice.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jmbbm.2015.10.00

Characterization of the Tomato ARF Gene Family Uncovers a Multi-Levels Post-Transcriptional Regulation Including Alternative Splicing

Background: The phytohormone auxin is involved in a wide range of developmental processes and auxin signaling is known to modulate the expression of target genes via two types of transcriptional regulators, namely, Aux/IAA and Auxin Response Factors (ARF). ARFs play a major role in transcriptional activation or repression through direct binding to the promoter of auxin-responsive genes. The present study aims at gaining better insight on distinctive structural and functional features among ARF proteins. Results: Building on the most updated tomato (Solanum lycopersicon) reference genome sequence, a comprehensive set of ARF genes was identified, extending the total number of family members to 22. Upon correction of structural annotation inconsistencies, renaming the tomato ARF family members provided a consensus nomenclature for all ARF genes across plant species. In silico search predicted the presence of putative target site for small interfering RNAs within twelve Sl-ARFs while sequence analysis of the 59-leader sequences revealed the presence of potential small uORF regulatory elements. Functional characterization carried out by transactivation assay partitioned tomato ARFs into repressors and activators of auxin-dependent gene transcription. Expression studies identified tomato ARFs potentially involved in the fruit set process. Genome-wide expression profiling using RNA-seq revealed that at least one third of the gene family members display alternative splicing mode of regulation during the flower to fruit transition. Moreover, the regulation of several tomato ARF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signaling pathways of these two hormones. Conclusion: All together, the data bring new insight on the complexity of the expression control of Sl-ARF genes at the transcriptional and post-transcriptional levels supporting the hypothesis that these transcriptional mediators might represent one of the main components that enable auxin to regulate a wide range of physiological processes in a highly specific and coordinated manner