A5035569855- Congenital heart defects research
- Photoreceptor and optogenetics research
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Neuroscience and Neural Engineering
- Neural dynamics and brain function
- Congenital Heart Disease Studies
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Multilevel Inverters and Converters
- Muscle Physiology and Disorders
- Cardiovascular Function and Risk Factors
- Cardiac electrophysiology and arrhythmias
- Photosynthetic Processes and Mechanisms
- MicroRNA in disease regulation
- Renal cell carcinoma treatment
- Spectroscopy and Quantum Chemical Studies
- Cancer Immunotherapy and Biomarkers
- Cardiovascular Effects of Exercise
- EEG and Brain-Computer Interfaces
- RNA modifications and cancer
- Cancer-related gene regulation
- Signaling Pathways in Disease
- Cancer, Lipids, and Metabolism
- Genomics and Chromatin Dynamics
Università degli Studi di Enna Kore
2024-2025
University of Padua
2013-2024
Neuroscience Institute
2015-2020
National Research Council
2002-2018
Italian Resuscitation Council
2018
University of Hohenheim
2017
Sapienza University of Rome
2008
Istituto Neurologico Mediterraneo
2008
Imperial College London
2008
University of Michigan
2008
Several members of the sarcomeric myosin heavy chain (MHC) gene family have been mapped in human genome but many them not yet identified. In this study we report identification two skeletal MHC genes as fast IIa and IIx based on pattern expression sequence homology with corresponding rat 3'-translated untranslated regions. The distribution these products well that beta/slow was analyzed muscles by situ hybridization. beta/slow, IIa, transcripts defines three major muscle fiber types...
During heart development, chamber myocardium forms locally from the embryonic of tubular heart. The atrial natriuretic factor ( ANF ) gene is specifically expressed in this developing and one first hallmarks formation. We investigated regulatory mechanism underlying selective expression. Transgenic analysis shows that a small fragment responsible for developmental pattern endogenous Furthermore, able to repress cardiac troponin I cTnI promoter activity selectively atrioventricular canal...
ABSTRACT Left-right asymmetry in vertebrates is controlled by activities emanating from the left lateral plate. How these signals get transmitted to forming organs not known. A candidate mediator mouse, frog and zebrafish embryos homeobox gene Pitx2. It asymmetrically expressed plate mesoderm, tubular heart early gut tube. Localized Pitx2 expression continues when undergo asymmetric looping morphogenesis. Ectopic of Xnr1 right induces transcription Xenopus. Misexpression affects situs...
Specific regions of the embryonic heart tube differentiate into atrial and ventricular chamber myocardium, whereas inflow tract, atrioventricular canal, inner curvatures, outflow tract do not. These express Tbx2, a transcriptional repressor. Here, we tested its role in formation. The temporal spatial pattern Tbx2 mRNA protein expression mouse hearts was found to be complementary that myocardium-specific genes Nppa, Cx40, Cx43, Chisel, conserved human. In vitro, repressed activity regulatory...
Individuals with 22q11 deletion syndrome (22q11DS; DiGeorge/velo-cardio-facial syndrome) have multiple congenital malformations, including cardiovascular defects. Most individuals this possess 1.5-3.0 Mb hemizygous 22q11.2 deletions. The T-box transcription factor TBX1, lies within the nested 1.5 interval and is a strong candidate for its etiology. Inactivation of Tbx1 in mouse results neonatal lethality owing to presence single cardiac outflow tract. One important goal understand molecular...
Extrasystoles lead to several consequences, ranging from uneventful palpitations lethal ventricular arrhythmias, in the presence of pathologies, such as myocardial ischemia. The role working versus conducting cardiomyocytes, well tissue requirements (minimal cell number) for generation extrasystoles, and properties leading ectopies become arrhythmia triggers (topology), normal diseased heart, have not been determined directly vivo. Here, we used optogenetics transgenic mice expressing...
Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery intracellular Ca2+ cycling. Experimental methods for manipulating AP electrical dynamics commonly use inhibitors that lack spatial temporal specificity. In this work, we propose an approach based on optogenetics to manipulate cardiac activity employing a light-modulated depolarizing current with intensities too low elicit APs (sub-threshold illumination), but...
A novel fast‐twitch motor unit type, called the IIX‐myosin heavy chain (MHC) unit, identified by glycogen depletion technique together with a series of monoclonal antibodies (mAbs) specific for MHCs, has been isolated recently in rat tibialis anterior muscle. In young animals, this physiological, biochemical and morphometrical properties which separate it from IIA‐ IIB‐MHC units. old age, on other hand, IIX‐MHC units display resembling Based these results was proposed that transition IIB to...
The Pitx2 gene regulates left-right (L/R) asymmetrical cardiac morphogenesis. Constitutive knock out (ko) mice die before birth and display, among other defects, right atrial isomerism, ventricular septal double outlet ventricle. myocardial role of the has not been dissected. In particular, how differential L/R identity program is clear. Additionally, relation between ko defects expression pattern understood. this article we analyze function during mouse heart development. By in situ...
The sinus venous myocardium, comprising the sinoatrial node (SAN) and horns (SH), is a region subject to congenital malformations cardiac arrhythmias. It differentiates from symmetric bilateral mesenchymal precursors, but morphological, molecular, functional left/right differences are progressively established through development. role of laterality gene Pitx2 in this process unknown. We aimed elucidate molecular events driving patterning venosus (SV) myocardium by using myocardial knockout...
During heart development, 2 fast-conducting regions of working myocardium balloon out from the slow-conducting primary tubular heart. Three persist: outflow tract, atrioventricular canal, and inflow which are contiguous throughout inner curvature The contribution tract to definitive atrial chambers has remained enigmatic largely because lack molecular markers that permit unambiguous identification this myocardial domain. We now report genes encoding natriuretic factor, myosin light chain...
We examined the myosin heavy-chain (MHC), troponin T (TnT), and I (TnI) isoform composition in rat soleus muscle after 21 days of hindlimb suspension using electrophoretic immunoblotting analysis with specific monoclonal antibodies. The suspended showed a shift MHC distribution marked increase (from 1.0 to 33%) relative amount type IIa IIx corresponding decrease MHC. However, IIb MHC, which represents major component fast-twitch muscles, was not detected muscles. TnT TnI also changed...
Total anomalous pulmonary venous return (TAPVR) is a congenital heart defect in which the veins fail to enter left atrium and drain instead into right or one of its tributaries. Although genetic basis for TAPVR has long been recognized, no single gene involved pathogenesis this disease identified date. We previously reported patient bearing de novo 10;21 balanced translocation. In work, we cloned both translocation breakpoints from mapped ANKRD1 gene, encoding cardiac transcriptional...
Although optogenetics has clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies lack capability to react acutely ongoing wave dynamics. Here, we developed an all-optical platform monitor and control electrical activity in real-time. The methodology was applied restore normal after atrioventricular block manipulate intraventricular propagation wavefront. closed-loop approach also simulate a re-entrant circuit across ventricle. development this...
Background The prognostic value of the Geriatric 8 (G8) screening score in metastatic renal cell carcinoma (mRCC) patients receiving first-line immunotherapy remains unclear. This study aimed to evaluate role G8 within context Meet-URO classification mRCC treated with ipilimumab-nivolumab. Methods retrospective multicentre analysed 106 and scores were calculated before treatment initiation. Primary endpoint was overall survival (OS), defined as duration from first administration Nivolumab...
The 22q11 deletion syndrome (22q11DS) is characterized by abnormal development of the pharyngeal apparatus. Mouse genetic studies have identified Tbx1 as a key gene in etiology syndrome, part, via interaction with fibroblast growth factor (Fgf) genes. Three murine Fgfs, Fgf3, Fgf8 and Fgf10 are coexpressed different combinations Tbx1. They all strongly downregulated Tbx1-/- embryos, implicating epistatic interactions. Supporting this, been shown to genetically interact fourth arch artery...
The gene coding for mouse cardiac troponin I (TnI) has been cloned and sequenced. TnI contains 8 exons an exon-intron organization similar to the quail fast skeletal except region of 1-3, which is highly divergent. Comparative analysis suggests that exon 1 corresponds 2 3, codes most cardiac-specific amino-terminal extension no counterpart in gene, evolved by insertion/deletion. amino acid sequence 4 shows limited homology (36% identity) with but remarkably (79% corresponding slow TnI,...
Goosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, role of Gsc has remained enigmatic. Using conditional gain-of-function approaches Xenopus mouse to maintain along axial midline, neural tube closure defects (NTDs) arose dorsal extension was compromised. Both phenotypes represent convergent (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling. Dvl2 recruitment...
Introduction: Mechanisms underlying cardiac arrhythmias are typically driven by abnormalities in conduction and/or heterogeneities repolarization time (RT) across the heart. While slowing can be caused either electrophysiological defects or physical blockade tissue, RT mainly related to action potential (AP) prolongation abbreviation specific areas of Importantly, size area with altered and difference between short long (RT gradient) have been identified as critical determinators...
The homeobox gene <i>goosecoid</i> has been implicated to play a central role in the Spemann organizer tissue of vertebrate embryo. Misexpression on ventral side <i>Xenopus laevis</i> gastrula embryo was shown result partial duplication primary body axis, reminiscent graft. Normal embryonic development thus requires tight temporal and spatial control genes instrumental for function. In present study we investigated transcriptional expression. Sequence analysis mouse human promoter region...