Real time dynamics and confinement in the Znschwinger-weyl lattice model for 1+1 QED

We study the out-of-equilibrium properties of 1 + 1 dimensional quantum electrodynamics (QED), discretized via the staggered-fermion Schwinger model with an Abelian Zngauge group. We look at two relevant phenomena: first, we analyze the stability of the Dirac vacuum with respect to particle/antiparticle pair production, both spontaneous and induced by an external electric field; then, we examine the string breaking mechanism. We observe a strong effect of confinement, which acts by suppressing both spontaneous pair production and string breaking into quark/antiquark pairs, indicating that the system dynamics displays a number of out-of-equilibrium features

Heregulin β1 induces the down regulation and the ubiquitin-proteasome degradation pathway of p185HER2 oncoprotein

AbstractAnalysis of the fate of the p185HER2 oncoprotein following activation by heregulin β1 revealed the induction of the tyrosine-phosphorylation, down-modulation, and polyubiquitination of p185HER2. Receptor ubiquitination was suppressed in cells treated with heregulin β1 in the presence of sodium azide, an inhibitor of ATP-dependent reactions, or genistein, a tyrosine kinase protein inhibitor, indicating the requirement for kinase activity and ATP in p185HER2 polyubiquitination. Ubiquitinated p185HER2 was degradated by the 26S proteasome proteolytic pathway. Kinetics and inhibition experiments indicated that endocytosis of the receptor occurs downstream of the initiation of the degradation process

Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy

The authors used 1H-MRS to investigate hypothalamic metabolism in 26 patients with cluster headache (CH) and 12 healthy subjects. Hypothalamic N-acetylaspartate/creatine was reduced in patients with CH vs controls (p < 0.01). Dividing the patients into episodic CH outside- and in-cluster periods and chronic CH, the hypothalamic N-acetylaspartate/creatine in all three subgroups of patients was reduced. The reduction of the neuronal marker N-acetylaspartate is consistent with hypothalamic neuronal dysfunction in patients with CH

Il CNR e i risultati della ricerca scientifica Progetti PRIN e FIRB 2007-2013

Il presente volume ha lo scopo di illustrare l'attività della rete scientifica del Consiglio Nazionale delle Ricerche (CNR) nell'ambito delle progettualità PRIN (Progetti di Ricerca di Interesse Nazionale) e FIRB (Fondo per gli Investimenti della Ricerca di Base) promosse dal Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR)

Il CNR e i risultati della ricerca scientifica_ Progetti PON 2007-2013

Il libro in oggetto raccoglie, sintetizza e presenta i risultati delle attività conseguiti dalla rete scientifica del CNR nell’ambito del Programma Operativo Nazionale “Ricerca e Competitività (PON R&C). Tale programma rappresenta lo strumento attraverso il quale il nostro Paese concorre allo sviluppo della Politica di Coesione della Unione europea a favore delle proprie aree territoriali più svantaggiate. Nel presente volume, si descrivono le caratteristiche generali del PON R&C 2007-2013 e le specifiche tecniche dei cinque bandi emanati dal MIUR: PON Ricerca Industriale (D.D. 1/Ric. del 18/01/2010); PON Distretti ad alta tecnologia e Laboratori pubblico-privati (D.D. 713/Ric. del 29/10/2010); PON Potenziamento Strutturale (D.D. 254/Ric. del 18/05/2011); PON Smart Cities and Communities and Social Innovation (D.D. 84/Ric. del 02/03/2012); PON Cluster Tecnologici Nazionali (D.D. 257/Ric. del 30/05/2012)

Targeting the Interaction between the SH3 Domain of Grb2 and Gab2

Gab2 is a scaffolding protein, overexpressed in many types of cancers, that plays a key role in the formation of signaling complexes involved in cellular proliferation, migration, and differentiation. The interaction between Gab2 and the C-terminal SH3 domain of the protein Grb2 is crucial for the activation of the proliferation-signaling pathway Ras/Erk, thus representing a potential pharmacological target. In this study, we identified, by virtual screening, seven potential inhibitor molecules that were experimentally tested through kinetic and equilibrium binding experiments. One compound showed a remarkable effect in lowering the affinity of the C-SH3 domain for Gab2. This inhibitory effect was subsequently validated in cellula by using lung cancer cell lines A549 and H1299. Our results are discussed under the light of previous works on the C-SH3:Gab2 interaction

Symmetry-protected topological phases in lattice gauge theories: Topological QED2

The interplay of symmetry, topology, and many-body effects in the classification of phases of matter poses a formidable challenge in condensed-matter physics. Such many-body effects are typically induced by inter- particle interactions involving an action at a distance, such as the Coulomb interaction between electrons in a symmetry-protected topological (SPT) phase. In this work we show that similar phenomena also occur in certain relativistic theories with interactions mediated by gauge bosons, and constrained by gauge symmetry. In particular, we introduce a variant of the Schwinger model or quantum electrodynamics (QED) in 1+1 dimensions on an interval, which displays dynamical edge states localized on the boundary. We show that the system hosts SPT phases with a dynamical contribution to the vacuum θ-angle from edge states, leading to a new type of topological QED in 1+1 dimensions. The resulting system displays an SPT phase which can be viewed as a correlated version of the Su-Schrieffer-Heeger topological insulator for polyacetylene due to non-zero gauge couplings. We use bosonization and density-matrix renormalization group techniques to reveal the detailed phase diagram, which can further be explored in experiments of ultra-cold atoms in optical lattices

Histone Acetylation Defects in Brain Precursor Cells: A Potential Pathogenic Mechanism Causing Proliferation and Differentiation Dysfunctions in Mitochondrial Aspartate-Glutamate Carrier Isoform 1 Deficiency

Mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) deficiency is an ultra-rare genetic disease characterized by global hypomyelination and brain atrophy, caused by mutations in the SLC25A12 gene leading to a reduction in AGC1 activity. In both neuronal precursor cells and oligodendrocytes precursor cells (NPCs and OPCs), the AGC1 determines reduced proliferation with an accelerated differentiation of OPCs, both associated with gene expression dysregulation. Epigenetic regulation of gene expression through histone acetylation plays a crucial role in the proliferation/differentiation of both NPCs and OPCs and is modulated by mitochondrial metabolism. In AGC1 deficiency models, both OPCs and NPCs show an altered expression of transcription factors involved in the proliferation/differentiation of brain precursor cells (BPCs) as well as a reduction in histone acetylation with a parallel alteration in the expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, histone acetylation dysfunctions have been dissected in in vitro models of AGC1 deficiency OPCs (Oli-Neu cells) and NPCs (neurospheres), in physiological conditions and following pharmacological treatments. The inhibition of HATs by curcumin arrests the proliferation of OPCs leading to their differentiation, while the inhibition of HDACs by suberanilohydroxamic acid (SAHA) has only a limited effect on proliferation, but it significantly stimulates the differentiation of OPCs. In NPCs, both treatments determine an alteration in the commitment toward glial cells. These data contribute to clarifying the molecular and epigenetic mechanisms regulating the proliferation/differentiation of OPCs and NPCs. This will help to identify potential targets for new therapeutic approaches that are able to increase the OPCs pool and to sustain their differentiation toward oligodendrocytes and to myelination/remyelination processes in AGC1 deficiency, as well as in other white matter neuropathologies

The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism

Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism

Il CNR e i risultati della ricerca scientifica_ Le nuove procedure di controllo interno Attività di AUDIT Progetti PRIN e FIRB

Nel presente volume sono evidenziate le procedure relative alla nuova disciplina dei controlli interni a valere sulle spese di progetto. Tale disciplina, dettata dal MIUR, ha fornito lo spunto per l’implementazione e la sperimentazione di un coordinamento interno CNR volto alla certificazione delle spese effettuate dalla Rete Scientifica