From the Sakai-Sugimoto Model to the Generalized Skyrme Model

We derive the generalized Skyrme model as a low-energy effective model of the Sakai-Sugimoto model. The novelty with the past is the presence of the sextic term equal to the topological charge squared. This term appears when the $\omega$ meson, and the tower of states on top of it, are integrated out. We claim that, in the small 't Hooft coupling limit, the instanton is well described by a Skyrmion arising from the low energy effective Lagrangian of the Sakai-Sugimoto model. The sextic term plays a dominant role in this limit. Moreover, when a pion mass term is added we recover the BPS Skyrme model in the small 't Hooft coupling limit.Comment: 17 pages, 6 figures. v2: minor correction

Neutron electric dipole moment from gauge/string duality

We compute the electric dipole moment of nucleons in the large $N_c$ QCD model by Witten, Sakai and Sugimoto with $N_f=2$ degenerate massive flavors. Baryons in the model are instantonic solitons of an effective five-dimensional action describing the whole tower of mesonic fields. We find that the dipole electromagnetic form factor of the nucleons, induced by a finite topological $\theta$ angle, exhibits complete vector meson dominance. We are able to evaluate the contribution of each vector meson to the final result - a small number of modes are relevant to obtain an accurate estimate. Extrapolating the model parameters to real QCD data, the neutron electric dipole moment is evaluated to be $d_n = 1.8 \cdot 10^{-16}\, \theta\;e\cdot \mathrm{cm}$. The electric dipole moment of the proton is exactly the opposite.Comment: Latex, 4 pages; v2: minor corrections, few comments adde

Bouganin, an attractive weapon for immunotoxins

Bougainvillea (Bougainvillea spectabilis Willd.) is a plant widely used in folk medicine and many extracts from different tissues of this plant have been employed against several pathologies. The observation that leaf extracts of Bougainvillea possess antiviral properties led to the purification and characterization of a protein, named bouganin, which exhibits typical characteristics of type 1 ribosome-inactivating proteins (RIPs). Beyond that, bouganin has some peculiarities, such as a higher activity on DNA with respect to ribosomal RNA, low systemic toxicity, and immunological properties quite different than other RIPs. The sequencing of bouganin and the knowledge of its three-dimensional structure allowed to obtain a not immunogenic mutant of bouganin. These features make bouganin a very attractive tool as a component of immunotoxins (ITs), chimeric proteins obtained by linking a toxin to a carrier molecule. Bouganin-containing ITs showed very promising results in the experimental treatment of both hematological and solid tumors, and one bouganin-containing IT has entered Phase I clinical trial. In this review, we summarize the milestones of the research on bouganin such as bouganin chemico-physical characteristics, the structural properties and de-immunization studies. In addition, the in vitro and in vivo results obtained with bouganin-containing ITs are summarized

Navigating the Chemical Space of Multitarget-Directed Ligands:From Hybrids to Fragments in Alzheimer's Disease

Multitarget drug discovery is one of the hottest topics and most active fields in the search for new molecules against Alzheimer’s disease (AD). Over the last 20 years, many promising multitarget-directed ligands (MTDLs) have been identified and developed at a pre-clinical level. However, how to design them in a rational way remains the most fundamental challenge of medicinal chemists. This is related to the foundational question of achieving an optimized activity towards multiple targets of interest, while preserving drug-like properties. In this respect, large hybrid molecules and small fragments are poles apart. In this review article, our aim is to appraise what we have accomplished in the development of both hybrid- and fragment-like molecules directed to diverse AD targets (i.e., acetylcholinesterase, NMDA receptors, metal chelation, BACE-1 and GSK-3β). In addition, we attempt to highlight what are the persistent needs that deserve to be improved and cared for, with the ultimate goal of moving an MTDL to AD clinical studies

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

Ribosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from Adenia heterophylla caudex, which has been named heterophyllin. Heterophyllin shows the enzymatic and lectin properties of type 2 RIPs. Interestingly, in immunoreactivity experiments, heterophyllin poorly cross-reacts with sera against all other tested RIPs. The cytotoxic effects and death pathways triggered by heterophyllin were investigated in three human-derived cell lines: NB100, T24, and MCF7, and compared to ricin, the most known and studied type 2 RIP. Heterophyllin was able to completely abolish cell viability at nM concentration. A strong induction of apoptosis, but not necrosis, and the involvement of oxidative stress and necroptosis were observed in all the tested cell lines. Therefore, the enzymatic, immunological, and biological activities of heterophyllin make it an interesting molecule, worthy of further in-depth analysis to verify its possible pharmacological application

Higgs at LHC

An overview of recent theoretical results on the Higgs boson and its discovery strategy at ATLAS and CMS will be presented, focusing on the main Higgs analysis effective with low integrated luminosity (less than 30 fb^-1).Comment: 10 pages, 9 figures, talk given at: V Workshop Italiano sulla fisica p-p ad LHC, Perugia, Italy, 30 Jan. - 2 Feb. 200

Xanthine Oxidoreductase In Atherosclerosis Pathogenesis: Not Only Oxidative Stress.

Endothelial xanthine oxidoreductase (XOR) together with NAD(P)H oxidase and nitric oxide (NO) synthase plays a physiologic role in inflammatory signalling, the regulation of NO production and vascular function. The oxidative stress generated by these enzymes may induce endothelial dysfunction, leading to atherosclerosis, cardiovascular diseases and metabolic syndrome. XOR activity creates both oxidant and anti-oxidant products that are implicated in the development of hypertension, smoking vascular injury, dyslipidemia and diabetes, which are the main risk factors of atherosclerosis. In particular, uric acid may have a protective as well as a detrimental role in vascular alterations, thus justifying the multi-directional effects of XOR inhibition. Moreover, XOR products are associated with cell differentiation, leading to adipogenesis and foam cell formation, as well as to the production of monocyte chemoattractant protein-1 from arterial smooth muscle cells, after proliferation and migration. The role of XOR in adipogenesis is also connected with insulin resistance and obesity, two main features of type 2 diabetes

Pathophysiology of circulating xanthine oxidoreductase: new emerging roles for a multi-tasking enzyme.

Abstract The enzyme xanthine oxidoreductase (XOR) catalyses the last step of purine degradation in the highest uricotelic primates as a rate-limiting enzyme in nucleic acid catabolism. Although XOR has been studied for more than a century, this enzyme continues to arouse interest because its involvement in many pathological conditions is not completely known. XOR is highly evolutionarily conserved; moreover, its activity is very versatile and tuneable at multiple-levels and generates both oxidant and anti-oxidant products. This review covers the basic information on XOR biology that is essential to understand its enzymatic role in human pathophysiology and provides a comprehensive catalogue of the experimental and human pathologies associated with increased serum XOR levels. The production of radical species by XOR oxidase activity has been intensively studied and evaluated in recent decades in conjunction with the cytotoxic consequences and tissue injuries of various pathological conditions. More recently, a role has emerged for the activity of endothelium-bound enzymes in inducing the vascular response to oxidative stress, which includes the regulation of pro-inflammatory and pro-thrombotic activities of endothelial cells. The possible physiological functions of circulating XOR and the products of its enzyme activity are presented here together with their implications in cardiovascular and metabolic diseases