Electrochemical Generation of N-Heterocyclic Carbenes for Use in Synthesis and Catalysis

The electrochemical generation of N-heterocyclic carbenes (NHCs) offers a mild and selective alternative to traditional synthetic methods that usually rely on strong bases and air-sensitive materials. The use of electrons as reagents results in an efficient and clean synthesis that enables the direct use of NHCs in various applications. Herein, the use of electrogenerated NHCs in organocatalysis, synthesis and organometallic chemistry is explored

Free-radical-mediated formation of trans-cardiolipin isomers, analytical approaches for lipidomics and consequences of the structural organization of membranes

Free-radical-mediated processes, such as peroxidation, isomerization and hydrogenation affecting fatty acid integrity and biological functions, have a trans-disciplinary relevance. Cardiolipins (CL, (1,3-diphosphatidyl-sn-glycerol)) and tetra-linoleoyl-CL are complex phospholipids, exclusively present in the Inner Mitochondrial Membrane (IMM) lipids, where they maintain membrane integrity and regulate enzyme functionalities. Peroxidation pathways and fatty acid remodeling are known causes of mitochondrial disfunctions and pathologies, including cancer. Free-radical-mediated isomerization with the change of the cis CL into geometrical trans isomers is an unknown process with possible consequences on the supramolecular membrane lipid organization. Here, the formation of mono-trans CL (MT-CL) and other trans CL isomers (T-CL) is reported using CL from bovine heart mitochondria and thiyl radicals generated by UV-photolysis from 2-mercaptoethanol. Analytical approaches for CL isomer separation and identification via 1H/13C NMR are provided, together with the chemical study of CL derivatization to fatty acid methyl esters (FAME), useful for lipidomics and metabolomics research. Kinetics information of the radical chain isomerization process was obtained using \u3b3-irradiation conditions. The CL isomerization affected the structural organization of membranes, as tested by the reduction in unilamellar liposome diameter, and accompanied the well-known process of oxidative consumption induced by Fenton reagents. These results highlight a potential new molecular modification pathway of mitochondrial lipids with wide applications to membrane functions and biological consequences

Sustainable approaches for asymmetric synthesis – from domino reactions to Chiral Carbon Dots as nano-organocatalysts

Organocatalysis is considered the third pilar of asymmetric synthesis and, due to the green aspects of organocatalytic procedures, has paved the way to the extensions of organic stereoselective synthesis horizons towards efficient, practical and more sustainable methodologies. For instance, organocatalyzed cascade reactions and sequential catalysis have been shown to be excellent candidates because of the number of steps that can occur under the same reaction conditions, thereby leading directly to high molecular complexity, in a cost-effective protocol.[1] Additionally, the technological advancement contributed to the application of other techniques such as electroorganic chemistry and photocatalysis to organocatalytic protocols, especially in the transferring of organocatalysis to heterogeneous processes. Within this context, carbon dots (CDs) are an emerging class of carbon-based nanoparticles, characterized by low-toxicity, biocompatibility, excellent suspensibility, and remarkable photoluminescent properties. CDs have therefore found many applications, including heterogeneous catalysis and photocatalysis.[2] In this presentation, some sustainable approaches for asymmetric synthesis will be described: i) the sequential stereoselective synthesis of spiro-decalin oxindoles; ii) electroorganic synthesis of Chiral Carbon Dots and their application as nano-organocatalysts for an asymmetric aldol reaction

Free radical-mediated formation of trans-cardiolipin isomers, analytical approaches for lipidomics and consequences for the structural organization of membranes

Free radical-mediated processes, such as peroxidation, isomerization and hydrogenation affecting fatty acid integrity and biological functions have a trans-disciplinary relevance. Cardiolipins [CL, (1,3-diphosphatidyl-sn-glycerol)] and tetra-linoleoyl-CL are complex phospholipids, exclusively present in the Inner Mitochondrial Membrane (IMM) lipids where they maintain membrane integrity and regulate enzyme functionalities. Peroxidation pathways and fatty acid remodeling are known causes of mitochondrial disfunctions and pathologies, including cancer. Free radical-mediated isomerization with the change of the cis CL into geometrical trans isomers is an unknown process with possible consequences on the supramolecular membrane lipid organization. Here, the formation of mono-trans CL and all-trans CL is reported using CL from bovine heart mitochondria and thiyl radicals generated by UV-photolysis from 2-mercaptoethanol. Analytical approaches for CL isomer separation and identification via 1H/13C NMR are provided, together with chemical study of CL derivatization to fatty acid methyl esters (FAME), useful for lipidomics and metabolomics research. Kinetics information of the radical chain isomerization process was obtained using γ-irradiation conditions. The CL isomerization affected the structural organization of membranes, as tested by reduction of unilamellar liposome diameter, and accompanied the well-known process of oxidative consumption induced by Fenton reagents. These results highlight a new molecular modification pathway of mitochondrial lipids with wide applications to membrane functions and biological consequences

A CASE OF ACUTE POLYRADICULONEUROPATHY, DRUG-INDUCED HYPERSENSITIVITY, AND HHV-6 INFECTION

[No abstract available

Late onset invasive pneumococcal disease in a liver transplanted patient: beyond the Austrian syndrome

Invasive disease caused by Streptococcus pneumoniae is a major cause of morbidity and mortality in high-risk individuals with severe comorbidities, including asplenia, chronic alcoholism, and altered immune status. The risk of invasive pneumococcal disease has been significantly higher in transplant patients compared with the general population. Here, we report an unusual case of a disseminated pneumococcal infection with meningitis, endocarditis, spondylodiscitis, and muscle abscess in an asplenic patient on chronic immunosuppressive therapy for liver transplantation performed 17 years before. © 2013 John Wiley & Sons A/S

A C. elegans model of human α1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover

The accumulation of serpin oligomers and polymers within the endoplasmic reticulum (ER) causes cellular injury in patients with the classical form α1-antitrypsin deficiency (ATD). To better understand the cellular and molecular genetic aspects of this disorder, we generated transgenic C. elegans strains expressing either the wild-type (ATM) or Z mutant form (ATZ) of the human serpin fused to GFP. Animals secreted ATM, but retained polymerized ATZ within dilated ER cisternae. These latter animals also showed slow growth, smaller brood sizes and decreased longevity; phenotypes observed in ATD patients or transgenic mouse lines expressing ATZ. Similar to mammalian models, ATZ was disposed of by autophagy and ER-associated degradation pathways. Mutant strains defective in insulin signaling (daf-2) also showed a marked decrease in ATZ accumulation. Enhanced ATZ turnover was associated with the activity of two proteins central to systemic/exogenous (exo)-RNAi pathway: the dsRNA importer, SID-1 and the argonaute, RDE-1. Animals with enhanced exo-RNAi activity (rrf-3 mutant) phenocopied the insulin signaling mutants and also showed increased ATZ turnover. Taken together, these studies allude to the existence of a novel proteostasis pathway that mechanistically links misfolded protein turnover to components of the systemic RNAi machinery

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy : data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naive for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death