N-dimensional electron in a spherical potential: the large-N limit

We show that the energy levels predicted by a 1/N-expansion method for an N-dimensional Hydrogen atom in a spherical potential are always lower than the exact energy levels but monotonically converge towards their exact eigenstates for higher ordered corrections. The technique allows a systematic approach for quantum many body problems in a confined potential and explains the remarkable agreement of such approximate theories when compared to the exact numerical spectrum.Comment: 8 pages, 1 figur

Extracellular Vesicle miRNAs in the Promotion of Cardiac Neovascularisation

Cardiovascular disease (CVD) is the leading cause of mortality worldwide claiming almost 17. 9 million deaths annually. A primary cause is atherosclerosis within the coronary arteries, which restricts blood flow to the heart muscle resulting in myocardial infarction (MI) and cardiac cell death. Despite substantial progress in the management of coronary heart disease (CHD), there is still a significant number of patients developing chronic heart failure post-MI. Recent research has been focused on promoting neovascularisation post-MI with the ultimate goal being to reduce the extent of injury and improve function in the failing myocardium. Cardiac cell transplantation studies in pre-clinical models have shown improvement in cardiac function; nonetheless, poor retention of the cells has indicated a paracrine mechanism for the observed improvement. Cell communication in a paracrine manner is controlled by various mechanisms, including extracellular vesicles (EVs). EVs have emerged as novel regulators of intercellular communication, by transferring molecules able to influence molecular pathways in the recipient cell. Several studies have demonstrated the ability of EVs to stimulate angiogenesis by transferring microRNA (miRNA, miR) molecules to endothelial cells (ECs). In this review, we describe the process of neovascularisation and current developments in modulating neovascularisation in the heart using miRNAs and EV-bound miRNAs. Furthermore, we critically evaluate methods used in cell culture, EV isolation and administration

Colle chirurgicale OMNEX dans la réparation extracorporelle des anévrysmes de l'artère rénale

OMNEX (Ethicon, Inc. ; Somerville, NJ, USA) est une colle chirurgicale synthétique de cyanoacrylate. Jusqu'ici, l'utilisation d'OMNEX a été seulement décrite dans un nombre limité de procédures de chirurgie vasculaire. Nous présentons les cas de deux malades qui ont eu la cure extracorporelle réussie d'anévrysmes de l'artère rénale à l'aide de la colle OMNEX. Ce rapport est la première démonstration de l'utilité d'OMNEX en chirurgie réno-vasculaire

OMNEX Surgical Sealant in the Extracorporeal Repair of Renal Artery Aneurysms

OMNEX (Ethicon, Inc.; Somerville, NJ) is a cyanoacrylate-based synthetic surgical sealant. To date, the use of OMNEX has only been described in a limited number of vascular surgery procedures. We present the cases of two patients who underwent successful extracorporeal renal artery aneurysm repair with the aid of OMNEX sealant. This report is the first evidence to suggest the utility of OMNEX in renovascular surgery

Selective Targeting of the Interconversion between Glucosylceramide and Ceramide by Scaffold Tailoring of Iminosugar Inhibitors

A series of simple C-alkyl pyrrolidines already known as cytotoxic inhibitors of ceramide glucosylation in melanoma cells can be converted into their corresponding 6-membered analogues by means of a simple ring expansion. This study illustrated how an isomerisation from iminosugar pyrrolidine toward piperidine could invert their targeting from glucosylceramide (GlcCer) formation toward GlcCer hydrolysis. Thus, we found that the 5-membered ring derivatives did not inhibit the hydrolysis reaction of GlcCer catalysed by lysosomal β-glucocerebrosidase (GBA). On the other hand, the ring-expanded C-alkyl piperidine isomers, non-cytotoxic and inactive regarding ceramide glucosylation, revealed to be potent inhibitors of GBA. A molecular docking study showed that the positions of the piperidine ring of the compound 6b and its analogous 2-O-heptyl DIX 8 were similar to that of isofagomine. Furthermore, compound 6b promoted mutant GBA enhancements over 3-fold equivalent to that of the related O-Hept DIX 8 belonging to one of the most potent iminosugar-based pharmacological chaperone series reported to date

Concise asymmetric synthesis of new enantiomeric C -alkyl pyrrolidines acting as pharmacological chaperones against Gaucher disease

International audienceA concise and asymmetric synthesis of the enantiomeric pyrrolidines 2 and ent-2 are herein reported. Both enantiomers were assessed as β-GCase inhibitors. While compound ent-2 acted as a poor competitive inhibitor, its enantiomer 2 proved to be a potent non-competitive inhibitor. Docking studies were carried out to substantiate their respective protein binding mode. Both pyrrolidines were also able to enhance lysosomal β-GCase residual activity in N370S homozygous Gaucher fibroblasts. Notably, the non-competitive inhibitor 2 displayed an enzyme activity enhancement comparable to that of reference compounds IFG and NN-DNJ. This work highlights the impact of inhibitors chirality on their protein binding mode and shows that, beyond competitive inhibitors, the study of non-competitive ones can lead to the identification of new relevant parmacological chaperones