NMR interaction studies of Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc with influenza-virus hemagglutinin expressed in transfected human cells

The emergence of escape-mutants of influenza hemagglutinin (HA) following vaccination compels the yearly re-formulation of flu vaccines. Since binding the sialic acid receptor remains in all cases essential for infection, small-molecule inhibitors of HA binding to sialic acid could be interesting therapeutic complements or alternatives to immuno-prophylaxis in the control of flu epidemics. In this work, we made use of NMR spectroscopy to study the interaction between a derivative of sialic acid (the Neu5Ac-\u3b1-(2,6)-Gal-\u3b2-(1-4)-GlcNAc trisaccharide) and HAs (H1 and H5) from human and avian strains of influenza virus, directly expressed on the surface of stable transfected 293 T human cells. The HAs were shown to retain their native trimeric conformation and binding properties. Exploiting the magnetization transfer between the proteins and the ligand, we obtained evidence of the binding event and mapped the (non-identical) sugar epitopes recognized by the two HA species. The rapid and reliable method for screening sialic acid-related HA ligands we have developed could yield useful information for an efficient drug design

Eguaglianza di genere in Magistratura : quanto ancora dobbiamo aspettare?

Le donne rappresentano oggi la met\ue0 dei magistrati italiani (52%), ma sono pressoch\ue9 assenti dalle posizioni di vertice e dal Consiglio Superiore della Magistratura. Come risolvere tale squilibrio? \uc8 necessario intervenire per via legislativa? A questi interrogativi rispondono, in questo volume, studiosi del diritto, parlamentari, avvocati, magistrati e componenti del CSM, ripercorrendo la lunga strada dell\u2019attuazione del principio di parit\ue0 e analizzando le novit\ue0 pi\uf9 recenti in materia, come la proposta di legge (A.C. 4512, Ferranti ed altri, del 25 maggio 2017), volta a favorire il riequilibrio di genere nel Consiglio Superiore della Magistratura. Dalla lettura dei contributi emerge chiaramente come il tema della rappresentanza di genere negli organi di vertice e decisionali della Magistratura tocchi nel profondo alcuni principi fondamentali, come l\u2019eguaglianza e il buon funzionamento della giustizia: principi di cui il legislatore dovr\ue0 necessariamente farsi carico anche nella prossima legislatura

Plasma concentrations of boosted and unboosted atazanavir are predicted by 63396C>T SNP in the PXR gene

Purpose of the study Atazanavir (ATV) is administered at the usual adult dose of 300 mg with 100 mg of ritonavir (RTV) once a day (boosted). However, 400 mg once a day (unboosted) is also used in some settings. ATV plasma concentrations are influenced by efflux transporters, influx transporters and metabolism enzymes. The expression of many of these proteins is regulated by nuclear receptors such as PXR. Recently polymorphisms in the regulatory region of the PXR gene have been reported to influence its expression and the activity of downstream genes, such as CYP3A4 and ABCB1. The aim of this study was to investigate whether polymorphisms in PXR influence trough concentrations (Ctrough) of boosted or unboosted ATV

A Human Monoclonal Antibody with Neutralizing Activity against Highly Divergent Influenza Subtypes

The interest in broad-range anti-influenza A monoclonal antibodies (mAbs) has recently been strengthened by theidentification of anti-hemagglutinin (HA) mAbs endowed with heterosubtypic neutralizing activity to be used in the designof ‘‘universal’’ prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bindand neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenzaphylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, amongothers, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all testedisolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belongingto group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable ofneutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes withpandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residueshighly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent auseful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for thedevelopment of universal vaccinal strategies

Towards A Grid Infrastructure For Hydro-Meteorological Research

The Distributed Research Infrastructure for Hydro-Meteorological Study (DRIHMS) is a coordinatedaction co-funded by the European Commission. DRIHMS analyzes the main issuesthat arise when designing and setting up a pan-European Grid-based e-Infrastructure for researchactivities in the hydrologic and meteorological fields. The main outcome of the projectis represented first by a set of Grid usage patterns to support innovative hydro-meteorologicalresearch activities, and second by the implications that such patterns define for a dedicatedGrid infrastructure and the respective Grid architecture