Two-dimensional supramolecular assemblies involving neoglycoplipids: Self-organization and insertion properties into Langmuir monolayers

In nature, interfacial molecular recognition and chirality are of fundamental significance for the construction of biological assemblies. Lipid monolayers at liquid interface can be used as biomimetic models for studying molecular interactions in such assemblies. In this article, we will focus on the use of Langmuir monolayers for studying self-organization and insertion properties of several neoglycolipids. Two types of glycolipids have been considered, one in the context of the analysis of glycoconjugates of biological relevance, and one dealing with the ability of some glycoprobes to insert into a monolayer in relation with their efficiency for serving as membrane imaging systems.     

A preliminary analysis of sleep-like states in the cuttlefish Sepia officinalis

Sleep has been observed in several invertebrate species, but its presence in marine invertebrates is relatively unexplored. Rapid-eye-movement (REM) sleep has only been observed in vertebrates. We investigated whether the cuttlefish Sepia officinalis displays sleep-like states. We find that cuttlefish exhibit frequent quiescent periods that are homeostatically regulated, satisfying two criteria for sleep. In addition, cuttlefish transiently display a quiescent state with rapid eye movements, changes in body coloration and twitching of the arms, that is possibly analogous to REM sleep. Our findings thus suggest that at least two different sleep-like states may exist in Sepia officinalis.     

Progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein-mediated multidrug efflux: Design, synthesis, characterization and biological evaluation

Bivalent ligands were designed on the basis of the described close proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of 19 progesterone-adenine hybrids are described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone. The hybrid with a hexamethylene linker chain showed the best inhibitory potency. The efficiency of these progesterone-adenine hybrids depends on two main factors: (i) the nature of the linker and (ii) its attachment point on the steroid skeleton.     

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Project Study: protocol for a randomised controlled trial comparing methadone and buprenorphine for opiate detoxification

Many research-funding agencies now require open access to the results of research they have funded, and some also require that researchers make available the raw data generated from that research. Similarly, the journal Trials aims to address inadequate reporting in randomised controlled trials, and in order to fulfil this objective, the journal is working with the scientific and publishing communities to try to establish best practice for publishing raw data from clinical trials in peer-reviewed biomedical journals. Common issues encountered when considering raw data for publication include patient privacy – unless explicit consent for publication is obtained – and ownership, but agreed-upon policies for tackling these concerns do not appear to be addressed in the guidance or mandates currently established. Potential next steps for journal editors and publishers, ethics committees, research-funding agencies, and researchers are proposed, and alternatives to journal publication, such as restricted access repositories, are outlined.     

Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study

Introduction  

The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX.     

The disulphide mapping,folding and characterisation of recombinant Ber e 1, an allergenic protein,and SFA8, two sulphur-rich 2S plant albumins

We have cloned and expressed genes encoding the allergenic brazil nut 2S albumin (Ber e 1) and the sunflower albumin 8 (SFA8) in the methylotrophic yeast Pichia pastoris. We show that both proteins were secreted at high levels and that the purified proteins were properly folded. We also showed that Ber e 1 is glycosylated during secretion and that the glycan does not interfere with the folding or immunoreactivity. The disulphide map of the Ber e 1 protein was experimentally established and is in agreement with the conserved disulphide structure of other members of the 2S albumin family. A model three-dimensional structure of the allergen was generated. During the expression studies and through mutation we have also shown that alteration of the sequences around the Kex2 endoproteolytic processing site in the expressed fusion protein can compromise the secretion by targeting part of the protein for possible degradation. The secreted production of these properly folded sulphur-rich plant albumins presents an opportunity to delineate the attributes that make an allergen and to facilitate the diagnosis and therapy of type I allergy.     

Probing the origins, diagnosis and treatment of amyloid diseases using antibodies

The deposition of proteins in the form of amyloid fibrils is the characteristic feature of more than 20 medical conditions affecting the central nervous system or a variety of peripheral tissues. These disorders, which include Alzheimer's disease, the prion diseases and type II diabetes, are of enormous importance in the context of present-day human health and welfare. Extensive research is therefore being carried out to define the molecular details of the mechanism of the pathological conversion of amyloidogenic proteins from their soluble forms into fibrillar structures. This review focuses on recent studies that demonstrate the power of using antibodies or antibody fragments to probe the process of fibril formation, and discusses the emerging potential of these species as diagnostic and therapeutic agents.     

Towards the development of a DNA-sequence based approach to serotyping of <Emphasis Type="Italic">Salmonella enterica</Emphasis>

Background  

The fliC and fljB genes in Salmonella code for the phase 1 (H1) and phase 2 (H2) flagellin respectively, the rfb cluster encodes the majority of enzymes for polysaccharide (O) antigen biosynthesis, together they determine the antigenic profile by which Salmonella are identified. Sequencing and characterisation of fliC was performed in the development of a molecular serotyping technique.