Thermophysical Properties of Amino Acid-Based Ionic Liquids

Ionic liquids (ILs) having either cations or anions derived from naturally occurring amino acids have been synthesized and characterized as amino acid-based ionic liquids (AAILs) In this work, the experimental measurements of the temperature dependence or density. viscosity, heat capacity, and thermal conductivity of several AAILs, namely, tributylmethylammonium serinate ([N-444][Ser], tributylmethylammonium taurmate ([N-444][Tau]) tributylmethylammonium lysinate a [N-444][ Lys]), tributylmethylammonium threonate ([N-444][Thr]), tetrabutylphosphonium serinate ([P-4444][Ser]), tetrabutylphosphonium taurmate ([P-4444][Tau]), tetrabutylphosphonium lysinate ([P-4444][Lys]), tetrabutylphosphonium threonate P-4444 Thr tetrabutylphosphonium prolinate P-4444 ((Pro(), tetrabutylphosphonium valinate ([P-4444][Val]), and tetrabutylphosphonium cysteinate ([P-4444][Cys]), are presented The influence of cations and anions on studied properties is discussed. On the basis of experimental data. the QSPR (quantitative structure property relationship) correlations and group contribution methods for thermophysical properties of AAILs have been developed, which form the basis for the development of the computer-aided molecular design (CAMD) of AAILs It has also been demonstrated that that the predictive data obtained by con elation methods ale in good agreement with the experimental data The correlations developed, herein. can thus be used to evaluate the studied thermophysical properties of AAILs for use in process design or in the CAMD of new AAILs

Ginkgolide B and bilobalide block the pore of the 5-HT3 receptor at a location that overlaps the picrotoxin binding site

Extracts from the Ginkgo biloba tree are widely used as herbal medicines, and include bilobalide (BB) and ginkgolides A and B (GA and GB). Here we examine their effects on human 5-HT(3)A and 5-HT(3)AB receptors, and compare these to the effects of the structurally related compounds picrotin (PTN) and picrotoxinin (PXN), the two components of picrotoxin (PTX), a known channel blocker of 5-HT3, nACh and GABA(A) receptors. The compounds inhibited 5-HT-induced responses of 5-HT3 receptors expressed in Xenopus oocytes, with IC50 values of 470 mu M (BB), 730 mu M (GB), 470 mu M (PTN), 11 mu M (PXN) and > 1 mM (GA) in 5-HT(3)A receptors, and 3.1 mM (BB), 3.9 mM (GB), 2.7 mM (PTN), 62 mu M (PXN) and > 1 mM (GA) in 5-HT(3)AB receptors. Radioligand binding on receptors expressed in HEK 293 cells showed none of the compounds displaced the specific 5-HT3 receptor antagonist [H-3]granisetron, confirming that they do not act at the agonist binding site. Inhibition by GB at 5-HT(3)A receptors is weakly use-dependent, and recovery is activity dependent, indicating channel block. To further probe their site of action at 5-HT(3)A receptors, BB and GB were applied alone or in combination with PXN, and the results fitted to a mathematical model; the data revealed partially overlapping sites of action. We conclude that BB and GB block the channel of the 5-HT(3)A receptor. Thus these compounds have comparable, although less potent, behaviour than at some other Cys-loop receptors, demonstrating their actions are conserved across the family. (C) 2010 Published by Elsevier Ltd.

Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice

Physiological secretion of bile acids has previously been linked to the regulation of blood glucose. GLP-1 is an intestinal peptide hormone with important glucose-lowering actions, such as stimulation of insulin secretion and inhibition of glucagon secretion. In this investigation, we assessed the ability of several bile acid compounds to secrete GLP-1 in vitro in STC-1 cells. Bile acids stimulated GLP-1 secretion from 3.3- to 6.2-fold but some were associated with cytolytic effects. Glycocholic and taurocholic acids were selected for in vivo studies in normal and GLP-1R(-/-) mice. Oral glucose tolerance tests revealed that glycocholic acid did not affect glucose excursions. However, taurocholic acid reduced glucose excursions by 40% in normal mice and by 27% in GLP-1R(-/-) mice, and plasma GLP-1 concentrations were significantly elevated 30 min post-gavage. Additional studies used incretin receptor antagonists to probe involvement of GLP-1 and GIP in taurocholic acid-induced glucose lowering. The findings suggest that bile acids partially aid glucose regulation by physiologically enhancing nutrient-induced GLP-1 secretion. However, GLP-1 secretion appears to be only part of the glucose-lowering mechanism and our studies indicate that the other major incretin GIP is not involved.

A critical appraisal of tools available for monitoring epigenetic changes in clinical samples from patients with myeloid malignancies

Research over the past decade has confirmed that epigenetic alterations act in concert with genetic lesions to deregulate gene expression in acute myeloid leukemia and myelodysplastic syndromes. In addition, we now have the capability to pharmaceutically target epigenetic modifications, and there is an urgent need forearly validation of the efficacy of the drugs. Also, an improved understanding of the functionality of epigenetic modifications may further pave the road towards an individualized therapy. Here, we provide the pros and cons of the currently most feasible methods used for characterizing the methylome in clinical samples, and give a brief introduction to novel approaches to sequencing that may revolutionize our abilities to characterize the genomes and epigenomes in acute myeloid leukemia and myelodysplastic syndrome patients.

A quorum-quenching approach to investigate the conservation of quorum-sensing-regulated functions within the Burkholderia cepacia complex

Taxonomic studies of the past few years have shown that the Burkholderia cepacia complex, a heterogeneous group of B. cepacia-like organisms, consists of at least nine species. B. cepacia complex strains are ubiquitously distributed in nature and have been used for biocontrol, bioremediation, and plant growth promotion purposes. At the same time, B. cepacia complex strains have emerged as important opportunistic pathogens of humans, particularly those with cystic fibrosis. All B. cepacia complex species investigated thus far use quorum-sensing (QS) systems that rely on N-acylhomoserine lactone (AHL) signal molecules to express certain functions, including the production of extracellular proteases, swarming motility, biofilm formation, and pathogenicity, in a population-density-dependent manner. In this study we constructed a broad-host-range plasmid that allowed the heterologous expression of the Bacillus sp. strain 240B1 AiiA lactonase, which hydrolyzes the lactone ring of various AHL signal molecules, in all described B. cepacia complex species. We show that expression of AiiA abolished or greatly reduced the accumulation of AHL molecules in the culture supernatants of all tested B. cepacia complex strains. Phenotypic characterization of wild-type and transgenic strains revealed that protease production, swarming motility, biofilm formation, and Caenorhabditis elegans killing efficiency was regulated by AHL in the large majority of strains investigated.

Emergence time and foraging activity in Pallas' mastiff bat, Molossus molossus (Chiroptera: Molossidae) in relation to sunset/sunrise and phase of the moon

The decision on when to emerge from the safety of a roost and forage for prey is thought to be a result of the trade off between peak insect abundance and predation pressure for bats. In this study we show that the velvety free-tailed bat Molossus molossus emerges just after sunset and just before sunrise for very short foraging bouts (average 82.2 min foraging per night). Contrary to previous studies, bats remain inactive in their roost between activity patterns. Activity was measured over two complete lunar cycles and there was no indication that phase of the moon had an influence on emergence time or the numbers of bats that emerged from the roost. This data suggests that M. molossus represents an example of an aerial hawking bat whose foraging behaviour is in fact adapted to the compromise between the need to exploit highest prey availability and the need to avoid predation.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial:a double-blind, active and placebo-controlled study

The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection):a randomised placebo-controlled trial

Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients.

Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases

Elafin is a 6-kDa innate immune protein present at several epithelial surfaces including the pulmonary epithelium. It is a canonical protease inhibitor of two neutrophil serine proteases [neutrophil elastase (NE) and proteinase 3] with the capacity to covalently bind extracellular matrix proteins by transglutamination. In addition to these properties, elafin also possesses antimicrobial and immunomodulatory activities. The aim of the present study was to investigate the effect of Pseudomonas aeruginosa proteases on elafin function. We found that P aeruginosa PAO1-conditioned medium and two purified Pseudomonas metalloproteases, pseudolysin (elastase) and aeruginolysin (alkaline protease), are able to cleave recombinant elafin. Pseudolysin was shown to inactivate the anti-NE activity of elafin by cleaving its protease-binding loop. Interestingly, antibacterial properties of elafin against PAO1 were found to be unaffected after pseudolysin treatment. In contrast to pseudolysin, aeruginolysin failed to inactivate the inhibitory properties of elafin against NE. Aeruginolysin cleaves elafin at the amino-terminal Lys6-Gly7 peptide bond, resulting in a decreased ability to covalently bind purified fibronectin following transglutaminase activity. In conclusion, this study provides evidence that elafin is susceptible to proteolytic cleavage at alternative sites by P aeruginosa metalloproteinases, which can affect different biological functions of elafin.