Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1

Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the RCT pathway. Twenty-three healthy men (45-65 years) participated in a randomized, partially diet-controlled, crossover trial. They consumed four glasses of whisky (40 g of alcohol) or water daily for 17 days. After 17 days of whisky consumption, serum capacity to induce ABCA1-dependent cholesterol efflux from J774 mouse macrophages was increased by 17.5% (P = 0.027) compared with water consumption. Plasma capacity to induce cholesterol efflux from Fu5AH cells increased by 4.6% (P = 0.002). Prebeta-HDL, apolipoprotein A-I (apoA-I), and lipoprotein A-I:A-II also increased by 31.6, 6.2, and 5.7% (P < 0.05), respectively, after whisky consumption compared with water consumption. Changes of cAMP-stimulated cholesterol efflux correlated (r = 0.65, P < 0.05) with changes of apoA-I but not with changes of prebeta-HDL (r = 0.30, P = 0.18). Cholesterol efflux capacities from serum of lean men were higher than those from overweight men. In conclusion, this study shows that moderate alcohol consumption increases the capacity of serum to induce cholesterol efflux from J774 mouse macrophages, which may be mediated by ABCA1.     

Structural characterization of a K-antigen capsular polysaccharide essential for normal symbiotic infection in Rhizobium sp. NGR234: deletion of the rkpMNO locus prevents synthesis of 5,7-diacetamido-3,5,7,9-tetradeoxy-non-2-ulosonic acid

Many early molecular events in symbiotic infection have been documented, although factors enabling Rhizobium to progress within the plant-derived infection thread and ultimately survive within the intracellular symbiosome compartment as mature nitrogen-fixing bacteroids are poorly understood. Rhizobial surface polysaccharides (SPS), including the capsular polysaccharides (K-antigens), exist in close proximity to plant-derived membranes throughout the infection process. SPSs are essential for bacterial survival, adaptation, and as potential determinants of nodulation and/or host specificity. Relatively few studies have examined the role of K-antigens in these events. However, we constructed a mutant that lacks genes essential for the production of the K-antigen strain-specific sugar precursor, pseudaminic acid, in the broad host range Rhizobium sp. NGR234. The complete structure of the K-antigen of strain NGR234 was established, and it consists of disaccharide repeating units of glucuronic and pseudaminic acid having the structure -->4)-beta-d-glucuronic acid-(1-->4)-beta-5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-nonulosonic acid-(2-->. Deletion of three genes located in the rkp-3 gene cluster, rkpM, rkpN, and part of rkpO, abolished pseudaminic acid synthesis, yielding a mutant in which the strain-specific K-antigen was totally absent: other surface glycoconjugates, including the lipopolysaccharides, exopolysaccharides, and flagellin glycoprotein appeared unaffected. The NGRDeltarkpMNO mutant was symbiotically defective, showing reduced nodulation efficiency on several legumes. K-antigen production was found to decline after rhizobia were exposed to plant flavonoids, and the decrease coincided with induction of a symbiotically active (bacteroid-specific) rhamnan-LPS, suggesting an exchange of SPS occurs during bacterial differentiation in the developing nodule.     

Structural homology of storage proteins coded by the Hor-1 locus of barley (Hordeum vulgare L.)

Three C hordein fractions were prepared by ion-exchange chromatography of a total hordein preparation on carboxymethyl cellulose at pH 4.6 Polyacrylamide gel electrophoresis at pH 3.2 and sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) at pH 8.9 showed that each fraction contained a single major band. The apparent molecular weights of these were determined by SDS-PAGE as 58, 57, and 54,000. When compared by isoelectric focusing, however, the 58 and 57,000 components each separated into two major bands and the 54,000 component into four. Amino acid analysis showed that although the three fractions had similar compositions with high glutamate+glutamine (38–39%), proline (30–32%) and phenylalanine (8–9%) contents, some differences were present, notably in the relative content of lysine. The three fractions had identical amino acid sequences for the first ten residues at the N-terminal end. They also had identical sequences for the first five residues at the C-terminal end, with the exception that a mixture of two amino acids were released from position 4 of the 58,000 fraction only. Peptide mapping with three enzymes (trypsin, chymotrypsin and V8 protease) indicated that the 58 and 57,000 fractions were more closely related to each other than to the 54,000 fraction. It is suggested that the 57 and 58,000 fractions and the 54,000 fraction constitute two families of closely related polypeptides which are coded by genes derived from the duplication and divergence of a single ancestral gene.     

A New and Convenient Approach for the Synthesis of Ribo- and 2′-Deoxyribo-β-L-Furanonucleosides Starting From β-L-Xylofuranonucleosides

Abstract

Ribo- and 2′-deoxyribo-β-L-furanosyladenine have been synthesized. Although these compounds have been already reported in the literature, it seemed to us that a more convenient approach for their synthesis deserved to be developed. Intramolecular substitution as well as Mitsunobu reaction were used to invert the configuration of carbon 3′ of starting β-L-xylofuranosyl intermediates.     

Synthesis of New Fluorescent Nucleoside Analogues and Application to the Study of Human Deoxycytidine Kinase

Abstract

We have determined the affinity of human deoxycytidine kinase with respect to new fluorescent N-methylanthraniloyl cytidine derivatives or non fluorescent enantiomeric cytidine analogues. New results regarding the enantioselectivity and the mechanism of the enzyme are presented.     

Enderleinellus tamiasis Fahrenholz, 1916 (Anoplura: Enderleinellidae), an introduced species, and a new sucking louse for the French fauna

A new sucking louse is recorded for the French Anopluran fauna, Enderleinellus tomiasis found on the introduced Sciurid Tamias sibiricus. This observation highlights the maintenance of parasites when introduced with their hosts and when their hosts settle into a novel environments. It suggests a common origin for two out of four populations of Siberian chipmunks examined. The authors describe the morphological criteria that allow the distinction between the two species of Enderleinellus and each infecting a sciurid host found in our country.     

Cell transplantation with a catheter-based approach: an efficient method for the treatment of heart failure with multiple lesions

Cell transplantation is emerging as a potential therapeutic approach for the treatment of heart failure. At present, popular methods of cell delivery may not be efficient in perfusing cells through the whole myocardium. We have developed a novel catheter-based method for global transplantation of cells. Heart failure was induced in rabbit by intravenous administration of doxorubicin. Autologous bone marrow mononuclear cells were transplanted into failing hearts via the root of the aorta. Bilateral sinus aortae and coronary arteries were visualized by angiography during the cell transplantation procedure; there was no intraprocedural death. Four weeks after cell transplantation, there was an improvement in the mean left ventricular ejection fraction from baseline 72.13% to 81.54% (P = 0.034). Transplanted cells were observed throughout the cardiac layers of left and right ventricles. In conclusion, cell transplantation through the root of the aorta is a useful approach to globally supply cells into the heart.     

p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.     

Molecular mechanisms of ATP secretion during immunogenic cell death

The immunogenic demise of cancer cells can be induced by various chemotherapeutics, such as anthracyclines and oxaliplatin, and provokes an immune response against tumor-associated antigens. Thus, immunogenic cell death (ICD)-inducing antineoplastic agents stimulate a tumor-specific immune response that determines the long-term success of therapy. The release of ATP from dying cells constitutes one of the three major hallmarks of ICD and occurs independently of the two others, namely, the pre-apoptotic exposure of calreticulin on the cell surface and the postmortem release of high-mobility group box 1 (HMBG1) into the extracellular space. Pre-mortem autophagy is known to be required for the ICD-associated secretion of ATP, implying that autophagy-deficient cancer cells fail to elicit therapy-relevant immune responses in vivo. However, the precise molecular mechanisms whereby ATP is actively secreted in the course of ICD remain elusive. Using a combination of pharmacological screens, silencing experiments and techniques to monitor the subcellular localization of ATP, we show here that, in response to ICD inducers, ATP redistributes from lysosomes to autolysosomes and is secreted by a mechanism that requires the lysosomal protein LAMP1, which translocates to the plasma membrane in a strictly caspase-dependent manner. The secretion of ATP additionally involves the caspase-dependent activation of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1)-mediated, myosin II-dependent cellular blebbing, as well as the opening of pannexin 1 (PANX1) channels, which is also triggered by caspases. Of note, although autophagy and LAMP1 fail to influence PANX1 channel opening, PANX1 is required for the ICD-associated translocation of LAMP1 to the plasma membrane. Altogether, these findings suggest that caspase- and PANX1-dependent lysosomal exocytosis has an essential role in ATP release as triggered by immunogenic chemotherapy.