Edible Myrciaria vexator fruits: bioactive phenolics for potential COPD therapy

The edible fruits of Myrciaria vexator McVaugh (Myrtaceae), from northern South America, are eaten in certain locales, either fresh or processed into jellies and drinks. Activity-guided fractionation of M. vexator resulted in identification of ellagic acid (1), cyanidin-3-O-glucoside (2), delphinidin-3-O-glucoside (3), 2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid (4), and jaboticabin (5), and latter two compounds are being reported for the first time in this species. Ellagic acid was further examined, and found to inhibit cigarette smoke extract induced MMP-1 expression in vitro, and may be of significance in the treatment of chronic obstructive pulmonary (COPD). Other compounds identified for the first time from M. vexator include cyanidin-3-O-galactoside (6), cyanidin-3-O-arabinoside (7), cyanidin-3-O-rutionoside (8), petunidin (9), peonidin-3-O-galactoside (10) malvidin (11), hyperoside (12), querecetin-3-O-glucoside (13), and guajaverin (14), methyl protocatechuate (15), and protocatechuic acid (16).     

Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

Smokers with airflow obstruction have an increased risk of atherosclerosis, but the relationship between the pathogenesis of these diseases is not well understood. To determine whether hypercholesterolemia alters lung inflammation and emphysema formation, we examined the lung phenotype of two hypercholesterolemic murine models of atherosclerosis at baseline and on a high-fat diet. Airspace enlargement developed in the lungs of apolipoprotein E-deficient (Apoe(-/-)) mice exposed to a Western-type diet for 10 wk. An elevated number of macrophages and lymphocytes accompanied by an increase in matrix metalloproteinase-9 (MMP-9) activity and MMP-12 expression was observed in the lungs of Apoe(-/-) mice on a Western-type diet. In contrast, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice did not exhibit lung destruction or inflammatory changes. Most importantly, we revealed augmented expression of the downstream targets of the Toll-like receptor (TLR) pathway, interleukin-1 receptor-associated kinase 1, and granulocyte colony-stimulating factor, in the lungs of Apoe(-/-) mice fed with a Western-type diet. In addition, we demonstrated overexpression of MMP-9 in Apoe(-/-) macrophages treated with TLR4 ligand, augmented with the addition of oxidized LDL, suggesting that emphysema in these mice results from the activation of the TLR pathway secondary to known abnormal cholesterol efflux. Our findings indicate that, in Apoe(-/-) mice fed with an atherogenic diet, abnormal cholesterol efflux leads to increased systemic inflammation with subsequent lung damage and emphysema formation.     

Geographic variation and positive selection on M7 lysin, an acrosomal sperm protein in mussels (Mytilus spp.)

Successful fertilization in free-spawning marine organisms depends on the interactions between genes expressed on the surfaces of eggs and sperm. Positive selection frequently characterizes the molecular evolution of such genes, raising the possibility that some common deterministic process drives the evolution of gamete recognition genes and may even be important for understanding the evolution of prezygotic isolation and speciation in the marine realm. One hypothesis is that gamete recognition genes are subject to selection for prezygotic isolation, namely, reinforcement. In a previous study, positive selection on the gene coding for the acrosomal sperm protein M7 lysin was demonstrated among allopatric populations of mussels in the Mytilus edulis species group (M. edulis, Mytilus galloprovincialis, and Mytilus trossulus). Here, we expand sampling to include M7 lysin haplotypes from populations where mussel species are sympatric and hybridize to determine whether there is a pattern of reproductive character displacement (RCD), which would be consistent with reinforcement driving selection on this gene. We do not detect a strong pattern of RCD; neither are there unique haplotypes in sympatry nor is there consistently greater population structure in comparisons involving sympatric populations. One distinct group of haplotypes, however, is strongly affected by natural selection, and this group of haplotypes is found within M. galloprovincialis populations throughout the Northern Hemisphere concurrent with haplotypes common to M. galloprovincialis and M. edulis. We suggest that balancing selection, perhaps resulting from sexual conflicts between sperm and eggs, maintains old allelic diversity within M. galloprovincialis.     

Genetic diversity in the blackberry rust pathogen, Phragmidium violaceum, in Europe and Australasia as revealed by analysis of SAMPL

Indigenous to Europe, the blackberry rust fungus Phragmidium violaceum was introduced to Australia and subsequently appeared in New Zealand, with the most recent authorised introductions to Australia specifically for the biological control of European blackberry. Markers for ‘selective amplification of microsatellite polymorphic loci’ (SAMPL) were developed for studying the population genetics of P. violaceum. Modification of one of the two SAMPL primers with a HaeIII adapter (H) revealed significantly greater levels of genetic variation than primers used to generate AFLPs, the latter revealing little or no variation among 25 Australasian and 19 European isolates of P. violaceum. SAMPL was used to describe genetic variation among these 44 isolates of P. violaceum from 51 loci generated using primer pairs (GACA)₄ + H–G and R1 + H–G. The European isolates were more diverse than Australasian isolates, with 37 and 22 % polymorphic loci, respectively. Cluster analysis revealed geographic clades, with Australasian isolates forming one cluster separated from two clusters comprising the European isolates. However, low bootstrap support at these clades suggested that Australian isolates had not differentiated significantly from European isolates since the first record of P. violaceum in Australia in 1984. In general, the results support two hypotheses. First, that the population of P. violaceum in Australia was founded from a subset of individuals originating from Europe. Second, that P. violaceum in New Zealand originated from the Australian population of P. violaceum, probably by wind dispersal of urediniospores across the Tasman Sea. The application of SAMPL markers to the current biological control programme for European blackberry is discussed.     

Synthesis and evaluation of two 18F-labeled imidazo[1,2-a]pyridine analogues as potential agents for imaging beta-amyloid in Alzheimer's disease

Two new fluorinated imidazo[1,2-a]pyridine derivatives, 6-(2'-fluoroethyl)-2-(4'-dimethylamino)phenylimidazo[1,2-a]pyridine (FEPIP) and 6-(3'-fluoropropyl)-2-(4'-dimethylamino)phenylimidazo[1,2-a]pyridine (FPPIP), were synthesized. The binding affinity for FEPIP and FPPIP to amyloid plaques in human AD cortical tissues was determined. Radiolabeling, in vitro film autoradiography, and micro-PET study were performed with [18F]FPPIP to determine its utility as a radioligand for amyloid plaque imaging in the brain of AD patients.     

PATERNAL LEAKAGE OF MITOCHONDRIAL DNA IN A FUCUS (PHAEOPHYCEAE) HYBRID ZONE1

Eukaryotic mitochondria are mostly uniparentally (maternally) inherited, although mtDNA heteroplasmy has been reported in all major lineages. Heteroplasmy, the presence of more than one mitochondrial genome in an individual, can arise from recombination, point mutations, or by occasional transmission of the paternal mtDNA (=paternal leakage). Here, we report the first evidence of mtDNA paternal leakage in brown algae. In Denmark, where Fucus serratus L. and Fucus evanescens C. Agardh have hybridized for years, we found eight introgressed individuals that possessed the very distinct haplotypes of each parental species. The finding of heteroplasmy in individuals resulting from several generations of backcrosses suggests that paternal leakage occurred in earlier generations and has persisted through several meiotic bottlenecks.     

Consequence of omitting or adding a meal in man on body composition, food intake, and metabolism

Objective: To investigate in man the consequence on body composition and related biological and metabolic parameters of omitting or adding a meal. Research Methods and Procedures: Twenty‐four young normal‐weight male subjects were recruited, 12 usual four‐meal and 12 usual three‐meal eaters, differing only in the consumption of an afternoon meal. They omitted or added a fourth meal during a 28‐day habituation period and were asked to report their intake on three 3‐day occasions. Before and after this habituation period, subjects participated in a session with a time‐blinded procedure, and blood was collected continuously from lunch to the spontaneously requested dinner. Body composition, respiratory quotient, and biochemical parameters were measured in the late evening preceding each session. Results: Omitting a meal was followed by increases in fat mass (360 ± 115 grams, p < 0.05), late evening leptin concentration (20.7 ± 11.0%, p < 0.05), and respiratory quotient (3.7 ± 1.4%, p < 0.05). Increase in the percentage of dietary fat during the habituation period (+4.1 ± 2.0%, p < 0.05) was correlated with fat mass (r = 0.66, p < 0.05). Adding a meal had no effect, but, in both groups, the change in energy content at this fourth eating occasion was correlated with the change in adiposity. Discussion: Our results suggest that adiposity may increase when young lean male subjects switch from a four‐ to a three‐meal pattern by removing their usual afternoon meal. This effect could be partly mediated by a change in the macronutrient composition of the diet.     

Microsomal Ca2+ flux modulation as an indicator of heavy metal toxicity

Inositol 1,4,5-trisphosphatee (IP3), an intracellular messenger, releases Ca2+ from microsomes. Ca2+ plays a major role in regulating various cellular events like neural transmission and regulation of hormones and growth factors. Aluminum (Al), lead (Pb) and mercury (Hg) were reported to alter Ca(2+)-regulated events thereby causing neurotoxicity. Hence, an attempt was made characterize IP3 mediated Ca2+ release from rat brain microsomes under the influence of Al, Pb and Hg. Different concentrations of metals were tested over a designated time scale and their effects on IP3 mediated Ca2+ release from microsomes were monitored using Fura-2 technique. All the three metals inhibited IP3 mediated Ca2+ release, Pb being more potent. The order of potency of these three metals was Pb>Hg>Al. Except for Al, both Hg and Pb independently released Ca2+ from microsomes. Re-uptake of Ca2+ into microsomes was inhibited by all the three metals, Pb being more potent. Microsomal Ca(2+)-ATPase activity was also inhibited by all the three metals. These results suggest that neurotoxicity exerted by Al, Pb and Hg may be due to the interference of these metals with IP3 mediated calcium release and also interfering with the microsomal Ca2+ sequestration mechanism. Differential effects of heavy metal induced changes in Ca2+ flux can be used as an index of relative toxicity.     

Decreased Levels of Bisecting GlcNAc Glycoforms of IgG Are Associated with Human Longevity

Background

Markers for longevity that reflect the health condition and predict healthy aging are extremely scarce. Such markers are, however, valuable in aging research. It has been shown previously that the N-glycosylation pattern of human immunoglobulin G (IgG) is age-dependent. Here we investigate whether N-linked glycans reflect early features of human longevity.

Methodology/Principal Findings

The Leiden Longevity Study (LLS) consists of nonagenarian sibling pairs, their offspring, and partners of the offspring serving as control. IgG subclass specific glycosylation patterns were obtained from 1967 participants in the LLS by MALDI-TOF-MS analysis of tryptic IgG Fc glycopeptides. Several regression strategies were applied to evaluate the association of IgG glycosylation with age, sex, and longevity. The degree of galactosylation of IgG decreased with increasing age. For the galactosylated glycoforms the incidence of bisecting GlcNAc increased as a function of age. Sex-related differences were observed at ages below 60 years. Compared to males, younger females had higher galactosylation, which decreased stronger with increasing age, resulting in similar galactosylation for both sexes from 60 onwards. In younger participants (<60 years of age), but not in the older age group (>60 years), decreased levels of non-galactosylated glycoforms containing a bisecting GlcNAc reflected early features of longevity.

Conclusions/Significance

We here describe IgG glycoforms associated with calendar age at all ages and the propensity for longevity before middle age. As modulation of IgG effector functions has been described for various IgG glycosylation features, a modulatory effect may be expected for the longevity marker described in this study.