Activation of peroxisome proliferator-activated receptor-β/-δ (PPARβ/δ) prevents endothelial dysfunction in type 1 diabetic rats

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease. Herein, we have analyzed if the peroxisome proliferator-activated receptor-β/-δ (PPARβ/δ) agonist GW0742 exerts protective effects on endothelial function in type 1 diabetic rats. The rats were divided into 4 groups: control, control-treated (GW0742, 5mgkg(-1)day(-1) for 5 weeks), diabetic (streptozotocin injection), and diabetic-treated. GW0742 administration in diabetic rats did not alter plasma glucose, systolic blood pressure, or heart rate, but reduced plasma triglyceride levels. The vasodilatation induced by acetylcholine was decreased in aortas from diabetic rats. GW0742 restored endothelial function, increasing eNOS phosphorylation. Superoxide production, NADPH oxidase activity, and mRNA expression of prepro endothelin-1, p22(phox), p47(phox), and NOX-1 were significantly higher in diabetic aortas, and GW0742 treatment prevented these changes. In addition, GW0742 prevented the endothelial dysfunction and the upregulation of prepro endothelin-1and p47(phox) after the in vitro incubation of aortic rings with high glucose and these effects were prevented by the PPARβ/δ antagonist GSK0660. PPARβ/δ activation restores endothelial function in type 1 diabetic rats. This effect seems to be related to an increase in nitric oxide bioavailability as a result of reduced NADPH oxidase-driven superoxide production and downregulation of prepro endothelin-1.     

Colonization of the Galápagos Islands by plants with no specific syndromes for long‐distance dispersal: a new perspective

Since nobody has witnessed the arrival of early plant colonists on isolated islands, the actual long‐distance dispersal (hereafter LDD) has historically been a matter of speculation. In the present study, we offer a new approach that evaluates whether particular syndromes for LDD (i.e. the set of traits related to diaspore dispersal by animals, wind and sea currents) have been favourable in the natural colonization of the Galápagos Islands by plants. Dispersal syndromes of the 251 native genera (509 angiosperm species) presently acknowledged as native were carefully studied, combining data from floristic lists of the Galápagos Islands, diaspore traits, characteristics of continental relatives and our own observations. We used these genera (and occasionally infrageneric groups) as the working units to infer the number of introductions and colonists. A final number of native plants was inferred and analysed after correcting by pollen records of six species from six genera previously considered exotic (palaeobotanical correction). The number of early colonists was also corrected by incorporating information from the few (n= 12) phylogenetic studies of genera from both the Galápagos Islands and the Americas (phylogenetic correction). A total of 372 colonization events were inferred for the native flora using the latest check‐list. The proportions of native colonists grouped into five categories were: endozoochory 16.4%, epizoochory 15.7%, hydrochory 18.6%, anemochory 13.3%, and unassisted diaspores 36.0%. These figures did not vary significantly on analysing only the 99 genera that include endemic species in order to rule out any human‐mediated introductions. Irrespective of the roles of the different agents involved in LDD, diaspores with no special syndrome for LDD (unassisted diapores), such as many dry fruits, have been successful in reaching and colonizing the Galápagos archipelago. This finding leads us to suggest that unpredictable and so far unknown LDD mechanisms should be further considered in the theory of island biogeography.     

New 1,2,3,4-tetrahydro-1-aza-anthraquinones and 2-aminoalkyl compounds from norlapachol with molluscicidal activity

New nitrogen derivatives from norlapachol, including four new diastereomeric 1,2,3,4-tetrahydro-1-aza-anthraquinones obtained from the Prins cyclization on suitable aminoacetaldehyde dimethylacetal derivatives with formic acid, were found to exhibit molluscicidal activity against Biomphalaria glabrata. These derivatives showed low to medium LC(50) values, similar to those reported previously for the homologous series of nitrogen derivatives of lapachol. The toxicity profile against Artemia salina was also determined for all compounds.     

Preparing to Grasp Emotionally Laden Stimuli

Background

Contemporary theories of motor control propose that motor planning involves the prediction of the consequences of actions. These predictions include the associated costs as well as the rewarding nature of movements’ outcomes. Within the estimation of these costs and rewards would lie the valence, that is, the pleasantness or unpleasantness of a given stimulus with which one is about to interact. The aim of this study was to test if motor preparation encompasses valence.

Methodology/Principal Findings

The readiness potential, an electrophysiological marker of motor preparation, was recorded before the grasping of pleasant, neutral and unpleasant stimuli. Items used were balanced in weight and placed inside transparent cylinders to prompt a similar grip among trials. Compared with neutral stimuli, the grasping of pleasant stimuli was preceded by a readiness potential of lower amplitude, whereas that of unpleasant stimuli was associated with a readiness potential of higher amplitude.

Conclusions/Significance

We show for the first time that the sensorimotor cortex activity preceding the grasping of a stimulus is affected by its valence. Smaller readiness potential amplitudes found for pleasant stimuli could imply in the recruitment of pre-set motor repertoires, whereas higher amplitudes found for unpleasant stimuli would emerge from a discrepancy between the required action and their aversiveness. Our results indicate that the prediction of action outcomes encompasses an estimate of the valence of a stimulus with which one is about to interact.     

Correlation of serotype-specific dengue virus infection with clinical manifestations

Background

Disease caused by the dengue virus (DENV) is a significant cause of morbidity throughout the world. Although prior research has focused on the association of specific DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) with the development of severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, relatively little work has correlated other clinical manifestations with a particular DENV serotype. The goal of this study was to estimate and compare the prevalence of non-hemorrhagic clinical manifestations of DENV infection by serotype.

Methodology and Principal Findings

Between the years 2005–2010, individuals with febrile disease from Peru, Bolivia, Ecuador, and Paraguay were enrolled in an outpatient passive surveillance study. Detailed information regarding clinical signs and symptoms, as well as demographic information, was collected. DENV infection was confirmed in patient sera with polyclonal antibodies in a culture-based immunofluorescence assay, and the infecting serotype was determined by serotype-specific monoclonal antibodies. Differences in the prevalence of individual and organ-system manifestations were compared across DENV serotypes. One thousand seven hundred and sixteen individuals were identified as being infected with DENV-1 (39.8%), DENV-2 (4.3%), DENV-3 (41.5%), or DENV-4 (14.4%). When all four DENV serotypes were compared with each other, individuals infected with DENV-3 had a higher prevalence of musculoskeletal and gastrointestinal manifestations, and individuals infected with DENV-4 had a higher prevalence of respiratory and cutaneous manifestations.

Conclusions/Significance

Specific clinical manifestations, as well as groups of clinical manifestations, are often overrepresented by an individual DENV serotype.     

Evidence for multiple hybrid groups in Trypanosoma cruzi

A role for parasite genetic variability in the spectrum of Chagas disease is emerging but not yet evident, in part due to an incomplete understanding of the population structure of Trypanosoma cruzi. To investigate further the observed genotypic variation at the sequence and chromosomal levels in strains of standard and field-isolated T. cruzi we have undertaken a comparative analysis of 10 regions of the genome from two isolates representing T. cruzi I (Dm28c and Silvio X10) and two from T. cruzi II (CL Brener and Esmeraldo). Amplified regions contained intergenic (non-coding) sequences from tandemly repeated genes. Multiple nucleotide polymorphisms correlated with the T. cruzi I/T. cruzi II classification. Two intergenic regions had useful polymorphisms for the design of classification probes to test on genomic DNA from other known isolates. Two adjacent nucleotide polymorphisms in HSP 60 correlated with the T. cruzi I and T. cruzi II distinction. 1F8 nucleotide polymorphisms revealed multiple subdivisions of T. cruzi II: subgroups IIa and IIc displayed the T. cruzi I pattern; subgroups IId and IIe possessed both the I and II patterns. Furthermore, isolates from subgroups IId and IIe contained the 1F8 polymorphic markers on different chromosome bands supporting a genetic exchange event that resulted in chromosomes V and IX of T. cruzi strain CL Brener. Based on these analyses, T. cruzi I and subgroup IIb appear to be pure lines, while subgroups IIa/IIc and IId/IIe are hybrid lines. These data demonstrate for the first time that IIa/IIc are hybrid, consistent with the hypothesis that genetic recombination has occurred more than once within the T. cruzi lines.     

MHC allele-specific binding of a malaria peptide makes it become promiscuous on fitting a glycine residue into pocket 6

Peptide 1585 (EVLYLKPLAGVYRSLKKQLE) has a highly conserved amino-acid sequence located in the Plasmodium falciparum main merozoite surface protein (MSP-1) C-terminal region, required for merozoite entry into human erythrocytes and therefore represents a vaccine candidate for P. falciparum malaria. Original sequence-specific binding to five HLA DRB1* alleles (0101, 0102, 0401, 0701, and 1101) revealed this peptide's specific HLA DRB1*0102 allele binding. This peptide's allele-specific binding to HLA DRB1*0102 took on broader specificity for the DRB1*0101, -0401, and -1101 alleles when lysine was replaced by glycine in position 17 (peptide 5198: EVLYLKPLAGVYRSLKG(17)QLE). Binding of the identified G(10)VYRSLKGQLE(20) C-terminal register to these alleles suggests that peptide promiscuous binding relied on fitting Y(12), L(15), and G(17) into P-1, P-4, and P-6, respectively. The implications of the findings and the future of this synthetic vaccine candidate are discussed.     

Stromal cell-derived receptor 2 and cytochrome b561 are functional ferric reductases

Iron has a variety of functions in cellular organisms ranging from electron transport and DNA synthesis to adenosine triphosphate (ATP) and neurotransmitter synthesis. Failure to regulate the homeostasis of iron can lead to cognition and demyelination disorders when iron levels are deficient, and to neurodegenerative disorders when iron is in excess. In this study we show that three members of the b561 family of predicted ferric reductases, namely mouse cytochrome b561 and mouse and fly stromal cell-derived receptor 2 (SDR2), have ferric reductase activity. Given that a fourth member, duodenal cytochrome b (Dcytb), has previously been shown to be a ferric reductase, it is likely that all remaining members of this family also exhibit this activity. Furthermore, we show that the rat sdr2 message is predominantly expressed in the liver and kidney, with low expression in the duodenum. In hypotransferrinaemic (hpx) mice, sdr2 expression in the liver and kidney is reduced, suggesting that it may be regulated by iron. Moreover, we demonstrate the presence of mouse sdr2 in the choroid plexus and in the ependymal cells lining the four ventricles, through in situ hybridization analysis.     

Chloroplast and nuclear evidence for multiple origins of polyploids and diploids of Hedera (Araliaceae) in the Mediterranean basin

Chloroplast (trnT-L) and nuclear rDNA (ITS) sequence analyses of the Araliaceae provide strong molecular evidence for the monophyly of the genus Hedera. Phylogenetic reconstructions suggest multiple origins and an active polyploidization process not only in the formation of tetraploids (2n = 96), hexaploids (2n = 144), and octoploids (2n = 192), but also of diploids (2n = 48). A high basic chromosome number of x = 24, extensive polyphyly in widespread diploids, and terminal placement of Hedera in phylogenies of the Araliaceae reveal that extant diploid taxa may be, in fact, assemblages of ancestral polyploids from plants of n = 12. Four major lineages containing four types of chloroplast (chlorotypes I, II, III, and IV), which are defined by different trnT-L nucleotide substitutions and two large insertions (50- and 30-bp), provide evidence for evolutionary processes and historical biogeography in Hedera. We propose a scenario where an initial colonization in the Mediterranean basin by Asian ancestors (carrying the ancestral Araliaceae chlorotype I) is followed by differentiation into the four chlorotypes of the Mediterranean region, and then recolonization of Asia and northern Europe only by chlorotype III. The Macaronesian taxa (Hedera azorica, Hedera maderensis ssp. maderensis, and Hedera canariensis) appear to have originated from a single-colonization event to each archipelago with no further contact either with continental or insular species.