Environmental heterogeneity enhances clonal interference

Clonal interference (CI) is a phenomenon that may be important in several asexual microbes. It occurs when population sizes are large and mutation rates to new beneficial alleles are of significant magnitude. Here we explore the role of gene flow and spatial heterogeneity in selection strength in the adaptation of asexuals. We consider a subdivided population of individuals that are adapting, through new beneficial mutations, and that migrate between different patches. The fitness effect of each mutation depends on the patch and all mutations considered are assumed to be unconditionally beneficial. We find that spatial variation in selection pressure affects the rate of adaptive evolution and its qualitative effects depend on the level of gene flow. In particular, we find that both low migration and high levels of heterogeneity lead to enhanced CI. In contrast, for high levels of migration the rate of fixation of adaptive mutations is higher when environmental heterogeneity is present. In addition, we observe that the level of fitness variation is higher and simultaneous fixation of multiple mutations tends to occur in the regime of low migration rates and high heterogeneity.     

Oxidative stress plays a permissive role in α2-adrenoceptor-mediated events in immortalized SHR proximal tubular epithelial cells

Objective To test the hypothesis that the identification of mutation in the carboxypeptidase E (CPE) gene which leads to marked hyperproinsulinaemia is consistent with a possible role for mutations in CPE in the development of coronary heart disease. Methods The study subjects consisted of 51 consecutive patients (34 males and 17 females) who will undergo coronary angiography for suspected or known coronary atherosclerosis. Coronary heart disease (CHD) was defined as having a luminal diameter stenosis ≥50% in at least one of three major coronary arteries by coronary angiography or based on the Rose Questionnaire. The insulin and proinsulin level were measured using highly sensitive two-site sandwich ELISA methods. Screening for mutations of the eight exons of the CPE gene was performed by polymerase chain reaction followed by bidirectional sequencing. Results We scanned eight exons and exon–intron junctional region. Overall, we found 12 distinct variants in the intron region and three variants in the exon region. Among the 15 variants, 10 mutations were rare. The further explored study reveal that the above five non-rare variants would not affect the level of glucose, insulin, and proinsulin. However, the results suggest that the prevalence of the coronary heart disease was significant difference between the wild type group and mutant type group according to the A4545G (P = 0.020). The results from the logistic regression reveal that the subjects with the CPE mutation of A4545G, the odds ratio for the coronary heart disease was 0.196 (95% CI: 0.046 to 0.830, P = 0.027). Conclusions In the present study, the mutation of CPE gene would not affect the level of glucose, insulin, and proinsulin. The hypothesis of a possible role for mutations in CPE in the development of coronary heart disease needs further study.     

Inhibition and uncoupling of photosynthetic electron transport by diterpene lactone amide derivatives

Nine diterpene lactone amide derivatives 1-9 were synthesized from 6-oxovouacapan-7beta,17beta-lactone, which was obtained from 6alpha,7beta-dihydroxyvouacapan-17beta-oic acid isolated from Pterodon polygalaeflorus Benth., and tested for their activity on photosynthetic electron transport. Amide derivatives 3-5 behaved as electron transport chain inhibitors; they inhibited the photophosphorylation and uncoupled non-cyclic electron transport from water to methylviologen (MV). Furthermore, 4 and 5 enhanced the basal electron rate acting as uncouplers. Compound 6 behaved as an uncoupler; it enhanced the light-activated Mg2+-ATPase and basal electron flow, without affecting the uncoupled non-cyclic electron transport. Compounds 1-2 and 7-9 were less active or inactive. Compounds 3-5 did not affect photosystem I (PSI); they inhibited photosystem II (PSII) from water to 2,6-dichlorophenol indophenol (DCPIP). Compound 4 inhibited PSII from water to silicomolybdate (SiMo), but it had no effect on the reaction from diphenylcarbazide (DPC) to DCPIP indicating that its inhibition site was at the water splitting enzyme complex (OEC). Compounds 3 and 5 inhibited PSII from water to DCPIP without any effect from water to SiMo, therefore they inhibited the acceptor site of PSII. Chlorophyll a fluorescence kinetics confirmed the behaviour of 3-5.     

The role of osmiophilic bodies and Pfg377 expression in female gametocyte emergence and mosquito infectivity in the human malaria parasite Plasmodium falciparum

Osmiophilic bodies are membrane-bound vesicles, found predominantly in Plasmodium female gametocytes, that become progressively more abundant as the gametocyte reaches full maturity. These vesicles lie beneath the subpellicular membrane of the gametocyte, and the release of their contents into the parasitophorous vacuole has been postulated to aid in the escape of gametocytes from the erythrocyte after ingestion by the mosquito. Currently, the only protein known to be associated with osmiophilic bodies in Plasmodium falciparum is Pfg377, a gametocyte-specific protein expressed at the onset of osmiophilic body development. Here we show by targeted gene disruption that Pfg377 plays a fundamental role in the formation of these organelles, and that female gametocytes lacking the full complement of osmiophilic bodies are significantly less efficient both in vitro and in vivo in their emergence from the erythrocytes upon induction of gametogenesis, a process whose timing is critical for fertilization with the short-lived male gamete. This reduced efficiency of emergence explains the significant defect in oocyst formation in mosquitoes fed blood meals containing Pfg377-negative gametocytes, resulting in an almost complete blockade of infection.     

Thermodynamic and kinetic properties of amino-terminal and S4-S5 loop HERG channel mutants under steady-state conditions

Gating kinetics and underlying thermodynamic properties of human ether-a-go-go-related gene (HERG) K⁺ channels expressed in Xenopus oocytes were studied using protocols able to yield true steady-state kinetic parameters. Channel mutants lacking the initial 16 residues of the amino terminus before the conserved eag/PAS region showed significant positive shifts in activation voltage dependence associated with a reduction of z_g values and a less negative ΔG_o, indicating a deletion-induced displacement of the equilibrium toward the closed state. Conversely, a negative shift and an increased ΔG_o, indicative of closed-state destabilization, were observed in channels lacking the amino-terminal proximal domain. Furthermore, accelerated activation and deactivation kinetics were observed in these constructs when differences in driving force were considered, suggesting that the presence of distal and proximal amino-terminal segments contributes in wild-type channels to specific chemical interactions that raise the energy barrier for activation. Steady-state characteristics of some single point mutants in the intracellular loop linking S4 and S5 helices revealed a striking parallelism between the effects of these mutations and those of the amino-terminal modifications. Our data indicate that in addition to the recognized influence of the initial amino-terminus region on HERG deactivation, this cytoplasmic region also affects activation behavior. The data also suggest that not only a slow movement of the voltage sensor itself but also delaying its functional coupling to the activation gate by some cytoplasmic structures possibly acting on the S4-S5 loop may contribute to the atypically slow gating of HERG.     

Plant Conservation in the Caribbean Island Biodiversity Hotspot

While the Caribbean is a recognized “biodiversity hotspot”, plant conservation has not received adequate attention; particularly, given the high levels of endemism in many plant groups. Besides establishing protected areas, there needs to be a sustained effort to study the taxonomy, systematics and ecology of the flora. Recent phylogenetic studies have shown high levels of endemism and conservation studies indicate a large propotion of the flora is threatened with extinction. Eight recommendations are given for plant conservation in the region.     

Distinct modulation of the endothelin-1 pathway in iNOS-/- and eNOS-/- mice

We hypothesized that constitutive endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) have opposite effects on the regulation of endothelin and its receptors. We therefore sought to determine whether deletions of iNOS or eNOS genes in mice modulate pressor responses to endothelin and the expression of ETA and ETB receptors in a similar fashion. Despite unchanged baseline hemodynamic parameters, anesthetized iNOS-/- mice displayed reduced pressor responses to endothelin-1, but not to that of IRL-1620, a selective ETB agonist. Protein content of cardiac ETA receptors was reduced in iNOS-/- mice compared with wild-type mice, but that of ETB receptors was unchanged. Anesthetized eNOS-/- mice presented a hypertensive state, accompanied by an enhanced pressor response to intravenous endothelin-1, whereas the pressor response to IRL-1620 was reduced. Protein levels were also found to be increased for ETA receptors, but reduced for ETB receptors, in cardiac tissues of eNOS-/- mice. In conscious animals, both strains responded equally to the hypotensive effect of an ETA antagonist, ABT-627, whereas orally administered A-192621, an ETB antagonist, increased MAP to a greater extent in eNOS-/- than in wild-type mice. Furthermore, significant levels of immunoreactive endothelin were found in mesenteric arteries in eNOS-/- but not in iNOS-/- or wild-type congeners. Our study shows that repression of iNOS or eNOS has differential effects on endothelin-1 and its receptors. We have also shown that the heart is the main organ in which iNOS or eNOS repression induces important alterations in protein content of endothelin receptors in adult mice.     

Sexual dimorphism in the andromonoecious Euphorbia nicaeensis: effects of gender and inflorescence development

BACKGROUND AND AIMS: In andromonoecious taxa with separate floral types along the inflorescence, architectural or plastic effects can simulate floral sexual dimorphism. Both the primary and secondary sexual characteristics of the cyathia of the protogynous andromonoecious species Euphorbia nicaeensis were analysed according to their sex and arrangement on the inflorescence. METHODS: The production of male and hermaphrodite cyathia at each inflorescence level was surveyed in two natural populations. The longevity, size, pollen production and viability, and nectar secretion of both types of cyathia were checked between inflorescence levels and between sexes at the only level at which they occur together. This sampling method makes it possible to know whether differences between cyathia types are based on sex or are attributable to inflorescence development. KEY RESULTS: Male cyathia were produced predominantly at the first and second inflorescence levels, whereas at levels 3-5, the cyathia were almost exclusively hermaphrodite. Viable pollen production by male cyathia at the second inflorescence level was higher than that of hermaphrodite cyathia at the third level but, when males and hermaphrodites at the same level were compared, their pollen production was similar. Male and hermaphrodite cyathia were similar in size, irrespective of the inflorescence level, although the exclusively hermaphrodite cyathia of the last level were smaller. Both cyathium types produced similar amounts of sugar. However, male cyathia produced nectar during their whole lifespans, whereas hermaphrodites produced it exclusively during their male phase. Moreover, the nectary activity of male cyathia started earlier in the day than that of hermaphrodites. CONCLUSIONS: An apparent floral dimorphism exists in the primary sexual characteristics of Euphorbia nicaeensis because differences in pollen production between cyathium types are due to theirs positions. Similarly, differences affecting most secondary sexual characteristics are only apparent between the two cyathium types. However, E. nicaeensis shows a true but slight floral dimorphism in some of the secondary sex characters related to nectar secretion. The lack of nectar production by the female phase of the hermaphrodite cyathia of E. nicaeensis indicates that this is a deceit-pollinated species.     

Stabilization studies of Fomes sclerodermeus laccases

Stability of laccase isoenzymes from a crude extract obtained from Fomes sclerodermeus grown on wheat bran medium was studied. The variables assessed were temperature, pH and additives. As revealed by PAGE, three bands of laccase, each with different thermal inactivation pattern, were detected in the crude extract: after 6h at 50 degrees C and pH 8, Lc2 was the most resistant, while the Lc1 and Lc3 bands were almost completely inactivated. This pattern of inactivation was observed at all temperatures and pH tested. Laccase activity was more stable in the 5-10 pH range when incubated at 40 and 50 degrees C; at 30 degrees C and 24h the enzyme remained fully active in the 3-11 pH range. The effect of additives (veratryl alcohol, trehalose, glycerol, mannitol, glutaraldehyde, CuSO(4) and 1-HBT) on laccase stability was tested. The stability was enhanced with CuSO(4) (1.25 mM), glycerol (0.2%) and mannitol (1%). The presence of both CuSO(4) and glycerol caused a 3-fold increase in the half-life values.