Antifungal activity of propolis extract against yeasts isolated from onychomycosis lesions

The aim of this study was to determine the in vitro activity of propolis extract against 67 yeasts isolated from onychomycosis in patients attending at the Teaching and Research Laboratory of Clinical Analysis of the State University of Maringá. The method used was an adaptation made from the protocol approved by the National Committee for Clinical Laboratory Standards. The yeasts tested were: Candida parapsilosis 35%, C. tropicalis 23%, C. albicans 13%, and other species 29%. The propolis extract showed excellent performance regarding its antifungal activity: the concentration capable of inhibiting the all of the yeasts was 5 x 10(-2) mg/ml of flavonoids and 2 x 10(-2) mg/ml of flavonoids stimulated their cellular death. Trichosporon sp. were the most sensitive species, showing MIC50 and MIC90 of 1.25 x 10(-2) mg/ml of flavonoids, and C. tropicalis was the most resistant, with CFM50 of 5 x 10(-2) mg/ml of flavonoids and MFC90 of 10 x 10(-2) mg/ml. In view of the fact that propolis is a natural, low cost, nontoxic product with proven antifungal activity, it should be considered as another option in the onychomycosis treatment.     

Xenopus ElrB, but not ElrA, binds RNA as an oligomer: possible role of the linker

We have shown that ElrA and ElrB, Xenopus ELAV homologues, bind the Vg1 mRNA 3'UTR translation element in Xenopus oocytes and implicated ElrB in mediating translational repression during oogenesis. Here we report that, while ElrA and ElrB are 69% identical and both exhibit RNA binding in the nM range, recombinant ElrB, but not ElrA, is able to oligomerise. This oligomerisation is also seen with the endogenous protein. Both RNA binding and oligomerisation require the linker region flanked with two RNA recognition motifs. Our data demonstrate a novel and unique property of ElrB which may be important for its function as a translational regulator.     

Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres

The African trypanosome, Trypanosoma brucei, is a flagellated pathogenic protozoan that branched early from the eukaryotic lineage. Unusually, it uses RNA polymerase I (Pol I) for mono-telomeric expression of variant surface glycoprotein (VSG) genes in bloodstream-form cells. Many other subtelomeric VSG genes are reversibly repressed, but no repressive DNA sequence has been identified in any trypanosomatid. Here, we show that artificially seeded de novo telomeres repress Pol I-dependent gene expression in mammalian bloodstream and insect life-cycle stages of T. brucei. In a telomeric VSG expression site, repression spreads further along the chromosome and this effect is specific to the bloodstream stage. We also show that de novo telomere extension is telomerase dependent and that the rate of extension correlates with the expression level of the adjacent gene. Our results show constitutive telomeric repression in T. brucei and indicate that an enhanced, developmental stage-specific repression mechanism controls antigenic variation.     

Mathematical models and lymphatic filariasis control: endpoints and optimal interventions

The current global initiative to eliminate lymphatic filariasis is a major renewed commitment to reduce or eliminate the burden of one of the major helminth infections from resource-poor communities of the world. Mathematical models of filariasis transmission can serve as an effective tool for guiding the scientific development and management of successful community-level intervention programmes by acting as analytical frameworks for integrating knowledge regarding parasite transmission dynamics with programmatic factors. However, the power of these tools for supporting control interventions will be realized fully only if researchers address the current uncertainties and gaps in data and knowledge of filarial population dynamics and the effectiveness of currently proposed filariasis intervention options.     

Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration

Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB. In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration). Further studies revealed that CS induced internalization of CFTR. Surprisingly, CS-internalized CFTR did not colocalize with lysosomal proteins. Instead, the bulk of CFTR shifted to a detergent-resistant fraction within the cell and colocalized with the intermediate filament vimentin, suggesting that CS induced CFTR movement into an aggresome-like, perinuclear compartment. To test whether airway dehydration could be reversed, we used hypertonic saline (HS) as an osmolyte to rehydrate ASL. HS restored ASL height in CS-exposed, dehydrated airway cultures. Similarly, inhaled HS restored mucus transport and increased clearance in patients with CB. Thus, we propose that CS exposure rapidly impairs CFTR function by internalizing CFTR, leading to ASL dehydration, which promotes mucus stasis and a failure of mucus clearance, leaving smokers at risk for developing CB. Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB.     

Interaction of the conceptus and endometrium to establish pregnancy in mammals: role of interleukin 1β

Implantation and the establishment of pregnancy in mammals involves an intricate interplay of hormones, cytokines, growth factors, proteins, lipids, ions and the extracellular matrix between the uterine epithelium, stroma, immune cells and the conceptus trophectoderm. The divergent nature of implantation in the mouse, human and pig provides not only an interesting contrast in the establishment of pregnancy and early embryonic development but also intriguing similarities with regard to early endometrial-conceptus signaling. An interesting pro-inflammatory cytokine expressed in a number of mammalian species during the period of implantation is interleukin-1β (IL1B). The presence of IL1B might be involved with immunotolerance at the maternal-placental interface and has been proposed as one of the mediators in placental viviparity. The production of IL1B and other proinflammatory cytokines might play a role in establishing pregnancy through modulation of the nuclear factor kappa-B (NFKB) system in a number of species. A model for the regulation of cellular progesterone receptor expression and NFKB activation for endometrial receptivity and conceptus attachment is continuing to evolve and is discussed in the present review.     

Context-dependent decisions among options varying in a single dimension

Contrary to theories of rational choice, adding alternatives to a choice set can change the choices made by both humans and animals. This is usually done by adding an inferior decoy to a choice set of two favoured options that are characterized on two distinct dimensions. We presented wild, free-living rufous hummingbirds (Selasphorus rufus) with choices between two or three options that varied in a single dimension only. The options varied in concentration, in volume or in corolla length. When the options varied in concentration, the addition of a medium option to a choice set of a low and a high concentration caused birds to increase their preference for the high option. However, they decreased their preference for the high concentration option when a low option was added to a choice set of high and medium concentrations. When the options varied only in volume, the addition of a high volume option to a choice set of low and medium options decreased the birds’ preference for the medium option. We saw no effects of adding a third option when the options varied in corolla length alone. Hummingbirds, then, make context-dependent decisions even when the options vary in only a single dimension although which effect occurs seems to depend on the dimension being manipulated. None of the current theories alone adequately explain these results.     

Demographic History of Shorea curtisii (Dipterocarpaceae) Inferred from Chloroplast DNA Sequence Variations

We assessed the variability of chloroplast DNA sequences in populations of the dipterocarp forest tree, Shorea curtisii. This species is widely distributed in hill and coastal hill dipterocarp forests of the Malay Peninsula, whereas isolated populations are found in the coastal hills of north Borneo. Two chloroplast DNA regions (1555 bp of trnH‐psbA‐trnK and 925 bp of trnL‐trnF) were sequenced from 123 individuals collected from six Malay Peninsula and two Bornean populations. There were 15 chloroplast haplotypes derived from 16 polymorphic sites. A haplotype network revealed two distinct haplogroups that correlate with two geographic regions, the Malay Peninsula and Borneo. These two haplogroups differed by a number of mutations, and no haplotypes were shared between populations from the different geographic regions. This suggests an ancient diversification of these haplogroups, and that long‐distance seed dispersal was unlikely to have occurred during the Pleistocene when the Sunda Shelf was a contiguous landmass. Phylogenetic analysis of the haplotypes together with those found in other Shorea species showed that two haplogroups in S. curtisii appear in different positions of the phylogenetic tree. This could be explained by the persistence of ancestral polymorphisms or by ancient chloroplast capture. Low levels of genetic differentiation were found between populations within each geographic region. Signature of a bottleneck followed by demographic expansion was detected in the Malay Peninsula haplogroup. The presence of two distinct evolutionary lineages in the different regions suggests that they should be managed independently to conserve the major sources of genetic diversity in S. curtisii.