Decrease in Ribosomal RNA in Candida albicans Induced by Serum Exposure

Candida albicans is an important polymorphic human pathogen. It can switch from a unicellular yeast form to germinating hypha, which may play a role in making it the successful pathogen it is. This hyphal transformation can be triggered by various extracellular stimuli, the most potent one being serum from any source. We have previously reported that Candida albicans transiently polyadenylates portions of both the large and small subunits of ribosomal RNA, shortly after serum exposure. Northern blots at the same time suggested that serum might induce a decrease in total ribosomal RNA. We have carried out a number of experiments to carefully assess this possibility and now report that serum significantly reduces ribosomal RNA in Candida albicans. Fluorometric measurements, Northern blotting and quantitative RT-PCR, have all confirmed this decrease. Timed experiments show that serum induces this decrease rapidly, as it was seen in as early as five minutes. Cell mass is not decreased as total cellular protein content remains the same and metabolic activity does not appear to slow, as assessed by XTT assay, and by the observation that cells form hyphal structures robustly. Another hyphal inducer, N-acetylglucosamine, also caused RNA decrease, but to a lesser extent. We also observed it in non-germinating yeast, such as Candida glabrata. The reason for this decrease is unknown and overall our data suggests that decrease in rRNA does not play a causal role in hyphal transformation. Rapid and significant decrease in a molecule so central to the yeast’s biology is of some importance, and further studies, such as its effect on protein metabolism, will be required to better understand its purpose.     

Social Capital as a Determinant of Pregnant Mother’s Place of Delivery: Experience from Kongwa District in Central Tanzania

Introduction

Maternal ill health contributes highly to the global burden of diseases in countries South of Sahara including Tanzania. Ensuring that all deliveries take place in health facilities and hence attended by skilled health personnel is one of the strategies advocated by global and national policies, including the Millennium Development Goals (MDGs). However, the number of women delivered by skilled health personnel has remained low in sub Saharan Africa despite of a number of interventions. We sought to determine the role of social capital in facilitating health facility delivery.

Methods

We randomly selected 744 households with children aged less than five years from two randomly selected wards in a rural area in Tanzania. Mothers were enquired about place of delivery of the last child. Social capital was assessed using a modified questionnaire with both structural and cognitive aspects of social capital, administered in face-to-face interviews. Principal Component Analysis (PCA) was used to develop asocial capital index measure. Uni-variate and multivariable regression models were run using STATA 12.

Results

Majority (85.9%) of the mothers reported to have delivered in a health facility during their last birth. Compared to the lowest social capital quintile, delivering in a health facility increased significantly with increase in social capital level: low (Adjusted Odds Ratio (AOR) = 2.9; Confidence Interval (CI): 1.4–6.1, p = 0.004); moderate (AOR = 5.5, CI: 2.3–13.3, p-value<0.001); high (AOR = 4.7; CI: 1.9–11.6, p-value<0.001) and highest (AOR = 5.6, CI: 2.4–13.4, p-value<0.001) and χ²-test for the trend was significant (χ² = 17.21, p<0.001).

Conclusion

Overall, social capital seems to play an important role in enhancing health facility delivery that may lead to improved maternal and child health. Concerted efforts should focus on promoting and supporting effective social capital and in particular cognitive social capital.     

Elicitation of Expert Prior Opinion: Application to the MYPAN Trial in Childhood Polyarteritis Nodosa

Objectives

Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa).

Methods

A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis.

Results

A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available.

Conclusions

We suggest that the methodological template we propose could be applied to trial design for other rare diseases.     

Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans

The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans‐cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone marrow‐derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C. albicans EV. We also evaluated the impact of EV on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering, we identified two populations ranging from 50 to 100 nm and 350 to 850 nm. Two predominant seroreactive proteins (27 kDa and 37 kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C. albicans EV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress, and several other functions. The major lipids detected by thin‐layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, interleukin (IL)‐12, transforming growth factor‐beta (TGF‐β) and IL‐10. Similarly, EV‐treated DC produced IL‐12p40, IL‐10 and tumour necrosis factor‐alpha. In addition, EV treatment induced the up‐regulation of CD86 and major histocompatibility complex class‐II (MHC‐II). Inoculation of G. mellonella larvae with EV followed by challenge with C. albicans reduced the number of recovered viable yeasts in comparison with infected larvae control. Taken together, our results demonstrate that C. albicans EV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.     

Fetal microchimerism in kidney biopsies of lupus nephritis patients may be associated with a beneficial effect

IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users.     

Genomic signatures of geographic isolation and natural selection in coral reef fishes

The drivers of speciation remain among the most controversial topics in evolutionary biology. Initially, Darwin emphasized natural selection as a primary mechanism of speciation, but the architects of the modern synthesis largely abandoned that view in favour of divergence by geographic isolation. The balance between selection and isolation is still at the forefront of the evolutionary debate, especially for the world's tropical oceans where biodiversity is high, but isolating barriers are few. Here, we identify the drivers of speciation in Pacific reef fishes of the genus Acanthurus by comparative genome scans of two peripheral populations that split from a large Central‐West Pacific lineage at roughly the same time. Mitochondrial sequences indicate that populations in the Hawaiian Archipelago and the Marquesas Islands became isolated approximately 0.5 Ma. The Hawaiian lineage is morphologically indistinguishable from the widespread Pacific form, but the Marquesan form is recognized as a distinct species that occupies an unusual tropical ecosystem characterized by upwelling, turbidity, temperature fluctuations, algal blooms and little coral cover. An analysis of 3737 SNPs reveals a strong signal of selection at the Marquesas, with 59 loci under disruptive selection including an opsin Rh2 locus. While both the Hawaiian and Marquesan populations indicate signals of drift, the former shows a weak signal of selection that is comparable with populations in the Central‐West Pacific. This contrast between closely related lineages reveals one population diverging due primarily to geographic isolation and genetic drift, and the other achieving taxonomic species status under the influence of selection.     

Local knowledge and exploitation of the avian fauna by a rural community in the semi-arid zone of northeastern Brazil

Background

The present study examined the exploitation of bird species by the residents of a rural community in the Brazilian semi-arid zone, and their preferences for species with different characteristics.

Methods

The 24 informants were identified using the “snowball” approach, and were interviewed using semi-structured questionnaires and check-sheets for the collection of data on their relationship with the bird species that occur in the region. The characteristics that most attract the attention of the interviewees were the song and the coloration of the plumage of a bird, as well as its body size, which determines its potential as a game species, given that hunting is an important activity in the region.

Results

A total of 98 species representing 32 families (50.7% of the species known to occur in the region) were reported during interviews, being used for meat, pets, and medicinal purposes. Three species were used as zootherapeutics – White-naped Jay was eaten whole as a cure for speech problems, the feathers of Yellow-legged Tinamou were used for snakebite, Smooth-billed Ani was eaten for “chronic cough” and Small-billed Tinamou and Tataupa Tinamou used for locomotion problems. The preference of the informants for characteristics such as birdsong and colorful plumage was a significant determinant of their preference for the species exploited. Birds with cynegetic potential and high use values were also among the most preferred species. Despite the highly significant preferences for certain species, some birds, such as those of the families Trochilidae, Thamnophilidae, and Tyrannidae are hunted randomly, independently of their attributes.

Conclusion

The evidence collected on the criteria applied by local specialists for the exploitation of the bird fauna permitted the identification of the species that suffer hunting pressure, providing guidelines for the development of conservation and management strategies that will guarantee the long-term survival of the populations of these bird species in the region.

     

Quality control by leaf-cutting ants: evidence from communities of endophytic fungi in foraged and rejected vegetation

Leaf-cutting ants of the genera Acromyrmex and Atta forage vegetation for incorporation into their mutualistic fungal gardens. However, the presence of certain endophytic fungi in this predominantly leaf-based material could affect the fungal garden and thus the choice of material by the ants. The present study was conducted to document the endophytic fungal communities occurring in the vegetation being transported by workers of Atta laevigata into their nests and to compare this community structure with that of the vegetative material subsequently rejected from the nests. We found considerable diversity in the fungi isolated. Acremonium, Cylindrocladium, Drechslera, Epicoccum, Fusarium, Trichoderma, Ulocladium and two unidentified morphospecies were significantly more common in rejected compared with foraged material, and some of these genera include mycoparasites, which could represent a threat to the fungal gardens. Conversely, Colletotrichum, Pestalotiopsis, Phomopsis, Xylaria and an unidentified morphospecies were more common in carried compared with rejected material. The possibility that ants have a ‘quality-control’ mechanism based on the presence of antagonistic fungal endophytes is discussed, as is the potential use of these fungi as biocontrol agents against Attini pests.