Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria.Methodology/Principal findingsThis study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed.Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test’s sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%–100.0%; capillary 93.8%–100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%–99.1%) and 97.8% on capillary (95% CI 97.0%–98.5%). At the 70% threshold, the test’s sensitivity was 96.9% on venous specimens (95% CI 83.8%–99.9%) and 94.3% on capillary (95% CI 80.8%–99.3%). Specificity was 96.5% (95% CI 95.0%–97.6%) and 92.3% (95% CI 90.3%–94.0%) on venous and capillary specimens, respectively.Conclusion/SignificanceThe STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil.Trial registrationThis study was registered with ClinicalTrials.gov (identifier: {"type":"clinical-trial","attrs":{"text":"NCT04033640","term_id":"NCT04033640"}}NCT04033640).     

Benefits,costs and reactivity of inducible defences: an experimental test with rotifers

1. A key aspect of the ecology and evolution of adaptive prey responses to predator risk is the timing by which the former develop a defensive trait in response to inducing signals released by the latter. This property, called reactivity, has been shown to affect population stability and persistence. 2. Theoretically, the minimal predator density required by prey to exhibit induced defences is expected to increase with the effectiveness of the defence and decrease with its cost. Likewise, the time required for the prey population to exhibit an induced defence is expected to increase together with cost. 3. The freshwater rotifers Brachionus calyciflorus and B. havanaensis and their predator Asplanchna brightwelli were used to test the hypothesis that prey species exhibiting defences that offer a larger fitness benefit and lower fitness cost are more reactive to predator signals, in terms of requiring shorter exposure time and lower signal concentration to trigger a morphological defence reaction. 4. Our results showed that both prey species exhibited costly and effective defences after induction by predator infochemicals. Faster reactions were observed at higher levels of predator cues. Nevertheless, the observed relationship between reactivity and benefit/cost of defences did not agree with our expectations. 5. To our knowledge, this is the first study in which the timing of induction of morphological defences is experimentally assessed over a gradient of risk signals. We propose new research directions to disentangle the mechanisms and project the consequences of prey decisions at the morphological level.     

The effect of seasonal variation in abiotic factors on fish community structure in temporary and permanent pools in a tropical wetland

1. Fish community structure depends on biotic interactions and abiotic variables. Abiotic variables appear to gain importance in highly variable freshwater systems, such as tropical wetlands where a marked seasonal hydroperiod (dry and wet seasons) modifies water quality and quantity, differentially affecting fish survival and, consequently, modifying species richness and abundance. 2. We evaluated the relationship between abiotic variables and fish community structure in variable (temporary) and stable (permanent) pools that were interconnected in a tropical wetland with marked annual dry and wet seasons. 3. All fish species were able to occupy any of the studied pools, but our results showed distinctive fish community structures in permanent and temporary pools. Community structure was related to temperature, depth, pH and macrophyte coverage. Total fish abundance in the wetland was negatively related to water depth and positively related to macrophyte coverage. 4. Null models of co‐occurrence indicated a non‐random pattern at the wetland scale and a random pattern within groups of pools with similar characteristics, suggesting that fish communities are structured according to habitat features. We conclude that seasonal abiotic variation and habitat characteristics in this highly variable pristine wetland play major roles in structuring fish communities.     

C3G down-regulates p38 MAPK activity in response to stress by Rap-1 independent mechanisms: Involvement in cell death

We present here evidences supporting a negative regulation of p38α MAPK activity by C3G in MEFs triggered by stress, which can mediate cell death or survival depending on the stimuli. Upon serum deprivation, C3G induces survival through inhibition of p38α activation, which mediates apoptosis. In contrast, in response to H₂O₂, C3G behaves as a pro-apoptotic molecule, as its knock-down or knock-out enhances survival through up-regulation of p38α activation, which plays an anti-apoptotic role under these conditions. Moreover, the C3G target, Rap-1, plays an opposite role, also through regulation of p38α MAPK activity.Our data also suggest that changes in the protein levels of some members of the Bcl-2 family could account for the regulation of cell death by C3G and/or Rap-1 through p38α MAPK. Bim/Bcl-x_L ratio appears to be important in the regulation of cell survival, both upon serum deprivation and in response to H₂O₂. In addition, the increase in BNIP-3 levels induced by C3G knock-down in wt cells treated with H₂O₂ might play a role preventing cell death.Therefore, we can conclude that C3G is a negative regulator of p38α MAPK in MEFs, while Rap-1 is a positive regulator, but both, through the regulation of p38α activity, can promote cell survival or cell death depending on the stimuli.     

Investigator activities reduce nest predation in blackbirds Turdus merula

The effect of investigator perturbance has been traditionally considered detrimental for avian nesting success in terms of enhanced nest predation. This conclusion was however based on a taxonomically biased group of species and, thus, the study of that effect in additional species was essential for reaching a more firm conclusion. Furthermore, although it has been suggested that the effect of nest visiting could also depend on nest predator community, no study has so far tested this hypothesis yet. Trying to detect possible influence of nest‐visiting rates and predator community on nesting success we visited European blackbird Turdus merula nests at two different experimental rates in two populations that considerably differ in the composition of their nest predator communities and natural nest predation rates. Contrary to the traditional ideas, our results not only show that investigator disturbance significantly reduces nest predation, but also that this reduction is maintained in both populations despite the difference in the community of nest predators. We discuss these findings and suggest that predators, especially mammals, might avoid places disturbed by investigators.     

A morphometrics‐based phylogeny of the temperate Gondwanan mite harvestmen (Opiliones,Cyphophthalmi, Pettalidae)

A phylogenetic estimation of the temperate Gondwanan mite harvestman family Pettalidae (Arachnida, Opiliones, Cyphophthalmi) was conducted using 143 morphological variables (59 raw and 84 scaled measurements) from 37 ingroup and 15 outgroup terminals. We used custom algorithms to do pairwise comparisons between characters and identify sets of dependent characters, which were collapsed using principal components analysis. We analysed the resulting data without discretization under the parsimony criterion. Monophyly or paraphyly of most groups suspected from previous molecular and morphological phylogenetic studies were recovered. Trees were optimized for monophyly of 20 different focus clades by varying character phylogenetic independence. This yielded a final tree with monophyly of 15 out of 20 focus clades, including the South African pettalids, which contains the troglomorphic species Speleosiro argasiformis Lawrence, 1931. Two of the remaining five clades were found paraphyletic, with the genera Aoraki, Rakaia, and Siro always being found polyphyeletic.     

Identification of HAVCR1 gene haplotypes associated with mRNA expression levels and susceptibility to autoimmune diseases

Human HAVCR1 gene maps on 5q33.2, a region linked with susceptibility to allergic and autoimmune diseases. The aims of the present study were to define the haplotypes of HAVCR1 gene taking into account both HapMap Project SNP haplotypes and exon 4 variants, to investigate a possible relationship between these haplotypes and mRNA expression levels, and to assess whether HAVCR1 gene is involved in susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Genotyping of three ins/del variants in the exon 4 was performed by fragment length analysis. Five tag SNPs genotypes and mRNA levels were determined using TaqMan assays. We defined four major haplotypes in our population: the two major haplotypes (named haplotypes A and B) bear both the 5383_5397del variant and the two most common SNP sets found in the CEU population. Quantification analysis revealed that genotype B/B had the highest median of mRNA expression levels (vs. BX + XX, p < 0.0001). Additionally, frequency of the genotype BB was significantly higher in RA patients than in controls (12.3 vs. 5.9% in controls, p = 0.0046, p _c = 0.014, OR = 2.23, 95% CI 1.23–4.10). Our results support a relationship between HAVCR1 haplotypes and mRNA expression levels, and suggest an association of this gene with autoimmune diseases.