THE IMPORTANCE OF MOSQUITO BEHAVIOURAL ADAPTATIONS TO MALARIA CONTROL IN AFRICA

Over the past decade the use of long‐lasting insecticidal nets (LLINs), in combination with improved drug therapies, indoor residual spraying (IRS), and better health infrastructure, has helped reduce malaria in many African countries for the first time in a generation. However, insecticide resistance in the vector is an evolving threat to these gains. We review emerging and historical data on behavioral resistance in response to LLINs and IRS. Overall the current literature suggests behavioral and species changes may be emerging, but the data are sparse and, at times unconvincing. However, preliminary modeling has demonstrated that behavioral resistance could have significant impacts on the effectiveness of malaria control. We propose seven recommendations to improve understanding of resistance in malaria vectors. Determining the public health impact of physiological and behavioral insecticide resistance is an urgent priority if we are to maintain the significant gains made in reducing malaria morbidity and mortality.     

Hereditary Angioedema Attacks Resolve Faster and Are Shorter after Early Icatibant Treatment

Background

Attacks of hereditary angioedema (HAE) are unpredictable and, if affecting the upper airway, can be lethal. Icatibant is used for physician- or patient self-administered symptomatic treatment of HAE attacks in adults. Its mode of action includes disruption of the bradykinin pathway via blockade of the bradykinin B₂ receptor. Early treatment is believed to shorten attack duration and prevent severe outcomes; however, evidence to support these benefits is lacking.

Objective

To examine the impact of timing of icatibant administration on the duration and resolution of HAE type I and II attacks.

Methods

The Icatibant Outcome Survey is an international, prospective, observational study for patients treated with icatibant. Data on timings and outcomes of icatibant treatment for HAE attacks were collected between July 2009–February 2012. A mixed-model of repeated measures was performed for 426 attacks in 136 HAE type I and II patients.

Results

Attack duration was significantly shorter in patients treated <1 hour of attack onset compared with those treated ≥1 hour (6.1 hours versus 16.8 hours [p<0.001]). Similar significant effects were observed for <2 hours versus ≥2 hours (7.2 hours versus 20.2 hours [p<0.001]) and <5 hours versus ≥5 hours (8.0 hours versus 23.5 hours [p<0.001]). Treatment within 1 hour of attack onset also significantly reduced time to attack resolution (5.8 hours versus 8.8 hours [p<0.05]). Self-administrators were more likely to treat early and experience shorter attacks than those treated by a healthcare professional.

Conclusion

Early blockade of the bradykinin B₂ receptor with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution.     

Long-term effects of timber harvesting on hemicellulolytic microbial populations in coniferous forest soils

Forest ecosystems need to be sustainably managed, as they are major reservoirs of biodiversity, provide important economic resources and modulate global climate. We have a poor knowledge of populations responsible for key biomass degradation processes in forest soils and the effects of forest harvesting on these populations. Here, we investigated the effects of three timber-harvesting methods, varying in the degree of organic matter removal, on putatively hemicellulolytic bacterial and fungal populations 10 or more years after harvesting and replanting. We used stable-isotope probing to identify populations that incorporated ¹³C from labeled hemicellulose, analyzing ¹³C-enriched phospholipid fatty acids, bacterial 16 S rRNA genes and fungal ITS regions. In soil microcosms, we identified 104 bacterial and 52 fungal hemicellulolytic operational taxonomic units (OTUs). Several of these OTUs are affiliated with taxa not previously reported to degrade hemicellulose, including the bacterial genera Methylibium, Pelomonas and Rhodoferax, and the fungal genera Cladosporium, Pseudeurotiaceae, Capronia, Xenopolyscytalum and Venturia. The effect of harvesting on hemicellulolytic populations was evaluated based on in situ bacterial and fungal OTUs. Harvesting treatments had significant but modest long-term effects on relative abundances of hemicellulolytic populations, which differed in strength between two ecozones and between soil layers. For soils incubated in microcosms, prior harvesting treatments did not affect the rate of incorporation of hemicellulose carbon into microbial biomass. In six ecozones across North America, distributions of the bacterial hemicellulolytic OTUs were similar, whereas distributions of fungal ones differed. Our work demonstrates that diverse taxa in soil are hemicellulolytic, many of which are differentially affected by the impact of harvesting on environmental conditions. However, the hemicellulolytic capacity of soil communities appears resilient.     

Cyto‐nuclear discordance suggests complex evolutionary history in the cave‐dwelling salamander,Eurycea lucifuga

Our understanding of the evolutionary history and ecology of cave‐associated species has been driven historically by studies of morphologically adapted cave‐restricted species. Our understanding of the evolutionary history and ecology of nonrestricted cave species, troglophiles, is limited to a few studies, which present differing accounts of troglophiles’ relationship with the cave habitat, and its impact on population dynamics. Here, we used phylogenetics, demographic statistics, and population genetic methods to study lineage divergence, dates of divergence, and population structure in the Cave Salamander, Eurycea lucifuga, across its range. In order to perform these analyses, we sampled 233 individuals from 49 populations, using sequence data from three gene loci as well as genotyping data from 19 newly designed microsatellite markers. We find, as in many other species studied in a phylogeographic context, discordance between patterns inferred from mitochondrial relationships and those inferred by nuclear markers indicating a complicated evolutionary history in this species. Our results suggest Pleistocene‐based divergence among three main lineages within E. lucifuga corresponding to the western, central, and eastern regions of the range, similar to patterns seen in species separated in multiple refugia during climatic shifts. The conflict between mitochondrial and nuclear patterns is consistent with what we would expect from secondary contact between regional populations following expansion from multiple refugia.     

Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via ¹H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects.     

Hydrogen isotopic differences between C3 and C4 land plant lipids: consequences of compartmentation in C4 photosynthetic chemistry and C3 photorespiration

The ²H/¹H ratio of carbon‐bound H in biolipids holds potential for probing plant lipid biosynthesis and metabolism. The biochemical mechanism underlying the isotopic differences between lipids from C₃ and C₄ plants is still poorly understood. GC‐pyrolysis‐IRMS (gas chromatography‐pyrolysis‐isotope ratio mass spectrometry) measurement of the ²H/¹H ratio of leaf lipids from controlled and field grown plants indicates that the biochemical isotopic fractionation (ε²H_{lipid_biochem}) differed between C₃ and C₄ plants in a pathway‐dependent manner: ε²H_C4 > ε²H_C3 for the acetogenic pathway, ε²H_C4 < ε²H_C3 for the mevalonic acid pathway and the 1‐deoxy‐D‐xylulose 5‐phosphate pathway across all species examined. It is proposed that compartmentation of photosynthetic CO₂ fixation into C₄ mesophyll (M) and bundle sheath (BS) cells and suppression of photorespiration in C₄ M and BS cells both result in C₄ M chloroplastic pyruvate – the precursor for acetogenic pathway – being more depleted in ²H relative to pyruvate in C₃ cells. In addition, compartmentation in C₄ plants also results in (i) the transferable H of NADPH being enriched in ²H in C₄ M chloroplasts compared with that in C₃ chloroplasts for the 1‐deoxy‐D‐xylulose 5‐phosphate pathway pathway and (ii) pyruvate relatively ²H‐enriched being used for the mevalonic acid pathway in the cytosol of BS cells in comparison with that in C₃ cells.     

Leaf vein fraction influences the Péclet effect and 18O enrichment in leaf water

The process of evaporation results in the fractionation of water isotopes such that the lighter ¹⁶O isotope preferentially escapes the gas phase leaving the heavier ¹⁸O isotope to accumulate at the sites of evaporation. This applies to transpiration from a leaf with the degree of fractionation dependent on a number of environmental and physiological factors that are well understood. Nevertheless, the ¹⁸O enrichment of bulk leaf water is often less than that predicted for the sites of evaporation. The advection of less enriched water in the transpiration stream has been suggested to limit the back diffusion of enriched evaporative site water (Péclet effect); however, evidence for this effect has been varied. In sampling across a range of species with different vein densities and saturated water contents, we demonstrate the importance of accounting for the relative ‘pool’ sizes of the vascular and mesophyll water for the interpretation of a Péclet effect. Further, we provide strong evidence for a Péclet signal within the xylem that if unaccounted for can lead to confounding of the estimated enrichment within the mesophyll water. This has important implications for understanding variation in the effective path length of the mesophyll and hence potentially the δ¹⁸O of organic matter.