Population Structure and Evidence for Both Clonality and Recombination among Brazilian Strains of the Subgenus Leishmania (Viannia)

Background/Objectives: Parasites of the subgenus Leishmania (Viannia) cause varying clinical symptoms ranging from cutaneous leishmaniases (CL) with single or few lesions, disseminated CL (DL) with multiple lesions to disfiguring forms of mucocutaneous leishmaniasis (MCL). In this population genetics study, 37 strains of L. (V.) guyanensis, 63 of L. (V.) braziliensis, four of L. (V.) shawi, six of L. (V.) lainsoni, seven of L. (V.) naiffi, one each of L. (V.) utingensis and L. (V.) lindenbergi, and one L. (V.) lainsoni/L. naiffi hybrid from different endemic foci in Brazil were examined for variation at 15 hyper-variable microsatellite markers. Methodology/Principal findings: The multilocus microsatellite profiles obtained for the 120 strains were analysed using both model- and distance-based methods. Significant genetic diversity was observed for all L. (Viannia) strains studied. The two cluster analysis approaches identified two principal genetic groups or populations, one consisting of strains of L. (V.) guyanensis from the Amazon region and the other of strains of L. (V.) braziliensis isolated along the Atlantic coast of Brazil. A third group comprised a heterogeneous assembly of species, including other strains of L. braziliensis isolated from the north of Brazil, which were extremely polymorphic. The latter strains seemed to be more closely related to those of L. (V.) shawi, L. (V.) naiffi, and L. (V.) lainsoni, also isolated in northern Brazilian foci. The MLMT approach identified an epidemic clone consisting of 13 strains of L. braziliensis from Minas Gerais, but evidence for recombination was obtained for the populations of L. (V.) braziliensis from the Atlantic coast and for L. (V.) guyanensis. Conclusions/Significance: Different levels of recombination versus clonality seem to occur within the subgenus L. (Viannia). Though clearly departing from panmixia, sporadic, but long-term sustained recombination might explain the tremendous genetic diversity and limited population structure found for such L. (Viannia) strains.     

Degradation kinetics of biochar from pyrolysis and hydrothermal carbonization in temperate soils

Background and Aims

Estimates of biochar residence times in soils range over three orders of magnitude. We present the first direct comparison between the biodegradation of a char from hydrothermal carbonization (htcBC) and pyrolysis (pyrBC) with high temporal resolution.

Methods

Mineralization of the biochars and their shared Miscanthus feedstock in three soils was determined directly by the ¹³CO₂ efflux using a novel method incorporating wavelength scanned cavity ring-down spectroscopy. Biochar half-life (t_1/2) was estimated with three empirical models.

Results

(1) The htcBC was readily biodegradable, whereas pyrBC was more recalcitrant. (2) Cumulative degradation of both biochars increased with soil organic carbon and nitrogen content. (3) The corrected Akaike information criterion (AIC_C) showed an overall preference for the double exponential model (DEM) reflecting a labile and a recalcitrant C-pool, over the first-order degradation model (FODM) and a logarithmic model. (4) The DEM resulted in t_1/2 ranging from 19.7–44.5, 0.7–2.1 and 0.8–1.3 years for pyrBC, htcBC and feedstock, respectively.

Conclusion

The degradation was rather similar between feedstock and htcBC but one order of magnitude slower for pyrBC. The AIC_C preferred FODM in two cases, where the DEM parameters indicated no distinction between a labile and recalcitrant carbon pool.     

Identification of a new membrane-permeable inhibitor against inositol-1,4,5-trisphosphate-3-kinase A

Ectopic expression of the neuron-specific inositol-1,4,5-trisphosphate-3-kinase A (ITPKA) in lung cancer cells increases their metastatic potential because the protein exhibits two actin regulating activities; it bundles actin filaments and regulates inositol-1,4,5-trisphosphate (InsP₃)-mediated calcium signals by phosphorylating InsP₃. Thus, in order to inhibit the metastasis-promoting activity of ITPKA, both its actin bundling and its InsP₃kinase activity has to be blocked. In this study, we performed a high throughput screen in order to identify specific and membrane-permeable substances against the InsP₃kinase activity. Among 341,44 small molecules, 237 compounds (0.7%) were identified as potential InsP₃kinase inhibitors. After determination of IC₅₀-values, the three compounds with highest specificity and highest hydrophobicity (EPPC-3, BAMB-4, MEPTT-3) were further characterized. Only BAMB-4 was nearly completely taken up by H1299 cells and remained stable after cellular uptake, thus exhibiting a robust stability and a high membrane permeability. Determination of the inhibitor type revealed that BAMB-4 belongs to the group of mixed type inhibitors. Taken together, for the first time we identified a highly membrane-permeable inhibitor against the InsP₃kinase activity of ITPKA providing the possibility to partly inhibit the metastasis-promoting effect of ITPKA in lung tumor cells.     

越南木樨科植物新记录

报道了越南木樨科(Oleaceae)植物1 新记录种大果素馨(Jasminum macrocarpum Merr.).该种产自越南中南部嘉来省的K’Bang, Kon Ha Nung 地区, 凭证标本保存在 HN, IBSC.     

The impact of simulated chronic nitrogen deposition on the biomass and N2-fixation activity of two boreal feather moss–cyanobacteria associations

Bryophytes achieve substantial biomass and play several key functional roles in boreal forests that can influence how carbon (C) and nitrogen (N) cycling respond to atmospheric deposition of reactive nitrogen (N_r). They associate with cyanobacteria that fix atmospheric N₂, and downregulation of this process may offset anthropogenic N_r inputs to boreal systems. Bryophytes also promote soil C accumulation by thermally insulating soils, and changes in their biomass influence soil C dynamics. Using a unique large-scale (0.1 ha forested plots), long-term experiment (16 years) in northern Sweden where we simulated anthropogenic N_r deposition, we measured the biomass and N₂-fixation response of two bryophyte species, the feather mosses Hylocomium splendens and Pleurozium schreberi. Our data show that the biomass declined for both species; however, N₂-fixation rates per unit mass and per unit area declined only for H. splendens. The low and high treatments resulted in a 29% and 54% reduction in total feather moss biomass, and a 58% and 97% reduction in total N₂-fixation rate per unit area, respectively. These results help to quantify the sensitivity of feather moss biomass and N₂ fixation to chronic N_r deposition, which is relevant for modelling ecosystem C and N balances in boreal ecosystems.     

Eligibility and Safety of Triple Therapy for Hepatitis C: Lessons Learned from the First Experience in a Real World Setting

Background

HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center.

Methods

All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12.

Results

208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12.

Conclusions

P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options.     

A time for every season: soil aggregate turnover stimulates decomposition and reduces carbon loss in grasslands managed for bioenergy

A primary goal of many next‐generation bioenergy systems is to increase ecosystem services such as soil carbon (C) storage and nutrient retention. Evaluating whether bioenergy management systems are achieving these goals is challenging in part because these processes occur over long periods of time at varying spatial scales. Investigation of microbially mediated soil processes at the microbe scale may provide early insights into the mechanisms driving these long‐term ecosystem services. Furthermore, seasonal fluctuations in microbial activity are rarely considered when estimating whole ecosystem functioning, but are central to decomposition, soil structure, and realized C storage. Some studies have characterized extracellular enzyme activity within soil structures (aggregates); however, seasonal variation in decomposition at the microscale remains virtually unknown, particularly in managed ecosystems. As such, we hypothesize that temporal variation in aggregate turnover is a strong regulator of microbial activity, with important implications for decomposition and C and nitrogen (N) storage in bioenergy systems. We address variation in soil microbial extracellular enzyme activity spatially across soil aggregates and temporally across two growing seasons in three ecosystems managed for bioenergy feedstock production: Zea mays L. (corn) agroecosystem, fertilized and unfertilized reconstructed tallgrass prairie. We measured potential N‐acetyl‐glucosaminidase (NAG), β‐glucosidase (BG), β‐xylosidase (BX), and cellobiohydrolase (CB) enzyme activity. Aggregate turnover in prairie systems was driven by precipitation events and seasonal spikes in enzyme activity corresponded with aggregate turnover events. In corn monocultures, soil aggregates turned over early in the growing season, followed by increasing, albeit low, enzyme activity throughout the growing season. Independent of management system or sampling date, NAG activity was greatest in large macroaggregates (>2000 μm) and CB activity was greatest in microaggregates (<250 μm). High microbial activity coupled with greater aggregation in prairie bioenergy systems may reduce loss of soil organic matter through decomposition and increase soil C storage.