Kinase activity profiling reveals active signal transduction pathways in pediatric acute lymphoblastic leukemia: A new approach for target discovery

Still about 20% of patients with acute lymphoblastic leukemia (ALL) struggle with relapse, despite intensive chemotherapy. We and others have shown that kinase activity profiling is able to give more insights in active signal transduction pathways and point out interesting signaling hubs as well as new potential druggable targets. With this technique the gap between newly designed drugs and ALL may be bridged. The aim of this study was to perform kinome profiling on 20 pediatric ALL samples (14 BCP‐ALL and six T‐ALL) to identify signaling proteins relevant to ALL. We defined 250 peptides commonly activated in both BCP‐ALL and T‐ALL representing major signal transduction pathways including MAPK, PI3K/Akt, and regulators of the cell cycle/p53 pathway. For 27 peptides, differentially phosphorylation between BCP‐ALL and T‐ALL was observed. Among these, ten peptides were more highly phosphorylated in BCP‐ALL while 17 peptides showed increased phosphorylation in T‐ALL. Furthermore we selected one lead of the list of commonly activated peptides (HGFR_Y1235) in order to test its efficacy as a potential target and provide proof of principle for this approach. In conclusion kinome profiling is an elegant approach to study active signaling and identify interesting potential druggable targets.     

Sediment toxicity testing of lightly contaminated dredged material in The Netherlands

In the Netherlands, the decision to permit the dumping of dredged material into the sea depends on the concentrations of about 33 chemical compounds (Anonymous, 1994a). This evaluation of dredged material quality can be improved by the use of bioassays in its assessment. In this note the use of bioassays in the evaluation of lightly contaminated marine dredged material from the Netherlands is illustrated with preliminary results of bioassays with Corophium volutator and Crassostrea gigas. It is concluded that the inclusion of bioassays in the assessment of lightly contaminated sediment is useful.     

Respiratory muscle activity in the assessment of bronchial responsiveness in asthmatic children

We investigatedwhether an increase in transcutaneous electromyographic (EMG) activityof the diaphragm and intercostal muscles corresponds with theconcentration of histamine that induces a 20% fall in the forcedexpiratory volume in one second(FEV₁; PC₂₀). Eleven asthmatic children(mean age 11.9 yr) were studied after they were given histaminechallenge. EMG activity atPC₂₀ or at the highest histamineconcentration was compared with activity at baseline by calculating theratio of the mean peak-to-peak excursion at the highest histamine doseto that at baseline [EMG activity ratio (EMGAR)]. In allchildren reaching PC₂₀, anincrease in diaphragmatic and intercostal EMGAR was observed. Noincrease was found at the dose step beforePC₂₀ was reached. In sixchallenges, no fall in FEV₁ wasinduced, and no increase in EMGAR was seen. In two challenges, no fallin FEV₁ was induced, but increasein diaphragmatic or intercostal EMGAR was observed. Increase in the electrical activity of the diaphragm and intercostal muscles in asthmatic children corresponds closely to a 20% fall inFEV₁ induced by histaminechallenge.

     

Light environment,sapling architecture,and leaf display in six rain forest tree species

Architecture and leaf display were compared in saplings of six rain forest tree species differing in shade tolerance. Saplings were selected along the whole light range encountered in a forest environment. Species differed largely in realized height and crown expansion per unit support biomass, but this could not be related to differences in shade tolerance. The results demonstrate that there exist various solutions to an effective expansion of plant height and crown area. It is argued that choice of the study species and the ontogenetic trajectory regarded determine to a large extent the outcome of interspecific comparisons. No evidence was found that pioneers were characterized by a multilayered and shade tolerants by a monolayered leaf distribution. Yet, sun plants had a similar crown area, a deeper crown, and a higher leaf area index compared to shade plants and their leaves were more evenly distributed along the stem. This suggests that differences in leaf layering are found between plants growing in different light environments, rather than between species differing in shade tolerance.     

Changes in cytokinin and auxin concentrations in seaweed concentrates when stored at an elevated temperature

Two seaweed concentrates were made from the kelps Ecklonia maxima and Macrocystis pyrifera using a cell burst method. Cytokinin- and auxin-like activities were measured using the soybean callus and mungbean bioassays, respectively. Cytokinin-like activity was detected in both seaweed concentrates, being equivalent to approximately 50 μg L⁻¹ kinetin. Auxin-like activity was also detected in both concentrates with the E. maxima derived concentrate having higher biological activity, equivalent to 10⁻⁵–10⁻⁴ M indole-butyric acid. Two replicates of each concentrate were stored at 54 °C for 14 days to accelerate the effects of storage. Both fresh and stored samples of the two seaweed concentrates were analysed for their endogenous cytokinin and auxin content. The samples were purified using a combined DEAE-Sephadex octadecylsilica column and immunoaffinity chromatography based on wide-range cytokinin and IAA specific monoclonal antibodies. These extracts were analysed by HPLC linked to a Micromass single quadrupole mass spectrophotometer. Eighteen and nineteen different cytokinins were detected, respectively, in the two concentrates, with trans-zeatin-O-glucoside being the main cytokinin present. Accelerated storage of the concentrates caused an increase in the total cytokinin concentration with a large increase in the aromatic meta-topolin. Indole-3-acetic acid was the main auxin in both seaweed concentrates. Indole conjugates, including amino acid conjugates, were also quantified. The total auxin concentration decreased with accelerated storage for both concentrates. This revised version was published online in August 2006 with corrections to the Cover Date.     

Light environment and tree strategies in a Bolivian tropical moist forest: an evaluation of the light partitioning hypothesis

Light partitioning is thought to contribute to the coexistence of rain forest tree species. This study evaluates the three premises underlying the light partitioning hypothesis; 1) there is a gradient in light availability at the forest floor, 2) tree species show a differential distribution with respect to light, and 3) there is a trade-off in species performance that explains their different positions along the light gradient. To address these premises, we studied the light environment, growth, and survival of saplings of ten non-pioneer tree species in a Bolivian moist forest. Light availability in the understorey was relatively high, with a mean canopy openness of 3.5% and a mean direct site factor of 6.8%. Saplings of two light demanding species occurred at significantly higher light levels than the shade tolerant species. The proportion of saplings in low-light conditions was negatively correlated with the successional position of the species. Light-demanding species were characterised by a low share of their saplings in low-light conditions, a high sapling mortality, a fast height growth and a strong growth response to light. These data show that all three premises for light partitioning are met. There is a clear gradient in shade-tolerance within the group of non-pioneer species leading to a tight packing of species along the small range of light environments found in the understorey. This revised version was published online in August 2006 with corrections to the Cover Date.     

Allometric equations for integrating remote sensing imagery into forest monitoring programmes

Remote sensing is revolutionizing the way we study forests, and recent technological advances mean we are now able – for the first time – to identify and measure the crown dimensions of individual trees from airborne imagery. Yet to make full use of these data for quantifying forest carbon stocks and dynamics, a new generation of allometric tools which have tree height and crown size at their centre are needed. Here, we compile a global database of 108753 trees for which stem diameter, height and crown diameter have all been measured, including 2395 trees harvested to measure aboveground biomass. Using this database, we develop general allometric models for estimating both the diameter and aboveground biomass of trees from attributes which can be remotely sensed – specifically height and crown diameter. We show that tree height and crown diameter jointly quantify the aboveground biomass of individual trees and find that a single equation predicts stem diameter from these two variables across the world's forests. These new allometric models provide an intuitive way of integrating remote sensing imagery into large‐scale forest monitoring programmes and will be of key importance for parameterizing the next generation of dynamic vegetation models.     

Biodiversity and climate determine the functioning of Neotropical forests

Aim

Tropical forests account for a quarter of the global carbon storage and a third of the terrestrial productivity. Few studies have teased apart the relative importance of environmental factors and forest attributes for ecosystem functioning, especially for the tropics. This study aims to relate aboveground biomass (AGB) and biomass dynamics (i.e., net biomass productivity and its underlying demographic drivers: biomass recruitment, growth and mortality) to forest attributes (tree diversity, community‐mean traits and stand basal area) and environmental conditions (water availability, soil fertility and disturbance).

Location

Neotropics.

Methods

We used data from 26 sites, 201 1‐ha plots and >92,000 trees distributed across the Neotropics. We quantified for each site water availability and soil total exchangeable bases and for each plot three key community‐weighted mean functional traits that are important for biomass stocks and productivity. We used structural equation models to test the hypothesis that all drivers have independent, positive effects on biomass stocks and dynamics.

Results

Of the relationships analysed, vegetation attributes were more frequently associated significantly with biomass stocks and dynamics than environmental conditions (in 67 vs. 33% of the relationships). High climatic water availability increased biomass growth and stocks, light disturbance increased biomass growth, and soil bases had no effect. Rarefied tree species richness had consistent positive relationships with biomass stocks and dynamics, probably because of niche complementarity, but was not related to net biomass productivity. Community‐mean traits were good predictors of biomass stocks and dynamics.

Main conclusions

Water availability has a strong positive effect on biomass stocks and growth, and a future predicted increase in (atmospheric) drought might, therefore, potentially reduce carbon storage. Forest attributes, including species diversity and community‐weighted mean traits, have independent and important relationships with AGB stocks, dynamics and ecosystem functioning, not only in relatively simple temperate systems, but also in structurally complex hyper‐diverse tropical forests.     

Functional diversity changes during tropical forest succession

Functional diversity (FD) ‘those components of biodiversity that influence how an ecosystem operates or functions’ is a promising tool to assess the effect of biodiversity loss on ecosystem functioning. FD has received ample theoretical attention, but empirical studies are limited. We evaluate changes in species richness and FD during tropical secondary forest succession after shifting cultivation in Mexico. We also test whether species richness is a good predictor of FD. FD was calculated based on a combination of nine functional traits, and based on two individual traits important for primary production (specific leaf area) and carbon sequestration (wood density). Stand basal area was a good predictor of successional changes in diversity and FD, in contrast to fallow age. Incidence-based FD indices increased logarithmically with stand basal area, but FD weighted by species’ importance values lacked pattern with succession. Species richness and diversity are strong predictors of FD when all traits were considered; linear relationships indicate that all species are equally functionally complementary, suggesting there is little functional redundancy. In contrast, when FD was calculated for individual traits and weighted for abundances, species richness may underestimate FD.Selection of functional trait(s) critically determines FD, with large consequences for studies relating biodiversity to ecosystem functioning. Careful consideration of the traits required to capture the ecosystem process of interest is thus essential.     

Estimating aboveground net biomass change for tropical and subtropical forests: Refinement of IPCC default rates using forest plot data

As countries advance in greenhouse gas (GHG) accounting for climate change mitigation, consistent estimates of aboveground net biomass change (?AGB) are needed. Countries with limited forest monitoring capabilities in the tropics and subtropics rely on IPCC 2006 default ?AGB rates, which are values per ecological zone, per continent. Similarly, research into forest biomass change at a large scale also makes use of these rates. IPCC 2006 default rates come from a handful of studies, provide no uncertainty indications and do not distinguish between older secondary forests and old‐growth forests. As part of the 2019 Refinement to the 2006 IPCC Guidelines for National Greenhouse Gas Inventories, we incorporate ?AGB data available from 2006 onwards, comprising 176 chronosequences in secondary forests and 536 permanent plots in old‐growth and managed/logged forests located in 42 countries in Africa, North and South America and Asia. We generated ?AGB rate estimates for younger secondary forests (≤20 years), older secondary forests (>20 years and up to 100 years) and old‐growth forests, and accounted for uncertainties in our estimates. In tropical rainforests, for which data availability was the highest, our ?AGB rate estimates ranged from 3.4 (Asia) to 7.6 (Africa) Mg ha^?1 year^?1 in younger secondary forests, from 2.3 (North and South America) to 3.5 (Africa) Mg ha^?1 year^?1 in older secondary forests, and 0.7 (Asia) to 1.3 (Africa) Mg ha^?1 year^?1 in old‐growth forests. We provide a rigorous and traceable refinement of the IPCC 2006 default rates in tropical and subtropical ecological zones, and identify which areas require more research on ?AGB. In this respect, this study should be considered as an important step towards quantifying the role of tropical and subtropical forests as carbon sinks with higher accuracy; our new rates can be used for large‐scale GHG accounting by governmental bodies, nongovernmental organizations and in scientific research.