Long‐term increases in intrinsic water‐use efficiency do not lead to increased stem growth in a tropical monsoon forest in western Thailand

Rising atmospheric carbon dioxide [CO₂] can accelerate tree growth by stimulating photosynthesis and increasing intrinsic water‐use efficiency (iWUE). Little evidence exists, however, for the long‐term growth and gas‐exchange responses of mature trees in tropical forests to the combined effects of rising [CO₂] and other global changes such as warming. Using tree rings and stable isotopes of carbon and oxygen, we investigated long‐term trends in the iWUE and stem growth (basal area increment, BAI) of three canopy tree species in a tropical monsoon forest in western Thailand (Chukrasia tabularis, Melia azedarach, and Toona ciliata). To do this, we modelled the contribution of ontogenetic effects (tree diameter or age) and calendar year to variation in iWUE, oxygen isotopes, and BAI using mixed‐effects models. Although iWUE increased significantly with both tree diameter and calendar year in all species, BAI at a given tree diameter was lower in more recent years. For one species, C. tabularis, differences in crown dominance significantly influence stable isotopes and growth. Tree ring Δ¹⁸O increased with calendar year in all species, suggesting that increasing iWUE may have been driven by relatively greater reductions in stomatal conductance – leading to enrichment in Δ¹⁸O – than increases in photosynthetic capacity. Plausible explanations for the observed declines in growth include water stress resulting from rising temperatures and El Niño events, increased respiration, changes in allocation, or more likely, a combination of these factors.     

Changes in net photosynthesis and growth of Pinus eldarica seedlings in response to atmospheric CO2 enrichment

Pinus eldarica L. trees, rooted in the natural soil of an agricultural field at Phoenix, Arizona, were grown from the seedling stage in clear-plastic-wall open-top enclosures maintained at four different atmospheric CO₂ concentrations for 15 months. Light response functions were determined for one tree from each treatment by means of whole-tree net CO₂ exchange measurements at the end of this period, after which rates of carbon assimilation of an ambient-treatment tree were measured across a range of atmospheric CO₂ concentrations. The first of these data sets incorporates the consequences of both the CO₂-induced enhancement of net photosynthesis per unit needle area and the CO₂-induced enhancement of needle area itself (due primarily to the production of more needles), whereas the second data set reflects only the first of these effects. Hence the division of the normalized results of the first data set by the normalized results of the second set yields a representation of the increase in whole-tree net photosynthesis due to enhanced needle production caused by atmospheric CO₂ enrichment. In the solitary trees we studied, the relative contribution of this effect increased rapidly with the CO₂ concentration of the air to increase whole-tree net photosynthesis by nearly 50% at a CO₂ concentration approximately 300 μmol mol⁻¹ above ambient.     

Alternative cell death of Apaf1-deficient neural progenitor cells induced by withdrawal of EGF or insulin

Background

Various forms of cell death, such as apoptotic, autophagic and non-lysosomal types, are implicated in normal physiological processes. Apoptotic protease activating factor 1 (Apaf1) is an important component of the intrinsic apoptotic pathway. Deficiency of Apaf1 results in an accumulation of neural progenitor cells (NPCs) in the developing central nervous system and thus, in perinatal lethality. A small percentage of the mutant mice, however, are viable and grow to maturity. The occurrence of such normal mutants implicates alternative cell death pathways during neurogenesis.

Methods

NPCs prepared from wild-type or Apaf1-deficient embryos were cultured in growth factor-deprived medium and examined for cell death, caspase activation and morphological alterations. Generation of reactive oxygen species (ROS) and the effects of antioxidants were examined.

Results

Wild-type NPCs underwent apoptosis within 24 hours of withdrawal of epidermal growth factor (EGF) or insulin, whereas Apaf1-deficient NPCs underwent cell death but showed no signs of apoptosis. Autophagy was not necessarily accompanied by cell death. Cell death of the Apaf1-deficient NPCs resembled necroptosis—necrosis-like programmed cell death. The necroptosis inhibitor necrostatin-1, however, failed to inhibit the cell death. ROS accumulation was detected in NPCs deprived of growth factors, and an antioxidant partially suppressed the non-apoptotic cell death of Apaf1-deficient NPCs.

Conclusions

These data indicate that after withdrawal EGF or insulin withdrawal, the Apaf1-deficient cells underwent non-apoptotic cell death. ROS generation may partially participate in the cell death.

General Significance

Non-apoptotic cell death in NPCs may be a compensatory mechanism in the developing CNS of Apaf1-deficient embryos.     

SQSTM1 mutations – Bridging Paget disease of bone and ALS/FTLD

Paget disease of bone (PDB) is a skeletal disorder common in Western Europe but extremely rare in the Indian subcontinent and Far East. The condition has a strong genetic element with mutations affecting the SQSTM1 gene, encoding the p62 protein, frequently identified. Recently SQSTM1 mutations have also been reported in a small number of patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), neurodegenerative disorders in which significant coexistence with PDB has not been previously recognized. Although several SQSTM1 mutations are common to both ALS/FTLD and PDB, many are ALS/FTLD-specific. The p62 protein regulates various cellular processes including NF-κB signaling and autophagy pathways. Here we consider how knowledge of the impact of PDB-associated SQSTM1 mutations (several of which are now known to be relevant for ALS/FTLD) on these pathways, as well as the locations of the mutations within the p62 primary sequence, may provide new insights into ALS/FTLD disease mechanisms.     

Array CGH analysis of a cohort of Russian patients with intellectual disability

The use of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated the identification of many new microdeletion/microduplication syndromes (MMSs). Furthermore, this method has allowed for the identification of copy number variations (CNVs) whose pathogenic role has yet to be uncovered. Here, we report on our application of array CGH for the identification of pathogenic CNVs in 79 Russian children with intellectual disability (ID). Twenty-six pathogenic or likely pathogenic changes in copy number were detected in 22 patients (28%): 8 CNVs corresponded to known MMSs, and 17 were not associated with previously described syndromes. In this report, we describe our findings and comment on genes potentially associated with ID that are located within the CNV regions.     

Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery

The epithelial and endothelial barriers of the human body are major obstacles for drug delivery to the systemic circulation and to organs with unique environment and homeostasis, like the central nervous system. Several transport routes exist in these barriers, which potentially can be exploited for enhancing drug permeability. Beside the transcellular pathways via transporters, adsorptive and receptor-mediated transcytosis, the paracellular flux for cells and molecules is very limited. While lipophilic molecules can diffuse across the cellular plasma membranes, the junctional complexes restrict or completely block the free passage of hydrophilic molecules through the paracellular clefts. Absorption or permeability enhancers developed in the last 40 years for modifying intercellular junctions and paracellular permeability have unspecific mode of action and the effective and toxic doses are very close. Recent advances in barrier research led to the discovery of an increasing number of integral membrane, adaptor, regulator and signalling proteins in tight and adherens junctions. New tight junction modulators are under development, which can directly target tight or adherens junction proteins, the signalling pathways regulating junctional function, or tight junction associated lipid raft microdomains. Modulators acting directly on tight junctions include peptides derived from zonula occludens toxin, or Clostridium perfringens enterotoxin, peptides selected by phage display that bind to integral membrane tight junction proteins, and lipid modulators. They can reversibly increase paracellular transport and drug delivery with less toxicity than previous absorption enhancers, and have a potential to be used as pharmaceutical excipients to improve drug delivery across epithelial barriers and the blood-brain barrier.     

Proteomic analysis of B-cell malignancies

The identification of proteins aberrantly expressed in malignant B-cells can potentially be used to develop new diagnostic, prognostic or therapeutic targets. Proteomic studies of B-cell malignancies have made significant progress, but further studies are needed to increase our coverage of the B-cell malignant proteome. To achieve this goal we stress the advantages of using sub-cellular fractionation, protein separation, quantitation and affinity purification techniques to identify hitherto unidentified signalling and regulatory proteins. For example, proteomic analysis of B-cell plasma membranes isolated from patients with mantle cell lymphoma (MCL) identified the voltage-gated proton channel (HVCN1,[1]). This protein has now been characterised as a key modulator of B-cell receptor (BCR) signalling and abrogation of HVCN1 function could have a role in the treatment of B-cell malignancies dependent on maintained BCR signalling [2]. Similarly, proteomic studies on cell lysates from prognostic subtypes of CLL, distinguished by the absence (UM-CLL) or presence (M-CLL) of somatic hypermutation of the immunoglobulin heavy chain locus identified nucleophosmin 1 (NMP1) as a potential prognostic marker [3,4]. Thus, targeted proteomic analysis on selected organelles or sub-cellular compartments can identify novel proteins with unexpected localisation or function in malignant B-cells that could be developed for clinical purposes.