Thinner bark increases sensitivity of wetter Amazonian tropical forests to fire

Understory fires represent an accelerating threat to Amazonian tropical forests and can, during drought, affect larger areas than deforestation itself. These fires kill trees at rates varying from < 10 to c. 90% depending on fire intensity, forest disturbance history and tree functional traits. Here, we examine variation in bark thickness across the Amazon. Bark can protect trees from fires, but it is often assumed to be consistently thin across tropical forests. Here, we show that investment in bark varies, with thicker bark in dry forests and thinner in wetter forests. We also show that thinner bark translated into higher fire‐driven tree mortality in wetter forests, with between 0.67 and 5.86 gigatonnes CO₂ lost in Amazon understory fires between 2001 and 2010. Trait‐enabled global vegetation models that explicitly include variation in bark thickness are likely to improve the predictions of fire effects on carbon cycling in tropical forests.     

The Role of Chromosome Missegregation in Cancer Development: A Theoretical Approach Using Agent-Based Modelling

Many cancers are aneuploid. However, the precise role that chromosomal instability plays in the development of cancer and in the response of tumours to treatment is still hotly debated. Here, to explore this question from a theoretical standpoint we have developed an agent-based model of tissue homeostasis in which to test the likely effects of whole chromosome mis-segregation during cancer development. In stochastic simulations, chromosome mis-segregation events at cell division lead to the generation of a diverse population of aneuploid clones that over time exhibit hyperplastic growth. Significantly, the course of cancer evolution depends on genetic linkage, as the structure of chromosomes lost or gained through mis-segregation events and the level of genetic instability function in tandem to determine the trajectory of cancer evolution. As a result, simulated cancers differ in their level of genetic stability and in their growth rates. We used this system to investigate the consequences of these differences in tumour heterogeneity for anti-cancer therapies based on surgery and anti-mitotic drugs that selectively target proliferating cells. As expected, simulated treatments induce a transient delay in tumour growth, and reveal a significant difference in the efficacy of different therapy regimes in treating genetically stable and unstable tumours. These data support clinical observations in which a poor prognosis is correlated with a high level of chromosome mis-segregation. However, stochastic simulations run in parallel also exhibit a wide range of behaviours, and the response of individual simulations (equivalent to single tumours) to anti-cancer therapy prove extremely variable. The model therefore highlights the difficulties of predicting the outcome of a given anti-cancer treatment, even in cases in which it is possible to determine the genotype of the entire set of cells within the developing tumour.     

What controls variation in carbon use efficiency among Amazonian tropical forests?

Why do some forests produce biomass more efficiently than others? Variations in Carbon Use Efficiency (CUE: total Net Primary Production (NPP)/ Gross Primary Production (GPP)) may be due to changes in wood residence time (Biomass/NPP_wood), temperature, or soil nutrient status. We tested these hypotheses in 14, one ha plots across Amazonian and Andean forests where we measured most key components of net primary production (NPP: wood, fine roots, and leaves) and autotrophic respiration (R_a; wood, rhizosphere, and leaf respiration). We found that lower fertility sites were less efficient at producing biomass and had higher rhizosphere respiration, indicating increased carbon allocation to belowground components. We then compared wood respiration to wood growth and rhizosphere respiration to fine root growth and found that forests with residence times <40 yrs had significantly lower maintenance respiration for both wood and fine roots than forests with residence times >40 yrs. A comparison of rhizosphere respiration to fine root growth showed that rhizosphere growth respiration was significantly greater at low fertility sites. Overall, we found that Amazonian forests produce biomass less efficiently in stands with residence times >40 yrs and in stands with lower fertility, but changes to long‐term mean annual temperatures do not impact CUE.     

Physical mapping of rDNA genes corroborates allopolyploid origin in apomictic Brachiaria brizantha

Brachiaria (Trin.) Griseb belongs to the family Poaceae, and within the genus, apomixis or sexuality is present in different accessions of the same species. The majority of Brachiaria species are polyploid and apomictic, making strategies for crop improvement by breeding very intricate. In spite of the high frequency of apomictic polyploids, the relationship of polyploidy and hybridization with apomixis in Brachiaria is still unclear. Further analysis requires detailed knowledge regarding the genomic composition of the polyploids. The present work introduces the use of fluorescent in situ hybridization (FISH) into cytogenetic analysis of Brachiaria. Physical mapping of heterologous rDNA sequences, associated with conventional karyotyping of the B. brizantha diploid sexual (BRA 002747) and the tetraploid apomictic (BRA000591) accessions, provided evidence of the latter being of allopolyploid origin. Based on our results and on previous knowledge on apomixis in B. brizantha, we suggest that the origin of apomixis was probably a consequence of hybridization.     

Production of recombinant proteins in clonal root cultures using episomal expression vectors

We have developed a fully contained system for expressing recombinant proteins that is based on clonal root cultures and episomal expression vectors. Clonal root lines expressing green fluorescent protein (GFP) or human growth hormone were generated from Nicotiana benthamiana leaves infected with the tobacco mosaic virus-based vector 30B after exposure to Agrobacterium rhizogenes. These lines accumulated GFP at over 50 mg per kg fresh tissue, a level that is comparable with other plant production systems in early stage development. Accumulation of both hGH and GFP in the clonal root lines was sustained over a 3-year period, and in the absence of antibiotic selection. This technology shows promise for commercial production of vaccine antigens and therapeutic proteins in contained facilities.     

TWEAK affects keratinocyte G2/M growth arrest and induces apoptosis through the translocation of the AIF protein to the nucleus

The soluble TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) binds to the fibroblast growth factor-inducible 14 receptor (FN14, TNFRSF12A) on the cell membrane and induces multiple biological responses, such as proliferation, migration, differentiation, angiogenesis and apoptosis. Previous reports show that TWEAK, which does not contain a death domain in its cytoplasmic tail, induces the apoptosis of tumor cell lines through the induction of TNFα secretion. TWEAK induces apoptosis in human keratinocytes. Our experiments clearly demonstrate that TWEAK does not induce the secretion of TNFα or TRAIL proteins. The use of specific inhibitors and the absence of procaspase-3 cleavage suggest that the apoptosis of keratinocytes follows a caspase- and cathepsin B-independent pathway. Further investigation showed that TWEAK induces a decrease in the mitochondrial membrane potential of keratinocytes. Confocal microscopy showed that TWEAK induces the cleavage and the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus, thus initiating caspase-independent apoptosis. Moreover, TWEAK induces FOXO3 and GADD45 expression, cdc2 phosphorylation and cdc2 and cyclinB1 degradation, resulting in the arrest of cell growth at the G2/M phase. Finally, we report that TWEAK and FN14 are normally expressed in the basal layer of the physiological epidermis and are greatly enhanced in benign (psoriasis) and malignant (squamous cell carcinoma) skin pathologies that are characterized by an inflammatory component. TWEAK might play an essential role in skin homeostasis and pathology.     

A history of the study of solid tumour growth: The contribution of mathematical modelling

A miscellany of new strategies, experimental techniques and theoretical approaches are emerging in the ongoing battle against cancer. Nevertheless, as new, ground-breaking discoveries relating to many and diverse areas of cancer research are made, scientists often have recourse to mathematical modelling in order to elucidate and interpret these experimental findings. Indeed, experimentalists and clinicians alike are becoming increasingly aware of the possibilities afforded by mathematical modelling, recognising that current medical techniques and experimental approaches are often unable to distinguish between various possible mechanisms underlying important aspects of tumour development. This short treatise presents a concise history of the study of solid tumour growth, illustrating the development of mathematical approaches from the early decades of the twentieth century to the present time. Most importantly these mathematical investigations are interwoven with the associated experimental work, showing the crucial relationship between experimental and theoretical approaches, which together have moulded our understanding of tumour growth and contributed to current anti-cancer treatments. Thus, a selection of mathematical publications, including the influential theoretical studies by Burton, Greenspan, Liotta et al., McElwain and co-workers, Adam and Maggelakis, and Byrne and co-workers are juxtaposed with the seminal experimental findings of Gray et al. on oxygenation and radio-sensitivity, Folkman on angiogenesis, Dorie et al. on cell migration and a wide variety of other crucial discoveries. In this way the development of this field of research through the interactions of these different approaches is illuminated, demonstrating the origins of our current understanding of the disease.     

A novel regulatory element in the dnmt1 gene that responds to co-activation by Rb and c-Jun

Rb, c-Jun and dnmt1 play critical roles in the process of cellular differentiation. We demonstrate that a regulatory region of murine dnmt1 contains an element which is responsible for transactivation by Rb and c-Jun in P19 embryocarcinoma cells which is not observed in Y1 adrenocarcinoma cells. During differentiation of P19 cells, the induction of Rb and c-Jun coincides with an increase of dnmt1 mRNA. Using linker scanning mutagenesis we identify the element that is responsible for this activation to be a non-canonical AP-1 site. Our data is an example of how a proto-oncogene activates its downstream effectors by recruiting a tumor suppressor. This interaction of Rb and a proto-oncogene might play an important role in differentiation. The responsiveness of dnmt1 to this type of signal is consistent with an important role for regulated expression of dnmt1 during cellular differentiation.     

Integrins modulate Sog activity in the Drosophila wing

Morphogenesis of the Drosophila wing depends on a series of cell-cell and cell-extracellular matrix interactions. During pupal wing development, two secreted proteins, encoded by the short gastrulation (sog) and decapentaplegic (dpp) genes, vie to position wing veins in the center of broad provein territories. Expression of the Bmp4 homolog dpp in vein cells is counteracted by expression of the Bmp antagonist sog in intervein cells, which results in the formation of straight veins of precise width. We screened for genetic interactions between sog and genes encoding a variety of extracellular components and uncovered interactions between sog and myospheroid (mys), multiple edematous wing (mew) and scab (scb), which encode betaPS, alphaPS1 and alphaPS3 integrin subunits, respectively. Clonal analysis reveals that integrin mutations affect the trajectory of veins inside the provein domain and/or their width and that misexpression of sog can alter the behavior of cells in such clones. In addition, we show that a low molecular weight form of Sog protein binds to alphaPS1betaPS. We find that Sog can diffuse from its intervein site of production into adjacent provein domains, but only on the dorsal surface of the wing, where Sog interacts functionally with integrins. Finally, we show that Sog diffusion into provein regions and the reticular pattern of extracellular Sog distribution in wild-type wings requires mys and mew function. We propose that integrins act by binding and possibly regulating the activity/availability of different forms of Sog during pupal development through an adhesion independent mechanism.     

Studies on the galactomannan-degrading enzymes produced bySporotrichum cellulophilum

Summary Extracellular mannanase activity produced bySporotrichum cellulophilum was purified into two components using acetone precipitation, SP-Sephadex C50 ion exchange chromatography and preparative polyacrylamide gel electrophoresis. The purified mannanse components, M1 and M2, had molecular weights of 108 000–112 000 and 32 200–36 000 respectively. Component M1 was shown to contain 2 subunits having molecular weights of 62 000 and 50 000. M1 and M2 had similar pH-activity profiles with pH optima of 5.5 and 6.0 respectively. M1 was more thermostable than M2: half lives of the enzymes at 70°C were 30 and 9 min for M1 and M2 respectively.