Ranking buffel: Comparative risk and mitigation costs of key environmental and socio‐cultural threats in central Australia

Changed fire regimes and the introduction of rabbits, cats, foxes, and large exotic herbivores have driven widespread ecological catastrophe in Australian arid and semi‐arid zones, which encompass over two‐thirds of the continent. These threats have caused the highest global mammal extinction rates in the last 200 years, as well as significantly undermining social, economic, and cultural practices of Aboriginal peoples of this region. However, a new and potentially more serious threat is emerging. Buffel grass (Cenchrus ciliaris L.) is a globally significant invader now widespread across central Australia, but the threat this ecological transformer species poses to biodiversity, ecosystem function, and culture has received relatively little attention. Our analyses suggest threats from buffel grass in arid and semi‐arid areas of Australia are at least equivalent in magnitude to those posed by invasive animals and possibly higher, because unlike these more recognized threats, buffel has yet to occupy its potential distribution. Buffel infestation also increases the intensity and frequency of wildfires that affect biodiversity, cultural pursuits, and productivity. We compare the logistical and financial challenges of creating and maintaining areas free of buffel for the protection of biodiversity and cultural values, with the creation and maintenance of refuges from introduced mammals or from large‐scale fire in natural habitats. The scale and expense of projected buffel management costs highlight the urgent policy, research, and financing initiatives essential to safeguard threatened species, ecosystems, and cultural values of Aboriginal people in central Australia.     

Ethanolamide Oxylipins of Linolenic Acid Can Negatively Regulate Arabidopsis Seedling Development

N-Acylethanolamines (NAEs) are fatty-acid derivatives with potent biological activities in a wide range of eukaryotic organisms. Polyunsaturated NAEs are among the most abundant NAE types in seeds of Arabidopsis thaliana, and they can be metabolized by either fatty acid amide hydrolase (FAAH) or by lipoxygenase (LOX) to low levels during seedling establishment. Here, we identify and quantify endogenous oxylipin metabolites of N-linolenoylethanolamine (NAE 18:3) in Arabidopsis seedlings and show that their levels were higher in faah knockout seedlings. Quantification of oxylipin metabolites in lox mutants demonstrated altered partitioning of NAE 18:3 into 9- or 13-LOX pathways, and this was especially exaggerated when exogenous NAE was added to seedlings. When maintained at micromolar concentrations, NAE 18:3 specifically induced cotyledon bleaching of light-grown seedlings within a restricted stage of development. Comprehensive oxylipin profiling together with genetic and pharmacological interference with LOX activity suggested that both 9-hydroxy and 13-hydroxy linolenoylethanolamides, but not corresponding free fatty-acid metabolites, contributed to the reversible disruption of thylakoid membranes in chloroplasts of seedling cotyledons. We suggest that NAE oxylipins of linolenic acid represent a newly identified, endogenous set of bioactive compounds that may act in opposition to progression of normal seedling development and must be depleted for successful establishment.     

Differential Sensitivities of Normal and Malignant Murine Lymphocytes to Purine Nucleosides

Abstract

Inherited human immunodeficiences associated with loss of adenosine deaminase or purine nucleoside phosphorylase are thought to result from accumulation of the nucleoside substrates. This work attempts to identify lymphocyte subpopulations that are uniquely-sensitive to the endogenous substrates or their analogs.     

Global Analysis of Apicomplexan Protein S‐Acyl Transferases Reveals an Enzyme Essential for Invasion

The advent of techniques to study palmitoylation on a whole proteome scale has revealed that it is an important reversible modification that plays a role in regulating multiple biological processes. Palmitoylation can control the affinity of a protein for lipid membranes, which allows it to impact protein trafficking, stability, folding, signalling and interactions. The publication of the palmitome of the schizont stage of Plasmodium falciparum implicated a role for palmitoylation in host cell invasion, protein export and organelle biogenesis. However, nothing is known so far about the repertoire of protein S‐acyl transferases (PATs) that catalyse this modification in Apicomplexa. We undertook a comprehensive analysis of the repertoire of Asp‐His‐His‐Cys cysteine‐rich domain (DHHC‐CRD) PAT family in Toxoplasma gondii and Plasmodium berghei by assessing their localization and essentiality. Unlike functional redundancies reported in other eukaryotes, some apicomplexan‐specific DHHCs are essential for parasite growth, and several are targeted to organelles unique to this phylum. Of particular interest is DHHC7, which localizes to rhoptry organelles in all parasites tested, including the major human pathogen P. falciparum. TgDHHC7 interferes with the localization of the rhoptry palmitoylated protein TgARO and affects the apical positioning of the rhoptry organelles. This PAT has a major impact on T. gondii host cell invasion, but not on the parasite's ability to egress.     

Cryptic organelle homology in apicomplexan parasites: insights from evolutionary cell biology

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Association mapping and meta-analysis: two complementary approaches for the detection of reliable Septoria tritici blotch quantitative resistance in bread wheat (Triticum aestivum L.)

Septoria tritici blotch (STB), caused by the ascomycete Mycosphaerella graminicola, is one of the most ubiquitous and important diseases of bread wheat worldwide. The aim of this study was to identify markers linked to loci conferring resistance to STB from seven biparental populations. Linkage analysis, meta-analysis and association mapping were combined to identify robust quantitative trait loci (QTLs) for resistance. Linkage analysis led to the detection of 115 QTLs for resistance to STB and 66 QTLs linked to plant height and/or earliness. Meta-analysis clustered these 115 QTLs into 27 Meta-QTLs (MQTLs) of pathogen resistance, of which 14 were found to be linked to plant height and/or earliness. Both the relationship between dwarfing and susceptibility to STB and the significant negative correlation between earliness and STB symptoms were confirmed. Eleven loci were linked to STB resistance by association mapping using a general linear model and/or a mixed linear model, of which eight co-located with STB MQTLs and two co-located with individual QTLs. Associated markers located in MQTL regions enhanced the relevance of the results and validated the potential of an association mapping approach. With several biparental populations, meta-analysis is the most relevant form of genetic analysis study, but association mapping can be used as a validation method. Regions linked to resistance in both methods should be relevant for use in breeding programs for improving resistance to STB in wheat varieties. The main interest in comparing both approaches is to detect robust loci that will be functional in many genetic backgrounds rather than just in one or a few specific backgrounds.     

Engagement of SIRPα Inhibits Growth and Induces Programmed Cell Death in Acute Myeloid Leukemia Cells

Background

Recent studies show the importance of interactions between CD47 expressed on acute myeloid leukemia (AML) cells and the inhibitory immunoreceptor, signal regulatory protein-alpha (SIRPα) on macrophages. Although AML cells express SIRPα, its function has not been investigated in these cells. In this study we aimed to determine the role of the SIRPα in acute myeloid leukemia.

Design and Methods

We analyzed the expression of SIRPα, both on mRNA and protein level in AML patients and we further investigated whether the expression of SIRPα on two low SIRPα expressing AML cell lines could be upregulated upon differentiation of the cells. We determined the effect of chimeric SIRPα expression on tumor cell growth and programmed cell death by its triggering with an agonistic antibody in these cells. Moreover, we examined the efficacy of agonistic antibody in combination with established antileukemic drugs.

Results

By microarray analysis of an extensive cohort of primary AML samples, we demonstrated that SIRPα is differentially expressed in AML subgroups and its expression level is dependent on differentiation stage, with high levels in FAB M4/M5 AML and low levels in FAB M0–M3. Interestingly, AML patients with high SIRPα expression had a poor prognosis. Our results also showed that SIRPα is upregulated upon differentiation of NB4 and Kasumi cells. In addition, triggering of SIRPα with an agonistic antibody in the cells stably expressing chimeric SIRPα, led to inhibition of growth and induction of programmed cell death. Finally, the SIRPα-derived signaling synergized with the activity of established antileukemic drugs.

Conclusions

Our data indicate that triggering of SIRPα has antileukemic effect and may function as a potential therapeutic target in AML.