Main conclusionProvides a first comprehensive review of integrated physiological and molecular aspects of desiccation toleranceXerophyta viscosa. A synopsis of biotechnological studies being undertaken to improve drought tolerance in maize is given.Xerophyta viscosa (Baker) is a monocotyledonous resurrection plant from the family Vellociacea that occurs in summer-rainfall areas of South Africa, Lesotho and Swaziland. It inhabits rocky terrain in exposed grasslands and frequently experiences periods of water deficit. Being a resurrection plant it tolerates the loss of 95 % of total cellular water, regaining full metabolic competency within 3 days of rehydration. In this paper, we review some of the molecular and physiological adaptations that occur during various stages of dehydration of X. viscosa, these being functionally grouped into early and late responses, which might be relevant to the attainment of desiccation tolerance. During early drying (to 55 % RWC) photosynthesis is shut down, there is increased presence and activity of housekeeping antioxidants and a redirection of metabolism to the increased formation of sucrose and raffinose family oligosaccharides. Other metabolic shifts suggest water replacement in vacuoles proposed to facilitate mechanical stabilization. Some regulatory processes observed include increased presence of a linker histone H1 variant, a Type 2C protein phosphatase, a calmodulin- and an ERD15-like protein. During the late stages of drying (to 10 % RWC) there was increased expression of several proteins involved in signal transduction, and retroelements speculated to be instrumental in gene silencing. There was induction of antioxidants not typically found in desiccation-sensitive systems, classical stress-associated proteins (HSP and LEAs), proteins involved in structural stabilization and those associated with changes in various metabolite pools during drying. Metabolites accumulated in this stage are proposed, inter alia, to facilitate subcellular stabilization by vitrification process which can include glass- and ionic liquid formation.
We report the syntheses and activities of a wide range of thiazolides [viz. 2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis B virus replication, with QSAR analysis of our results. The prototypical thiazolide, nitazoxanide [2-hydroxybenzoyl-N-(5-nitrothiazol-2-yl)amide; NTZ] 1 is a broad spectrum antiinfective agent, effective against anaerobic bacteria, viruses and parasites. By contrast, 2-hydroxybenzoyl-N-(5-chlorothiazol-2-yl)amide 3 is a novel, potent and selective inhibitor of hepatitis B replication (EC50 = 0.33 μm) but is inactive against anaerobes. Several 4′- and 5′-substituted thiazolides show good activity against HBV; by contrast, some related salicyloylanilides show a narrower spectrum of activity. The ADME properties of 3 are similar to 1, viz. the O-acetate is an effective prodrug and the O-aryl glucuronide is a major metabolite. The QSAR study shows a good correlation of observed EC90 s for intracellular virions with thiazolide structural parameters. Finally we discuss the mechanism of action of thiazolides in relation to the present results.
We report the activities of a number of thiazolides [2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis C virus (HCV) genotypes IA and IB, using replicon assays. The structure-activity relationships (SARs) of thiazolides against HCV are less predictable than against hepatitis B virus (HBV), though an electron-withdrawing group at C(5') generally correlates with potency. Among the related salicyloylanilides, the m-fluorophenyl analogue was most promising; niclosamide and close analogues suffered from very low solubility and bioavailability. Nitazoxanide (NTZ) 1 has performed well in clinical trials against HCV. We show here that the 5'-Cl analogue 4 has closely comparable in vitro activity and a good cell safety index. By use of support vector analysis, a quantitative structure-activity relationship (QSAR) model was obtained, showing good predictive models for cell safety. We conclude by updating the mode of action of the thiazolides and explain the candidate selection that has led to compound 4 entering preclinical development.
Desiccation tolerance is the ability to survive loss of 90% of cellular water or dehydration to water concentrations of <0.1g HrO g-1 dry mass. It is relatively common in reproductive stru such as seeds (termed orthodox), but is rare in vegetative tissues, occurring in some 350 spe higher plants (termed 'resurrection plants'). In this chapter we present an overview of the s associated with desiccation and review the current mechanisms proposed to explain how or seeds and resurrection plants tolerate such water Ioss. Physiological, biochemical and molecula esses involved in protection from mechanical stress, oxidative damage and metabolic disruptio
BackgroundThe role of tectonic uplift in stimulating speciation in South Africa’s only alpine zone, the Drakensberg, has not been explicitly examined. Tectonic processes may influence speciation both through the creation of novel habitats and by physically isolating plant populations. We use the Afrotemperate endemic daisy genus Macowania to explore the timing and mode (geographic versus adaptive) of speciation in this region. Between sister species pairs we expect high morphological divergence where speciation has happened in sympatry (adaptive) while with geographic (vicariant) speciation we may expect to find less morphological divergence and a greater degree of allopatry. A dated molecular phylogenetic hypothesis for Macowania elucidates species’ relationships and is used to address the potential impact of uplift on diversification. Morphological divergence of a small sample of reproductive and vegetative characters, used as a proxy for adaptive divergence, is measured against species’ range distributions to estimate mode of speciation across two subclades in the genus.ResultsThe Macowania crown age is consistent with the hypothesis of post-uplift diversification, and we find evidence for both vicariant and adaptive speciation between the two subclades within Macowania. Both subclades exhibit strong signals of range allopatry, suggesting that geographic isolation was important in speciation. One subclade, associated with dry, rocky environments at high altitudes, shows very little morphological and ecological differentiation but high range allopatry. The other subclade occupies a greater variety of habitats and exhibits far greater morphological differentiation, but contains species with overlapping distribution ranges.ConclusionsSpecies in Macowania are likely to have diversified in response to tectonic uplift, and we invoke uplift and uplift-mediated erosion as the main drivers of speciation. The greater relative morphological divergence in sympatric species of Macowania indicates that speciation in the non-sympatric taxa may not have required obvious adaptive differences, implying that simple geographic isolation was the driving force for speciation (‘neutral speciation’).
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