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Climate models project increases in globally averaged atmospheric specific humidity that are close to the Clausius–Clapeyron (CC) value of around 7% K−1 whilst projections for mean annual global precipitation (P) and evaporation (E) are somewhat muted at around 2% K−1. Such global projections are useful summaries but do not provide guidance at local (grid box) scales where impacts occur. To bridge that gap in spatial scale, previous research has shown that the \"wet get wetter and dry get drier\" relation, Δ(P − E) P − E, follows CC scaling when the projected changes are averaged over latitudinal zones. Much of the research on projected climate impacts has been based on an implicit assumption that this CC relation also holds at local (grid box) scales but this has not previously been examined. In this paper we find that the simple latitudinal average CC scaling relation does not hold at local (grid box) scales over either ocean or land. This means that in terms of P − E, the climate models do not project that the \"wet get wetter and dry get drier\" at the local scales that are relevant for agricultural, ecological and hydrologic impacts. In an attempt to develop a simple framework for local-scale analysis we found that the climate model output shows a remarkably close relation to the long-standing Budyko framework of catchment hydrology. We subsequently use the Budyko curve and find that the local-scale changes in P − E projected by climate models are dominated by changes in P while the changes in net irradiance at the surface due to greenhouse forcing are small and only play a minor role in changing the mean annual P − E in the climate model projections. To further understand the apparently small changes in net irradiance we also examine projections of key surface energy balance terms. In terms of global averages, we find that the climate model projections are dominated by changes in only three terms of the surface energy balance: (1) an increase in the incoming long-wave irradiance, and the respective responses (2) in outgoing long-wave irradiance and (3) in the evaporative flux, with the latter change being much smaller than the former two terms and mostly restricted to the oceans. The small fraction of the realised surface forcing that is partitioned into E explains why the hydrologic sensitivity (2% K−1) is so much smaller than CC scaling (7% K−1). Much public and scientific perception about changes in the water cycle has been based on the notion that temperature enhances E. That notion is partly true but has proved an unfortunate starting point because it has led to misleading conclusions about the impacts of climate change on the water cycle. A better general understanding of the potential impacts of climate change on water availability that are projected by climate models will surely be gained by starting with the notion that the greater the enhancement of E, the less the surface temperature increase (and vice versa). That latter notion is based on the conservation of energy and is an underlying basis of climate model projections.

Food production must increase significantly to sustain a growing global population. Reducing plant water loss may help achieve this goal and is especially relevant in a time of climate change. The plant cuticle defends leaves against drought, and so understanding water movement through the cuticle could help future proof our crops and better understand native ecology. Here, via mathematical modelling, we identify mechanistic properties of water movement in cuticles. We model water sorption in astomatous isolated cuticles, utilising three separate pathways of cellulose, aqueous pores and lipophilic. The model compares well to data both over time and humidity gradients. Sensitivity analysis shows that the grouping of parameters influencing plant species variations has the largest effect on sorption, those influencing cellulose are very influential, and aqueous pores less so but still relevant. Cellulose plays a significant role in diffusion and adsorption in the cuticle and the cuticle surfaces. The plant cuticle provides a barrier between internal leaf tissues and the environment. Here the authors develop a mathematical model of water movement through the cuticle and describe a prominent role for cellulose in controlling the dynamics of moisture diffusion and adsorption.

There is a pressing need to improve the water-use efficiency of rain-fed and irrigated crop production. Breeding crop varieties with higher water-use efficiency is seen as providing part of the solution. Three key processes can be exploited in breeding for high water-use efficiency: (i) moving more of the available water through the crop rather than it being wasted as evaporation from the soil surface or drainage beyond the root zone or being left behind in the root zone at harvest; (ii) acquiring more carbon (biomass) in exchange for the water transpired by the crop, i.e. improving crop transpiration efficiency; (iii) partitioning more of the achieved biomass into the harvested product. The relative importance of any one of these processes will vary depending on how water availability varies during the crop cycle. However, these three processes are not independent. Targeting specific traits to improve one process may have detrimental effects on the other two, but there may also be positive interactions. Progress in breeding for improved water-use efficiency of rain-fed wheat is reviewed to illustrate the nature of some of these interactions and to highlight opportunities that may be exploited in other crops as well as potential pitfalls. For C3 species, measuring carbon isotope discrimination provides a powerful means of improving water-use efficiency of leaf gas exchange, but experience has shown that improvements in leaf-level water-use efficiency may not always translate into higher crop water-use efficiency or yield. In fact, the reverse has frequently been observed. Reasons for this are explored in some detail. Crop simulation modelling can be used to assess the likely impact on water-use efficiency and yield of changing the expression of traits of interest. Results of such simulations indicate that greater progress may be achieved by pyramiding traits so that potential negative effects of individual traits are neutralized. DNA-based selection techniques may assist in such a strategy.

AMP-activated protein kinase (AMPK) is an important energy sensor that may be critical in regulating renal lipid accumulation. To evaluate the role of AMPK in mediating renal lipid accumulation, C57BL/6J mice were randomized to a standard diet, a high-fat diet, or a high-fat diet plus AICAR (an AMPK activator) for 14 weeks. Renal functional and structural studies along with electron microscopy were performed. Mice given the high-fat diet had proximal tubule injury with the presence of enlarged clear vacuoles, and multilaminar inclusions concurrent with an increase of tissue lipid and overloading of the lysosomal system. The margins of the clear vacuoles were positive for the endolysosomal marker, LAMP1, suggesting lysosome accumulation. Characterization of vesicles by special stains (Oil Red O, Nile Red, Luxol Fast Blue) and by electron microscopy showed they contained onion skin-like accumulations consistent with phospholipids. Moreover, cholesteryl esters and phosphatidylcholine-containing phospholipids were significantly increased in the kidneys of mice on a high-fat diet. AMPK activation with chronic AICAR treatment prevented the clinical and structural effects of high-fat diet. Thus, high-fat diet contributes to a dysfunction of the lysosomal system and altered lipid metabolism characterized by cholesterol and phospholipid accumulation in the kidney. AMPK activation normalizes the changes in renal lipid content despite chronic exposure to lipid challenge.

Greater yield per unit rainfall is one of the most important challenges in dryland agriculture. Improving intrinsic water-use efficiency (W(T)), the ratio of CO(2) assimilation rate to transpiration rate at the stomata, may be one means of achieving this goal. Carbon isotope discrimination (Delta(13)C) is recognized as a reliable surrogate for W(T) and there have now been numerous studies which have examined the relationship between crop yield and W(T) (measured as Delta(13)C). These studies have shown the relationship between yield and W(T) to be highly variable. The impact on crop yield of genotypic variation in W(T) will depend on three factors: (i) the impact of variation in W(T) on crop growth rate, (ii) the impact of variation in W(T) on the rate of crop water use, and (iii) how growth and water use interact over the crop's duration to produce grain yield. The relative importance of these three factors will differ depending on the crop species being grown and the nature of the cropping environment. Here we consider these interactions using (i) the results of field trials with bread wheat (Triticum aestivum L.), durum wheat (T. turgidum L.), and barley (Hordeum vulgare L.) that have examined the association between yield and Delta(13)C and (ii) computer simulations with the SIMTAG wheat crop growth model. We present details of progress in breeding to improve W(T) and yield of wheat for Australian environments where crop growth is strongly dependent on subsoil moisture stored from out-of-season rains and assess other opportunities to improve crop yield using W(T).

Heterotrimeric G proteins are molecular switches that control signal transduction, and their dysregulation can promote oncogenesis. Somatic mutations in GNAS, GNAI2 and GNAQ genes induce oncogenesis by rendering Gα subunits constitutively activated. Recently the first somatic mutation, arginine 243 → histidine (R243H) in the GNAO1 (Gαo) gene was identified in breast carcinomas and shown to promote oncogenic transformation when introduced into cells. Here, we provide the molecular basis for the oncogenic properties of the Gαo R243H mutant. Using limited proteolysis assays, nucleotide-binding assays, and single-turnover and steady-state GTPase assays, we demonstrate that the oncogenic R234H mutation renders Gαo constitutively active by accelerating the rate of nucleotide exchange; however, this mutation does not affect Gαo's ability to become deactivated by GTPase-activating proteins (GAPs) or by its intrinsic GTPase activity. This mechanism differs from that of previously reported oncogenic mutations that impair GTPase activity and GAP sensitivity without affecting nucleotide exchange. The constitutively active Gαo R243H mutant also enhances Src-STAT3 signaling in NIH-3T3 cells, a pathway previously shown to be directly triggered by active Gαo proteins to promote cellular transformation. Based on structural analyses, we propose that the enhanced rate of nucleotide exchange in Gαo R243H results from loss of the highly conserved electrostatic interaction of R243 with E43, located in the in the P-loop that represents the binding site for the α- and β-phosphates of the nucleotide. We conclude that the novel R234H mutation imparts oncogenic properties to Gαo by accelerating nucleotide exchange and rendering it constitutively active, thereby enhancing signaling pathways, for example, src-STAT3, responsible for neoplastic transformation.

Heterotrimeric G proteins are molecular switches that control signal transduction. Ligand-occupied, G protein-coupled receptors serve as the canonical guanine nucleotide exchange factors (GEFs) that activate heterotrimeric G proteins. A few unrelated nonreceptor GEFs have also been described, but little or nothing is known about their structure, mechanism of action, or cellular functions in mammals. We have discovered that GIV/Girdin serves as a nonreceptor GEF for Gαi through an evolutionarily conserved motif that shares sequence homology with the synthetic GEF peptide KB-752. Using the available structure of the KB-752·Gαi1 complex as a template, we modeled the Gαi-GIV interface and identified the key residues that are required to form it. Mutation of these key residues disrupts the interaction and impairs Akt enhancement, actin remodeling, and cell migration in cancer cells. Mechanistically, we demonstrate that the GEF motif is capable of activating as well as sequestering the Gα-subunit, thereby enhancing Akt signaling via the Gβγ-PI3K pathway. Recently, GIV has been implicated in cancer metastasis by virtue of its ability to enhance Akt activity and remodel the actin cytoskeleton during cancer invasion. Thus, the novel regulatory motif described here provides the structural and biochemical basis for the prometastatic features of GIV, making the functional disruption of this unique Gαi-GIV interface a promising target for therapy against cancer metastasis.

Wheat productivity is commonly limited by a lack of water essential for growth. Carbon isotope discrimination (Δ), through its negative relationship with transpiration efficiency, has been used in selection of higher wheat yields in breeding for rainfed environments. The potential also exists for selection of increased Δ for improved adaptation to irrigated and high rainfall environments. Selection efficiency of Δ would be enhanced with a better understanding of its genetic control. Three wheat mapping populations (Cranbrook/Halberd, Sunco/Tasman and CD87/Katepwa) containing between 161 and 190 F₁-derived, doubled-haploid progeny were phenotyped for Δ and agronomic traits in 3-5 well-watered environments. The range for Δ was large among progeny (c. 1.2-2.3[per thousand]), contributing to moderate-to-high single environment (h ² = 0.37-0.91) and line-mean (0.63-0.86) heritabilities. Transgressive segregation was large and genetic control complex with between 9 and 13 Δ quantitative trait loci (QTL) identified in each cross. The Δ QTL effects were commonly small, accounting for a modest 1-10% of the total additive genetic variance, while a number of chromosomal regions appeared in two or more populations (e.g. 1BL, 2BS, 3BS, 4AS, 4BS, 5AS, 7AS and 7BS). Some of the Δ genomic regions were associated with variation in heading date (e.g. 2DS, 4AS and 7AL) and/or plant height (e.g. 1BL, 4BS and 4DS) to confound genotypic associations between Δ and grain yield. As a group, high Δ progeny were significantly (P < 0.10-0.01) taller and flowered earlier but produced more biomass and grain yield in favorable environments. After removing the effect of height and heading date, strong genotypic correlations were observed for Δ and both yield and biomass across populations (r g = 0.29-0.57, P < 0.05) as might be expected for the favorable experimental conditions. Thus selection for Δ appears beneficial in increasing grain yield and biomass in favorable environments. However, care must be taken to avoid confounding genotypic differences in Δ with stature and development time when selecting for improved biomass and yield especially in environments experiencing terminal droughts. Polygenic control and small size of individual QTL for Δ may reduce the potential for QTL in marker-assisted selection for improved yield of wheat.

Genetic gain is characteristically slow when selecting directly for increased grain yield under water-limited conditions. Genetic increases in grain yield may be achieved through increases in aerial biomass following selection for greater transpiration efficiency (TE as aerial biomass/water transpired). Strong negative correlations between TE and carbon isotope discrimination (Δ) in wheat (Triticum aestivum L.) suggest that selection of progeny with low Δ may increase TE and aerial biomass under water-limited conditions. This study investigated how early generation, divergent selection for Δ affected aerial biomass and grain yield among 30 low- and 30 high-Δ, `Hartog'-like, B[C.sub.2][F.sub.4:6] progeny and the recurrent, high-Δ parent Hartog. Lines were evaluated in nine environments varying for seasonal rainfall (235-437 mm) and hence grain yield (1.3-6.2 Mg/ha). Selection for low Δ in early generation progeny was associated with significantly (P < 0.01) smaller Δ, higher grain yield (+5.8%), aerial biomass (+2.7%), harvest index (+3.3%), and kernel size (+4.8%) in tested lines. Kernel number was the same for low- and high-Δ selected groups. Grain yield advantage of the low Δ group increased with reductions in environment mean yield (r = -0.89, P < 0.01) and total seasonal rainfall (r = -0.85, P < 0.01) indicating the benefit of low Δ, and therefore high TE for genetic improvement of grain yield in lower rainfall environments. Narrow-sense heritability on a single-plot basis was much greater for Δ ([h.sup.2] = 0.63 ± 0.10) than for either aerial biomass (0.06 ± 0.05) or grain yield (0.14 ± 0.04). Strong genetic correlations between Δ and both aerial biomass ([r.sub.g] = -0.61 ± 0.14) and grain yield (-0.58 ± 0.12) suggest Δ could be used for indirect selection of these traits in early generations. Selection of low Δ (high TE) families for the advanced stages of multiple-environment testing should increase the probability of recovering higher-yielding wheat families for water-limited environments.