Showing papers by "University of Adelaide published in 2011"

Apixaban versus Warfarin in Patients with Atrial Fibrillation

Abstract: A b s t r ac t Background Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic em - bolism. The trial was designed to test for noninferiority, with key secondary objec - tives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the war - farin group (hazard ratio with apixaban, 0.79; 95% confidence interval (CI), 0.66 to 0.95; P<0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ra - tio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42). Conclusions In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.)

Primary forests are irreplaceable for sustaining tropical biodiversity

Abstract: Human-driven land-use changes increasingly threaten biodiversity, particularly in tropical forests where both species diversity and human pressures on natural environments are high. The rapid conversion of tropical forests for agriculture, timber production and other uses has generated vast, human-dominated landscapes with potentially dire consequences for tropical biodiversity. Today, few truly undisturbed tropical forests exist, whereas those degraded by repeated logging and fires, as well as secondary and plantation forests, are rapidly expanding. Here we provide a global assessment of the impact of disturbance and land conversion on biodiversity in tropical forests using a meta-analysis of 138 studies. We analysed 2,220 pairwise comparisons of biodiversity values in primary forests (with little or no human disturbance) and disturbed forests. We found that biodiversity values were substantially lower in degraded forests, but that this varied considerably by geographic region, taxonomic group, ecological metric and disturbance type. Even after partly accounting for confounding colonization and succession effects due to the composition of surrounding habitats, isolation and time since disturbance, we find that most forms of forest degradation have an overwhelmingly detrimental effect on tropical biodiversity. Our results clearly indicate that when it comes to maintaining tropical biodiversity, there is no substitute for primary forests.

The Internet Topology Zoo

Abstract: The study of network topology has attracted a great deal of attention in the last decade, but has been hampered by a lack of accurate data. Existing methods for measuring topology have flaws, and arguments about the importance of these have overshadowed the more interesting questions about network structure. The Internet Topology Zoo is a store of network data created from the information that network operators make public. As such it is the most accurate large-scale collection of network topologies available, and includes meta-data that couldn't have been measured. With this data we can answer questions about network structure with more certainty than ever before - we illustrate its power through a preliminary analysis of the PoP-level topology of over 140 networks. We find a wide range of network designs not conforming as a whole to any obvious model.

Roles of Arbuscular Mycorrhizas in Plant Nutrition and Growth: New Paradigms from Cellular to Ecosystem Scales

Abstract: Root systems of most land plants form arbuscular mycorrhizal (AM) symbioses in the field, and these contribute to nutrient uptake. AM roots have two pathways for nutrient absorption, directly through the root epidermis and root hairs and via AM fungal hyphae into root cortical cells, where arbuscules or hyphal coils provide symbiotic interfaces. New physiological and molecular evidence shows that for phosphorus the mycorrhizal pathway (MP) is operational regardless of plant growth responses (positive or negative). Amounts delivered cannot be determined from plant nutrient contents because when responses are negative the contribution of the direct pathway (DP) is reduced. Nitrogen (N) is also delivered to roots via an MP, but the contribution to total N requirement and the costs to the plant are not clear. The functional interplay between activities of the DP and MP has important implications for consideration of AM symbioses in ecological, agronomic, and evolutionary contexts.

The evolution of gene expression levels in mammalian organs

Abstract: Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across ten species that represent all major mammalian lineages (placentals, marsupials and monotremes) and birds (the evolutionary outgroup), with the goal of understanding the dynamics of mammalian transcriptome evolution. We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation. Although gene expression evolution in mammals was strongly shaped by purifying selection, we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals.

Roles of Arbuscular Mycorrhizas in Plant Phosphorus Nutrition: Interactions between Pathways of Phosphorus Uptake in Arbuscular Mycorrhizal Roots Have Important Implications for Understanding and Manipulating Plant Phosphorus Acquisition

Abstract: Arbuscular mycorrhizal (AM) symbiosis is the most common plant strategy that increases phosphorus (P) acquisition, involving approximately 80% of terrestrial plants The AM fungal symbionts provide a very effective pathway (the AM pathway) for uptake, scavenging P from large soil volumes and overcoming depletion in the rhizosphere that occurs when direct (epidermal) root uptake is faster than replacement from the bulk soil Recent physiological and molecular research has shown that the AM pathway makes very large contributions to total plant P even in plants that show no growth increases when AM, compared with non-mycorrhizal (NM) counterparts The AM contribution remains "hidden" unless radioactive tracers are used to track delivery via the AM pathway Importantly, this finding demonstrates that the direct pathway delivers less P to AM plants than to NM counterparts and implies fungus-to-plant signaling The mechanisms by which direct uptake is reduced are unknown, but the hidden contribution of AM uptake means that AM fungi cannot be regarded as parasites, because there is mutualistic exchange of P for organic C regardless of plant growth responses Furthermore, the dominance of the AM pathway helps to explain the persistence of AM symbiosis over evolutionary time, even in plants that apparently show no benefits

A gravitational wave observatory operating beyond the quantum shot-noise limit

Abstract: Around the globe several observatories are seeking the first direct detection of gravitational waves (GWs). These waves are predicted by Einstein’s general theory of relativity1 and are generated, for example, by black-hole binary systems2. Present GW detectors are Michelson-type kilometre-scale laser interferometers measuring the distance changes between mirrors suspended in vacuum. The sensitivity of these detectors at frequencies above several hundred hertz is limited by the vacuum (zero-point) fluctuations of the electromagnetic field. A quantum technology—the injection of squeezed light3—offers a solution to this problem. Here we demonstrate the squeezed-light enhancement of GEO 600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3–4 years. GEO 600 now operates with its best ever sensitivity, which proves the usefulness of quantum entanglement and the qualification of squeezed light as a key technology for future GW astronomy4.

Assessing the benefits and risks of translocations in changing environments : a genetic perspective

Abstract: Translocations are being increasingly proposed as a way of conserving biodiversity, particularly in the management of threatened and keystone species, with the aims of maintaining biodiversity and ecosystem function under the combined pressures of habitat fragmentation and climate change. Evolutionary genetic considerations should be an important part of translocation strategies, but there is often confusion about concepts and goals. Here, we provide a classification of translocations based on specific genetic goals for both threatened species and ecological restoration, separating targets based on ‘genetic rescue’ of current population fitness from those focused on maintaining adaptive potential. We then provide a framework for assessing the genetic benefits and risks associated with translocations and provide guidelines for managers focused on conserving biodiversity and evolutionary processes. Case studies are developed to illustrate the framework.

Plant and microbial strategies to improve the phosphorus efficiency of agriculture

Abstract: Background Agricultural production is often limited by low phosphorus (P) availability. In developing countries, which have limited access to P fertiliser, there is a need to develop plants that are more efficient at low soil P. In fertilised and intensive systems, P-efficient plants are required to minimise inefficient use of P-inputs and to reduce potential for loss of P to the environment.

Building evolutionary resilience for conserving biodiversity under climate change

Abstract: Evolution occurs rapidly and is an ongoing process in our environments. Evolutionary principles need to be built into conservation efforts, particularly given the stressful conditions organisms are increasingly likely to experience because of climate change and ongoing habitat fragmentation. The concept of evolutionary resilience is a way of emphasizing evolutionary processes in conservation and landscape planning. From an evolutionary perspective, landscapes need to allow in situ selection and capture high levels of genetic variation essential for responding to the direct and indirect effects of climate change. We summarize ideas that need to be considered in planning for evolutionary resilience and suggest how they might be incorporated into policy and management to ensure that resilience is maintained in the face of environmental degradation.

Evidence that the prevalence of childhood overweight is plateauing: Data from nine countries

Abstract: Until quite recently, there has been a widespread belief in the popular media and scientific literature that the prevalence of childhood obesity is rapidly increasing However, high quality evidence has emerged from several countries suggesting that the rise in the prevalence has slowed appreciably, or even plateaued This review brings together such data from nine countries (Australia, China, England, France, Netherlands, New Zealand, Sweden, Switzerland and USA), with data from 467,294 children aged 2-19 years The mean unweighted rate of change in prevalence of overweight and obesity was +000 (049)% per year across all age ×sex groups and all countries between 1995 and 2008 For overweight alone, the figure was +001 (056)%, and for obesity alone -001 (024)% Rates of change differed by sex, age, socioeconomic status and ethnicity While the prevalence of overweight and obesity appears to be stabilizing at different levels in different countries, it remains high, and a significant public health issue Possible reasons for the apparent flattening are hypothesised

Multifunctional shade‐tree management in tropical agroforestry landscapes – a review

Abstract: Summary 1. Agricultural intensification reduces ecological resilience of land-use systems, whereas paradoxically, environmental change and climate extremes require a higher response capacity than ever. Adaptation strategies to environmental change include maintenance of shade trees in tropical agroforestry, but conversion of shaded to unshaded systems is common practice to increase short-term yield. 2. In this paper, we review the short-term and long-term ecological benefits of shade trees in coffee Coffea arabica, C. canephora and cacao Theobroma cacao agroforestry and emphasize the poorly understood, multifunctional role of shade trees for farmers and conservation alike. 3. Both coffee and cacao are tropical understorey plants. Shade trees in agroforestry enhance functional biodiversity, carbon sequestration, soil fertility, drought resistance as well as weed and biological pest control. However, shade is needed for young cacao trees only and is less important in older cacao plantations. This changing response to shade regime with cacao plantation age often results in a transient role for shade and associated biodiversity in agroforestry. 4. Abandonment of old, unshaded cacao in favour of planting young cacao in new, thinned forest sites can be named ‘short-term cacao boom-and-bust cycle’, which counteracts tropical forest conservation. In a ‘long-term cacao boom-and-bust cycle’, cacao boom can be followed by cacao bust due to unmanageable pest and pathogen levels (e.g. in Brazil and Malaysia). Higher pest densities can result from physiological stress in unshaded cacao and from the larger cacao area planted. Risk-averse farmers avoid long-term vulnerability of their agroforestry systems by keeping shade as an insurance against insect pest outbreaks, whereas yield-maximizing farmers reduce shade and aim at short-term monetary benefits. 5. Synthesis and applications. Sustainable agroforestry management needs to conserve or create a diverse layer of multi-purpose shade trees that can be pruned rather than removed when crops mature. Incentives from payment-for-ecosystem services and certification schemes encourage farmers to keep high to medium shade tree cover. Reducing pesticide spraying protects functional

Species-specific responses of Late Quaternary megafauna to climate and humans

Abstract: Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.

Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis

Abstract: Context Low testosterone levels have been associated with outcomes that reduce survival in men. Objective Our objective was to perform a systematic review and meta-analysis of published studies to evaluate the association between endogenous testosterone and mortality. Data sources Data sources included MEDLINE (1966 to December 2010), EMBASE (1988 to December 2010), and reference lists. Study selection Eligible studies were published English-language observational studies of men that reported the association between endogenous testosterone and all-cause or cardiovascular disease (CVD) mortality. A two-stage process was used for study selection. 1) Working independently and in duplicate, reviewers screened a subset (10%) of abstracts. Results indicated 96% agreement, and thereafter, abstract screening was conducted in singlicate. 2) All full-text publications were reviewed independently and in duplicate for eligibility. Data extraction Reviewers working independently and in duplicate determined methodological quality of studies and extracted descriptive, quality, and outcome data. Data synthesis Of 820 studies identified, 21 were included in the systematic review, and 12 were eligible for meta-analysis [n = 11 studies of all-cause mortality (16,184 subjects); n = 7 studies of CVD mortality (11,831 subjects)]. Subject mean age and testosterone level were 61 yr and 487 ng/dl, respectively, and mean follow-up time was 9.7 yr. Between-study heterogeneity was observed among studies of all-cause (P Conclusion Low endogenous testosterone levels are associated with increased risk of all-cause and CVD death in community-based studies of men, but considerable between-study heterogeneity, which was related to study and subject characteristics, suggests that effects are driven by differences between cohorts (e.g. in underlying health status).

Hand Grip Strength: age and gender stratified normative data in a population-based study

Abstract: The North West Adelaide Health Study is a representative longitudinal cohort study of people originally aged 18 years and over. The aim of this study was to describe normative data for hand grip strength in a community-based Australian population. Secondary aims were to investigate the relationship between body mass index (BMI) and hand grip strength, and to compare Australian data with international hand grip strength norms. The sample was randomly selected and recruited by telephone interview. Overall, 3 206 (81% of those recruited) participants returned to the clinic during the second stage (2004-2006) which specifically focused on the collection of information relating to musculoskeletal conditions. Following the exclusion of 435 participants who had hand pain and/or arthritis, 1366 men and 1312 women participants provided hand grip strength measurement. The study population was relatively young, with 41.5% under 40 years; and their mean BMI was 28.1 kg/m2 (SD 5.5). Higher hand grip strength was weakly related to higher BMI in adults under the age of 30 and over the age of 70, but inversely related to higher BMI between these ages. Australian norms from this sample had amongst the lowest of the hand grip strength of the internationally published norms, except those from underweight populations. This population demonstrated higher BMI and lower grip strength in younger participants than much of the international published, population data. A complete exploration of the relationship between BMI and hand grip strength was not fully explored as there were very few participants with BMI in the underweight range. The age and gender grip strength values are lower in younger adults than those reported in international literature.

Experimental strategies for microRNA target identification

Abstract: MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression in most biological processes. They act by guiding the RNAi-induced silencing complex (RISC) to partially complementary sequences in target mRNAs to suppress gene expression by a combination of translation inhibition and mRNA decay. The commonly accepted mechanism of miRNA targeting in animals involves an interaction between the 5'-end of the miRNA called the 'seed region' and the 3' untranslated region (3'-UTR) of the mRNA. Many target prediction algorithms are based around such a model, though increasing evidence demonstrates that targeting can also be mediated through sites other than the 3'-UTR and that seed region base pairing is not always required. The power and validity of such in silico data can be therefore hindered by the simplified rules used to represent targeting interactions. Experimentation is essential to identify genuine miRNA targets, however many experimental modalities exist and their limitations need to be understood. This review summarizes and critiques the existing experimental techniques for miRNA target identification.

Lifestyle changes in women with polycystic ovary syndrome

Abstract: Background Polycystic ovary syndrome (PCOS) affects 4% to 18% of reproductive-aged women and is associated with reproductive, metabolic and psychological dysfunction Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions Objectives To assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS Search methods Electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL, AMED) (date of last search 7/9/2010), controlled trials register, conference abstracts, relevant journals, reference lists of relevant papers and reviews and grey literature databases, with no language restrictions applied Selection criteria Randomised controlled trials comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS Data collection and analysis Two authors independently selected trials, assessed methodological quality and risk of bias and extracted data Main results Six studies were included with n=164 participants Three studies compared physical activity to minimal dietary and behavioural advice or no advice Three studies compared combined dietary, exercise and behavioural interventions to minimal intervention Risk of bias varied with 4/6 having adequate sequence generation and clinician or outcome assessor blinding and 3/6 having adequate allocation concealment, complete outcome data and being free of selective reporting There were no studies assessing the fertility primary outcomes of pregnancy, live birth and miscarriage and no data for meta-analysis on ovulation or menstrual regularity Lifestyle intervention provided benefits when compared to minimal treatment for secondary reproductive, anthropometric and reproductive outcomes These included endpoint values for total testosterone (mean difference (MD) -027 nmol/L, 95% confidence interval (CI) -046 to -009, P = 0004), hirsutism or excess hair growth by the Ferriman-Gallwey score (MD -119, 95% CI -235 to -003, P = 004), weight (MD -347 kg, 95% CI -494 to -200, P < 000001), waist circumference (MD -195 cm, 95% CI -334 to -057, P = 0006) and fasting insulin (MD -202 µU/mL, 95% CI -328 to -077, P = 0002) There was no evidence of effect of lifestyle for body mass index, free androgen index, sex hormone binding globulin, glucose or cholesterol levels; and no data for quality of life, patient satisfaction or acne Authors' conclusions Lifestyle intervention improves body composition, hyperandrogenism (high male hormones and clinical effects) and insulin resistance in women with PCOS There was no evidence of effect for lifestyle intervention on improving glucose tolerance or lipid profiles and no literature assessing clinical reproductive outcomes, quality of life and treatment satisfaction

Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia

Abstract: We report the discovery of GATA2 as a new myelodysplastic syndrome (MDS)-acute myeloid leukemia (AML) predisposition gene. We found the same, previously unidentified heterozygous c.1061C>T (p.Thr354Met) missense mutation in the GATA2 transcription factor gene segregating with the multigenerational transmission of MDS-AML in three families and a GATA2 c.1063_1065delACA (p.Thr355del) mutation at an adjacent codon in a fourth MDS family. The resulting alterations reside within the second zinc finger of GATA2, which mediates DNA-binding and protein-protein interactions. We show differential effects of the mutations on the transactivation of target genes, cellular differentiation, apoptosis and global gene expression. Identification of such predisposing genes to familial forms of MDS and AML is critical for more effective diagnosis and prognosis, counseling, selection of related bone marrow transplant donors and development of therapies.

An autocrine TGF-β/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition

Abstract: Epithelial-mesenchymal transition (EMT) is a form of cellular plasticity that is critical for embryonic development and tumor metastasis. A double-negative feedback loop involving the miR-200 family and ZEB (zinc finger E-box-binding homeobox) transcription factors has been postulated to control the balance between epithelial and mesenchymal states. Here we demonstrate using the epithelial Madin Darby canine kidney cell line model that, although manipulation of the ZEB/miR-200 balance is able to repeatedly switch cells between epithelial and mesenchymal states, the induction and maintenance of a stable mesenchymal phenotype requires the establishment of autocrine transforming growth factor-β (TGF-β) signaling to drive sustained ZEB expression. Furthermore, we show that prolonged autocrine TGF-β signaling induced reversible DNA methylation of the miR-200 loci with corresponding changes in miR-200 levels. Collectively, these findings demonstrate the existence of an autocrine TGF-β/ZEB/miR-200 signaling network that regulates plasticity between epithelial and mesenchymal states. We find a strong correlation between ZEBs and TGF-β and negative correlations between miR-200 and TGF-β and between miR-200 and ZEBs, in invasive ductal carcinomas, consistent with an autocrine TGF-β/ZEB/miR-200 signaling network being active in breast cancers.

Time-dependent rates of molecular evolution.

Abstract: For over half a century, it has been known that the rate of morphological evolution appears to vary with the time frame of measurement. Rates of microevolutionary change, measured between successive generations, were found to be far higher than rates of macroevolutionary change inferred from the fossil record. More recently, it has been suggested that rates of molecular evolution are also time dependent, with the estimated rate depending on the timescale of measurement. This followed surprising observations that estimates of mutation rates, obtained in studies of pedigrees and laboratory mutation-accumulation lines, exceeded long-term substitution rates by an order of magnitude or more. Although a range of studies have provided evidence for such a pattern, the hypothesis remains relatively contentious. Furthermore, there is ongoing discussion about the factors that can cause molecular rate estimates to be dependent on time. Here we present an overview of our current understanding of time-dependent rates. We provide a summary of the evidence for time-dependent rates in animals, bacteria and viruses. We review the various biological and methodological factors that can cause rates to be time dependent, including the effects of natural selection, calibration errors, model misspecification and other artefacts. We also describe the challenges in calibrating estimates of molecular rates, particularly on the intermediate timescales that are critical for an accurate characterization of time-dependent rates. This has important consequences for the use of molecular-clock methods to estimate timescales of recent evolutionary events.

Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway

Abstract: Sclerostin is a product of mature osteocytes embedded in mineralised bone and is a negative regulator of bone mass and osteoblast differentiation. While evidence suggests that sclerostin has an anti-anabolic role, the possibility also exists that sclerostin has catabolic activity. To test this we treated human primary pre-osteocyte cultures, cells we have found are exquisitely sensitive to sclerostin, or mouse osteocyte-like MLO-Y4 cells, with recombinant human sclerostin (rhSCL) and measured effects on pro-catabolic gene expression. Sclerostin dose-dependently up-regulated the expression of receptor activator of nuclear factor kappa B (RANKL) mRNA and down-regulated that of osteoprotegerin (OPG) mRNA, causing an increase in the RANKL∶OPG mRNA ratio. To examine the effects of rhSCL on resulting osteoclastic activity, MLO-Y4 cells plated onto a bone-like substrate were primed with rhSCL for 3 days and then either mouse splenocytes or human peripheral blood mononuclear cells (PBMC) were added. This resulted in cultures with elevated osteoclastic resorption (approximately 7-fold) compared to untreated co-cultures. The increased resorption was abolished by co-addition of recombinant OPG. In co-cultures of MLO-Y4 cells with PBMC, SCL also increased the number and size of the TRAP-positive multinucleated cells formed. Importantly, rhSCL had no effect on TRAP-positive cell formation from monocultures of either splenocytes or PBMC. Further, rhSCL did not induce apoptosis of MLO-Y4 cells, as determined by caspase activity assays, demonstrating that the osteoclastic response was not driven by dying osteocytes. Together, these results suggest that sclerostin may have a catabolic action through promotion of osteoclast formation and activity by osteocytes, in a RANKL-dependent manner.

A Molecular Mechanism for Bacterial Susceptibility to Zinc.

Abstract: Transition row metal ions are both essential and toxic to microorganisms. Zinc in excess has significant toxicity to bacteria, and host release of Zn(II) at mucosal surfaces is an important innate defence mechanism. However, the molecular mechanisms by which Zn(II) affords protection have not been defined. We show that in Streptococcus pneumoniae extracellular Zn(II) inhibits the acquisition of the essential metal Mn(II) by competing for binding to the solute binding protein PsaA. We show that, although Mn(II) is the high-affinity substrate for PsaA, Zn(II) can still bind, albeit with a difference in affinity of nearly two orders of magnitude. Despite the difference in metal ion affinities, high-resolution structures of PsaA in complex with Mn(II) or Zn(II) showed almost no difference. However, Zn(II)-PsaA is significantly more thermally stable than Mn(II)-PsaA, suggesting that Zn(II) binding may be irreversible. In vitro growth analyses show that extracellular Zn(II) is able to inhibit Mn(II) intracellular accumulation with little effect on intracellular Zn(II). The phenotype of S. pneumoniae grown at high Zn(II):Mn(II) ratios, i.e. induced Mn(II) starvation, closely mimicked a ΔpsaA mutant, which is unable to accumulate Mn(II). S. pneumoniae infection in vivo elicits massive elevation of the Zn(II):Mn(II) ratio and, in vitro, these Zn(II):Mn(II) ratios inhibited growth due to Mn(II) starvation, resulting in heightened sensitivity to oxidative stress and polymorphonuclear leucocyte killing. These results demonstrate that microbial susceptibility to Zn(II) toxicity is mediated by extracellular cation competition and that this can be harnessed by the innate immune response.

Additive effects of Na+ and Cl– ions on barley growth under salinity stress

Abstract: Soil salinity affects large areas of the world's cultivated land, causing significant reductions in crop yield. Despite the fact that most plants accumulate both sodium (Na(+)) and chloride (Cl(-)) ions in high concentrations in their shoot tissues when grown in saline soils, most research on salt tolerance in annual plants has focused on the toxic effects of Na(+) accumulation. It has previously been suggested that Cl(-) toxicity may also be an important cause of growth reduction in barley plants. Here, the extent to which specific ion toxicities of Na(+) and Cl(-) reduce the growth of barley grown in saline soils is shown under varying salinity treatments using four barley genotypes differing in their salt tolerance in solution and soil-based systems. High Na(+), Cl(-), and NaCl separately reduced the growth of barley, however, the reductions in growth and photosynthesis were greatest under NaCl stress and were mainly additive of the effects of Na(+) and Cl(-) stress. The results demonstrated that Na(+) and Cl(-) exclusion among barley genotypes are independent mechanisms and different genotypes expressed different combinations of the two mechanisms. High concentrations of Na(+) reduced K(+) and Ca(2+) uptake and reduced photosynthesis mainly by reducing stomatal conductance. By comparison, high Cl(-) concentration reduced photosynthetic capacity due to non-stomatal effects: there was chlorophyll degradation, and a reduction in the actual quantum yield of PSII electron transport which was associated with both photochemical quenching and the efficiency of excitation energy capture. The results also showed that there are fundamental differences in salinity responses between soil and solution culture, and that the importance of the different mechanisms of salt damage varies according to the system under which the plants were grown.

Combining high biodiversity with high yields in tropical agroforests

Abstract: Local and landscape-scale agricultural intensification is a major driver of global biodiversity loss. Controversially discussed solutions include wildlife-friendly farming or combining high-intensity farming with land-sparing for nature. Here, we integrate biodiversity and crop productivity data for smallholder cacao in Indonesia to exemplify for tropical agroforests that there is little relationship between yield and biodiversity under current management, opening substantial opportunities for wildlife-friendly management. Species richness of trees, fungi, invertebrates, and vertebrates did not decrease with yield. Moderate shade, adequate labor, and input level can be combined with a complex habitat structure to provide high biodiversity as well as high yields. Although livelihood impacts are held up as a major obstacle for wildlife-friendly farming in the tropics, our results suggest that in some situations, agroforests can be designed to optimize both biodiversity and crop production benefits without adding pressure to convert natural habitat to farmland.