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Showing papers by "University of Melbourne published in 2004"


Journal ArticleDOI
TL;DR: The Global Land Data Assimilation System (GLDAS) as mentioned in this paper is an uncoupled land surface modeling system that drives multiple models, integrates a huge quantity of observation-based data, runs globally at high resolution (0.25°), and produces results in near-real time (typically within 48 h of the present).
Abstract: A Global Land Data Assimilation System (GLDAS) has been developed. Its purpose is to ingest satellite- and ground-based observational data products, using advanced land surface modeling and data assimilation techniques, in order to generate optimal fields of land surface states and fluxes. GLDAS is unique in that it is an uncoupled land surface modeling system that drives multiple models, integrates a huge quantity of observation-based data, runs globally at high resolution (0.25°), and produces results in near–real time (typically within 48 h of the present). GLDAS is also a test bed for innovative modeling and assimilation capabilities. A vegetation-based “tiling” approach is used to simulate subgrid-scale variability, with a 1-km global vegetation dataset as its basis. Soil and elevation parameters are based on high-resolution global datasets. Observation-based precipitation and downward radiation and output fields from the best available global coupled atmospheric data assimilation systems are employe...

3,857 citations


Journal ArticleDOI
TL;DR: Oxidative stress has been implicated in the progression of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and different strategies, including novel metal–protein attenuating compounds aimed at a variety of targets have shown promise in clinical studies.
Abstract: Oxidative stress has been implicated in the progression of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Oxygen is vital for life but is also potentially dangerous, and a complex system of checks and balances exists for utilizing this essential element. Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. The systems in place to cope with the biochemistry of oxygen are complex, and many questions about the mechanisms of oxygen regulation remain unanswered. However, this same complexity provides a number of therapeutic targets, and different strategies, including novel metal-protein attenuating compounds, aimed at a variety of targets have shown promise in clinical studies.

3,376 citations


Journal ArticleDOI
TL;DR: A novel parameter automation strategy for the particle swarm algorithm and two further extensions to improve its performance after a predefined number of generations to overcome the difficulties of selecting an appropriate mutation step size for different problems.
Abstract: This paper introduces a novel parameter automation strategy for the particle swarm algorithm and two further extensions to improve its performance after a predefined number of generations. Initially, to efficiently control the local search and convergence to the global optimum solution, time-varying acceleration coefficients (TVAC) are introduced in addition to the time-varying inertia weight factor in particle swarm optimization (PSO). From the basis of TVAC, two new strategies are discussed to improve the performance of the PSO. First, the concept of "mutation" is introduced to the particle swarm optimization along with TVAC (MPSO-TVAC), by adding a small perturbation to a randomly selected modulus of the velocity vector of a random particle by predefined probability. Second, we introduce a novel particle swarm concept "self-organizing hierarchical particle swarm optimizer with TVAC (HPSO-TVAC)". Under this method, only the "social" part and the "cognitive" part of the particle swarm strategy are considered to estimate the new velocity of each particle and particles are reinitialized whenever they are stagnated in the search space. In addition, to overcome the difficulties of selecting an appropriate mutation step size for different problems, a time-varying mutation step size was introduced. Further, for most of the benchmarks, mutation probability is found to be insensitive to the performance of MPSO-TVAC method. On the other hand, the effect of reinitialization velocity on the performance of HPSO-TVAC method is also observed. Time-varying reinitialization step size is found to be an efficient parameter optimization strategy for HPSO-TVAC method. The HPSO-TVAC strategy outperformed all the methods considered in this investigation for most of the functions. Furthermore, it has also been observed that both the MPSO and HPSO strategies perform poorly when the acceleration coefficients are fixed at two.

2,753 citations


Journal ArticleDOI
TL;DR: In this article, the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender was estimated.
Abstract: Objective: To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender.Methods: Summary prevalence estimates of drusen 125 pin or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD.Results: The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 pin or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons.Conclusion: Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.

2,389 citations


Journal ArticleDOI
TL;DR: In this article, the relationship between reflexivity and research ethics is examined, and the notion of reflexivity is used as a helpful way of understanding both the nature of ethics in qualitative research and how ethical practice in research can be achieved.
Abstract: Ethical tensions are part of the everyday practice of doing research—all kinds of research. How do researchers deal with ethical problems that arise in the practice of their research, and are there conceptual frameworks that they can draw on to assist them? This article examines the relationship between reflexivity and research ethics. It focuses on what constitutes ethical research practice in qualitative research and how researchers achieve ethical research practice. As a framework for thinking through these issues, the authors distinguish two different dimensions of ethics in research, which they term procedural ethics and “ethics in practice.” The relationship between them and the impact that each has on the actual doing of research are examined. The article then draws on the notion of reflexivity as a helpful way of understanding both the nature of ethics in qualitative research and how ethical practice in research can be achieved.

2,157 citations


Journal ArticleDOI
01 Oct 2004-Science
TL;DR: The 34 million-base-pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand base-pair mitochondrial genomes were reported in this article.
Abstract: Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.

1,945 citations


Journal ArticleDOI
TL;DR: In a qualitative study of the emerging field of HIV/AIDS treatment advocacy in Canada, it was found that institutional entrepreneurship involved three sets of critical activities: the occupation of “subject positions” that have wide legitimacy and bridge diverse stakeholders.
Abstract: In a qualitative study of the emerging field of HIV/AIDS treatment advocacy in Canada, we found that institutional entrepreneurship involved three sets of critical activities: (1) the occupation of “subject positions” that have wide legitimacy and bridge diverse stakeholders, (2) the theorization of new practices through discursive and political means, and (3) the institutionalization of these new practices by connecting them to stakeholders’ routines and values.

1,876 citations


Journal ArticleDOI
TL;DR: The CEAP classification for chronic venous disorders was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995.

1,695 citations


Journal ArticleDOI
TL;DR: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.
Abstract: background Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. methods To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. results New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. conclusions Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.

1,582 citations


Journal ArticleDOI
TL;DR: This paper developed a discursive model of institutionalization that highlights the relationships among texts, discourse, institutions, and action, and proposed a set of conditions under which institutionalization processes are most likely to occur, and conclude the article with an exploration of the model's implications for other areas of research.
Abstract: We argue that the processes underlying institutionalization have not been investigated adequately and that discourse analysis provides a coherent framework for such investigation. Accordingly, we develop a discursive model of institutionalization that highlights the relationships among texts, discourse, institutions, and action. Based on this discursive model, we propose a set of conditions under which institutionalization processes are most likely to occur, and we conclude the article with an exploration of the model's implications for other areas of research.

1,469 citations


Journal ArticleDOI
01 Jan 2004-Bone
TL;DR: There is a clear need for the development of more sensitive risk assessment tools, using not only BMD, but also other clinical predictors of fractures.

Journal ArticleDOI
TL;DR: Home is variously described in the literature as conflated with or related to house, family, haven, self, gender, and journeying, and many authors also consider notions of being-at-home, creating or making home and the ideal home as discussed by the authors.
Abstract: In recent years there has been a proliferation of writing on the meaning of home within the disciplines of sociology, anthropology, psychology, human geography, history, architecture and philosophy. Although many researchers now understand home as a multidimensional concept and acknowledge the presence of and need for multidisciplinary research in the field, there has been little sustained reflection and critique of the multidisciplinary field of home research and the diverse, even contradictory meanings of this term. This paper brings together and examines the dominant and recurring ideas about home represented in the relevant theoretical and empirical literature. It raises the question whether or not home is (a) place(s), (a) space(s), feeling(s), practices, and/or an active state of state of being in the world? Home is variously described in the literature as conflated with or related to house, family, haven, self, gender, and journeying. Many authors also consider notions of being-at-home, creating or making home and the ideal home. In an effort to facilitate interdisciplinary conversations about the meaning and experience of home each of these themes are briefly considered in this critical literature review.

Journal ArticleDOI
TL;DR: This perspective article seeks to clarify which cells fall under the NKT-cell umbrella, and which might be best considered as separate.
Abstract: Recent years have seen so-called natural killer T (NKT) cells emerge as important regulators of the immune response. The existence of NKT-cell subsets, and other types of T cell that resemble NKT cells, is an ongoing source of confusion in the literature. This perspective article seeks to clarify which cells fall under the NKT-cell umbrella, and which might be best considered as separate.

Journal ArticleDOI
TL;DR: Although there was substantial model mimicry, empirical conditions were identified under which the models make discriminably different predictions and the best accounts of the data were provided by the Wiener diffusion model, the OU model with small-to-moderate decay, and the accumulator model with long-tailed distributions of criteria.
Abstract: The authors evaluated 4 sequential sampling models for 2-choice decisions--the Wiener diffusion, Ornstein-Uhlenbeck (OU) diffusion, accumulator, and Poisson counter models--by fitting them to the response time (RT) distributions and accuracy data from 3 experiments. Each of the models was augmented with assumptions of variability across trials in the rate of accumulation of evidence from stimuli, the values of response criteria, and the value of base RT across trials. Although there was substantial model mimicry, empirical conditions were identified under which the models make discriminably different predictions. The best accounts of the data were provided by the Wiener diffusion model, the OU model with small-to-moderate decay, and the accumulator model with long-tailed (exponential) distributions of criteria, although the last was unable to produce error RTs shorter than correct RTs. The relationship between these models and 3 recent, neurally inspired models was also examined.

Journal ArticleDOI
TL;DR: BIS-guided anaesthesia reduces the risk of awareness in at-risk adult surgical patients undergoing relaxant general anaesthesia, and with a cost of routine BIS monitoring at US16 dollars per use in Australia and a number needed to treat of 138, the cost of preventing one case ofawareness in high-risk patients is about 2200 dollars.

Journal ArticleDOI
TL;DR: In this paper, the prevalence of diabetic retinopathy among adults 40 years and older in the United States was estimated by pooled analysis of data from 8 population-based eye surveys.
Abstract: Objective: To determine the prevalence of diabetic retinopathy among adults 40 years and older in the United States.Methods: Pooled analysis of data from 8 population-based eye surveys was used to estimate the prevalence, among persons with diabetes mellitus (DM), of retinopathy and of vision-threatening retinopathy-defined as proliferative or severe nonproliferative retinopathy and/or macular edema. Within strata of age, race/ethnicity, and gender, US prevalence rates were estimated by multiplying these values by the prevalence of DM reported in the 1999 National Health Interview Survey and the 2000 US Census population.Results: Among an estimated 10.2 million US adults 40 years and older known to have DM, the estimated crude prevalence rates for retinopathy and vision-threatening retinopathy were 40.3% and 8.2%, respectively. The estimated US general population prevalence rates for retinopathy and vision-threatening retinopathy were 3.4% (4.1 million persons) and 0.75% (899000 persons). Future projections suggest that diabetic retinopathy will increase as a public health problem, both with aging of the US population and increasing age-specific prevalence of DM over time.Conclusion: Approximately 4.1 million US adults 40 years and older have diabetic retinopathy; 1 of every 12 persons with DM in this age group has advanced, vision-threatening retinopathy.

Journal ArticleDOI
TL;DR: In this paper, the authors describe a model of earnings and earnings growth and demonstrate how this model may be used to obtain estimates of the expected rate of return on equity capital, and compare these estimates with estimates of expected rates of return implied by commonly used heuristics, such as the PEG ratio and the PE ratio.
Abstract: I describe a model of earnings and earnings growth and I demonstrate how this model may be used to obtain estimates of the expected rate of return on equity capital. These estimates are compared with estimates of the expected rate of return implied by commonly used heuristics—viz., the PEG ratio and the PE ratio. Proponents of the PEG ratio (which is the price‐earnings [PE] ratio divided by the short‐term earnings growth rate) argue that this ratio takes account of differences in short‐run earnings growth, providing a ranking that is superior to the ranking based on PE ratios. But even though the PEG ratio may provide an improvement over the PE ratio, it is arguably still too simplistic because it implicitly assumes that the short‐run growth forecast also captures the long‐run future. I provide a means of simultaneously estimating the expected rate of return and the rate of change in abnormal growth in earnings beyond the (short) forecast horizon—thereby refining the PEG ratio ranking. The method may also...

Journal ArticleDOI
TL;DR: Patterns of neural firing linked to eye movement decisions show that behavioral decisions are predicted by the differential firing rates of cells coding selected and nonselected stimulus alternatives, which provides a quantitative link between the time-course of behavioral decisions and the growth of stimulus information in neural firing data.

Journal ArticleDOI
TL;DR: The panel proposed a specific terminology for the different types of abnormal cells encountered in the cerebral cortex of patients with FCD, a reappraisal of the different histopathologic abnormalities usually subsumed under the term “microdysgenesis,” and a more detailed yet straightforward classification of the various histopathological features that usually are included under the heterogeneous term of “focal cortical dysplasia.”
Abstract: Background: There have been difficulties in achieving a uniform terminology in the literature regarding issues of classification with respect to focal cortical dysplasias (FCDs) associated with epilepsy. Objectives: To review and refine the current terminology and classification issues of potential clinical relevance to epileptologists, neuroradiologists, and neuropathologists dealing with FCD. Methods: A panel discussion of epileptologists, neuropathologists, and neuroradiologists with special expertise in FCD was held. Results: The panel proposed 1) a specific terminology for the different types of abnormal cells encountered in the cerebral cortex of patients with FCD; 2) a reappraisal of the different histopathologic abnormalities usually subsumed under the term “microdysgenesis,” and suggested that this terminology be abandoned; and 3) a more detailed yet straightforward classification of the various histopathologic features that usually are included under the heterogeneous term of “focal cortical dysplasia.” Conclusion: The panel hopes that these proposals will stimulate the debate toward more specific clinical, imaging, histopathologic, and prognostic correlations in patients with FCD associated with epilepsy.

Journal ArticleDOI
TL;DR: This review will explore the diverse influences of NKT cells in various disease models, their ability to suppress or enhance immunity, and the potential for manipulating these cells as a novel form of immunotherapy.
Abstract: NKT cells are a unique T lymphocyte sublineage that has been implicated in the regulation of immune responses associated with a broad range of diseases, including autoimmunity, infectious diseases, and cancer. In stark contrast to both conventional T lymphocytes and other types of Tregs, NKT cells are reactive to the nonclassical class I antigen-presenting molecule CD1d, and they recognize glycolipid antigens rather than peptides. Moreover, they can either up- or downregulate immune responses by promoting the secretion of Th1, Th2, or immune regulatory cytokines. This review will explore the diverse influences of these cells in various disease models, their ability to suppress or enhance immunity, and the potential for manipulating these cells as a novel form of immunotherapy.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the levels of precision and accuracy obtainable by laser ablation Hf-isotope analysis of zircons in real-world situations using a 193-nm ArF excimer laser coupled to a Nu Plasma MC-ICPMS.

Journal ArticleDOI
TL;DR: In this article, the authors investigated the variables that may be predictive of intention to leave a job, and tested a model that includes mediating variables such as emotional support from supervisors and self-esteem.
Abstract: This paper reports on an investigation of the variables that may be predictive of intentions to leave a job, and tests a model that includes mediating variables. A total of 173 retail salespeople completed questionnaires measuring commitment to the organization for which they worked, job satisfaction, stress, supervisor support, locus of control, self‐esteem, the perceived stressors in the job and their intention to quit. Path analysis was used to test the relationships hypothesized in the model. The majority of hypotheses were supported, with the variables included accounting for 52 per cent of the variance in intention to quit. Emotional support from supervisors and self‐esteem mediated the impact of stressors on stress reactions, job satisfaction, commitment to the organization and intention to quit. It is suggested that to ameliorate intention to quit and in turn reduce turnover, managers need to actively monitor workloads, and the relationships between supervisors and subordinates in order to reduce and manage stress. Managers also need to monitor both the extrinsic and intrinsic sources of job satisfaction available to employees. These activities could assist in maintaining and increasing job satisfaction and commitment to the organization.

Journal ArticleDOI
TL;DR: It appears possible to identify those individuals who are at particularly high risk of developing a psychotic disorder such as schizophrenia, given the very high PPV and low false positive rate with this two-step process, and it may be justifiable to target these individuals for intensive monitoring of mental state and even low-dose neuroleptic medication or other biological and psychosocial treatments.

Journal ArticleDOI
TL;DR: The placenta acts to provide oxygen and nutrients to the fetus, whilst removing carbon dioxide and other waste products, and metabolises a number of substances and can release metabolic products into maternal and/or fetal circulations.

Journal ArticleDOI
TL;DR: This review examines the molecular basis for cross‐presentation, discusses the role of DC subsets, and examines the contribution of this process to immunity, with some emphasis on DNA vaccination.
Abstract: Cross-presentation involves the uptake and processing of exogenous antigens within the major histocompatibility complex (MHC) class I pathway. This process is primarily performed by dendritic cells (DCs), which are not a single cell type but may be divided into several distinct subsets. Those expressing CD8alpha together with CD205, found primarily in the T-cell areas of the spleen and lymph nodes, are the major subset responsible for cross-presenting cellular antigens. This ability is likely to be important for the generation of cytotoxic T-cell immunity to a variety of antigens, particularly those associated with viral infection, tumorigenesis, and DNA vaccination. At present, it is unclear whether the CD8alpha-expressing DC subset captures antigen directly from target cells or obtains it indirectly from intermediary DCs that traffic from peripheral sites. In this review, we examine the molecular basis for cross-presentation, discuss the role of DC subsets, and examine the contribution of this process to immunity, with some emphasis on DNA vaccination.

Journal ArticleDOI
TL;DR: The evidence supportive of P2 being the result of independent processes is described and several features, such as its persistence from wakefulness into sleep, the general consensus that unlike most other EEG phenomena it increases with age, and the fact that it can be generated using respiratory stimuli are highlighted.

Journal ArticleDOI
TL;DR: In conclusion, weight loss after surgery provides major improvement or resolution of obesity and metabolic syndrome‐associated abnormal liver histological features in severely obese subjects.

Journal ArticleDOI
TL;DR: A deficient therapeutic evidence base suggests that extrapolation of risk-benefit ratios from younger adults to geriatric populations is not necessarily valid, and therapeutic advances generally may convert healthy longevity from an asset of fortunate individuals into a general social benefit.
Abstract: Population aging evokes doomsday economic and sociological prognostication, despite a minority of older people suffering significant dependency and the potential for advances in therapeutics of age-related disease and primary aging. Biological aging processes are linked mechanistically to altered drug handling, altered physiological reserve, and pharmacodynamic responses. Parenteral loading doses need only be adjusted for body weight as volumes of distribution are little changed, whereas oral loading doses in some cases may require reduction to account for age-related increases in bioavailability. Age-related reduction of hepatic blood flow and hepatocyte mass and primary aging changes in hepatic sinusoidal endothelium with effects on drug transfer and oxygen delivery reduce hepatic drug clearance. Primary renal aging is evident, although renal clearance reduction in older people is predominantly disease-related and is poorly estimated by standard methods. The geriatric dosing axiom, "start low and go slow" is based on pharmacokinetic considerations and concern for adverse drug reactions, not from clinical trial data. In the absence of generalizable dosage guidelines, individualization via effect titration is required. Altered pharmacodynamics are well documented in the cardiovascular system, with changes in the autonomic system, autacoid receptors, drug receptors, and endothelial function to modify baseline cardiovascular tone and responses to stimuli such as postural change and feeding. Adverse drug reactions and polypharmacy represent major linkages to avoidable morbidity and mortality. This, combined with a deficient therapeutic evidence base, suggests that extrapolation of risk-benefit ratios from younger adults to geriatric populations is not necessarily valid. Even so, therapeutic advances generally may convert healthy longevity from an asset of fortunate individuals into a general social benefit.

Journal ArticleDOI
TL;DR: While PTSD and comorbid PTSD/depression are indistinguishable, the findings support the existence of depression as a separate construct in the acute, but not the chronic, aftermath of trauma.
Abstract: Objective: Posttraumatic stress disorder (PTSD) and major depression occur frequently following traumatic exposure, both as separate disorders and concurrently. This raises the question of whether PTSD and depression are separate disorders in the aftermath of trauma or part of a single general traumatic stress construct. This study aimed to explore the relationships among PTSD, depression, and comorbid PTSD/depression following traumatic injury. Method: A group of 363 injury survivors was assessed just prior to discharge from hospital and 3 and 12 months postinjury. Canonical correlations were used to examine the relationship between PTSD and depression symptom severity and a set of predictor variables. Multinomial logistic regression was used to identify whether the diagnostic categories of PTSD, depression, and comorbid PTSD/depression were associated with different groups of predictors. Results: The majority of psychopathology in the aftermath of trauma was best conceptualized as a general traumatic stress factor, suggesting that when PTSD and depression occur together, they reflect a shared vulnerability with similar predictive variables. However, there was also evidence that in a minority of cases at 3 months, depression occurs independently from PTSD and was predicted by a different combination of variables. Conclusions: While PTSD and comorbid PTSD/depression are indistinguishable, the findings support the existence of depression as a separate construct in the acute, but not the chronic, aftermath of trauma.

Journal ArticleDOI
TL;DR: Observations indicate a primary role for HMA2 and HMA4 in essential Zn homeostasis and increased sensitivity to Cd in a phytochelatin-deficient mutant background, suggesting that they may also influence Cd detoxification.
Abstract: Arabidopsis thaliana has eight genes encoding members of the type 1B heavy metal–transporting subfamily of the P-type ATPases. Three of these transporters, HMA2, HMA3, and HMA4, are closely related to each other and are most similar in sequence to the divalent heavy metal cation transporters of prokaryotes. To determine the function of these transporters in metal homeostasis, we have identified and characterized mutants affected in each. Whereas the individual mutants exhibited no apparent phenotype, hma2 hma4 double mutants had a nutritional deficiency phenotype that could be compensated for by increasing the level of Zn, but not Cu or Co, in the growth medium. Levels of Zn, but not other essential elements, in the shoot tissues of a hma2 hma4 double mutant and, to a lesser extent, of a hma4 single mutant were decreased compared with the wild type. Together, these observations indicate a primary role for HMA2 and HMA4 in essential Zn homeostasis. HMA2promoter- and HMA4promoter-reporter gene constructs provide evidence that HMA2 and HMA4 expression is predominantly in the vascular tissues of roots, stems, and leaves. In addition, expression of the genes in developing anthers was confirmed by RT-PCR and was consistent with a male-sterile phenotype in the double mutant. HMA2 appears to be localized to the plasma membrane, as indicated by protein gel blot analysis of membrane fractions using isoform-specific antibodies and by the visualization of an HMA2-green fluorescent protein fusion by confocal microscopy. These observations are consistent with a role for HMA2 and HMA4 in Zn translocation. hma2 and hma4 mutations both conferred increased sensitivity to Cd in a phytochelatin-deficient mutant background, suggesting that they may also influence Cd detoxification.